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Drugs Used in the Management of Central Nervous System Disorders

Drugs Used in the Management of Central Nervous System Disorders

Drugs Used in the Treatment of Depression

Depression is a mental state characterized by diverse psychological symptoms such as low mood, loss of interest and enjoyment of activities, and reduced energy. Depression is associated with physical symptoms such as:

  • Fatigue
  • Anxiety
  • Sleep disturbance
  • Reduction in libido
  • Decreased productivity
  • Changes in appetite or weight
  • Loss of concentration
  • Loss of interest (depressed mood)
  • Thoughts of death and suicide

Drugs used in the treatment of depression include:

  • Tricyclic antidepressants
  • Selective Serotonin Reuptake Inhibitors (SSRIs)
  • Monoamine Oxidase Inhibitors (MAOIs)
  • Other antidepressant drugs (Atypical antidepressants)

Tricyclic Antidepressants

These drugs inhibit the reuptake of norepinephrine and serotonin at the presynaptic neuron, prolonging neuronal activity.

Examples:

  • Amitriptyline
  • Imipramine
  • Clomipramine

Amitriptyline

Available Preparations:

  • Tablets: 25 mg

Available Brands: Laroxyl®

Pharmacokinetics: Amitriptyline is absorbed rapidly from the GIT, distributed widely into the body, including the CNS and breast milk, metabolized in the liver to active metabolites, and excreted in urine.

Indications:

  • Depression where sedation is required
  • Nocturnal enuresis in children
  • Peripheral neuropathy
  • Post-herpetic neuralgia
  • Migraine prophylaxis
  • Tension headache
  • Adjuvant in pain management

Contraindications:

  • Known hypersensitivity to the drug
  • Recent myocardial infarction
  • Severe liver disease
  • Manic phase
  • Coma or severe respiratory depression
  • Prostatic hypertrophy
  • Glaucoma

Dosage:

Depression:

  • Adult: Initially 75 mg daily in divided doses or as a single dose at bedtime. Increased gradually according to response to 150 mg.

Nocturnal Enuresis:

Children:

  • 7-10 years: 10-20 mg at night
  • 11-16 years: 25-50 mg at night. Maximum period of treatment is 3 months.

Peripheral Neuropathy: Initially 10-25 mg daily at night, increased if necessary to 75 mg daily.

Migraine Prophylaxis: Initially 10 mg at night, increased according to response to a maintenance dose of 50-75 mg at night.

Adjuvant Pain Management: 10-25 mg at night, up to a max of 150 mg.

Side Effects:

  • Dry mouth
  • Sedation
  • Constipation
  • Postural hypotension
  • Difficulty with micturition
  • Blurred vision
  • Cardiac arrhythmias
  • Unpleasant taste
  • Somnolence
  • Photosensitivity
  • Interference with sexual function
  • Nausea
  • Tremors
  • Sweating
  • Skin rashes
  • Headache
  • Urticaria
  • Hypomania
  • Weight gain
  • Increased appetite

Drug Interactions:

  • Cimetidine, valproic acid may increase amitriptyline blood concentration and risk of toxicity
  • Alcohol, anticonvulsants, phenothiazines, and sedative hypnotics may increase CNS depression caused by amitriptyline
  • Carbamazepine reduces the serum concentration of amitriptyline
  • Concurrent use of amitriptyline with phenylephrine, ephedrine may increase blood pressure
  • Amitriptyline may decrease the hypotensive effect of methyldopa

Key Issues to Note:

  • Inform the patient that full therapeutic effect may delay up to 4 weeks
  • Avoid alcoholic beverages while taking this drug
  • Warn the patient not to stop taking the drug suddenly
  • The drug causes drowsiness and may impair activities that need mental alertness

Selective Serotonin Reuptake Inhibitors (SSRIs)

Their efficacy is similar to that of tricyclic antidepressants but with fewer side effects because of low affinity for muscarinic, histaminergic, and adrenergic receptors.

Examples:

  • Fluoxetine
  • Paroxetine
  • Sertraline
  • Citalopram

Mode of Action: The antidepressant action of SSRIs is by inhibiting the reuptake of the neurotransmitter serotonin.

Fluoxetine

Available Preparations:

  • Capsules: 20 mg

Available Brands: Prozac®, Nuzac®, Trizac®, Fludac®, Flocept®

Pharmacokinetics: Fluoxetine is well absorbed after oral administration, metabolized in the liver to active metabolites, and excreted in urine.

Indications:

  • Major depression
  • Obsessive-compulsive disorder
  • Bulimia nervosa
  • Premenstrual dysphoric disorder
  • Panic disorders
  • Post-traumatic stress disorder
  • Hot flushes

Contraindications:

  • Hypersensitivity to fluoxetine
  • Severe renal failure
  • Unstable epilepsy
  • Manic phase

Dosage:

  • Depression: 20 mg once daily, increased after 3-4 weeks if necessary. Find at appropriate intervals thereafter, max 60 mg once daily.
  • Elderly: 20-40 mg once daily, max 60 mg.
  • Bulimia Nervosa: 60 mg once daily, max 80 mg once daily.
  • Obsessive-Compulsive Disorder: Initially 20 mg once daily, increased after 2 weeks if necessary, max dose 60 mg.
  1. Elderly: 20-40 mg once daily, max 60 mg.
  • Panic Disorders: 10 mg once daily, do not exceed 20 mg daily.
  • Premenstrual Dysphoric Disorder: 20 mg once daily.

Side Effects:

  • Headache
  • Insomnia
  • Somnolence
  • Constipation
  • Abdominal pain
  • Dry mouth
  • Dizziness
  • Anxiety
  • Tremor
  • Sedation
  • Fatigue
  • Mania
  • Sweating
  • Pharyngitis
  • Euphoria
  • Dyspnea
  • Nervousness
  • Sleep disturbance
  • Drowsiness

Drug Interactions:

  • Alcohol and other CNS depressants may increase CNS depression
  • Fluoxetine may increase phenytoin blood concentration and risk of toxicity
  • Fluoxetine may increase the effect of warfarin; therefore, the dose may need adjustments
  • Fluoxetine may increase the blood levels and toxicity of lithium
  • Fluoxetine inhibits the metabolism of carbamazepine and haloperidol

Key Issues to Note:

  • Full antidepressant effect may be delayed until 4 weeks of treatment
  • Give a lower dose in patients with hepatic and renal impairment
  • Avoid taking alcohol during drug therapy

Drugs Used in the Treatment of Manic Disorders

Mania is a state of mind characterized by excessive cheerfulness and increased activity.

Signs and Symptoms:

  • Hyperactivity
  • Excessive enthusiasm
  • Decreased need for sleep
  • Flight of ideas
  • Inflated self-esteem
  • Talkativeness
  • Extreme self-confidence
  • Delusions

Acute mania usually begins abruptly and symptoms increase over several days. Manic episodes may be precipitated by:

  • Use of antidepressants
  • Lack of enough sleep
  • Stressors
  • CNS stimulants
  • Bright light

Bipolar disorder (manic depression) is a mixed affective disorder in which the patient experiences alternating episodes of hypomania or mania and depression.

Management of Manic Disorders:

  • Mild Symptoms of Mania: Lithium alone or in combination with benzodiazepine
  • Severe Symptoms of Mania: Lithium plus antipsychotic drugs

Note: In acute attack of mania, lithium carbonate may be given concurrently with antipsychotic in order to bring the symptoms under control. Lithium carbonate has a slow onset of action which takes up to 2 weeks before therapeutic benefit is fully achieved.

Drugs used in the treatment of mania include:

  • Lithium carbonate
  • Sodium valproate
  • Carbamazepine
  • Lamotrigine

Lithium Carbonate

Available Preparations:

  • Tablets: 300 mg

Available Brands: Camcolit®

Pharmacokinetics: It is completely absorbed from the GIT after oral administration, distributed widely into the body including breast milk. It is not metabolized and is excreted unchanged in urine.

Indications:

  • Prophylaxis of mania
  • Treatment of acute mania
  • Manic phase of bipolar disorder
  • Recurrent depression
  • Aggressive or self-mutilating behavior

Contraindications:

  • Pregnancy

  • Severe renal impairment

  • Cardiac disease

  • Lactation

  • Untreated hypothyroidism

  • Disturbance of electrolyte balance

  • Hypersensitivity to the drug

Dosage:

Adult and Children over 12 years:

  • Acute Mania: 300 mg 3-4 times, maintenance dose 2.4 g/day.

  • Prophylaxis: Initially 300-400 mg daily.

Side Effects:

  • Nausea

  • Diarrhea

  • Muscle weakness

  • Polyuria

  • Vertigo

  • Tremors

  • Loss of concentration

  • Hypothyroidism

  • Impaired renal function

  • Hypermagnesemia

  • Disturbances of thyroid function

  • Exacerbation of psoriasis

  • Weight gain

  • Oedema

  • Mild drowsiness

  • Sexual dysfunction

Drug Interactions:

  • Concurrent use of lithium with thiazide diuretics may decrease renal excretion and enhance lithium toxicity

  • Lithium may interfere with pressor effects of sympathomimetic agents and may decrease the effects of chlorpromazine

  • Tetracyclines, phenytoin, carbamazepine, and methyldopa may increase lithium toxicity

  • Concomitant use with haloperidol or other antipsychotic agents may result in severe encephalopathy

  • Use of lithium with SSRIs may increase GI and CNS adverse effects

  • Indomethacin and other NSAIDs decrease renal excretion of lithium

Key Issues to Note:

  • The drug may be taken with food or milk to reduce GI upset

  • Lithium should be discontinued before electroconvulsive therapy

  • Patient should maintain adequate water intake

  • Avoid large amounts of caffeine, which will interfere with drug’s effectiveness

  • The drug should not be stopped abruptly

Drugs Used in the Treatment of Epilepsy

Epilepsy is a disorder of brain function characterized by recurrent seizures that have a sudden onset. A patient should not be described as having epilepsy until a second non-febrile seizure occurs.

Seizure: A seizure is a paroxysmal discharge of cerebral neurons accompanied by a clinical phenomenon apparent to the patient or to an observer.

Classification of Epilepsy

Epileptic seizures (fits) present in several different forms depending on the site of the discharge and whether the discharge remains localized or spreads.

Partial Seizures: These are epileptic seizures in which the neuronal discharge remains localized in one area of the brain. They result in a disturbance of function such as abnormal sensation or movement of the limb without loss of consciousness. Partial seizures are subdivided as follows:

  • Simple partial seizures (consciousness is not impaired)
  • Complex partial seizures (consciousness is impaired)

Partial seizures may become secondarily generalized seizures if the neuronal discharge spreads to involve the entire brain.

Generalized Seizures: Generalized seizures are characterized by a neuronal discharge involving the whole brain with loss of consciousness. They are subdivided as follows:

  • Tonic-clonic seizures (grand mal)

  • Myoclonic seizures

  • Atonic seizures

  • Absence seizures (petit mal)

Absence Seizures (Petit Mal): These are generalized seizures characterized by a sudden loss of consciousness lasting for a few seconds. It is usually accompanied by motor activity which may vary from eyelid blinking to more extensive tonic body movement. It is common in children and juveniles.

Myoclonic Seizures: These are characterized by brief jerks in the limbs which may be single or multiple. The duration of the seizure is a few seconds. It mainly occurs in children and juveniles.

Atonic Seizures: Atonic seizures are characterized by loss of postural tone; the head sags or the patient falls down.

Generalized Tonic-Clonic Seizures (Grand Mal Fits): These are characterized by a sudden attack with loss of consciousness and violent body jerking lasting 3-5 minutes. The patient regains consciousness spontaneously; incontinence, tongue biting, or other injuries may occur during the episode. Grand mal fits may be due to:

  • Family history of epilepsy

  • Uncontrolled febrile convulsions in children

  • Head injuries

  • Infections (e.g., meningitis, HIV)

  • Birth trauma to an infant

  • Alcohol and drug abuse

Status Epilepticus: It is a seizure lasting for more than 30 minutes or several fits following one another without restoration of consciousness in between the fits. Status epilepticus is a common complication of grand mal epilepsy and it’s a medical emergency.

Management of Status Epilepticus:

  • Position the patient to avoid injury

  • Give oxygen to support respiration

  • If hypoglycemia is suspected, give a bolus of 50 ml of 50% glucose IV

  • Consider giving parenteral thiamine if alcohol abuse is suspected

  • Give anticonvulsants such as diazepam IV, lorazepam IV, clonazepam, midazolam

  • Slow intravenous injection of phenytoin may be given if seizures recur or fail to respond to diazepam 30 minutes after it began

  • Phenytoin by intravenous infusion should be given at a dose of 15 mg/kg body weight at a rate not greater than 50 mg/minute.

  • Monitoring of blood pressure and ECG is necessary and phenytoin should be diluted with sodium chloride (normal saline) at a ratio of 1 mg of phenytoin: 1 ml of normal saline

Table 1: Summary of Choices of Antiepileptic Drugs

Seizure Type

Treatment Options

Partial Seizures

Carbamazepine, sodium valproate, pregabalin, lamotrigine, gabapentin, phenytoin

Generalized Tonic-Clonic Seizures (Grand Mal)

Carbamazepine, lamotrigine, sodium valproate, phenytoin

Absence Seizures (Petit Mal)

Ethosuximide, sodium valproate

Myoclonic Seizures

Sodium valproate, clonazepam

Status Epilepticus

Diazepam, clonazepam, midazolam, and phenytoin

Note: Monotherapy is preferable to a multiple-drug regimen and treatment is therefore initiated with a single drug, increasing the dose gradually until seizures are brought under control or adverse effects become severe. If treatment with the first drug fails, it is preferable to try alternative single first-line antiepileptics before giving combinations of drugs. The change-over from one antiepileptic to another should be made cautiously, withdrawing the first drug only when the new regimen has been largely established. Drugs with different modes of action should be selected for combined therapy, to reduce the risk of additive adverse effects. Many antiepileptic drugs interact with each other; therefore, precautions must be taken during prescribing.

Carbamazepine

Available Preparations:

  • Tablets: 100 mg, 200 mg

  • Syrup: 20 mg/ml

Available Brands: Tegretol®, Storilat®, Carbatol®, Carbadac®, Carbazina®

Pharmacokinetics: It is absorbed slowly from the GIT, distributed widely throughout the body, crosses the placenta, and accumulates in fetal tissue. It is metabolized by the liver to an active metabolite and is excreted in urine and feces.

Indications:

  • Partial and secondary generalized tonic-clonic seizures

  • Mixed partial or generalized seizure disorder

  • Trigeminal neuralgia

  • Prophylaxis in bipolar disorder

  • Neuropathic pain

  • Alcohol withdrawal

Contraindications:

  • Hypersensitivity to carbamazepine and TCAs

  • History of bone marrow depression

  • Porphyria

Dosage:

  • Epilepsy: Initially 100-200 mg 1-2 times daily, increased gradually after 2 weeks to the usual dose 400-1200 mg daily in divided doses. In some cases up to 1.6-2 g daily may be needed.

  • Elderly: Initially 50 mg twice daily then increase to 400-1200 mg daily.

  • Children 1 month – 12 years: Initially 5 mg/kg at night or 2.5 mg/kg twice daily, increased as necessary by 2.5-5 mg/kg every 3-7 days. Maintenance dose 5 mg/kg 2-3 times daily. Doses up to 20 mg/kg daily may be used.

  • Trigeminal Neuralgia: Initially 100 mg 1-2 times daily, increased gradually according to response to 200 mg 3-4 times daily. Up to 1 g daily may be required in some cases.

  • Prophylaxis of Bipolar Disorder Unresponsive to Lithium: Initially 400 mg daily in divided doses, increased until symptoms are controlled. Usual range 400-600 mg daily, max 1.6 g daily.

  • Neuropathic Pain: Initially 100 mg twice daily, increased gradually until pain is relieved. Maintenance dose 200-600 mg daily. Do not exceed 1.2 g daily.

Side Effects:

  • Nausea

  • Ataxia

  • Vomiting

  • Dizziness

  • Drowsiness

  • Dry mouth

  • Blurred vision

  • Headache

  • Anorexia

  • Agitation

  • Diarrhea

  • Confusion

  • Constipation

  • Impotence

  • Thrombocytopenia

  • Arthralgia

  • Stevens-Johnson syndrome

  • Gynaecomastia

Drug Interactions:

  • Clarithromycin, erythromycin, cimetidine, isoniazid may inhibit hepatic metabolism of carbamazepine with resultant increase of its serum concentration and toxicity

  • Rifampicin, phenytoin, and phenobarbital may decrease serum concentrations of carbamazepine

  • Antimalarial drugs may antagonize the activity of carbamazepine

  • Use with alcohol and other CNS drugs may potentiate adverse effects of carbamazepine

  • Use with verapamil may significantly increase the serum levels of carbamazepine

  • Carbamazepine may decrease the effectiveness of theophylline and oral contraceptives

  • Carbamazepine may increase the metabolism of warfarin, valproic acid, haloperidol, and phenytoin

Key Issues to Note:

  • Take carbamazepine with food to prevent stomach upset

  • Swallow controlled-release tablets whole, do not chew or crush them

  • Grapefruit juice may increase the absorption and blood concentration of carbamazepine

  • The drug is structurally similar to TCAs; some risk of activating latent psychosis or agitation in elderly patients exists

  • Avoid alcohol during therapy

  • The drug may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination

  • The drug may cause dry mouth and photosensitivity reactions

Phenytoin

Available Preparations:

  • Tablets: 100 mg

  • Injection: 50 mg/ml

Available Brands: Phenyto-S®, Epanutin®

Pharmacokinetics: It is absorbed slowly from the small intestine, distributed widely throughout the body, metabolized by the liver to inactive metabolites, and excreted in urine.

Indications:

  • Generalized tonic-clonic seizures

  • Partial seizures

  • Status epilepticus

  • Cardiac arrhythmias

  • Trigeminal neuralgia or severe pain

  • Control of seizures associated with neurosurgery or traumatic injury to the head

Contraindications:

  • Hypersensitivity to phenytoin or other hydantoins

  • Sinus bradycardia

  • Avoid parenteral use in sinus bradycardia

  • Sino-atrial block

  • 2nd and 3rd degree heart block

  • Stokes-Adams syndrome (IV)

  • Hepatitis

Dosage:

Oral:

  • Adult: Initially 150-300 mg daily as a single dose or in 2 divided doses, increased gradually according to response to the usual dose 200-500 mg daily.
  • Children: Initially 5 mg/kg daily in 2 divided doses, usual dose range 4-8 mg/kg daily, max 300 mg daily.

Arrhythmias:

  • Adults: Loading dose 250 mg 4 times a day for 1 day, then 250 mg/day for 2 days, maintenance dose 300-400 mg/day 1-4 times a day.

Side Effects:

  • Gastric intolerance

  • Drowsiness

  • Confusion

  • Slurred speech

  • Gum hyperplasia

  • Headache

  • Sedation

  • Insomnia

  • Blurred vision

  • Skin rashes

  • Acne

  • Hirsutism

  • Nausea

  • Nystagmus

  • Vomiting

  • Diplopia

  • Behavioral disturbance

  • Tremors

  • Anorexia

  • Constipation

  • Blood disorders

  • Coarse facies

  • Fever

Drug Interactions:

  • Alcohol and other CNS depressants may increase CNS depression

  • Anticoagulants, cimetidine, fluoxetine, fluconazole, ketoconazole, isoniazid, and sulphonamides may increase phenytoin blood concentration and risk of toxicity

  • Lidocaine, propranolol may increase cardiac depressant effects caused by phenytoin

  • Phenytoin may decrease the effects of oral contraceptives, corticosteroids, haloperidol, furosemide, doxycycline, etc.

  • Therapeutic effects of phenytoin may be decreased by barbiturates, carbamazepine, ethanol, folic acid, antacids, charcoal, and pyridoxine among others

Key Issues to Note:

  • To ensure consistent absorption, phenytoin should be administered at the same time with regards to meals

  • Phenytoin may be taken with food or milk to decrease GI upset

  • Avoid alcohol during therapy

  • Abrupt withdrawal may precipitate status epilepticus

  • Advise the patient to maintain good oral hygiene

Sodium Valproate

Available Preparations:

  • Tablets: 200 mg, 300 mg

  • Syrup: 200 mg/5 ml

Available Brands: Epilim®, Petilin®, Valparin Chrono®

Indications:

  • Generalized tonic-clonic seizures

  • Partial seizures

  • Atonic seizures

  • Absence seizures

  • Myoclonic seizures

  • Acute manic phase of bipolar disorder

  • Prophylaxis of migraine

Contraindications:

  • Hypersensitivity to sodium valproate

  • Family history of severe hepatic dysfunction

  • Pregnancy

  • Active liver disease

  • Porphyria

  • Pancreatitis

Dosage:

  • Adult: Initially 600 mg daily in 2 divided doses, preferably after food, increased by 200 mg daily every 3 days to a max of 2.5 g daily, usual maintenance dose 1-2 g daily.

  • Children under 12 years with body weight over 20 kg: Initially 400 mg daily in divided doses, increased according to response, usual range 20-30 mg/kg daily, max 35 mg/kg daily.

  • Children < 20 kg: Initially 20 mg/kg daily in divided doses.

Side Effects:

  • Nausea

  • Vomiting

  • Increased appetite

  • Abdominal cramps

  • Sedation

  • Thrombocytopenia

  • Behavioral disturbance

  • Hyperammonemia

  • Menstrual disturbances

  • Tremor

  • Ataxia

  • Oedema

  • Diarrhea

  • Weight gain

  • Gastric irritation

  • Transient hair loss

  • Drowsiness

Drug Interactions:

  • Sodium valproate increases plasma concentrations of phenobarbital, primidone, phenytoin, zidovudine

  • Aspirin may increase the effect of sodium valproate

  • Sodium valproate absorption may be reduced by colestyramine

  • Cimetidine and erythromycin may increase the effect of sodium valproate

  • Concomitant use with clonazepam may cause absence seizures

  • Antacids may increase the oral absorption of sodium valproate

Key Issues to Note:

  • Avoid alcohol during therapy

  • The drug may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination

  • The drug should not be withdrawn abruptly

Phenobarbitone

Available Preparations:

  • Tablets: 30 mg

Available Brands: B-tone®

Pharmacokinetics: Phenobarbitone is well absorbed after oral administration, distributed widely to body tissues, metabolized by the liver, and excreted in urine.

Indications:

  • Generalized tonic-clonic seizures

  • Partial seizures

  • Neonatal seizures

  • Febrile convulsions

  • Status epilepticus

Contraindications:

  • Hypersensitivity to phenobarbitone

  • Absence seizures

  • Porphyria

  • Respiratory depression

  • Severe liver impairment

Dosage:

Generalized Tonic-Clonic Seizures, Partial Seizures:

  • Adult: 60-180 mg once daily at night
  • Children: 5-8 mg/kg daily

Febrile Convulsions:

  • Children: Up to 8 mg/kg daily

Side Effects:

  • Sedation

  • Ataxia

  • Nystagmus

  • Somnolence

  • Respiratory depression

  • Behavioral disturbance

  • Megaloblastic anemia

  • Mental depression

  • Allergic skin reaction

  • Confusion

  • Constipation

  • Hypotension

  • Drowsiness

  • Slurred speech

Drug Interactions:

  • Phenobarbitone may increase the metabolism of carbamazepine

  • Phenobarbitone may decrease the effect of digoxin, corticosteroids, oral anticoagulants, tricyclic antidepressants, oral contraceptives, and metronidazole

  • The sedative effect of phenobarbitone is enhanced by other CNS depressants including alcohol

  • Sodium valproate increases the blood concentration and risk of toxicity of phenobarbitone

Key Issues to Note:

  • Avoid alcoholic beverages during therapy

  • The drug may cause drowsiness and impair ability to perform activities requiring mental alertness

  • The drug should not be withdrawn abruptly after prolonged use

Anxiolytics, Sedatives, and Hypnotics

Anxiety is an emotional condition characterized by feelings such as apprehension and fear, accompanied by symptoms such as tachycardia, increased respiration, sweating, and tremor.

Drugs used in the treatment of anxiety include:

  • Benzodiazepines
  • Antidepressants (Anxiety frequently co-exists with depression)
  • Beta blockers (may help to control physical symptoms such as tremor)

Note:

  • Antidepressants can initially exacerbate anxiety (their therapeutic response takes at least 2 weeks), therefore combined therapy with benzodiazepines may be required initially.

  • Benzodiazepines should be used for a maximum of 4 weeks, and the dose should be gradually reduced after the first 2 weeks to avoid the risk of dependence.

Insomnia

Insomnia is the inability to achieve or maintain sleep. It often leaves sufferers feeling unrefreshed by sleep and may lead to impaired daytime performance.

Insomnia is classified as follows:

  • Transient Insomnia: It may occur in those who normally sleep well and may be due to environmental stress such as noise, shift work, or jet lag. It may also be associated with acute disorders.

  • Short-term Insomnia: It is often related to an emotional problem (e.g., ongoing personal stress) or medical illness such as acute pain.

  • Chronic Insomnia: Most cases of chronic insomnia are caused by psychiatric disorders such as depression, anxiety, dementia, psychosis, or substance abuse, or physical causes such as pain or pruritus.

Drugs used in the treatment of insomnia include:

  • Benzodiazepines

  • Antidepressants

Benzodiazepines

This class includes:

  • Diazepam

  • Midazolam

  • Bromazepam

  • Alprazolam

  • Clonazepam

  • Nitrazepam

  • Chlordiazepoxide

  • Lorazepam

Diazepam

Available Preparations:

  • Tablets: 5 mg

  • Rectal: 10 mg

  • Injection: 10 mg/2 ml

Available Brands: Valium®, Cozepam®, Solina®

Pharmacokinetics: Diazepam is rapidly absorbed from the GIT following oral administration, distributed widely throughout the body, metabolized in the liver to the active metabolite, and excreted in urine and a small amount in feces.

Indications:

  • Status epilepticus

  • Febrile convulsions

  • Convulsions due to poisoning

  • Anxiety disorders

  • Insomnia

  • Control of muscle spasms

  • Management of alcohol withdrawal

Contraindications:

  • Hypersensitivity to diazepam

  • Respiratory depression

  • Severe hepatic impairment

  • Acute pulmonary insufficiency

  • Sleep apnea

  • Comatose patients

  • Acute narrow-angle glaucoma

  • Acute alcohol intoxication

  • Infants less than 1 month

Dosage:

Oral:

  • Anxiety: 2-10 mg 2-4 times daily
  • Insomnia Associated with Anxiety: 5-15 mg at bedtime
  • Muscle Spasms: 2-10 mg 2-4 times a day
  • Acute Alcohol Withdrawal: 10 mg 2-4 times for the first 24 hours, reduce to 5 mg 3-4 times on the next day as required
  • Severe Acute Anxiety, Control of Acute Panic Attacks, Acute Alcohol Withdrawal, Muscle Spasms:
  1. By IM or slow IV injection: 10 mg repeated if necessary after not less than 4 hours
  • Status Epilepticus: By slow IV at a rate of 5 mg/min
  1. Adult: 10-20 mg repeated if necessary after 30-60 minutes
  2. Children: 200-300 mcg/kg or 1 mg/year of age
  • Seizures Associated with Poisoning: By slow IV at a rate of 5 mg/min
  1. Adult: 10-20 mg

By Rectum as a Rectal Solution:

  • Adult and Children over 3 years: 10 mg, repeat the dose after 5 minutes if necessary
  • Children 1-3 years and elderly: 5 mg, repeat the dose after 5 minutes if necessary

Side Effects:

  • Drowsiness

  • Sedation

  • Dependence

  • Muscle weakness

  • Hypotension

  • Visual disturbance

  • Changes in libido

  • Urinary retention or incontinence

  • Hypersensitivity reactions

  • Ataxia

  • Headache

  • Confusion

  • Vertigo

  • Skin rash

  • Tremor

  • Blood disorders

  • Amnesia

Drug Interactions:

  • Alcohol and other CNS depressants may increase CNS depression caused by diazepam

  • Antacids may decrease the rate of absorption of diazepam

  • Heavy smoking accelerates diazepam metabolism, thus lowering clinical effectiveness

  • Oral contraceptives may impair the metabolism of diazepam

  • Cimetidine, isoniazid, erythromycin may inhibit the breakdown of diazepam leading to increased levels in blood

  • Diazepam may inhibit the therapeutic effect of levodopa

Key Issues to Note:

  • Administer the drug with food or water but not grapefruit juice

  • Avoid alcohol and caffeine during therapy

  • The drug may cause drowsiness and impair the ability to perform activities requiring mental alertness

  • Diazepam should not be discontinued suddenly; instead, decrease the dosage slowly over 8-12 weeks after long-term therapy

Drugs Used in the Treatment of Parkinsonism

Parkinson’s disease is a neurodegenerative disorder characterized by tremor, muscle rigidity, slowed movement, and postural instability as a result of an imbalance between dopamine and acetylcholine neurotransmitters in the striatum.

Drugs used in the treatment of Parkinson’s disease aim at restoring the natural balance between dopamine deficiency and relative cholinergic excess in the brain.

Classification of Drugs Used for Parkinson’s Disease

Dopaminergics

These drugs increase or enhance the action of dopamine in the brain.

Examples:

  • Bromocriptine
  • Carbidopa
  • Levodopa
  • Cabergoline

Antimuscarinics

These drugs inhibit the action of acetylcholine in the brain.

Examples:

  • Benzhexol

  • Benztropine mesylate

Antimuscarinics are often effective in the early stages of Parkinson’s disease and are effective in the treatment of drug-induced Parkinsonism.

Bromocriptine

Available Preparations:

  • Tablets: 2.5 mg

Available Brands: Lactodel®, Parlodel®, Dopagon®, Brameston®

Pharmacokinetics: Bromocriptine is poorly absorbed when given orally, undergoes first-pass metabolism. It is metabolized completely in the liver and majorly excreted through bile.

Indications:

  • Parkinson’s disease
  • Suppression of lactation
  • Puerperal breast engorgement
  • Male hyperprolactinemia
  • Premenstrual symptoms
  • Benign breast diseases
  • Prolactinomas
  • Female infertility
  • Amenorrhoea
  • Acromegaly

Contraindications:

  • Patients hypersensitive to ergot alkaloids
  • Pregnancy
  • Severe ischemic heart disease
  • Uncontrolled hypertension

Dosage:

  • Parkinson’s Disease and Infertility: 1.25 mg at night for 7 days, increase to 2.5 mg for the second week, 2.5 mg twice daily for the third week, and then 2.5 mg 3 times daily for the fourth week. Then increasing by 2.5 mg every 3-14 days according to response to a usual range of 10-40 mg daily taken with food
  • Suppression of Lactation: 2.5 mg daily for 2-3 days, increased to 2.5 mg twice daily for 2 weeks
  • Amenorrhoea and Benign Breast Disease: Initially 1.25 mg once daily at bedtime, gradually increased to 2.5 mg 2-3 times daily

Side Effects:

  • Dizziness
  • Dry mouth
  • Confusion
  • Headache
  • Constipation
  • Leg cramps
  • Allergic skin reactions
  • Fatigue
  • Cold fingers and toes
  • Nausea
  • Postural hypotension
  • Hair loss
  • Lightheadedness
  • Abdominal cramps
  • Vomiting
  • Insomnia
  • Nasal congestion

Drug Interactions:

  • Antipsychotic drugs may oppose the action of bromocriptine and increase the risk of Parkinsonism
  • Erythromycin and other macrolide antibiotics may lead to increased levels of bromocriptine and the risk of adverse effects
  • Domperidone and metoclopramide may reduce the hypoprolactinemic effects of bromocriptine
  • Alcohol intolerance may result when high doses of bromocriptine are administered together with alcohol

Key Issues to Note:

  • Side effects may be minimized by gradual introduction of the drug
  • The drug may be administered with meals to minimize GI distress
  • Take precautions while driving or operating machines since dizziness or drowsiness may occur at the beginning of therapy
  • Advise the patient to limit alcohol use during treatment
  • Inform the patient that it may take 6-8 weeks or longer for menses to be reinstated

Levodopa with Carbidopa

Available Preparations:

  • Tablets

Available Brands: Sinemet® (Levodopa/Carbidopa) 100/10

Pharmacokinetics: Levodopa is fairly well absorbed when given orally, though food reduces the rate and extent of its absorption. Carbidopa enhances levodopa bioavailability. It is metabolized in the liver to dopamine and excreted in urine.

Indications:

  • Parkinson’s disease

Contraindications:

  • Closed-angle glaucoma
  • Hypersensitivity to any of the ingredients
  • Bronchial asthma
  • Severe cardiovascular disease
  • Undiagnosed skin lesions or history of melanoma

Dosage:

  • Initially 50-100 mg of levodopa with 10-12.5 mg of carbidopa 3-4 times daily (1/2 – 1 tablet of Sinemet 110, 3-4 times daily). Increased by 50-100 mg daily or on alternate days according to response up to 800 mg levodopa with 80-100 mg carbidopa in divided doses

Side Effects:

  • Nausea
  • Dizziness
  • Palpitations
  • Dark urine
  • Abnormal movements
  • Visual abnormalities
  • Nervousness/agitation
  • Dry mouth
  • Depression
  • Headache
  • Fluid retention
  • Tongue irritation
  • Muscle twitching

Drug Interactions:

  • Pyridoxine reverses the effect of levodopa
  • Absorption of levodopa may be reduced by iron
  • Antipsychotic drugs may reduce the effect of levodopa
  • Antacids may increase the absorption of levodopa

Key Issues to Note:

  • Gastric irritation may be reduced by taking the drug after food
  • Treatment should be started with low doses, then gradually increased according to the response
  • Inform the patient that therapeutic response may be slow
  • Warn the patient of the possible dizziness and orthostatic hypotension, especially at the beginning of therapy

Antipsychotics (Neuroleptic) Drugs

Schizophrenia

Schizophrenia is a chronic psychotic illness characterized by a disintegration of the process of thinking, contact with reality, and emotional responsiveness. 

It is more common in males and usually begins in late adolescence to the early twenties.

Clinical Features of Schizophrenia

Clinical features of schizophrenia are often presented as positive or negative symptoms:

Positive Symptoms:

  • Delusions
  • Hallucinations
  • Thought disorders
  • Disorganized behaviors
  • Agitation

Negative Symptoms:

  • Lack of drive
  • Apathy
  • Social withdrawal
  • Poor self-care
  • Poverty of speech

Positive symptoms are seen as exaggeration of normal function and are common in the acute phase. Negative symptoms are viewed as loss of normal function and are prominent in the chronic phase.

Most drugs are effective against positive symptoms except atypical antipsychotics such as olanzapine which are effective against both positive and negative symptoms.

Drugs used in the treatment of schizophrenia can be classified as either typical (first generation) or atypical (second generation) antipsychotics.

Table 1: Classification of Antipsychotic Drugs and Their Target Symptoms

Class

Drug

Target Symptoms

Phenothiazines (Typical)

Chlorpromazine

Hallucinations

Delusion

Irrational behavior

Fluphenazine

Trifluoperazine

Promethazine

Thioridazine

Butyrophenone (Typical)

Haloperidol

Elevated mood, expansive self-image, grandiose delusion

Droperidol

Atypical Antipsychotic

Risperidone

Hallucinations, delusions

Clozapine

Olanzapine

Note:

  • Drug treatment must be started as soon as possible for better results
  • Acute psychotic symptoms such as hallucination or delusions can be controlled using drugs such as haloperidol or chlorpromazine
  • Positive symptoms tend to respond better to drugs than negative symptoms
  • Treatment for schizophrenia is not curative and long-term maintenance therapy (2-5 years) is usually required to prevent relapse

Haloperidol

Available Preparations:

  • Tablets: 5 mg, 10 mg
  • Injection: 5 mg/ml, 50 mg/ml

Available Brands: Decanoas®, Haldol®, Haloxen®, Haldol

Pharmacokinetics: Haloperidol is relatively well absorbed following oral administration, distributed widely into the body, with high concentrations in adipose tissue. It is metabolized by the liver and excreted in urine and a small amount in feces.

Indications:

  • Schizophrenia
  • Behavior disturbance
  • Nausea and vomiting
  • Mania
  • Severe anxiety
  • Intractable hiccups

Contraindications:

  • CNS depression
  • Comatose states
  • Severe hepatic disease
  • Known hypersensitivity to haloperidol

Dosage:

Oral:

  • Schizophrenia and Other Psychosis, Mania, Psychomotor Agitation, Violent Behavior, and Severe Anxiety (Adjunct):
  1. Adult: Initially 0.5-5 mg 2-3 times daily, increased as needed up to 20 mg/day, maintenance usually 2-10 mg/day
  • Acute Psychosis: 2-10 mg IM 6-8 hourly interval until symptoms are controlled
  • Long-term Therapy: 10-20 mg up to max of 100 mg deep IM of decanoate injection may be given
  • Nausea and Vomiting: 0.5-2 mg daily by IM injection
  • Intractable Hiccups: Orally 0.5 mg 3 times daily, adjusted according to response

IM or Slow IV Injection:

  • Acute Psychosis: 2-10 mg IM 6-8 hourly interval until symptoms are controlled

Side Effects:

  • Dry mouth
  • Weight gain
  • Lethargy
  • Sedation
  • Restlessness or akathisia
  • Constipation
  • Muscle stiffness
  • Hypotension
  • Muscle cramping
  • Blurred vision
  • Increased appetite
  • Tinnitus
  • Swelling of female breasts
  • Depression
  • Decreased sexual function
  • Peripheral edema

Drug Interactions:

  • Alcohol and other CNS depressants may increase CNS depression
  • Rifampicin accelerates the metabolism of haloperidol resulting in reduced plasma concentration
  • Haloperidol enhances the hypotensive effect of prazosin
  • Haloperidol enhances the sedative effect of clonazepam, codeine, and diazepam
  • Carbamazepine accelerates the metabolism of haloperidol
  • Haloperidol may inhibit blood pressure response to centrally acting antihypertensives such as methyldopa
  • Beta blockers may inhibit haloperidol metabolism, increasing plasma levels and toxicity
  • Haloperidol may antagonize the therapeutic effect of bromocriptine on prolactin secretion
  • Haloperidol may inhibit metabolism and increase toxicity of phenytoin

Key Issues to Note:

  • Tardive dyskinesia may occur after prolonged use and may disappear spontaneously or persist for life
  • Protect the drug from light; slight yellowing of the injection is common and does not affect potency
  • Advise the patient to report side effects such as extrapyramidal reactions
  • Elderly patients usually require lower initial doses and a more gradual dosage adjustment
  • The drug is not recommended for children under 3 years because they are prone to extrapyramidal reactions
  • Avoid alcohol and other medications that cause sedation

Drugs Used in the Management of Central Nervous System Disorders Read More »

Endocrine and Metabolic Drugs

Endocrine and Metabolic Drugs

Drugs Used in Diabetes Mellitus

Diabetes mellitus is a chronic disorder characterized by hyperglycemia, altered metabolism of carbohydrates, proteins, and fats, due to insulin deficiency or resistance.

Classification of Diabetes Mellitus

Diabetes mellitus is classified into two:

  • Type 1 diabetes mellitus
  • Type 2 diabetes mellitus

Type 1 Diabetes Mellitus

This type of diabetes is due to autoimmune destruction of the beta cells. It is more common in young children than adults. Patients with type 1 diabetes require exogenous insulin for survival.

Type 2 Diabetes Mellitus

Type 2 diabetes usually presents in obese adults and has a strong family history. It is caused by insulin deficiency and insulin resistance.

Drugs used in the treatment of diabetes mellitus include:

  • Oral antidiabetic drugs
  • Insulin

Oral Antidiabetic Drugs

Oral antidiabetic drugs are used in the treatment of type 2 diabetes mellitus which has not responded to lifestyle modification.

Classification of Oral Antidiabetics

Oral antidiabetics are classified as follows:

  • Sulfonylureas
  • Biguanides
  • Thiazolidinediones
  • Alpha-glucosidase inhibitors
Sulfonylureas

Sulfonylureas are structurally related to sulfonamides. They are divided into generations as follows:

First Generation

  • Tolbutamide
  • Chlorpropamide

Second Generation

  • Glibenclamide
  • Glimepiride
  • Gliclazide
  • Glipizide

Mode of Action

Sulfonylureas act by stimulating insulin secretion from the beta cells of the pancreas, thus increasing insulin levels. Increased insulin secretion results in lowering of blood glucose levels. These drugs are only effective in the presence of functioning beta cells.

Tolbutamide

Available Preparations:

  • Tablets: 500 mg

Pharmacokinetics

Tolbutamide is readily absorbed after oral administration, metabolized in the liver, and excreted in the urine and feces chiefly as metabolites.

Indications

  • Type 2 diabetes mellitus

Contraindications

  • Severe hepatic and renal impairment
  • Presence of ketoacidosis
  • Breastfeeding
  • Pregnancy
  • Porphyria
  • Insulin-dependent diabetes mellitus

Dosage

  • Adult: 500-1500 mg daily in 2 divided doses, max 2 g daily

Side Effects

  • Nausea and vomiting
  • Constipation
  • Dyspepsia
  • Hypoglycemia
  • Headache
  • Diarrhea
  • Skin rash
  • Tinnitus
  • Taste alteration

Drug Interactions

  • Beta-blockers may mask hypoglycemic symptoms caused by tolbutamide
  • Hypoglycemic effect caused by tolbutamide may be reduced by corticosteroids
  • Disulfiram-like reaction may occur when tolbutamide is taken concurrently with alcohol
  • Hypoglycemic effect of tolbutamide may be increased by sulfonamide antibiotics, ranitidine, and cimetidine

Key Issues to Note

  • Tolbutamide should be given with or immediately after food
  • Elderly, debilitated patients, and those with impaired renal or hepatic function usually require a lower initial dose
  • Because of its complete metabolism and short duration of action, it is recommended in the elderly
  • The drug should not be taken at bedtime because of the potential for nocturnal hypoglycemia
  • Avoid alcohol while taking tolbutamide

Glibenclamide

Available Preparations:

  • Tablets: 5 mg

Available Brands: Daonil®, Glibol®, Glibetics®, Euglucon®, Betanase®, Diaben®, Glamide®

Combinations: Duotrol® (Glibenclamide/Metformin) 5/500

Pharmacokinetics

Glibenclamide is reliably and almost completely absorbed when taken orally, metabolized in the liver to weakly active metabolites, and excreted in urine and feces.

Indications

  • Type 2 diabetes mellitus

Contraindications

  • Presence of ketoacidosis
  • Type 1 diabetes mellitus
  • Severe renal and hepatic impairment
  • Pregnancy and breastfeeding
  • Previous hypersensitivity to the drug

Dosage

  • Initially 5 mg in the morning, dose adjusted according to response, max 15 mg/day

Side Effects

  • Headache
  • Weakness
  • Epigastric fullness
  • Hypoglycemia
  • Dizziness
  • Nausea
  • Weight gain
  • Heartburn

Drug Interactions

  • Beta-blockers may mask warning symptoms of hypoglycemia caused by glibenclamide
  • Hypoglycemic effect of glibenclamide is reduced by drugs which are insulin antagonists such as bendrofluazide, oral contraceptives, and glucocorticoids
  • Metformin has a synergistic hypoglycemic action with glibenclamide
  • Alcohol increases the hypoglycemic effect caused by glibenclamide and may also cause disulfiram-like reaction
  • An enhanced hypoglycemic response to glibenclamide may occur when given together with drugs such as aspirin, cimetidine, fluconazole, and ketoconazole

Key Issues to Note

  • Glibenclamide should be given with or 30 minutes before a meal
  • Warn the patient of the possibility of hypoglycemia and advise on how to manage it
  • Encourage the patient to maintain lifestyle modifications
  • Glibenclamide tablets should be stored in a cool, dry place and protected from light
  • Avoid alcohol while taking the drug
Biguanides

Biguanides are the drugs of choice in the treatment of type 2 diabetes mellitus in overweight patients. They do not increase insulin secretion; therefore, they do not usually cause hypoglycemia or weight gain. Metformin is the only available biguanide. It may be combined with a sulfonylurea to provide better glycemic control.

Mode of Action

Biguanides act by decreasing the production of glucose by the liver and also promote the uptake of glucose by tissues.

Metformin

Available Preparations:

  • Tablets: 500 mg, 850 mg, 1000 mg

Available Brands: Glyformin®, Glucophage®, Glucomet®, Metformin-Denk®, Glycomet®, Bigomet®

Combinations:

  • Avandamet® (Rosiglitazone/Metformin) 2/500
  • Pionorm-M® (Pioglitazone/Metformin) 30/500
  • Piosafe-M® (Pioglitazone/Metformin) 15/500

Pharmacokinetics

Metformin is slowly and incompletely absorbed when taken orally. Food delays or decreases the extent of absorption. It is excreted mainly as unchanged drug in urine.

Indications

  • Type 2 diabetes mellitus
  • Polycystic ovary syndrome

Contraindications

  • Pregnancy
  • Hepatic dysfunction
  • Acute metabolic acidosis
  • Pancreatitis
  • Renal dysfunction
  • Breastfeeding

Dosage

  • Initially 500 mg with breakfast for 1 week, then 500 mg with breakfast and evening meal for at least 1 week, then 500 mg with breakfast, lunch, and evening meal, max 2 g daily in divided doses

Side Effects

  • Nausea
  • Anorexia
  • Rash
  • Lactic acidosis
  • Malabsorption of vitamin B12
  • Vomiting
  • Diarrhea
  • Metallic taste
  • Abdominal pain

Drug Interactions

  • There is an increased risk of hypoglycemia when metformin is given with digoxin or furosemide
  • Alcohol increases the risk of lactic acidosis associated with metformin
  • Nifedipine may enhance the absorption of metformin
  • Metformin may interfere with vitamin B12 absorption
  • Cimetidine increases peak metformin blood concentrations

Key Issues to Note

  • Advise the patient not to change or discontinue the drug without consulting the prescriber
  • Avoid alcohol during treatment
  • Advise the patient to take the drug with meals
  • Extended-release tablets should be taken whole without chewing or crushing

Insulin

Insulin is a hormone produced by the beta cells of the pancreatic islets of Langerhans.

It plays an important role in the regulation of carbohydrate, protein, and fat metabolism. Insulin lowers blood glucose by inhibiting glycogenolysis and gluconeogenesis in the liver and stimulates glucose uptake by muscles and adipose tissues.

Insulin is used in the treatment of type 1 diabetes mellitus and is also used in type 2 diabetes mellitus in the following cases:

  • Severe infection
  • Major surgery
  • Ketoacidosis
  • During pregnancy
  • When hyperglycemia does not respond to non-pharmacological measures and oral antidiabetics

Sources of Insulin

Insulin for therapeutic use is extracted from the pancreas of any of the following:

  • Cattle
  • Pig
  • Human

Types of Insulin Preparations

There are 3 main types of insulin preparations which differ in time of onset and duration of action. They include:

  • Short-acting insulin (e.g., insulin soluble) – It is the only insulin that can be given by IV bolus, IV infusion, or IM
  • Intermediate-acting insulin (e.g., insulin zinc suspension – Lente) – Have slower onset of action but with prolonged duration of action. They are formulated to dissolve more gradually when administered
  • Long-acting insulin (e.g., glargine – Lantus) – Has a duration of action of 24 hours

Insulin Administration

Insulin is usually given subcutaneously in the buttock, abdomen, anterior thigh, and dorsal arm. Absorption is usually most rapid from the abdomen, followed by the arm, then the buttock and thigh. The rate of absorption is increased by massage, hot bath, or exercise. The type of insulin used depends on the type of diabetes, patient’s age, and blood glucose levels.

Soluble Insulin

Available Preparations:

  • Injection: 100 IU/ml

Available Brands: Actrapid®

Indications

  • Type 1 diabetes mellitus
  • Diabetic ketoacidosis
  • During pregnancy, surgery, trauma, infections, and fever

Contraindications

  • Hypersensitivity to insulin
  • Hypoglycemia

Dosage

  • Insulin dosage is individualized and determined in accordance with the needs of the patient, usual range 0.3-1 unit/kg/day

Side Effects

  • Hypoglycemia
  • Skin rash
  • Edema
  • Fat hypertrophy at injection site
  • Local reaction
  • Urticaria
  • Abdominal bloating
  • Blurred vision

Drug Interactions

  • Alcohol may increase the effects of insulin
  • Beta-blockers may mask signs and symptoms of hypoglycemia
  • Corticosteroids antagonize effects of insulin and result in increased glucose levels
  • ACE inhibitors may increase the hypoglycemic effect of insulin

Key Issues to Note

  • Advise the patient to watch out for symptoms of hypoglycemia such as fatigue, confusion, headache, hunger, rapid breathing
  • Advise the patient to always carry a quick source of sugar to rectify hypoglycemia when it occurs
  • Injection sites should be rotated to avoid lipodystrophy

Endocrine and Metabolic Drugs Read More »

Drugs Used in the Treatment of Cardiovascular Disorders

Drugs Used in the Treatment of Cardiovascular Disorders

These drugs are used in the treatment of conditions such as:

  • Hypertension
  • Angina pectoris
  • Heart failure
  • Hyperlipidemia
  • Arrhythmias

Drugs Used in the Treatment of Hypertension

Hypertension

Hypertension is the persistent elevation of blood pressure higher than normal (140/90 mmHg).

Common Terms Used in Hypertension

  • Blood Pressure: This is the pressure of blood against the walls of the main arteries.
  • Diastolic Blood Pressure: This is the pressure exerted in the vessels when the ventricles are relaxing and refilling.
  • Systolic Pressure: This is the pressure exerted in the vessels when the ventricles are contracting.
  • Orthostatic Hypotension (Postural Hypotension): This is the decrease in blood pressure that occurs when a person stands erect.
  • Peripheral Vascular Resistance: This is the pressure that blood must overcome as it flows in the vessels.
  • Isolated Systolic Hypertension: This is defined as systolic blood pressure greater than or equal to 140 mmHg with diastolic blood pressure less than 90 mmHg. It is common in elderly patients.
  • Malignant Hypertension: This is a rapidly progressing, potentially fatal form of hypertension with diastolic pressure exceeding 120 mmHg.
  • Hypertensive Emergency: This is characterized by severe elevation in blood pressure > 180/120 mmHg complicated by target organ dysfunction. These situations require immediate reduction of blood pressure to limit target organ damage.
  • Hypertensive Urgency: This is a situation with severe elevation of blood pressure without target organ dysfunction.

Table 1: Stages of Hypertension

Category

Systolic

Diastolic

Normal

< 130

< 80

High Normal (Pre-hypertension)

130-139

81-89

Mild Hypertension (Stage I)

140-159

90-99

Moderate Hypertension (Stage 2)

160-179

100-109

Severe Hypertension (Stage 3)

180-209

110-119

Very Severe Hypertension (Stage 4)

> 209

> 119

Classification of Hypertension

Hypertension may be classified as:

  • Essential (Primary) Hypertension
  • Secondary Hypertension

Essential Hypertension

Essential hypertension is the most common type of hypertension, contributing to over 90% of the cases of hypertension encountered in medical practice. The cause of essential hypertension is not known.

Secondary Hypertension

Secondary hypertension is an elevation of blood pressure due to an identifiable cause such as:

  • Renal disease
  • Drugs like oral contraceptives
  • Pre-eclampsia
  • Renovascular disease

Treatment is directed at elimination of the cause.

Management of Hypertension

Non-Pharmacological Measures

  • Encourage regular exercise (e.g., walking, jogging)
  • Advise the patient to lose weight (if overweight)
  • Advise the patient to limit alcohol intake
  • Advise the patient to restrict salt intake
  • Advise the patient to stop smoking
  • Encourage a diet high in fruits and vegetables
  • Advise the patient to relax and manage stress
  • Diet should be low in saturated fats and cholesterol

Note: Non-pharmacological measures may be employed alone in pre-hypertension or in combination with drugs in mild to severe hypertension.

Drugs used in the treatment of hypertension may be classified as follows:

  • Beta blockers
  • ACE inhibitors
  • Alpha-II blockers
  • Diuretics
  • Centrally acting antihypertensives
  • Calcium channel blockers
  • Angiotensin II antagonists
  • Direct vasodilators

Table 2: Choice of Antihypertensives in Different Conditions

Comorbid Disease

Drugs Recommended

Diabetes mellitus

Calcium channel blockers, ACE inhibitors

Congestive heart failure

Diuretics, ACE inhibitors

Angina pectoris

Beta blockers, calcium channel blockers, ACE inhibitors, and diuretics as alternative

Asthma, chronic pulmonary disease

Calcium channel blockers, diuretics, and ACE inhibitors

Hyperlipidemia

ACE inhibitors, calcium channel blockers

Previous myocardial infarction

Beta blockers, calcium channel blockers, ACE inhibitors, and diuretics

Chronic renal disease

Diuretics, calcium channel blockers, beta blockers, and ACE inhibitors

Beta Blockers

These drugs are recommended in the treatment of hypertension, angina pectoris, and post-myocardial infarction.

Beta blockers are classified as follows:

Non-selective beta blockers

  • Propranolol
  • Sotalol

Selective beta-1 blockers

  • Atenolol
  • Bisoprolol
  • Metoprolol

Alpha and beta blockers

  • Carvedilol
  • Labetalol

Mode of Action

Beta blockers competitively block the response to beta receptors, resulting in a decrease in heart rate and heart contractility, thereby lowering blood pressure.

Atenolol

Available Preparations:

  • Tablets: 25 mg, 50 mg, 100 mg

Available Brands: Tenormin®, Totamol®, Velorin®, Atelor®, Betagard®, Cardinol®, Tensimin®

Combinations:

  • Tenoret® (Atenolol/Chlorthalidone) 50/12.5 mg
  • Tenoretic® (Atenolol/Chlorthalidone) 100/25 mg

Pharmacokinetics

About half of the dose is absorbed following oral administration, crosses the placenta, and is distributed into breast milk. Atenolol undergoes little or no hepatic metabolism and is excreted unchanged in the urine.

Indications

  • Hypertension
  • Angina pectoris
  • Cardiac arrhythmias
  • Prophylaxis in migraine
  • Acute myocardial infarction

Contraindications

  • Hypersensitivity to atenolol
  • Sinus bradycardia
  • Second and third-degree heart block
  • Symptomatic heart failure

Dosage

  • Hypertension: 25-100 mg once daily (100 mg is only slightly better than 50 mg)
  • Angina: 100 mg once daily or 50 mg twice daily
  • Arrhythmias: 50-100 mg daily
  • Migraine Prophylaxis: 50-100 mg daily

Side Effects

  • Fatigue
  • Hypotension
  • Impotence
  • Muscle ache
  • Dizziness
  • Wheezing
  • Insomnia

Drug Interactions

  • Cimetidine may increase atenolol blood concentration
  • Diuretics and other antihypertensives may increase the hypotensive effect of atenolol
  • Atenolol may mask the symptoms of hypoglycemia and prolong the hypoglycemic effect of insulin and oral hypoglycemics
  • NSAIDs may decrease the antihypertensive effects of atenolol
  • Alcohol enhances the hypotensive effect of atenolol
  • Concurrent use with digoxin increases the risk of AV block and bradycardia
  • Oral contraceptives antagonize the hypotensive effect of atenolol
  • Concurrent use with verapamil results in severe hypotension and heart failure

Key Issues to Note

  • Atenolol should be used with caution in patients with diabetes since it may mask symptoms of hypoglycemia
  • Atenolol may be administered with or without food
  • Abrupt withdrawal of the drug should be avoided; it should be discontinued over 1-2 weeks through gradual reduction of the dose
Calcium Channel Blockers

These drugs are used in the treatment of hypertension and angina pectoris and are safe for patients with asthma, hyperlipidemia, diabetes, and renal dysfunction. They are subdivided into two groups:

  • Dihydropyridines

  • Non-dihydropyridines

Dihydropyridines: Drugs in this group produce significant blockage of calcium channels in blood vessels and minimal in the heart.

Examples:

  • Nifedipine
  • Amlodipine
  • Felodipine

Non-Dihydropyridines: These drugs act on vascular smooth muscle and the heart. Since they suppress AV conduction, they are useful in cardiac arrhythmias.

Examples:

  • Verapamil
  • Diltiazem

Mode of Action

Calcium channel blockers decrease the influx of calcium into smooth muscles, thereby reducing vascular tone, which results in a reduction of peripheral resistance and blood pressure.

Nifedipine

Available Preparations:

  • Tablets: 10 mg, 20 mg retard, 30 mg long-acting

Available Brands: Adalat®, Nifelat®, Nifedipine-denk®

Pharmacokinetics

Nifedipine is rapidly and almost completely absorbed from the gastrointestinal tract, but bioavailability is reduced by first-pass metabolism. It is extensively metabolized in the liver and excreted in the urine as inactive metabolites.

Indications

  • Hypertension
  • Prophylaxis of angina pectoris

Contraindications

  • Hypersensitivity to nifedipine
  • Unstable or acute attacks of angina
  • Porphyria
  • Cardiogenic shock

Dosage

The dose and frequency of administration vary depending on the preparations used.

  • Short-acting nifedipine is given 3 times a day
  • Nifedipine retard is given twice daily
  • Long-acting nifedipine is given once daily

Hypertension:

  • Adults: 10-20 mg twice daily, increased to 20-40 mg twice daily (Nifedipine retard)
  • Nifedipine long-acting: 30-90 mg once daily

Angina Pectoris:

  • Nifedipine retard: 10-40 mg twice daily or nifedipine long-acting: 30-90 mg once daily

Side Effects

  • Oedema of ankle
  • Headache
  • Flushing
  • Dizziness
  • Tachycardia
  • Palpitations
  • Impotence
  • Tremors
  • Muscle cramps
  • Dry mouth
  • Constipation
  • Nausea

Drug Interactions

  • Beta blockers may have additive hypotensive effects when given together with nifedipine
  • Nifedipine may increase digoxin blood concentration
  • Nifedipine increases the plasma concentration of digoxin
  • Rifampicin increases the metabolism of nifedipine, leading to reduced plasma concentrations

Key Issues to Note

  • Administer nifedipine with food and swallow sustained-release tablets without chewing
  • Advise the patient to avoid alcohol
  • Advise the patient to rise slowly from a prolonged sitting or lying position
  • Advise the patient not to stop using the drug suddenly
  • Inform the patient that excessive hypotension may occur, especially at the beginning of treatment

Amlodipine

Available Preparations:

  • Tablets: 5 mg, 10 mg
  • Capsules: 5 mg, 2.5 mg

Available Brands: Norvasc®, Amtas®, Asomex®, Amlong®, Lovasc®, Lofral®, Amlodac®, Amedin®

Pharmacokinetics

Amlodipine is well absorbed following oral administration. It is extensively metabolized in the liver and excreted in the urine.

Indications

  • Hypertension
  • Prophylaxis of angina pectoris

Contraindications

  • Unstable angina
  • Known hypersensitivity to amlodipine
  • Breastfeeding

Dosage

  • Hypertension or Angina: Initially 5 mg once daily, increased after 10-14 days to a max of 10 mg once daily if necessary

Side Effects

  • Headache
  • Dizziness
  • Oedema
  • Fatigue
  • Flushes
  • Hypotension
  • Malaise
  • Bradycardia
  • Palpitations
  • Taste disturbances
  • Abdominal pain

Drug Interactions

  • Cimetidine increases serum levels of amlodipine
  • Rifampicin may decrease serum concentrations of amlodipine
  • Erythromycin may reduce clearance of amlodipine
  • Barbiturates reduce plasma concentrations of amlodipine

Key Issues to Note

  • Amlodipine may be administered without regard to food but take with caution with grapefruit juice
  • Inform the patient not to discontinue the drug abruptly
  • Inform the patient to report to the clinician in case of irregular heartbeat, shortness of breath, swelling of the feet and hands, pronounced dizziness, and hypotension
Angiotensin-Converting Enzyme Inhibitors (ACEIs)

These drugs are useful in the treatment of hypertension and heart failure.

Examples:

  • Captopril
  • Enalapril
  • Ramipril
  • Lisinopril
  • Quinapril

Mode of Action

ACE inhibitors act by inhibiting the conversion of angiotensin I to angiotensin II (a powerful vasoconstrictor). This results in relaxation of blood vessels, which lowers blood pressure.

Captopril

Available Preparation:

  • Tablets: 25 mg

Available Brands: Epistron®, Angiopril®

Pharmacokinetics

Captopril is absorbed throughout the GIT, and the presence of food may reduce absorption. It is distributed to body tissues except the CNS, metabolized in the liver, and excreted in the urine and small amounts in feces.

Indications

  • Mild to moderate hypertension
  • Congestive heart failure
  • Diabetic nephropathy
  • Prophylaxis after infarction

Contraindications

  • Hypersensitivity to captopril and other ACE inhibitors
  • Pregnancy
  • Hereditary or idiopathic angioedema
  • Bilateral or single renal artery stenosis

Dosage

  • Hypertension: Initially 12.5 mg twice daily. Maintenance dose: 25 mg twice daily, max 50 mg twice daily in severe hypertension
  • Heart Failure (Adjunct): Initially 6.25-12.5 mg under close supervision. Maintenance dose: 25 mg 2-3 times daily, max 150 mg daily
  • Diabetic Nephropathy: 75-100 mg daily in divided doses

Side Effects

  • Hypotension
  • Chest pain
  • Palpitations
  • Fatigue
  • Non-productive cough
  • Tachycardia
  • Dyspepsia
  • Hyperkalemia
  • Taste disturbances
  • Malaise

Drug Interactions

  • Alcohol, diuretics may increase the effect of captopril
  • NSAIDs may decrease the effect of captopril
  • Potassium-sparing diuretics, potassium supplements may cause hyperkalemia

Key Issues to Note

  • Advise the patient to rise slowly to sitting or standing position to minimize orthostatic hypotension
  • Inform the patient that dizziness, fainting, lightheadedness may occur during the first few days of treatment
  • Advise the patient to take the drug on an empty stomach about one hour before food
  • Captopril should not be administered together with antacids because they hinder its absorption
  • The dose administered and frequency of administration should be reduced in renal impairment
Angiotensin II Receptor Antagonists

These drugs include:

  • Losartan
  • Valsartan
  • Telmisartan

They are normally used as an alternative in patients who cannot tolerate side effects such as dry cough associated with ACE inhibitors.

Mode of Action

They produce a fall in blood pressure by direct antagonism of the vasoconstrictor angiotensin II at the AT1 receptor site.

Losartan

Available Preparations:

  • Tablets: 50 mg, 100 mg

Available Brands: Losacar®, Tozaar®, Losartec®, Losartas®

Combinations:

  • Presartan-H50® (Losartan/Hydrochlorothiazide)
  • Tozaar-H®

Pharmacokinetics

Losartan is readily absorbed from the gastrointestinal tract following oral administration, undergoes first-pass metabolism forming active and inactive metabolites. Losartan is excreted in the urine and feces.

Indications

  • Hypertension
  • Diabetic nephropathy

Contraindications

  • Known hypersensitivity to losartan
  • Pregnancy (2nd and 3rd trimester)
  • Lactation

Dosage

  • Usually 50 mg once daily, increased after several weeks to 100 mg once daily if necessary

Side Effects

  • Dizziness
  • Taste disturbance
  • Myalgia
  • Fatigue
  • Diarrhea
  • Urticaria
  • Vertigo
  • Migraine

Drug Interactions

  • Fluconazole may decrease conversion of losartan to active metabolites resulting in loss of anti-hypertensive effects
  • NSAIDs may reduce the hypotensive effect of losartan
  • Potassium-sparing diuretics may increase the risk of hyperkalemia when given together with losartan
  • Cimetidine may increase the effect of losartan
  • Alcohol may potentiate the hypotensive effect of losartan

Key Issues to Note

  • Avoid tasks that require alertness until response to drug is established (possible dizziness effect)
  • Advise the patient not to take any OTC preparations or nasal decongestants without recommendation of a clinician
  • Advise the patient not to stop taking the medication unless told by the clinician
  • The drug may be taken with or without meals
Direct-Acting Vasodilators

These drugs are rarely used as first-line drugs and are reserved for resistant cases of hypertension and for treatment of hypertensive emergencies. These drugs also cause sodium and water retention; therefore, they are useful when combined with diuretics to counteract the sodium retention. They are also combined with beta blockers to prevent the reflex tachycardia.

Examples:

  • Hydralazine
  • Minoxidil

Mode of Action

Hydralazine reduces blood pressure by acting directly on the arterial smooth muscle to cause vasodilation and reduction in total peripheral vascular resistance.

Hydralazine

Available Preparations:

  • Injection: 20 mg/ml
  • Tablets: 25 mg

Available Brands: Apresoline®

Pharmacokinetics

Orally administered hydralazine is rapidly and completely absorbed from the gastrointestinal tract but undergoes considerable first-pass metabolism in the gastrointestinal mucosa and liver. It is widely distributed, metabolized in the liver by acetylation, and excreted in the urine as metabolites.

Indications

  • Hypertensive crisis
  • Moderate to severe hypertension
  • Moderate to severe chronic congestive heart failure (in combination with long-acting nitrates)
  • Hypertension secondary to pre-eclampsia/eclampsia

Contraindications

  • Known hypersensitivity to hydralazine
  • Severe tachycardia
  • Heart failure with high cardiac output
  • Myocardial insufficiency due to mechanical obstruction
  • Idiopathic systemic lupus erythematosus
  • Porphyria

Dosage

  • Hypertension: By mouth 25 mg twice daily, increased to usual max 50 mg twice daily
  • Heart Failure: 25 mg 3-4 times daily, increased every 2 days if necessary. Maintenance dose: 50-75 mg 4 times daily
  • By Intravenous Infusion, Hypertension with Renal Complications and Hypertensive Crisis: Initially 200-300 micrograms/minute, maintenance 50-150 micrograms/minute

Side Effects

  • Headache
  • Severe tachycardia
  • Hypotension
  • Angina
  • Oedema
  • Heart failure
  • Dizziness
  • Flushing
  • Palpitations
  • Joint swelling
  • Anorexia
  • Gastrointestinal disturbances

Drug Interactions

  • Diuretics, other antihypertensives may increase hypotensive effects of hydralazine
  • Indomethacin may decrease hypotensive effects of hydralazine

Key Issues to Note

  • Prolonged treatment of more than 6 months may induce lupus-like syndrome
  • Beta blockers and thiazides are often used with hydralazine to prevent tachycardia and fluid retention
  • Advise the patient to avoid driving until the effect of the drug is established
Centrally Acting Antihypertensive Drugs

These drugs are effective antihypertensives but are no longer considered drugs of choice as they are less tolerated than other antihypertensives. Methyldopa is a drug of choice in the treatment of hypertension in pregnancy.

Examples:

  • Methyldopa
  • Clonidine

Mode of Action

These drugs reduce blood pressure by acting in the CNS to reduce the activity of the sympathetic nervous system.

Methyldopa

Available Preparations:

  • Tablets: 250 mg

Available Brands: Aldomet®, Medopress®

Pharmacokinetics

Methyldopa is variably absorbed from the gastrointestinal tract when taken orally, crosses the blood-brain barrier, is extensively metabolized in the liver, and excreted in urine.

Indications

  • Hypertension, especially in pregnancy

Contraindications

  • Hypersensitivity to methyldopa
  • Active liver disease
  • Depression
  • Phaeochromocytoma
  • Porphyria

Dosage

  • Adult: Initially 250 mg 2-3 times daily, increased gradually at an interval of at least 2 days until the desired response is obtained, max 3 g daily
  • Elderly: Initially 125 mg twice daily, increased gradually, max 2 g daily

Side Effects

  • Sedation
  • Dry mouth
  • Stomatitis
  • Myalgia
  • Impaired mental acuity
  • Impotence
  • Hemolytic anemia
  • Dizziness
  • Constipation
  • Oedema
  • Postural hypotension
  • Decreased libido
  • Bradycardia

Drug Interactions

  • Enhanced hypotensive effect when methyldopa is given with ACE inhibitors, alcohol, atenolol, or propranolol
  • Methyldopa may impair tolbutamide metabolism, enhancing its hypoglycemic effects
  • Hypotensive effect of methyldopa is antagonized by NSAIDs
  • Hypotensive effect of methyldopa is antagonized by estrogen
  • Oral iron therapy reduces the bioavailability of methyldopa

Key Issues to Note

  • Methyldopa may be administered with or without regard to food
  • Advise the patient to avoid alcohol during treatment
  • Warn the patient that methyldopa may cause drowsiness and impair activities requiring mental alertness
  • Advise the patient to rise slowly from a prolonged sitting or lying position
  • Inform the patient that transient sedation or depression may occur
  • Advise the patient not to stop the drug abruptly
Alpha Adrenoceptor Blocking Drugs

These drugs may be used in combination with other drugs in the treatment of resistant hypertension. In addition to lowering blood pressure, they also improve urinary flow rates in benign prostatic hypertrophy.

Examples:

  • Prazosin
  • Doxazosin
  • Terazosin

Mode of Action

These drugs competitively inhibit postsynaptic alpha receptors, which results in vasodilation of veins and arterioles. This leads to a decrease in total peripheral resistance and blood pressure. They also block alpha receptors in non-vascular smooth muscle (e.g., the bladder neck), where alpha-blockade reduces resistance to urinary flow.

Prazosin

Available Preparations:

  • Tablets: 1 mg, 2 mg, 5 mg

Available Brands: Hypovase®, Minipress®

Pharmacokinetics

Prazosin is well absorbed after oral administration, extensively metabolized in the liver, and excreted in urine.

Indications

  • Hypertension
  • Congestive heart failure
  • Benign prostatic hyperplasia
  • Raynaud’s syndrome

Contraindications

  • Hypersensitivity to quinazolines
  • Congestive heart failure due to mechanical obstruction

Dosage

  • Hypertension: 0.5 mg twice daily, increased to 1 mg 2-3 times daily after 3-7 days, maintenance dose 20 mg daily in 2-3 divided doses
  • Heart Failure: 0.5 mg 2-4 times daily, increased to 4 mg daily in divided doses, maintenance dose 4-20 mg daily in divided doses
  • Benign Prostate Hyperplasia: Initially 0.5 mg twice daily for 3-7 days, maintenance dose 2 mg twice daily
  • Raynaud’s Syndrome: Initially 0.5 mg twice daily, increased if necessary after 3-7 days to the usual maintenance dose 1-2 mg twice daily

Side Effects

  • Headache
  • Dry mouth
  • Drowsiness
  • Oedema
  • Postural hypotension
  • Urinary incontinence
  • Priapism
  • Urinary frequency
  • Weakness
  • Palpitations
  • Nausea
  • Somnolence

Drug Interactions

  • Estrogen, NSAIDs may decrease the effect of prazosin
  • Concomitant use with propranolol or other beta blockers may cause severe hypotension

Key Issues to Note

  • Advise the patient to avoid alcohol
  • Inform the patient that prazosin may cause dizziness or drowsiness and impair the ability to perform activities requiring alertness
  • Advise the patient to rise slowly from sitting or lying position
  • Advise the patient to take the first dose of prazosin at bedtime to avoid dizziness

Drugs for Heart Failure

Heart failure is a clinical syndrome caused by the inability of the heart to pump sufficient blood to meet the metabolic demands of the body. Inadequate perfusion of the tissues leads to a variety of symptoms such as breathlessness, fatigue, and oedema. Drugs used in the treatment of heart failure include:

  • Diuretics

  • Cardiac glycosides

  • ACE inhibitors

  • Beta blockers
Diuretics

Diuretics are the first-line drugs in the treatment of heart failure. They are recommended in all patients with clinical evidence of fluid retention.

Classification of Diuretics

Diuretics are classified as follows:

  • Loop diuretics
  • Thiazide diuretics
  • Potassium-sparing diuretics
  • Carbonic anhydrase inhibitors

Loop Diuretics

Loop diuretics are potent diuretics used in the treatment of moderate to severe heart failure. They may be used alone or in combination with thiazides, especially metolazone, to achieve a profound diuresis.

Examples:

  • Frusemide
  • Bumetanide

Mode of Action

Loop diuretics inhibit reabsorption of sodium chloride from the ascending limb of the loop of Henle.

Frusemide

Available Preparations:

  • Tablets: 40 mg
  • Injection: 20 mg/ml

Available Brands: Lasix®, Agomide®, Frusina®

Pharmacokinetics

Frusemide is well absorbed from the GIT and excreted in the urine and partially metabolized in the liver and feces.

Indications

  • Oedema
  • Hypertension

Contraindications

  • Renal failure with anuria
  • Dehydration
  • Known hypersensitivity to frusemide
  • Hyponatraemia
  • Severe hypokalaemia
  • Severe hypernatraemia
  • Hypercalcaemia
  • Associates with liver cirrhosis

Dosage

Adult:

  • Oedema: Oral, initially 40 mg in the morning, maintenance 20-40 mg, 80 mg or more in resistant oedema
  • Children: 1-3 mg/kg daily, max 40 mg daily

Hypertension: 20-40 mg twice daily

Slow IV/IM: Initially 20-50 mg, increased if necessary in steps of 20 mg, not less than every 2 hours, doses greater than 50 mg by IV infusion only, max 20 mg daily

Side Effects

  • Gout
  • Rash
  • Nausea
  • Hypotension
  • Hypokalaemia
  • Hyponatraemia
  • Hypomagnesaemia
  • Hyperglycaemia
  • Tinnitus
  • Deafness
  • Dehydration
  • Abdominal cramps
  • Diarrhoea or constipation

Drug Interactions

  • Amphotericin B may increase the risk of nephrotoxicity caused by frusemide
  • Frusemide may decrease the effect of anticoagulants
  • Frusemide may increase the risk of lithium toxicity
  • Gentamycin may increase the risk of ototoxicity when given concurrently with frusemide
  • Cephalosporins enhance the nephrotoxicity caused by frusemide
  • Frusemide may increase the risk of digoxin toxicity

Key Issues to Note

  • Frusemide may be administered with food or milk to minimize GI distress
  • Frusemide may cause photosensitivity reactions (e.g., exposure to sunlight may cause severe sunburn)

Thiazide and Related Diuretics

Thiazide diuretics are used in the treatment of mild heart failure and are the diuretics of choice in the treatment of hypertension. They are relatively weak to be used alone in heart failure.

Examples:

  • Bendrofluazide
  • Hydrochlorothiazide
  • Chlorthalidone
  • Metolazone

Mode of Action

They act by inhibiting sodium and chloride reabsorption at proximal sites of the distal convoluted tubule. Excretion of potassium and magnesium is also enhanced, while calcium excretion is diminished.

Bendrofluazide

Available Preparations:

  • Tablets: 5 mg

Available Brands: Aprinox®, Benduric®

Pharmacokinetics

Bendrofluazide is completely absorbed from the gastrointestinal tract, a small percentage is metabolized in the liver, and is excreted unchanged in the urine.

Indications

  • Oedema
  • Hypertension

Contraindications

  • Hypersensitivity to bendrofluazide
  • Refractory hypokalaemia
  • Hyponatraemia
  • Symptomatic hyperuricaemia
  • Hypercalcaemia
  • Addison’s disease

Dosage

  • Oedema: Initially 5-10 mg daily in the morning or on alternate days, maintenance 5-10 mg 1-3 times weekly
  • Hypertension: 2.5 mg daily in the morning, higher doses rarely necessary

Side Effects

  • Gout
  • Fatigue
  • Impotence
  • Hypokalaemia
  • Hyperglycaemia
  • Hyponatraemia
  • Nausea
  • Dizziness
  • Postural hypotension
  • Hypomagnesaemia

Drug Interactions

  • The effects of digoxin may be increased by bendrofluazide
  • NSAIDs may reduce the diuretic effect of bendrofluazide
  • Bendrofluazide may increase lithium levels in the blood

Potassium-Sparing Diuretics

These drugs are relatively weak diuretics as single drugs for heart failure and are not effective for use alone in heart failure. They are used in combination with other diuretics to prevent loss of potassium caused by thiazide or loop diuretics.

Example:

  • Spironolactone

Mode of Action

They inhibit sodium reabsorption in the distal tubule by antagonizing aldosterone. As a result, distal tubule sodium-potassium exchange is reduced.

Spironolactone

Available Preparations:

  • Tablets: 25 mg, 50 mg

Available Brands: Aldactone®

Pharmacokinetics

Spironolactone is well absorbed from the gastrointestinal tract, metabolized in the liver, and excreted in urine and feces.

Indications

  • Liver cirrhosis associated with refractory oedema and ascites
  • Ascites associated with malignancy
  • Oedema in congestive heart failure
  • Nephrotic syndrome
  • Hypertension
  • Primary hyperaldosteronism

Contraindications

  • Pregnancy
  • Hyperkalaemia
  • Addison’s disease
  • Breastfeeding
  • Hyponatraemia
  • Severe renal impairment

Dosage

  • Congestive Heart Failure: 100 mg daily, increased to 400 mg daily in severe cases, maintenance dose 25-200 mg/day
  • Oedema: Initially 100 mg daily, maintenance 25-200 mg daily
  • Hypertension: 25-100 mg once daily
  • Nephrotic Syndrome: 100-200 mg/day

Side Effects

  • Ataxia
  • Nausea and vomiting
  • Confusion
  • Diarrhoea
  • Dehydration
  • Deepening of the voice
  • Menstrual irregularities
  • Hyperkalaemia
  • Hyponatraemia
  • Fever
  • Weakness
  • Headache
  • Impotence
  • Skin rash
  • Drowsiness
  • Renal impairment
  • Gynaecomastia

Drug Interactions

  • Serum concentration of digoxin may be increased when given together with spironolactone
  • NSAIDs may decrease the antihypertensive effects of spironolactone
  • Potassium supplements, ACE inhibitors, angiotensin II antagonists may increase the risk of hyperkalaemia caused by spironolactone
  • Spironolactone may decrease the anticoagulant effect of heparin

Key Issues to Note

  • Spironolactone may be administered with food
  • It may cause drowsiness and impair the ability to perform activities requiring mental alertness

Osmotic Diuretics

These drugs include:

  • Mannitol

Mode of Action

Osmotic diuretics induce diuresis by elevating the osmolarity of the glomerular filtrate, thereby hindering the tubular reabsorption of water. Excretion of sodium and chloride is increased.

Mannitol

Available Preparation:

  • Intravenous infusion: 20%

Pharmacokinetics

Following intravenous infusion, mannitol is excreted rapidly by the kidneys before any significant metabolism can take place in the liver.

Indications

  • Cerebral oedema
  • Acute anuria
  • Acute renal failure due to massive haemorrhage, trauma, shock, and major surgery
  • To promote urinary excretion of toxic substances (e.g., lithium and salicylates)

Contraindications

  • Pulmonary oedema
  • Intracranial bleeding
  • Congestive heart failure
  • Hypersensitivity to mannitol
  • Severe dehydration
  • Renal failure (anuria)

Dosage

  • Cerebral Oedema: By IV infusion 1 g/kg as a 20% solution
  • Diuresis: By IV infusion 50-200 g over 24 hours, preceded by a test dose of 200 mg/kg by slow intravenous injection

Side Effects

  • Oedema
  • Thrombophlebitis
  • Chills
  • Hypotension
  • Headache
  • Fever
  • Thirst
  • Electrolyte imbalance
  • Circulatory overload
  • Nausea and vomiting
  • Increased urinary frequency and urine volume

Drug Interactions

  • Mannitol may increase the risk of digoxin toxicity associated with mannitol-induced hypokalaemia

Hyperlipidaemia

Hyperlipidaemia refers to the presence in the blood of an abnormally high concentration of cholesterol and/or triglycerides in the form of lipoproteins. It may be divided into two:

  • Primary hyperlipidaemia
  • Secondary hyperlipidaemia

Primary hyperlipidaemia is where the raised plasma lipid concentration is the result of a genetic defect. 

Secondary hyperlipidaemia may be due to metabolic problems such as diabetes mellitus, chronic renal failure, excessive alcohol intake, hypothyroidism, etc. 

The main risk is atherosclerosis, in which fatty deposits called atheroma build up in the arteries, restricting and disrupting the flow of blood. The restriction of blood flow may lead to the formation of blood clots resulting in a stroke or heart attack.

Drugs used in the treatment of hyperlipidaemia include:

  • Statins
  • Bile acid binding resins
  • Fibrates
  • Nicotinic acid and its derivatives
  • Others (omega-3)
Statins

Statins include drugs such as:

  • Simvastatin
  • Atorvastatin
  • Fluvastatin
  • Pravastatin

Mode of Action

Statins competitively inhibit 3-hydroxy methylglutaryl co-enzyme (HMG-CoA) reductase enzyme, the rate-limiting enzyme in cholesterol synthesis, especially in the liver.

Atorvastatin

Available Preparations:

  • Tablets: 10 mg, 20 mg

Available Brands: Lipitor®, Atorva®, Atostin®, Lipiget®

Pharmacokinetics

Atorvastatin is rapidly absorbed from the gastrointestinal tract, undergoes first-pass metabolism, is metabolized in the liver, and excreted as metabolites in bile.

Indications

  • Combined or mixed hyperlipidaemia
  • Prevention of cardiovascular events in patients with type 2 diabetes
  • Primary hypercholesterolemia

Contraindications

  • Hypersensitivity to atorvastatin
  • Active liver disease
  • Pregnancy
  • Lactation

Dosage

  • Adults: Initially 10 mg daily, adjusted according to response at intervals of 4 weeks to 40 mg/day max
  • Children (10-17 years): 10 mg once daily
  • Prevention of Cardiovascular Events: 10 mg once daily

Side Effects

  • Insomnia
  • Weight gain
  • Back pain
  • Nausea
  • Skin rash
  • Impotence
  • Anorexia
  • Dizziness
  • Chest pain
  • Malaise
  • Headache
  • Muscle pain or weakness
  • Tinnitus
  • Peripheral neuropathy
  • Angina

Drug Interactions

  • Atorvastatin may increase the anticoagulant effect of warfarin, digoxin, itraconazole, oral contraceptives
  • May increase atorvastatin blood concentration resulting in severe muscle inflammation, pain, and weakness
  • Antacids and propranolol decrease atorvastatin activity
  • Clarithromycin and erythromycin elevate plasma concentrations of atorvastatin

Key Issues to Note

  • Take atorvastatin with or without regard to meals but preferably in the evening
  • Advise the patient to report symptoms of myalgia, muscle tenderness, weakness, or gastric upset
  • Female patients of childbearing age should be advised to use effective contraception

Blood and Blood Forming Organs

Anticoagulants

These are drugs that prevent the clotting of blood. Anticoagulants help to maintain normal blood flow in people who are at risk of clot formation. They can either prevent the formation of blood clots or stabilize an existing clot so that it does not break.

Anticoagulants are divided into two categories:

  • Parenteral anticoagulants
  • Oral anticoagulants

Parenteral Anticoagulants

These drugs are normally used when immediate action is required.

Examples:

  • Heparin
  • Enoxaparin (low molecular weight heparin)

Heparin

Available Preparations:

  • Injection: 5000 IU/ml

Available Brands: Cal-heparin®, Heparen®

Pharmacokinetics: After intravenous or subcutaneous injection, the onset of action is immediate, within 1-2 hours. Heparin is extensively bound to plasma proteins and is excreted in the urine mainly as metabolites.

Indications:

  • Deep vein thrombosis
  • Pulmonary embolism
  • Prophylaxis in general and gynecological surgery
  • Prophylaxis in orthopedic surgery
  • Myocardial infarction
  • Unstable angina

Contraindications:

  • Hemophilia
  • Severe hypertension
  • Recent eye surgery
  • Peptic ulcers
  • Known hypersensitivity to heparin
  • Acute bacterial endocarditis
  • Thrombocytopenia
  • Severe liver disease

Dosage:

Deep Venous Thrombosis, Pulmonary Embolism, and Unstable Angina:

  • Adults: By IV injection, loading dose of 5000 units (10,000 units in severe pulmonary embolism), followed by continuous infusion of 18 units/kg/hour or by SC injection of 15,000 units every 12 hours.
  • Children and small adults: Loading dose 50 units/kg, then 15-25 units/kg/hour by intravenous infusion or subcutaneous injection of 250 units/kg every 12 hours.

Side Effects:

  • Hemorrhage
  • Hyperkalemia
  • Chills
  • Epistaxis
  • Thrombocytopenia
  • Anaphylaxis
  • Headache
  • Nausea and vomiting
  • Urticaria

Drug Interactions:

  • Heparin increases the risk of hemorrhage when given together with oral anticoagulants like warfarin.

Key Issues to Note:

  • Advise the patient to report any signs of bleeding from the gums, under the skin, urine, or stool.
  • Advise the patient to limit alcohol intake during treatment.
  • Do not administer IM due to pain, irritation, and hematoma formation.
  • When given together with oral anticoagulants, heparin should be withdrawn once effective oral anticoagulation is established.

Oral Anticoagulants

Oral anticoagulants are effective in the primary and secondary prevention of venous thromboembolism.

Examples:

  • Warfarin

Warfarin

Available Preparations:

  • Tablets: 3 mg, 5 mg

Available Brands: Marevan®

Pharmacokinetics: Warfarin is readily absorbed from the gastrointestinal tract, crosses the placenta but does not occur in significant quantities in breast milk. It is extensively metabolized in the liver and excreted in urine and bile.

Indications:

  • Prophylaxis of embolism in rheumatic heart disease and atrial fibrillation
  • Prophylaxis after insertion of prosthetic heart valve
  • Prophylaxis and treatment of venous thrombosis and pulmonary embolism
  • Myocardial infarction

Contraindications:

  • Hypersensitivity to the drug
  • Peptic ulcer
  • Severe hypertension
  • Bacterial endocarditis
  • Pregnancy
  • Alcoholism
  • Bleeding disorders

Dosage:

  • Initially 5 mg daily for 2-5 days, then adjust according to response to the usual maintenance dose of 3-9 mg daily.

Side Effects:

  • Hemorrhage
  • Rash
  • Jaundice
  • Hepatic dysfunction
  • Vomiting
  • Skin rash
  • Nausea and vomiting
  • Hypersensitivity
  • Diarrhea
  • Headache
  • Pancreatitis
  • Urticaria
  • Abdominal cramps

Drug Interactions:

  • Drugs that decrease warfarin anticoagulant effect include alcohol, carbamazepine, phenytoin, cholestyramine, rifampicin, oral contraceptives, and vitamin K.
  • Concomitant use with amiodarone, metronidazole, cimetidine, and streptokinase may increase the anticoagulant effect of warfarin.

Key Issues to Note:

  • Warn the patient that bleeding may occur, especially at the beginning of treatment and with high doses.
  • Warfarin may be administered on an empty or full stomach.
  • Adequate anticoagulation is not observed until about 3-4 days after initial administration of warfarin; heparin should be used concurrently if immediate effect is required.
Antiplatelet Drugs

Antiplatelet drugs inhibit thrombus formation by decreasing platelet aggregation. They are used to prevent further thromboembolic events in patients who have suffered myocardial infarction, ischemic stroke or transient ischemic attacks, or unstable angina.

Examples:

  • Aspirin (low dose)
  • Clopidogrel
  • Dipyridamole

Aspirin

Available Preparations:

  • Tablets: 75 mg, 100 mg

Available Brands: Ecorin®, Aspirem®, Ascard®, Bayer Aspirin Cardio®

Indications:

  • Acute myocardial infarction
  • Unstable angina
  • Primary and secondary prevention of stroke

Contraindications:

  • Children and adolescents under 16 years
  • Hypersensitivity to aspirin or NSAIDs
  • Aspirin-sensitive asthma
  • Active peptic ulcer
  • Breastfeeding
  • Hemophilia

Dosage:

  • 75 mg daily. 150-300 mg daily may be required in acute conditions (MI, acute ischemic stroke, unstable angina).

Side Effects:

  • Bronchospasms
  • Nausea and vomiting
  • Increased bleeding time
  • Urticaria
  • Ringing in the ears
  • Dizziness
  • Heartburn
  • Gastrointestinal bleeding

Drug Interactions:

  • Aspirin increases the risk of bleeding when given together with oral anticoagulants and heparin.
  • Aspirin decreases the diuretic effect of spironolactone and frusemide.
  • Aspirin decreases the antihypertensive effect of captopril and beta-blockers.

Key Issues to Note:

  • The drug should be administered with food.
  • Avoid alcohol while taking aspirin.
  • Avoid use of OTC preparations for pain without recommendation of a clinician.
Thrombolytics

Thrombolytics are drugs used to break up or dissolve blood clots that have already formed. Thrombolytic enzymes are used to lyse the thrombi that obstruct coronary or pulmonary arteries.

Examples:

  • Streptokinase
  • Urokinase

Mode of Action: They act by converting plasminogen to plasmin, which catalyzes the breakdown of fibrin and therefore is able to dissolve blood clots.

Streptokinase

Available Preparations:

  • Injection: 1,500,000 IU

Available Brands: Stpase®

Indications:

  • Acute myocardial infarction
  • Deep vein thrombosis
  • Pulmonary embolism
  • Acute arterial thromboembolism

Contraindications:

  • Active internal bleeding
  • Recent trauma to the head
  • Severe uncontrollable hypertension
  • Uncontrollable clotting disorders
  • Intracranial surgery
  • Recent cerebral vascular accident
  • Severe allergic reactions
  • Recent abortion or delivery

Dosage:

  • Myocardial Infarction: IV infusion 1,500,000 units over 30-60 minutes.
  • Deep Vein Thrombosis, Pulmonary Embolism, Acute Arterial Thromboembolism, Arterial Thrombosis: By IV infusion 250,000 units infused over 30 minutes, then 100,000 units/hour for up to 12-72 hours according to the patient’s condition.

Side Effects:

  • Fever
  • Headache
  • Skin rash and itching
  • Vomiting
  • Convulsions
  • Nausea
  • Nephritis
  • Hypotension
  • Malaise
  • Superficial bleeding at puncture site

Drug Interactions:

  • Heparin, oral anticoagulants, aspirin, dipyridamole may increase the risk of bleeding when given together with streptokinase.
Antifibrinolytic Drugs

These drugs inhibit the dissolution of blood clots.

Examples:

  • Tranexamic acid

Tranexamic Acid

Available Preparations:

  • Tablets/Capsules: 500 mg

Available Brands: Tranlok®, Hemsamic®

Combinations: Tranfib-MF® (tranexamic acid/mefenamic acid) 500/250

Mode of Action: Tranexamic acid acts primarily by blocking the binding of plasminogen and plasmin to fibrin.

Pharmacokinetics: Tranexamic acid is rapidly and completely absorbed from the GIT, crosses the placenta, distributes into breast milk. It is metabolized in the liver and excreted in urine.

Indications:

  • Menorrhagia
  • Prevention of bleeding in prostatectomy and dental extraction in patients with hemophilia
  • Epistaxis
  • Thrombolytic overdose
  • Prophylaxis of hereditary angioedema

Contraindications:

  • Hypersensitivity to tranexamic acid
  • Severe renal impairment
  • Thromboembolic disease

Dosage:

Oral:

  • Menorrhagia (inhibited when menstruation has started): 1 g 3 times daily for 3-4 days
  • Hereditary Angioedema: 1-1.5 g 2-3 times daily
  • Epistaxis: 1 g 3 times daily for 7 days

Side Effects:

  • Nausea
  • Diarrhea
  • Thrombosis
  • Vomiting
  • Hypotension
  • Disturbances in color vision

Drug Interactions:

  • Heparin, oral anticoagulants, aspirin, dipyridamole may increase the risk of bleeding when given together with tranexamic acid.

Drugs Used in the Treatment of Anaemia

Anaemia is defined as a decrease in hemoglobin concentration below that necessary for tissue oxygenation. It may be caused by increased RBC loss, decreased production of RBCs, or increased destruction of RBCs.

Ferrous Sulphate

Available Preparations:

  • Tablets: 200 mg

Available Brands: Cyano Iron®, Ferol®

Indications:

  • Iron deficiency anaemia

Contraindications:

  • Haemolytic anaemias
  • Peptic ulcer disease
  • Patients receiving blood transfusion
  • Hemosiderosis
  • Haemochromatosis

Dosage:

  • Iron Deficiency Anaemia: 200 mg 2-3 times daily
  • Prophylaxis of Anaemia: 200 mg daily

Side Effects:

  • Constipation
  • Diarrhea
  • Anorexia
  • Epigastric pain
  • Dark stool
  • Gastrointestinal irritation
  • Nausea

Drug Interactions:

  • Antacids and cimetidine decrease the absorption of ferrous sulphate
  • Chloramphenicol may increase the serum levels of ferrous sulphate
  • Ferrous sulphate decreases the anti-infective effect of quinolones when given concurrently
  • The drug may be given with meals

Folic Acid

Available Preparations:

  • Tablets: 5 mg

Available Brands: Folacid®, Asflic®, Folon®

Pharmacokinetics: Folic acid is rapidly absorbed from the gastrointestinal tract, distributed to all body tissues, metabolized in the liver to the active form, and excreted in urine.

Indications:

  • Folate-deficient megaloblastic anaemia
  • Prophylaxis in chronic hemolytic states or renal dialysis
  • Prevention of neural tube defects in pregnancy
  • Nutritional supplement

Contraindications:

  • Folate-dependent malignant disease
  • Aplastic anaemia
  • Hypersensitivity to folic acid

Dosage:

  • Megaloblastic Anaemia: 5 mg once daily for 4 months, up to 15 mg daily may be given in malabsorption states
  • Prevention of Neural Tube Defect: 400 micrograms daily before conception and during the first 12 weeks of pregnancy
  • Prevention of Recurrence of Neural Tube Defect: 5 mg daily from at least 4 weeks before conception until 12 weeks of pregnancy
  • Children (Folic Acid Deficiency): 1-2 mg daily

Side Effects:

  • Nausea
  • Headache
  • Insomnia
  • Irritability
  • Skin rash
  • Fever
  • Diarrhea
  • Bronchospasm

Drug Interactions:

  • Folic acid may decrease serum phenytoin concentrations
  • Antifolate drugs such as trimethoprim may interfere with folic acid metabolism and may cause deficiency in patients with low folic acid stores
  • Chloramphenicol may antagonize the hematologic response to folic acid

Combination Preparations: Ferrous Salts with Folic Acid

Available Preparations:

  • Capsules
  • Suscaps
  • Tablets

Available Brands: Aktiferrin-F®, Fefol®, Fef®, Fefan®

Indications:

  • Prevention of iron and folic acid deficiencies in pregnancy, after delivery, and lactation

Contraindications:

  • Known hypersensitivity to any of the ingredients

Dosage:

  • One capsule/suscap/tablet once daily

Side Effects:

  • Sensation of fullness
  • Nausea and vomiting
  • Diarrhea
  • Constipation

Drugs Used in the Treatment of Cardiovascular Disorders Read More »

Drugs Acting on the Respiratory System

Drugs Acting on the Respiratory System

Drugs used in the treatment of respiratory tract disorders include:

  • Drugs for Asthma
  • Drugs for Allergic Rhinitis
  • Drugs for Cough
  • Drugs for Common Cold and Flu

Drugs Used in the Treatment of Asthma

Asthma is a chronic disease of the airways characterized by inflammation and reversible bronchospasm. It is associated with symptoms such as wheezing, breathlessness, chest tightness, and cough. Drugs used in the treatment of asthma are broadly divided into two categories:

  • Bronchodilators
  • Anti-inflammatory drugs

Table 1: Classification of Anti-Asthmatic Drugs

Class

Examples

Bronchodilators

Beta2 agonists, Xanthine derivatives, Anticholinergics

Anti-inflammatory drugs

Corticosteroids, Mast cell stabilizers, Leukotriene receptor antagonists

Beta2 Agonists

Beta2 agonists promote bronchodilation by stimulating beta2 receptors in bronchial smooth muscles. They are further divided into short-acting and long-acting beta2 agonists.

  • Short-acting beta2 agonists such as salbutamol and terbutaline have a rapid onset and short duration of action. They are recommended for the treatment of acute asthma attacks.
  • Long-acting beta2 agonists such as salmeterol and formoterol have a delayed onset and long duration of action. These drugs are usually combined with inhaled corticosteroids such as budesonide for the long-term control of chronic asthma.

Salbutamol

Available Preparations:

  • Inhaler: 100 mcg
  • Nebulized solution: 5 mg/ml
  • Syrup: 2 mg/5 ml
  • Tablets: 4 mg

Available Brands: Ventolin®, Vental®, Kamvent®

Pharmacokinetics: Salbutamol is readily absorbed from the gastrointestinal tract, metabolized in the liver, rapidly excreted in the urine as metabolites and as unchanged drug, and a small amount is excreted in the feces.

Indications:

  • Prophylaxis and treatment of asthma
  • Chronic obstructive pulmonary disease
  • Arrest premature labor

Contraindications:

  • Hypersensitivity to salbutamol
  • Eclampsia and severe preeclampsia

Dosage:

Oral:

Adults: 4 mg 3-4 times daily, max single dose 8 mg

Children:

  • 7-12 years: 2 mg 3-4 times daily
  • 2-6 years: 1-2 mg 3-4 times daily
  • 1 month-2 years: 100 mcg/kg 3-4 times daily

Aerosol Inhalation:

  • Adults: 100-200 mcg (1-2 puffs, for persistent symptoms up to 4 times daily)
  • Children: 100 mcg (1 puff), increased to 200 mcg (2 puffs) if necessary, for persistent symptoms up to 4 times daily

Nebulized Solution:

  • Children: > 2 years: 2.5-5 mg, repeat 3-4 times daily as necessary
  • Children: < 2 years: 0.1 mg/kg up to 2.5 mg, repeat 3-4 times daily

Prophylaxis in Exercise-Induced Bronchospasm:

  • Adults: 200-400 mcg (2 puffs)
  • Children: 100-200 mcg up to 4 times daily

Side Effects:

  • Tachycardia
  • Arrhythmias
  • Nervousness
  • Angioedema
  • Fine tremor, especially of hands
  • Hypersensitivity reactions
  • Palpitations
  • Insomnia
  • Muscle cramps
  • Headache

Drug Interactions:

  • Diuretics or digoxin: risk of cardiac arrhythmias is increased
  • Corticosteroids: risk of hypokalemia and hyperglycemia is increased

Key Issues to Note:

  • Salbutamol may delay labor in pregnant mothers near term
  • Patients should swallow tablets whole with a glass of water
  • Do not administer salbutamol within 1 hour of ingesting antacids, milk, or dairy products
  • Salbutamide is habit-forming; therefore, long-term use may result in laxative dependency and loss of normal bowel function
  • Onset of action is 6-12 hours for tablets, 15-60 minutes for suppository
  • Warn the patient that prolonged use of salbutamol suppositories may cause proctitis
Xanthines

Xanthines include:

  • Aminophylline
  • Theophylline

They act by relaxing bronchial smooth muscle by inhibiting phosphodiesterase, the enzyme which breaks down cyclic AMP. Aminophylline is usually preferred to theophylline when greater solubility in water is required, particularly in intravenous formulations.

Aminophylline

Available Preparations:

  • Tablets: 100 mg
  • Injection: 250 mg/10 ml

Indications:

  • Acute severe asthma
  • Reversible airway obstruction
  • Relieve apnea in neonates
  • Nocturnal asthma

Contraindications:

  • Porphyria
  • Known hypersensitivity to aminophylline

Dosage:

Chronic Asthma:

  • Oral: 100-200 mg 3-4 times daily, after food

Acute Severe Asthma (not treated with theophylline before):

Adults: IV loading dose 5-6 mg/kg slowly over 20-30 min diluted in normal saline or dextrose 5%

Maintenance: IV infusion 0.5 mg/kg/hour

Children: IV loading dose 4-6 mg/kg slowly over 20-30 min suitably diluted and 1.5-2.5 mg per kg in those using oral theophylline

Maintenance: By IV infusion

  • 6 months-9 years: 1 mg/kg/hour
  • 10-16 years: 0.8 mg/kg/hour

Side Effects:

  • Restlessness
  • Anxiety
  • Palpitations
  • Insomnia
  • Convulsions
  • Urticaria
  • Gastrointestinal irritation
  • Hypotension, especially if given by rapid injection
  • Tremor
  • Headache
  • Dizziness
  • Arrhythmias
  • Epigastric pain

Drug Interactions:

  • Beta blockers: may decrease the effects of aminophylline
  • Cimetidine, ciprofloxacin, erythromycin, norfloxacin: may increase aminophylline blood concentration and risk of aminophylline toxicity
  • Phenytoin, rifampicin, carbamazepine: may increase aminophylline metabolism
  • Smoking: may decrease aminophylline blood concentration
  • Caffeine: may intensify the adverse effects of aminophylline on the CNS and heart

Key Issues to Note:

  • Rapid IV injection should be avoided as it may result in hypotension, seizures, and arrhythmias (less than 20-25 mg/min) is required
  • Patients taking oral aminophylline should not receive intravenous aminophylline unless plasma concentration is available to guide dosage
  • Patients should avoid caffeine-containing beverages and other sources of caffeine
Corticosteroids

Corticosteroids may be given parenterally, orally, or as inhalers. Inhaled corticosteroids include:

  • Beclomethasone
  • Budesonide
  • Fluticasone

These drugs are the most effective in the treatment of chronic asthma. Corticosteroids reduce bronchial mucosal inflammation and bronchial hyper-reactivity. They are recommended for the prophylaxis of asthma in patients who have not responded to beta2 agonists or if symptoms disturb sleep more than once a week. Corticosteroid inhalers must be used regularly for effective control of symptoms. Alleviation of symptoms usually occurs after 7 days of initiating treatment.

Beclomethasone

Available Preparations:

  • Metered Inhaler: 50 mcg

Available Brands: Becotide®, Beclate®

Indications:

  • Prophylaxis of asthma

Contraindications:

  • Status asthmaticus
  • Hypersensitivity to beclomethasone
  • Acute infections uncontrolled by antimicrobial chemotherapy

Dosage:

  • Adults: 200 mcg twice daily or 100 mcg 3-4 times daily
  • Children: 50-100 mcg 2-4 times daily or 100 mcg twice daily

Side Effects:

  • Oropharyngeal candidiasis
  • Hoarseness
  • Paradoxical bronchospasm
  • Adrenal suppression
  • Impaired bone metabolism
  • Glaucoma and cataracts

Systemic Corticosteroids

These drugs are given either orally or by injection. Examples include:

  • Prednisolone/Prednisone
  • Betamethasone
  • Triamcinolone
  • Hydrocortisone
  • Dexamethasone
  • Methylprednisolone

Table 2: Characteristics of Corticosteroids

Class

Examples

Short-acting

Hydrocortisone

Intermediate-acting

Prednisolone, Prednisone, Methylprednisolone, Triamcinolone

Long-acting

Dexamethasone, Betamethasone

Prednisolone

Available Preparations:

  • Tablets: 5 mg

Available Brands: Kampred®

Indications:

  • Bronchial asthma
  • Cerebral edema
  • Allergic reactions
  • Acute leukemia
  • Rheumatic disease
  • Inflammatory bowel disease
  • Suppression of inflammatory reactions
  • Acute or chronic adrenal insufficiency

Contraindications:

  • Systemic infection (unless life-threatening)
  • Avoid live virus vaccines
  • Hypersensitivity to prednisolone

Dosage:

  1. Initially: 10-20 mg daily (up to 60 mg in severe diseases) preferably taken in the morning after breakfast, and often be reduced within a few days but may need to be continued for several weeks or months
  2. Maintenance: 2.5-15 mg daily but higher doses may be needed
  3. Children:
  • 1-6 years: 5 mg daily up to 15 mg in severe cases
  • 7-12 years: 5-10 mg daily up to 30 mg in severe cases

Side Effects:

  • Dyspepsia
  • Osteoporosis
  • Glaucoma
  • Skin atrophy
  • Weight gain
  • Menstrual irregularities
  • Peptic ulcer
  • Increased appetite
  • Acne
  • Adrenal suppression
  • Striae

Drug Interactions:

  • Prednisolone may decrease the effect of diuretics, insulin, oral antidiabetics, and potassium supplements
  • Prednisolone may increase the risk of digoxin toxicity caused by hypokalemia
  • Prednisolone may decrease the patient’s antibody response to vaccines

Key Issues to Note:

  • Take the drug after meals, with food or milk to decrease GI upset
  • Advise the patient to avoid alcohol, limit caffeine
  • Advise the patient not to decrease the dose or discontinue without doctor’s approval

Dexamethasone

Available Preparations:

  • Tablets: 0.5 mg
  • Injection: 4 mg/ml

Available Brands: Dexona®

Pharmacokinetics: Dexamethasone is readily absorbed from the gastrointestinal tract, crosses the placenta with minimal inactivation, and is excreted in urine within 24 hours.

Indications:

  • Cerebral edema
  • Rheumatic diseases
  • Anaphylaxis
  • Septic shock
  • Nausea and vomiting due to anti-cancer drugs
  • Bacterial meningitis (in combination with antibiotics)
  • Acute exacerbation of chronic allergic disorders

Contraindications:

  • Hypersensitivity to dexamethasone
  • Systemic infections
  • Avoid live virus vaccines

Dosage:

Oral:

  • Adults: 0.5-2 mg daily but higher doses may be required depending on the severity of the condition
  • Children: 100-1000 mcg/kg daily in 1-2 divided doses

Injection:

  • Adults: 1M or slow IV or infusion: 0.5-24 mg daily
  • Children: 200-400 mcg/kg daily in 1-2 divided doses

Cerebral Edema Associated with Malignancy:

  • IV injection (as dexamethasone phosphate): initially 10 mg then 4 mg by IM every 6 hours for 2-4 days gradually reduced and stopped over 5-7 days
  • Children: IV 0.25 mg/kg/day in divided doses for up to 2 days then gradually taper down over the next 5 days

Side Effects:

  • Hypertension
  • Hyperglycemia
  • Edema
  • Glaucoma
  • Weight gain
  • Growth suppression in children
  • Increased appetite
  • Muscle atrophy
  • Cataracts
  • Peptic ulcer
  • Hypokalemia

Drug Interactions:

  • Increased risk of hypokalemia when used concurrently with amphotericin B or loop diuretics
  • Concurrent use with aspirin may lead to increased gastrointestinal tract side effects

Key Issues to Note:

  • Administer the drug with food or milk to minimize GI side effects
  • Advise the patient to avoid alcohol and limit caffeine intake
  • Advise the patient to avoid exposure to measles or chickenpox
  • Inform the patient not to decrease the dose or stop treatment without doctor’s recommendation

Hydrocortisone

Available Preparations:

  • Injection: 100 mg

Available Brands: Cardilan®, Primacort®, Stricort®

Indications:

  • Hypersensitivity reactions including anaphylaxis
  • Inflammatory bowel disease
  • Asthmatic attack
  • Hemorrhoids
  • Rheumatic diseases
  • Adrenocortical insufficiency
  • Angioedema

Contraindications:

  • Systemic infections
  • Avoid live virus vaccines in those receiving immunosuppressive doses
  • Hypersensitivity to hydrocortisone

Dosage:

Anaphylaxis; Acute Severe Asthma and Shock:

IV slow IV injection or infusion:

Adults: 100-500 mg 3-4 times daily

Children:

  • 6-12 years: 100 mg 3-4 times daily
  • 1-5 years: 50 mg 3-4 times daily
  • Up to 1 year: 25 mg 3-4 times daily

Side Effects:

  • Dyspepsia
  • Adrenal suppression
  • Weight gain
  • Glaucoma
  • Nausea
  • Peptic ulceration
  • Menstrual irregularities
  • Increased appetite
  • Acne
  • Malaise

Drug Interactions:

  • Anti-convulsants, rifampicin: reduce the effectiveness of hydrocortisone
  • Hydrocortisone: reduces the action of antidiabetic drugs
  • Hydrocortisone: reduces the effect of antihypertensive drugs
  • Hydrocortisone: may decrease the patient’s antibody response to vaccines, increase vaccine side effects, and potentiate virus replication when given with live virus vaccine
Leukotriene Receptor Antagonists

This class includes:

  • Zafirlukast
  • Montelukast

These drugs act by suppressing the effects of leukotrienes, compounds that promote bronchoconstriction as well as eosinophil infiltration, mucus production, and airway edema.

Zafirlukast

Available Preparations:

  • Tablets: 20 mg

Available Brands: Accolate®

Pharmacokinetics: Zafirlukast is rapidly absorbed after oral administration, extensively metabolized in the liver, and excreted in feces.

Indications:

  • Prophylaxis of asthma
  • Exercise-induced asthma

Contraindications:

  • Hypersensitivity to zafirlukast
  • Breastfeeding
  • Hepatic impairment

Dosage:

  • Adults: 20 mg twice daily at least 1 hour before or 2 hours after meals
  • Children under 12 years: Not recommended

Side Effects:

  • Headache
  • Diarrhea
  • Insomnia
  • Dyspepsia
  • Dizziness
  • Nausea
  • Fever
  • Malaise
  • Vomiting
  • Abdominal pain

Drug Interactions:

  • Blood levels are increased by aspirin
  • Blood levels are decreased by erythromycin and theophylline
  • Zafirlukast increases the effects and risk of bleeding with warfarin

Key Issues to Note:

  • Give the drug at least 1 hour before or 2 hours after a meal
  • Advise the patient to take the drug as prescribed even during symptom-free periods
  • Do not use the drug to treat acute episodes of asthma
  • Advise the patient not to decrease the dose or stop unless instructed by the doctor
  • Nursing women should not take zafirlukast
  • Inform the patient to report symptoms such as abdominal pain, nausea, fatigue, itching, or anorexia

Drugs for Allergic Rhinitis

Rhinitis is an inflammation of the nasal mucous membrane and is characterized by periods of nasal discharge, sneezing, and nasal congestion. 

Rhinitis may be allergic or non-allergic in origin.

Allergic Rhinitis

Allergic rhinitis is defined as a nasal mucous membrane inflammation caused by a hypersensitivity response to foreign allergens mediated by IgE antibodies.

Drugs used in the treatment of allergic rhinitis include:

  • Antihistamines
  • Decongestants
  • Corticosteroids
  • Mast cell stabilizers

Antihistamines

Antihistamines are the mainstay in the treatment of seasonal and perennial allergic rhinitis. They relieve symptoms such as rhinorrhea, edema, nasal itching, sneezing, and ocular symptoms such as conjunctivitis. They are more effective when taken before the start of symptoms.

Classification of Antihistamines

Antihistamines are classified as follows:

  1. Sedating antihistamines
  2. Non-sedating antihistamines

Sedating Antihistamines

They are also called first-generation antihistamines. Sedating antihistamines cross the blood-brain barrier and are associated with marked sedation and depression.

Examples:

  • Chlorpheniramine
  • Hydroxyzine
  • Promethazine
  • Cyproheptadine

Chlorpheniramine

Available Preparations:

  • Tablets: 4 mg
  • Syrup: 2 mg/5 ml

Available Brands: Piriton®, Piton®

Pharmacokinetics: Chlorpheniramine is well absorbed following oral administration, distributed to body tissues, including the placenta. It is metabolized in the liver and excreted in urine.

Indications:

  • Conjunctivitis
  • Allergic rhinitis
  • Pruritus of allergic origin
  • Acute urticaria
  • Insect stings
  • Severe angioedema

Contraindications:

  • Hypersensitivity to chlorpheniramine
  • Acute attack of asthma
  • Third trimester of pregnancy
  • Breastfeeding
  • Narrow-angle glaucoma

Dosage:

Adults and Children over 12 years: 4 mg every 4-6 hours

Children:

  • 6-12 years: 2 mg every 4-6 hours
  • 1-5 years: 1 mg 3 times daily
  • 6 months-12 months: 1 mg twice daily

Side Effects:

  • Drowsiness
  • Dizziness
  • Epigastric pain
  • Headache
  • Palpitations
  • CNS depression
  • Urinary retention
  • Dry mouth
  • Blurred vision
  • Sweating
  • Tremor

Drug Interactions:

  • Chlorpheniramine potentiates sedative effects of barbiturates, hypnotics, opioid analgesics
  • Increased sedative effects with alcohol

Key Issues to Note:

  • Advise the patient to take the drug after food to minimize GI distress
  • Inform the patient that chlorpheniramine may cause drowsiness and impair the ability to perform activities requiring mental alertness
  • Advise the patient to avoid direct exposure to sunlight since it may cause severe sunburn
  • Avoid alcohol while taking chlorpheniramine

Non-Sedating Antihistamines

Non-sedating antihistamines are less sedating than the first generation.

Examples:

  • Cetirizine
  • Loratadine
  • Desloratadine
  • Levocetirizine
  • Ebastine

Cetirizine

Available Preparations:

  • Tablets: 10 mg
  • Syrup: 5 mg/5 ml

Available Brands: Zyrtec®, Finallergy®, Zyncet®, Allercet®, Alerid®

Pharmacokinetics: Cetirizine is rapidly and almost completely absorbed from the GIT, undergoes slow first-pass metabolism, and is excreted in urine primarily as unchanged drug.

Indications:

Symptomatic relief of allergy such as:

  • Allergic rhinitis
  • Allergic conjunctivitis
  • Atopic dermatitis
  • Chronic urticaria

Contraindications:

  • Hypersensitivity to cetirizine
  • Breastfeeding
  • Pregnancy
  • Acute attacks of asthma

Dosage:

Adults and Children over 6 years: 10 mg daily or 5 mg twice daily

Children:

  • 2-5 years: 2.5 mg once daily or 2.5 mg twice daily
  • 6 months-1 year: 2.5 mg once daily

Side Effects:

  • Somnolence
  • Insomnia
  • Headache
  • Dizziness
  • Dry mouth
  • Abdominal pain
  • Nausea and vomiting
  • Diarrhea
  • Bronchospasm
  • Pharyngitis
  • Malaise

Drug Interactions:

  • Alcohol and other CNS depressants may increase CNS depression

Key Issues to Note:

  • The drug can be given without regard to food
  • Cetirizine may cause drowsiness and impair the ability to perform activities requiring mental alertness
  • Cetirizine may cause dry mouth; therefore, advise the patient to drink a lot or to use sugarless gum
  • Avoid alcohol while taking cetirizine

Drugs Used in the Treatment of Cough

Cough is a useful natural response to irritation of the lungs and airways aimed at removing foreign substances or excessive secretions.

Cough may occur as a symptom of an underlying disorder such as asthma, pneumonia, sinusitis, or gastroesophageal reflux disease.

It may be classified as follows:

  • Non-productive cough
  • Productive cough

Productive Cough

Productive cough is characterized by the presence of sputum and may be associated with conditions such as chronic bronchitis, asthma, and pneumonia. It is commonly treated with cough expectorants or mucolytics.

Non-Productive Cough

This type of cough is associated with no mucus production and is regarded as a useless cough. It is commonly associated with the common cold and is treated with cough suppressants or antitussives.

Cough Expectorants

Cough expectorants facilitate the expulsion of mucus and other materials from the lungs. Cough expectorants contain one or more of the following:

  • Guaifenesin
  • Ammonium chloride
  • Ipecacuanha
  • Squill
  • Volatile oils
  • Guaiacol
  • Iodides
  • Sodium citrate
  • Creosote

Preparations which contain cough expectorants include:

  • Cadistin syrup®
  • Cadiphen syrup®
  • Histalin syrup®
  • Hydrylin syrup®
  • Delased chesty®
  • Actified expectorant®
  • Menthodex syrup®
  • Zecuf herbal syrup®
Mucolytic Expectorants

Mucolytics reduce the viscosity of bronchial secretions by breaking down the structure of tenacious sputum, thereby facilitating its removal by coughing. Mucolytics are often used in chronic bronchitis and chronic asthma where sputum production is high.

Examples:

  • Bromhexine
  • Carbocisteine
  • Ambroxol
Common compound preparations containing mucolytics include:
  • Rhinathiol syrup®
  • Brozedex®
  • Ascoril®
  • Bisolvin®
  • Ambrodil®

Demulcents

Demulcent cough preparations coat the mucosa of the pharynx and provide short-lived relief of the irritation that provokes the cough reflex. They contain soothing substances such as:

  • Glycerol
  • Honey
  • Liquorice
  • Sucrose syrup

Compound preparations containing demulcents include:

  • Simple linctus
  • Menthodex lozenges
  • Zecuf lozenges
Cough Suppressants

Cough suppressants act centrally to reduce the sensitivity of the cough center. They should be avoided in chronic obstructive airway diseases as they may also depress respiration. Most cough suppressants are opiate derivatives and may cause constipation and abuse. They should be avoided in children below one year.

Examples include codeine, pholcodine, and dextromethorphan; the latter two generally have fewer adverse effects than codeine.

Compound preparations containing cough suppressants include: Benylin with codeine®, Benylin DM®, Rhinathiol dry cough®, Piritex with codeine®, Hydryllin DM®, Piritex Junior®, Actifed syrup®, Delased dry cough®, and Zedex®.

Drugs Acting on the Respiratory System Read More »

Medicines Acting on Specific Body Systems

Medicines Acting on Specific Body Systems

Medicines play a big role in modern healthcare, providing solutions to a wide range of diseases and disorders. The human body is a network of interconnected systems, each with its functions and challenges. To address these challenges, pharmacologists have developed drugs that act on specific body systems, ensuring targeted and effective treatment for various conditions.

These medicines are designed to interact with specific organs, tissues, or biochemical pathways, either by enhancing normal physiological functions or by correcting pathological imbalances. For example, cardiovascular drugs regulate heart function and blood pressure, while respiratory drugs help manage conditions like asthma and chronic obstructive pulmonary disease (COPD). Similarly, gastrointestinal drugs address issues such as acid reflux, ulcers, and irritable bowel syndrome, and endocrine drugs help manage hormonal imbalances like diabetes or thyroid disorders.

Drugs Acting on the Gastrointestinal System

Drugs Acting on the Gastrointestinal System

Drugs for Peptic Ulcer Disease

Peptic Ulcer Disease (PUD)

Peptic ulcer disease develops when there is an imbalance between mucosal protective substances such as mucus and bicarbonate, and destructive substances like acid, H. pylori bacteria, and pepsin. Drugs used in the treatment of peptic ulcer disease include:

  • Antacids
  • H2 receptor antagonists
  • Proton pump inhibitors
  • Mucosal protectives
  • Antibiotics
Antacids

These are alkaline compounds that neutralize stomach acid, raising the gastric pH and thereby relieving pain. They are often given concurrently with acid-suppressing drugs such as H2 receptor antagonists and proton pump inhibitors in the treatment of peptic ulcers and reflux esophagitis. Most antacids contain aluminum hydroxide, magnesium hydroxide, sodium bicarbonate, or calcium carbonate. Other ingredients added to antacids include simethicone and alginic acid.

  • Simethicone: Added to antacids to relieve flatulence and dyspepsia. It may be beneficial in relieving colic pain in infants. Common brands containing simethicone include Maalox Plus®, Alcid®, and Gestid®.
  • Alginates: Added to antacids as protectants and are useful in the treatment of reflux esophagitis. Common brands containing alginate include Gaviscon®.
  • Local anesthetics: Such as oxethazaine are added to antacids to reduce the pain associated with dyspepsia. Common brands containing oxethazaine include Mucogel® suspension and Mucaine® suspension.

Antacids containing sodium bicarbonate have a fast onset of action, but their absorption may worsen hypertension and heart failure.

Indications

Symptomatic relief of:

  • Dyspepsia
  • Gastroesophageal reflux disease
  • Peptic ulcer disease
  • Gastritis
  • Heartburn

Contraindications

  • Patients with severe abdominal pain of unknown cause
  • Lactation
  • Patients with cardiovascular problems (antacids with sodium)

Side Effects

  • Magnesium-containing antacids tend to cause diarrhea, whereas aluminum-containing antacids may cause constipation and delay gastric emptying. A combination of the two may reduce the side effects of each.

Key Issues to Note

  • Antacids should be taken between meals or at bedtime when symptoms are expected to occur.
  • Optimum antacid effect is obtained if taken 1-3 hours after meals.
  • Liquid antacids are generally more effective than tablets and have a rapid onset of action.
  • Antacids are effective for a short period and should be given on a 6-hourly basis.
  • Antacids may interact with numerous other drugs, affecting the rate and extent of their absorption. For example, tetracycline, ciprofloxacin, iron, indomethacin, and digoxin. A minimum interval of at least 2 hours should be left between the administration of antacids and other drugs.
Common Antacid Preparations

ACICONE-S®

Available Preparations: Tablets, Suspension

Composition:

  • Tablets: Magaldrate 720 mg, Simethicone 25 mg
  • Suspension: Magaldrate 540 mg, Simethicone 40 mg

Indications:

  • Heartburn in reflux esophagitis
  • Prophylaxis against ulcer complications
  • Adjunct to the treatment of peptic ulcers

Dosage:

  • Tablets: 1 tablet to be chewed 4 times daily after meals or at bedtime
  • Suspension: 5-10 ml 4 times daily after meals or at bedtime

AGOCID®

Available Preparations: Suspension

Composition: Dried aluminum gel 250 mg, Magnesium hydroxide 250 mg, Simethicone 50 mg

Indications:

  • Acid dyspepsia
  • Heartburn
  • Pregnancy heartburn
  • Adjunct to peptic ulcer treatment
  • Reflux esophagitis

Dosage: 5-10 ml 4 times daily between meals

ALCID®

Available Preparations: Suspension

Composition: Aluminum hydroxide gel 400 mg, Magnesium hydroxide 400 mg, Simethicone 50 mg

Indications:

  • Gastritis
  • Flatulence
  • Hiatus hernia
  • Adjunct to the treatment of peptic ulcers
  • Heartburn associated with reflux esophagitis
  • Heartburn in pregnancy

Dosage: 5-10 ml 4 times a day between meals and at bedtime

CENTACID®

Available Preparations: Suspension

Composition: Aluminum hydroxide gel 250 mg, Magnesium hydroxide 200 mg, Simethicone 40 mg

Indications:

  • Acid dyspepsia
  • Reflux esophagitis
  • Gastritis
  • Pregnancy heartburn
  • Hiatus hernia

Dosage: 5-10 ml 4 times a day between meals and at bedtime

RELCERGEL®

Available Preparations: Suspension

Composition: Aluminum hydroxide gel 6 g, Magnesium hydroxide 80 mg, Simethicone 100 mg, Deglycyrrhizinated liquorice 400 mg

Indications:

  • Gastritis
  • Flatulence
  • Heartburn associated with reflux esophagitis
  • Heartburn in pregnancy
  • Adjunct to the treatment of peptic ulcers

Dosage: 5-10 ml 3-4 times daily after meals

Mucosal Protective Drugs

Bismuth Subsalicylate

  • Has cytoprotective properties and is bactericidal against H. pylori. It promotes healing of peptic ulcers by forming a complex (bismuth/glycoprotein) that coats the base of the peptic ulcer.
  • It needs an acidic environment to work; hence, it should not be used in combination with antacids.

Available Preparations: Tablets (262 mg), Suspension

Available Brands: Pepto-Bismol®, Bismol®

Pharmacokinetics: Following oral administration, the drug is only slightly absorbed. Increased gastric pH may increase bismuth absorption. Unabsorbed drug is excreted in feces. The absorbed portion of the drug is distributed throughout body tissues and is slowly excreted in urine and bile.

Indications:

  • Peptic ulcer
  • Nausea
  • Diarrhea
  • Abdominal cramps
  • Indigestion
  • Prevention of traveler’s diarrhea

Contraindications:

  • Hypersensitivity to bismuth salts
  • Moderate to severe renal impairment
  • Children under 3 years

Dosage:

Adults: 30 ml or 2 tablets 4 times daily, 30 minutes before food

Children:

  • 9-12 years: 15 ml or 1 tablet 4 times daily
  • 6-9 years: 10 ml 4 times daily
  • 3-6 years: 5 ml 4 times daily

Side Effects:

  • Black stool
  • Discolors mucous membranes, tongue, and teeth
  • Constipation
  • Metallic taste
  • Skin reactions
  • Stomatitis

Drug Interactions:

  • Bismuth subsalicylate decreases the absorption of tetracyclines.
  • It increases the toxicity of aspirin due to the absorption of salicylate.

Key Issues to Note:

  • Chew or dissolve tablets in the mouth before swallowing.
  • Shake suspension before using.
  • Stop use if symptoms do not improve within 2 days.
Prostaglandin Analogues

Misoprostol

Available Preparations: Tablets (200 mcg)

Available Brands: Cytotec®

Mode of Action: Misoprostol helps to protect the stomach by suppressing secretion of gastric acid, promoting secretion of bicarbonate and cytoprotective mucus, and maintaining blood flow.

Indications:

  • Peptic ulcer disease
  • Prophylaxis of NSAID-induced ulcers
  • Induction of labor
  • Management of postpartum hemorrhage

Contraindications:

  • Pregnancy or those planning to become pregnant
  • Women in childbearing age
  • Breastfeeding
  • Patients allergic to prostaglandin derivatives
  • Inflammatory bowel disease

Dosage:

  • By mouth: 800 mcg daily in 2-4 divided doses with food for 4-8 weeks
  • Prophylaxis of NSAID-induced ulcers: 200 mcg 2-4 times daily taken with NSAID

Side Effects:

  • Diarrhea
  • Flatulence
  • Abdominal cramps
  • Dyspepsia
  • Dizziness
  • Nausea
  • Vomiting
  • Abnormal vaginal bleeding
  • Rashes

Drug Interactions:

  • Misoprostol diminishes the bioavailability of aspirin.
  • Magnesium antacids enhance diarrhea associated with misoprostol.
H2 Receptor Antagonists

H2 receptor antagonists reduce gastric acid secretion by blocking the action of histamine at the H2 receptor in the parietal cells of the stomach.

Examples:

  • Cimetidine
  • Famotidine
  • Nizatidine
  • Ranitidine

Ranitidine

Available Preparations: Tablets (150 mg, 300 mg), Injection (25 mg/ml, 2 ml)

Available Brands: Zantac®, Ranidenk®, Ranitin®, Rantac®, Aciloc®, R-Loc®

Pharmacokinetics: Ranitidine is readily absorbed from the gastrointestinal tract, widely distributed, metabolized in the liver, and excreted in urine.

Indications:

  • Peptic ulcer
  • Prophylaxis of NSAID-induced duodenal or gastric ulcer
  • Stress ulcer prophylaxis
  • Gastroesophageal reflux disease
  • Zollinger-Ellison syndrome
  • Dyspepsia

Contraindications:

  • Patients allergic to ranitidine
  • Children less than 8 years

Dosage:

Peptic ulcer:

  • Adults and children over 12 years: 150 mg twice daily or 300 mg at night for 4 to 8 weeks

Prophylaxis of NSAID-induced duodenal or gastric ulcer: 150 mg twice daily

Gastroesophageal reflux disease: 150 mg twice daily or 300 mg at night up to 8 weeks; moderate to severe cases: 150 mg every 6 hours daily for up to 12 weeks

Zollinger-Ellison syndrome: 150 mg 3 times daily

Stress ulcer prophylaxis: 150 mg twice daily until the risk factor is removed

Dyspepsia: 150 mg twice daily for 4-8 weeks

  • IV: 50 mg diluted to 20 ml with normal saline or dextrose 5% every 6-8 hours by slow injection over not less than 5 minutes
  • IV Infusion: 25 mg/hour for 2 hours may be repeated every 6-8 hours

Side Effects:

  • Skin rash
  • Visual disturbance
  • Gynecomastia
  • Headache
  • Diarrhea
  • Malaise
  • Tachycardia
  • Constipation
  • Hypersensitivity reaction
  • Myalgia

Drug Interactions:

  • Antacids may decrease the absorption of ranitidine.
  • Ranitidine may decrease the absorption of ketoconazole, cefpodoxime, cefuroxime.
  • Ranitidine may increase the hypoglycemic effects of glipizide.
  • Ranitidine may interfere with warfarin clearance.
Proton Pump Inhibitors

Proton pump inhibitors (PPIs) act by irreversibly binding to and inhibiting the enzyme H+/K+-ATPase (proton pump) of the gastric parietal cells, resulting in long-lasting but reversible acid suppression. PPIs inhibit gastric acid secretion more than H2 receptor antagonists.

Examples:

  • Omeprazole
  • Lansoprazole
  • Pantoprazole
  • Esomeprazole
  • Rabeprazole

Omeprazole

Available Preparations: Enteric-coated capsules/tablets (20 mg)

Available Brands: Gasec®, Omepren®, Omizac®, Ocid®, Belifax®

Pharmacokinetics: Omeprazole is rapidly but variably absorbed after oral administration. Absorption is not affected by food. It is almost completely metabolized in the liver, and 80% of the metabolites are excreted mainly in urine and the rest in feces.

Indications:

  • Peptic ulcers
  • Zollinger-Ellison syndrome
  • NSAID-associated duodenal or gastric ulcer
  • Gastric acid reduction during anesthesia
  • Gastroesophageal reflux disease
  • Acid-related dyspepsia

Contraindications:

  • Allergy to omeprazole or any other component in the capsule
  • Pregnancy
  • Lactation

Dosage:

  • Gastric ulcer or reflux esophagitis: 20-40 mg once daily for 4-8 weeks
  • Duodenal ulcer: 20 mg once daily for 4 weeks; continued for a further 4 weeks if not fully healed
  • NSAID-associated duodenal or gastric ulcer: 20 mg once daily for 4 weeks; continued for a further 4 weeks if not fully healed
  • Zollinger-Ellison syndrome: Initially 60 mg once daily, usual range 20-120 mg; doses over 80 mg given in 2 divided doses
  • Acid-related dyspepsia: 20 mg once daily for 2-4 weeks
  • Prophylaxis of acid aspiration: 40 mg on the evening before, then 40 mg 2-6 hours before surgery

Side Effects:

  • Headache
  • Nausea
  • Flatulence
  • Vomiting
  • Constipation
  • Skin rashes
  • Diarrhea
  • Abdominal pain
  • Dry mouth
  • Gynecomastia
  • Impotence

Drug Interactions:

  • Omeprazole increases the plasma concentration of diazepam, carbamazepine, digoxin, phenytoin
  • Omeprazole decreases the plasma concentration of itraconazole, ketoconazole, cefpodoxime, cefuroxime, iron salts, and cyanocobalamin
  • Omeprazole may increase the absorption and potential for hypoglycemia of glipizide, tolbutamide

Key Issues to Note:

  • Administer before food and the capsule should be swallowed whole without chewing
  • Capsules should be used within one month of opening the package
  • Possible malignancy must be excluded prior to starting treatment to avoid delay in diagnosis
  • Dosage reduction may be required in hepatic disease

Esomeprazole

Available Preparations: Tablets (20 mg, 40 mg)

Available Brands: Nexium®, S-prazo®, Nexpro®, Esoz®

Pharmacokinetics: Esomeprazole is rapidly absorbed following oral administration. It is extensively metabolized by the liver and excreted in urine and a small percentage in feces.

Indications:

  • Gastroesophageal reflux disease
  • Zollinger-Ellison syndrome
  • Peptic ulcer disease
  • Prevention of relapse of H. pylori-associated peptic ulcer
  • Prevention of gastric and duodenal ulcers associated with NSAID therapy

Contraindications:

  • Known hypersensitivity to benzimidazoles
  • Pregnancy

Dosage:

  • Peptic ulcer disease: Triple therapy regimen: 40 mg of esomeprazole once daily with amoxicillin 1 g twice daily and clarithromycin 500 mg twice daily for 7 days
  • Gastroesophageal reflux disease: 40 mg once daily for 4-8 weeks depending on the response; maintenance: 20 mg daily
  • Gastric ulcer associated with NSAID therapy: 20 mg once daily for 4-8 weeks

Side Effects:

  • Taste disturbances
  • Dizziness
  • Diarrhea
  • Nausea
  • Headache
  • Abdominal pain
  • Skin rash
  • Vomiting
  • Flatulence
  • Dry mouth

Drug Interactions:

  • Reduction in gastric acidity due to esomeprazole use may decrease the absorption of ketoconazole, itraconazole, digoxin, and iron

Key Issues to Note:

  • Food delays and decreases the absorption of esomeprazole; therefore, take it at least 1 hour before meals
  • The tablet should be swallowed whole; do not chew or crush

Lansoprazole

Available Preparations: Capsule (30 mg)

Available Brands: Lancid®, Lan-30®, Zolanas-30®

Pharmacokinetics: Lansoprazole is rapidly absorbed after oral administration, extensively metabolized in the liver, and metabolites are excreted primarily in feces via the bile.

Indications:

  • Peptic ulcers
  • Zollinger-Ellison syndrome
  • Gastroesophageal reflux disease
  • Acid-related dyspepsia
  • Prophylaxis of NSAID-associated duodenal and benign gastric ulcer

Contraindications:

  • Hypersensitivity to lansoprazole
  • Breastfeeding
  • Pregnancy

Dosage:

  • Benign gastric ulcer: 30 mg daily in the morning for 8 weeks
  • Duodenal ulcer: 30 mg daily in the morning for 4 weeks; maintenance: 15 mg daily
  • Zollinger-Ellison syndrome: Initially 60 mg once daily, adjusted according to response to a daily dose of 120 mg or more in two divided doses
  • Gastroesophageal reflux disease: 30 mg daily in the morning for 4-8 weeks; maintenance: 15-30 mg daily
  • Acid-related dyspepsia: 30 mg daily in the morning for 2-4 weeks

Side Effects:

  • Abdominal pain
  • Diarrhea or constipation
  • Fatigue
  • Nausea
  • Dizziness
  • Flatulence
  • Headache
  • Skin rash
  • Altered appetite
  • Impotence
  • Malaise
  • Vomiting

Drug Interactions:

  • Lansoprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability such as ketoconazole, itraconazole, ampicillin, iron salts, digoxin
  • Antacids may reduce the absorption of lansoprazole when given at the same time
  • Lansoprazole may reduce the effect of oral contraceptives, phenytoin, carbamazepine, warfarin, and theophylline

Key Issues to Note:

  • Swallow capsule whole without crushing or chewing
  • For patients unable to swallow, open the capsule and pour the contents onto a teaspoon and swallow
  • Take the drug after meals

Drugs for Nausea and Vomiting

Common Terms Used

  • Nausea: A sensation often leading to the urge to vomit.
  • Vomiting (Emesis): The forceful expulsion of gastric contents through the mouth, occurring due to stimulation of the vomiting center situated in the medulla oblongata of the brain.
  • Vomiting Center: The area in the brain involved in stimulating the events that lead to nausea and vomiting.
  • Chemoreceptor Trigger Zone: The area in the brain involved with the sensation of nausea and vomiting.
  • Prokinetic Drug: Drugs that increase the activity of gastrointestinal smooth muscles.
  • Antiemetic Drug: A drug given to relieve nausea and vomiting.

Vomiting is not a disease but a symptom of an underlying disease or disorder of the gastrointestinal tract (GIT). Common causes of vomiting include:

  • Drugs such as opioid analgesics and digoxin
  • Gastrointestinal disease
  • Motion sickness
  • Vestibular disorders like migraine headache
  • Early pregnancy (morning sickness)
  • Psychological factors
  • Infectious diseases

Drugs used in the treatment of vomiting include:

  • Promethazine
  • Dimenhydrinate
  • Metoclopramide
  • Prochlorperazine
  • Cinnarizine
  • Meclozine
  • Chlorpromazine
  • Domperidone
  • Cyclizine
  • Granisetron
  • Haloperidol

Key Issues to Note

  • Identify and treat the cause if possible
  • Ensure adequate hydration
  • Antiemetics should be prescribed only when the cause of vomiting is known
  • Antiemetics are more effective when given prophylactically than when given to stop vomiting that has already started
  • They are unnecessary and sometimes harmful, especially when the cause can be treated

Promethazine

Available Preparations:

  • Tablets: 25 mg
  • Injection: 25 mg/ml, 2 ml
  • Syrup: 5 mg/5 ml

Available Brands: Intamine®, Prozin®, Phenergan®

Pharmacokinetics: Promethazine is well absorbed after oral or intramuscular administration, widely distributed, metabolized in the liver, and excreted in urine and bile.

Indications:

  • Nausea and vomiting
  • Urticaria and angioedema
  • Vertigo
  • Postoperative emesis
  • Motion sickness
  • Allergic rhinitis
  • Pruritus in eczema

Contraindications:

  • Known hypersensitivity to promethazine
  • Porphyria
  • Children under 2 years
  • Severe CNS depression or coma
  • Vomiting of unknown cause
  • Lactation
  • Concomitant therapy with MAOIs

Dosage:

Nausea and Vomiting:

  • Adult (Oral): 25 mg repeated every 4-6 hours, max 100 mg daily
  • Adult (IM): 12.5-25 mg every 6 hours as needed
  • Children (5-12 years): 6.25-12.5 mg
  • Children (12-16 years): 12.5-25 mg

Morning Sickness:

  • Adult: 25 mg at bedtime or 2 hours before traveling, repeated if needed up to 4 times daily
  • Children (5-10 years): 10 mg at bedtime and the following morning if necessary
  • Children (2-5 years): 5 mg at night and the following morning if necessary

Side Effects:

  • Drowsiness
  • Anorexia
  • Dry mouth
  • Constipation
  • Sedation
  • Disorientation
  • Urinary retention
  • Hypotension
  • Skin rashes
  • Dizziness
  • Headache
  • Fatigue
  • Epigastric pain

Drug Interactions:

  • Alcohol and other CNS depressants may increase CNS depressant effects of promethazine
  • Promethazine may block the anti-Parkinsonian action of levodopa
  • Additive anticholinergic effects with anticholinergic drugs

Key Issues to Note:

  • Inform the patient that promethazine may cause drowsiness and impair the ability to perform activities requiring mental alertness
  • Advise the patient to avoid prolonged exposure to sunlight since promethazine may cause photosensitivity reactions
  • Maintain fluid intake
  • Avoid alcohol intake

Chlorpromazine

Available Preparations:

  • Tablets: 25 mg, 100 mg
  • Injection: 100 mg/2 ml

Available Brands: Largactil®

Pharmacokinetics: Chlorpromazine is readily absorbed from the gastrointestinal tract, undergoes first-pass metabolism, and is distributed to the body tissues. It is extensively metabolized in the liver and excreted in the urine.

Indications:

  • Nausea and vomiting due to radiation therapy and chemotherapy
  • Acute and chronic schizophrenia
  • Acute mania, as in bipolar disorder
  • Anxiety disorders
  • Intractable hiccup
  • Severe behavioral disturbances in children
  • Nausea and vomiting of terminal illness

Contraindications:

  • Hypersensitivity to chlorpromazine
  • Comatose states
  • Severe CNS depression
  • Bone marrow depression
  • Parkinson’s disease
  • Liver damage
  • Cerebral or coronary arteriosclerosis

Dosage:

Schizophrenia, Mania, Severe Anxiety: Initially 25 mg 3 times daily or 75 mg at night, adjusted according to response. Maintenance dose: 75-300 mg daily

Intractable Hiccup: 25-50 mg 3-4 times daily

Severe Nausea and Vomiting: 10-25 mg 4 times daily

Children: 0.5-1 mg/kg 6 hourly

Deep Intramuscular Injection:

  • Adult: 25-50 mg every 4-6 hours until vomiting stops
  • Children (1-12 years): 0.5-1 mg/kg every 6-8 hours

Side Effects:

  • Drowsiness
  • Dry mouth
  • Slurred speech
  • Poor coordination
  • Hypotension
  • Blurred vision
  • Constipation
  • Urinary retention
  • Somnolence
  • Dizziness

Drug Interactions:

  • Chlorpromazine may reduce the effect of drugs for Parkinsonism
  • Alcohol and other CNS depressants may increase respiratory depression and hypotensive effects of chlorpromazine
  • Lithium may decrease the absorption of chlorpromazine and produce adverse neurologic effects
  • Concurrent use with antihypertensives may result in additive hypotensive effects

Key Issues to Note:

  • Administer chlorpromazine with water, food, or milk to decrease GI upset
  • Inform the patient that chlorpromazine may cause drowsiness and impair the ability to perform activities requiring mental alertness

Metoclopramide

Available Preparations:

  • Tablets: 10 mg
  • Injection: 5 mg/ml, 2 ml ampoule

Available Brands: Plasil®, Reglan®, Camet®

Pharmacokinetics: Metoclopramide is rapidly and almost completely absorbed from the gastrointestinal tract following oral administration, undergoes hepatic first-pass metabolism, and is widely distributed in the body. It is excreted in feces via the bile.

Indications:

Disorders of decreased gastrointestinal motility such as:

  • Dyspepsia
  • Gastroesophageal reflux disease
  • Diabetic gastroparesis
  • Stimulation of lactation

Nausea and vomiting due to:

  • Migraine
  • Following gastric surgery
  • Cancer therapy or radiotherapy

Contraindications:

  • Gastrointestinal obstruction
  • Intestinal perforation
  • 3-4 days after gastrointestinal surgery
  • History of seizure disorders
  • Pheochromocytoma

Dosage:

Nausea and Vomiting:

  • Adult and Children (over 60 kg): 10 mg 3 times daily
  • Children (9-18 years): 5 mg 3 times daily
  • Children (5-9 years): 2.5 mg 3 times daily
  • Children (3-5 years): 2 mg 2-3 times daily
  • Children (1-3 years): 1 mg 2-3 times daily
  • Neonate: 100 mcg/kg every 6-8 hours

Stimulation of Lactation: 10 mg 3 times daily, reduce dose gradually over 7-10 days before stopping

Cancer Chemotherapy: Initial dose of up to 2 mg/kg by intravenous infusion over at least 15 minutes may be given in combination with dexamethasone before cancer therapy and repeated every 2 or 3 hours

Side Effects:

  • Hyperprolactinemia
  • Drowsiness
  • Tardive dyskinesia
  • Diarrhea
  • Edema
  • Skin rash
  • Hypotension
  • Depression
  • Dizziness
  • Pruritus
  • Headache
  • Restlessness
  • Parkinsonism

Drug Interactions:

  • Metoclopramide reduces the absorption of oral digoxin
  • Metoclopramide increases the absorption of aspirin, paracetamol, and diazepam

Key Issues to Note:

  • May cause drowsiness; therefore, warn the patient not to drive or operate machinery that requires mental alertness
  • Advise the patient to take the drug 30 minutes before meals and at bedtime

Drugs for Hemorrhoids and Piles

Hemorrhoids (Piles)

Hemorrhoids are clusters of venous swellings of the tissues around the anus caused by straining during bowel movements. They are associated with constipation, diarrhea, and prolonged straining. Hemorrhoids may be divided into two:

  • Internal hemorrhoids
  • External hemorrhoids

Most preparations for hemorrhoids contain any of the following:

  • Astringents (e.g., bismuth subgallate, zinc oxide, resorcinol)
  • Local anesthetics (e.g., lignocaine, cinchocaine)
  • Corticosteroids (e.g., hydrocortisone)
  • Lubricants
  • Vasoconstrictors
  • Antiseptics

Key Issues to Note:

  • Creams or ointments are used for external hemorrhoids
  • Suppositories are preferred for internal hemorrhoids
  • Hemorrhoids developing during pregnancy should be managed conservatively as most will resolve after delivery
  • Local anesthetics are used to relieve pain associated with hemorrhoids
  • Corticosteroids are used to reduce inflammation where infection is not present
  • In case of infection, metronidazole 400 mg 8 hourly for 5 days is used
  • Surgery may be required in resistant cases

Commonly Used Compound Preparations:

  • Anusol ointment/suppository
  • Preparation-H ointment
  • Scheriproct ointment/suppository
  • Sediproct ointment/suppository
  • Pylocaine ointment

Anusol

Available Preparations:

  • Ointment
  • Suppository

Composition:

  • Bismuth subgallate 59 mg
  • Bismuth oxide 24 mg
  • Zinc oxide 296 mg

Indications:

  • Soothe the pain and irritation of hemorrhoids

Contraindications:

  • Serious rectal pathology

Dosage:

  • Suppository: Insert 1 suppository at night and morning
  • Ointment: Apply twice daily, at night and morning

Side Effects:

Hypersensitivity reactions such as:

  • Redness
  • Irritation
  • Swelling

Sediproct

Available Preparations:

  • Cream
  • Suppository

Composition:

  • Hydrocortisone 500 mg
  • Cinchocaine 500 mg

Indications:

  • Hemorrhoids associated with inflammation
  • Anal fissures
  • Anal pruritus
  • Proctitis

Contraindications:

  • Hypersensitivity to any of the active ingredients

Dosage:

  • Cream: Apply the cream into the rectum twice daily, at night and morning after bowel movement
  • Suppository: Insert 1 suppository twice daily, at night and morning

Side Effects:

  • Local irritation
  • Skin rash

Scheriproct

Available Preparations:

  • Suppository
  • Ointment

Composition:

  • Cinchocaine 0.5%
  • Prednisolone 0.19%

Indications:

  • Hemorrhoids

Contraindications:

  • Known hypersensitivity to the active ingredients

Dosage:

  • Ointment: Apply twice daily for 5-7 days, then once daily for a few days after symptoms have cleared
  • Suppository: Insert 1 suppository daily after a bowel movement for 5-7 days (in severe cases, initially apply 2-3 times daily)

Side Effects:

  • Local irritation
  • Skin rash

Drugs for Inflammatory Bowel Disease

Inflammatory bowel disease is a chronic non-specific inflammatory condition of the gastrointestinal tract. 

It is divided into two:

  • Crohn’s disease (affects the gut from mouth to anus)
  • Ulcerative colitis (affects only the large bowel)

Both ulcerative colitis and Crohn’s disease frequently run a course characterized by exacerbations and remissions, tend to be chronic in nature, have similar extra-intestinal manifestations, and may be associated with a positive family history of inflammatory bowel disease. 

Drugs used in the treatment of inflammatory bowel disease either control symptoms or modify the disease by inducing and maintaining long-term bowel healing.

Examples:

  • Aminosalicylates
  • Corticosteroids

Aminosalicylates

This group of drugs includes:

  • Sulfasalazine
  • Mesalazine

Aminosalicylates treat mild to moderate inflammatory bowel disease and are equally effective. The choice is based on the location of the disease and the side effect profile of the individual drugs.

Sulfasalazine

Available Preparation: Tablets: 500 mg

Available Brands: Salazopyrin®

Indications:

  • Active ulcerative colitis
  • Severe rheumatoid arthritis
  • Active Crohn’s disease

Contraindications:

  • Children less than 2 years
  • Pregnancy at term and lactation
  • Severe hepatic impairment
  • Severe renal dysfunction
  • Salicylate and sulfonamide hypersensitivity

Dosage:

Acute Attack:

  • Adult: 1-2 g 4 times daily until remission occurs (3 weeks), reduced to a maintenance dose of 500 mg 4 times daily
  • Children over 2 years:
  • Acute attack: 10-15 mg/kg 4-6 times daily until remission occurs
  • Maintenance: 30 mg/kg/day in 4 divided doses

Rheumatoid Arthritis:

  • Adult: 500-1000 mg/day for 1 week, increased by 0.5 g/week up to 3 g/day

Side Effects:

  • Anorexia
  • Vomiting
  • Fever
  • Skin rash
  • Abdominal discomfort
  • Nausea
  • Headache
  • Folate deficiency
  • Reversible male infertility

Drug Interactions:

  • Sulfasalazine may increase the effect of anticonvulsants, methotrexate, oral anticoagulants, and oral antidiabetics
  • Sulfasalazine may decrease the absorption of digoxin

Key Issues to Note:

  • Administer the drug with food to reduce stomach upset
  • Do not administer the drug with antacids
  • Sulfasalazine impairs the absorption of folic acid; therefore, folic acid supplements may be necessary during treatment

Corticosteroids

Corticosteroids are used for the treatment of both ulcerative colitis and Crohn’s disease. They are often able to induce the remission of ulcerative colitis but have proved less valuable in maintaining remission.

Drugs for Constipation (Laxatives)

Constipation is a reduced frequency of defecation characterized by hardening of the stool, straining on defecation, or a feeling of incomplete evacuation. 

It may be caused by any of the following:

  • Lack of fluid or fiber intake
  • Lack of exercise
  • Pregnancy
  • Drugs like aluminum-containing antacids, codeine, or iron
  • Irritable bowel syndrome
  • Anorectal conditions like hemorrhoids
  • Psychiatric and neurological disorders

Laxatives are drugs that stimulate defecation by forming bulk, stimulating peristalsis, or providing lubrication. 

They increase the frequency of bowel evacuation or the passage of softer or bulkier stool. Laxatives are used in the treatment of constipation and for bowel evacuation before investigational procedures, such as endoscopy, radiological examination, or before surgery.

Classification of Laxatives

Laxatives are classified according to their mode of action as follows:

  • Bulk-forming laxatives
  • Saline laxatives
  • Lubricant laxatives
  • Stimulant laxatives
  • Osmotic laxatives
Bulk-Forming Laxatives

Mode of Action: Bulk-forming laxatives relieve constipation by absorbing water, thereby increasing fecal bulk, which stimulates peristalsis. They are useful for mild constipation, small hard stools, patients with hemorrhoids, fissures, and irritable bowel disease, and as adjuncts in ulcerative colitis. Adequate fluid intake is important to lubricate the colon and minimize the risk of intestinal obstruction.

Examples:

  • Methylcellulose
  • Wheat bran
  • Ispaghula husk

Ispaghula Husk

Available Preparations:

  • Granules: 3.5 g sachet

Available Brands: Fybogel®

Indications:

  • Constipation, especially in diverticular disease and irritable bowel syndrome
  • Constipation following anorectal surgery, hemorrhoids, pregnancy
  • Management of diarrhea
  • Adjusting fecal consistency in patients with colostomies

Contraindications:

  • Difficulty in swallowing
  • Intestinal obstruction
  • Colonic atony
  • Fecal impaction
  • Hypersensitivity to any of the ingredients

Dosage:

  • Adult: 1 sachet or 2 level 5 ml spoonfuls in water given morning and evening after meals
  • Children (6-12 years): 1/2 – 1 level 5 ml spoonful in water twice daily
  • Children (below 6 years): Give on doctor’s advice only

Side Effects:

  • Flatulence and abdominal distension during the first few days of treatment
  • Gastrointestinal obstruction or impaction
  • Hypersensitivity reaction
Osmotic Laxatives

Mode of Action: Osmotic laxatives are poorly absorbed; therefore, the unabsorbed solute in the intestine draws water from the body into the bowel by osmosis, causing bowel distention, which in turn increases peristalsis. These drugs are used for acute and rapid evacuation of the bowel, except for lactulose.

Examples:

  • Lactulose
  • Magnesium salts

Lactulose

Available Preparations: Syrup: 3.350 g/5 ml

Available Brands: Laxolac®, Duphalac®, Sedalac®

Indications:

  • Constipation
  • Hepatic encephalopathy

Contraindications:

  • Intestinal obstruction
  • Known hypersensitivity to lactulose
  • Galactosemia

Dosage:

Constipation:

  • Adults: 15 ml twice daily
  • Children (6-12 years): 10 ml twice daily, adjusted according to response
  • Children (1-5 years): 5 ml twice daily, adjusted according to response
  • Children (less than 1 year): 2.5 ml twice daily, adjusted according to response

Hepatic Encephalopathy: 30-45 ml 3 times daily, adjust dose to produce 2-3 soft stools per day

Side Effects:

  • Flatulence
  • Cramps
  • Diarrhea
  • Nausea
  • Abdominal discomfort
  • Vomiting if excess doses are given

Key Issues to Note:

  • Administer the drug with juice, milk, or water to increase palatability
  • Do not take other laxatives while on lactulose therapy
Lubricants and Fecal Softeners

Mode of Action: They promote stool passage by coating the fecal surface with an oil layer that retains fecal fluid and prevents absorption of fecal water by the colon.

Examples:

  • Glycerol
  • Docusate sodium
  • Liquid paraffin
  • Mineral oil

Glycerol

Available Preparations:

  • Suppositories: 4 g

Indications:

  • Constipation

Contraindications:

  • Patients with known hypersensitivity to glycerin
  • Glycerin suppositories are contraindicated in patients who are recovering from rectal surgery

Dosage:

By rectum:

  • Adults: 4 g suppository moistened with water before use, once daily when required
  • Children (1-12 years): 2 g suppositories as required
  • Children (1 month – 1 year): 1 g suppository once daily when required

Side Effects:

  • Rectal discomfort
  • Diarrhea
  • Rectal mucosal erosion
  • Dizziness
  • Mild headache
  • Nausea
  • Mild hyperglycemia
  • Vomiting

Drug Interactions:

  • Concomitant use with diuretics may result in an additive effect

Key Issues to Note:

  • Onset of action is 5-30 minutes
  • Do not use longer than 1 week
  • Prolonged or frequent use may result in dependency
Stimulant Laxatives

Mode of Action: Stimulant laxatives increase peristalsis by directly stimulating nerve endings in the colonic mucosa, thereby increasing intestinal motility. They are useful for more severe forms of constipation, but tolerance is common with regular use, and they can produce abdominal cramps.

Examples:

  • Bisacodyl
  • Senna
  • Castor oil

Bisacodyl

Available Preparations:

  • Tablets: 5 mg
  • Suppository: 10 mg

Available Brands: Dulcolax®

Pharmacokinetics: Absorption of bisacodyl after oral administration is minimal; the absorbed drug is metabolized in the liver and excreted in urine, feces, and breast milk.

Indications:

  • Constipation
  • Bowel evacuation before investigational procedures or surgery

Contraindications:

  • Intestinal obstruction
  • Appendicitis
  • Severe dehydration
  • Acute inflammatory bowel disease
  • Hypersensitivity to the drug

Dosage:

Constipation:

  • Adults: 5-10 mg daily administered at night or 10 mg as a suppository or enema administered in the morning
  • Children (10-18 years): 5-10 mg at night, increased if necessary to max. 20 mg
  • Children (5-10 years): 5 mg at night
  • Children (2-5 years): 5 mg in the morning (rectally)

Complete Bowel Evacuation:

  • Adult: 10-20 mg followed by 10 mg as a suppository the next morning
  • Children (4-10 years): 5 mg at bedtime for 2 days before the procedure, increased if necessary by suppository 10 mg 1 hour before the procedure

Side Effects:

  • Nausea
  • Vomiting
  • Diarrhea
  • Faintness
  • Mild cramps
  • Abdominal discomfort
  • Suppositories may cause irritation and proctitis

Drug Interactions:

  • Antacids, cimetidine, famotidine, ranitidine, milk, and other drugs that increase gastric pH level may cause premature dissolution of the enteric coating of bisacodyl, resulting in abdominal cramping

Key Issues to Note:

  • Patients should swallow tablets whole with a glass of water
  • Do not administer bisacodyl within 1 hour of ingesting antacids, milk, or dairy products
  • Bisacodyl is habit-forming; therefore, long-term use may result in laxative dependency and loss of normal bowel function
  • Onset of action is 6-12 hours for tablets, 15-60 minutes for suppository
  • Warn the patient that prolonged use of bisacodyl suppositories may cause proctitis

Antidiarrheal Drugs

Diarrhea is the frequent passage of watery stools at least 3 times or more in a day. It affects all age groups and is more severe and life-threatening in children and immunocompromised patients. Diarrhea may be caused by any of the following:

  • Infections
  • Inflammation
  • Drugs such as antacids
  • Malabsorption

Drugs used in the treatment of diarrhea include:

  • Adsorbents
  • Antimotility drugs
  • Antisecretory compounds
  • Antimicrobials
  • Intestinal microflora

Adsorbent Drugs

Examples:

  • Kaolin
  • Pectin
  • Activated charcoal

Adsorbent drugs act by absorbing the toxins produced by pathogens, thereby reducing GIT motility. These drugs are used for symptomatic relief of diarrhea. They are not recommended for infectious acute diarrhea and when the patient is taking other drugs (prevent absorption of other drugs).

Antisecretory Drugs

Examples:

  • Bismuth subsalicylate

Bismuth subsalicylate appears to produce its antidiarrheal effect by inhibiting intestinal secretions. It is recommended in the treatment of infectious diarrhea such as traveler’s diarrhea. It is available in the form of tablets and suspension.

Intestinal Microflora

Example: Lactobacillus

These drugs are intended to replace colonic microflora, which restores intestinal function and suppresses the growth of pathogenic microorganisms.

Antimotility Drugs

Examples:

  • Loperamide
  • Codeine
  • Diphenoxylate

Antimotility drugs act by reducing GIT motility, thereby allowing enough time for fluid absorption from gut contents. They are recommended in the treatment of acute and chronic diarrhea in combination with fluid replacement. They are not recommended in children less than 2 years and infectious diarrhea.

Loperamide

Available Preparations:

  • Capsules: 2 mg
  • Tablets: 2 mg

Available Brands: Imodium®, Loperium®, Loperax®, Kamodium®, Gallop®

Pharmacokinetics: About 40% of loperamide is absorbed from the gastrointestinal tract, undergoes first-pass metabolism in the liver, and is excreted in the feces as unchanged drug and a small amount in urine.

Indications:

  • Acute diarrhea
  • Chronic diarrhea
  • Traveler’s diarrhea

Contraindications:

  • Known hypersensitivity to loperamide
  • Infants below 2 years of age
  • Abdominal distension
  • Acute inflammatory bowel disease
  • Antibiotic-associated colitis
  • Patients who must avoid constipation

Dosage:

Acute Diarrhea:

  • Adult: 4 mg start followed by 2 mg after each loose stool until diarrhea is relieved. Max dose 16 mg daily
  • Children (9-12 years): 2 mg 4 times daily up to 5 days
  • Children (4-8 years): 1 mg 3-4 times daily for up to 3 days only

Chronic Diarrhea:

  • Adult: 4-8 mg daily in 2 divided doses

Side Effects:

  • Flatulence
  • Blurred vision
  • Drowsiness
  • Headache
  • Fatigue
  • Constipation
  • Dry mouth
  • Hypersensitivity reaction
  • Abdominal cramps
  • Dizziness
  • Nausea and vomiting
  • Abdominal bloating
  • Urticaria
  • Toxic megacolon
  • Paralytic ileus

Drug Interactions:

  • Concomitant use of loperamide with opioid analgesics may cause severe constipation

Key Issues to Note:

  • Advise the patient to drink plenty of fluids to prevent dehydration
  • Do not exceed the maximum daily dosage
  • Loperamide may impair the ability to perform activities requiring mental alertness
  • Advise the patient to avoid the use of alcohol during treatment
  • Loperamide should not be used alone in patients with dysentery

Codeine

Available Preparations:

  • Tablets: 30 mg

Pharmacokinetics: Codeine is absorbed from the gastrointestinal tract, metabolized in the liver to morphine and other metabolites, and excreted in urine.

Indications:

  • Diarrhea
  • Pain
  • Cough suppression (lower dosage)

Contraindications:

  • Hypersensitivity to codeine
  • Premature infants
  • Conditions where inhibition of peristalsis should be avoided such as abdominal distension, ulcerative colitis, acute respiratory depression

Dosage:

  • Adults: 30-60 mg 3-4 times daily
  • Children: Not recommended

Side Effects:

  • Headache
  • Constipation
  • Anorexia
  • Abdominal pain
  • Dizziness
  • Hypotension
  • Sedation
  • Dry mouth
  • Nausea and vomiting
  • Respiratory depression
  • Somnolence
  • Decreased urination

Drug Interactions:

  • Alcohol, narcotic analgesics, hypnotics, and tricyclic antidepressants may increase CNS or respiratory depression

Key Issues to Note:

  • Administer codeine with water or food to decrease nausea and GI upset
  • Avoid long-term use because of addictive potential
  • Codeine may cause drowsiness; therefore, do not drive or operate machinery

Prokinetic Drugs

Prokinetic drugs enhance the tone and motility of the gastrointestinal tract. Examples include metoclopramide, domperidone, and cisapride. These drugs are used to treat gastroesophageal reflux disease (GERD), chemotherapy-induced nausea and vomiting, and diabetic gastroparesis. Metoclopramide, specifically, is used to suppress nausea and vomiting caused by anticancer drugs (e.g., cisplatin, dacarbazine), postoperative vomiting, radiation therapy-induced emesis, toxins, and opioids. It also treats diabetic gastroparesis and GERD.

Drugs for Obesity

Obesity is linked to numerous health problems, including diabetes mellitus, hypertension, and hyperlipidemia. Increased abdominal fat and waist circumference further elevate health risks.

Orlistat

Available preparations: 120mg capsules (brand name: Xenical®)

Mode of action: Inhibits lipases in the stomach and small intestine, preventing dietary fat absorption.

Indications: Obesity in adults with a body mass index (BMI) > 30, or > 27 with additional risk factors like hypertension or diabetes.

Contraindications: Chronic malabsorption syndrome, breastfeeding, cholestasis.

Dosage: Adults and children over 12 years: 120mg three times daily with each meal.

Side effects: Flatulence, fecal incontinence, headache, anxiety.

Drug interactions: Orlistat may reduce the absorption of fat-soluble vitamins. Supplementation with fat-soluble vitamins (including vitamin D and beta-carotene) may be necessary.

Key note: If a meal is fat-free, the dose can be omitted.

Medicines Acting on Specific Body Systems Read More »

Antimicrobial-Agents

ANTIBIOTICS

Antibiotics are chemical substances derived from microorganisms that either inhibit the growth of or destroy other microorganisms. 

They are pivotal in combating bacterial infections and are divided into two primary categories:

  1. Bacteriostatic Antibiotics: Inhibit bacterial growth.
  2. Bactericidal Antibiotics: Directly kill bacteria.

Classification of Antibiotics

Antibiotics can be classified based on their:

  1. Mechanism of Action
  2. Spectrum of Activity
  3. Chemical Structure

Mechanism of Action

Type

Description

Examples

Bacteriostatic

Inhibit bacterial growth, relying on the immune system to eliminate the pathogen.

Tetracyclines, Chloramphenicol, Erythromycin

Bactericidal

Kill bacteria directly, do not depend on the immune system.

Penicillins, Cephalosporins, Aminoglycosides, Fluoroquinolones

Spectrum of Activity

Type

Description

Examples

Narrow Spectrum

Effective against a limited group of bacteria (e.g., Gram-positive or Gram-negative).

Penicillin G, Aminoglycosides, Clindamycin

Broad Spectrum

Effective against a wide variety of Gram-positive and Gram-negative bacteria.

Tetracyclines, Ciprofloxacin, Chloramphenicol

Chemical Structure

Class

Examples

Mechanism of Action

Beta-Lactams

Penicillins, Cephalosporins, Carbapenems

Inhibit bacterial cell wall synthesis

Macrolides

Erythromycin, Azithromycin, Clarithromycin

Inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit

Tetracyclines

Tetracycline, Doxycycline, Minocycline

Inhibit protein synthesis by binding to the 30S ribosomal subunit

Aminoglycosides

Gentamicin, Amikacin

Inhibit protein synthesis by binding to the 30S ribosomal subunit, bactericidal

Quinolones

Ciprofloxacin, Levofloxacin

Inhibit bacterial DNA gyrase and topoisomerase IV

Sulphonamides

Cotrimoxazole, Sulphadoxine

Inhibit folic acid synthesis, essential for bacterial DNA replication

Nitroimidazoles

Metronidazole, tinidazole, nimorazole,

Disrupt the DNA of the susceptible bacteria and inhibit the protein synthesis of the cell wall leading to cell death; they act as bactericidal and antimicrobial agents.

  •  

During Pregnancy

Penicillins and Cephalosporins are drugs of choice in pregnancy and breastfeeding .

In pregnancy, avoid quinolones, tetracyclines, aminoglycosides, unless severe or life threatening infection, 

high dose metronidazole, trimethoprim (in first trimester – folate antagonist) and nitrofurantoin (at term – risk of neonatal haemolysis).


British National Formulary (BNF) guidance with respect to antibiotic use in pregnancy states:

  • checkedpenicillins and cephaloridines are safe to use throughout pregnancy
  • uncheckedsulfonamides interfere with the bile conjugating mechanism of the neonate, thus sulphonamides should be avoided if delivery is imminent
  • uncheckedtetracyclines should not be used in pregnancy. This group of drugs stains developing bone and teeth in the foetus. Also the use of tetracyclines, when administered intramuscularly, has occasionally produced maternal liver failure
  • uncheckederythromycin – not known to be harmful
  • uncheckedmetronidazole – manufacturer advises avoidance of high-dose regimens
  • uncheckedstreptomycin may cause foetal auditory nerve damage
  • uncheckedtrimethoprim – this is safe after the first trimester. However, the sulfonamide warning applies for trimethoprim – sulfonamide preparations

Breastfeeding

Penicillins and Cephalosporins are drugs of choice in breastfeeding.

Penicillins in breastfeeding :

  • all penicillin antibitotics can be used during breastfeeding with precautionary infant monitoring

  • flucloxacillin, phenoxymethylpenicillin (penicillin V) and the broad-spectrum penicillins, such as amoxicillin and ampicillin, are the preferred choices as there is more evidence and experience to support their use

  • pharmacokinetic properties and characteristics of all the penicillins are very similar although protein binding and bioavailability vary between the different penicillins, they are all acidic in nature and therefore only negligible quantities pass into milk

  • treatment choice should be primarily based on clinical indications and in line with national and local antimicrobial policy, with suitability in breastfeeding as a secondary consideration ideally treatment should be at the lowest therapeutic dose for shortest duration of time

A review has stated :

Safe for administration:

  • aminoglycosides
  • amoxicillin
  • amoxicillin-clavulanate
  • antitubercular drugs
  • cephalosporins
  • macrolides
  • trimethoprim-sulfamethoxazole
  • trimethoprim – the BNF states that ‘..short-term use not known to be harmful’

Effects not known/to be used with caution:

  • chloramphenicol
  • clindamycin
  • dapsone
  • mandelic acid
  • nalidixic acid
  • nitrofurantoin – the BNF states ‘..avoid; only small amounts in milk but could be enough to produce haemolysis in G6PD-deficient infants..’
  • tetracyclines

Not recommended:

  • quinolones

BETA-LACTAM ANTIBIOTICS

Definition: Beta-lactam antibiotics are a class of antibiotics characterized by a beta-lactam ring in their chemical structure. They primarily include:

  • Penicillins
  • Cephalosporins
  • Carbapenems

Mechanism of Action: Beta-lactam antibiotics inhibit bacterial cell wall synthesis by targeting peptidoglycan, a crucial component that provides rigidity to bacterial cell walls. They inhibit transpeptidases, also known as penicillin-binding proteins (PBPs), which are essential for peptidoglycan synthesis.

 

PENICILLINS

Origin: Penicillins are derived from the fungus Penicillium chrysogenum.

Classification:

  • Natural Penicillins
  • Semisynthetic Penicillins

Examples:

Natural Penicillins:

  • Sodium Penicillin G
  • Procaine Penicillin G
  • Benzathine Penicillin G
  • Phenoxymethyl Penicillin (Penicillin V)

Semisynthetic Penicillins:

  • Cloxacillin
  • Ampicillin
  • Amoxicillin
  • Amoxicillin + Clavulanic Acid

Pharmacokinetics of Penicillin G

  • Absorption: Destroyed by gastric acid; food interferes with absorption.
  • Distribution: Therapeutic concentrations can reach the CSF in the presence of inflammation.
  • Excretion: Primarily through the kidneys.

Dosage:

  • Benzylpenicillin: 0.5-4 million units (MU)
  • Procaine Penicillin: 0.5-2 MU
  • Benzathine Penicillin: 1.2 -2.4 MU

 

Indications for Penicillins

  • Pneumococcal Infections: Pneumonia, meningitis, osteomyelitis.
  • Streptococcal Infections: Pharyngitis, sinusitis, pneumonia, endocarditis.
  • Meningococcal Infections
  • Other Infections: Syphilis, diphtheria, tetanus, gas gangrene, anthrax, necrotizing fasciitis, prevention of rheumatic fever, bites, and mouth infections.

Side Effects

  • Allergic Reactions: Skin rashes, urticaria, fever, bronchospasm, serum sickness, anaphylaxis.
  • Neurological: Confusion, muscle twitching, convulsions, coma (from large doses).
  • Injection Site Reactions: Pain at the site of injection, thrombophlebitis with intravenous administration.

Drug Interactions

  • Probenecid: Inhibits renal excretion of penicillins.
  • Oral Contraceptives: Reduced effectiveness.
  • Methotrexate: May increase toxicity due to reduced excretion.

Nursing Considerations

  • Intramuscular administration of benzyl penicillin can be painful.
  • Intravenous penicillin must be given separately to avoid incompatibility.
  • Avoid large doses of intravenous benzyl penicillin to prevent convulsions.
  • Administer benzathine penicillin as two injections at separate sites.

AMPICILLIN

Description: Ampicillin is a semisynthetic penicillin with broad-spectrum activity against both gram-positive and gram-negative bacteria.

Pharmacokinetics:

  • Absorption: Poorly absorbed; food reduces its absorption.
  • Distribution: Widely distributed throughout the body.
  • Excretion: Primarily through the kidneys.

Dosage: 500 mg – 2 g.

Indications:

  • Infections: Bronchitis, septicaemia, urinary tract infections, endocarditis, gonorrhea, acute cholecystitis, pneumonia, typhoid, meningitis, sinusitis, otitis media.

Contraindications:

  • Hypersensitivity to penicillins.
  • Infectious mononucleosis.

Side Effects:

  • Nausea and vomiting, fever, diarrhea, rash, urticaria, antibiotic-related colitis, serum sickness-like reaction, pain at injection site.

Drug Interactions:

  • Allopurinol may increase the incidence of skin rashes.
  • May reduce the effectiveness of oral contraceptives.
  • Increased toxicity risk when combined with methotrexate or anticoagulants.

Nursing Considerations:

  • Take oral ampicillin 30 minutes before food.
  • Monitor for allergic reactions after administration.
  • Avoid mixing aminoglycosides with ampicillin during IV administration.

AMOXICILLIN

Dosage: 250-500 mg every 8 hours.

Pharmacokinetics:

  • Well absorbed orally; not affected by food.
  • Distributed in lungs, prostate, ears, tonsils, and sputum.
  • Partially metabolized in the liver and excreted in urine.

Indications:

  • Pneumonia, urinary tract infections, dental abscess, Lyme disease, otitis media, Helicobacter pylori eradication, biliary tract infections, sinusitis, chronic bronchitis.

Contraindications:

  • Known hypersensitivity to penicillin, infectious mononucleosis, penicillin-associated jaundice.

Side Effects:

  • Nausea, vomiting, diarrhea, skin rash, hepatitis, serum sickness-like syndrome, hemolytic anemia, urticaria.

Drug Interactions:

  • May decrease effectiveness of oral contraceptives.
  • Allopurinol may increase the incidence of skin rashes.
  • Probenecid may increase blood concentration and risk of toxicity.

Nursing Considerations:

  • Ensure the client completes the prescribed course of treatment.

CLOXACILLIN

Description: Cloxacillin is resistant to destruction by penicillinase, making it effective against beta-lactamase-producing Staphylococcus aureus.

Pharmacokinetics:

  • Poorly absorbed (50%); absorption reduced by food.
  • Partially metabolized in the liver and excreted unchanged in urine.

Indications:

  • Septicaemia, impetigo, staphylococcal endocarditis, pyomyositis, cellulitis, pneumonia, septic arthritis, osteomyelitis, prophylaxis in bone and joint surgery.

Contraindications:

  • Known hypersensitivity.

Side Effects:

  • Serum sickness-like reactions, antibiotic-associated colitis, joint pains, hemolytic anemia, candidiasis, diarrhea, skin rashes, nausea, vomiting, urticaria, hepatitis, pain, and inflammation at the injection site.

Drug Interactions:

  • Synergistic effect with aminoglycosides; probenecid decreases renal excretion and oral contraceptive effectiveness.

Nursing Considerations:

  • Administer on an empty stomach or one hour before meals.
  • Complete the prescribed treatment to avoid relapse.

AMOXICILLIN + CLAVULANIC ACID

Mechanism: Clavulanic acid binds to beta-lactamase, protecting amoxicillin from degradation.

Indications:

  • Pneumonia, sinusitis, urinary tract infections, wound infections, cellulitis, dental infections, animal bites, otitis media, tonsillitis, urethritis, boils, osteomyelitis, intra-abdominal sepsis, septic abortion, acute exacerbation of chronic bronchitis.

Contraindications:

  • Known hypersensitivity to penicillin.
  • History of jaundice or hepatic dysfunction associated with penicillin or amoxicillin.

Side Effects:

  • Diarrhea, nausea, vomiting, skin rashes, urticaria, gastritis, abdominal discomfort, vaginitis, anorexia, antibiotic-associated colitis.

Drug Interactions:

  • Reduces effectiveness of oral contraceptives.
  • Allopurinol may increase skin rash incidence.
  • Probenecid decreases renal excretion.

Nursing Considerations:

  • Take with meals to minimize gastrointestinal disturbance.
  • Maintain adequate hydration to prevent crystalluria.
  • Store parenteral clavulanic acid immediately after mixing; tablets in airtight containers due to degradation risk.

CEPHALOSPORINS

Description: Cephalosporins are semisynthetic beta-lactam antibiotics that are broad-spectrum and less susceptible to beta-lactamases. They are used when penicillins prove ineffective.

Mechanism of Action: Cephalosporins are bactericidal, inhibiting bacterial cell wall synthesis.

Classification:

  • First Generation: Cephalexin, Cefadroxil, Cefazolin (effective against gram-positive bacteria, limited gram-negative activity).
  • Second Generation: Cefuroxime, Cefaclor (increased gram-negative activity).
  • Third Generation: Ceftriaxone, Ceftazidime (more effective against resistant gram-negative bacteria).
  • Fourth Generation: Cefepime (increased activity against gram-negative organisms).

PHARMACOKINETICS OF CEPHALOSPORINS

CEFTRIAXONE

Definition: Ceftriaxone is a broad-spectrum cephalosporin antibiotic, primarily used to treat various bacterial infections. It is effective against a wide range of Gram-positive and Gram-negative bacteria.

Mechanism of Action:

Ceftriaxone works by inhibiting bacterial cell wall synthesis, leading to cell lysis and death. It binds to penicillin-binding proteins (PBPs), which are essential for cell wall integrity.

Available Preparations:

  • Injection: Available as a powder for reconstitution in vials (1 g, 2 g).

Dosage:

Adults:

  • Typical dose: 1-2 g IV/IM once daily.
  • In severe infections, doses may be increased to 4 g daily.

Children:

  • For children over 12 years or those weighing more than 50 kg, doses similar to adults may be used.
  • For younger children: 50-75 mg/kg/day, given once daily or divided every 12 hours.

Pharmacokinetics:

  • Absorption: Administered parenterally (IV or IM); not absorbed well from the gastrointestinal tract.
  • Distribution: Widely distributed in body tissues and fluids, including the central nervous system (CNS). It crosses the placenta and is excreted in breast milk.
  • Metabolism: Minimal hepatic metabolism.
  • Excretion: Primarily excreted unchanged in urine; about 50-60% of a dose is eliminated by the kidneys.

Indications:

Ceftriaxone is used to treat a variety of infections, including:

  • Respiratory Tract Infections: Pneumonia, bronchitis, and infections caused by Streptococcus pneumoniae and Haemophilus influenzae.
  • Skin and Soft Tissue Infections: Including cellulitis and abscesses.
  • Bone and Joint Infections: Such as osteomyelitis and septic arthritis.
  • Intra-abdominal Infections: Complicated intra-abdominal infections (often combined with metronidazole).
  • Meningitis: Effective against common pathogens causing bacterial meningitis.
  • Gonorrhea: Treatment of uncomplicated gonococcal infections.
  • Sepsis: Empirical treatment for severe infections and septic shock.

Contraindications:

  • Known hypersensitivity to ceftriaxone or other cephalosporins.
  • Severe allergic reactions to penicillin (cross-reactivity possible).
  • Newborns (particularly those requiring calcium treatment, due to risk of precipitation).

Side Effects:

Common Side Effects:

  • Nausea and vomiting
  • Diarrhea
  • Abdominal pain
  • Rash
  • Local irritation at injection site

Serious Side Effects:

  • Allergic reactions (anaphylaxis)
  • Superinfection (overgrowth of non-susceptible organisms)
  • Clostridium difficile-associated diarrhea (CDAD)
  • Hemolytic anemia
  • Liver enzyme elevations

Drug Interactions:

  • Probenecid: Can increase ceftriaxone levels by inhibiting renal excretion.
  • Calcium: Caution when administered simultaneously, especially in neonates, as it may lead to precipitation in the lungs and kidneys.
  • Anticoagulants: May enhance the anticoagulant effect of warfarin; monitoring is advised.

Nursing Considerations:

Administration: Ceftriaxone should be given IV or IM; ensure proper reconstitution if using the powder form.

Monitoring:

  • Monitor for signs of allergic reactions, especially after the first dose.
  • Assess liver and kidney function, as well as blood counts.
  • Watch for gastrointestinal symptoms and signs of superinfection.

Patient Education:

  • Advise patients to report any signs of rash, itching, or swelling.
  • Instruct on the importance of completing the full course of antibiotics.
  • Inform about potential side effects, including diarrhea, and when to seek medical attention.

CARBAPENEMS

Description: Carbapenems are broad-spectrum beta-lactam antibiotics resistant to most beta-lactamases.

Examples:

  • Imipenem + Cilastatin
  • Meropenem
  • Ertapenem

Pharmacokinetics:

  • Poor oral absorption; administered IV.
  • Widely distributed with high tissue concentrations.
  • Eliminated primarily through renal excretion.

Indications:

  • Complicated infections, intra-abdominal infections, CNS infections, skin and soft tissue infections, septicemia, and respiratory tract infections.

Contraindications:

  • Known hypersensitivity.

Side Effects:

  • Nausea, vomiting, diarrhea, hypersensitivity reactions, seizures, rash, headache.

Drug Interactions:

  • Probenecid can increase levels of carbapenems; concurrent use with valproic acid may reduce levels.

Nursing Considerations:

  • Monitor renal function and signs of hypersensitivity.
  • Educate patients about potential side effects.
  • Administer as a slow IV infusion.

MACROLIDES

Macrolides are a group of antibiotics derived from Streptomyces species. They exhibit primarily bacteriostatic activity but can be bactericidal against some bacteria at higher concentrations.

Mechanism of Action:

Macrolides inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit. This action disrupts the translation process, ultimately preventing the growth and replication of bacteria.

Examples of Macrolides:

  1. Erythromycin
  2. Azithromycin
  3. Clarithromycin
  4. Roxithromycin

Erythromycin

Available Preparations:

  • Tablet: 250 mg
  • Powder for Oral Suspension: 125 mg/5 mL

Dosage:

  • Adults: 250-500 mg
  • Children: 125-250 mg

Pharmacokinetics:

  • Absorption: Adequately absorbed from the gastrointestinal tract; optimal absorption occurs 1-2 hours after meals.
  • Distribution: Widely distributed in tissues; crosses the placenta and is secreted in breast milk.
  • Metabolism: Primarily metabolized in the liver.
  • Excretion: Excreted in bile.

Indications:

  • Pneumonia
  • Campylobacter enteritis
  • Acne vulgaris
  • Chancroid
  • Prostatitis
  • Acute otitis media
  • Sinusitis
  • Whooping cough
  • Lymphogranuloma venereum
  • Skin and soft tissue infections
  • Non-gonococcal urethritis
  • Bronchitis
  • Neonatal conjunctivitis
  • Pharyngitis and tonsillitis

Contraindications:

  • Allergy to macrolides
  • Porphyria
  • Severe hepatic impairment

Side Effects:

  • Nausea
  • Abdominal discomfort
  • Urticaria
  • Reversible hearing loss
  • Vomiting
  • Diarrhea
  • Skin rash
  • Pancreatitis

Drug Interactions:

  • Increases plasma concentrations of carbamazepine.

  • May inhibit the metabolism of dexamethasone, hydrocortisone, and prednisolone.

  • Increases the anticoagulant effect of warfarin.

Nursing Considerations for Erythromycin:

  • Administer on an empty stomach for optimal absorption unless gastrointestinal upset occurs, in which case it can be taken with food.

  • Inform the patient about potential drug interactions and the necessity to consult a healthcare provider before taking additional medications.

  • Monitor liver function, and discontinue use if severe hepatic dysfunction occurs.

Azithromycin

Available Preparations:

  • Capsules/Tablets: 250 mg, 500 mg
  • Powder for Oral Suspension: 200 mg/5 mL

Dosage:

  • Adults: 500 mg once daily
  • Children: 200 mg-500 mg once daily

Pharmacokinetics:

  • Absorption: Rapidly absorbed from the gut; food reduces its absorption.
  • Distribution: Widely distributed in body tissues.
  • Metabolism: Partially metabolized in the liver.
  • Excretion: Excreted in bile, both unchanged and as metabolites.

Indications:

  • Pneumonia
  • Skin and soft tissue infections
  • Typhoid fever
  • Pharyngitis/Tonsillitis
  • Trachoma
  • Pelvic inflammatory disease
  • Bronchitis
  • Pertussis (whooping cough)
  • Sinusitis
  • Otitis media
  • Traveler’s diarrhea
  • Mycobacterium avium complex (MAC) infections
  • Non-gonococcal urethritis

indications:

  • Known hypersensitivity to macrolides

  • Severe hepatic impairment

Side Effects:

  • Anorexia

  • Nausea

  • Vomiting

  • Dyspepsia

  • Constipation

  • Headache

  • Dizziness

  • Taste disturbances

  • Vertigo

  • Flatulence

  • Abdominal discomfort

  • Convulsions

  • Somnolence

  • Skin rash

Drug Interactions:

  • Concurrent administration of antacids containing aluminum or magnesium salts can reduce the absorption rate but not the extent of absorption.

  • Avoid concomitant use with lumefantrine and artemether.

  • Plasma concentrations of azithromycin may be increased by ritonavir.

  • Azithromycin increases the plasma concentration of digoxin.

  • Enhances the anticoagulant effect of warfarin.

  • The effectiveness of oral contraceptives may be reduced by azithromycin.

Nursing Considerations for Azithromycin:

  • Shake the suspension well before use.
  • Administer on an empty stomach (one hour before or two hours after meals).
  • Once-daily dosing is recommended due to its long half-life.

TETRACYCLINES

Tetracyclines are broad-spectrum antibacterial drugs derived from Streptomyces species. They are effective against both gram-positive and gram-negative bacteria and are active against organisms like mycoplasma, chlamydiae, spirochetes, and rickettsiae. However, due to widespread bacterial resistance, they are no longer the first-line treatment for many infections.

Mode of Action:

  • Bacteriostatic, inhibiting bacterial protein synthesis by reversibly binding to the 30S subunit of the bacterial ribosome.

Types of Tetracyclines:

  • Tetracycline
  • Doxycycline
  • Minocycline
  • Oxytetracycline

Tetracycline

Available Preparations:

  • Capsules 250mg
  • Eye ointment 1%
  • Skin ointment 3%

Pharmacokinetics:

  • Well absorbed but reduced by food presence.
  • Widely distributed to body tissues and fluids.
  • Partially metabolized in the liver.
  • Excreted unchanged in the urine.

Dose:

  • Adults: 250-500mg

Indications:

  • Brucellosis
  • Acne vulgaris
  • Trachoma
  • Lymphogranuloma venereum
  • Bronchitis
  • Non-gonococcal urethritis
  • Malaria
  • Gonorrhea
  • Shigellosis
  • Rosacea
  • Cholera
  • Pharyngitis
  • Sinusitis
  • Periodontal disease

Contraindications:

  • Children below 12 years
  • Pregnant and breastfeeding mothers
  • Known hypersensitivity to tetracyclines

Side Effects:

  • Anorexia
  • Nausea
  • Diarrhea
  • Sore throat
  • Photosensitivity
  • Epigastric distress
  • Vomiting
  • Stomatitis
  • Headache
  • Hypersensitivity reactions

Doxycycline

Available Preparations:

  • Capsules 100mg
  • Tablets 100mg

Dose:

  • Adults: 100mg twice daily (bd)

Pharmacokinetics:

  • Well absorbed orally.
  • Widely distributed to body tissues and fluids.
  • Excreted in feces.

Indications:

  • Acne vulgaris
  • Anthrax
  • Syphilis
  • Exacerbation of chronic bronchitis
  • Acute bacterial sinusitis
  • Pelvic inflammatory disease (PID)
  • Non-gonococcal urethritis
  • Malaria treatment and prevention
  • Recurrent aphthous ulcer

Contraindications:

  • Children under 8 years (causes staining and occasionally dental hypoplasia)
  • Pregnant and breastfeeding mothers
  • Hypersensitivity to tetracyclines
  • Porphyria

Side Effects:

  • Nausea
  • Vomiting
  • Loss of appetite
  • Esophageal irritation
  • Permanent staining of teeth
  • Vaginal candidiasis
  • Flushing
  • Diarrhea
  • Headache
  • Tinnitus
  • Photosensitivity

Drug Interactions:

  • Antacids, iron, calcium, and magnesium preparations impair absorption.
  • Doxycycline may increase the anticoagulant effect of oral anticoagulants.
  • Decreases therapeutic effect of penicillins.
  • May reduce the efficacy of oral contraceptives.

Nursing Considerations:

  • Should be taken with plenty of water to reduce esophageal irritation risk.
  • Avoid use in children below 12 years.
  • Photosensitivity may occur with prolonged sun exposure.

AMINOGLYCOSIDES

Aminoglycosides are antibacterial drugs derived from Actinomycetes species (Streptomyces and Micromonospora). They are poorly absorbed from the gastrointestinal tract, so they are administered via injection for systemic infections or topically for skin, mucous membrane, and ocular infections. Co-administration with cell wall-acting drugs like penicillins enhances their effectiveness.

Mode of Action:

  • Bactericidal, inhibiting protein synthesis by irreversibly binding to the 30S ribosomal subunit and causing cell membrane damage.

Types of Aminoglycosides:

  • Gentamicin
  • Streptomycin
  • Tobramycin
  • Paromomycin
  • Amikacin
  • Neomycin
  • Kanamycin

Gentamicin

Available Preparations:

  • Injection 80mg/2mL
  • Ear/Eye drops 0.3%
  • Skin ointment 0.1%

Pharmacokinetics:

  • Completely absorbed from IM injection sites.
  • Distributed to tissues and fluids, including urine (poor CSF penetration).
  • Excreted unchanged in urine; accumulates in renal impairment.

Dose:

  • Adults: 3-5 mg/kg daily (IM/IV)
  • Children (1 month-12 years): 2.5 mg/kg

Indications:

  • Urinary tract infections
  • Bacterial endocarditis
  • Pelvic inflammatory disease
  • Skin infections (burns, ulcers)
  • Surgical prophylaxis
  • Biliary tract infections
  • Otitis externa
  • Brucellosis
  • Pneumonia
  • Septicemia
  • Neonatal sepsis

Contraindications:

  • Hypersensitivity to aminoglycosides
  • Myasthenia gravis

Side Effects:

  • Nephrotoxicity
  • Ototoxicity
  • Headache
  • Rash
  • Nausea

  • Diarrhea

  • Blood disorders

Drug Interactions:

  • Increases nephrotoxicity risk with amphotericin B.
  • Increases ototoxicity risk with frusemide.
  • Vancomycin increases nephrotoxicity and ototoxicity risks.
  • Suxamethonium increases muscle relaxation effects.

Nursing Considerations:

  • Administer penicillins or cephalosporins at least one hour before or after gentamicin to avoid incompatibility.
  • Adjust dose in renal impairment.
  • Use cautiously in elderly patients due to the risk of renal and auditory impairment.

SULPHONAMIDES & TRIMETHOPRIM

Sulphonamides are a class of antibacterial agents structurally related to para-aminobenzoic acid (PABA). Their therapeutic importance has decreased due to widespread resistance. Trimethoprim is often combined with sulphonamides, specifically sulfamethoxazole, to form co-trimoxazole, increasing their effectiveness.

Mode of Action:

  • Sulphonamides are bacteriostatic, inhibiting bacterial folic acid synthesis.
  • Trimethoprim blocks bacterial dihydrofolate reductase, further inhibiting folate synthesis.

Types of Sulphonamides:

  • Cotrimoxazole (Trimethoprim + Sulfamethoxazole)
  • Sulphadiazine
  • Sulfasalazine
  • Sulphamethoxazole
  • Silver sulphadiazine
  • Sulphadoxine

Classification of Sulphonamides:

  • Rapidly absorbed and excreted: Sulphamethoxazole, Sulphadiazine
  • Poorly absorbed, active in bowel lumen: Sulfasalazine
  • Topical use: Silver sulphadiazine
  • Long-acting: Sulphadoxine

Cotrimoxazole (Trimethoprim + Sulfamethoxazole)

Available Preparations:

  • Tablets: 480mg, 960mg
  • Oral suspension: 240mg/5mL
  • Injection for infusion: 960mg/3mL

Dose:

  • Adults (oral): 960mg per dose
  • Children: 24mg/kg per dose

Pharmacokinetics:

  • Well absorbed after oral administration.
  • Widely distributed to tissues and fluids.
  • Excreted in urine.

Indications:

  • Urinary tract infections
  • Granuloma inguinale
  • Toxoplasmosis
  • Brucellosis
  • Shigellosis
  • Pneumocystis carinii pneumonia (PCP)
  • Pneumonia
  • Bronchitis
  • Otitis media
  • Traveler’s diarrhea

Contraindications:

  • Hypersensitivity to sulphonamides or trimethoprim
  • Severe renal or hepatic failure
  • Neonates

Side Effects:

  • Nausea
  • Headache
  • Skin rash
  • Urticaria
  • Anorexia
  • Photosensitivity reactions
  • Diarrhea
  • Itching
  • Renal failure
  • Hyperkalemia
  • Stomatitis

Drug Interactions:

  • Co-trimoxazole may increase digoxin levels.
  • Oral contraceptive efficacy may be reduced.
  • Co-trimoxazole increases the anticoagulant effect of warfarin.
  • May enhance the blood glucose-lowering effects of oral antidiabetics.

Nursing Considerations:

  • Ensure patients on co-trimoxazole take plenty of fluids to reduce crystalluria and potential kidney damage.
  • Monitor patients closely for life-threatening reactions and discontinue if any signs appear.

QUINOLONES

Quinolones are a class of synthetic antibacterial agents that inhibit bacterial DNA synthesis by targeting DNA gyrase and topoisomerase IV. They are bactericidal and effective against a broad range of gram-negative and some gram-positive bacteria. Quinolones are classified into generations based on their spectrum of activity.

Classification of Quinolones:

  • First-generation: Nalidixic acid
  • Second-generation: Ciprofloxacin, Norfloxacin, Ofloxacin, Pefloxacin, Lomefloxacin
  • Third-generation: Levofloxacin, Sparfloxacin, Gatifloxacin, Moxifloxacin

Nalidixic Acid

Available Preparations:

  • Tablets: 500mg

Pharmacokinetics:

  • Well absorbed from the gastrointestinal tract.
  • Concentrates in renal tissues and seminal fluid.
  • Metabolized in the liver to a more active form.
  • Excreted in urine.

Indications:

  • Urinary tract infections
  • Shigellosis

Contraindications:

  • Hypersensitivity
  • History of epilepsy
  • CNS lesions

Dose:

  • Adults: 500mg-1g every 6 hours
  • Children (>3 months): 15-50mg/kg every 6 hours

Side Effects:

  • Nausea
  • Dizziness
  • Confusion
  • Vomiting
  • Vertigo
  • Weakness
  • Skin rash
  • Urticaria
  • Headache
  • Cranial nerve palsy
  • Diarrhea
  • Visual disturbances
  • Abdominal pain
  • Convulsions

Drug Interactions:

  • Probenecid prolongs the half-life of nalidixic acid.
  • Increased risk of bleeding with oral anticoagulants.

Nursing Considerations:

  • Advise patients to take nalidixic acid on an empty stomach, preferably one hour before meals.

Ciprofloxacin

Available Preparations:

  • Tablets: 500mg, 1g
  • Injection: 200/100mL
  • Eye drops: 0.3% w/v

Pharmacokinetics:

  • Rapidly and well absorbed when taken orally, with 70-80% bioavailability.
  • Widely distributed throughout the body, with good tissue and bone penetration.
  • Metabolized in the liver.
  • Excreted in urine and feces.

Indications:

  • Urinary tract infections
  • Surgical prophylaxis
  • Chronic prostatitis
  • Traveler’s diarrhea
  • Shigellosis
  • Peritonitis
  • Gonorrhea
  • Respiratory tract infections
  • Prophylaxis of meningococcal meningitis
  • Septicemia
  • Typhoid
  • Chancroid
  • Cholera
  • Otitis externa
  • Bone and joint infections
  • Anthrax

Contraindications:

  • Breastfeeding
  • Pregnancy
  • Allergy to ciprofloxacin
  • Children below 18 years

Dose:

  • Oral (adults): 250-750mg twice daily

Side Effects:

  • Headache
  • Restlessness
  • Palpitations
  • Diarrhea
  • Drowsiness
  • Depression
  • Nausea and vomiting
  • Urticaria
  • Anorexia
  • Dizziness
  • Lightheadedness
  • Skin rash
  • Convulsions
  • Dyspepsia
  • Tremors
  • Abdominal discomfort
  • Insomnia

Drug Interactions:

  • Antacids containing aluminum and magnesium interfere with absorption.
  • Concomitant use with probenecid increases ciprofloxacin plasma levels.
  • Ciprofloxacin increases phenytoin, theophylline, and anticoagulant blood levels.
  • Efficacy is reduced by iron salts and sucralfate.
  • May increase the effects of oral anticoagulants.

Nursing Considerations:

  • Ciprofloxacin should be taken one hour before or two hours after meals for optimal absorption.
  • Advise patients to drink plenty of fluids while on ciprofloxacin.
  • Patients should avoid taking dairy products, antacids, iron, zinc, or calcium supplements with ciprofloxacin.
  • Ciprofloxacin may increase the effects of caffeine, so advise patients to reduce caffeine intake.
  • It may worsen seizures in epileptic patients.

NITROIMIDAZOLES

Nitroimidazoles are a class of antimicrobial agents that are primarily effective against anaerobic bacteria and protozoa. They work by disrupting DNA synthesis in these microorganisms.

Mechanism of Action: Nitroimidazoles, including metronidazole, are prodrugs that require reduction by anaerobic bacteria or protozoa to become active. The reduced form interacts with DNA, causing strand breakage and inhibiting nucleic acid synthesis, ultimately leading to cell death.

METRONIDAZOLE

Description: Metronidazole is a synthetic nitroimidazole antibiotic with antiprotozoal and antibacterial properties, particularly effective against anaerobic bacteria and certain protozoa such as Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia.

Pharmacokinetics:

  • Absorption: Rapidly and well absorbed from the gastrointestinal tract; food does not significantly affect absorption.
  • Distribution: Widely distributed in body tissues and fluids, including the CNS and saliva.
  • Metabolism: Primarily metabolized in the liver.
  • Excretion: Excreted mainly through urine as metabolites.

Dosage:

  • Adult Dose: Varies based on infection; typically, 500 mg orally 2-3 times daily for infections.

Indications

  • Bacterial Infections: Anaerobic infections, including intra-abdominal infections, pelvic inflammatory disease, and skin and soft tissue infections.
  • Protozoal Infections:
  1. Trichomoniasis
  2. Giardiasis
  3. Amoebic dysentery
  • Clostridium difficile Infection: Used in treatment of mild to moderate cases.
  • Surgical Prophylaxis: Particularly in colorectal surgery.

  • Other Uses: Treatment of H. pylori eradication in peptic ulcer disease, rosacea, and bacterial vaginosis.

Contraindications

  • Known Hypersensitivity: Avoid in patients with a history of hypersensitivity to metronidazole or other nitroimidazoles.
  • First Trimester of Pregnancy: Use with caution; avoid unless absolutely necessary.

Side Effects

  • Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain, metallic taste.
  • Neurological: Headaches, dizziness, peripheral neuropathy (with long-term use).
  • Dermatological: Rash, urticaria, Stevens-Johnson syndrome (rare).
  • Other: Darkening of urine, seizures (rare, with overdose).

Drug Interactions

  • Alcohol: Concurrent use can lead to a disulfiram-like reaction (flushing, nausea, vomiting).
  • Anticoagulants: May enhance the effects of warfarin and other anticoagulants, increasing bleeding risk.
  • Lithium: Metronidazole may increase lithium levels, leading to toxicity.
  • CYP450 Inhibitors: May interact with drugs metabolized by CYP enzymes, potentially increasing their effects.

Nursing Considerations

  • Administering Medication: Metronidazole can be given orally or intravenously; for intravenous administration, infuse slowly to prevent infusion reactions.
  • Patient Education:
  1. Instruct patients to avoid alcohol during treatment and for at least 48 hours after discontinuation.
  2. Advise patients about potential side effects, including gastrointestinal disturbances and metallic taste.
  • Monitoring:
  1. Monitor liver function tests, especially in patients with hepatic impairment.
  2. Assess for signs of peripheral neuropathy, particularly with prolonged use.
  3. Ensure patients complete the full course of therapy to prevent resistance.

Specific Anti-microbial Agents Read More »

DRUGS USED IN PAEDIATRICS

DRUGS USED IN PAEDIATRICS

The field of pediatric pharmacology focuses on the safe and effective use of medications in children, from infancy to adolescence. 

Pediatric patients require special consideration due to their developing physiology, which affects how drugs are absorbed, distributed, metabolized, and excreted. Here is an introduction to the key aspects of drugs used in pediatrics:

Nursing Considerations in Pediatric Pharmacology

1. Developmental Pharmacokinetics:

  • Absorption: The gastrointestinal tract of infants and young children is still developing, which can affect the absorption of oral medications.
  • Distribution: The distribution of drugs can vary due to differences in body composition, such as higher total body water and lower fat content in infants.
  • Metabolism: The liver enzymes responsible for drug metabolism are not fully mature in newborns and infants, leading to slower drug clearance.
  • Excretion: Renal function is also immature in newborns, affecting the excretion of drugs and their metabolites.

2. Dosing Considerations:

  • Dosing in pediatrics is often based on body weight or body surface area rather than fixed doses used in adults.
  • Growth and development can rapidly change, requiring frequent adjustments in dosing.

3. Safety and Adverse Effects:

  • Children are more susceptible to certain adverse effects due to their developing organs and systems.
  • Long-term effects of medications on growth, development, and future health must be considered.

4. Off-Label Use:

  • Many medications used in pediatrics are not specifically approved for use in children, leading to off-label prescribing based on clinical experience and available data.

1. Antibiotics

Ampicillin

Ampicillin

  • Dose: 50 mg/kg
  • Class: Beta-lactam antibiotic, specifically a penicillin derivative.
  • Mechanism of Action: Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins.

Indications:

  • Effective against Gram-positive bacteria like Streptococcus pneumoniae, Enterococcus faecalis, and some Gram-negative bacteria like Haemophilus influenzae.
  • Bacterial infections (e.g., pneumonia, meningitis)
  • Urinary tract infections
  • Otitis media
  • Sepsis
  • Endocarditis prophylaxis
  • Gastrointestinal infections
  • Skin and soft tissue infections

Contraindications:

  • Hypersensitivity to penicillin or cephalosporins
  • History of severe allergic reactions (anaphylaxis)
  • Severe renal impairment
  • Infectious mononucleosis (risk of rash)

Nursing Considerations:

  • Monitor for allergic reactions (e.g., rash, difficulty breathing).
  • Assess renal function prior to administration.
  • Administer with caution in patients with a history of seizures.
  • Confirm proper dosing based on weight and age.
  • Pharmacokinetics: Ampicillin is absorbed in the gastrointestinal tract but is susceptible to degradation by stomach acids. It has good tissue penetration and crosses the placenta.
  • Adverse Effects: Diarrhea, allergic reactions, including anaphylaxis in susceptible patients.

Gentamicin-InjectionIntogen-2ml-scaled

Gentamicin

  • Dose: 7.5 mg/kg
  • Class: Aminoglycoside antibiotic.
  • Mechanism of Action: Bactericidal, inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.

Indications:

  1. Treatment of severe infections caused by Gram-negative bacteria like E. coli and Klebsiella; also used in neonatal sepsis.
  2. Serious bacterial infections (e.g., sepsis, pneumonia)
  3. Urinary tract infections
  4. Infections in immunocompromised patients
  5. Endocarditis (in combination with other antibiotics)
  6. Osteomyelitis
  7. Intra-abdominal infections

  8. Meningitis (if caused by susceptible organisms)

Contraindications:

  1. Hypersensitivity to aminoglycosides
  2. Pre-existing renal impairment
  3. Myasthenia gravis
  4. Concurrent use of other nephrotoxic or ototoxic drugs

Nursing Considerations:

  • Monitor renal function and drug levels (peak and trough).
  • Assess for signs of ototoxicity (e.g., tinnitus, dizziness).
  • Administer IV slowly to reduce the risk of toxicity.
  • Ensure hydration to minimize nephrotoxicity.
  • Pharmacokinetics: Poor oral absorption; given intravenously or intramuscularly. Mainly excreted through the kidneys.
  • Adverse Effects: Ototoxicity, nephrotoxicity, vestibular damage.

Benzyl Penicillin (Penicillin G)

  • Dose: 50,000 IU/kg
  • Class: Beta-lactam antibiotic.
  • Mechanism of Action: Inhibits cell wall synthesis, particularly effective against Gram-positive bacteria.

Indications:

  1. Severe infections (e.g., pneumonia, meningitis)
  2. Syphilis
  3. Streptococcal and staphylococcal infections
  4. Endocarditis
  5. Bacterial endophthalmitis
  6. Bone and joint infections
  7. Meningitis

Contraindications:

  1. Hypersensitivity to penicillin
  2. History of anaphylaxis to related antibiotics
  3. Severe liver impairment
  4. Caution in patients with asthma

Nursing Considerations:

  • Monitor for allergic reactions after administration.
  • Review liver and renal function tests.
  • Administer via appropriate route and ensure correct dilution.
  • Educate families on signs of allergic reactions.
  • Pharmacokinetics: Poor oral absorption, so it is administered intramuscularly or intravenously.
  • Adverse Effects: Hypersensitivity reactions, including rash and anaphylaxis.

Amoxicillin

Amoxicillin

  • Dose: Based on age.
  1. 2-12 months: 250 mg every 12 hours for 5 days
  2. 1-3 years: 500 mg every 12 hours for 5 days
  3. 3-5 years: 750 mg every 12 hours for 5 days
  • Class: Aminopenicillin.
  • Mechanism of Action: Inhibits bacterial cell wall synthesis.

Indications:

  1. Otitis media
  2. Lower respiratory tract infections, and bacterial sinusitis.
  3. Pneumonia
  4. Urinary tract infections
  5. Skin and soft tissue infections
  6. Gastrointestinal infections (e.g., H. pylori eradication)
  7. Endocarditis prophylaxis

Contraindications:

  1. Hypersensitivity to penicillin
  2. History of jaundice or liver disease with prior amoxicillin use
  3. Pregnant women with a history of certain liver conditions
  4. Severe renal impairment without dosage adjustment

Nursing Considerations:

  • Observe for allergic reactions.
  • Administer with or without food (food may help with stomach upset).
  • Educate about the full course of treatment completion.
  • Assess for superinfection (e.g., oral thrush).
  • Pharmacokinetics: Well absorbed orally, widely distributed, and excreted in urine.
  • Adverse Effects: Rash, gastrointestinal disturbances like nausea and diarrhea.

Ciprofloxacin

Ciprofloxacin

  • Dose: 15 mg/kg every 12 hours for 3 days.
  1. If using a 500 mg tablet:
  2. Child < 6 months: ¼ tab.
  3. Child 6 months–5 years: ½ tab.
  • Class: Fluoroquinolone antibiotic.
  • Mechanism of Action: Inhibits bacterial DNA gyrase and topoisomerase IV, inhibiting DNA replication.

Indications:

  1. Urinary tract infections
  2. Gastrointestinal infections (e.g., shigellosis. Gastroenteritis (certain pathogens)
  3. Skin and soft tissue infections
  4. Bone and joint infections
  5. Anthrax prophylaxis
  6. Respiratory infections
  7. Infectious diarrhea

Contraindications:

  1. Hypersensitivity to fluoroquinolones
  2. History of tendon disorders related to fluoroquinolones
  3. Myasthenia gravis
  4. Children under 18 years (except for specific infections)

Nursing Considerations:

  • Monitor for signs of tendon pain or rupture.
  • Educate on potential side effects (e.g., gastrointestinal symptoms).
  • Administer with caution in patients with seizure history.
  • Encourage hydration to prevent crystallization in urine.
  • Pharmacokinetics: Well absorbed orally but may be reduced by antacids. Mainly excreted unchanged in the urine.
  • Adverse Effects: Tendon rupture (rare but more frequent in children), photosensitivity, nausea.

2. Antimalarials

artesunate

Rectal Artesunate

  • Dose: 10 mg/kg
  • Class: Antimalarial, artemisinin derivative.
  • Mechanism of Action: Produces reactive oxygen species that damage the parasite’s proteins and membranes.

Indications:

  1. Severe malaria in children unable to take oral medications
  2. Malaria in pregnant women
  3. Alternative for first-line treatments in specific situations
  4. Emergency treatment for life-threatening malaria

Contraindications:

  1. Hypersensitivity to artemisinin and derivatives
  2. Patients with a known history of severe allergic reactions
  3. Caution in patients with severe hepatic or renal impairment
  4. Infants under a specific weight threshold

Nursing Considerations:

  • Monitor vital signs and blood glucose levels due to potential hypoglycemia.
  • Educate families on the administration technique.
  • Assess for neurologic changes or adverse reactions.
  • Ensure proper storage conditions for the medication.
  • Pharmacokinetics: Rapid absorption and action when given rectally. Metabolized in the liver.
  • Adverse Effects: Nausea, vomiting, dizziness, and occasional allergic reactions.

Artemether

Artemether/Lumefantrine (Coartem)

  • Dose: Every 12 hours for 3 days.
  1. 2-12 months: 1 tablet
  2. 1-3 years: 1 tablet
  3. 3-5 years: 2 tablets
  • Class: Antimalarial.
  • Mechanism of Action: Artemether kills rapidly, while lumefantrine has a longer half-life and helps prevent recrudescence.

Indications:

  1. Uncomplicated malaria caused by Plasmodium falciparum
  2. Malaria prophylaxis in certain regions
  3. Alternative in cases of drug resistance
  4. Combination therapy for effective treatment regimen

Contraindications:

  1. Hypersensitivity to artemether, lumefantrine, or any excipient
  2. History of severe allergic reactions
  3. Severe liver dysfunction
  4. Caution in patients with underlying cardiac arrhythmias

Nursing Considerations:

  • Monitor for cardiac effects (QT prolongation).
  • Administer with food to increase absorption.
  • Educate about possible side effects (nausea, headache).
  • Assess for resolution of malaria symptoms.
  • Pharmacokinetics: Oral absorption is enhanced with fatty meals.
  • Adverse Effects: Dizziness, weakness, and gastrointestinal disturbances.

 

3. Antiparasitics

Mebendazole

Mebendazole

  • Dose:
  1. Child 1-2 years: 250 mg single dose.
  2. Child > 2 years: 500 mg single dose.
  • Class: Anthelmintic.
  • Mechanism of Action: Inhibits the uptake of glucose by parasitic worms, leading to their immobilization and death.

Indications:

  1. Enterobiasis (pinworm infection)
  2. Ascariasis (roundworm infection)
  3. Hookworm infections
  4. Whipworm infections
  5. Other intestinal helminthic infections
  6. Strongyloidiasis
  7. Preventive treatment in endemic areas

Contraindications:

  1. Hypersensitivity to mebendazole or any excipients
  2. Pregnancy (especially in the first trimester)
  3. Caution in patients with liver dysfunction
  4. Infants under 2 years (consult a physician)

Nursing Considerations:

  • Administer with or without food; it is often preferred to take it with food for better absorption.
  • Monitor for gastrointestinal side effects (e.g., diarrhea).
  • Educate on hygiene measures to prevent reinfection.
  • Assess for any signs of infection or allergic reactions.
  • Pharmacokinetics: Poorly absorbed from the gastrointestinal tract, primarily excreted unchanged in the feces.
  • Adverse Effects: Abdominal pain, diarrhea, headache.

Albendazole

Albendazole

  • Dose:
  1. Child 1-2 years: 200 mg single dose.
  2. Child > 2 years: 400 mg single dose.
  • Class: Anthelmintic.
  • Mechanism of Action: Inhibits glucose uptake by helminths, disrupting their energy production.

Indications:

  1. Broad-spectrum treatment for intestinal parasites, including pinworms and roundworms.
  2. Neurocysticercosis
  3. Echinococcal disease (hydatid cyst disease)
  4. Ascariasis (roundworm)
  5. Enterobiasis (pinworm)
  6. Hookworm infections
  7. Whipworm infections
  8. Giardiasis (in certain cases)

Contraindications:

  1. Hypersensitivity to albendazole or any excipients
  2. Pregnant women (especially in the first trimester)
  3. Severe liver disease
  4. Caution in patients with a history of bone marrow suppression

Nursing Considerations:

  • Monitor liver function tests during treatment.
  • Administer with food to enhance absorption.
  • Educate about potential side effects (e.g., headache, dizziness).
  • Assess for signs of hypersensitivity or allergic reactions.
  • Pharmacokinetics: Poor absorption; metabolized in the liver.
  • Adverse Effects: Nausea, vomiting, dizziness, headache.

4. Analgesics/Antipyretics

More on Opioids later.

Paracetamol (Acetaminophen)

  • Dose: Every 6 hours (4 doses in 24 hours).
  1. 2 months–3 years: 125 mg.
  2. 3-5 years: 250 mg.
  • Class: Analgesic and antipyretic.
  • Mechanism of Action: Inhibits prostaglandin synthesis, reducing pain and fever.
  • Indications: Relief of mild to moderate pain, and fever reduction.

Indications:

  1. Fever management
  2. Pain relief (e.g., headache, toothache)
  3. Post-immunization fever
  4. Musculoskeletal pain (mild to moderate)
  5. Management of pain in children post-surgery
  6. Fever due to infections
  7. Rheumatic disease pain

Contraindications:

  1. Severe liver dysfunction
  2. Known hypersensitivity to paracetamol
  3. Active liver disease
  4. Caution in patients with chronic alcohol use

Nursing Considerations:

  1. Monitor for signs of overdose (e.g., nausea, vomiting).
  2. Educate caregivers on dosage based on weight.
  3. Assess liver function in patients with prolonged use.
  4. Reinforce the importance of not exceeding the recommended dose.
  5. Pharmacokinetics: Well absorbed orally; metabolized in the liver.
  6. Adverse Effects: Hepatotoxicity in overdose, rash, nausea.

5. Vitamins and Supplements

Folic Acid

  • Dose: 2.5 mg daily.
  • Class: Vitamin, essential for DNA synthesis.
  • Indications: Prevents and treats folic acid deficiency anemia, often given to malnourished children or those with megaloblastic anemia.

Indications:

  1. Megaloblastic anemia due to folate deficiency
  2. Prevention of neural tube defects during pregnancy
  3. Supplementation in malabsorptive conditions
  4. Certain leukemias or malignancies
  5. Alcoholism
  6. Patients on methotrexate or other drugs that inhibit folate metabolism
  7. Growth periods (infancy, adolescence)

Contraindications:

  1. Known hypersensitivity to folate or any excipients
  2. Untreated cobalamin deficiency (may worsen this condition)
  3. Caution in patients overusing alcohol
  4. Certain malignancies (without close supervision)

Nursing Considerations:

  • Monitor for signs of deficiency (e.g., anemia symptoms).
  • Educate patients about the importance of diet rich in folate.
  • Assess history of medication use that affects folate metabolism.
  • Encourage supplementation before and during pregnancy.
  • Pharmacokinetics: Absorbed from the small intestine, metabolized in the liver.
  • Adverse Effects: Rare at therapeutic doses; may cause nausea or rash.

Iron

Iron (Ferrous Sulfate)

  • Dose: Once daily for 14 days.
  1. Tablet 200 mg (1/2 tablet for children 1-5 years).
  2. Syrup 25 mg/mL (1 mL for children < 1 year).
  • Class: Mineral supplement.
  • Mechanism of Action: Replenishes iron stores for hemoglobin synthesis.
  • Indications: Treatment of iron deficiency anemia.

Indications:

  1. Iron-deficiency anemia
  2. Prevention of iron deficiency in at-risk populations (e.g., pregnant women, infants)
  3. Chronic blood loss (e.g., GI bleeding)
  4. Nutritional deficiency in vegetarians/vegans
  5. Hemodialysis patients requiring iron replacement
  6. Post-surgical patients with significant blood loss
  7. Patients with malabsorption syndromes

Contraindications:

  1. Hemochromatosis (iron overload)
  2. Hemosiderosis
  3. Known hypersensitivity to iron preparations
  4. Certain gastrointestinal conditions (e.g., peptic ulcer disease)

Nursing Considerations:

  • Monitor hemoglobin and hematocrit levels during therapy.
  • Administer on an empty stomach to enhance absorption (unless gastrointestinal upset occurs).
  • Assess for gastrointestinal side effects (constipation, nausea).
  • Educate on dietary sources of iron and adherence to therapy.
  • Adverse Effects: Constipation, gastrointestinal discomfort, dark stools.

6. Antiepileptics/Anticonvulsants

Diazepam in Paediatrics

Class: Benzodiazepine
Pediatric Dose: 0.5 mg/kg (rectal)

Key Points:

  1. Mechanism of Action: Diazepam acts on the gamma-aminobutyric acid (GABA) receptors, enhancing inhibitory neurotransmission, which results in sedation, muscle relaxation, and anti-convulsant effects.
  2. Indications in Pediatrics: Used for febrile seizures, status epilepticus, and acute anxiety disorders in children.

Indications:

  1. Management of anxiety disorders
  2. Treatment of muscle spasm (e.g., from cerebral palsy)
  3. Control of seizures (status epilepticus)
  4. Sedation for medical procedures (preoperative sedation)
  5. Management of acute alcohol withdrawal symptoms
  6. Treatment of hyperactivity in specific cases
  7. Treatment of insomnia in short-term use
  8. Management of panic attacks

Contraindications:

  1. Hypersensitivity to benzodiazepines
  2. Severe respiratory insufficiency (e.g., sleep apnea)
  3. Acute narrow-angle glaucoma
  4. Myasthenia gravis
  5. Pregnancy (especially during the first trimester)
  6. Lactation (not recommended in breastfeeding mothers)
  7. Children under six months of age (unless in severe cases)

Nursing Considerations:

  1. Monitor vital signs (respiration, heart rate) closely during treatment.
  2. Assess for sedation levels and degree of muscle relaxation.
  3. Educate families about the potential for dependence and withdrawal symptoms.
  4. Administer the drug slowly intravenously (if applicable) to prevent hypotension.
  5. Side Effects: Sedation, dizziness, hypotension, and respiratory depression. In children, excessive drowsiness and ataxia can occur.

7. Antifungals

Nystatin

Nystatin in Pediatrics

Class: Antifungal (Polyene)
Pediatric Dose: 1 mL (oral suspension), four times daily for 7 days

Key Points:

  1. Mechanism of Action: Nystatin binds to ergosterol in the fungal cell membrane, causing membrane disruption and leading to leakage of cellular contents, ultimately killing the fungal cells.
  2. Indications in Pediatrics: Primarily used for oral candidiasis (thrush) and fungal infections in the gastrointestinal tract. It’s often prescribed for neonates and young infants due to its safety profile.

Indications:

  1. Treatment of oral thrush (candida stomatitis)
  2. Management of esophageal candidiasis
  3. Treatment of skin infections caused by Candida
  4. Prophylaxis for fungal infections in immunocompromised children
  5. Treatment of diaper dermatitis due to yeast
  6. Treatment of vaginal candidiasis (in specific cases)
  7. Treatment of gastrointestinal candidiasis

Contraindications:

  1. Hypersensitivity to nystatin or any component of the formulation
  2. Caution in patients with severe gastrointestinal disease
  3. Topical use in patients with open wounds or burns
  4. Not recommended for systemic fungal infections (not effective)
  5. Caution in patients with adrenal insufficiency

Nursing Considerations:

  1. Monitor for improvement of symptoms (e.g., resolution of thrush).
  2. Instruct parents on proper administration techniques (oral and topical).
  3. Assess for side effects (e.g., gastrointestinal upset).
  4. Evaluate the necessity for concurrent antifungal medications in systemic infections.
  5. Administration: Nystatin is given orally in the form of a suspension. For oral candidiasis, the suspension is swished in the mouth and swallowed.
  6. Side Effects: Generally well-tolerated. Some children may experience mild gastrointestinal disturbances such as nausea, vomiting, or diarrhea. Rarely, allergic reactions like rash may occur.

Griseofulvin

Griseofulvin in Pediatrics

Class: Antifungal (Fungistatic)
Pediatric Dose:

  • 10-20 mg/kg/day (depending on the type and severity of the fungal infection)

Key Points:

  1. Mechanism of Action: Griseofulvin disrupts fungal cell mitosis by binding to microtubules, inhibiting fungal cell division.
  2. Indications in Pediatrics: Primarily used for dermatophytosis (fungal infections of the skin, hair, and nails), such as tinea capitis (scalp ringworm) and tinea corporis (body ringworm).

Indications:

  1. Treatment of tinea capitis (scalp ringworm)
  2. Treatment of tinea corporis (ringworm of the body)
  3. Treatment of tinea cruris (jock itch)
  4. Treatment of tinea pedis (athlete’s foot)
  5. Onychomycosis (fungal infection of the nails)
  6. Prophylaxis against dermatophyte infections in specific cases
  7. Infection of the hair and nails caused by fungi

Contraindications:

  1. Hypersensitivity to griseofulvin or any component of the formulation
  2. Liver dysfunction or active hepatic disease
  3. Pregnancy (known teratogenic effects)
  4. Porphyria
  5. Caution in patients with penicillin allergy (cross-reactivity)

Nursing Considerations:

  1. Monitor for liver function tests periodically during therapy.
  2. Assess for gastrointestinal side effects (nausea, vomiting).
  3. Ensure patients comply with a full course of treatment to prevent recurrence.
  4. Educate parents on the importance of using the medication consistently and checking for signs of fungal infection.
  5. Administration: Administered orally. Absorption is enhanced when taken with fatty foods (e.g., milk or ice cream), which helps improve its efficacy.
  6. Side Effects: Common side effects include gastrointestinal upset, headache, dizziness, fatigue, and skin rashes. Prolonged use may cause photosensitivity (increased sensitivity to sunlight).

Clotrimazole in Pediatrics

Class: Antifungal (Imidazole)
Pediatric Dose: 1% cream or lotion (applied topically)

Key Points:

  1. Mechanism of Action: Clotrimazole interferes with fungal cell membrane integrity by inhibiting ergosterol synthesis, leading to fungal cell death.
  2. Indications in Pediatrics: Topical clotrimazole is commonly used to treat fungal skin infections such as tinea pedis (athlete’s foot), tinea corporis, and cutaneous candidiasis.

Indications:

  1. Topical treatment of dermatophyte infections (e.g., ringworm)
  2. Treatment of candidiasis (fungal infections) of the skin
  3. Management of tinea pedis (athlete’s foot)
  4. Treatment of tinea cruris (jock itch)
  5. Treatment of vulvovaginal candidiasis (in females)
  6. Oral candidiasis (thrush) (topical formulations)
  7. Prevention of fungal infections in at-risk pediatric populations

Contraindications:

  1. Hypersensitivity to clotrimazole or any of its components
  2. Open wounds or extensive areas of burns (topical use)
  3. Known hepatic impairment (with caution)
  4. Use in pregnancy (especially during the first trimester) should be monitored
  5. Caution in pediatric patients under two years old

Nursing Considerations:

  1. Monitor the skin for improvement of fungal infections.
  2. Educate patients and parents on the proper application technique.
  3. Instruct about maintaining skin hygiene to prevent recurrence of infection.
  4. Assess for any signs of hypersensitivity reaction (rash, itching) after application.
  5. Side Effects: Mild skin irritation, burning, and redness are the most common adverse effects

OPIOID ANALGESICS

Opioid analgesics are drugs derived from opium or synthetic analogs, primarily prepared from the poppy plant (Papaver somniferum). They are the most effective pain relievers available and are commonly used as first-line therapy for the management of:

  • Acute severe pain
  • Moderate to severe chronic pain associated with cancer, AIDS, or other life-threatening conditions

Classification:

  1. Weak opioid analgesics: e.g., codeine.
  2. Strong opioid analgesics: e.g., morphine, pethidine, and methadone.

Mechanism of Action:
Opioids relieve pain by mimicking the effects of endogenous opioid peptides (like endorphins), primarily by binding to the mu-opioid receptors. These receptors are found in both the ascending and descending pain pathways in the brain and spinal cord. By binding to these receptors, opioids alter pain perception and can produce euphoria and relaxation, which help alleviate the stress and emotional distress that often accompanies severe pain.

Codeine

Available Preparations:

  • Tablets: 30 mg

Indications:

  • Mild to moderate pain
  • Cough suppression
  • Diarrhea

Contraindications:

  • Respiratory depression
  • Obstructive airway disease
  • Hypersensitivity to codeine
  • Acute alcoholism
  • Risk of paralytic ileus
  • Raised intracranial pressure or head injury

Dosage:

  • Relief of pain:
  1. Adults: 30 mg–60 mg every 4–6 hours, maximum dose of 240 mg/day.
  2. Children (1–12 years): 0.5 mg–1 mg/kg every 4–6 hours.
  • Diarrhea:
  1. Adults: 30 mg 4–6 times daily.

Pharmacokinetics:

  • Well absorbed after oral administration.
  • Widely distributed in the body, crosses the placenta, and enters breast milk.
  • Metabolized in the liver and excreted primarily in urine.

Side Effects:

  • Constipation
  • Dry mouth
  • Facial flushing
  • Nausea and vomiting
  • Difficulty urinating
  • Headache and dizziness
  • Sweating

Drug Interactions:

  • Alcohol and other CNS depressants increase the sedative effects of codeine.
  • Rifampicin and phenytoin may increase the accumulation of codeine.
  • Severe cardiovascular depression may occur when used with general anesthetics.

Nursing Considerations:

  • Encourage increased fluid and fiber intake to prevent constipation.
  • Avoid alcohol during codeine therapy.
  • Avoid abrupt discontinuation after prolonged use to prevent withdrawal symptoms.
  • Codeine is not recommended for productive cough.
  • Administer with food to minimize nausea and GI upset.

Morphine

Type:
Strong, centrally acting opioid analgesic.

Available Preparations:

  • Oral solution: 5 mg/5 ml, 10 mg/5 ml, 50 mg/5 ml
  • Injection: 10 mg/ml, 15 mg/ml

Indications:

  • Severe pain (e.g., post-operative, cancer pain)
  • Myocardial infarction
  • Premedication before surgery
  • Sickle cell crisis
  • Acute pulmonary edema
  • Chronic pain

Contraindications:

  • Acute respiratory depression
  • Hypersensitivity to morphine
  • Acute alcoholism
  • Head injury
  • Acute abdominal pain
  • Raised intracranial pressure
  • Avoid injections in patients with pheochromocytoma

Pharmacokinetics:

  • Absorbed variably from the gastrointestinal tract (GIT).
  • Widely distributed throughout the body.
  • Metabolized mainly in the liver.
  • Excreted in urine and bile.

Mechanism of Action:
Morphine binds to opioid receptors in the central nervous system (CNS), altering both the perception of and emotional response to pain. It has both depressing and stimulating effects on the CNS:

Depressing effects:

  1. Reduces the brain’s appreciation of pain.
  2. Depresses respiration.
  3. Depresses the cough reflex.
  4. Acts as a mild hypnotic, inducing sleep or drowsiness.
  5. Causes euphoria and reduces anxiety.

Stimulating effects:

  1. Stimulates the chemoreceptor trigger zone, causing nausea and vomiting in some patients.
  2. Causes pupil constriction due to effects on the third cranial nerve.
  3. Decreases bowel peristalsis, leading to constipation.

Dosage:

Acute pain (post-operative pain):

  1. Oral: 5–20 mg every 4 hours.
  2. Subcutaneous (SC) or intramuscular (IM):
  • Adults: 10 mg every 4 hours if necessary.
  • Children (6–12 years): 5–10 mg every 4 hours.
  • Children (1–5 years): 2.5–5 mg every 4 hours.
  • Neonates: 150 mcg/kg 4 times a day.

Chronic pain:

  1. Adults: 10–15 mg every 4 hours.
  2. Children (1–12 years): 200–400 mcg/kg every 4 hours.

Side Effects:

  • Nausea and vomiting
  • Constipation
  • Respiratory depression
  • Postural hypotension
  • Urinary retention
  • Euphoria or hallucinations
  • Sweating
  • Bradycardia
  • Decreased libido
  • Dependency

Drug Interactions:

  • Increases sedative effects when combined with antidepressants, antipsychotics, or sedating antihistamines.
  • May lead to severe cardiovascular depression when used with drugs metabolized by the liver (e.g., phenytoin, rifampicin).

Nursing Considerations:

  • Avoid alcohol during morphine therapy.
  • Prolonged use may lead to dependence, and abrupt discontinuation should be avoided.
  • Caution patients about the potential for low blood pressure and blurred vision.
  • Naloxone can be used to treat morphine overdose.
  • Watch for urinary retention, especially in patients with prostatic hypertrophy.

Pethidine

Type:
Synthetic opioid, less potent than morphine but equally effective in pain management.

Available Preparations:

  • Injection: 50 mg/ml, 100 mg/ml

Routes of Administration:
Intramuscular (IM), intravenous (IV), subcutaneous (SC), or oral.

Indications:

  • Pre-operative medication
  • Acute analgesia (e.g., post-operative, obstetric)
  • Moderate to severe acute pain

Contraindications:

  • Hypersensitivity to pethidine
  • Acute respiratory depression
  • Severe renal or liver disease
  • Head injury and raised intracranial pressure

Pharmacokinetics:

  • Well absorbed orally, with a bioavailability of 50%.
  • Onset of action: 10–15 minutes after oral administration.
  • Short duration of action: 2–3 hours.
  • Metabolized in the liver; excreted in urine.

Dosage:

Acute pain:

  • Adults: 50–150 mg, repeated after 4 hours if necessary.
  • Children: 0.5–2 mg/kg every 4 hours.

Obstetric analgesia:

  • 50–100 mg, repeated every 1–3 hours, with a maximum dose of 400 mg/day.

Side Effects:

  • Nausea and vomiting
  • Constipation
  • Respiratory depression
  • Postural hypotension
  • Urinary retention
  • Sweating, palpitations
  • Dependency, hallucinations
  • Bradycardia

Drug Interactions:

  • Phenothiazines may cause severe hypotensive episodes and prolonged respiratory depression.
  • Alcohol and other CNS depressants potentiate respiratory depression.
  • Cimetidine may decrease pethidine elimination, increasing the risk of toxic effects.

Nursing Considerations:

  • Prolonged use may lead to physical dependence.
  • Use the lowest effective dose, especially in labor.
  • Avoid alcohol during therapy.

Opioid/Narcotic Antagonist:

Naloxone

Type:
A drug that reverses the effects of opioid analgesics.

Indications:

  • Opioid overdose (e.g., morphine overdose)
  • Neonatal asphyxia due to opioid use during labor
  • Diagnosis of opioid dependence (it worsens withdrawal symptoms)
  • Opioid-induced respiratory depression

Dosage:
0.4 mg intravenously (IV).

Mechanism of Action:
Naloxone competitively blocks the actions of opioid peptides at opioid receptors, reversing their effects.

Pharmacokinetics:

  • Well absorbed via IV, with an onset of action in 2–3 minutes.
  • Undergoes first-pass metabolism when given orally.
  • Metabolized in the liver, excreted in urine.
  • Duration of action: 3–4 hours.

Side Effects:
Rare at normal doses, but adverse effects may include:

  • Hypertension
  • Tachycardia
  • Hyperventilation
  • Nausea and vomiting

Nursing Considerations:

  • Monitor the patient’s response and adjust the dose as needed.

DRUGS USED IN PAEDIATRICS Read More »

DRUGS USED IN MIDWIFERY

DRUGS USED IN MIDWIFERY

Drugs used in midwifery are drugs specifically used during pregnancy, labor, delivery, and postpartum care to ensure the health of the mother and baby.

They may induce labor, prevent complications, manage pain, or treat postpartum conditions.

Examples;

  • Oxytocics: e.g., Oxytocin (induces or augments labor), Misoprostol (induces labor or manages postpartum hemorrhage).
  • Tocolytics: e.g., Nifedipine, Terbutaline (delay preterm labor).
  • Anticoagulants: e.g., Heparin (prevents thromboembolism during pregnancy).
  • Antiemetics: e.g., Doxylamine + Pyridoxine (treat nausea and vomiting in pregnancy).
  • Analgesics/Anesthetics: e.g., Epidural anesthesia (manages labor pain).
  • Magnesium Sulfate: Prevents seizures in preeclampsia/eclampsia.
  • Rh Immunoglobulin: Prevents Rh incompatibility complications.

Clinical Use;

  • Inducing or augmenting labor.
  • Managing preterm labor.
  • Preventing or treating postpartum hemorrhage.
  • Managing pregnancy-related conditions like preeclampsia, nausea, or pain.

DRUGS USED IN LABOUR

Drugs in Labor refers to the medications that are administered to a woman during labor to manage pain, assist with the process of childbirth, or address complications. These drugs can be used for pain relief, induction or augmentation of labor, and management of medical conditions that may arise during labor.

Drugs used in labor can be grouped according to the effect they have on the uterus.

  • Uterine relaxants (Tocolytics): These drugs relax the uterus, slowing or stopping contractions such as Nifedipine, Magnesium Sulfate.
  • Uterine Stimulants/Uterine Motility drugs. (Oxytocics): These drugs stimulate the uterus to contract, helping to induce or strengthen labor, such as Oxytocin (Pitocin).
Uterine-Relaxants

Uterine Relaxants

Uterine relaxants, also known as tocolytics, are a group of medications used to suppress uterine contractions and delay labor. 

Their primary goal is to prolong pregnancy, allowing the fetus to develop further and increasing the chances of neonatal survival. These drugs are primarily used to prevent premature labor, particularly when cervical dilation is less than 4 cm.

Types of Uterine Relaxants

Beta-adrenergic agonists (Beta-2 agonists):

  • Salbutamol.
  • Terbutaline.

Calcium channel blockers:

  • Nifedipine.

Magnesium sulfate

Nonsteroidal anti-inflammatory drugs (NSAIDs):

  • Indomethacin.

Oxytocin receptor antagonists:

  • Atosiban.

Corticosteroids:

  • Dexamethasone: (used for fetal lung maturity rather than directly for uterine relaxation but is often used in combination with tocolytics in premature labor)
Salbutamol

Salbutamol (A Beta-2 Adrenergic Agonist)

Legal Class: Class B controlled drugs
Medical Class: Tocolytic agent
Form: Tablets, sterile solution for injection
Dosage: Tablets 4 mg; Solution for injection 50 mg/mL

Mechanism of Action

Salbutamol stimulates beta-2 adrenergic receptors in the uterine smooth muscle, leading to increased levels of cAMP, which inhibits myosin light-chain kinase, thereby reducing uterine contractions.

Indications

  • Uncomplicated premature labor between 24 to 33 weeks of gestation
  • Asthma (as it also has bronchodilatory effects)

Contraindications

  • Cardiac diseases (risk of tachycardia and other arrhythmias)
  • Antepartum hemorrhage (APH)
  • Intrauterine fetal death (IUFD)
  • Intrauterine infections
  • Ruptured membranes
  • Eclampsia and pre-eclampsia
  • First and second trimester of pregnancy (risk of fetal malformations)

Dosage

  • Premature labor: IV infusion 10 mcg/min, gradually increase according to response at 10-minute intervals until contractions diminish, with a maximum dose of 45 mcg/min. Maintain rate for 1 hour, then gradually reduce by IV or IM injection 100-250 mg, repeated according to response, followed by oral administration of 4 mg every 6-8 hours.
  • Duration of use: Do not use for more than 48 hours due to the risk of maternal and fetal complications.

Side Effects

  • Hypoglycemia (especially in diabetic patients)
  • Vomiting and nausea
  • Sweating and tremors
  • Hypotension
  • Pulmonary edema
  • Maternal and fetal tachycardia
  • Headache and palpitations
  • Urticaria

Adverse Effects

  • Severe hypotension
  • Pulmonary edema
  • Cardiac arrhythmias
  • Hyperglycemia
Magnesium Sulfate

Magnesium Sulfate (MgSO4)

Legal Class: Class B controlled drugs
Medical Class: Tocolytic and anticonvulsant
Form: Sterile solution for injection
Strength/Dosage: 50% of 5 grams/10 mL

Mechanism of Action

Mechanism of Action

Magnesium sulfate acts as a calcium antagonist by competing with calcium for entry into the cells, which decreases the action potential in uterine smooth muscle, leading to muscle relaxation. It also stabilizes membranes by interacting with sodium and potassium channels.

USING MAGNESIUM SULPHATE (MgSO₄) TO PREVENT OR STOP SEIZURES

LOADING DOSE:

1. Give 4 g of 20% MgSO₄ solution IV over 20 min. prepared as stated below:

  • Take one 20 ml syringe and draw 8 ml of 50% MgSO₄ (4 g)
  • Add 12 ml water for injection to make 20% solution
  • Give IV over 20 minutes (each 2mls has 1g

2. Immediately follow this with 10 g of 50% solution deep IM as shown below:

  • Take two 10 ml syringes
  • Draw 10 ml of 50% MgSO₄ (undiluted) = 5 g into each syringe
  • Add 1 ml of 2% lignocaine to each syringe to reduce pain
  • Give 10 ml (5 g) deep IM in each buttock
  • Prepare to refer to a comprehensive EmOC(Emergency Obstetric Care) facility if delivery is imminent
  • If delivery is not imminent and mother cannot reach referral unit within 4 hours give Maintenance dose (see 3 below)

3. If fits re-occur:

  • Give another 4 ml = 2 g of MgSO₄, 20% IV slowly over 20 minutes

MAINTENANCE DOSE:

Give 5 g of 50% MgSO₄ deep IM in alternate buttocks every 4 hours as shown below:

  • Take one 10 ml syringe and draw 10 ml of 50% MgSO₄ (5 g) in each syringe
  • Add 1 ml of 2% lignocaine in the same syringe
  • Give 5 g deep IM in alternate buttocks every 4 hours
  • Continue treatment for 24 hours after birth or the last fit, whichever is later

TOXICITY:

  • Before repeating MgSO₄, always monitor for toxicity.
  • Withhold or delay next IM dose if any of the following occurs:
  • Respiratory rate <16/minute. STOP MgSO₄, and give calcium gluconate
  • Patellar reflexes absent. STOP MgSO₄
  • Urine output <30 ml/hour over preceding 4 hours

ANTIDOTE: Calcium Gluconate

  • Assist ventilation with mask and ambu-bag, anaesthesia apparatus, intubation
  • Give calcium gluconate 1 g (10 ml of 10% solution) IV slowly (over 10 minutes) until it begins to counteract the effect of MgSO₄ and respiration returns to normal
  • Give oxygen

Dosage

  • Loading Dose: 4 g of MgSO4 given slowly IV over 15 to 20 minutes, followed by 10 g IM (5 g in each buttock) with 1 mL of 2% lignocaine to reduce pain.
  • Maintenance Dose: 5 g of 50% MgSO4 IM on alternate buttocks every 4 hours. Treatment continues for 24 hours from the start or after the last seizure.

Indications

  • Severe eclampsia and pre-eclampsia (prevention and treatment of seizures)
  • Hypomagnesemia
  • Severe asthma
  • Short-term treatment of constipation (acts as a laxative)
  • Myocardial infarction (as an adjunct)

Contraindications

  • Hypermagnesemia
  • Hypersensitivity to MgSO4
  • Renal impairment
  • Hepatic failure
  • Hypotensive patients
  • Patients with epilepsy

Side Effects

  • Drop in blood pressure
  • Flushing of the skin
  • Dizziness and confusion
  • Muscle weakness and loss of deep tendon reflexes (e.g., knee-jerk reflex)
  • Prolonged bleeding time
  • Diarrhea

Adverse Effects

  • Hypermagnesemia (risk of respiratory depression, cardiac arrest, and coma)
  • Magnesium toxicity, leading to respiratory paralysis
  • Shock in hypertensive patients

Nifedipine (A Calcium Channel Blocker)

Legal Class: Class B controlled drugs
Medical Class: Tocolytic and antihypertensive
Form: Tablets

Mechanism of Action

Nifedipine inhibits calcium influx through voltage-dependent calcium channels in the smooth muscle, including the uterus, which leads to relaxation and reduced contractility.

Dosage

  • Initial Dose: 20 mg, repeat after 30 minutes if contractions persist.
  • Maintenance Dose: If contractions continue after 3 hours, give 20 mg every 3-8 hours until contractions cease. The maximum dose is 160 mg/day.

Indications

  • Threatened abortion
  • Preterm labor less than 34 weeks of gestation
  • Hypertension (both chronic and pregnancy-induced)

Contraindications

  • Maternal cardiac diseases
  • Uncontrolled hypertension
  • Intrauterine infections
  • Conditions where prolonging pregnancy is contraindicated
  • Intrauterine fetal death

Side Effects

  • Dizziness and headache
  • Flushing and warmth sensation
  • Peripheral edema
  • Fatigue
  • Nausea

Adverse Effects

  • Severe hypotension
  • Reflex tachycardia
  • Congestive heart failure (CHF) exacerbation

Uterine Stimulants/Uterine Motility Drugs (Oxytocics)

Uterine motility drugs, also known as oxytocics, are agents used to stimulate uterine contractions. 

These medications are primarily used to induce or augment labor, manage postpartum hemorrhage, and facilitate uterine evacuation in cases of incomplete abortion or fetal death. They are also employed as abortifacients to induce abortion.

Oxytocics

Oxytocics are drugs that stimulate uterine contractions, mimicking the action of the natural hormone oxytocin. They are used to induce or augment labor, control postpartum bleeding, and in some cases, manage incomplete or missed abortions.

Types of Oxytocics

Oxytocin (Pitocin, Syntocinon)

  • Legal Class: Class B controlled drugs
  • Medical Class: Oxytocic drugs
  • Form: Sterile solution for injection
  • Strength: 10 IU per ampule

Indications of Oxytocin:

  • Induction of Labor: When labor is not progressing naturally.
  • Augmentation of Labor: To strengthen contractions when labor is slow or stalled.
  • Control of Postpartum Bleeding (PPH): To contract the uterus after delivery and prevent excessive bleeding.
  • Active Management of the Third Stage of Labor: To help deliver the placenta and reduce the risk of PPH.

Others include;

  • Management of hypotonic uterine contractions
  • Treatment of intrauterine fetal death
  • Prevention and treatment of postpartum hemorrhage (PPH)
  • Active management of the third stage of labor
  • Management of preeclampsia and eclampsia
  • Treatment of congestive heart failure secondary to fluid overload in pregnancy
  • Management of post-term pregnancies
  • Incomplete or missed abortion

Contraindications of Oxytocin.

  • Hypertonic Uterine Contractions: When the uterus is already contracting too strongly.
  • Fetal and Maternal Distress: When the baby or mother is experiencing complications.
  • Multiple Pregnancy: Increased risk of complications.
  • Trial of Labor: When a woman is attempting a vaginal delivery after a previous Cesarean section.
  • Malpresentation: When the baby is in a position that makes vaginal delivery difficult (e.g., breech, brow).
  • Cephalo Pelvic Disproportion: When the baby’s head is too large to fit through the mother’s pelvis.
  • Low Blood Pressure: Oxytocin can further lower blood pressure.

Dosage of Oxytocin

  • Induction/Augmentation of Labor: 5 IU in 500 mL of IV infusion, initially at 5 drops per minute, titrated as needed.
  • Prevention of PPH: 5 IU slow IV injection after delivery of the placenta, with an increase in rate if necessary during the third stage of labor.
  • PPH: 10 unit IM after delivery of placenta

Routes of Administration:

  • Intramuscular (IM)
  • Intravenous (IV), often in combination with normal saline or dextrose

Side Effects of Oxytocin

  • Dizziness
  • Nausea and vomiting
  • Skin rashes
  • Fetal bradycardia
  • Hypotension

Adverse Effects:

  • Uterine rupture, particularly in cases of hyperstimulation
  • Severe hypotension
  • Tachycardia
  • Fetal anoxia and hypoxia leading to birth asphyxia

Pharmacokinetics:

  • Absorption: Rapid following IV injection
  • Distribution: Distributed throughout the extracellular fluid, with some crossing into fetal circulation
  • Metabolism: Primarily in the liver and kidneys, with rapid metabolism and excretion in the urine
Syntometrine

Syntometrine

Syntometrine is a combination drug containing both ergometrine and oxytocin, designed to provide a synergistic effect in controlling postpartum bleeding.

  • Legal Class: Class B controlled drug
  • Medical Class: Oxytocic drug
  • Form: Sterile solution for injection
  • Strength: Combination of ergometrine 0.5 mg + oxytocin 5 IU (International Units)
  • Dosage: 1 mL as a single dose, but can be repeated if necessary if bleeding is not controlled.

Route:

  • Intramuscular: Injection into a muscle.
  • Intravenous: Injection into a vein.

Indications:

  • Multigravidas: Women who have had multiple pregnancies, as they are at higher risk for PPH.
  • History of Postpartum Hemorrhage: Women with a previous history of PPH.
  • Multiple or Twin Delivery: Due to the larger placental site.
  • Heavy Lochia: Excessive vaginal discharge after delivery.
  • Abortion: When the fundal height (measurement of the uterus) is less than 12 weeks.

Contraindications:

  • Cardiac Disease: Syntometrine can worsen heart conditions.
  • Preeclampsia and Eclampsia: Syntometrine can exacerbate these conditions.
  • Hypertension: Syntometrine can raise blood pressure.

Adverse Effects:

  • Retained Placenta: The placenta may not be fully expelled.
  • IUFD (Intrauterine Fetal Death) in Undiagnosed Second Twin: If a second twin is present and undiagnosed, Syntometrine can lead to its death.
  • Retained Second Twin: The second twin may not be fully expelled.
  • Uterine Rupture: If given during abortion after 20 weeks of gestation, especially if the products of conception are not fully expelled.
  • Hypoxia and Anoxia: Lack of oxygen to the fetus or mother.

Side Effects:

  • Nausea and Vomiting
  • Headache
  • Hypotension: Low blood pressure.
  • Dyspnea: Difficulty breathing.
  • Muscle Pain
Methyl-Ergometrine

Ergometrine

Ergometrine is a potent oxytocic that acts directly on the uterine muscle to cause sustained contractions.

Legal Class: Class B controlled drug

Medical Class: Oxytocic drug

Form: Tablet and sterile solution

Strength/Dosage:

  1. Tablets: 0.25 to 0.5 mg
  2. Injection: 200 mcg/mL or 0.5 mg/mL

Effects: Causes sudden, prolonged, intermittent uterine contractions.

Indications: Similar to Syntometrine, primarily used to control postpartum bleeding.

Contraindications: Similar to Syntometrine.

Side Effects: Similar to Syntometrine.

Dangers: Similar to Syntometrine.

indomethacin

Indomethacin (An NSAID)

Legal Class: Prescription-only medication
Medical Class: NSAID, tocolytic
Form: Tablets, rectal suppositories, oral suspension

Mechanism of Action

Indomethacin inhibits the cyclooxygenase (COX) enzymes, leading to reduced synthesis of prostaglandins, which are crucial for uterine contractions.

Dosage

  • Preterm labor: 50-100 mg rectally or orally, followed by 25-50 mg every 6-8 hours. The treatment duration is limited to 48 hours to minimize fetal side effects.

Indications

  • Preterm labor (especially when caused by polyhydramnios)
  • Patent ductus arteriosus (PDA) closure in neonates

Contraindications

  • Fetal distress
  • Intrauterine fetal death
  • Peptic ulcer disease
  • Renal impairment
  • Bleeding disorders

Side Effects

  • Gastrointestinal discomfort (nausea, vomiting, epigastric pain)
  • Dizziness and headache
  • Rash

Adverse Effects

  • Oligohydramnios (reduced amniotic fluid)
  • Premature closure of the ductus arteriosus in the fetus
  • Renal impairment in both mother and fetus

Abortifacients

Abortifacients are drugs that induce abortion by causing strong uterine contractions, leading to the expulsion of uterine contents. They are often used in the first and second trimesters of pregnancy for medical termination,  and are often used in conjunction with other medications.

Types of Abortifacients

Misoprostol

Misoprostol

  • Legal Class: Class B controlled drugs
  • Medical Class: Oxytocic drugs/Cervical ripening agent
  • Form: Tablets
  • Strength: 100 mcg or 200 mcg per tablet

Indications of Misoprostol:

  • Induction of Labor: When labor is not progressing naturally.
  • Control of Postpartum Hemorrhage: Due to uterine atony.
  • Cervical Ripening: To soften the cervix before labor induction.
  • Intrauterine Fetal Death: To induce labor and expel the fetus.
  • Gastric and Duodenal Ulcerations: Off-label use for treating ulcers.
  • Medical termination of pregnancy in combination with mifepristone

Contraindications of Misoprostol:

  • Malpresentation: When the baby is in a position that makes vaginal delivery difficult.
  • Placenta Previa Grade 3 and 4: When the placenta is covering the cervix.
  • Multiparous Mothers: Increased risk of complications.
  • Cephalo Pelvic Disproportion: When the baby’s head is too large to fit through the mother’s pelvis.
  • Hypersensitivity to Misoprostol: Allergic reaction.

Dosage of Misoprostol:

  • Induction of Labor: 25-50 mcg vaginally every 4-6 hours until adequate uterine contractions are achieved
  • NSAID-Induced Ulceration: 200 mcg orally four times daily

Routes of Administration:

  • Sublingual: Under the tongue.
  • Rectal: Inserted into the rectum.
  • Vaginal: Inserted into the vagina.
  • Oral: Swallowed

Side Effects:

  • Headache
  • Dizziness
  • Fever and shivering
  • Nausea and vomiting
  • Uterine rupture (rare but serious)

Adverse Effects:

  • Fetal distress and bradycardia
  • Uterine hyperstimulation leading to rupture
  • Severe gastrointestinal disturbances

Pharmacokinetics:

  • Absorption: Rapidly absorbed after oral, sublingual, or vaginal administration
  • Distribution: Well distributed throughout the body, crossing into fetal circulation
  • Metabolism: Hepatically metabolized to active prostaglandin analogs
  • Excretion: Primarily excreted in urine.

Dysmenorrhea: Drug Treatment

Dysmenorrhoea refers to pain during menstruation, caused by excessive prostaglandin production, leading to strong uterine contractions.

Dysmenorrhea, or painful menstruation, is categorized into primary and secondary types, based on the presence or absence of an identifiable underlying cause. 

I. Primary Dysmenorrhea:

  1. Cause: Unknown; believed to be related to excessive prostaglandin production leading to intense uterine contractions.
  2. Risk Factors: Early menarche, heavy menstrual bleeding, family history of dysmenorrhea, smoking.
  3. Signs and Symptoms: Cramping abdominal pain, headache, nausea/vomiting, diarrhea, lower back pain, loss of appetite.
  4. Non-Pharmacological Management: Regular exercise, hot water bottles/warm baths, adequate rest and sleep, back massage, low-fat diet, nutritional supplements (Vitamin E, zinc, Vitamin B1). Educate the patient that the condition isn’t a gynecological abnormality.
  5. Pharmacological Management:
  • Non-Steroidal Anti-inflammatory Drugs (NSAIDs): Reduce prostaglandin production. Start 1-2 days before anticipated menstruation for optimal effectiveness.
  1. Mefenamic acid: 500mg three times daily for 3-4 days.
  2. Ibuprofen: 400mg three times daily for 3-4 days.
  3. Indomethacin: 50mg three times daily for 3-4 days.
  4. Diclofenac: 50mg three times daily for 3-4 days.
  5. Aceclofenac: 100mg twice daily for 3-4 days. (Note: The provided text lists 10mg, but 100mg is a more common and appropriate dosage.)
  • Hormonal Therapy: Used if NSAIDs are ineffective. These suppress ovulation, reducing prostaglandin production.
  1. Combined Oral Contraceptives (COCs): Examples include Pilplan and Microgynon.
  2. Norethisterone (Primolut-N): A progestogen.
  • Antispasmodics: Relax uterine smooth muscle, providing relief from spasms. May be used alone or in combination with NSAIDs for severe cases.
  1. Drotaverine (Nospa): 80mg three times daily for 3 days.

II. Secondary Dysmenorrhea:

  • Cause: Identifiable underlying condition, such as: pelvic inflammatory disease (PID), endometriosis, fibroids, ovarian cysts, intrauterine devices (IUDs).
  • Signs and Symptoms: Abdominal bloating, backache, pain starting 3-5 days before menstruation, pain during sexual intercourse.
  • Management: Treatment focuses on addressing the underlying cause. NSAIDs may provide temporary pain relief while the underlying condition is treated.

Others;

Analgesics and Anesthetics for Labor Pain

Analgesics and Anesthetics for Labor Pain

Purpose: Provide pain relief during labor and delivery.

Examples:

Epidural Anesthesia:

  • Mechanism: Local anesthetics (e.g., bupivacaine) injected into the epidural space to block pain signals.
  • Indications: Pain relief during labor.
  • Administration: Continuous infusion via epidural catheter.

Nitrous Oxide:

  • Mechanism: Inhaled analgesic that provides mild pain relief.
  • Indications: Labor pain.
  • Administration: Inhalation.

Opioids:

  • Mechanism: Bind to opioid receptors in the brain to reduce pain perception.
  • Examples: Fentanyl, Remifentanil.
  • Indications: Moderate to severe labor pain.
  • Administration: IV or IM.
Drugs for Postpartum Hemorrhage (PPH) (1)

Drugs for Postpartum Hemorrhage (PPH)

Purpose: Prevent or treat excessive bleeding after delivery.

Examples:

Oxytocin:

  • Mechanism: Stimulates uterine contractions to reduce bleeding.
  • Indications: First-line treatment for PPH.
  • Administration: IV or IM.
  • Dosage: 10-40U in 1L normal saline infused at 200-500mL/hr.

Misoprostol:

  • Mechanism: Induces uterine contractions.
  • Indications: PPH, especially in resource-limited settings.
  • Administration: Oral, sublingual, or rectal.
  • Dosage: 800-1000 mcg PR(Per Rectal) once.

Carboprost:

A medication used after the delivery of a baby to control bleeding from the uterus that has not resolved with other treatments.

  • Mechanism: Strong uterine contractor.
  • Indications: PPH unresponsive to oxytocin.
  • Administration: IM.

Tranexamic Acid:

A medication used to control episodes of heavy bleeding.

  • Mechanism: Antifibrinolytic that reduces bleeding.
  • Indications: PPH.
  • Administration: IV.
  • Dosage: 1g over 10 minutes

Rh Immunoglobulin :

A medication used to prevent unwanted immune reactions in blood transfusions or pregnancy.

Human Rho(D) immune globulin is a solution of antibodies used to prevent isoimmunization of Rho(D) negative patients exposed to Rho(D) positive blood in pregnancy or transfusion.

  • Purpose: Prevent Rh sensitization in Rh-negative mothers.
  • Mechanism: Prevents the mother’s immune system from producing antibodies against Rh-positive fetal blood cells.
  • Indications: Rh-negative mothers with Rh-positive babies.
  • Administration: IM, usually at 28 weeks of pregnancy and within 72 hours of delivery. 

Antiemetics for Nausea and Vomiting in Pregnancy

Purpose: Manage nausea and vomiting, including hyperemesis gravidarum.

Examples:

First-Line Pharmacotherapy:

This is the initial treatment approach. Two options are presented:

Pyridoxine (Vitamin B6) 

  • Dosage: 10-25mg orally every 6-8 hours: This is a common first-line treatment for mild NVP.

Doxylamine + Pyridoxine:

This combination therapy is often more effective than pyridoxine alone, particularly for moderate NVP.

  • Mechanism: Antihistamine and vitamin B6 combination.
  • Indications: Nausea and vomiting in pregnancy.
  • Administration: Oral.

If symptoms persist despite first-line treatment and dehydration occurs, proceed to:

Second-Line Pharmacotherapy:

This stage involves intravenous (IV) fluid resuscitation to correct dehydration in addition to one of the following antiemetic medications given intravenously:

Metoclopramide

  • Dosage:  5-10 mg every 8 hours: This medication stimulates gastric motility and can help with nausea.

Ondansetron:

  • Mechanism: Serotonin 5-HT3 receptor antagonist.
  • Indications: Severe nausea and vomiting.
  • Administration:  8mg every 12 hours, Oral or IV.

Promethazine 

  • Dosage: 12.5-25mg every 4-6 hours: An antihistamine with antiemetic properties.

If vomiting remains uncontrolled (“refractory vomiting”) despite second-line therapy, proceed to:

Third-Line Pharmacotherapy:

This is reserved for severe, persistent cases. Again, IV fluid resuscitation is crucial, and one of the following medications is added:

Methylprednisolone 

  • Dosage: 16mg every 8 hours orally or intravenously for 3 days (tapering over 2 weeks, continuing for a total of 6 weeks if effective): A corticosteroid with potent anti-inflammatory and antiemetic effects. The tapering schedule is crucial to minimize side effects.

Chlorpromazine 

  • Dosage: 25-50mg intravenously or intramuscularly every 4-6 hours: A phenothiazine derivative with antiemetic and sedative properties. Use cautiously due to side effects.

Chlorpromazine 

  • Dosage: 10-25mg orally every 4-6 hours: Oral alternative to the IV/IM route.
betamethazone

Corticosteroids for Fetal Lung Maturation

Purpose: Accelerate fetal lung development in preterm labor.

Examples:

Betamethasone:

  • Mechanism: Stimulates surfactant production in fetal lungs.
  • Indications: Preterm labor (24–34 weeks gestation).
  • Administration: Two 12 mg doses given IM 24 hours apart.

Dexamethasone:

  • Mechanism: Similar to betamethasone.
  • Indications: Preterm labor.
  • Administration: Four 6 mg doses given IM every 12 hours.

Iron and Folic Acid Supplements

  • Purpose: Prevent or treat anemia during pregnancy.
  • Mechanism: Supports red blood cell production and fetal development.
  • Indications: Routine supplementation during pregnancy.
  • Administration: Oral.
Drugs for Hypertension in Pregnancy

Drugs for Hypertension in Pregnancy

Hypertension in pregnancy is a serious condition requiring careful management due to potential risks to both mother and fetus. 

Types of Hypertension in Pregnancy:

  1. Chronic Hypertension: This pre-existing condition is diagnosed before pregnancy or before 20 weeks gestation. 
  2. Gestational Hypertension: Onset occurs after 20 weeks of gestation and resolves postpartum. It’s characterized by elevated blood pressure without proteinuria (protein in the urine). 
  3. Pre-eclampsia: A more serious condition, diagnosed after 20 weeks gestation. It involves hypertension with proteinuria, often accompanied by other symptoms like edema (swelling), headaches, visual disturbances, and abdominal pain. 
  4. Eclampsia: The most severe form, characterized by seizures in a woman with pre-eclampsia. This is a life-threatening emergency requiring immediate medical intervention.

Management Strategies:

Treatment depends heavily on the type and severity of hypertension and the presence of complications. The primary goals are to prevent seizures, reduce blood pressure to a safe level, and deliver the baby at an appropriate time.

Anticonvulsants (Primarily for Eclampsia):

Magnesium Sulfate: This is the first-line treatment for eclampsia to prevent seizures.

  • Dosage: A loading dose of 4g intravenously (IV) is administered over 10-15 minutes, followed by a maintenance dose of 10g intramuscularly (IM), typically divided into two 5g injections (one in each buttock). Continuous monitoring of magnesium levels is essential to prevent toxicity.
  • Toxicity Management: Calcium gluconate 1-2g IV is the antidote for magnesium sulfate toxicity. Symptoms of toxicity include decreased deep tendon reflexes, respiratory depression, and cardiac arrhythmias.

Diazepam: Used for immediate seizure control in eclampsia, although it’s not the primary preventative agent like magnesium sulfate. Diazepam 10mg IV is usually administered.

Antihypertensives:

The choice of antihypertensive medication depends on several factors, including the type of hypertension, severity of blood pressure elevation, and the presence of any co-existing conditions. The goal is to gradually lower blood pressure to avoid sudden drops that could compromise placental perfusion.

Severe Hypertension (Emergency):

  • Hydralazine 5-10mg IV: A vasodilator that acts quickly to lower blood pressure. Careful monitoring is essential due to its potential side effects.
  • Nifedipine 20mg sublingual: A calcium channel blocker with rapid-onset action. It’s typically given sublingually for fast-acting effects in hypertensive emergencies.

Chronic Hypertension (Non-Emergency):

  • Methyldopa 250mg twice daily to three times daily: A centrally acting alpha-2 agonist that is generally considered safe in pregnancy. The dosage is adjusted based on blood pressure response.
  • Nifedipine retard 20mg twice daily: A long-acting calcium channel blocker that offers sustained blood pressure control. Again, dose adjustments are necessary based on clinical monitoring.

ANTIMALARIAL DRUGS

Malaria is an acute febrile illness caused by protozoa of the genus Plasmodium. It is transmitted from person to person through the bite of a female Anopheles mosquito.

The Four Species of Malaria Parasites:

  1. Plasmodium falciparum
  2. Plasmodium vivax
  3. Plasmodium ovale
  4. Plasmodium malariae

Life Cycle of Malaria Parasites

Malaria parasites undergo both a sexual cycle (in the female Anopheles mosquito) and an asexual cycle (in humans).

  • Mosquito Bite: The mosquito injects sexual forms of the parasite (sporozoites) into the bloodstream.
  • Hepatic Cycle: Sporozoites enter liver cells, forming tissue schizonts, which rupture and release merozoites. Some sporozoites become dormant forms (hypnozoites), which may reactivate later.
  • Erythrocytic Cycle: Merozoites invade red blood cells (RBCs), forming blood schizonts. The schizonts rupture the RBCs, causing the clinical symptoms of malaria.
  • Gametocyte Formation: Some merozoites develop into male and female gametocytes. If taken up by a mosquito, they complete the life cycle, forming sporozoites.

Classification of Antimalarial Drugs

Classification I

  • Tissue Schizonticides: Act on malaria parasites in the liver (Primaquine, Pyrimethamine, Proguanil).
  • Blood Schizonticides: Act on schizonts in RBCs (Chloroquine, Amodiaquine, Proguanil, Pyrimethamine, Mefloquine, Quinine, Artemisinin).
  • Gametocides: Prevent transmission by destroying gametocytes (Primaquine).

Classification II

  • 4-Aminoquinolines: Chloroquine, Amodiaquine
  • 8-Aminoquinolines: Primaquine
  • 4-Methanolquinolines (Quinoline Methanols): Quinine, Mefloquine
  • Biguanides: Proguanil
  • Sulphonamides: Sulfadoxine
  • Artemisinin Derivatives: Artemether, Artesunate, Dihydroartemisinin, Artemisinin
  • Antibiotics: Doxycycline, Tetracycline, Clindamycin

QUININE

  • Type: Alkaloid derived from the bark of the cinchona tree.
  • Classification: 4-Methanolquinoline
  • Action: Rapid blood schizonticide active against Plasmodium falciparum, vivax, ovale, malariae.
  • Mechanism: Inhibits haem polymerase, preventing the polymerization of haem to haemozoin.

Available Preparations:

  • Tablets 300 mg
  • Injection 300 mg/ml
  • Syrup 100 mg/5 ml

Pharmacokinetics:

  • Absorbed from the gastrointestinal tract, widely distributed, metabolized in the liver, excreted mainly in urine.

Indications:

  • Uncomplicated and severe malaria.

Dosage:

  • Oral: Adults 600 mg 8-hourly for 7 days.
  • IV: Adults 600 mg 8-hourly in dextrose 5%, to run for 4 hours.
  • Children: 10 mg/kg 8-hourly for 7 days (oral), or same dose IV in dextrose.

Contraindications:

  • Hypersensitivity, cardiac abnormalities (e.g., AV block), myasthenia gravis, haemoglobinuria, visual/auditory problems.

Side Effects:

  • Headache, blurred vision, abdominal pain, diarrhea, tinnitus, hypersensitivity reactions, nausea, hypoglycemia, “cinchonism” (tinnitus, dizziness, visual disturbances).

Drug Interactions:

  • Increases digoxin and warfarin levels.
  • Delayed absorption with aluminum antacids.
  • Cimetidine increases quinine blood levels.

SULFADOXINE WITH PYRIMETHAMINE (FANSIDAR)

  • Action: Synergistically inhibit folic acid synthesis in parasites.
  • Available Preparations: Tablets (500 mg sulfadoxine/25 mg pyrimethamine).

Pharmacokinetics:

  • Well absorbed, widely distributed, metabolized in the liver, and slowly excreted.

Indications:

  • Malaria prophylaxis and intermittent presumptive treatment (IPT) in pregnancy.

Dosage:

  • IPT in Pregnancy: 3 tablets during 2nd and 3rd trimesters.

Contraindications:

  • Hypersensitivity, severe renal failure, infants < 2 months, first trimester pregnancy.

Side Effects:

  • Urticaria, vomiting, diarrhea, nausea, headache, Stevens-Johnson syndrome.

Drug Interactions:

  • Increased antifolate effect with methotrexate and cotrimoxazole, raises phenytoin plasma concentration.

ARTEMISININ AND DERIVATIVES

  • Derived from Artemesia annua (Chinese herb Qinghaosu).
  • Action: Rapidly acting blood schizonticides effective against multidrug-resistant Plasmodium falciparum.
  • Derivatives: Artesunate (water-soluble), Artemether (lipid-soluble).

Artemether:

  • Available Forms: Injection (20 mg/ml, 40 mg/ml, 80 mg/ml).
  • Indications: Uncomplicated and severe malaria.
  • Dose: Adults 300 mg loading dose, followed by 100 mg once daily for 4 days.

Side Effects:

  • Nausea, vomiting, diarrhea, dizziness, tinnitus.

Contraindications:

  • Hypersensitivity, first trimester of pregnancy.

 

ARTEMETHER + LUMEFANTRINE

  • Available Forms: Tablets (20 mg/120 mg, 40 mg/240 mg), suspension (15 mg/90 mg/5 ml).
  • Indications: First-line treatment for uncomplicated malaria.

Dosage:

Weight

Age

Day 1

Day 2

Day 3

5-14 kg

4 months-3 yrs

1 tablet 12-hourly

1 tablet 12-hourly

1 tablet 12-hourly

15-24 kg

3-7 yrs

2 tablets 12-hourly

2 tablets 12-hourly

2 tablets 12-hourly

25-34 kg

7-12 yrs

3 tablets 12-hourly

3 tablets 12-hourly

3 tablets 12-hourly

≥35 kg

12+ yrs

4 tablets 12-hourly

4 tablets 12-hourly

4 tablets 12-hourly

Contraindications:

  • Cardiac arrhythmias, bradycardia, breastfeeding.

Side Effects:

  • Abdominal pain, diarrhea, nausea, headache, fatigue, skin rash.

Drug Interactions:

Avoid concurrent use with amiodarone, ciprofloxacin, fluconazole, mefloquine.

ARTESUNATE

Type: Derivative of artemisinin, water-soluble.

Classification: Blood schizonticide and gametocide, particularly effective against Plasmodium falciparum, including multidrug-resistant strains.

Mechanism of Action: Artesunate is a prodrug that is rapidly converted to dihydroartemisinin, its active form. It works by producing free radicals within the parasite’s food vacuole, leading to the destruction of the parasite.

Available Preparations:

  • Tablets: 50 mg, 100 mg
  • Injection: 60 mg vial (for intravenous and intramuscular use)

Pharmacokinetics:

  • Rapidly absorbed
  • Widely distributed in body tissues
  • Metabolized in the liver to dihydroartemisinin
  • Excreted mainly in urine

Indications:

  • Severe and complicated malaria
  • Uncomplicated malaria (especially when caused by Plasmodium falciparum resistant to other drugs)

Dosage:

  • Severe malaria: Initial IV dose of 2.4 mg/kg at 0, 12, and 24 hours, then once daily.
  • Uncomplicated malaria: 4 mg/kg once daily for 3 days (used in combination therapy).

Contraindications:

  • Known hypersensitivity to artemisinin derivatives.
  • First trimester of pregnancy (unless the benefits outweigh the risks).

Side Effects:

  • Nausea
  • Vomiting
  • Dizziness
  • Diarrhea
  • Low neutrophil count (rare)
  • Injection site reactions (for IV/IM administration)

Drug Interactions:

  • Caution with drugs affecting the heart’s electrical activity (e.g., antiarrhythmics like amiodarone).
  • Avoid concurrent use with drugs that prolong QT interval (e.g., quinidine, erythromycin).

DRUGS USED IN MIDWIFERY Read More »

Legal aspects and national policies

The National Drug Authority (NDA)

The National Drug Authority (NDA) is a regulatory body comprised of individuals of high integrity, tasked with overseeing the implementation of the national drug policy. 

Its core objective is to ensure the availability, quality, and safe use of pharmaceuticals across the country. 

The NDA plays a big role in maintaining public health by regulating drugs, pharmacies, and ensuring that essential medications are accessible to all who need them.

Functions of the National Drug Authority

The NDA’s mandate covers various areas critical to pharmaceutical regulation and public health:

  1. Development and Regulation of Pharmacies and Drugs: The NDA formulates policies for establishing and managing pharmacies. It also ensures that the drugs sold within the country meet regulatory standards and are safe for use.
  2. Approving the National List of Essential Drugs: The NDA is responsible for approving the list of essential drugs that are deemed necessary for the healthcare system. They also periodically revise this list in consultation with the Minister of Health.
  3. Estimating Drug Needs: The NDA estimates the country’s pharmaceutical requirements to ensure that drugs are available in sufficient quantities and economically accessible to the population.
  4. Control of Importation, Exportation, and Sale of Pharmaceuticals: The authority regulates the flow of drugs in and out of the country, ensuring that only safe and approved pharmaceuticals enter the market.
  5. Quality Control of Drugs: It ensures that the drugs circulating in the market are of assured quality through stringent control measures such as inspections and laboratory testing.
  6. Promotion of Local Drug Production: The NDA promotes local manufacturing of essential drugs to boost self-sufficiency and reduce reliance on imported medicines.
  7. Encouragement of Herbal Medicine Research: It supports research and development of herbal medicines, integrating traditional medicine into the mainstream healthcare system.
  8. Promotion of Rational Drug Use: The NDA promotes the rational use of medicines by training healthcare professionals and providing information that ensures the appropriate prescription, dispensing, and use of drugs.
  9. Establishment of Professional Guidelines: The NDA creates and updates guidelines for healthcare professionals, ensuring they have the necessary information to prescribe and use drugs appropriately.
  10. Advisory Role: It advises the Minister of Health and other related bodies on implementing the national drug policy.
  11. Other Functions as Provided by Law: The NDA may take on additional roles as required by the country’s legal framework.

The National List of Essential Drugs

The National List of Essential Drugs contains medicines that are vital to addressing the healthcare needs of the majority of the population. 

This list is reviewed periodically to ensure that it remains relevant and effective in meeting public health needs.

  • The National Formulary is a document that contains the National List of Essential Drugs and other approved medicines. It serves as a guideline for healthcare professionals in prescribing medications.

Essential Drugs

Essential drugs are those that meet the health care needs of the majority of the population. 

These drugs are selected based on disease prevalence, efficacy, safety, and cost-effectiveness.

Characteristics of Essential Drugs:
  • Availability: These drugs must be available at all times.
  • Adequate Supply: There should be sufficient quantities to meet demand.
  • Assured Quality: Drugs should meet stringent quality standards.
  • Appropriate Dosage Forms: Available in the correct forms for administration.
  • Affordability: Priced in a way that is affordable to individuals and the community.
Selection Criteria for Essential Drugs:
  • Disease Prevalence: Drugs are selected based on the most common diseases in the population.
  • Efficacy: There must be solid evidence of the drug’s ability to treat the condition.
  • Safety: The drug must have a favorable safety profile, with acceptable risk/benefit ratios.
  • Cost-effectiveness: The drug must be economical for both patients and the health system.
  • Scientific Data: Sufficient scientific evidence regarding the drug’s effectiveness must be available.
  • Safety Monitoring: Drugs should undergo continuous safety assessments.
  • Single Active Ingredient: Preferably, drugs should contain one active ingredient, unless combinations are required for compliance or synergy.
Essential Drugs in Uganda

Class

Drug Name(s)

Antimalarials

Artemether, Artemether/lumefantrine, Dihydroartemisinin/piperaquine, Quinine, Primaquine

Antiamoebics

Metronidazole, Tinidazole

Antibacterials

Amoxicillin, Amoxicillin + clavulanic acid, Benzathine penicillin, Benzylpenicillin, Ceftriaxone, Cefuroxime, Flucloxacillin, Cloxacillin, Chloramphenicol, Ciprofloxacin, Cotrimoxazole, Doxycycline, Gentamicin, Erythromycin

Antituberculosis

Ethambutol, Isoniazid, Pyrazinamide, Rifampicin, Streptomycin

Antifungal

Amphotericin B, Clotrimazole, Fluconazole, Griseofulvin, Ketoconazole, Miconazole, Nystatin

Antileprosy

Clofazimine, Dapsone, Rifampicin, Thalidomide

Antiepileptics/Anticonvulsants

Carbamazepine, Clonazepam, Diazepam, Ethosuximide, Magnesium sulfate injection, Phenobarbitone, Phenytoin, Valproic acid

Anthelmintics

Mebendazole, Albendazole, Ivermectin, Praziquantel, Diethylcarbamazine

Analgesics/Antipyretics

Acetylsalicylic acid (Aspirin), Diclofenac, Paracetamol (Acetaminophen)

Antigout

Allopurinol, Colchicine, Indomethacin, Probenecid

Opioid Analgesics

Codeine, Morphine, Pethidine, Dihydrocodeine

Antivirals

Acyclovir, Ganciclovir

Cardiovascular

Atenolol, Isosorbide dinitrate, Nifedipine, Propranolol, Verapamil, Captopril, Hydralazine, Methyldopa, Lisinopril, Digoxin

Dermatological

Benzoic acid + salicylic acid, Miconazole, Clotrimazole, Benzyl peroxide, Coal tar, Dithranol, Podophyllum resin, Salicylic acid (2%, 5%), Silver nitrate pencil (40%), Betamethasone cream, Calamine lotion (15%), Hydrocortisone cream/ointment (1%), Malathion lotion (0.5%), Benzyl benzoate lotion (25%), Silver sulphadiazine cream (1%), Neomycin + bacitracin ointment, Chlorhexidine cream (5%)

Antiulcer

Cimetidine, Omeprazole, Ranitidine, Magnesium trisilicate compound

Antiemetics

Domperidone, Promethazine, Metoclopramide, Cyclizine

Laxatives

Bisacodyl, Senna

Antidiabetics

Insulin, Glibenclamide, Metformin, Tolbutamide

Cytotoxic Drugs

Asparaginase, Calcium folinate, Cyclophosphamide, Cytarabine, Dacarbazine, Dactinomycin, Fluorouracil, Doxorubicin, Hydroxyurea, Mercaptopurine, Methotrexate, Mustine, Stilboestrol, Thioguanine, Vincristine

Rational Use of Medicines

Rational use of medicines means that patients receive the appropriate drug for their clinical needs, in the correct dosage, for an adequate period, and at a cost that is affordable for them and the community.

Rational Drug Use

Rational drug use aims to optimize treatment while minimizing risks.

Principle

Description

Right indication

Prescribe only when necessary, based on a proper diagnosis

Right drug

Select the most effective, safe, and cost-efficient option

Right dose

Tailor dose to patient needs, considering individual factors

Right duration/time

Administer for the correct length of time

Patient education

Inform patients about correct use, side effects, and adherence

Right patient, Right medicine, Right dosage, Right route., Right time, Right storage., Right formulation, Right disposal, Right site, Right equipment.

Irrational Use of Medicines

Irrational drug use occurs when:

  • Too many drugs are prescribed per patient.
  • Wrong drugs are chosen for specific conditions.
  • Inadequate doses are given.
  • Unnecessary use of injections instead of oral medications.
  • Indiscriminate use of antibiotics, such as for viral infections like the common cold or diarrhea.
Factors Contributing to Irrational Use of Medicines:
  • Heavy Patient Load: Overworked healthcare professionals may rush prescriptions without thorough evaluation.
  • Poor Communication Skills: Inadequate interaction between healthcare providers and patients leads to misunderstandings.
  • Lack of Ethics: Some health professionals may act unethically by overprescribing medications.
  • Misinterpretation of Lab Results: Inaccurate interpretation of diagnostic results can lead to incorrect treatment.
  • Poor Attitude towards Work: A lack of motivation may result in careless prescribing practices.
  • Patient Misconceptions: Patients may insist on injections or antibiotics due to false beliefs about their efficacy.
  • Inconsistent Drug Supply: Unpredictable availability of medications may force healthcare providers to prescribe alternatives.
  • Lack of Medicine Formulary: Absence of a formal guide for medication use can lead to inconsistent prescribing.
  • Misleading Promotions: Drug companies may advertise their products in ways that mislead both patients and providers.
  • Inadequate Regulation: Insufficient oversight can allow for substandard or unnecessary drugs to enter the market.
Consequences of Irrational Drug Use
  • Antibiotic Resistance: Overuse of antibiotics contributes to the development of resistant bacteria, making infections harder to treat.
  • Resource Wastage: Irrational drug use wastes valuable healthcare resources.
  • Increased Costs: Patients bear higher financial burdens due to unnecessary or inappropriate prescriptions.
  • Adverse Drug Reactions: Polypharmacy (the use of multiple drugs) increases the risk of harmful interactions and side effects.
  • Loss of Patient Confidence: Inconsistent or ineffective treatment can erode trust in the healthcare system.
  • Poor Health Outcomes: Patients are more likely to experience complications, delays in recovery, or even worsening of their conditions.

Legal aspects and national policies Read More »

Drug Classification legal, prescription, schedule

Classifications of Drugs

A drug is any substance that, when introduced into a living organism, alters its structure or function. This includes anything from medications used to treat illnesses to recreational substances. Drugs are used for various reasons:

  • Treatment: To cure or manage diseases and health conditions.
  • Prevention: To protect against illnesses (e.g., vaccines).
  • Diagnosis: To help identify medical conditions (e.g., contrast dyes used in medical imaging).
  • Symptom Relief: To ease the discomfort associated with various ailments (e.g., pain relievers).

Drug Nomenclature: The Three Names of a Drug

Each drug typically has three names:

  1. Chemical Name: This is a complex, detailed description of the drug’s precise chemical structure and composition. It’s very long and complicated, rarely used in everyday practice (e.g., (+/-)-2-(p-isobutylphenyl) propionic acid).
  2. Generic Name: This is the official, non–proprietary name assigned to a drug by a regulatory body like the FDA (Food and Drug Administration) or EMA (European Medicines Agency). It’s simpler than the chemical name and universally recognized (e.g., ibuprofen). Doctors commonly use generic names when prescribing, and pharmacists usually use this name when dispensing medication.
  3. Brand Name (Trade Name or Proprietary Name): This is the name under which the drug is marketed and sold by a specific pharmaceutical company. It is a copyrighted name and often includes a trademark symbol (®) (e.g., Brufen®, Advil®, Motrin® – all brand names for ibuprofen). Many different companies may produce the same drug, each with a different brand name.

Examples of Generic and Brand Names: Note that a single generic drug can have many different brand names. Similarly, some brand names may combine multiple active ingredients, while others may simply repackage an existing generic drug.

Generic Name

Brand Name(s)

Indication/Use

Amoxicillin

Amoxil®, Duramox®, Amoxapen®, and many more

Antibiotic (treats bacterial infections)

Ibuprofen

Brufen®, Advil®, Motrin®, Nurofen®, and many more

Pain reliever, anti-inflammatory

Paracetamol

Panadol®, Tylenol®, Acetaminophen®, and many more

Pain reliever, fever reducer

Propranolol

Inderal®, InnoPran XL®, and others

Treats high blood pressure, angina, and tremors

Salbutamol

Ventolin®, Proventil®, and others

Bronchodilator (treats asthma and other lung conditions)

Diazepam

Valium®, Diastat®, and others

Anti-anxiety medication, muscle relaxant

Metformin

Glucophage®, Fortamet®, and others

Treats type 2 diabetes

Lisinopril

Prinivil®, Zestril®, and others

Treats high blood pressure

Atorvastatin

Lipitor®, and others

Reduces cholesterol levels

Important Note: While brand-name and generic drugs contain the same active ingredient, there might be slight differences in inactive ingredients (fillers, binders). These differences usually don’t affect the drug’s efficacy, but some individuals might experience minor differences in how the medication affects them. This is usually not clinically significant, but it’s important to be aware of.

Drug Classification

Drugs can be categorized in several ways, each serving a specific purpose in understanding their use, regulation, and pharmacological properties. The primary classifications include:

  1. Prescription Classification
  2. Pharmacological Classification
  3. Legal Classification

Prescription Classification

This classification system divides drugs based on whether they require a prescription from a healthcare provider or can be obtained over the counter.These need a doctor’s prescription because they’re powerful, can have serious side effects if misused, or are easily abused.

Prescription-Only Medicines (POM): 

These drugs necessitate a prescription due to their potential for harm if misused or self-administered. Examples include:

  • Antibiotics: Amoxicillin (treats bacterial infections), Ciprofloxacin (treats various bacterial infections), and others targeting specific bacterial strains. The choice of antibiotic depends heavily on the identified pathogen and its susceptibility.
  • Analgesics: Diclofenac (a nonsteroidal anti-inflammatory drug, NSAID, for pain and inflammation). Other NSAIDs like ibuprofen and naproxen also fall into this category, differing in their mechanisms and side-effect profiles.
  • Cardiovascular Medications: Nifedipine (a calcium channel blocker used to treat hypertension and angina). Numerous other cardiovascular drugs exist, targeting various aspects of the cardiovascular system, including blood pressure, heart rate, and cholesterol levels. Each drug has specific indications and contraindications.
  • Antidepressants: Sertraline (Zoloft), Fluoxetine (Prozac). These treat depression and other mood disorders. They should only be taken under a doctor’s supervision due to potential side effects and the need for careful dose adjustment.
  • Anti-anxiety Medications: Alprazolam (Xanax), Diazepam (Valium). These are used for anxiety and panic disorders, and can be habit-forming.
  • Asthma Inhalers: Many inhalers containing corticosteroids or bronchodilators require a prescription to ensure appropriate use and monitoring for side effects.
  • Diabetes Medications: Insulin (various types), Metformin. These require careful monitoring and adjustment by a doctor to maintain blood sugar levels within a safe range.
Over-the-Counter (OTC) Drugs: 

These are considered safe for self-administration when used as directed. These are considered safe enough for you to buy without a prescription. They’re readily available in pharmacies and other retail outlets. Examples include:

  • Analgesics: Panadol® (paracetamol/acetaminophen), Hedex® (containing paracetamol and other ingredients). The specific formulation of OTC analgesics varies widely, influencing their effectiveness and potential side effects.

  • Vitamins and Minerals: Numerous vitamin and mineral supplements are sold OTC, but their efficacy and safety depend on factors like dosage, individual needs, and potential interactions with other medications or underlying health conditions.

  • Cough and Cold Remedies: Goodmorning syrup® (and similar products) containing ingredients intended to alleviate cough symptoms. It’s crucial to consider the specific active ingredients and potential interactions before use.

  • Antacids: Tums, Rolaids. These neutralize stomach acid for heartburn relief. Overuse can be problematic.

  • Antihistamines: Diphenhydramine (Benadryl), Cetirizine (Zyrtec). These relieve allergy symptoms. Some can cause drowsiness.

  • Laxatives: Many types exist for treating constipation. Overuse can lead to dependence.

 

Pharmacological Classification 

This system categorizes drugs based on their mechanism of action or their effect on the body. This focuses on what the drug does in the body.

By Target Body System:

 Drugs are grouped according to the organ system they primarily affect. Examples include:

  • Cardiovascular Drugs: Affecting the heart and blood vessels (e.g., beta-blockers, ACE inhibitors, diuretics). Each class within cardiovascular drugs has specific actions and clinical applications.
  • Neurological Drugs: Affecting the nervous system (e.g., antidepressants, antipsychotics, anticonvulsants). The choice of neurological medication is highly individualized based on diagnosis and patient response.
  • Gastrointestinal Drugs: Affecting the digestive system (e.g., antacids, laxatives). Different gastrointestinal drugs target specific aspects of digestive function.
  • Respiratory Drugs: Affecting the lungs and airways (e.g., bronchodilators, corticosteroids). Respiratory drugs are crucial in managing conditions like asthma and COPD.
By Activity on Microorganisms: 

This is particularly important for antimicrobial drugs:

  • Antibiotics: Targeting bacteria (e.g., penicillin, tetracycline, cephalosporins). Antibiotic classes differ in their mechanisms of action and spectrum of activity.
  • Antivirals: Targeting viruses (e.g., acyclovir, oseltamivir). Antiviral drugs often have highly specific targets and mechanisms.
  • Antifungals: Targeting fungi (e.g., fluconazole, ketoconazole). Antifungal drugs can have differing effects depending on the type of fungus being treated.

Legal Classification

Legal classification divides drugs into categories based on their potential for abuse and medical use. In otherwords, Drugs are classified based on their therapeutic use, abuse potential, and legal status.

Class A Drugs:

These include highly controlled substances such as:

  • Morphine
  • Pethidine
  • Cocaine (Schedule I and II)
Class B Drugs:

These include a broader range of controlled substances such as:

  • Phenobarbitone
  • Ciprofloxacin
  • Amoxicillin
  • Diazepam
  • Codeine
  • Griseofulvin
  • Metformin (Schedule 3, 4, and 5)
Class C Drugs:

These include over-the-counter drugs that are generally considered safe for public use without a prescription.

Class

Description

Examples

Class A

High abuse potential, controlled substances

Morphine, pethidine

Class B

Prescription required, lower abuse potential

Amoxicillin, antihypertensives

Class C

Over-the-counter, safe for self-medication

Paracetamol, aspirin

Schedule of Controlled Substances

Controlled substances are further categorized into schedules based on their potential for abuse and accepted medical uses. That is to say, this classification is based on the potential for abuse and the drug’s medical usefulness. 

Schedule I Drugs (High Abuse Potential, No Accepted Medical Use): Heroin, lysergic acid diethylamide (LSD). These are typically subject to the strictest control measures.

  • Examples: Heroin, Lysergide (LSD)
  • Characteristics: High abuse potential and no currently accepted medical use.

Schedule II Drugs (High Abuse Potential, Accepted Medical Use): Morphine, codeine, pethidine (meperidine), methadone, cocaine. These drugs are tightly regulated, requiring specific prescribing protocols and record-keeping. Their use is generally reserved for situations where the benefits outweigh the substantial risks of addiction and misuse.

  • Examples: Morphine, Codeine, Pethidine, Methadone, Cocaine
  • Characteristics: High abuse potential but accepted medical uses. These drugs can lead to severe physical and psychological dependence.

Schedule III Drugs (Moderate Abuse Potential, Accepted Medical Use): Phenobarbitone, preparations containing limited quantities of opioids (e.g., codeine combined with paracetamol/acetaminophen – co-codamol). These have less stringent control measures than Schedule I and II drugs but still require careful monitoring.

  • Examples: Phenobarbitone, preparations containing limited quantities of opioids, and combinations with non-controlled substances like Paracetamol with Codeine (Co-codamol)
  • Characteristics: Less abuse potential than Schedule I and II drugs, with accepted medical uses.

Schedule IV Drugs (Low Abuse Potential, Accepted Medical Use): Diazepam, lorazepam (benzodiazepines). While considered less prone to abuse, these can still cause dependence with prolonged use.

  • Examples: Diazepam, Lorazepam
  • Characteristics: Lower abuse potential than Schedule I-III drugs, with accepted medical uses.

Schedule V Drugs (Lowest Abuse Potential, Accepted Medical Use): Drugs for cough or diarrhea containing limited quantities of opioid substances (e.g., loperamide in some formulations, piritex with codeine syrup, kaolin). These are often available with less stringent regulatory oversight than higher scheduled drugs.

  • Examples: Drugs generally used for relief of cough or diarrhea, containing limited quantities of certain opioids like Loperamide, Kaolin, and Piritex with Codeine Syrup
  • Characteristics: Lower abuse potential due to their low strength, with accepted medical uses.

Drug Administration

Drug administration refers to how drugs are delivered to patients.

Route

Description

Advantages

Disadvantages

Enteral (Oral)

Taken by mouth

Convenient, safe

Slow onset, GI absorption variability

Parenteral (IV, IM, SC)

Injections directly into the body

Rapid effect, precise control

Requires skill, painful, risk of infection

Topical

Applied to skin or mucous membranes

Localized effect, non-invasive

Slow absorption, limited drug types

Inhalational

Inhaled gases or aerosols

Quick relief for respiratory conditions

Requires technique, potential for irritation

Prescription Writing and Dispensing

Prescription Writing and Dispensing

Prescription Writing 

A prescription is a legal document—a written order from a licensed healthcare professional (doctor, nurse practitioner, physician assistant, etc.) to a pharmacist or other authorized dispenser, instructing them to provide a specific medication to a patient. 

The prescriber has a legal and ethical responsibility to ensure the prescription is accurate, clear, and safe.

A good prescription must include the following essential information:

1. Legibility: Written clearly in indelible ink (permanent ink that won’t fade or smear).

2. Date: The date the prescription was written.

3. Patient Information: The patient’s full name and address. For children, their age and weight are crucial for accurate dosing.

4. Diagnosis: The medical reason for prescribing the medication. While not always explicitly stated on every prescription, this is medically critical information used to justify the treatment and assess the appropriateness of the drug.

5. Medication Details:

  • Drug Name: The full name of the medication (generic name preferred for clarity).
  • Dosage Form: Tablet, capsule, liquid, injection, etc.
  • Strength: The amount of active ingredient per dosage unit (e.g., 500mg).
  • Quantity: The total amount of medication to be dispensed.
  • Duration: The length of treatment (e.g., “take for 7 days”).
  • Frequency: How often the medication should be taken (e.g., “twice daily”).

6. Patient Instructions: Clear, concise directions on how to take the medication, including when to take it (with or without food, at bedtime, etc.).

7. Prescriber Information: The prescriber’s full name, address, and contact information (phone number, etc.).

8. Facility Information: The name and address of the healthcare facility where the prescription is written.

Qualities of a Good Prescriber 

A good prescriber is knowledgeable, careful, and patient-centered. They:

  1. Prescribe Only When Necessary: Avoid unnecessary medication.
  2. Choose Appropriate Regimens: Select the most effective and safest treatment based on the patient’s specific condition and other health factors (allergies, other medications).
  3. Adjust Treatment as Needed: Monitor the patient’s response to treatment and adjust the dosage or medication as needed.
  4. Explain Treatment Clearly: Communicate effectively with the patient, explaining their condition, the medication’s purpose, potential side effects, and how to take it properly.
  5. Monitor Patient Progress: Follow up with the patient to assess their progress and make adjustments as needed.

The Rational Prescribing Process

Good prescribing follows a structured process:

  1. Define the Problem: Accurately diagnose the patient’s condition.
  2. Specify Therapeutic Objectives: Clearly define the desired outcome of treatment (e.g., pain relief, blood pressure control).
  3. Choose Appropriate Treatment: Select the most effective, safe, and well-tolerated medication, considering the patient’s overall health, potential drug interactions, and cost.
  4. Write an Accurate Prescription: Follow all the guidelines above.
  5. Inform the Patient: Educate the patient about their condition, treatment, and potential side effects.
  6. Review and Adjust Treatment: Regularly monitor the patient’s response and make changes as needed.

Over-Prescribing vs. Under-Prescribing: Both are problematic:

  • Over-prescribing: Wastes resources, increases the risk of side effects and adverse drug reactions, and can lead to addiction and increased healthcare costs.
  • Under-prescribing: Leads to ineffective treatment, potentially worsening the condition, delaying recovery, and ultimately increasing the cost of treatment over time due to the need for more extensive treatment down the road.

The Dispensing Process 

Dispensing is the process of providing medication to the patient as directed by the prescription. 

It’s performed by a licensed pharmacist or other authorized personnel (nurse, pharmacy technician).

Roles of a Dispenser

  1. Medication Dispensing: Accurately filling prescriptions.
  2. Patient Education: Providing medication information and instructions to patients.
  3. Record Keeping: Maintaining accurate drug records.
  4. Drug Storage: Ensuring proper storage conditions.
  5. Consultation with Prescriber: Advising prescribers on medication issues. (in some settings)
  6. Drug Procurement: Assisting with ordering drugs. (in some settings)

The Dispensing Procedure

  1. Receiving the Prescription: Checking for completeness and accuracy.
  2. Interpreting the Prescription: Understanding the instructions.
  3. Retrieving the Medication: Obtaining the correct medication from stock.
  4. Patient Counseling: Explaining how to take the medication and what to expect.
  5. Packaging: Ensuring the medication is properly packaged and labeled.
  6. Record Keeping: Documenting the dispensing process.
  7. Providing the Medication: Giving the medication to the patient.

Knowledge Required for Dispensing

Dispensers need comprehensive knowledge of:

  • Drug formulations and dosages
  • Indications and uses of medications
  • Precautions and contraindications
  • Potential side effects
  • Packaging, labeling, and storage requirements
  • Legal requirements for controlled substances
  • Medication administration techniques
  • Basic disease processes

Prescribing Medications

Prescribing involves selecting the appropriate drug, dose, route, and duration for treatment.

Consideration

Details

Patient factors

Age, weight, sex, pregnancy status, organ function, allergies, comorbidities

Drug factors

Efficacy, safety, side effects, interactions, cost

Compliance

Ensuring patient understanding and adherence to the regimen

Prescription Requirements:

A legal prescription must include patient details, drug information, and prescriber information.

Prescription Element

Description

Patient Information

Name, age, address

Drug Details

Name, strength, dosage, quantity, instructions

Prescriber Information

Name, signature, registration number

Abbreviations Used in Drug Administration

A wide range of abbreviations are used by doctors when making a prescription. These abbreviations are utilized to save time and space on prescriptions. They are categorized as follows:

1) Abbreviations Related to Frequency of Drug Administration

Abbreviation

Meaning

OD

Once daily

BID

Twice daily

TDS

3 Times daily

QID

4 Times daily

PRN

When necessary

Stat

Immediately

Ac

Before meals

Pc

After meals

2) Abbreviations Related to Dosage Form

Abbreviation

Meaning

Caps

Capsules

Tabs

Tablets

Syr

Syrup

Gut

Eye drops

Inf.

Infusion

Pess.

Pessaries

Mist

Mixture

Iv

Intravenous

Drug Classification Read More »

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