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

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