Uncategorised - Midwives Revision

Brucellosis (Undulant Fever, Malta Fever, Abortus Fever)

Brucellosis is a zoonotic bacterial infection of acute onset, commonly known as undulant fever, Malta fever, or abortus fever.

It’s primarily an occupational disease among people working with infected livestock or associated fresh animal products. This includes butchers, farmers, abattoir workers, and vendors of contaminated roasted meat (muchomo).

Incubation Period:

The incubation period for brucellosis is typically 2-4 weeks, but can range from 1 to 8 weeks.

Forms of Transmission:

Direct Contact: Contact with infected animals, particularly during handling, slaughtering, or birthing, can lead to transmission.
Ingestion: Consuming unpasteurized milk, cheese, or other dairy products from infected animals is a common route of transmission.
Inhalation: Inhaling contaminated aerosols, particularly in settings where animal products are processed or handled, can lead to infection.
Accidental Exposure: Laboratory workers or those handling animal products in agricultural settings may be at risk of accidental exposure.

Routes of Transmission:

Occupational Exposure: Farmers, veterinarians, slaughterhouse workers, and laboratory workers are at increased risk of exposure due to their close contact with infected animals.
Consumption of Contaminated Products: Consuming unpasteurized milk, cheese, or other dairy products from infected animals is a common route of transmission.
Accidental Exposure: Accidental exposure to contaminated materials or aerosols, particularly in laboratory settings, can lead to infection.

Causes/Aetiology:

Brucella Species: The most common species of Brucella that infect humans are:

Brucella abortus (cattle)
Brucella melitensis (goats and sheep)
Brucella suis (pigs)
Brucella canis (dogs)

Clinical Features:

Brucellosis is known for its diverse range of symptoms, which can appear anywhere from a few days to several weeks after infection. Common features include:

Fever: High-grade fever, often accompanied by chills and sweats.
Fatigue and Weakness: Profound fatigue, lethargy, and muscle aches.
Headache and Stiff Neck: Persistent headache, often accompanied by neck stiffness.
Arthritis and Muscle Pain: Pain and inflammation in joints, particularly in the spine and large joints.
Sweating: Excessive sweating, particularly at night.
Weight Loss: Unintentional weight loss due to poor appetite and decreased food intake.
Depression: Emotional disturbances, including depression, anxiety, and irritability.
Splenomegaly and Hepatomegaly: Enlargement of the spleen and liver.
Orchitis: Inflammation of the testicles in men.
Endocarditis: Infection of the heart valves.
Meningitis: Inflammation of the meninges (membranes surrounding the brain and spinal cord).

Differential Diagnosis:

Typhoid fever: Similar symptoms, including high fever, headache, and muscle aches.
Malaria: Fever episodes that coincide with mosquito bites.
Tuberculosis: Chronic cough, night sweats, and weight loss.
Trypanosomiasis (sleeping sickness): Fever, headache, and fatigue, often accompanied by neurological symptoms.
Other causes of prolonged fever: Other infections, autoimmune disorders, and certain cancers can also cause prolonged fever.

Definitive Diagnosis and Investigations:

Blood Culture: A positive blood culture for Brucella is considered the definitive diagnosis.
Serological Tests: Serological tests, such as the agglutination test and the enzyme-linked immunosorbent assay (ELISA), can detect antibodies against Brucella bacteria.
Other Tests: Additional tests, such as bone marrow culture, urine culture, or biopsy, may be necessary depending on the clinical presentation.
Blood: Complement fixation test or agglutination test (where possible).
Isolation of the infectious agent from blood, bone marrow, or other tissues by culture.

Management:

Treatment:

Adults and children > 8 years:

Doxycycline 100 mg every 12 hours for 6 weeks
Plus gentamicin 5-7 mg/kg IV daily for 2 weeks
Or ciprofloxacin 500 mg twice daily for 2 weeks

Children < 8 years:

Cotrimoxazole 24 mg/kg every 12 hours for 6 weeks
Plus gentamicin 5-7 mg/kg IV in single or divided doses for 2 weeks

Caution:

Treatment duration must be adhered to at all times.
Ciprofloxacin is contraindicated in children <12 years.
Doxycycline and gentamicin are contraindicated in pregnancy.

Prevention:

Public health education:

Drinking only pasteurized or boiled milk.
Careful handling of pigs, goats, dogs, and cattle, especially if a person has wounds or cuts.

Veterinary services: Provide veterinary services for domestic animals to prevent the spread of infection.
Safe handling practices: Use proper hygiene practices when handling animals and wear protective clothing.
Occupational safety: Implement safety protocols and use PPE in occupational settings where exposure to infected animals or their products is likely.
Food safety: Consume only pasteurized milk, cheese, and other dairy products. Avoid eating raw or undercooked meat from animals suspected of being infected with Brucella.
Travel precautions: Advise travelers to countries where brucellosis is endemic to be aware of the risks and take necessary precautions.

Complications:

Endocarditis: Infection of the heart valves, which can be life-threatening.
Meningitis: Inflammation of the meninges, which can lead to neurological complications.
Arthritis: Inflammation of joints, particularly in the spine and large joints.
Osteomyelitis: Infection of the bone, which can lead to bone damage and disability.
Hepatitis: Inflammation of the liver.
Orchitis: Inflammation of the testicles in men.
Chronic Fatigue Syndrome: Persistent fatigue and other symptoms, which can significantly impact quality of life.
Neurological complications: Neurological complications can occur in severe cases and may include encephalitis, seizures, and coma.

Brucellosis Read More »

HOME VISITING IN COMMUNITY HEALTH

Home visiting is highly essential to community health services, as a large number of patients are found in their homes.

Home visiting refers to the process of providing nursing care to patients at their residences.

Objectives of Home Visiting:

Establish close relationships with the community and families.
Assess the living conditions of families and identify how these conditions affect their health.
Promote family health by providing health education tailored to the age and developmental stage of each family member.
Monitor the skills learned during health education sessions.
Demonstrate to families how to administer necessary healthcare to other family members.
Refer families to appropriate specialized services when needed.

Factors Influencing the Growth of Home Visiting Services:

Increasing elderly population facing chronic illnesses.
Increased prevalence of HIV/AIDS.
Advanced technology enabling home-based healthcare services.
Rising cost of healthcare.
Growing demand for consumer satisfaction.

Principles of Home Visiting:

When conducting home visits, community nurses should adhere to these essential principles:

Purposeful and beneficial: Home visits should be planned with a clear objective and be beneficial to the patients.
Needs-driven: The purpose of each visit should align with the specific needs of the patient.
Beyond surveys and statistics: Home visits shouldn’t solely rely on surveys or data collection but should incorporate health education and practical support.
Regular and flexible: Visits should be scheduled regularly but adjusted according to the patient’s needs.
Educational: Home visits provide excellent opportunities for health education.
Convenient and acceptable: Visits should be convenient for the patient and respect their preferences.
Demonstrative: Home visits should provide nurses with the opportunity to demonstrate hygienic principles.

Effective Home Visiting Practices:

Family-centered approach: The nurse should actively involve each family member in the care process.
Positive relationships: Nurses and families should work collaboratively to build strong, trusting relationships that support goal achievement.
Respect for patient autonomy: Nurses must respect the patient’s right to accept or refuse care and participate in setting and reaching goals.
Record-keeping: Home visits should be documented in the patient’s medical records to ensure continuity of care.

Advantages of Home Visits:

Provides an ideal setting for implementing the nursing process.
Offers an opportunity to assess the home and family situation.
Allows nurses to provide services in the patient’s familiar environment.
Facilitates strong relationships between nurses and families.
Addresses family concerns and clarifies doubts.
Enables nurses to observe family practices and the progress of care.
Supports modification of care plans based on observations.
Offers a viable option for patients unable or unwilling to travel.
Creates a comfortable atmosphere for discussing concerns and needs.

Components of Home Visiting:

1. Initiation Phase: The community health nurse clarifies the source of referral for the visit, its purpose, and shares this information with the family.

2. Pre-visit Activities: Prior to the visit, nurses gather information about the family, including location, distance, address, and the reason for the visit. This may involve reviewing family folders, consulting other nurses or family members, or contacting health agencies. Information gathered may include age, sex, family structure, culture, values, problems, current care, etc. This information helps the nurse plan appropriately for the visit and address the patient’s needs effectively.

3. Activities During Home Visits: Community health nurses use their skills to build rapport and trust with the family, which is crucial for a positive relationship. The nurse-patient relationship is vital for providing healthcare services in the community. The nurse introduces herself, establishes her professional identity, and builds the nurse-patient relationship. This relationship should be characterized by:

One person possessing knowledge and skills that can benefit another.
The needs of the person receiving assistance taking priority.
The relationship being self-limiting based on the goals to be achieved.
The person receiving assistance needing and utilizing the support.
The assistance being provided competently.
During visits, the nurse assesses the family’s needs and plans nursing care accordingly.

4. Termination Phase: The termination of home visits occurs when:

The nurse-patient goals are achieved, health is restored, and the patient can function without nursing assistance.
The patient changes residence or moves to another care setting.
The nurse transfers the patient’s care to another nurse or caregiver.

5. Post-visit Activities: These include recording and reporting. The nurse documents important events within the family, reports necessary information to higher authorities, discusses family problems with colleagues and other health team members, and plans accurately to meet the family’s needs.

Areas Associated with Home Visiting:

General cleanliness
Solid waste disposal
Latrine/Toilet facilities
Personal hygiene
Infant vaccination (under 1 year)
Women’s vaccination
Antenatal care
Presence of insects or rodents in the home
Feeding practices for children over 2 years old
Family planning
Presence of sick individuals in the house and actions taken.

Limitations of Home Visiting:

Time-consuming
Limited equipment can be transported to homes.
Appointments may not be kept.
Uncooperative or violent family members.
Some homes may be geographically inaccessible.
Language barriers.

Problems with Home Visits:

Time and energy consumption: Community health nurses may spend a considerable amount of time traveling to and from homes, which can impact the time available for providing care.
Non-acceptance: Families may not accept the nurse due to cultural differences, personal characteristics, or socioeconomic status.
Language barriers: Communication difficulties can arise if the nurse is unfamiliar with the local language.
Role confusion: Some individuals or families may not fully understand the role of a nurse in home visiting, leading to confusion about expectations.

HOME VISITING IN COMMUNITY HEALTH Read More »

Vaccines and Immunoglobulins

Vaccines are special preparations of antigenic materials that can be used to stimulate the development of antibodies and thus confer active immunity against a specific disease or a number of diseases.

Vaccines may be single component or mixed combined vaccines.

Types of Vaccines

Live Attenuated Vaccines: These vaccines contain live microbes that have been weakened (attenuated). Live attenuated vaccines usually confer immunity with a single dose which is of long duration. They may be dangerous in recipients who are immunocompromised because these patients are unable to mount an effective immune response.

Examples:

Mumps vaccines
Measles vaccines
BCG vaccines
Rubella vaccines
Chickenpox vaccines

Killed or Inactivated Vaccines: This type of vaccine contains whole inactivated microbes. Inactivated vaccines may require a series of injections in order to produce an adequate body response and in most cases booster doses are required.

Examples:

Polio vaccines

Toxoids: Toxoid vaccines use bacterial toxins that have been rendered harmless. Administration of the toxoid causes the recipient’s immune system to manufacture antitoxins directed against the bacterial toxins.

Examples:

Tetanus toxoid

Immunity

Immunity is the body’s ability to resist infections afforded by the presence of circulating antibodies and white blood cells.

Types of Immunity

Active Immunity: Active immunity is induced by the administration of microorganisms or their products which act as antigens to induce the body to produce antibodies.
Passive Immunity: Passive immunity is obtained by injecting preparations made from the plasma of immune individuals with adequate levels of antibodies to the disease for which protection is sought. Treatment should be given as soon as possible after exposure for effective results. This type of immunity lasts for only a few weeks.

Poliomyelitis Vaccine

Available Preparations:

Oral suspension of live attenuated poliomyelitis virus

Indications:

Active immunization against poliomyelitis

Contraindications:

Hypersensitivity to any of the ingredients
Patients with diarrhea or vomiting
Immunocompromised patients
Pregnancy

Dosage:

2 drops at birth
2 drops at 6 weeks
2 drops at 10 weeks
2 drops at 14 weeks

Side Effects:

Rarely seen

Drug Interactions:

Concomitant administration with immunosuppressant drugs

Key Issues to Note:

Live polio vaccine loses potency once the container has been opened; therefore, discard any unused preparation
Breastfeeding does not interfere with immunization even though polio antibodies may be excreted in breast milk
If the vaccine is vomited, repeat the dose immediately
A child who has previously had polio should nevertheless be immunized to offer complete protection

Measles Vaccine

Available Preparations:

Injection powder for solution (live attenuated measles virus)

Available Brands: Sii® measles vaccine live

Indications:

Active immunization against measles

Contraindications:

Hypersensitivity to any antibiotic present in the vaccine
Hypersensitivity to eggs

Dosage:

0.5 ml SC at 9 months (left upper arm)

Side Effects:

Fever
Malaise
Thrombocytopenia
Headache
Rashes

Key Issues to Note:

Vaccination is recommended in all children at the age of 9 months
Maternal antibodies may interfere with an effective immune response to the vaccine if given in the first 6 months of life
The vaccine may be given at 6 months in case there is an outbreak in the community
Vaccination should not be given to patients with untreated active tuberculosis

Measles, Mumps, and Rubella Vaccine (MMR Vaccine)

Available Preparations:

Injection of live attenuated measles, mumps, and rubella virus

Available Brands: Sii® measles, mumps, and rubella vaccine, Trimovax®, Priorix®

Indications:

Active immunization against measles, mumps, and rubella

Contraindications:

Pregnancy
Hypersensitivity to any antibacterial such as neomycin or kanamycin used in the manufacturing process
Immunosuppressed patients

Dosage:

By deep SC or by intramuscular injection 0.5 ml (12-15 months)

Side Effects:

Fever
Parotid swelling
Malaise
Rash

Drug Interactions:

Concomitant administration with immunosuppressant drugs

BCG Vaccine

Available Preparations:

Powder for injection of live bacteria of a strain derived from the bacillus of Calmette and Guerin

Indications:

Active immunization against tuberculosis

Contraindications:

Generalized edema
Immunosuppressed patients
Antimycobacterial treatment
Previous TB infections
Generalized skin diseases
Tuberculin reaction > 5 mm

Dosage:

0.05 ml intradermally in the right upper arm (infants less than 12 months)
0.1 ml intradermally on the right upper arm (adults and children greater than 12 months)

Side Effects:

Keloid formation
Lymphadenitis
Localized necrotic ulceration
Anaphylaxis
Disseminated BCG infection in immunosuppressed patients

Drug Interactions:

Concomitant administration with immunosuppressant drugs

DPT Vaccine

Available Preparations:

Powder for injection

Available Brands: TriPacel®, Infanrix®

Indications:

Active immunization against diphtheria, tetanus, and pertussis

Dosage:

Infant: 0.5 ml by intramuscular or deep SC injection at 6, 10, and 14 weeks

Side Effects:

Irritability
Restlessness
Limb swelling
Malaise
Peripheral neuropathy
Myalgia
Urticaria
Headache
Fever
Loss of appetite

Tetanus Toxoid Vaccine

Available Preparations:

Injection

Available Brands: Sii® tetanus toxoid vaccine, Tetavax®

Indications:

Active immunization against tetanus and neonatal tetanus

Dosage:

Women 15-45 years of age including pregnant women: 0.5 ml deep SC or intramuscular injection at first contact or as early as possible during pregnancy (TT1)
TT2 (0.5 ml) at least 4 weeks after TT1 or during subsequent pregnancy
TT3 (0.5 ml) at least 6 months after TT2 or during the subsequent pregnancy
TT4 (0.5 ml) at least 1 year after TT3 or during subsequent pregnancy
TT5 (0.5 ml) at least 1 year after TT4 or during subsequent pregnancy

Note: To achieve lifelong protection against tetanus, 5 doses of TT are required.

Side Effects:

Peripheral neuropathy

Anti-Tetanus Immunoglobulin

Available Preparations:

Injection 1500 IU

Available Brands: Tetanea®

Indications:

Passive immunization against tetanus as part of the management of tetanus-prone wounds

Dosage:

Adult and Children: 1 ml by IM injection. Give additional dose if wound is older than 12 hours or heavily contaminated

Side Effects:

Local reactions
Fever
Pain and tenderness at the site of injection
Headache

Yellow Fever Vaccine

Available Preparations:

Injection powder + solvent of live attenuated virus

Available Brands: Stamaril®

Indications:

Active immunization against yellow fever

Contraindications:

Immunosuppressed patients
Known hypersensitivity to any of the ingredients
Infants under 4 months of age
Hypersensitivity to eggs

Dosage:

Infants at 9 months: 0.5 ml by SC injection
Immunization of travelers and others at risk:

Adult and Children over 9 months: 0.5 ml
Infants 4-9 months: 0.5 ml only if the risk of yellow fever is unavoidable

Side Effects:

Headache
Fever
Weakness
Diarrhea
Myalgia
Influenza-like symptoms
Nausea

Drug Interactions:

Concomitant administration with immunosuppressant drugs
Cholera vaccine should not be given together with yellow fever vaccine

Typhoid Vaccine

Available Preparations:

Injection VI capsular polysaccharide typhoid 25 mcg/0.5 ml

Available Brands: Typhim Vi®, Typherix®

Indications:

Active immunization against typhoid

Contraindications:

Immunosuppressed patients
Febrile illness
Known hypersensitivity to any of the ingredients

Dosage:

Adult and children over 2 years: By deep SC (subcutaneous) or intramuscular 0.5 ml with booster doses every 3 years for those at continued risk

Side Effects:

Headache
Allergic reaction
Myalgia
Fever
Nausea
Malaise
Swelling and pain

Key Issues to Note:

Typhoid fever prevention becomes effective after 2-3 weeks after injection
Typhoid is rare in children under 2 years; therefore, to immunize in this age group should be based on the risk of exposure
The vaccine offers protection for a minimum duration of 3 years

Pneumococcal Vaccine

Available Preparations:

Injection in form of 23-valent polysaccharide vaccine 25 mcg/0.5 ml

Available Brands: Pneumo 23®

Indications:

Immunization against pneumococcal infections in:

Sickle cell disease in children over 2 years of age
Immunocompromised patients over 5 years at increased risk of pneumococcal infection

Contraindications:

Severe allergic reaction to any of the ingredients

Dosage:

Adult and children over 2 years: 0.5 ml deep SC or IM as a single dose

Side Effects:

Fever
Myalgia
Pain and erythema at injection site

Key Issues to Note:

Revaccination is recommended every 5-10 years in high-risk patients

Meningococcal Vaccine

Available Preparations:

Injection

Bivalent vaccine from group A and C
Tetravalent vaccine from groups A, C, Y, and W135

Available Brands: Meningo A + C®, Mencevax ACWY®

Indications:

Active immunization against Neisseria meningitidis infections such as meningitis and septicemia

Contraindications:

Allergy to diphtheria toxoid
Febrile conditions

Dosage:

Bivalent: 0.5 ml deep SC or IM injection as a single dose
Tetravalent: 0.5 ml deep SC injection as a single dose

Side Effects:

Allergic reaction
Anaphylaxis
Erythema

Key Issues to Note:

Do not use in children under 2 years except in epidemic situations

Cholera Vaccine

Available Preparations:

Oral vaccine containing live attenuated or inactivated

Available Brands: Dukoral®

Indications:

Immunization for travelers over 2 years of age at high risk of cholera infections

Contraindications:

History of hypersensitivity to any of the ingredients
Acute GIT or febrile

Dosage:

Children 2-6 years: 3 doses given at intervals of at least 1 week. Give a booster after 6 months if still at risk
Adult and Children over 6 years of age: 2 doses given at 1-week intervals. Give a booster after 2 years if still at risk

Side Effects:

Abdominal discomfort
Headache
Diarrhea
Fever

Key Issues to Note:

Avoid food and drinks 1 hour before and after taking the vaccine

Rabies Vaccine

Available Preparations:

Injection 2.5 IU/dose

Available Brands: Sii rabivax®, Lyssavac berna®, Verorab®

Indications:

Active immunization against rabies
Post-exposure treatment to prevent rabies in patients who have been bitten by rabid animals
Pre-exposure prophylaxis in persons at high risk of being bitten by rabid animals

Contraindications:

Known hypersensitivity to any of the ingredients

Dosage:

Pre-exposure prophylaxis: 1 ml by deep subcutaneous or intramuscular injection on days 0, 7, and 28
Post-exposure treatment: 1 ml by deep subcutaneous or intramuscular injection on days 0, 3, 7, 14, and 30

Side Effects:

Pain at injection site
Fever
Erythema at injection site
Malaise
Nausea
Myalgia
Headache
Hypersensitivity reaction

Hepatitis B Vaccine

Available Preparations:

Injection containing inactivated hepatitis B surface antigen

Available Brands: Euvax B adult®, Euvax B paed®, Engerix B®

Indications:

Active immunization against hepatitis B infection

Contraindications:

History of hypersensitivity

Dosage:

Adult and Children over 15 years: 1 ml with an interval of 1 month between the 1st and 2nd dose and 5 months between the 2nd and 3rd doses. Total of 3 doses
Children below 15 years: 0.5 ml with 1 month between the 1st and 2nd dose, and 5 months between the 2nd and 3rd dose
Infants: 0.5 ml intramuscular injection at 6 weeks, 10 weeks, and 14 weeks of age

Side Effects:

Abdominal pain
GIT disturbance
Sleep disturbance
Lymphadenopathy
Muscle and joint pains
Dizziness
Peripheral neuropathy
Myalgia

Key Issues to Note:

Immunocompromised patients may need further doses

Anti-D (Rho) Immunoglobulin

A Rhesus-negative mother may develop antibodies against Rho antigen red cells when she carries a Rhesus-positive fetus and fetal red cells enter her circulation during childbirth, abortion, or miscarriage. Rho immunoglobulin is used to prevent non-sensitized mothers from producing antibodies which may cause hemolytic disease of the newborn.

Available Preparations:

Injection

Indications:

Prevention of Rhesus D sensitization in females who are Rhesus D negative

Contraindications:

Rhesus-positive individuals
Isolated immunoglobulin A deficiency

Dosage:

Following birth of Rhesus-positive infant: 500 units deep IM immediately or within 72 hours
Following stillbirth: 250 units per episode immediately or within 72 hours
Antenatal prophylaxis: 500 units given at 28 and 34 weeks of pregnancy. A further dose is still needed immediately or within 72 hours of delivery

Side Effects:

Local tenderness and stiffness
Fever
Nausea
Vomiting
Back pain
Abdominal pain
Myalgia
Malaise
Sweating
Skin rash

Vaccines and Immunoglobulins Read More »

Drugs Used in Anaesthesia

Anaesthesia is defined as the absence of feelings, sensation, or pain. Anaesthetics are drugs that reduce or abolish sensation, affecting either the whole body (general anaesthetics) or a particular area or region (local anaesthetics).

Local Anaesthetics

Local anaesthetics provide brief periods of anaesthesia in a small localized area of the skin and adjacent tissues. They may be administered in two ways: topically for surface anaesthesia and by injection for infiltration anaesthesia.

Topical anaesthetics are usually applied to the skin or the mucous membrane to relieve itching, insect bites, hemorrhoids, pruritus, and minor surgical procedures.

Infiltration anaesthesia may be achieved by injecting a local anaesthetic into the immediate area of surgery. It is commonly used during dental extraction and biopsies.

Examples:

Lidocaine (lignocaine)
Bupivacaine
Mepivacaine

Note: Lignocaine is sometimes combined with epinephrine (adrenaline), a powerful vasoconstrictor, that decreases blood flow to the tissue where it is injected. Adrenaline controls bleeding and also prolongs the anaesthetic action of lignocaine.

General Anaesthetics

General anaesthetic drugs are normally given IV or by inhalation to produce rapid, reversible loss of consciousness and insensibility to surgical stimuli.

Examples:

Inhaled Anaesthetics:

Halothane
Nitrous oxide
Ether

Intravenous Anaesthetics:

Ketamine
Midazolam
Propofol

Ketamine

Available Preparations:

Injection: 50 mg/ml

Available Brands: Ketajex®, Ketalar®

Pharmacokinetics: Ketamine is rapidly and well absorbed after IM injection, rapidly enters the CNS, metabolized by the liver, and excreted in urine.

Indications:

Induction and maintenance of anaesthesia
Pain relief
Diagnostic maneuvers and procedures not involving intense pain

Contraindications:

Thyrotoxicosis
Hypertension (including pre-eclampsia)
History of cerebrovascular accident
Raised intracranial pressure
Psychiatric disorders, particularly hallucinations
Severe cardiac disease
Recent myocardial infarction
Stroke
Known hypersensitivity to ketamine
Cerebral trauma
Eye injury

Dosage:

Induction:

Intravenous Injection: 1-4.5 mg/kg (2 mg/kg usually produces anaesthesia lasting 5-10 minutes)
Intramuscular Injection: 6.5-13 mg/kg (duration of anaesthesia up to 25 minutes)
IV Infusion: 0.5-2 mg/kg initially, then infuse at 10-45 mcg/kg/minute, adjust according to response

Maintenance:

Intravenously: Increments of half or full dose repeated as required
Analgesic for painful procedures: IV 1-1.5 mg/kg slowly over 2-5 minutes. Give half dose every 10 minutes if required for prolonged procedures

Administration Instructions:

Dilute dose with an equal volume of water for injection, sodium chloride 0.9%, or glucose 5% before IV injection
Give IV slowly; rapid administration may result in respiratory depression and enhanced hypertensive response

Side Effects:

Raised blood pressure and pulse rate
Increased muscle tone
Lacrimation
Hypersalivation
Raised intracranial pressure
Redness of the skin
Postoperative nausea and vomiting
Pain on injection
Irrational behavior during recovery

Drug Interactions:

Inhalation anaesthetics such as halothane may prolong the effect of ketamine and delay recovery
Prolonged recovery occurs when barbiturates or opioids are given concurrently with ketamine
Ketamine should not be used with ergometrine
Concomitant use with thyroid hormones may cause hypertension and tachycardia

Key Issues to Note:

Warn the patient to avoid tasks requiring motor coordination and/or mental alertness for 24 hours after anaesthesia
Keep verbal, tactile, and visual stimulation to a minimum during induction and recovery

Lidocaine

Available Preparations:

Solution: 1%, 2%
Topical Gel: 2-4%
Combinations: Xylocaine® (Lidocaine + epinephrine)

Note: Epinephrine is often added to delay absorption and thus reduce anaesthetic systemic toxicity and keep it in contact with nerve fibers, prolonging the duration of action.

Pharmacokinetics: Lidocaine is effectively absorbed from the mucous membranes, widely distributed throughout the body, metabolized in the liver, and excreted in urine.

Indications:

Infiltration anaesthesia
Surface anaesthesia of mucous membrane
Dental anaesthesia
Ventricular arrhythmias
Relief of pain in hemorrhoids

Contraindications:

Adjacent skin infection
Hypersensitivity
Heart block
Hypovolemia
Severe anemia
Myasthenia gravis
Spinal anaesthesia in dehydrated patients

Dosage:

Dental Anaesthesia: Using 2% solution with epinephrine

Adult: 20-100 mg (1-5 ml)

Local Infiltration and Peripheral Nerve Block: Using 1% solution with epinephrine

Adult: Up to 400 mg (up to 40 ml)

Note: Use lower doses for elderly, epileptic, or acutely ill patients. Do not use solution containing preservatives for spinal, epidural, intravenous, or regional anaesthesia.

Side Effects:

Dizziness
Lightheadedness
Tremors
Numbness
Restlessness
Convulsions
Unconsciousness
Headache
Blurred vision
Hypotension
Cardiac arrest
Backache
Sense of heat
Hypersensitivity reaction
Urinary retention

Drug Interactions:

Anti-convulsants may increase the cardiac depressant effect of lidocaine
Cimetidine and beta-blockers may increase plasma concentration of lidocaine, leading to increased risk of toxicity
Use of opioid analgesics peri-operatively may have additive respiratory and cardiac depressant effects

Key Issues to Note:

Doses should be reduced in acute and chronic hepatic diseases
If solutions discolor or precipitate, they should be discarded

Drugs Used in Anaesthesia Read More »

Drugs Used in the Treatment of Cancer

Cancer is a disease characterized by a shift in the control mechanisms that govern cell survival, proliferation, and differentiation.

Uncontrolled multiplication of cells leads to the formation of tumors that may be benign or malignant. Benign tumors do not spread to other tissues, while malignant tumors do.

Types of Cancer

Carcinoma: Affects the skin and cells in the tissue lining internal organs.
Sarcoma: Affects muscles, bones, and fibrous tissues.
Leukemia: Affects white blood cells.
Lymphoma: Affects the lymph glands.

Drugs used in the treatment of cancer either kill cancer cells or modify their growth.

Table 1: Classification of Anticancer Drugs

Class	Examples
Antimetabolites	Methotrexate, 5-Fluorouracil, Cytarabine, 6-Mercaptopurine
Antitumor Antibiotics	Bleomycin, Dactinomycin
Alkylating Agents	Cyclophosphamide, Busulfan, Chlorambucil, Carmustine, Dacarbazine, Melphalan
Anthracyclines	Daunorubicin, Doxorubicin, Idarubicin
Vinca Alkaloids	Vincristine, Vinblastine
Platinum Analogs	Cisplatin
Hormonal Agents	Tamoxifen, Estrogen
Others	Hydroxyurea, Procarbazine

Bleomycin

Available Preparations:

Powder for Injection: 15 units/vial

Available Brands: Blenoxane®

Pharmacokinetics: IM administration results in lower serum levels than those occurring after equivalent IV doses. It distributes widely into total body water, mainly in the skin, lungs, kidneys, peritoneum, and lymphatic tissue. It undergoes extensive tissue inactivation in the liver and kidney; bleomycin and its metabolites are excreted primarily in urine.

Indications:

Squamous cell carcinoma (head, neck, penis, cervix)
Testicular carcinoma
Non-Hodgkin’s lymphoma
Lymphosarcoma

Contraindications:

Pregnancy
Breastfeeding
Previous allergic reaction

Dosage:

A test dose of 1-2 units given 2-4 hours prior to therapy is recommended.
0.25-0.5 unit/kg body weight or 10-20 units/m² body surface area given IV, IM, or SC once or twice weekly.

Side Effects:

Skin rash
Striae
Redness of the skin
Fever
Acute anaphylactoid reaction
Anorexia
Urticaria
Pruritus
Hyperpigmentation
Stomatitis
Hyperkeratosis
Weight loss
Progressive pulmonary fibrosis
Mucositis
Pneumonitis
Phlebitis
Vomiting

Drug Interactions:

Cisplatin may decrease bleomycin clearance and increase the risk of bleomycin toxicity.
Concomitant use may decrease serum levels of phenytoin and digoxin.

Key Issues to Note:

Increased pigmentation, particularly affecting the flexures and subcutaneous sclerotic plaques, may occur.
A test dose should be administered before starting therapy to check for hypersensitivity reactions.
Monitor pulmonary function tests during treatment.

Doxorubicin

Available Preparations:

Powder for Injection: 10 mg/vial, 50 mg/vial

Available Brands: Doxorubin®

Pharmacokinetics: It distributes widely into body tissues, with the highest concentrations found in the liver, heart, kidneys, skin, and muscles; it does not cross the blood-brain barrier. It is metabolized both in the liver and plasma; excreted largely in feces, with small amounts in urine.

Indications:

Acute leukemia
Lymphomas
Breast carcinoma
Thyroid carcinoma
Non-Hodgkin’s lymphoma
Ovarian carcinoma
Bone and soft tissue sarcomas
Hodgkin’s disease
Kaposi’s sarcoma in patients with AIDS
Transitional cell bladder carcinoma

Contraindications:

Hepatic dysfunction
Cardiomyopathy
Pregnancy and lactation
Persistent myelosuppression
Severe cardiac failure
Recent myocardial infarction

Dosage:

60-74 mg/m² or 1.2-2.4 mg/kg once every 3 weeks as a single intravenous injection of a solution in sodium chloride 0.9% or glucose 5% over 3 minutes or more.
Children: 35-75 mg/m² as a single intravenous injection, once every 3 weeks.

Side Effects:

Bone marrow depression
Anorexia
Hyperpigmentation of nail beds
Diarrhea
Irreversible CHF
Reversible alopecia
Nausea and vomiting
Stomatitis
Fever and chills
Urticaria
Conjunctivitis
Lacrimation

Drug Interactions:

Cholestasis induced by mercaptopurine may be potentiated by the concurrent administration of doxorubicin.
Concomitant use of daunorubicin or cyclophosphamide may potentiate the cardiotoxicity of doxorubicin through additive effects on the heart.
Serum digoxin, carbamazepine, and phenytoin levels may be decreased if used concomitantly with doxorubicin.
Phenobarbitone increases the elimination of doxorubicin.

Key Issues to Note:

Notify the patient that the urine may turn red for the first 1-2 days.
Doxorubicin may induce hyperuricemia; therefore, monitor the patient’s blood uric acid levels.
Encourage the patient to take adequate fluid intake to increase urine output and facilitate excretion of uric acid.
Advise the patient to call if fever, bleeding, and sore throat occur.
Avoid exposure to sunlight to prevent sunburns.
Warn the patient that alopecia will occur. Explain that hair growth should resume 2-5 months after the drug is stopped.
Tell the patient not to receive any immunization during therapy and for several weeks after.
Advise the patient to avoid exposure to people with infections.

Methotrexate

Available Preparations:

Tablets: 2.5 mg
Injection: 25 mg/ml

Available Brands: Texol®

Indications:

Treatment and palliation of solid tumors
Burkitt’s lymphoma
Leukemia
Psoriasis

Contraindications:

Known hypersensitivity to methotrexate
Pregnancy and lactation
Severe hepatic and renal impairment
Bone marrow suppression
Anemia
Immunodeficiency syndromes
Active infection

Dosage:

Leukemia: 15-30 mg/m² orally, intramuscularly, or intravenously; once a week.

Side Effects:

Nausea and vomiting
Stomatitis
Diarrhea
Anorexia
Malaise
Headache
Skin rash
Dermatitis
Pruritus
Dizziness
Blurred vision

Drug Interactions:

Concomitant use with probenecid and salicylates increases the therapeutic and toxic effects of methotrexate by inhibiting its renal clearance.
Alcohol enhances the hepatotoxicity caused by methotrexate.
Phenytoin, co-trimoxazole may give additive antifolate activity and increase the risk of methotrexate toxicity.

Key Issues to Note:

Full blood count, urea, and liver function tests should be carried out prior to and during treatment.
Folinic acid is required for rescue procedures.
Patients with hyperuricemia should maintain adequate fluid intake and alkalinization of urine.

Vincristine

Available Preparations:

Solution for Injection: 1 mg/ml, 0.1 mg/ml

Available Brands: Cristol®

Indications:

Leukemias
Lymphomas
Some solid tumors

Contraindications:

Demyelinating form of Charcot-Marie-Tooth syndrome
Pregnancy
Breastfeeding mothers
Current radiotherapy to the liver
Known hypersensitivity to vincristine

Dosage:

Adult: IV 1.4 mg/m² up to a max weekly dose of 2 mg/m².
Children: IV 2 mg/m² once a week.
Children < 10 kg: 0.05 mg/kg once a week.

Side Effects:

Hair loss
Stomatitis
Constipation
Abdominal cramps
Diarrhea
Skin rash
Headache
Jaw pain
Hoarseness
Diplopia
Nausea and vomiting
Abdominal distention
Urinary tract disturbance
Peripheral neuropathy

Drug Interactions:

Vincristine may decrease digoxin plasma levels and renal excretion.
Vincristine may reduce phenytoin plasma levels.

Key Issues to Note:

Allopurinol may be given to prevent uric acid nephropathy.
Stool softeners should be used for constipation prophylaxis.
Vincristine is a tissue irritant; care should be taken to avoid extravasation.

Tamoxifen

Available Preparations:

Tablets: 10 mg, 20 mg

Available Brands: Nolvadex®

Pharmacokinetics: Tamoxifen is well absorbed after oral administration, distributed widely into total body water, metabolized extensively in the liver, and excreted primarily in feces.

Indications:

Breast cancer
Female infertility (induction of ovulation)

Contraindications:

Known hypersensitivity to tamoxifen
History of deep vein thrombosis or pulmonary embolism in high-risk women
Pregnancy

Dosage:

Breast cancer: 20 mg daily.
Induction of ovulation (infertility): 20 mg daily on days 2, 3, 4, and 5 of the cycle; if necessary, the daily dose may be increased to 40 mg then 80 mg for subsequent courses.

Side Effects:

Hot flushes
Nausea
Vomiting
Lightheadedness
Bone pain
Confusion
Vaginal bleeding
Vaginal discharge
Headache
Decreased libido
Weakness

Drug Interactions:

Estrogen may decrease the effect of tamoxifen.
The anticoagulant effect of oral anticoagulants may be increased by tamoxifen.
Bromocriptine may elevate serum levels of tamoxifen.

Key Issues to Note:

Adverse effects may be controlled by dosage reduction.
Use cautiously in pre-existing leukopenia and thrombocytopenia.
Advise women not to become pregnant during therapy with tamoxifen.

Drugs Used in the Treatment of Cancer Read More »

Drugs Used in the Treatment of Obstetric and Gynecological Disorders

Drugs for Menstrual Disorders

The main disorders associated with menstruation that may require treatment include:

Amenorrhoea
Dysmenorrhoea
Menorrhagia
Premenstrual syndrome
Menopause

Amenorrhoea

Amenorrhoea is the absence of menstruation. A break in menstruation of 6 months or more is considered pathological in an adult woman who is not pregnant, lactating, or has reached menopause.

Amenorrhoea may be classified as:

Primary Amenorrhoea: Occurs when a female fails to have her first menstrual cycle by age 16 in the presence of normal secondary sexual characteristics.
Secondary Amenorrhoea: The absence of menses for 6 months or more in a woman whose normal menstruation has been established.

Management

Identification and correction of any underlying disorder

Dysmenorrhoea

Dysmenorrhoea is painful menstruation that prevents normal activity and requires medication.

Dysmenorrhoea may be classified as:

Primary Dysmenorrhoea: Usually begins with the first menstrual period and is characterized by cramping lower abdominal pain, nausea, vomiting, headache, and faintness. The cause is thought to be due to excessive prostaglandin production that causes the uterus to contract painfully.
Secondary Dysmenorrhoea: Usually affects older women who complain of congested ache with lower abdominal cramps which usually starts a few days before menstruation. It is associated with various disorders such as endometriosis, pelvic inflammatory disease, fibroids, or the presence of an IUD.

Drugs used in the treatment of primary dysmenorrhoea inhibit either ovulation or prostaglandin production.

Examples:

NSAIDs such as mefenamic acid, ibuprofen, indomethacin, naproxen, piroxicam, and diclofenac
Oral contraceptives
Progestogens (norethisterone)
Antispasmodics (hyoscine and drotaverin)

Menorrhagia

Menorrhagia is excessive menstrual bleeding. It may be associated with pelvic disorders such as fibroids, use of copper intrauterine devices, complications of pregnancy, malignant tumors, or dysfunctional bleeding. Menorrhagia may lead to iron deficiency anemia as well as impairing the quality of life of the patient.

Drugs used in the treatment of menorrhagia include:

Combined oral contraceptives
Mefenamic acid
Norethisterone
Medroxyprogesterone
Tranexamic acid

Pre-menstrual Syndrome

Pre-menstrual syndrome is a cyclic recurrence of psychological and physical symptoms that affect women in the days before menstruation. Symptoms include increased irritability, depression, anxiety, bloating, headache, and breast tenderness.

Drugs used in the treatment of pre-menstrual syndrome include:

Calcium supplements
Pyridoxine (vitamin B6)
Bromocriptine
Spironolactone
Mefenamic acid
Fluoxetine
Paroxetine
Atenolol

Note:

Bromocriptine, mefenamic acid, and spironolactone suppress physical symptoms.
Fluoxetine, paroxetine, and atenolol mostly suppress psychological symptoms.

Menopause

Menopause is the occurrence of no menstrual periods for one year after the age of 40 or permanent cessation of ovulation after loss of ovarian activity.

Signs and Symptoms:

Atrophic vaginitis
Dyspareunia
Complete cessation of menses
Heavier bleeding
Osteoporosis
Anxiety
Depression
Insomnia
Inability to concentrate
Irritability
Decreased libido
Urinary incontinence
Hot flashes
Night sweats
Headache
Tiredness

Treatment involves the use of hormone replacement therapy and vaginal lubricants.

Norethisterone

Available Preparations:

Tablets: 5 mg

Available Brands: Regulate-N®, Primolut-N®

Indications:

Dysfunctional uterine bleeding
Pre-menstrual syndrome
Delay of menstruation
Endometriosis
Dysmenorrhoea
Contraception

Contraindications:

Pregnancy
Severe liver impairment
Previous or existing liver tumors
Severe arterial disease
Undiagnosed vaginal bleeding
Porphyria
Hypersensitivity to norethisterone

Dosage:

Dysfunctional Bleeding:

To stop bleeding: 5 mg 3 times daily for 10 days
To prevent bleeding: 5 mg twice daily from day 19-26 of the cycle

Dysmenorrhoea: 5 mg 3 times daily from day 5-24 for 3-4 cycles
Endometriosis: 10-15 mg daily for 4-6 months or longer starting on day 5 of cycle (if spotting occurs, increase dose to 20-25 mg daily, reduce once bleeding has stopped)
Delay of Menstruation: 5 mg 3 times daily starting 3 days before anticipated onset of menstruation (menstruation occurs 2-3 days after stopping)
Pre-menstrual Syndrome: 5 mg 2-3 times daily from day 19-26 for seven cycles

Side Effects:

Nausea
Dizziness
Headache
Menstrual disturbance
Weight gain
Depression
Insomnia

Dydrogesterone

Available Preparations:

Tablets: 10 mg

Available Brands: Duphaston®

Indications:

Endometriosis
Dysfunctional uterine bleeding
Pre-menstrual syndrome
Habitual and threatened abortion
Hormone replacement therapy
Infertility
Dysmenorrhoea
Amenorrhoea
Irregular cycles

Contraindications:

Severe liver impairment
Previous or existing liver tumors
Severe arterial disease
Undiagnosed vaginal bleeding
Porphyria
Known hypersensitivity to dydrogesterone

Dosage:

Endometriosis: 10 mg 2-3 times daily from day 5-25 of cycle or continuously
Dysfunctional Bleeding:

To stop bleeding: 10 mg twice daily (together with an estrogen) for 5-7 days
To prevent bleeding: 10 mg twice daily (together with an estrogen) from day 11-25 of cycle

Dysmenorrhoea: 10 mg twice daily from day 5-25 of cycle
Amenorrhoea: 10 mg twice daily from day 11-25 of cycle with estrogen therapy from day 1-25 of cycle
Pre-menstrual Syndrome: 10 mg twice daily from day 12-26 of cycle
Irregular Cycles: 10 mg twice daily from day 11-25 of cycle
Habitual Abortion: 10 mg twice daily from day 11-25 of cycle until conception, then continuously until week 20 of pregnancy

Side Effects:

Nausea
Dizziness
Headache
Menstrual disturbance
Weight gain
Depression
Insomnia

Drugs for Infertility

Infertility refers to the inability of a woman to conceive or of a man to induce conception. The most common cause of infertility is the failure of either ovulation in females or spermatogenesis in males. In females, infertility may also be due to obstruction of the fallopian tubes or diseases of the lining of the uterus (endometrium).

Drugs used in the treatment of infertility include:

Clomifene
Bromocriptine
Tamoxifen

Clomifene

Available Preparations:

Tablets: 50 mg

Available Brands: Clomid®, Clominol®

Pharmacokinetics: It is readily absorbed from the GIT, metabolized by the liver, and excreted in feces.

Indications:

Anovulatory infertility

Contraindications:

Liver disease
Ovarian cysts
Hormone-dependent tumors
Known hypersensitivity to clomifene
Pregnancy (exclude before treatment)
Undiagnosed abnormal uterine bleeding

Dosage:

Adult: 50 mg daily for 5 days, starting within 5 days of the onset of menstruation (preferably on the second day) or at any time if cycles have ceased.
If ovulation does not occur, a second course of 100 mg daily for 5 days may be given starting as early as 30 days after the previous one. In general, 3 courses of therapy are adequate to assess whether ovulation is obtainable.

Side Effects:

Visual disturbance
Hot flushes
Abdominal discomfort
Abnormal uterine bleeding
Headache
Intermenstrual spotting
Insomnia
Endometriosis
Ovarian hyperstimulation
Dizziness
Hair loss
Nausea and vomiting
Breast tenderness
Weight gain
Depression
Menorrhagia

Key Issues to Note:

Advise the patient of the possibility of multiple births. The risk increases with higher doses.
Since the drug may cause dizziness or visual disturbances, warn the patient to avoid hazardous tasks until the response to the drug is known.

Drugs Used in the Treatment of Pre-eclampsia and Eclampsia

Pre-eclampsia is a condition that develops late in pregnancy after the 20th week of gestation, characterized by hypertension, proteinuria, and edema of the legs, hands, and face. Severe pre-eclampsia (BP > 160/110 mmHg) may result in morbidity and mortality for the mother or baby. It can lead to poor intrauterine growth and early delivery.

Eclampsia

Eclampsia is the occurrence of seizures or coma in a mother with pre-eclampsia occurring at greater than 20 weeks of gestation or less than 48 hours postpartum. Eclampsia is a threat to both mother and baby and must be treated immediately.

Drugs used in eclampsia include:

Magnesium sulphate
Hydralazine

Magnesium Sulphate

Available Preparations:

Injection: 50%

Indications:

Eclampsia (prevention of recurrent seizures)
Severe renal failure
Myocardial damage
Intestinal obstruction

Dosage:

By Intravenous Injection:

Start with a loading dose of 4 g by IV infusion in 0.9% sodium chloride over 15 to 20 minutes. Then administer a maintenance dose of 1 g per hour by continuous IV infusion for at least 24 hours until the last seizure.
Alternatively, start with a loading dose of 4 g by IV infusion in 0.9% sodium chloride over 15 to 20 minutes. Then administer by IM 10 g (5 g in each buttock) followed by 5 g every 4 hours for at least 24 hours after delivery or the last seizure.
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Side Effects:

Nausea and vomiting
Flushing of skin
Respiratory depression
Coma
Arrhythmias
Thirst
Hypotension
Confusion
Muscle weakness
Loss of tendon reflexes

Drug Interactions:

Magnesium sulphate potentiates the effects of calcium channel blockers and neuromuscular blockers.
Concomitant use with alcohol and other CNS depressants may increase the CNS depressant effects of magnesium sulphate.

Key Issues to Note:

IV bolus must be injected slowly to avoid respiratory or cardiac arrest.
Discontinue the drug as soon as the needed effect is achieved.
When giving repeated doses, test knee jerk reflex before each dose; if absent, discontinue magnesium.

Drugs for Endometriosis

Endometriosis is a medical condition characterized by the growth of endometrial tissue outside the uterine cavity.

It affects women in their reproductive years. Patients may be asymptomatic or have pelvic pain, menstrual changes, bowel symptoms, or infertility.

Drugs used in the treatment of endometriosis include:

Danazol
NSAIDs
Progesterone
Combined oral contraceptives

Danazol

Available Preparations:

Capsules: 50 mg, 100 mg, 200 mg

Available Brands: Gonablok®

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

Indications:

Endometriosis
Benign fibrocystic breast disease
Dysfunctional uterine bleeding
Prevention of hereditary angioedema
Gynaecomastia in males
Pre-menstrual syndrome
Prolactinomas
Female infertility
Amenorrhoea
Acromegaly

Contraindications:

Markedly impaired renal, hepatic, or cardiac function
Undiagnosed abnormal vaginal bleeding
Pregnancy and lactation
Porphyria
Androgen tumor
History of thromboembolic disease

Dosage:

Endometriosis: 100-400 mg twice daily for 3-9 months
Benign Breast Disorder: 50-200 mg twice daily, adjusted according to response for 3-6 months
Dysfunctional Uterine Bleeding: 200 mg daily for 3-6 months
Hereditary Angioedema: 200 mg 2-3 times daily reduced according to patient response
Gynaecomastia: 200 mg daily increased after 2 months to 400 mg daily if no response occurs

Side Effects:

Acne
Oily skin
Weight gain
Mild hirsutism
Nausea
Skin rash
Menstrual disturbance
Hot flashes
Changes in libido
Oedema
Hair loss
Headache
Backache
Tremors
Amenorrhoea
Sweating
Vaginal dryness and irritation
Deepening of the voice

Drug Interactions:

Warfarin anticoagulant effects may be enhanced by danazol.
Danazol may increase the effect of carbamazepine.
Danazol may cause decreases in blood glucose levels, which may require adjustment of insulin or oral hypoglycemic drugs.

Key Issues to Note:

The drug should not be discontinued without consulting the prescriber.
Therapy may take up to several months for full benefit depending on the purpose of treatment.
The drug may cause photosensitivity; therefore, avoid direct exposure to sunlight.
To treat endometriosis and fibrocystic breast disease, danazol therapy should begin during menstruation.
Advise the patient to report voice changes.
Advise female patients that amenorrhea usually occurs after 6-8 weeks of therapy.
Avoid administration of danazol with a fatty meal.
Use non-hormonal contraceptive measures and discontinue the drug if you suspect pregnancy.

Drugs for Contraception

Contraception refers to the various methods used to prevent pregnancy. These methods can be either medical or non-medical and may be used by men, women, or both.

Common methods of contraception include:

Abstinence
Barrier methods (male and female condoms)
Intrauterine devices (IUD)
Hormonal contraceptives
Female or male sterilization
Emergency contraceptives

Oral Contraceptives

Oral contraceptives are divided into two:

Combined oral contraceptives
Progestogen-only pills

Combined Oral Contraceptives

Oral combined contraceptives contain low doses of estrogen and progesterone. They are the most widely used contraceptives and have the lowest failure rate in terms of unwanted pregnancies. They are suitable for women who regularly experience exceptionally painful, heavy, or prolonged periods.

Mode of Action: They inhibit ovulation, reduce receptivity of endometrium to implantation, and thicken cervical mucus to form a barrier to sperm.

Indications:

Contraception
Dysfunctional uterine bleeding
Dysmenorrhoea
Endometriosis
Pre-menstrual syndrome
Menorrhagia

Contraindications:

Pregnancy
History of thromboembolic disorder
Pulmonary hypertension
Active viral hepatitis
Unexplained uterine bleeding
History of breast or hepatic cancer
Migraine
Atrial fibrillation
Severe cirrhosis

Side Effects:

Breakthrough bleeding
Changes in weight
Changes in libido
Venous thromboembolism
Fluid retention
Amenorrhoea
Photosensitivity
Breast enlargement and tenderness
Nausea and vomiting
Depression
Acne
Cervical cancer
Headache
Stroke
Increased blood pressure

Examples of Combined Oral Contraceptives:

MICROGYNON®/NEF®:

Composition: Levonorgestrel 0.15 mg, Ethinylestradiol 0.03 mg, Ferrous fumarate 75 mg (7 brown tablets)
Dosage: 1 tablet daily for 28 days starting on day 1 of the menstruation cycle with the active tablets.

PILL PLAN®:

Composition: Norgestrel 0.3 mg, Ethinylestradiol 0.03 mg, Ferrous fumarate 75 mg (7 brown tablets)
Dosage: 1 tablet daily for 28 days starting on day 1 of the menstruation cycle with the active tablets.

LO-FEMENAL®:

Composition: Norgestrel 0.3 mg, Ethinylestradiol 0.03 mg, Ferrous fumarate 75 mg (7 brown tablets)
Dosage: 1 tablet daily starting on day 1 of the menstruation cycle with the active tablets.

Progestogen-Only Pills

Progestogen-only pills are often recommended for women who react to estrogen in the combined pill or where combined pills are not suitable because of age or medical history. They may be used by breastfeeding mothers since they do not affect the quantity and quality of the milk produced. Progestogen-only pills have a higher failure rate compared to combined pills and must be taken at the same time each day for maximum contraceptive effect.

Mode of Action: Progestogen thickens the cervical mucus, which impedes the passage of sperm, disrupts the menstrual cycle including preventing the release of the eggs from the ovaries, and changes the endometrium reducing the potential for implantation.

Indications:

Contraception
Emergency contraception
Endometriosis
Menstrual disorders

Contraindications:

Pregnancy
Undiagnosed vaginal bleeding
Porphyria
Active viral hepatitis
Breast or liver cancer
Severe arterial disease
Severe cirrhosis

Side Effects:

Nausea
Spotting
Dizziness
Breast discomfort
Depression
Amenorrhoea
Vomiting
Weight gain
Headache
Prolonged bleeding
Acne

Examples:

OVRETTE®:

Composition: Norgestrel 0.075 mg
Dosage: 1 tablet daily starting on day 1 of the menstruation cycle.

SOFT SURE®:

Composition: Levonorgestrel 0.03 mg
Dosage: 1 tablet daily at the same time each day.

Emergency Contraceptives

Emergency contraceptives are effective if the dose is taken ideally within 12 hours but not later than 72 hours of unprotected intercourse.

Examples:

POSTINOR®:

Composition: Levonorgestrel 0.75 mg
Dosage: 1.5 mg (2 tablets) as a single dose as soon as possible within 12 hours but not later than 72 hours.

POSTINOR-2®:

Composition: Levonorgestrel 0.75 mg
Dosage: 1.5 mg (2 tablets) as a single dose as soon as possible within 12 hours but not later than 72 hours.

Parenteral Progestogen-Only Contraceptives

Parenteral progestogen-only contraceptives provide reliable suppression of ovulation by suppressing the luteinizing hormone.

Indications:

Contraception

Side Effects:

Menstrual irregularities
Spotting
Breast tenderness
Loss of bone mineral density
Prolonged bleeding
Amenorrhoea
Weight gain

Contraindications:

History of breast cancer
Pregnancy

Examples:

Medroxyprogesterone

Medroxyprogesterone

Available Preparations:

150 mg/ml

Available Brands: Depo-Provera, Injecta Plan

Dosage:

By deep intramuscular injection: 150 mg within the first 5 days of the cycle, repeated every 12 weeks (3 months).

Drugs Used in the Treatment of Obstetric and Gynecological Disorders Read More »

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.

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:

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

Adult: 10-20 mg repeated if necessary after 30-60 minutes
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

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):

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

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

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 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:

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
Maintenance: 2.5-15 mg daily but higher doses may be needed
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:

Sedating antihistamines
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®.

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