Adverse Drug Effects

Undesirable or harmful effects which can occur at therapeutic doses and need a reduction of dose or drug withdrawal. Adverse drug effects include:

Nausea and vomiting
Deafness with gentamycin
Death with penicillin

All drugs are poisons until used judicially. Every drug acts on all systems of the body, e.g. aspirin used for headache also acts on GIT and blood producing side effects.

Types of adverse drug reactions

Adverse drug reactions are of five types; A, B, C, D and E

1) Type A reactions

Type A reactions are common and constitute 75 % of all adverse reactions. These are related to pharmacological actions and are dose-dependent. Type A reactions are predictable and can be avoided by adjusting the dosage regimen. Most of them are reversible upon stopping drug. Examples include

– Hypotension (antihypertensives)

– Hypoglycaemia (insulin)

a. Excessive therapeutic effect

Unwanted effects related to the main pharmacological actions of the drug that occur when the drug produces greater therapeutic effect than is necessary.

e.g. Warfarin is an anticoagulant but may lead to bleeding tendency.

Insulin is used for normoglycemia but may produce hypoglycaemia

b. Side Effects

Unwanted effects unrelated to the main pharmacological actions of the drug but due to other normal actions of the drug

e.g. morphine may cause constipation during its use as analgesic.

2) Type B reactions

Type B reactions are bizarre reactions, not related to the normal pharmacological actions of the drug. They are unpredictable and not dose-related. They occur only in minority of patients. Test dose can be given for judgement.

Types

a. Allergic reactions (Hypersensitivity)

b. Genetic disorders (Idiosyncrasy)

a) Hypersensitivity (allergic reactions)

Abnormal response to the drug due to antigen- antibody reactions e.g. Penicillin. These are the allergic responses to a drug.

They include rashes, hypotension and bronchospasm (anaphylactic reaction).

b) Idiosyncrasy

Idiosyncrasy is abnormal response to the drug due to genetic disorders. E.g.

Succinylcholine apnea

Malignant hyperthermia

Favism

Porphyria

Secondary Effects

Unwanted effects that occur secondary to the wanted actions of the drug. Examples include overgrowth of microorganisms following use of broad spectrum antibiotics.

Type C reactions (Continuous reactions)

Type C reactions are due to long term use e.g. NSAIDs causing analgesic nephropathy due to long term usage of drugs and changing doses.

Type D reactions (Delayed adverse reactions)

Teratogenesis Is congenital malformations occurring in the foetus due to exposure to drugs during
pregnancy e.g. Thalidomide may produce phocomelia (abnormal limbs)

Carcinogenesis is the ability of some substances to induce cancer. E.g. Stilbesterol may cause adenocarcinoma of vagina in female off springs.

Mechanisms:

1. DNA alteration

Griesofulvin (antifungal) & alkylating cytotoxics (cancer), they are anti-mitotic, acting on spindle formation

2. Immunosuppression

Immunosuppressant increase incidence of cancer e.g. organ transplantation & methotrexate in rheumatoid arthritis

3. Hormonal

Long term use of estrogen replacement in post menopausal therapy may induce endometrial cancer

Type E reactions (Ending of drug)

Sudden discontinuation (abrupt withdrawal) may lead to rebound adrenal insufficiency
e.g. corticosteroids

Treatment should be started with smaller dose, which can be gradually increased. Patient compliance is poor if adverse reactions occur.

Risk benefit ratio

Disease healing is important at the risk of side effects, especially in life threatening situations. This depends on the expertise of the doctor.