Adverse Drug Reactions (ADRs) are unintended and harmful effects that occur when medicines are used at normal doses. Monitoring, identifying, and evaluating ADRs is crucial for ensuring patient safety and optimizing therapeutic outcomes. Understanding the classification, mechanisms, risk factors, and methods of causality assessment enables healthcare professionals to detect ADRs early and take appropriate preventive measures.
Definition of Adverse Drug Reaction
An Adverse Drug Reaction is defined as any noxious, unintended, and undesired effect of a drug that occurs at doses normally used in humans for prevention, diagnosis, or therapy.
Classification of Adverse Drug Reactions
ADRs can be classified in multiple ways, but the most widely accepted method is the WHO classification, which categorizes ADRs into several major types:
1. Type A (Augmented)
- Predictable and dose-dependent.
- Related to the pharmacological action of the drug.
- Examples: bleeding with warfarin, hypoglycemia with insulin.
2. Type B (Bizarre)
- Unpredictable and not dose-related.
- Often involves immunological or genetic mechanisms.
- Examples: anaphylaxis to penicillin, Stevens–Johnson syndrome.
3. Type C (Chronic)
- Associated with long-term therapy.
- Examples: adrenal suppression with corticosteroids.
4. Type D (Delayed)
- Reactions appear long after the drug is discontinued.
- Examples: carcinogenicity, teratogenicity.
5. Type E (End-of-use)
- Withdrawal reactions when drug therapy is stopped abruptly.
- Examples: anxiety after benzodiazepine discontinuation.
6. Type F (Failure of Therapy)
- Unexpected inefficacy of a drug.
- Often caused by drug interactions or resistance.
Mechanisms of Adverse Drug Reactions
The mechanisms by which ADRs occur vary widely. Understanding these mechanisms helps in predicting and preventing reactions.
1. Pharmacological Mechanisms
- Extension of the drug’s therapeutic effect.
- Example: excessive beta-blockade causing bradycardia.
2. Allergic (Immunological) Mechanisms
Involve immunological reactions categorized into four types:
- Type I – IgE mediated (anaphylaxis).
- Type II – cytotoxic reactions.
- Type III – immune complex reactions.
- Type IV – delayed hypersensitivity.
3. Idiosyncratic Reactions
- Genetically determined abnormal reactions.
- Example: hemolysis in G6PD deficiency.
4. Metabolic Mechanisms
- Due to altered metabolism of drugs.
- Example: accumulation of toxic metabolites.
5. Drug–Drug Interactions
- Pharmacokinetic or pharmacodynamic interactions leading to ADRs.
Predisposing Factors of Adverse Drug Reactions
Certain factors increase the likelihood of developing an adverse reaction.
1. Patient-Related Factors
- Age: Elderly and pediatric patients are more vulnerable.
- Genetics: Enzyme deficiencies or genetic polymorphisms.
- Gender: Females may experience ADRs more frequently.
- Pregnancy: Altered physiology increases risk.
- Concurrent Diseases: Renal, hepatic, and cardiac disorders.
2. Drug-Related Factors
- High doses or narrow therapeutic index drugs.
- Polypharmacy increasing drug interaction risks.
- Route of administration affecting absorption and metabolism.
3. Social and Environmental Factors
- Alcohol consumption.
- Smoking.
- Exposure to chemicals or pollutants.
Causality Assessment of ADRs
Causality assessment helps determine whether a drug is responsible for an observed adverse event. Standardized tools and algorithms are used to ensure consistent and objective evaluation.
1. WHO-UMC Causality Categories
- Certain: Clear relationship, reaction disappears on withdrawal and reappears on re-challenge.
- Probable: Strong relationship with no alternative explanation.
- Possible: Drug may be responsible but other factors exist.
- Unlikely: Relationship doubtful.
- Conditional/Unclassified: More information required.
- Unassessable: Insufficient data.
2. Naranjo’s Algorithm
A widely used questionnaire consisting of 10 questions. Each answer carries a positive or negative score.
- Score ≥ 9: Definite ADR
- Score 5–8: Probable ADR
- Score 1–4: Possible ADR
- Score 0: Doubtful ADR
3. Karch and Lasagna Method
Focuses on temporal association, dechallenge, re-challenge, and exclusion of alternative causes.
4. European ABO System
Categorizes ADRs based on probability and strength of association.
Importance of ADR Assessment in Clinical Practice
- Enhances patient safety by early identification of harmful reactions.
- Improves therapeutic decision-making.
- Reduces hospital admissions caused by drug-related complications.
- Supports pharmacovigilance programs and national reporting systems.
Detailed Notes:
For PDF style full-color notes, open the complete study material below:
