P02.004 Adverse drug effects

Adverse drug effects (ADEs) are unintended and harmful reactions that occur at normal drug doses used for prophylaxis, diagnosis, or therapy. Understanding ADEs is crucial for the PLAB exam, as it ensures the safe and effective use of medications in clinical practice.

Definition

Adverse drug effects are any undesired actions or effects of a drug. They can range from mild to severe and can occur shortly after administration or develop over time.

Types of Adverse Drug Effects

1. Type A (Augmented) Reactions
   • Predictable and dose-dependent.
   • Related to the pharmacological action of the drug.
   • Example: Hypoglycemia from insulin.
2. Type B (Bizarre) Reactions
   • Unpredictable and not dose-dependent.
   • Often immune-mediated or idiosyncratic.
   • Example: Anaphylaxis from penicillin.
3. Type C (Chronic) Reactions
   • Occur due to long-term drug use.
   • Example: Osteoporosis from long-term corticosteroid use.
4. Type D (Delayed) Reactions
   • Occur after prolonged use or with a delayed onset.
   • Example: Carcinogenesis from immunosuppressants.
5. Type E (End-of-use) Reactions
   • Occur after discontinuation of the drug.
   • Example: Withdrawal symptoms from opioids.
6. Type F (Failure) Reactions
   • Result from ineffective drug therapy.
   • Example: Antibiotic resistance.

Mechanisms of Adverse Drug Effects

1. Pharmacological Mechanisms
   • Direct extension of the drug’s therapeutic effects.
   • Example: Beta-blockers causing bradycardia.
2. Immunological Mechanisms
   • Allergic reactions mediated by the immune system.
   • Example: Urticaria from sulfa drugs.
3. Genetic Mechanisms
   • Variations in genetic makeup affecting drug metabolism and response.
   • Example: G6PD deficiency leading to hemolysis with certain drugs.
4. Drug-Drug Interactions
   • Adverse effects from interactions between two or more drugs.
   • Example: Increased risk of bleeding with warfarin and aspirin.
5. Drug-Food Interactions
   • Adverse effects from interactions between drugs and certain foods.
   • Example: Grapefruit juice increasing statin levels.

Common Adverse Drug Effects

1. Gastrointestinal Effects
   • Nausea, vomiting, diarrhea, constipation.
   • Example: NSAIDs causing gastritis.
2. Central Nervous System Effects
   • Dizziness, sedation, confusion, seizures.
   • Example: Benzodiazepines causing sedation.
3. Cardiovascular Effects
   • Hypertension, hypotension, arrhythmias.
   • Example: Antihypertensives causing hypotension.
4. Dermatological Effects
   • Rash, urticaria, photosensitivity.
   • Example: Antibiotics causing skin rashes.
5. Hematological Effects
   • Anemia, leukopenia, thrombocytopenia.
   • Example: Chemotherapy causing bone marrow suppression.

Monitoring and Management

1. Prevention
   • Thorough patient history and medication review.
   • Use of the lowest effective dose.
   • Educating patients about potential ADEs.
2. Detection
   • Regular monitoring of clinical and laboratory parameters.
   • Patient self-reporting of symptoms.
3. Management
   • Discontinuation or adjustment of the offending drug.
   • Symptomatic treatment of the adverse effect.
   • Reporting to pharmacovigilance programs.

Reporting Adverse Drug Effects

• Importance: Enhances patient safety and drug efficacy.
• Systems: National reporting systems such as the Yellow Card Scheme in the UK.
• Process: Healthcare professionals should report any suspected ADEs, even if not conclusively proven.

Points to Remember

• ADEs can be predictable or unpredictable and can range from mild to severe.
• Knowing the types and mechanisms of ADEs helps in early identification and management.
• Regular monitoring and patient education are key in preventing and managing ADEs.
• Reporting ADEs is crucial for improving drug safety and patient care.

Bibliography

1. Rang, H.P., Dale, M.M., Ritter, J.M., Flower, R.J., & Henderson, G. (2015). Rang & Dale’s Pharmacology. Elsevier.
2. Katzung, B.G., Trevor, A.J. (2018). Basic and Clinical Pharmacology. McGraw-Hill.
3. British National Formulary (BNF). Available at: https://bnf.nice.org.uk/
4. World Health Organization (WHO). Adverse Drug Reactions. Available at: https://www.who.int/medicines/areas/quality_safety/safety_efficacy/pharmvigi/en/