Types of Adverse Drug Reactions (ADRs)
Type A (Augmented) Reactions
- Predictable from known pharmacology
- Dose-dependent
- Common
- Management: dose adjustment or withdrawal
| Feature | Example |
|---|---|
| Bleeding | Warfarin (excess INR) |
| Hypoglycaemia | Insulin, sulfonylureas |
| Bradycardia | Beta-blockers |
| Sedation | Benzodiazepines |
Type B (Bizarre) Reactions
- Unpredictable, not dose-related
- Often immune-mediated or idiosyncratic
- Uncommon but serious
| Mechanism | Examples |
|---|---|
| Allergy (immediate/IgE) | Anaphylaxis to penicillin |
| Cytotoxic (Type II) | Drug-induced haemolytic anaemia (e.g. methyldopa) |
| Immune complex (Type III) | Serum sickness from antitoxins |
| T-cell mediated (Type IV) | Morbilliform drug eruption, SJS/TEN, DRESS |
| Idiosyncratic non-immune | Halothane hepatitis, isoniazid hepatotoxicity |
Hypersensitivity Classification (Gell and Coombs)
Used specifically for immune-mediated drug reactions
| Type | Mechanism | Onset | Examples |
|---|---|---|---|
| I | IgE-mediated | Minutes–hours | Anaphylaxis, urticaria, angioedema |
| II | Cytotoxic (IgG/IgM + complement) | Hours–days | Haemolytic anaemia, thrombocytopenia |
| III | Immune complex | 1–3 weeks | Serum sickness, vasculitis |
| IV | T-cell mediated (delayed) | Days–weeks | Morbilliform rash, SJS/TEN, DRESS |
Other Classifications
| Category | Example |
|---|---|
| Type C (Chronic) | Adrenal suppression (long-term steroids) Mechanism: Associated with long-term drug use. Examples: Adrenal suppression with corticosteroids. Features: Develops over time with continuous exposure |
| Type D (Delayed) | Mechanism: Occurs after a prolonged period post-exposure. Examples: Carcinogenesis, teratogenesis. Features: Latency period between exposure and reactio |
| Type E (End of use) | Mechanism: Related to drug withdrawal. Examples: Withdrawal seizures after stopping benzodiazepines. Features: Symptoms emerge upon cessation of therap |
| Type F (Failure) | Mechanism: Unexpected failure of therapy. Examples: Resistance to antimicrobial agents. Features: Lack of therapeutic efficacy |
| Type G (Genetic/Genomic) | Mechanism: Genetic variations affecting drug response. Examples: G6PD deficiency leading to hemolysis with certain drugs. Features: Pharmacogenetic considerations. |
Summary Table
| Type | Description | Predictable | Mechanism | Examples |
|---|---|---|---|---|
| A | Augmented | Yes | Dose-dependent | Hypotension with antihypertensives |
| B | Bizarre | No | Immunologic or idiosyncratic | Anaphylaxis, DRESS |
| C | Chronic | Yes | Cumulative toxicity | Steroid-induced osteoporosis |
| D | Delayed | No | Latent effects | Cancer, teratogenesis |
| E | End-of-use | No | Withdrawal | Rebound hypertension after clonidine stop |
| F | Failure of therapy | No | Drug interaction/resistance | Contraceptive failure with antibiotics |
Drug Rash Classification
drug rashes can be formally classified in several clinically useful ways, depending on:
- Mechanism (immunologic vs non-immunologic)
- Morphology (maculopapular, urticarial, blistering, pustular, etc.)
- Timing (immediate vs delayed)
- Severity (benign vs life-threatening)
- Pattern-based clinical classification (commonly used in dermatology)
Based on Mechanism
| Type | Description | Examples |
|---|---|---|
| Allergic (immune) | IgE-mediated (Type I) or T-cell mediated (Type IV) | Urticaria morbilliform SJS/TEN DRESS (Drug hypersensitivity syndrome) |
| Non-allergic | Direct toxicity, pseudoallergy, or idiosyncratic | AGEP (Acute generalised exanthematous pustulosis) vasculitis fixed drug eruption |
Based on Timing
| Type | Onset Time | Typical Examples |
|---|---|---|
| Immediate | Within <1 hour | Anaphylaxis urticaria angioedema |
| Accelerated | 1–72 hours | Morbilliform fixed drug eruption |
| Delayed | >72 hours to weeks | DRESS (Drug hypersensitivity syndrome) AGEP SJS/TEN vasculitis |
Based on Morphology / Dermatological Pattern
| Pattern | Description | Example Drugs |
|---|---|---|
Morbilliform / Exanthematous | Symmetric maculopapular rash Most common drug eruption; spares mucosa 5–14 days (1–3 days if re-exposed) SSx – Mild fever, itch | Beta-lactams sulfonamides |
Urticarial / Angioedema | Transient wheals, swelling Minutes–hours Anaphylaxis if systemic IgE-mediated; raised, itchy, migratory lesions | Penicillin NSAIDs |
Fixed Drug Eruption (FDE) | Dusky red/violaceous plaque recurs same site 30 min–8 hours Rarely systemic T Post-inflammatory hyperpigmentation | Tetracycline NSAIDs barbiturates |
| Pustular (AGEP) Acute generalised exanthematous pustulosis  | Pinpoint pustules on erythematous base 2 days of exposure to the responsible medication. Viral infections (Epstein-Barr virus, enterovirus, adenovirus, cytomegalovirus, hepatitis B virus and others) are common triggers of AGEP in children may be associated with a fever and malaise, but often the patient is not particularly unwell. | Aminopenicillins diltiazem |
Bullous / Vesiculobullous | Targetoid lesions → bullae → denudation 4–28 days Mucosal involvement, pain Nikolsky +, extensive desquamation, ≥2 mucosae | SJS/TEN (sulfa, AEDs) |
Erythroderma | Generalised erythema and scaling >90% BSA | Allopurinol antiepileptics |
Phototoxic / Photoallergic | Sun-exposed areas with erythema/blisters | Tetracyclines thiazides |
Lichenoid | Violaceous, flat-topped papules | Antimalarials thiazides |
Purpuric / Vasculitic | Palpable purpura, ulceration Days–weeks Arthralgia, systemic features Often lower legs; biopsy confirms small vessel vasculitis | Hydralazine minocycline |
Intertriginous (SDRIFE) Symmetrical Drug-Related Intertriginous and Flexural Exanthema (SDRIFE) | Bright red flexural plaques 1–2 days None Beta-lactams Localised to folds; sharply demarcated | Beta-lactams IV contrast |
Based on Severity
| Severity | Clinical Syndromes | Features |
|---|---|---|
| Benign | Morbilliform, FDE, SDRIFE | Self-limited, no systemic involvement |
| Moderate | Urticaria, AGEP, drug-induced vasculitis | May need inpatient monitoring |
| Severe (SCAR) | SJS, TEN, DRESS | High morbidity/mortality, hospitalisation needed |
Based on WHO-UMC and RegiSCAR Classifications (Specialist Use)
- WHO-UMC: Used for pharmacovigilance; classifies causality of adverse drug reactions.
- RegiSCAR: Standardised clinical criteria for diagnosing SJS/TEN, DRESS, AGEP (e.g., scoring systems, organ involvement, biopsy findings).
Summary Table (Pattern-Based)
| Clinical Pattern | Immune Type | Common Drugs | Severity |
|---|---|---|---|
| Morbilliform rash | Type IV (T-cell) | Penicillins, sulfa, AEDs | Mild–moderate |
| Urticaria/angioedema | Type I (IgE) | NSAIDs, penicillin | Mild–severe |
| DRESS | Type IV (delayed) | Aromatic AEDs, allopurinol | Severe (SCAR) |
| AGEP | Mixed (neutrophilic) | Macrolides, CCBs | Moderate–severe |
| SJS/TEN | Type IV | Sulfonamides, AEDs | Severe (SCAR) |
| Fixed drug eruption | Type IV (T-cell) | NSAIDs, tetracyclines | Mild |
| Vasculitis | Type III | Allopurinol, minocycline | Variable |