Drug Reactions

Drug reactions are unwanted or harmful responses that occur after administration of a medication at normal doses used for prevention, diagnosis, or treatment. They are broadly divided into predictable (dose-dependent) and unpredictable (hypersensitivity-type) reactions.

Predictable adverse reactions

• Overdose (incorrect dose or impaired drug metabolism)

• Side effects (e.g., sedation from antihistamines)

• Indirect effects (e.g., antibiotics altering normal flora)

• Drug interactions (commonly via cytochrome P-450 enzyme system)

Unpredictable adverse reactions

• Allergic reaction (immune-mediated hypersensitivity requiring prior exposure or cross-reactivity)

• Pseudo-allergic reaction (non-immune mast cell activation)

• Idiosyncratic reaction (unusual non-dose-related response without clear mechanism)

Note: Approximately 80% of allergic and pseudo-allergic reactions are associated with beta-lactam antibiotics, aspirin, NSAIDs, and sulfonamides.

Signs & Symptoms

Clinical presentation varies depending on the reaction type and organ system involved.

Cutaneous

• Maculopapular rash

• Urticaria (hives)

• Angioedema

• Pruritus

• Fixed drug eruptions

• Severe reactions (SJS/TEN, exfoliative dermatitis)

Systemic

• Fever

• Malaise

• Arthralgia

• Lymphadenopathy

• Eosinophilia

Respiratory

• Wheezing

• Bronchospasm

• Dyspnea

• Anaphylaxis

Gastrointestinal

• Nausea and vomiting

• Diarrhea

• Hepatitis (drug-induced liver injury)

Hematologic

• Hemolytic anemia

• Thrombocytopenia

• Agranulocytosis

Diagnostic Criteria

Diagnosis is mainly clinical and supported by history.

• Temporal relationship between drug exposure and reaction

• Improvement after drug withdrawal (de-challenge)

• Recurrence after re-exposure (re-challenge) — usually avoided if severe

• Characteristic morphology of lesions

• Laboratory evidence (eosinophilia, liver enzyme elevation)

Investigations

• Full blood count (look for eosinophilia, cytopenias)

• Liver function tests

• Renal function tests

• Skin biopsy (if severe or unclear)

• Serum tryptase (suspected anaphylaxis)

• Patch testing (selected delayed hypersensitivity reactions)

• Drug-specific IgE testing (limited utility)

Treatment

Non-Pharmacological Treatment

• Immediate withdrawal of suspected drug

• Identify and document culprit medication

• Supportive care (hydration, wound care in severe reactions)

• Patient education and drug allergy card

Pharmacological Treatment

Mild reactions

• Oral antihistamines

• Topical corticosteroids

Moderate reactions

• Systemic antihistamines

• Short course oral corticosteroids

Severe reactions

• Intramuscular adrenaline (anaphylaxis)

• Intravenous fluids

• Oxygen therapy

• Systemic corticosteroids

• Intensive care / burn unit care for severe cutaneous reactions

Prevention

• Careful drug history before prescribing

• Avoid re-exposure to offending drug

• Cross-reactivity awareness (e.g., penicillins and cephalosporins)

• Use lowest effective dose

• Pharmacogenetic screening where available (e.g., high-risk drugs)

• Patient education and medical alert identification