Drug Allergy - Adverse Drug Reactions (ADR)

Drug Allergy

·        = Specifically altered potential reactivity to a drug or breakdown product of a drug

·        Recognition of an allergic drug reaction:

o  Always a delay in allergic reaction following initial exposure

o  Once established, a reaction can be precipitated by minute amounts of the drug

o  There is recurrence on re-exposure

o  The reaction doesn‟t resemble the pharmacological activity of the drug

o  Symptoms suggest an allergic response

·        Four main mechanisms for inducing an immunotoxic reaction:

o  Drug may be an immunogenic protein

o  Drug or metabolite may form a hapten by combining with endogenous proteins

o  Drug/metabolite may cause a reaction between a modified self-antigen and an antibody 

o  Drug/metabolite may cause the synthesis of auto-antibodies, but its continued presence is not required for binding between the antibody and the antigen

·        Four types of reaction (Coombs-Gell types): 

o  Type 1 (immediate) hypersensitivity: Drug or drug conjugate binds a specific IgE on the surface of basophils and mast cells ® degranulation ® mediator release ® bronchospasm, urticaria, anaphylaxis 

o  Type 2 (cytotoxic) hypersensitivity: IgG or IgM + drug-protein conjugate ® complement release ® complement activation ® haemolysis or neutropenia or thrombocytopenia (depends on which cell surface reaction takes place). Eg quinine 

o  Type 3 (immune complex) hypersensitivity: (actually rare) protein complexes + Igs ® insoluble matrices ® complement activation ® localised vascular damage with Serum Sickness/Antibiotic Fever (fever, joint pain, lymphadenopathy, neutropenia, glomerulonephritis). Eg Presents 1 – 3 weeks after penicillin/cephalosporin/sulphonamide treatment. 

o  Type 4: (delayed) hypersensitivity (cell mediated): drug-protein complex + target cell ® recognised by T-lymphocyte ® direct cytotoxicity/macrophage activation. Eg contact dermatitis due to chlorpromazine

·        Symptoms:

o  Localised: urticaria (weals, always itch), bronchospasm, angioedema

o  Generalised: hypotension, bronchospasm, urticaria, laryngeal oedema

·        Examples:

o  Haemolytic anaemia: eg levodopa, captopril (ACE inhibitor), penicillins

o  SLE: eg phenytoin, gold, procainamide (antiarrhythmic)

o  Glomerulonephritis: eg gold, drugs with sulphydril group

o  Aplastic anaemia: eg phenytoin

·        Factors influencing occurrence of allergic reactions

o  Duration and the number of courses or treatment

o  Any route (although anaphylaxis more common with iv) 

o  IV anaphylaxis occurs with the same frequency in the general population and atopic individuals. Anaphylaxis by other routes more common in atopic individuals

o  More common in adults than children (?less exposure to drug antigens)

o  Previous history of any allergic reactions and co-existing disease states