Drug Allergies - Adverse Drug Reactions (ADRs) and ...

Drug Allergies - Adverse Drug Reactions (ADRs) and Hypersensitivity Reactions

Adverse Drug Reactions (ADRs): (J Allergy Clinic Immunol. 2010; 125: S126)

Type A = Predictable (~85-90%)

 • Dose-dependent, related to drug’s known pharmacological action, & occur in otherwise healthy pts if given sufficient dose / exposure (e.g., diarrhea from antibiotics, gastritis from NSAIDs, aminoglycoside nephrotoxicity)

 • Type B = Unpredictable (10-15% of ADRs): usually dose independent; unrelated to pharm action; occur only in susceptible pts

 • Drug Intolerance (undesirable pharmacologic effect @ low / subtherapeutic doses without underlying disorder of

metabolism/excretion/bioavailability of drug) – e.g., tinnitus after aspirin

 • Drug Idiosyncrasy (abnormal effect caused by underlying abnormalities of metabolism/excretion/bioavailability) –e.g., hemolysis after antioxidant drug in G6PD deficiency

 • Pseudo-allergic reaction - Anaphylactoid (drug causes direct release of mediators from mast cells/basophils) – e.g. flushing during vancomycin infusion, exacerbation of asthma/rhinitis w/ aspirin in AERD

 • Drug Allergy (immunologically mediated Hypersensitivity Reactions – see table below)

Hypersensitivity Reactions

Type I (Immediate, min - 1 hr) - IgE

 • Ag-IgE complex-mediated activation of mast cells & basophils → release of histamine, prostaglandins

 • Anaphylaxis (WHEAL: Wheezing, Hives, Edema [laryngeal], Angioedema, Low BP)

Type II (Delayed, variable) - Cytotoxic 

 • Ab binds to Ag-coated cells → cell injury 

 • Hemolysis, thrombocytopenia, neutropenia

Type III (Delayed, 1-3 wks) - Immunecomplex

 • Ag-Ab complex deposition in vessels/tissue → complement activation and inflammation

 • Serum sickness, arthus reaction, vasculitis

Type IV (Delayed, 2-7 days) - T Cell-mediated

 • Ag exposure activates T cells → cytokine release leading to tissue injury

 • Contact dermatitis, SJS/TEN, DRESS

#Drug #Allergy #classification #reactions #Hypersensitivity #types #adrs #pharmacology #diagnosis 
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