Idiosyncrasy
Definition
A qualitatively abnormal response to a normal dose, traceable to genetic polymorphism in metabolising enzymes, transporters or receptor targets. Not the same as allergy.
- Definition
- Abnormal response to a normal drug dose
- Mechanism
- Genetic polymorphism in enzymes, transporters, or receptors
- Distinguished from
- Allergy, which is immune-mediated
- Predictability
- Not dose-dependent in the usual sense
- Relevance
- Complicates interpretation of toxicological findings
Common questions
Why does the idiosyncrasy versus allergy distinction matter in a toxicology case?+
An allergic reaction involves prior sensitisation and an immune response, while an idiosyncratic reaction is a direct pharmacological or metabolic quirk present from the first exposure. Mislabelling one as the other can lead an examiner to wrongly assume prior drug exposure or to miscalculate expected blood levels.
Can a genetic idiosyncrasy make a normally safe dose fatal?+
Yes. A poor metaboliser variant of an enzyme such as CYP2D6 can cause a drug to accumulate far beyond expected levels at a standard dose, or a rapid metaboliser variant can convert a prodrug to its active form unusually fast, either of which can produce toxicity that a simple dose calculation would not predict.
Related terms
- First-Pass Metabolism
- Hepatic and gut wall biotransformation of orally absorbed drug before it reaches systemic circulation. Bypassed by IV, intramuscular, inhalation and most dermal...
- LD50
- Median lethal dose; the dose of a substance that kills 50% of a test population, expressed as mg/kg body weight. The classical...
- Pharmacogenomics
- Study of how inherited variation in drug-metabolising genes (CYP2D6, CYP2C19, NAT2, G6PD) changes drug response. The Indian Genome Variation Consortium and ICMR...
- Tolerance
- Reduced response to a given dose after repeated exposure. Pharmacokinetic tolerance is enzyme induction or transporter upregulation; pharmacodynamic tolerance is receptor downregulation...
- Volume of Distribution (Vd)
- The apparent volume in which a drug is distributed in the body, calculated as dose divided by plasma concentration at time zero....