Tolerance
Definition
Reduced response to a given dose after repeated exposure. Pharmacokinetic tolerance is enzyme induction or transporter upregulation; pharmacodynamic tolerance is receptor downregulation or adaptation.
- Definition
- Reduced drug response after repeated exposure
- Pharmacokinetic type
- Enzyme induction or transporter upregulation
- Pharmacodynamic type
- Receptor downregulation or adaptation
- Relevance
- Complicates interpreting poisoning severity from dose alone
Common questions
Why does tolerance matter when interpreting a suspected poisoning case?+
A tolerant chronic user can survive, or show milder symptoms at, a blood concentration that would be lethal or severely toxic in a naive individual, so toxicologists must consider tolerance history rather than reading severity off concentration alone.
How does pharmacokinetic tolerance differ practically from pharmacodynamic tolerance?+
Pharmacokinetic tolerance means the body metabolises or clears the substance faster, so less reaches target tissues at a given dose. Pharmacodynamic tolerance means the same tissue concentration produces a smaller effect because receptors have adapted, which is a separate mechanism that concentration measurements alone will not reveal.
Does tolerance protect against every effect of a substance equally?+
No, tolerance often develops unevenly across different effects of the same substance, so a person can be tolerant to sedation while remaining fully susceptible to respiratory depression or cardiac effects, which is a recognised factor in overdose deaths among chronic users.
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...
- Idiosyncrasy
- A qualitatively abnormal response to a normal dose, traceable to genetic polymorphism in metabolising enzymes, transporters or receptor targets. Not the same...
- 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...
- 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....