Tolerance
A pharmacodynamic adaptation in which repeated administration of a drug leads to a diminished pharmacological response, requiring higher doses to achieve the original effect. Tolerance can develop through receptor downregulation, desensitization, altered signal transduction, or enhanced drug metabolism (pharmacokinetic tolerance). The rate and extent of tolerance vary by drug class and target organ.
Beispiele
- Opioid tolerance: mu-receptor phosphorylation and beta-arrestin recruitment reduce signaling
- Nitrate tolerance: depletion of sulfhydryl groups required for NO generation from nitroglycerin
- Benzodiazepine tolerance: GABA-A receptor conformational changes reduce allosteric enhancement
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A pharmacodynamic adaptation in which repeated administration of a drug leads to a diminished pharmacological response, requiring higher doses to achieve the original effect. Tolerance can develop through receptor downregulation, …