Biotransformation Metabolism of Drugs课件1.pptVIP

Other drugs: Barbiturates Phenytoin Carbamazepine Rifampicin dexamethasone Biotransformation (Metabolism) of Drugs General properties Biotransformation is a major mechanism for drug elimination; Results of biotransformation: Production of metabolites that are more polar than the parent drug usually terminates the pharmacologic action of the parent drug After phase I reactions, similar or different pharmacologic activity, or toxicologic activity. Results of biotransformation Many drugs undergo several sequential biotransformation reactions. Biotransformation is catalyzed by specific enzyme systems Sites of biotransformation: The liver: the major site other tissues. Biotransformation of drugs can be affected by many parameters, including: prior administration of the drug in question or of other drugs diet hormonal status genetics disease (e.g., decreased in cardiac and pulmonary disease) age and developmental status liver function Possible consequences of biotransformation include the production of: inactive metabolites (most common) metabolites with increased or decreased potencies metabolites with qualitatively different pharmacologic actions toxic metabolites active metabolites from inactive prodrugs. Metabolites are often more polar than the parent compounds. This increased polarity may lead to: a more rapid rate of clearance because of possible secretion by acid or base carriers in the kidney it may lead to decreased tubular reabsorption. Classification of biotransformation reactions Reactions that involve enzyme-catalyzed biotransformation of the drug without any conjugations. Phase I reactions include: oxidations reductions hydrolysis reactions they introduce a functional group (e.g., -OH) that serves as the active center for sequential conjugation in a phase II reaction. Reactions that include conjugation reactions, which involve the enzyme-catalyzed combination of a drug (or drug metabolite) with an endogenous substance.