Drug elimination metabolism excretion.ppt

 Drug elimination (metabolism, excretion) Anton Kohút DRUG METABOLISM major site of drug metabolism – liver,  exceptions:- suxamethonium and procaine  - plasma cholinesterase- tyramine - intestinal wall  Phase 1 - lipophilic molecules are converted into more polar molecules Reactions are catalyzed by the cytochrome P-450 (CYP) by: ? oxidation ? reduction ? hydrolysis - products are often less eactive than the parent compounds - after metabolism may be excreted by kidneys - each of the enzyme has a low specificity Phase 2 consists of conjugation reactions Most often involved groups in conjugation are: ? glucuronyl ? sulphate ? methyl ? acetyl ? glycyl ? glutamyl The two phases of drug metabolism Metabolism of imipramine Involvement of some isoform of CYP  in the metabolism FACTORS INFLUENCING DRUG METABOLISM - systemic pathological processes - liver diseases, heart failure - age - sex - body temperature - genetic factors - polymorhism - drug interactions? enzyme inhibition, enzyme induction Drug interactions - enzyme induction Drug induction increase of enzyme activity can decrease drug potency, - result is an increased synthesis of microsomal enzymes after repeated use of drugs - generally, metabolism of inducers itself is increased as well as various other compounds, - increase of metabolism may increase toxicity of paracetamol – toxic metabolites Drugs that cause induction barbiturates, carbamazepine, ethanol (chronic use), glutethimide, griseofulvin, meprobamate, phenytoin, rifampicin, sulphinpyrazone, Drug interactions - enzyme inhibition Drug inhibition - enzyme inhibition can slow down the metabolism - action of coadministrated drug may be increased and prolonged Drugs that cause inhibitio