NADPH- Cyt. P450 reductase P450 S SOH O 2 H 2 O e NADPH NADP +

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    13-Jan-2016

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<ul><li><p>Aromatic hydroxylation</p></li><li><p>Aliphatic hydroxylation</p></li><li><p>Epoxidation</p></li><li><p>Dealkylation</p></li><li><p>CYP1A Metabolize polycyclic hydrocarbons Are induced by polycyclic hydrocarbonsFound in cigarette smokeAssociated with cancerCYP1A1 is inducibleextrahepaticCYP1A2 is constitutively expressed only in liverIs inducible</p></li><li><p>CYP1APolymorphisms (primarily CYP1A1)Expression polymorphismStructural gene polymorphismIn vivo assay (CYP1A2)Caffeine metabolism</p></li><li><p>CYP 2ACYP2A6 and CYP2A13CYP2A6 is polymorphicResponsible for nicotine metabolism</p><p>CYP 2BCYP2B6 CYP2B1 and CYP2B2 are major forms in ratswas originally thought to be a minor form in humans</p></li><li><p>CYP2CCYP2C8, CYP2C9, CYP2C18, and CYP2C19 are major forms in humansHormonally regulated in rodents (growth hormone)Metabolize about 30% of commonly used drugsOmeprazoleDiazepamIn vivo substratesS-mephenytoin (CYP2C19)Flurbiprofen (CYP2C9)</p></li><li><p>CYP2D6Metabolize many important drugsCodeineDextromethorphanPolymorphismsMutation in the structural geneRelated to increased cancer risk (rapid metabolizers)In vivo substrateDebrisoquineDextromethorphan</p></li><li><p>CYP2E1Is uncoupledProduces superoxide and hydrogen peroxideForms reactive intermediatesNitrosamine carcinogensacetaminophen</p></li><li><p>CYP2E1Is uncoupled Forms reactive intermediatesAssociated with acetaminophen toxicityEthanol induciblePolymorphisms Linked to cancer Role in alcohol-related liver dysfunctionIn vivo substratechlorzoxazone</p></li><li><p>CYP3A4/5Major P450 in humans - metabolizes over 50% of commonly used drugsIs inducible by numerous drugsCYP3A4 not polymorphic but wide variation in activity (due to CYP3A5)In vivo substrates (hepatic and intestinal)ErythromycinAlfentanil </p></li><li><p>Hydrolysis reactionsPlasma, liver, kidney, and all tissuesEsteraseSuccinylcholine apneaAmidaseEpoxide hydrolaseFound in liver and all tissuesBoth microsomal and soluble formsInducible by phenobarbital and 3-methylcholanthrene</p></li><li><p>Hydrolysis reactionsEsterase (plasma, liver, and kidney)Succinylcholine apneaAmidase (liver)Epoxide hydrolaseFound in liver and all tissuesBoth microsomal and soluble formsInducible by phenobarbital and 3-methylcholanthrene</p></li><li><p>Hydrolysis reactionsEsterase (plasma, liver, and kidney)Succinylcholine apneaAmidase (liver)Epoxide hydrolaseFound in liver and all tissuesBoth microsomal and soluble formsInducible by phenobarbital and 3-methylcholanthrene</p></li><li><p>Conjugations reactions(phase 2)GlucuronidationSulfate conjugationAcetylationGlutathione conjugationMethylationGlycine conjugation</p></li><li><p>AcetylationN-acetyl transferase</p></li><li><p>Glutathione conjugation</p></li><li><p>MethylationMethytransferasesCytoplasm and endoplasmic reticulumS-adenosymethionineAmino acid conjugationUsually as glycine conjugatesMitochonria and cytoplasm</p></li><li><p>One Compartment ModelIntravascular Bolus</p></li><li><p>One Compartment ModelExtravascular</p></li><li><p>Two Compartment ModelIntravascular Bolus</p></li><li><p>Two Compartment ModelExtravascular </p></li><li><p>Apparent Volume of Distribution</p></li><li><p>Continuous IV Infusion</p></li><li><p>Multiple IV Administration</p></li><li><p>Multiple Extravascular Administration</p></li></ul>

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