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19 Cards in this Set
- Front
- Back
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Why is drug biotransformation needed?
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not all drugs can be ingested in their active form, sometimes its the metabolic products that have a therapeutic effect
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What are phase 1 reactions?
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convert drug into a more polar metabolite (using small substituents like -OH); good for excretion,
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What are phase 2 reactions?
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conjugation of drugs to make them more polar (using larger amino acids etc.), good for excretion
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Where do most biotransformations occur?
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liver (first pass effect), intestines
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What are microsomes?
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vesicles of remaining ER membranes; they contain monooxygenases
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Function of mono-oxygenase
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oxidize compounds
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Function of NADPH reductase
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reduce compounds
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Function of cytochrome p450 oxidase
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oxidize compounds
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Increased p450 induction requires the use of what class of receptors?
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steroid retinoid receptors (bind to hormone response element on DNA to up-regulate p450 synthesis)
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How does imidazole inhibit p450?
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binds to the heme iron to reduce breakdown capability
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What are suicide inhibitors?
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some p450 species breakdown compounds into metabolites that attack their heme groups. basically the p450 created the compound that will inactivate the p450
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What enzymes are dominant in phase 2 reactions?
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transferases that will assist the conjugation reactions
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What enzymes are dominant in phase 1 reactions?
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p450 enzymes
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Which reactions are typically faster? Phase 1 or Phase 2
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Phase 2. the transferase enzymes (phase 2) are generally faster than the p450 enzymes (phase 1)
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Acetaminophen at normal doses is broken into non-toxic glucuronides and sulfates. What can happen at high [acetaminophen]?
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if there is more acetaminiophen than there is glucaronic acid or sulfate, then formation of toxic metabolites can occur. A p450 pathway takes over and can lead to liver death as GSH levels fall. when there is eventually nothing to conjugate it with, it stays as a highly reactive nucleophile
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What is the slow acetylator phenotype?
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genetic defect in NAT2 synthesis = less acetylation = less phase 2 reactions = less drug metabolism; autosomal recessive
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Some patients have ultrarapid metabolisms. How should their doses be altered?
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higher doses normally, but sometimes these higher doses can lead to higher levels of specific adverse metabolites
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Why do cigarette smokers have a higher rate of drug metabolism?
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smoking = induction of p450 for detox = higher ability of body to make p450 = more/quick drug detox
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If a drug's degradation is "blood-flow limited", what do we know about its ability to be degraded?
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it is quickly degraded; this means that any drugs that get to the liver are almost immediately degraded, so the blood flow to the liver is the limiting factor
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