Pharmacology Exam 1: Biotransformation Flashcards

Terms Definitions
Elimination processes of biotransformation:
Hepatic metabolism: Phase I and IIBiliary secretion in stoolsRenal elimination in urineMinor routes in breath, sweat, tears, breast, milk
body's basic strategy for drug elimination:
make the parent drug more soluble so that it can be more easily excreted by the kidneys
phase I reactions, especially ____ __, convert or unmask a ___ group such as ___, ___, or ___ via ___, ___, or ____.
- cytochrome p450s- functional- OH- NH2- SH- oxidation- reduction- hydroxylation
Phase II are ___ reactions via ____, ____, or ____.
- conjugation- glucuronidation, sulfation, acetylation
Exceptions to the RulesSome drugs undergo Phase II before Phase I reactions, e.g., INHSome drugs are prodrugs (inactive) that are bioactivated through enzymatic actionSome conjugated drugs are more active than the parent, e.g., morphine glucuronideMany dr
Biotransformation leads to the ___ of L-dopa to dopamine.
activation
Biotransformation of active diazepam goes to active oxazepam.
biotransformation of active sulfanilamide to ____N-acetyl.
inactive
Oral administration of drugs all go to the ____.
liver
First pass effect:
drug> GI tract> absorbed> portal circulation> liver metabolism
first pass effect can also be __ metabolism before absorption.
GI
Entero-hepatic recycling:
- conjugated drug gets excreted in the bile> drug is reabsorbed in the GI tract> drug duration is prolonged
Entero-hepatic recycling occurs with ___ ___. Antibiotics inhibit the entero-hepatic recycling and thus can make ___ less effective.
oral contraceptivesbirth control
Bioavailability signifies how much __ ___ drug reaches the ___ ___.
in tactgeneral circulation
drug oxidation requires:
- p450: drug- P450 reductase- NADPH- O2
P450 – drugP450 reductase – reduced by NADPHReduction of P450 – drug complexReduced O2 – P450 – drug complexTransfer of activated O2 to drug
cytochrome p450 is a ___ of ___ located in the ___ ___ of the ____.
family of enzymeendoplasmic reticulum of the liver
cytochrome p450s ___ a wide variety of compounds foreign to the body.
oxidize
There are at least 17 different families of cytochrome P450 identified in humans, each the product of a separate gene.Approximately 50 different isoforms are present in humans
CYPletternumber:
letter= isoformnumber= type of isoform
___ metabolizes 60% of drugs marketed in the US. It recognizes a wide range of substrates.
CYP3A4
classic enzyme inducers:
Phenobarbital (and other barbiturates)RifampinGlucocorticoidsTobacco (benzo[a]pyrene)Charcoal Broiled FoodsCruciferous VegetablesPCBs, dioxin (environmental)Ethanol (Chronic)
smokers activate their p450s enzymes, so they need higher doses of drugs for asthma.
CY3PA4 enzymes bind ___ ___ receptors which causes coactivators to ____gene expression of CYP3A4.
rxr retinoidincreaseexample of a drug that increases own metabolism
some drugs inhibit metabolizing enzymes. what is a well known one?
grapfruit juice
Factors affecting drug biotransformation:
Age and SexVery young and very old- slower metabolismMales have faster rates than females DiseaseLiver disease- reduction of metabolismCV disease- lower liver perfusionLung disease- impaired metabolism of some drugsHypothyroidism- reduction of metabolismHyperthyroidism- enhancement of metabolism
factors affecting drug biotransformation:
Genetic polymorphisms- CYP’s, othersMendelian Inheritance PatternsMany are autosomal recessive traitsSome inhibit metabolismSome enhance metabolism
pharmacogenetic testing:
rarely used in clinical practice, except for general anesthesia
polymorphism in pseudocholinesterase:
reduces metabolism of succinylcholine, increased skeletal muscle block
individual patients differ in ___ ___ and their ___ of metabolism and elimination.
- drug distribution- rates
Metabolism of drugs can lead to generation of ___ ___ __ that damage tissues if present in high concentrations. Example of this.
free radicalsAcetaminophen overdose (quinone forms, liver failure and death)
acetominophine is mostly metabolized by phase II enzymes, but these enzymes can get saturated, so you get a p450 reaction to a toxic quinone.But if you have enough glutathione, the quinone combines with it to form nontoxic mercapturic acid. But you can de
give glutathione so mercapturic acid is formed instead of quinone
overdose of acetaminophen:
Phase II enzymes are saturatedAcetaminophen is metabolized by p450 enzymes to a toxic quinoneGlutathione (GSH) inactivates this quinoneIf GSH is depleted, the quinone interacts with tissues (liver) and causes toxicity
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