Drug Metabolism

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  • Created by: Rscottqub
  • Created on: 05-03-20 13:15
Drug metablism makes drugs more
water soluble, increased excretion, decreased half life
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Phase 1
simple reactions- redox, hydrolysis
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Phase 2
conjugation reactions- of drug with P1 metabolites or endogenous substances
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Main site of metabolism
main site is the liver , but it can occur anywhere
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why does the body eliminate drugs
if for example a drug was very lipid soluble it would keep re circulating if it wasn't metabolised
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prodrug
parent is inactive, when metabolised the metabolite is active
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Phase 1 involves
CYP450 enzymes - they are monooxygenase enzymes
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how to CYP450 typically work
they use O2 and NADH to add on a reactive group - ie OH
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P1 reactions can produce
more reactive molecules, which sometimes are toxic - if they are not fruther metabolised by P2 they can cause damage to cells
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types of P1 reactions
oxidation, reduction, carboxylation, hydrolysis
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CYP450
haemoproteins , split the O2- 1 atom is introduced into the drug - the other ends up in water
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how many CYP450 enzymes are there
at least 33
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Oxidation of exposed alkyl group
OH added
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oxidation of alkenes and aromatics
aromatics becomes a phenol, alkene double bond opens up, O added in
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Oxidation of N-aklyl
H replaces aklyl
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FCM stands for
flavin containing monooxygenases
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what are FCM
they are another metabolic enzyme found in the liver
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role of FCM
oxidation at nucleophilic regions - N, S or P rather than carbons - but CYP can also catalyse these reactions
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other metabolic enzymes
ADH and ALDH
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ADH
alcohol dehydroxygenase
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ALDH
aldehyde dehydroxgenase
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whats does ADH catalyse
the conversion of OH -> aldehyde
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what does ALDH catalyse
conversion of aldehyde--> COOH
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Aldehyde in the body is often
toxic
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which enzyme works faster ?
ADH- explaining reasoning behind hangover
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2ndry OH --> ketone catalysed by
ADH, but remember this cannot be catalysed any further
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P1 reduction reactions are
less common - but many oxidative reactions are reversible and carried out by reductase enzymes
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nitro groups are reduced to
amines
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ketones are reduced to
secondary OHs
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azo groups N=N reduced to
amines
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essentially reduction is
gain of a Hydrogen
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P2 most common conjugation
glucorinc acid
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other types of conjugation
sulfate, AA, glutathione
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P2 conjugation requires a
cofactor - ie Acetyl Co - acetylation. UDP-GA for glucoronic acid . SAM fro methylation
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how to name the enzymes involved with conjugation
TRANSFERASE- glucoronyl transferase, sulfotransferase, acteyl transferase etc
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whe is P1 not required
if drug already has functional groups capable of comjugation
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Tobacco smoke contains
benzopyrene - activates CYP450 - and can act like a carcinogen as well as increasing metabolism of other drugs - sub theraputic levels ?
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other drugs which effect CYP activity
phenobarbitone - increases act . Cimetidine - decreases act
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Hard Vs soft
way of classing drugs base on susceptibility to metabolism
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hard
drugs resistant to metabolism - remain unchanged in the body
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soft
predictable + controlled metabolism . they are inactived by met and excreted
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Grapefruit juice
decreases activity of CYP - may result in OD
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Sprouts and cig smoke
increase activty - may result in under dose
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Terbafenadine
prodrug for fexofenadine - but met slowed by GFJ
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why doe we use prodrugs
increase absoprtion, alter metabolism, alter distribution
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transactivation
when a metabolite has equal activity to the parent - example diazepam and nordiazepam - this can increase the duration of action
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Promoities / carriers
drug attached to a metabolically labile bond - the promoiety alters physical propettie sie water sol
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example of prodrug using a carrier
chloramphenicol - ester itself is no active AB - but water sol to be aborbed into eye
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Card 2

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Phase 1

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simple reactions- redox, hydrolysis

Card 3

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Phase 2

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Card 4

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Main site of metabolism

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Card 5

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why does the body eliminate drugs

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