3 drug metabolism Flashcards
examples of routes for drug excretion and their properties
water soluble: liver and kidneys (lipid soluble must be converted)
volatile drugs: lungs
paracetamol and toxicity affects
antidote and conditions for it to be taken
metabolised by CYP
if overdose to NAPQI toxic metabolite
N-acetylcysteine as ‘antidote (NAC)
Plasma sample needs to be 4 hours after OD as enables drug to redistribute to see plasma conc
Contains sulfur like gluthatione, binds and conjugates metabolites
Critical time is within 8 hours
routes of drug metabolism
phase I: intro or unmasking of functional group- some increase water solublility (involves cyt p450)
phase II: conjugation with endogenous chemicals at functional centre- greater increase in water solubility
phase I of drug metabolism
Cyt p450,
genetic variants - SNPs
15 isoforms
sites of drug interactions: induction and inhibition
what is the significance of CYP having many different isoforms
difficult to predict drug interaction for some forms
some drugs like warfarin don’t have alt pathway so can be affected
mechanisms of phase I
Oxidations: Microsomal Mixed Function Oxidase (Monooxygenase) System
Located in endoplasmic reticulum of liver
oxidation (non P450 systems- alcohol)
reductions
hydrolyses/ deacetylations
significance of phase II
mutiple metabolic pathways
some intermediates can have side effects eg. sedation and may have longer 1/2 life
CYP metabolism
two possible interaction mechanisms
many metabolised by multiple CYPs, some single
inhibition- macrolides
induction- eg rifampicin
factors effecting metabolism
age- reduced level of metabolism at both extremes of age
liver disease- decreased metabolism in hep and CLF
pharmacogenetics- genetic variations, SNPs affecting cytp450- slow and ultra fast metabolisers,
ethnicity- differences in cyt p450, ADRs
