Phase 1 drug metabolism Flashcards
2 outcomes of drug metab.
- change in activity - more, less, same
2. facilitate excretion - make more water soluble
enzyme class that does most drug metabolism
cytochrome P450 - CYP
4 ways to make drugs more soluble
- add functional group
- oxidation
- reduction
- hydrolysis
where in the cell is CYP located
on lipid bilayer of ER
what is CYP complexed with
NADPH
what is basic step to CYP action
uses an Fe and donates e to break an O-O bond and end up with a hydroxylated product
**end result of CYP action
adds a hydroxyl group
how are so may drugs biotranformed (2)
- many enzymes
2. broad substrate selevtivity for enzymes
what are enzymatic options for outcomes
- many diff enzymes can make same metabolite
2. single drug can be metabolized in very different reactions
how are CYPs named (3)
- (40% identical at AA level) - same family - first number
- 55% identical - same subfamily - letter
- individual members - isoforms - second number
what is most common CYP in liver
3A4/5
what are 2 possible effects of other substances on these enzymes
- inhibition
2. induction
Why do smokers drink more coffee
the enzyme that breaks down caffeine (CYP1A2) is induced by nicotine
why is drinking and tylenol a bad combo
acetominophen has multiple metabolisms, but one (CYP2E1) creates a toxic metabolite (NAPQI) and is induced by alcohol
how are enzymes induced
ligands bind to nuclear receptors that set off chain of events leading to new protein expression - not immediate
5 generalizations about CYP inducers
- induce multiple CYPs
- stimulate their own biotransformation
- multispecies
- act in multiple tissue
- increase rate of gene transcription
what is effect of grapefruit juice
inhibitor of CYP3A4, which metabolizes 50% of drugs
what are steps of alc. degradation
alc dehydrogenase>acetaldehyde (makes you sick)>aldehyde dehydrogenase> acetic acid
what are MAOs
monoamine oxidazes - work on epi, serotonin, dopamine
problems with MAOi’s
not very specific, so get lots of side effects
