Drug Metabolism Flashcards
What is cometabolism?
enzymes that are present to metabolize endogenous material also metabolize exogenous material
What are the Phase I reactions?
oxidation and hydrolysis
What are the Phase II reactions?
SAGGMeth: sulfation, acetylation, glucuronidatin, glutathionation, methylation
What does CYP stand for and what is its function?
CYP: 450 monooxygenase system
requires cosubstrate of NADPH reductase
does oxidation
What is the Phase I metabolism of benzodiazepines?
allopathic hydroxylation (oxidation) by CYP3A4
What is the Phase I metabolism of propranolol (beta blockers)?
aromatic hydroxylation (oxidation) by CYP2D6
What is the Phase I metabolism of cimetidine?
histidine H2 receptor competitive inhibitor
metabolized by S-oxidation by CYP
What is the effect of cimetidine on CYPs?
inhibits all CYPs except CYP2E1
What is the Phase I metabolism of diphenhydramine (Benadryl)?
treats mild allergic reactions through competitive inhibition of H1 receptor
metabolized by N-oxidation by CYPs
What is the Phase I metabolism of caffeine and theophylline?
adenosine receptor antagonists
n-dealkylation by CYPs
What is the Phase I metabolism of ethanol?
dehydrogenase (alcohol then aldehyde)
What is the Phase I metabolism of succinylcholine?
two molecules of acetylcholine, blocks ACh from binding
hydrolyzed by acetylcholinerase
What is the Phase II metabolism of albuterol?
used to treat asthma by stimulating B2 receptor
sulfation inactivates it
What is the Phase II metabolism of acetaminophen?
sulfation and glucoronidation metabolize it to a non-toxic metabolite
What is the Phase II metabolism of benzodiazepines?
glucoronidation (main inactivation pathway)
What is the function of glutathione?
protects cells from electrophiles/epoxides decreasing DNA damage
What leads to toxic metabolism of acetominophen?
Phase I metabolism by CYP2E1 and CYP3A4 leads to reactive toxic intermediate of NAPQI
How can toxic intermediates of acetaminophen be detoxified?
through glutathionation, but if GSH is depleted then liver cell death occurs
How does ethanol consumption affect acetaminophen metabolism?
ethanol induces CYP2E1 which causes more acetaminophen to be metabolized into toxic intermediates
Which CYP has the most polymorphisms?
CYP2D6
What drugs are metabolized by CYP2D6?
beta blockers (like metoprolol) and opioids (codeine and hydrocodone) and other CNS drugs
What drugs are metabolized by CYP2C19?
benzodiazepines, -prazoles (proton pump inhibitors)
What drugs are metabolized by CYP2C9?
warfarin, NSAIDs (ibuprofen, celecoxib)
What drugs are metabolized by CYP2E1?
ethanol, acetominophen
