Kruse Biotransformation DSA Flashcards
what are xenobiotics
foreign substances within the body
properties of xenobiotics eliminated through renal excretion
polar compounds and small molecular volume compounds
biotransformation is the chem mod of what types of compounds
lipophilic, unionized, large compounds
inactivation biotransformation example
acetylsalicyclic acid (aspirin) to acetic acid and salicylate
activation example biotransformation
L-Dopa to Dopa
active compound to active compound example
diazepam to oxazepam
what are the other sites of biotransformation besides the liver
kidney, GI, skin, lungs
normal GI flora can increase bioavailability of certain drugs like estrogens used in contraception so antibiotics
decrease efficacy
classic example of drug that undergoes extensive first pass biotransformation is
morphine, only 25% available orally
gen rules: phase I rxn vs phase II
phase I makes drug biologically inactivation
phase II makes it more water soluble and increases molecular weight which facilitates elimnation of drug from body
phase I reactions are carried out by
cytochrome P450s
FMOs
epoxide hydrolases (mEH, sEH)
phase I enzymes are located in the ______ of the ___
lipophilic ER membranes of the liver (and other tissues)
what types of phase II rxns are there
adding: glucuronic acid, sulfuric acid, acetic acid, or an amino acid
phase I or phase II rxns occur at faster rates
phase II
where do most conjugation rxns take place
liver
genetic factors and succinylcholine
individuals with genetic defects in pseudocholinesterase can metabolize succinylcholine at 50% the rate as normal individuals
slow acetylator phenotype
decrease in N-acetyltransferase levels
- isoniazid (TB drug), hydralazine (BP med), and caffeine are metabolized at slower rates, can lead to hepatotoxicity (hepatitis)
- 50% of US and 83% of french
well characterized inducers of P450s
phenytoin chronic ethanol benzo pyrene (tobacco smoke) rifampin (anti-TB) phenobarbital and other barbiturates
consumption of grapefruit juice with drugs can what
irreversibly inhibit intestinal CYP3A4
allopurinol and mercaptopurine
allopurinol inhibits XO to treat gout
XO is key enzyme in biotransformation path of immuosuppresive agent mercaptopurine (to treat cancer)
- coadministration allows mercaptopurine to work for longer and enhances chemotherpaeutic and toxic effects
- doses of mercaptopurine must be reduced bc of this
premature infants have ___ conjugation activity
effect
decreased
- hyperbilirubinemia in newborn bc cant conjugate UDP-glucose to bilirubin so bilirubin cannot be excreted
- can lead to bilirubin-induced encephalopathy
metabolism of drugs with age has what change
not much change bc drug half-life is more dependent on the drug itself
what in the elderly is perhaps the most important factor accounting for decreased drug metab
liver and kidney disease
for drugs whose biotransformation is flow limited
cardiac disease may cause specific drug levels to rise
- alprenolol and propranolol
- isoniazid
- lidocaine
- morphine
- verapamil
