Kruse Biotransformation DSA

Question 1

what are xenobiotics

Answer 1

foreign substances within the body

Question 2

properties of xenobiotics eliminated through renal excretion

Answer 2

polar compounds and small molecular volume compounds

Question 3

biotransformation is the chem mod of what types of compounds

Answer 3

lipophilic, unionized, large compounds

Question 4

inactivation biotransformation example

Answer 4

acetylsalicyclic acid (aspirin) to acetic acid and salicylate

Question 5

activation example biotransformation

Answer 5

L-Dopa to Dopa

Question 6

active compound to active compound example

Answer 6

diazepam to oxazepam

Question 7

what are the other sites of biotransformation besides the liver

Answer 7

kidney, GI, skin, lungs

Question 8

normal GI flora can increase bioavailability of certain drugs like estrogens used in contraception so antibiotics

Answer 8

decrease efficacy

Question 9

classic example of drug that undergoes extensive first pass biotransformation is

Answer 9

morphine, only 25% available orally

Question 10

gen rules: phase I rxn vs phase II

Answer 10

phase I makes drug biologically inactivation

phase II makes it more water soluble and increases molecular weight which facilitates elimnation of drug from body

Question 11

phase I reactions are carried out by

Answer 11

cytochrome P450s
FMOs
epoxide hydrolases (mEH, sEH)

Question 12

phase I enzymes are located in the ______ of the ___

Answer 12

lipophilic ER membranes of the liver (and other tissues)

Question 13

what types of phase II rxns are there

Answer 13

adding: glucuronic acid, sulfuric acid, acetic acid, or an amino acid

Question 14

phase I or phase II rxns occur at faster rates

Answer 14

phase II

Question 15

where do most conjugation rxns take place

Answer 15

liver

Question 16

genetic factors and succinylcholine

Answer 16

individuals with genetic defects in pseudocholinesterase can metabolize succinylcholine at 50% the rate as normal individuals

Question 17

slow acetylator phenotype

Answer 17

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

Question 18

well characterized inducers of P450s

Answer 18

phenytoin
chronic ethanol
benzo pyrene (tobacco smoke)
rifampin (anti-TB)
phenobarbital and other barbiturates

Question 19

consumption of grapefruit juice with drugs can what

Answer 19

irreversibly inhibit intestinal CYP3A4

Question 20

allopurinol and mercaptopurine

Answer 20

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

Question 21

premature infants have ___ conjugation activity

effect

Answer 21

decreased

• hyperbilirubinemia in newborn bc cant conjugate UDP-glucose to bilirubin so bilirubin cannot be excreted
• can lead to bilirubin-induced encephalopathy

Question 22

metabolism of drugs with age has what change

Answer 22

not much change bc drug half-life is more dependent on the drug itself

Question 23

what in the elderly is perhaps the most important factor accounting for decreased drug metab

Answer 23

liver and kidney disease

Question 24

for drugs whose biotransformation is flow limited

Answer 24

cardiac disease may cause specific drug levels to rise

• alprenolol and propranolol
• isoniazid
• lidocaine
• morphine
• verapamil