Pharmacokinetics I Flashcards
in general, metabolism generates more ___, ___ metabolites that are readily excreted from the body
in general, metabolism generates more polar, inactive metabolites that are readily excreted from the body
phase I reactions include which 5 reactions?
phase I reactions include:
oxidations
reductions
decarboxylations
deaminations
hydrolytic reactions
one example of a prodrug (which is converted to a biologically active metabolite) is the drug ____, which is activated by metabolism to an active anticancer metabolite
one example of a prodrug (which is converted to a biologically active metabolite) is the drug cyclophosphamide, which is activated by metabolism to an active anticancer metabolite
prodrugs are converted to biologically active metabolites, often by ____ or ____
prodrugs are converted to biologically active metabolites, often by hydrolysis of an ester or amide linkage
phase II consists of ____ reactions, which form a covalent bond between the drug molecule and glucuronate, acetate, glutathione, amino acids or sulfate
phase II consists of conjugation reactions, which form a covalent bond between the drug molecule and glucuronate, acetate, glutathione, amino acids or sulfate
phase II consists of conjugation reactions, which form a covalent bond between the drug molecule and _____
phase II consists of conjugation reactions, which form a covalent bond between the drug molecule and glucuronate, acetate, glutathione, amino acids or sulfate
phase I reactions are located primarily in ____
phase II conjugation enzyme systems are mainly _____
phase I reactions are located primarily in the membrane of the ER
phase II conjugation enzyme systems are mainly cytosolic
which (3) drugs increase the synthesis of P450 isoforms?
phenobarbital
rifampin
carbamazepine
____ increases the metabolism of various drugs by inducing CYP3A4
St. John’s wort increases the metabolism of various drugs by inducing CYP3A4
name 6 drugs that inhibit cytochrome P450
amiodarone
cimetidine
ketoconazole
erythromycin
chloramphenicol
grapefruit juice
____ actively transports drugs back into the intestinal lumen, which ultimately limits the oral bioavailability of several drugs
P-glycoprotein actively transports drugs back into the intestinal lumen, which ultimately limits the oral bioavailability of several drugs
____ can inhibit P-glycoprotein
how does this affect serum levels of the drug?
macrolide antibiotics can inhibit P-glycoprotein
this inhibition can lead to increased serum levels of drugs, such as digoxin
the antidote for acetaminophen toxicity is ____ which supplies ___ for ____ production also reacts directly with NAPQI
the antidote for acetaminophen toxicity is N-acetylcysteine which supplies cysteine for glutathione production also reacts directly with NAPQI
grapefruit juice inhibits both ___ and ____ in the ____
grapefruit juice inhibits both CYP3A4 and P-glycoprotein in the small intestine
____ in cigarette smoke cause AhR-mediated P450 enzyme induction
aromatic hydrocarbons in cigarette smoke cause AhR-mediated P450 enzyme induction
charcoal-broiled foods and cruciferous vegetables induce ____
charcoal-broiled foods and cruciferous vegetables induce CPY1A enzymes
what are the 3 basic processes involved in renal excretion of drugs?
- glomerular filtration
- active tubular secretion
- passive diffusion across tubular epithelium
what is the only variable that determines glomerular filtration?
SIZE; MW < 20,000 = diffusion in the glomerular filtrate
lipid solubility and pH DON’T influence the passage of drugs into the glomerular filtrate
how does the proximal tubule affect drug excretion?
in the proximal tubule, drug molecules are pumped into the lumen of the tubule by 2 active transport systems; one for anions and one for cations
____ drugs can be passively reabsorbed in the proximal tubule
liposoluble drugs can be passively reabsorbed in the proximal tubule
