IV - Drug Metabolism

Question 1

Convert the parent drug to a more polar (water-soluble) or more reactive product by unmasking or inserting a polar functional group

Answer 1

Phase I Reactions

Question 2

Phase I Reactions

Answer 2

hydrolysis, oxidation, reduction, deamination

Question 3

Mixed-function oxidases, not highly selective in their substrates

Answer 3

Cytochrome P450 Enzymes

Question 4

Cytochrome P450 enzymes have high concentration in

Answer 4

smooth endoplasmic reticulum of the liver

Question 5

75% of phase I drug metabolism is catalyzed by

Answer 5

CYP3A4, CYP2D6

Question 6

Involve conjugation of subgroups -OH, -NH2 and -SH functions on the drug molecule, not very selective

Answer 6

Phase II Reactions

Question 7

Phase II Reactions

Answer 7

glucuronidation, acetylation, glutathione conjugation, glycine conjugation, sulfation, methylation

Question 8

Site of Drug Metabolism

Answer 8

liver, kidneys, tissue compartments

Question 9

Primary determinant of clearance, most often due to genetic or drug-induced differences

Answer 9

Biotransformation

Question 10

Study of different polymorphisms among families or populations affecting drug-metabolizing systems

Answer 10

Pharmacogenomics

Question 11

Results from increased synthesis of cytochrome P450 enzymes and heme

Answer 11

Enzyme Induction

Question 12

Cytochrome P450 Inducers

Answer 12

ethanol, barbiturates, phenytoin, rifampicin, griseofulvin, carbamazepine, St. John’s wort, smoking

Question 13

Results from decreased blood flow to the metabolizing organ

Answer 13

Enzyme Inhibition

Question 14

Metabolized to products that irreversibly inhibit the metabolizing enzyme

Answer 14

Suicide Inhibitors

Question 15

Cytochrome P450 Inhibitors

Answer 15

isoniazid, cimetidine, sulfonamides, amiodarone, ketoconazole, erythromycin, grapefruit juice, quinidine, ritonavir, valproic acid