Drug Biotransformation

Question 1

biotransformation

Answer 1

substance changed from one chemical to another

Question 2

xenobiotics

Answer 2

foreign substance in body

Question 3

facilitate elimination

Answer 3

of lipophilic, unionized, or large compounds

via biotransformation
-make more polar and sometimes larger

Question 4

biotransformation to more active compound

Answer 4

L-dopa > dopamine

diazepam > oxazepam

Question 5

prodrug

Answer 5

inactive drug undergoes biotransformation to active drug

Question 6

liver

Answer 6

site of most metaboism of drugs

also GI tract, lung, skin, kidneys

Question 7

first pass effect

Answer 7

hepatic portal system

• ingested drugs in small intestine to liver
• undergo extensive metabolism
• limits bioavailability

Question 8

morphine

Answer 8

undergoes extensive first pass biotransformation

-prefer parenteral administration

Question 9

phase 1 reactions

Answer 9

catabolic

-more polar metabolite by unmasking functional group

Question 10

MFOs

Answer 10

mixed function oxidases

• monooxygenases
• cytochrome P450s, FMO, EH enzymes

phase 1 reactions**

Question 11

phase 1 enzymes

Answer 11

in ER membrane of liver

Question 12

phase 2 reactions

Answer 12

anabolic
-conjugation reactions

polar with higher MW
-readily excreted

FASTER rate than phase 1

Question 13

conjugation rxns

Answer 13

phase 2

-glucuronic acid, sulfuric acid, acetic acid, amino acids

Question 14

CYP3A4

Answer 14

metabolism of 50% of clinical drugs

Question 15

cytochrome P450 enzymes

Answer 15

contain heme

-use O2 and H+ to oxidize substrates

Question 16

genetic defect in pseudocholinesterase

Answer 16

altered metabolism of succinylcholine

Question 17

slow acetylator phenotype

Answer 17

autosomal recessive
-decreased N-acetyltransferase in liver

-isoniazid (for TB), hydralazine (for HTN), caffeine, and other amines are metabolized slower

can lead to hepatotoxicity

Question 18

enzyme induction

Answer 18

by certain chemicals
-accelerated substrate metabolism and decreased pharmacologic action of inducer and coadministered drugs

may exacerbate certain drugs - if form more active form

Question 19

phenytoin

Answer 19

p450 inducer

Question 20

ethanol

Answer 20

p450 inducer

-CYP2E1

Question 21

tobacco smoke

Answer 21

p450 inducer

aromatic hydrocarbons
-benzo alpha pyrene

Question 22

rifampin

Answer 22

p450 inducer

-anti-TB

Question 23

phenobarbitol

Answer 23

p450 inducer

sedation and anesthesia

Question 24

grapefruit juice effect

Answer 24

inhibit intestinal CYP3A4

-alters bioavailability of many drug classes

Question 25

coadmin of allopurinol and mercaptopurine

Answer 25

allopurinol - gout mercaptopurin - cancer prolongs action of mercaptopurine - enhances chemotherapeutic and toxic effects - most decreased dose in patient taking allopurinol

Question 26

hepatic enzyme activity

Answer 26

low in neonate - increased in postnatal period - hetero in elderly

Question 27

premature infants

Answer 27

decreased conjugating activity - hyperbilirubinemia - metabolism of fetal Hg - bilirubin in blood - cannot conjugated with UDP glucuronic acid

Question 28

neonate

Answer 28

poor BBB and weak biotransformation -susceptible to toxicity

Question 29

acetaminophen toxicity

Answer 29

exceed therapeutic dose - GSH depleted - toxic metabolites accumulate - results in hepatotoxicity