Drug Biotransformation Flashcards Preview

RENAL II Exam 1 > Drug Biotransformation > Flashcards

Flashcards in Drug Biotransformation Deck (29):
1

biotransformation

substance changed from one chemical to another

2

xenobiotics

foreign substance in body

3

facilitate elimination

of lipophilic, unionized, or large compounds

via biotransformation
-make more polar and sometimes larger

4

biotransformation to more active compound

L-dopa > dopamine

diazepam > oxazepam

5

prodrug

inactive drug undergoes biotransformation to active drug

6

liver

site of most metaboism of drugs

also GI tract, lung, skin, kidneys

7

first pass effect

hepatic portal system
-ingested drugs in small intestine to liver
-undergo extensive metabolism
-limits bioavailability

8

morphine

undergoes extensive first pass biotransformation

-prefer parenteral administration

9

phase 1 reactions

catabolic
-more polar metabolite by unmasking functional group

10

MFOs

mixed function oxidases
-monooxygenases
-cytochrome P450s, FMO, EH enzymes

phase 1 reactions**

11

phase 1 enzymes

in ER membrane of liver

12

phase 2 reactions

anabolic
-conjugation reactions

polar with higher MW
-readily excreted

FASTER rate than phase 1

13

conjugation rxns

phase 2
-glucuronic acid, sulfuric acid, acetic acid, amino acids

14

CYP3A4

metabolism of 50% of clinical drugs

15

cytochrome P450 enzymes

contain heme
-use O2 and H+ to oxidize substrates

16

genetic defect in pseudocholinesterase

altered metabolism of succinylcholine

17

slow acetylator phenotype

autosomal recessive
-decreased N-acetyltransferase in liver

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

can lead to hepatotoxicity

18

enzyme induction

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

may exacerbate certain drugs - if form more active form

19

phenytoin

p450 inducer

20

ethanol

p450 inducer
-CYP2E1

21

tobacco smoke

p450 inducer

aromatic hydrocarbons
-benzo alpha pyrene

22

rifampin

p450 inducer
-anti-TB

23

phenobarbitol

p450 inducer

sedation and anesthesia

24

grapefruit juice effect

inhibit intestinal CYP3A4
-alters bioavailability of many drug classes

25

coadmin of allopurinol and mercaptopurine

allopurinol - gout
mercaptopurin - cancer

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

26

hepatic enzyme activity

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

27

premature infants

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

28

neonate

poor BBB
and weak biotransformation
-susceptible to toxicity

29

acetaminophen toxicity

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