Exam 3: Lecture 12, toxicity of Drugs via Genetic Polymorphism

Question 1

Most important metabolizing enzyme?

Answer 1

Cytochrome P450

Question 2

2 Mixed function Oxidase?

Answer 2

Cytochrome P-450
Flavin monooxygenase systems

name due to fact that oxygen is split into 2 atoms

Question 3

3 protein components CyP450

Answer 3

Cytochrome P450
NADPH-cytochrome P450 reductase
Cytochrome b5

Question 4

How do P450s get reduced?

Answer 4

2 electrons probed by cofactor NADPH

transferred to enzyme 1 at time via co-enzyme Cyp450 reductase
some cases b5 inputs 2nd electron

Question 5

clinically most important polymorphism is seen with….

Answer 5

CYP2C9, CYP2C19, and CYP2D6

Question 6

% of drugs metabolized by CYP2D6?

Answer 6

~15-20% even though minor expression in liver

Question 7

Extensive Metabolizer (CYP2D6)

Answer 7

normal pop, normal rate of metabolism

Question 8

Intermediate Metabolizer (CYP2D6)

Answer 8

Low residual activity

major variants: 2D69,10,*41

Question 9

Ultra Metabolizer (CYP2D6)

Answer 9

very low plasma drug level, loss of drug efficacy, use higher dose

1-2% white, 30% ethiopian
very high enzyme activity

Question 10

Poor Metabolizer (CYP2D6)

Answer 10

5-10% white, 1-2% Chinese
high plasma drug level, risk of side effects, use lower dose
enzyme inactive

Question 11

Morphine 6-glucuronide is….

Answer 11

more potent than morpine as analgesic

Question 12

Tramadol toxicity

Answer 12

predominantly eliminated by kidneys

mean elimination 1/2 life is about 5-6 hrs but depends on CYP2D6 activity

Question 13

Patients that are UM CYP2D6 at risk for toxic response to tramadol treatment?

Answer 13

true

Question 14

CYP2D6 Ums might be at greater risk for opiate related adverse effects and might benefit from….

Answer 14

lower dosage of prodrugs such as codeine and tramadol

Question 15

Fatal poisonings of methadone occur between conc of

Answer 15

0.4 and 1.8mg/ml

some individuals it can be lower

Question 16

How to treat ST syndrome>

Answer 16

Cyproheptadine 4mg and diazepam 5mg

Question 17

Debrisoquin/4-hydroxydebrisoquin ratio

Answer 17

if very high ratio, the poor metabolizer