5/6 drug metabolism and excretion caldwell

Question 1

Give two inducers of the CYP4503A4 enzyme and two drugs whose metabolism is enhanced by this.

Answer 1

nducers: Macrolides, St. John’s Wart. Enhanced> Spironolactone, diazepam.

Question 2

Describe metabolic enzyme inducers and inhibitors and analyze how they influence drug interactions.

Answer 2

Inducer: increase activity. Lower effective duration.

Inhibitor: reduce activity. Increases the effective duration.

Question 3

Give the effect of grapefruit juice on the CYP4503A4 enzyme, two drugs whose metabolism is decreased by it and what could be done to compensate.

Answer 3

Inhibitor of 3A4, decreased metabolism of diazepam and spironolactone. Decrease dose or eliminate grapefruit.

Question 4

Define clearance and elimination.

Answer 4

Clearance: volume of blood cleared of drug per unit time.

Elimination: clearance predicts rate of elimination. Reduction of drug concentration.

Question 5

Calculate clearance (CL) given rate of elimination and concentration of drug.

Answer 5

CL = rate of elimination / concentration.

Question 6

Calculate rate of elimination in a first-order clearance model given drug concentration and clearance.

Answer 6

K = CL x Plasma conc

Question 7

Apply the calculation of t1/2 in a first-order model given volume of distribution and clearance to a clinically relevant scenario.

Answer 7

time required to change the amount of drug in the body by one- half during elimination.

t1/2 = 0.7 x Vd / CL

Question 8

Define steady state concentration

Answer 8

Drug in equals drug out. Plateau concentration that is reached in 4- 5 half lives.

Question 9

Describe three differences between first- and zero-order clearance kinetics.

Answer 9

First order: 1) Not saturated; 2) Constant percent eliminated; 3) Related to dose.

Zero order: 1) Saturated; 2) Constant amount eliminated; 3) Independent of dose.

Question 10

Give how many half-lives it takes to reach steady state regardless of dosing.

Answer 10

4-5

Question 11

Given the dose, t1/2, frequency of dosing, and number of doses calculate plasma drug concentration.

Answer 11

Use (dose x interval)/half life and number of half lives to calculate how much of the drug would be left in circulation

Question 12

Differentiate between target concentration and steady state concentration.

Answer 12

Target concentration (TC): concentration that produces the desired therapeutic effect.

Steady state concentration: amount in equals amount out. Plateau concentration obtained in 4-5 half lives. Independent of
dose size and frequency of elimination, only depends on half-life.