13. Drug Dosing in Chronic Liver Disease

Question 1

What factors affect hepatic elimination of drugs?

Answer 1

• liver blood flow
• hepatic intrinsic clearance
• protein binding
• biliary excretion

Question 2

How is drug clearance determined?

Answer 2

The rate of blood flow delivering drug to the organ of metabolism or elimination AND the ability of the organ to extract drug molecules from the bloodstream.

Question 3

What are Phase I reactions?

Answer 3

oxidation and reduction

Question 4

What are Phase II reactions?

Answer 4

conjugation, glucuronidation, and sulfonation

Question 5

High E drugs are _____ limited.

Answer 5

flow

Question 6

Low E drugs are ______ limited.

Answer 6

capacity

Question 7

Patients with chronic liver disease have ___ volume of distribution.

Answer 7

larger

Question 8

CYP1A1 are found where?

Answer 8

extrahepatic: lungs

Question 9

CYP1A2 are found where?

Answer 9

liver

Question 10

What is the most important xenobiotic metabolizing isoform?

Answer 10

CYP3A4

Question 11

How does biliary excretion impact drug metabolism?

Answer 11

reduced formation or secretion of bile into the duodenum will lead to decreased clearance

Question 12

In chronic liver disease ______ receptor sensitivity has been observed with some drugs.

Answer 12

increased

Question 13

What is one issue with determining level of hepatic clearance?

Answer 13

lack of a good marker for hepatic function

Question 14

Which of the following is a factor that affects the hepatic elimination of drugs?
A. Hepatic blood flow 
B. Protein binding 
C. Biliary excretion 
D. A & B only 
E. All of the above

Answer 14

E. All of the above

Question 15

Which of the following drugs is considered a perfusion-limited drug?
A. Diltiazem (E=0.55) 
B. Morphine (E=0.76) 
C. Amitriptyline (E=0.6) 
D. More than one of the above 
E. None of the above

Answer 15

B. Morphine (E=0.76)

Question 16

Low extraction drugs are less affected by changes in protein binding compared to high extraction drugs. (T/F)

Answer 16

False

Question 17

What is the most important xenobiotic metabolizing isoform?
A. CYP2D6 
B. CYP1A2 
C. CYP2C19 
D. CYP3A4 
E. CYP2E1

Answer 17

D. CYP3A4

Question 18

The Child-Pugh Score evaluates all of the following markers except:
A. Presence of ascites 
B. Serum bilirubin 
C. Serum AST/ALT 
D. Prothrombin time 
E. Presence of encephalopathy

Answer 18

C. Serum AST/ALT

Question 19

High E drugs are extracted at __%

Answer 19

> 70%

Question 20

Low E drugs are extracted at __%

Answer 20

< 30%

Question 21

Child-Pugh scores asses what?

Answer 21

• serum bilirubin
• serum albumin
• PT
• ascites
• encephalopathy