Pharmacokinetics Liver + Renal Dysfunction

Question 1

What is biliary excretion?

Answer 1

Secretion of endogenous + exogenous drugs/substances from hepatocytes into bile

Question 2

What can impaired bile secretion be due to?

Answer 2

Bile duct stones
Sclerosing cholangitis
Cancer of biliary tree
Pancreas

Question 3

What can bacteria in GI do?

Answer 3

Reform drug again
= go back to liver

Question 4

Describe liver structure

Answer 4

Central in the middle
Triads are on each corner

Question 5

What flows between the triads?

Answer 5

Rich O2

Question 6

What is triad made up of?

Answer 6

Bile duct
Hepatic artery
Portal vein

Question 7

Where is there low oxygen?

Answer 7

At central
= hepatic vein is draining
= low O2

Question 8

Where does Phase II happen?

Answer 8

Between cells
= requires lots of oxygen

Question 9

What is compensated liver damage?

Answer 9

Body cannot compensate for it = puffer cells activated

Question 10

What does liver damage do?

Answer 10

Put pressure on pathway
= restrict flow
= body can’t compensate

Question 11

What are some common liver diseases?

Answer 11

Alcohol-related liver disease
Non-alcoholic fatty liver disease
Hep A, B, C
Haemochromatosis
Primary biliary cirrhosis

Question 12

What is liver cirrhosis?

Answer 12

Scarring of liver caused by long-term damage

Question 13

What can liver cirrhosis ead to?

Answer 13

Reduce hepatic blood flow = higher serum levels
Impaired renal excretion = increased serum conc
Hypoalbuminemia = reduce protein binding = higher serum conc of free drug
Bowel edema = impaired absorption
Reduced cytochrome activity = reduced 1st-pass/clearance

Question 14

What happens to bilirubin in the body?

Answer 14

It is recycled

Question 15

What are the different types of bilirubin?

Answer 15

Bilirubin-albumin
Bilirubin-diglucuronide
Bilirubin-glucuronide

Question 16

How long would it take to see no more albumin if liver stopped functioning?

Answer 16

t1/2 X 5
= 20 days = 100 days

Question 17

What are the intracellular things?

Answer 17

AST
ALT
GGTP
Alkaline phosphatase
= if seen in the blood = PROBLEM

Question 18

What does increased ALT indicate?

Answer 18

Liver damage

Question 19

How is INR calculated?

Answer 19

Centrifuge
Ca2+ added to serum
Gel forms
Time taken = prothrombin time

INR = PT test
—————
PT normal

Question 20

What is Phase I?

Answer 20

CYP enzymes
Oxidative

Question 21

What is Phase II?

Answer 21

Transferases
Conjugate drug

Question 22

Describe competitive inhibition

Answer 22

Inhibitor competes for active sites
= stretches the curve

Question 23

Describe non-competitive inhibition

Answer 23

Reduces enzyme activity BUT does not bind to active site
= reduces Vmax

Question 24

What happens if we have no blood flow to enzymes?

Answer 24

Mimics “competitive inhibition”

Question 25

Is Phase II less affected by liver dysfunction?

Answer 25

YES until decompensation

Question 26

How do you calculate AUC hepatic function?

Answer 26

AUC total