Unit 2 - Biological barriers & ADME 3

Question 1

What can dyslipidaemias affect?

Answer 1

Metabolic capacity
- liver biotransformations
Pharmacological response

Question 2

What effect does hyperlipidaemia have?

Answer 2

Increases sequestration of the lipophilic binding drugs

- more lipoproteins available for drug to bind to

Question 3

How does blood flow through the liver?

Answer 3

Through sinusoids which surround the hepatocytes

- perfused on both sides

Question 4

What is a bile canaliculus?

Answer 4

Small canal formed by opposed grooves in the surface of adjacent hepatocytes

Question 5

What volume of plasma flows through the glomerulus per minute?

Answer 5

660 ml/min

Question 6

What percentage of plasma is filtered through the glomerulus?

Answer 6

20%

Question 7

What is the Glomerular Filtration Rate?

Answer 7

125 mL/min

Question 8

Where are transporters found to secrete drugs into the nephron?

Answer 8

Proximal tubule epithelium

Question 9

What are OAT?

Answer 9

Organic Anion Transporters

Question 10

Where are OATs found?

Answer 10

Both surfaces of renal proximal tubule epithelium

• apical
• basolateral

Question 11

Where are P-glycoproteins found?

Answer 11

Apical membrane of the renal proximal tubule epithelial cell

Question 12

What GFR suggests chronic kidney disease?

Answer 12

< 60 ml/min

Question 13

What can be used to calculate eGFR?

Answer 13

Serum creatinine

Question 14

What is produced as a byproduct of muscle metabolism?

Answer 14

Creatinine

Question 15

How is creatinine used as a measure of eGFR?

Answer 15

Creatinine is removed unchanged from the blood
- glomerular filtration
- mainly
- proximal tubular secretion
- small amount
Little to no reabsorption occurs

Question 16

What effect does kidney failure have on serum creatinine?

Answer 16

Serum creatinine levels rise

Question 17

What assumptions can be made to calculate a drug’s renal clearance?

Answer 17

No reabsorption of drug back from the nephron to the blood
No active secretion of drug from blood into the nephron
Knowledge of fraction unbound

Question 18

What are the implications of a drug pharmacokinetics being first order?

Answer 18

Concentration of drug in the body is proportional to dose
- a doubling of dose will see a doubling in concentration of drug in the body
Rate of elimination of drug from the body is proportional to concentration of the drug in the body