Drug interactions

Question 1

An example of a DDI that decreases absorption of antihistamine

Answer 1

Fexofenadine (an antihistamine) plus orange juice or grapefruit juice, inhibits OATP1A2 (fexofenadine is a substrate for this transporter) - an uptake transporter
and reduced therapeutic effect

Question 2

Describe the interaction between Digoxin and Propafenone

Answer 2

Digoxin (low therapeutic index), normally effluxed by P-gp - MDR-1.
Propafenone (1c), commonly prescribed with Digoxin, block efflux pathway, absorb more Digoxin, may have side effects

Question 3

How does P-gp work? Where are 3 exceptions to the direction of efflux?

Answer 3

Efflux transporter - often into the lumen of the gut into feces/urine, but exception is Brain and testes… and placenta

Question 4

Describe the interaction between Nicardipine and BCRP

Answer 4

Nicardipine is a calcium channel blocker like Nifedipine, Blocks the action of the BCRP (which normally acts as an efflux pump toget drug back into maternal circulation). Blocking this action raises the levels of Glyburide in the fetus for example

Question 5

Describe the DDI between OATPs and Statins

Answer 5

Pravastatin is not extensively metabolized, In the presence of clarithromycin, plasma concentrations go up. Because the OATP UPTAKE transporters block the entry of the drug into the hepatocytes (pump located on the basolateral surface)

Question 6

What is the difference between the ABC transporters and the OATP transporters

Answer 6

OATP transporters often uptake transporters

ABC transporters often efflux transporters

Question 7

Describe the interaction between Terfenadine/Seldane and ketoconazole

Answer 7

1. Seldane/Trefenadine is an antihistamine and prodrug that gets converted to Fexofenadine (Allegra)
2. Metabolized by CYP3A4
3. Erythromycin and Ketoconazole both inhibit CYP3A4

Question 8

Name 3 CYP3A4 inhibitors

Answer 8

1. Erythromycin
2. Ketoconazole
3. Grapefruit juice

Question 9

Name 3 examples of inducers of CYPs

Answer 9

1. Reduced OCP efficacy when Rifampin and Carbamazepine are taken at same time (CYP3A4)
2. Phenobarbital reduces effects of warfarin by inducing CYP2C9

Question 10

What drug is involved in inducing the biotransformation of methadone

Answer 10

Phenytoin

Question 11

Describe the inhibition of drug transporters with reference to Penicilin

Answer 11

Penicillin, organic anion, eliminated by kidney by OAT1A1. Probenecid inhibits renal tubular secretion of penicillin

Question 12

What else is Probenacid useful for

Answer 12

Oseltamivir, Tamiflu

Question 13

Give 2 examples of DDI with St John’s wort (inducer of both CYP3A4 and P-GP)

Answer 13

1. Cyclosporine and immunosuppresant action

2. Digoxin, induction faster metabolism