Drug Interactions

Question 1

How do warfarin drug interactions occur?

Answer 1

Warfarin is metabolised by CYP2C9 and CYP3A4.
Eg. Rifampicin INDUCES these enzymes (therefore INCREASED warfarin metabolism)
Phenobarbitone INDUCES these enzymes
Cimetidine INHIBITS CYP3A4 (DECREASES metabolism of warfarin, therefore increasing plasma levels, and increasing clotting time).

Question 2

How do Phenytoin and Valproate interactions occur?

Answer 2

• Valproate binds to 2 sites on albumin.
• Phenytoin binds 1 site.
• Valproate has a higher affinity for the binding site than phenytoin, displacing phenytoin and increasing free fraction of phenytoin.

Question 3

Tetracyclines (eg. Penicillins) interactions

Answer 3

Tetracyclines can undergo complexation with di and trivalent cations.
Eg. Iron, Antacids (Al hydroxide), Milk (Ca2+)
–> reduces absorption of tertracyclines

Question 4

Digoxin and verapamil interaction?

Answer 4

• Digoxin is renally excreted by the PgP efflux transporter.
• Verapamil INHIBITS PgP –> therefore reduced digoxin excretion via the kidney –> increased digoxin plasma concentration.

Question 5

Probenocid and Cephalosporin interaction

Answer 5

• Cephalosporins are excreted via the kidney using OAT transporters.
• Probenocid inhibits OAT and therefore excretion of cephalosporins. INCREASES plasma concentrations of cephalosporins

Question 6

Metoclopramide interactions

Answer 6

• metoclopramide increases gastric emptying
• paracetamol –> absorbed in the intestine so increases in gastric emptying means faster absorption and increased plasma concentration.
• digoxin –> requires dissolution by acids for absorption in stomach - increased gastric emptying means decreased dissolution and poor absorption (reduced plasma concentration)