Drug interactions

Question 1

A patient with acute MI was told not to eat grapefruit. Why?

Answer 1

Grapefruit causes simvastatin clearance to be lowered due to decreased CYP enzyme activity.

Question 2

Drug interactions can be…

Answer 2

Additive/synergystic (potentiation/toxicity)

Antagonistic (antidote/ loss of effect)

Question 3

If you have a pharmacokinetic drug interaction what does this change

Answer 3

The drug concentration- absorption,metabolism, elimination

Question 4

If you have a pharmacodynamic effect what does this change?

Answer 4

The drug effect

Question 5

An 87 yo f is brought to ED with large intracerebral haemorrhage. She is taking warfarin, the haemorrhage is due to an interaction… why?

Answer 5

There is a large list of medicines that increased the concentration of warfarin due to reduced metabolism

Question 6

What are the four levels where pharmacokinetic drug interactions can occur?

Answer 6

Absorption, distribution, metabolism, elimination

Question 7

What are some causes of drug interactions that alter absorption

Answer 7

• Change in GI pH
• Drug binding in GI tract (e.g. drugs bind to each other and become ineffective)
• Change in gut motility
• Malabsorption

Question 8

What is a substrate

Answer 8

An agent that is metabolised by an enzyme (CYP) into a metabolic end product and eventually excreted

Question 9

What do inhibitors do in relation to the substrate?

Answer 9

They interfere with the ability of the enzyme to metabolize the substrate, decreased metabolism leads to increased concentrations of the substrate

Question 10

What do inducers do in relation to substrates

Answer 10

They increase the production of the enzyme responsible for metabolising the substrate. Increased metabolism, decreased concentrations of substrate

Question 11

What is the time course of inhibitors and why

Answer 11

Rapid increase in the blood level of substrates because there is no metabolism occurring

Question 12

What is the time course of inducers and why

Answer 12

Cause a slow change in the increased to metabolism because it takes time to synthesize new enzymes

Question 13

Inducers of CYP3A4

Answer 13

Phenytoin

St Johns wort

Question 14

Inhibitors of CYP3A4

Answer 14

Erythromycin
Calcium channel blockers
HIV antivirals
Grapefruit juice

Question 15

Substrates of CYP2C9

Answer 15

Warfarin
NSAIDs
Oral hypoglycaemics
Phenytoin

Question 16

Inhibitors of CYP2C9

Answer 16

Amiodarone (ventricular arrythmia)
Fluoxetine (depression)
Fluconazole (fungal infections)

Question 17

Inducers of CYP2C9

Answer 17

Carbamazepine
Rifampicin (antibiotic)
St Johns wart

Question 18

What do proton pump inhibitors do to clopidogrel

Answer 18

Inhibit its action. Its an anti platelet drug

Question 19

Substrates of CYP2C19

Answer 19

Proton pump inhibitors, anti depressants, anti-epileptics, clopidogrel

Question 20

Inhibitors of CYP2C19

Answer 20

Omeprazole

Fluoxetine

Question 21

Inducers of CYP2C19

Answer 21

Carbamazepine

Phenytoin