Drug Interactions

Question 1

What is a drug interaction?

Answer 1

A change in one drug’s effect when administered with another substance

Question 2

What are the two potential additive effects?

Answer 2

Potentiation and toxicity

Question 3

What are the two potential antagonist effects?

Answer 3

Antagonism and loss of effect

Question 4

What are pharmacokinetic drug interactions?

Answer 4

Interacting drug alters the concentration
Absorption, metabolism, elimination
Difficult to anticipate

Question 5

What are pharmacodynamic drug interactions?

Answer 5

Interacting drug alters the effect
Receptor mediated or non receptor mediated
Can be anticipated

Question 6

What are the four levels that drugs can interact on?

Answer 6

Absorption
Distribution
Metabolism
Elimination

Question 7

What is an example of absorption interactions?

Answer 7

Metoclopramide increases gastric emptying and reduces absorption of digoxin from the stomach

Question 8

What is a substrate?

Answer 8

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

Question 9

What are inhibitors of drug metabolism and what effect do these have?

Answer 9

Interfere with the ability of the enzyme to metabolise substrate and lead to increased concentrations of the substrate

Question 10

What are the inducers of drug metabolism and what effect do these have?

Answer 10

Increase production of enzyme responsible for metabolising substrate which leads to decreased concentrations of the substrate

Question 11

What is the time course of an inhibitor like?

Answer 11

Enzyme inhibitors cause rapid increases (24 hours) in the blood level of substrates. The time to maximal drug interaction is determined by half life and time required for substrate to reach a new steady state

Question 12

What is the time course of an enzyme inducer like?

Answer 12

Enzyme inducers cause slow changes because it requires synthesis of the enzyme and max effect may not be reached for two to three weeks

Question 13

Which enzyme metabolises 50% of medicines?

Answer 13

CYP3A4

Question 14

How do grape fruit juice, erythromycin, sildenafil and st John’s wort effect CYP3A4?

Answer 14

Grape fruit juice= inhibitor
Erythromycin= inhibitor and substrate
St John’s wort= inducer (can cause organ rejection with cyclosporin therapy)
Sildenafil= substrate (can cause hypotension if taken with CYP3A4 inhibitors)

Question 15

What is a key substrate of CYP2C9?

Answer 15

Warfarin

Question 16

What is a key interaction of the CYP2C19 enzyme?

Answer 16

Clopidogrel (substrate) vs proton pump inhibitors (substrate)

Question 17

What are some examples of drugs interacting to alter elimination?

Answer 17

NSAIDs inhibit prostaglandins which leads to reduced renal blood flow which reduces elimination
Drugs can also compete for ionic transport in the kidney
These are more important in patients with reduced kidney function

Question 18

What is important about P-glycoprotein?

Answer 18

Transports drugs out of intestines into gut lumen and maintains blood brain barrier
A key substrate of this is digoxin

Question 19

What was the problem with “be happy tea”?

Answer 19

Contained St John’s Wort and when taken with antidepressants caused serotonin syndrome

Question 20

What is a pharmacokinetic drug interaction?

Answer 20

Does not effect concentrations of drugs but does alter the overall effect (be happy tea)

Question 21

What are the two ways that a pharmacokinetic drug interaction is possible?

Answer 21

Shared receptor (common receptor between two drugs)-beta blockers and asthma medications
Shared effect (both drugs act upon the same system but through two different receptors)-aspirin and warfarin=bleeding