Drug Interactions

Question 1

3 features of drugs that put them at high risk of causing adverse events

Answer 1

Steep dose-response curve
Low (narrow) therapeutic index
High 1st pass metabolism

Question 2

4 aspects of pharmacokinetics

Answer 2

Absorption
Distribution
Metabolism
Excretion

Question 3

2 pharmacodynamic drug interactions

Answer 3

Additive (2 drugs with similar clinical effects - can be used to advantage or can cause harm)
Antagonistic (2 drugs with opposing clinical effects)

Question 4

3 ways absorption effects pharmacokinetics

Answer 4

Gastric emptying
Gastric pH
P-glycoprotein pump (drug efflux pump)

Question 5

Pgp

Answer 5

P-glycoprotein pump
It is a drug efflux pump
Involved in absorption, distribution, and excretion
If it is inhibited, drug concentration can increase and cause potential toxicity
If it is induced, it can decrease drug concentration and cause potential therapeutic failure

Question 6

Phase 1 vs 2 metabolism

Answer 6

1: cytochrome P450 enzymes
2: conjugate enzymes are less involved

Question 7

2 main P450 families

Answer 7

3A4

2D6

Question 8

4 common P450 inhibitors

Answer 8

SSRIs (paroxetine, fluoxetine)
-Azole antifungals (fluconazole)
Macrolife antibiotics
Grapefruit juice

Question 9

5 P450 inducers

Answer 9

St John's Wort
Chronic alcohol use
Benzos
Cigarette smoking
Grilled meat

Question 10

What P450 enzyme does grapefruit juice inhibit?

Answer 10

CYP3A4

Grapefruit juice and pulp, seville oranges and marmalade, pomelos

Question 11

2 drug examples that interact with grapefruit juice

Answer 11

Felodipine

Terfenadine

Question 12

Excretion: Li and thiazides

Answer 12

Thiazides cause a compensatory increase in Na (and Li)
Li has a small therapeutic index
Thiazides can increase the plasma concentration by 20-40% which can be life threatening (neurotoxicity, proarrythmogenic)