Drug Interaction

Question 1

Definition of drug interaction

Answer 1

when the effects of one drug are changed by the presence of another drug, food, drink, or an environmental chemical agent

Question 2

What may drug interactions cause

Answer 2

Basically:
May increase toxicity
Or
Reduce activity – failure of therapy

Question 3

What are interactions increased by

Answer 3

Poly pharmacy

Renal impairment and other conditions

Question 4

Mechanisms of interaction

Answer 4

Absorption
pH
Binding

Question 5

Absorption pharmacokinetic mechanism

Answer 5

2 drugs may interact to alter rate of uptake

Eg. Tetracycline and Fe2+ salts or Ca2+ (milk)

Question 6

pH pharmacokinetic mechanisms

Answer 6

Passive absorption of drugs best in uncharged form, governed by pKa value
Roses in pH may influence absorption of other drugs
Separate by several hours

Question 7

Binding pharmacokinetic mechanism

Answer 7

Colestyramine

Question 8

Potential effect of drugs on absorption

Answer 8

Can induce/inhibit absorption of other drugs
Eg. MDR1 transporter, digoxin is substrate and induction of MDR1 reduces bioavailability
Multiple drug resistance transporter

Question 9

Interaction between digoxin and another drug

Answer 9

Substrate of p-glycoprotein
Rifampicin induces p-glycoprotein
Decreases absorption of digoxin as efflux process of intestinal epithelial cells is increased to the intestinal lumen

Question 10

Displacement

Answer 10

Drugs may compete for binding sites resulting in displacement
Increases in toxicity but then increased elimination

Question 11

Another effect of drug interactions on each other

Answer 11

Can induce/inhibit metabolism of another drug

Question 12

What causes inhibition of enzyme cyt P450

Answer 12

Macrolide eg. erythromycin, clarithromycin
Rapid
Often reverse quickly upon stopping
Warfarin is an example , increases risk of bleeding therefore monitor

Question 13

Interaction with macrolides

Answer 13

Warfarin - unpredictable

Monitor INR and reduce dose if appropriate to maintain INR

Question 14

What does cytochrome P450 do?

Answer 14

Many drugs metabolised by multiple CYPs
Some metabolised by multiple or single
Single more likely to be involved in clinically relevant interactions
Some drugs are inducers or inhibitors of cytochrome P450

Question 15

Warfarin and quinolone antibiotics

Answer 15

Severe
Ciprofloxacin may interfere with Cyt P450 dependent metabolism
May alter gut flora and reduce vitamin k levels

Question 16

What is contraindicated with macrolides

Answer 16

Simvastatin
Severe, increases side effects
Interaction with calcium channel blockers eg. amlodipine, verapamil, diltiazem

Question 17

Enzyme induction

Answer 17

Increase activity of metabolising enzymes 
Eg. Rifampicin
Reduces plasma conc of warfarin 
Monitor INR
May take a week or two
Effect may persist

Question 18

NSAIDs and warfarin

Answer 18

Significant
Aspirin - enhances bleeding
NSAIDs - gastric bleeding, enhanced by warfarin

Question 19

Warfarin and diet

Answer 19

Avoid vitamin k rich foods
May reduce activity of warfarin
Diet may alter anticoagulant control

Question 20

Interactions of warfarin with food/drink

Answer 20

Cranberry juice shown to potentiate warfarin, leading to fatalities

Question 21

Grapefruit juice

Answer 21

Interacts with simvastatin and some Ca antagonists
Psoralen in the juice may interfere with Cyt P450 dependent metabolism and increase levels of simvastatin
May also inhibit P-glycoprotein transport

Question 22

Clopidogrel and PPIs

Answer 22

PPI eg Omeprazole
Makes clopidogrel less effective
Due to both being biotransformed by same Cyt P450
No longer converted to active metabolite
Use pantoprazole

Question 23

Beneficial interactions?

Answer 23

Combinations of anti hypertensive drugs

Eg. ACE inhibitors and calcium channel blockers

Question 24

Key interactions

Answer 24

Warfarin and NSAIDs: leading to enhanced bleeding
Warfarin and antibiotics (erythromycin and ciprofloxacin): leading to enhanced bleeding
Simvastatin and macrolides: avoid
Ms and amlodipine: caution dose

Question 25

Inducer effect on cytochrome p450 and other drugs

Answer 25

More enzyme available for breakdown of drug

Lower concentration of drug, lower than TW

Question 26

Inhibitor effect on cytochrome P450 and drug

Answer 26

Inhibits enzyme, less broken down

Drug in higher concentration, higher than therapeutic window