Drug Interaction Flashcards
Definition of drug interaction
when the effects of one drug are changed by the presence of another drug, food, drink, or an environmental chemical agent
What may drug interactions cause
Basically:
May increase toxicity
Or
Reduce activity – failure of therapy
What are interactions increased by
Poly pharmacy
Renal impairment and other conditions
Mechanisms of interaction
Absorption
pH
Binding
Absorption pharmacokinetic mechanism
2 drugs may interact to alter rate of uptake
Eg. Tetracycline and Fe2+ salts or Ca2+ (milk)
pH pharmacokinetic mechanisms
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
Binding pharmacokinetic mechanism
Colestyramine
Potential effect of drugs on absorption
Can induce/inhibit absorption of other drugs
Eg. MDR1 transporter, digoxin is substrate and induction of MDR1 reduces bioavailability
Multiple drug resistance transporter
Interaction between digoxin and another drug
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
Displacement
Drugs may compete for binding sites resulting in displacement
Increases in toxicity but then increased elimination
Another effect of drug interactions on each other
Can induce/inhibit metabolism of another drug
What causes inhibition of enzyme cyt P450
Macrolide eg. erythromycin, clarithromycin
Rapid
Often reverse quickly upon stopping
Warfarin is an example , increases risk of bleeding therefore monitor
Interaction with macrolides
Warfarin - unpredictable
Monitor INR and reduce dose if appropriate to maintain INR
What does cytochrome P450 do?
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
Warfarin and quinolone antibiotics
Severe
Ciprofloxacin may interfere with Cyt P450 dependent metabolism
May alter gut flora and reduce vitamin k levels
What is contraindicated with macrolides
Simvastatin
Severe, increases side effects
Interaction with calcium channel blockers eg. amlodipine, verapamil, diltiazem
Enzyme induction
Increase activity of metabolising enzymes Eg. Rifampicin Reduces plasma conc of warfarin Monitor INR May take a week or two Effect may persist
NSAIDs and warfarin
Significant
Aspirin - enhances bleeding
NSAIDs - gastric bleeding, enhanced by warfarin
Warfarin and diet
Avoid vitamin k rich foods
May reduce activity of warfarin
Diet may alter anticoagulant control
Interactions of warfarin with food/drink
Cranberry juice shown to potentiate warfarin, leading to fatalities
Grapefruit juice
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
Clopidogrel and PPIs
PPI eg Omeprazole
Makes clopidogrel less effective
Due to both being biotransformed by same Cyt P450
No longer converted to active metabolite
Use pantoprazole
Beneficial interactions?
Combinations of anti hypertensive drugs
Eg. ACE inhibitors and calcium channel blockers
Key interactions
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
Inducer effect on cytochrome p450 and other drugs
More enzyme available for breakdown of drug
Lower concentration of drug, lower than TW
Inhibitor effect on cytochrome P450 and drug
Inhibits enzyme, less broken down
Drug in higher concentration, higher than therapeutic window
