Drug interactions Flashcards
Drug interactions
Many involve the effect of one drug on the metabolism of another
Object drug
Drug whose effect or action is altered by introduction of another agent
Precipitant drug
Drug which alters or precipitates a change in the effect of the other drug
Examples of drugs prone to concentration-dependent toxicity
e.g., Digoxin, Lithium, Aminoglycosides, Cytotoxic agents, Warfarin
Examples of drugs prone to steep dose-response curve
e.g., Verapamil, Sulphonylureas, Levodopa
Patient factors affecting drug interactions
Polypharamcy
Elderly
Critically ill/multiple co-morb
Chronic illness
What are the 3 mechanisms of drug interactions?
Pharmaceutical incompatibilities Pharmacodynamic interactions Pharmacokinetic interactions (ADME)
Pharmaceutical incompatibilities
Occur before drugs introduced to the body
Often involves precipitation of additives to IV fluids and other formulations
Pharmacodynamic Interactions
Related to drug mechanism or site of action
Generally predictable
Classified as either competitive or additive at the same drug target
Examples of pharmacodynamic interactions
Direct competition at receptor sites - morphine/naloxone or salbutamol/metoprolol
Additive effects at same receptor sites - use of 2 NSAIDs or 2 beta-blockers concurrently
Indirect additive effects via different sites of action - Verapamil/betablockers or NSAIDs and warfarin
Pharmacokinetic Interactions
Occurs during the 4 phases of pharmacokinetics (ADME)
Pharmacokinetic Interactions: absorption
changes in pH
binding and chelation
GI motility
Pharmacokinetic Interactions - distribution
Care in people with hypoalbuminaemia
Increased free levels of drugs
Pharmacokinetic Interactions - Metabolism
Large number of drug interactions occur at this phase
Importance of individuals CYP profile - CYP450 enzymes involved in phase 1 metabolism in the liver
Enzyme induction or inhibition is the basis of many DIs
Enzyme inhibitors
Inhibit CYP enzymes - thus reducing the metabolism of object drugs using the same metabolic pathway
Object drug will accumulate and if it has a low therapeutic index adverse effects will occur
