Drug Interactions Flashcards
What is a drug interaction?
A change in one drug’s effect when administered with another substance
What are the two potential additive effects?
Potentiation and toxicity
What are the two potential antagonist effects?
Antagonism and loss of effect
What are pharmacokinetic drug interactions?
Interacting drug alters the concentration
Absorption, metabolism, elimination
Difficult to anticipate
What are pharmacodynamic drug interactions?
Interacting drug alters the effect
Receptor mediated or non receptor mediated
Can be anticipated
What are the four levels that drugs can interact on?
Absorption
Distribution
Metabolism
Elimination
What is an example of absorption interactions?
Metoclopramide increases gastric emptying and reduces absorption of digoxin from the stomach
What is a substrate?
An agent that is metabolised by an enzyme into a metabolic end product and eventually excreted
What are inhibitors of drug metabolism and what effect do these have?
Interfere with the ability of the enzyme to metabolise substrate and lead to increased concentrations of the substrate
What are the inducers of drug metabolism and what effect do these have?
Increase production of enzyme responsible for metabolising substrate which leads to decreased concentrations of the substrate
What is the time course of an inhibitor like?
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
What is the time course of an enzyme inducer like?
Enzyme inducers cause slow changes because it requires synthesis of the enzyme and max effect may not be reached for two to three weeks
Which enzyme metabolises 50% of medicines?
CYP3A4
How do grape fruit juice, erythromycin, sildenafil and st John’s wort effect CYP3A4?
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)
What is a key substrate of CYP2C9?
Warfarin
What is a key interaction of the CYP2C19 enzyme?
Clopidogrel (substrate) vs proton pump inhibitors (substrate)
What are some examples of drugs interacting to alter elimination?
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
What is important about P-glycoprotein?
Transports drugs out of intestines into gut lumen and maintains blood brain barrier
A key substrate of this is digoxin
What was the problem with “be happy tea”?
Contained St John’s Wort and when taken with antidepressants caused serotonin syndrome
What is a pharmacokinetic drug interaction?
Does not effect concentrations of drugs but does alter the overall effect (be happy tea)
What are the two ways that a pharmacokinetic drug interaction is possible?
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
