lecture 10 - drug interactions Flashcards
what is a drug interaction
a change in one drug’s effect when administered with another drug, food or other substance
types of drug interactions
desirable effects = synergistic effect or antagonism
undesirable effects = toxicity or loss of effect
pharmacokinetic interaction
effects the concentration of the drug
- absorption
- metabolism
- elimination
more difficult to anticipate as they are not predictable from the clinical effects of the drugs involved
pharmacodynamic interaction
alters the effect of the drug
- receptor-mediated
- non-receptor mediated
can be anticipated based on known drug effects
what are drug-drug interactions that alter the plasma concentration of 1 or both drugs referred to? And how can these interactions occur
pharmacokinetic interactions
occur at the level of:
- absorption
- distribution
- metabolism (liver)
- elimination (kidneys)
Pharmacokinetic interactions with drug absorption
• can change GI pH, drug binding in tract, gut motility, absorption
• eg. calcium binds thyroxine and reduces absorption (recommended to be taken at least 4 hours
apart)
Pharmacokinetic interactions with hepatic metabolism
• enzyme inhibitors cause rapid increases in serum [substrate], time to maximal interaction determined by:
- half-life and time to steady state of inhibitor
- time to new steady state of substrate
• enzyme inducers cause slow change (requires enzyme synthesis)
define substrate
an agent that is metabolized by an enzyme into a metabolic end product and eventually excreted
(CYP)
CYP inhibitors
interfere with the ability of an enzyme to metabolize substrate
- decreased metabolism –> increased conc of substrate
CYP inducers
increase production of enzyme(s) responsible for metabolizing substrate
- increased metabolism –> decreased conc of substrate
time course of enzyme inhibitors
cause rapid increases (24hours) in the blood levels of substrates.
time to maximal drug interaction determined by:
- half-life and time to steadys tate of inhibitor drug
- time required for the substrate to reach a new steady state
time course of enzyme inducers
cause slow change (days to weeks) because it requires synthesis of the enzyme.
maximal effect may not be reached for 2-3 weeks (and take 2-3 weeks to ‘wear off’)
CYP3A4 enzyme
- metabolises > 50% of medicines
- important substrates include erythromycin, calcium channel blockers
- St John’s Wort can cause organ rejection when taken with cyclosporin (inducing CYP3A4)
- viagra can cause dangerously low BP when taken with CYP3A4 inhibitors
CYP2C9 enzyme
- inducer and inhibitor
substrate = warfarin
inhibitors = amiodarone
inducer = St John’s Wort
CYP2C19
proton pump inhibitors inhibit the activation of the anti-platelet drug, clopidogrel
