Drug Interactions Flashcards
what are 2 ways drugs can interact?
pharmacokinetics (drug availability) and pharmacodynamics (receptor/pathway)
what are 3 effects of drug interactions?
decr drug action, incr drug action, incr toxicity/adverse effects
where are interactions for a drug usually listed?
product monographs
what TI range is more susceptible to drug interaction?
narrow range
what does a narrow TI suggest?
small changes to drug response/availability can lead to adverse outcomes (toxic effects or loss of drug action)
what are antagonistic interactions?
drug A is an antagonist at receptor for drug B (decr effectiveness of drug B)
what is an example of an antagonistic interaction?
Vitamine K rich foods and Warfarin (anticoagulant)
what kind of drug interaction is an antagonistic interaction?
pharmacodynamic
how do warfarin and vitamin k interact?
warfarin inhibits vit K epoxide reductase which decr blood clotting (incr possibility for hemorrhage)
what is vit K epoxide reductase?
enzyme that reduces oxidized vit K (KO to KH2) so it can act as a cofactor for blood clotting
what is prothrombin time (PT)?
measure of time required for blood to clot under standard conditions
how is PT usually recorded?
as INR (international normalized ratio) which compares PT to ‘average’ clotting time
what does a high INR mean?
blood takes longer than average to clot
how does vit K rich food interact w/ warfarin?
vit K will compete w/ warfarin (taken for anticoagulation) for epoxide reductase and incr blood clotting
how can warfarin effects be enhanced?
if vit k is diminished (antibiotics, etc.)
what is synergism vs additive interactions?
synergism: 2 drugs act on same receptor to have greater than individual effects
additive: 2 drugs act on same receptor to have sum of individual effects
what is an example of excessive receptor activation (additive/synergism)?
alcohol w/ benzodiazepines, barbiturates, or other GABAa modulators
what is the GABAa receptor?
chloride channel
what do alcohol, benzodiazepines, barbiturates, and zolpidem all have in common?
all positive allosteric modulators at GABAa receptor (incr activity of GABA, therefore decr brain activity)
what are indirect drug interactions?
drugs interact in same pathway but not same receptos
what is an example of an indirect drug interaction?
serotonin syndrome (drugs incr 5-HT/overstimulate 5-HT1A and 2A)
what are 5 symptoms of serotonin syndrome?
incr body temp, agitation, sweating, dilated pupils, twitching, incr BP (and others)
what are 6 key drugs/receptors involved in serotonin syndrome?
MAO inhibitors, tricyclics/SSRIs/SNRIs, opioids, St. John’s wort, MDMA/meth, 5-HT precursors
how do MAO inhibitors incr availability of 5-HT in CNS?
decr 5-HT breakdown by MAO-A enzyme (incr intracell conc.)
how do tricyclics/SSRIs/SNRIs, opioids, and St. John’s wort incr availability of 5-HT in CNS?
decr 5-HT reuptake (incr synaptic conc.)
how do recreational drugs (MDMA, meth) incr availability of 5-HT in CNS?
incr 5-HT release (can cause uptake pumps to work in reverse)
how can drugs have pharmacokinetic interactions? (2)
incr CYP activity (decr lifetime) or decr CYP activity (incr lifetime)
what is the most common CYP enzyme?
CYP 3A4
how do warfarin and CYP3A4 inducers interact? effect?
incr breakdown of warfarin by CYP3A4; leads to lower INR (incr clotting)
what is an ex of a CYP3A4 inhibitor?
grapefruits
how do warfarin and CYP3A4 inhibitors interact? effect?
decr breakdown of warfarin by CYP3A4; leads to higher INR (incr bleeding)
