Drug Interactions

Question 1

what are 2 ways drugs can interact?

Answer 1

pharmacokinetics (drug availability) and pharmacodynamics (receptor/pathway)

Question 2

what are 3 effects of drug interactions?

Answer 2

decr drug action, incr drug action, incr toxicity/adverse effects

Question 3

where are interactions for a drug usually listed?

Answer 3

product monographs

Question 4

what TI range is more susceptible to drug interaction?

Answer 4

narrow range

Question 5

what does a narrow TI suggest?

Answer 5

small changes to drug response/availability can lead to adverse outcomes (toxic effects or loss of drug action)

Question 6

what are antagonistic interactions?

Answer 6

drug A is an antagonist at receptor for drug B (decr effectiveness of drug B)

Question 7

what is an example of an antagonistic interaction?

Answer 7

Vitamine K rich foods and Warfarin (anticoagulant)

Question 8

what kind of drug interaction is an antagonistic interaction?

Answer 8

pharmacodynamic

Question 9

how do warfarin and vitamin k interact?

Answer 9

warfarin inhibits vit K epoxide reductase which decr blood clotting (incr possibility for hemorrhage)

Question 10

what is vit K epoxide reductase?

Answer 10

enzyme that reduces oxidized vit K (KO to KH2) so it can act as a cofactor for blood clotting

Question 11

what is prothrombin time (PT)?

Answer 11

measure of time required for blood to clot under standard conditions

Question 12

how is PT usually recorded?

Answer 12

as INR (international normalized ratio) which compares PT to ‘average’ clotting time

Question 13

what does a high INR mean?

Answer 13

blood takes longer than average to clot

Question 14

how does vit K rich food interact w/ warfarin?

Answer 14

vit K will compete w/ warfarin (taken for anticoagulation) for epoxide reductase and incr blood clotting

Question 15

how can warfarin effects be enhanced?

Answer 15

if vit k is diminished (antibiotics, etc.)

Question 16

what is synergism vs additive interactions?

Answer 16

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

Question 17

what is an example of excessive receptor activation (additive/synergism)?

Answer 17

alcohol w/ benzodiazepines, barbiturates, or other GABAa modulators

Question 18

what is the GABAa receptor?

Answer 18

chloride channel

Question 19

what do alcohol, benzodiazepines, barbiturates, and zolpidem all have in common?

Answer 19

all positive allosteric modulators at GABAa receptor (incr activity of GABA, therefore decr brain activity)

Question 20

what are indirect drug interactions?

Answer 20

drugs interact in same pathway but not same receptos

Question 21

what is an example of an indirect drug interaction?

Answer 21

serotonin syndrome (drugs incr 5-HT/overstimulate 5-HT1A and 2A)

Question 22

what are 5 symptoms of serotonin syndrome?

Answer 22

incr body temp, agitation, sweating, dilated pupils, twitching, incr BP (and others)

Question 23

what are 6 key drugs/receptors involved in serotonin syndrome?

Answer 23

MAO inhibitors, tricyclics/SSRIs/SNRIs, opioids, St. John’s wort, MDMA/meth, 5-HT precursors

Question 24

how do MAO inhibitors incr availability of 5-HT in CNS?

Answer 24

decr 5-HT breakdown by MAO-A enzyme (incr intracell conc.)

Question 25

how do tricyclics/SSRIs/SNRIs, opioids, and St. John’s wort incr availability of 5-HT in CNS?

Answer 25

decr 5-HT reuptake (incr synaptic conc.)

Question 26

how do recreational drugs (MDMA, meth) incr availability of 5-HT in CNS?

Answer 26

incr 5-HT release (can cause uptake pumps to work in reverse)

Question 27

how can drugs have pharmacokinetic interactions? (2)

Answer 27

incr CYP activity (decr lifetime) or decr CYP activity (incr lifetime)

Question 28

what is the most common CYP enzyme?

Answer 28

CYP 3A4

Question 29

how do warfarin and CYP3A4 inducers interact? effect?

Answer 29

incr breakdown of warfarin by CYP3A4; leads to lower INR (incr clotting)

Question 30

what is an ex of a CYP3A4 inhibitor?

Answer 30

grapefruits

Question 31

how do warfarin and CYP3A4 inhibitors interact? effect?

Answer 31

decr breakdown of warfarin by CYP3A4; leads to higher INR (incr bleeding)