Drug Interactions

Question 1

pharmacokinetic considerations

Answer 1

drug A may influence the effectiveness of drug B by altering its ‘availability’

Question 2

pharmacodynamic considerations

Answer 2

drug A may influence the effectiveness of drug B by altering its interaction with its receptor

Question 3

interactions

Answer 3

could lead to loss or enhancement of drug action
or enhanced drug toxicity/adverse effects

listed in product monographs by manufacturers → contraindicated conditions, potential drug interactions

Question 4

therapeutic index

Answer 4

narrow TI = most susceptible to issues with drug interactions
→ small changes in responsiveness can lead to toxic outcomes

Question 5

pharmacodynamic interactions

Answer 5

antagonistic interaction
synergism or additive interactions
indirect interactions

Question 6

antagonistic interaction

Answer 6

drug A may act as an antagonist at receptor for drug B → reduce effectiveness of drug B

ex. Vitamin K and warfarin

Question 7

vitamin K cycle

Answer 7

oxidized vitamin K (KO) is reduced to KH2 by vitamin K epoxide reductase → generate prothrombin
→ production of active clotting factors

balance of clotting factors is important (too much = clots; too little = unstoppable bleeding)

Question 8

warfarin + vitamin K

Answer 8

anticoagulant for patients with blood clot issues

inhibitor of vitamin K epoxide reductase
= reduces level of clotting factors (no prothrombin)

foods rich in vitamin K will weaken effectiveness of warfarin (compete for occupancy of enzyme)
lower vitamin K (antibiotic that inhibits production) → stronger warfarin effectiveness

Question 9

INR

Answer 9

international normalized ratio: ratio of clotting time compared to a ‘normal’ sample
measure prothrombin time

high INR → sample requires long time to form a clot

Question 10

synergism or additive interactions

Answer 10

multiple agonists/modulators act on same receptor → excessive activation

effect is greater than individual effects (synergism) or roughly the sum of individual effects (additive)

ex. alcohol and GABA-A receptor modulators

Question 11

GABA-A receptor drugs

Answer 11

act on GABA-A receptor (chloride channel) and enhance activity

benzodiazepines: PAM of GABA-A
barbituates: PAM or agonists of GABA-A
alcohol: PAM
zolpidem: PAM

combination of multiple drugs at low concentrations enhance GABA-mediated activation of receptors → sedation, unconsciousness

Question 12

indirect interactions

Answer 12

effects of multiple drugs might influence the same signalling pathway, but not necessarily the same receptor
- acting on different components of same signalling pathway

ex. serotonin syndrome

Question 13

serotonin syndrome

Answer 13

arises from combinations of drugs that lead to overabundance of 5-HT in CNS and overstimulation of 5-HT receptors (especially 5-HT2a and 1a)

characterized by high body temperature, agitation, sweating, dilated pupils, muscle twitching, elevated blood pressure

Question 14

monoamine oxidase inhibitors

Answer 14

prevent breakdown of 5-HT by MAO-A → increased cellular levels of 5-HT
many act irreversibly = long lasting effects → increase susceptibility to serotonin syndrome when combined with other drugs

Question 15

tricyclic antidepressants, SSRIs, SNRIs

Answer 15

prevent reuptake of 5-HT from synaptic cleft → prolonging lifetime of 5-HT in synapse
= increased stimulation on postsynaptic neuron

Question 16

various opioids

Answer 16

metabolites may have direct serotonergic effects or interfere with serontonin reuptake

Question 17

St. John’s wort

Answer 17

herbal remedy
acts as serotonin reupatke inhibitor

Question 18

recreational drugs (MDMA, methamphetamine)

Answer 18

promote serotonin release by causing uptake transporters’pumps to operate in reverse
ex. ecstasy

Question 19

precursors of serotonin

Answer 19

used as anti-depressants
body is making more 5-HT → releasing more

Question 20

pharmacokinetic interactions

Answer 20

alter drug availability (absorption or distribution)

1. drugs that alter gut motility, pH → alter absorption
2. drugs that alter local blood flow → alter distribution

alter metabolism - CYP enzymes

Question 21

lidocaine

Answer 21

co-administration of lidocaine with epinephrine for local vasoconstriction
lidocaine blocks sodium channels in nerve to block pain transmission
epinephrine constricts blood vessels to prevent diffusion away
= lidocaine lasts longer at site of injection

Question 22

CYP enzymes

Answer 22

induction of CYP enzymes → increased metabolism of other drugs

CYP3A4 - common for biotransformation

expression is induced by rifampicin, anti-convulsants, glucocorticoids, etc.

Question 23

CYP3A4 and warfarin

Answer 23

CYP3A4 metabolizes warfarin
= individuals taking a drug that induces CYP3A4 will be resistant to warfarin

enhancer of CYP3A4 = higher expression → faster breakdown of warfarin = reduced effectiveness

Question 24

CYP3A4 and grapefruit juice

Answer 24

grapefruit juice inhibits CYP3A4 enzyme
high amounts of grapefruit juice→ heightened sensitivity to drugs metabolized by CYP3A4 (like warfarin)

with warfarin → high INR; prone to bleeding