Drug Interactions

Question 1

Where are Benefits and Harms of the Drug Listed?

Answer 1

CYdrug interactions are usually listed in ‘product monographs’

• information in the product monogram should inform about contraindicated conditions or possible drug indications

Question 2

Therapeutic Index/ Window

Answer 2

• drugs are more susceptible to issues with drug interactions when they have a narrow TI

if the TI is narrow:
- small changes in our responsiveness to a drug can lead to toxic outcomes
- small changes in availiability of a drug can lead to significant changes in outcome

Question 3

Antagonist Interaction

Answer 3

-type of pharmacodynamic interaction
-drug A may act as an antagonist at a receptor for drug B
- this will reduce the effectiveness of drug B
- ex. effect of Vitamin K rich foods on Warfarin

Question 4

Synergism or Additive Interactions

Answer 4

• type of pharmacodynamic interaction
• multiple agonists/modulators may act on the same receptor leading to excessive activation
  -synergism: effects that are greater than the individual effects of two drugs
• additive: effects that are roughly the sum of the individual effects of two drugs

-ex. use of benzodiazepines, alcohol, barbituates and other modulators of GABAA receptors (combination of multiple drugs at low concentrations can significantly enhance GABA mediated activation of these receptors leading to sedation, unconsciousness,etc.

Question 5

Indirect Interaction

Answer 5

-type of pharmacodynamic interaction
- the effects of multiple drugs might influence the same signalling pathway, but not necessarily the same receptor
-ex. serotonin syndrome (arising from combination of drugs that lead to overabundance of 5-HT/serotonin in the CNS and overstimulation of 5-HT receptors) - is characterized by high body temp, agitation, sweating, dilated pupils, muscle twitching, high bp, etc.

Question 6

pharmacokinetic Interaction

Answer 6

alter drug availability
- there are many possible mechanisms that affect absorption or distribution
1. drugs that alter gut motility, pH, can alter the absorption of a drug
2. drugs that alter local blood flow can alter absorption of a drug

Question 7

CYP3A4

Answer 7

-is the most common enzyme for biotransformation of drugs
-is induced/enhanced by many factors
- also metabolizes/breaks down warfarin

Question 8

give an example of a food that can inhibit specific CYP enzymes leading to increased availabity of target drugs

Answer 8

inhibition of CYP3A4 by grapefruit juice
- regular grapefruit eater/drinker will have heightened sensitivity to warfarin or other drugs that are metabolized by CYP3A4