Module 6

Question 1

Give examples of how drug interactions can be due to interactions at the receptor level.

Answer 1

○ There are classic examples of ß-blockers inhibiting ß-agonists used to treat asthma leading to serious adverse events.
○ Of course atropine and other drugs that have anticholinergic effects inhibit cholinergic drugs, but there are not many examples of drugs that target the cholinergic receptor.
○ However, drugs used to treat Alzheimer’s disease usually target the cholinergic neurons, and anticholinergic agents can worsen dementia.

Question 2

Give several examples of tolerance. What are some of the possible mechanisms involved in tolerance?

Answer 2

Typical mechanisms include down-regulation of receptors, induction of metabolic enzymes to eliminate drugs and toxins, immune tolerance to foreign agents that do not pose a significant threat, etc.

Question 3

There are ethnic differences in enzymes involved in drug metabolism that result in pharmacokinetic differences between ethnic groups. There are also analogous differences in receptors and other determinants in drug response that lead to ethnic differences in the “usual” pharmacodynamic response. Provide examples.

Answer 3

there is evidence that African Americans are less sensitive and East Asians are more sensitive to ß-blockers than Caucasians. Therefore, a ß-blocker would not usually be the initial treatment of choice for hypertension in an African American patient, although it is possible that it would be effective.
○ Another example of a racial difference is in genes coding for cytokines. There is a polymorphism in the gene that codes for IL-28B, and patients with the TT and TC genotypes have a lower response rate to interferon treatment of hepatitis C than those patients who carry the CC genotype.
The CC genotype is less common in people of African American origin than other populations, and therefore on average they do not respond as well to treatment of hepatitis C.
○ African Americans have a higher response to the combination of thiazide, hydralazine, and isosorbide dinitrate, and there is a formulation of this combination targeted for the treatment of hypertension in African Americans, but this is controversial.
○ In contrast, ACE inhibitors are on average less effective in African Americans.
○ Gefitinib, an EGRF inhibitor used to treat cancer, appears to be more effective in East Asian patients who have a higher incidence of EGFR mutations that are associated with a better cancer response.