A 60-year-old Caucasian male is diagnosed with exertional angina. His treatment regimen includes metoprolol, isosorbide dinitrate and aspirin. He takes isosorbide dinitrate early in the morning and again in the afternoon, but he does not take an evening dose. Such a pattern of drug administration is intended to decrease which of the following?

Question

A 60-year-old Caucasian male is diagnosed with exertional angina.  His treatment regimen includes metoprolol, isosorbide dinitrate and aspirin.  He takes isosorbide dinitrate early in the morning and again in the afternoon, but he does not take an evening dose.  Such a pattern of drug administration is intended to decrease which of the following?

Quizplus · Accepted Answer

Around-the-clock nitrate administration (in any form) rapidly results in development of tolerance to nitrates. This is why a nitrate-free interval must be provided every day in patients that are using daily long acting nitrates. The mechanism by which this occurs has not been fully demonstrated, but it is theorized that it is due to a decreased vascular sensitivity to nitrates and an increased sensitivity to endogenous vasoconstricting agents. Usually the nitrate-free period is timed to occur during the night when the patient is sleeping and cardiac work is the least. (Choice A) A pharmacokinetic drug interaction refers to how drugs that are used together in a patient affect the absorption and elimination of each other. An example of this is the ability of rifampin to increase the metabolism and elimination of warfarin by inducing cytochrome P-450. This is not the reason for providing a nitrate-free interval. (Choice B) Pharmacodynamic drug antagonism refers to the ability of a drug, as part of its mechanism of action, to antagonize, or prevent, the effect of another drug or endogenous substance. An example of this is the effect that labetalol has on alpha-1 and beta adrenergic receptors - it prevents the binding of catecholamines to these receptors. (Choice C) Effect potentiation refers to one drug's ability to increase the pharmacologic effect of another agent. The drugs mentioned in this question stem do not potentiate the effects of each other, and this is not the reason for providing a nitrate-free period. Beta-adrenergic blockers are often prescribed along with nitrates to prevent reflex tachycardia as well as to provide decreased cardiac work by a mechanism different from that of nitrates. (Choice E) Withdrawal symptoms occur when a patient forms a physiologic dependence on a drug or medication and that drug or medication is then discontinued. This is common in patients using alcohol, opiates, benzodiazepines, stimulants and some antidepressants. This is not the reason for providing a nitrate-free period in patients taking nitrates. (Choice F) Drug noncompliance is a problem where patients do not take the medications prescribed to them properly or at all. It is frequent among patients who do not understand their disease, can not afford medications, or simply can not remember to take them. The latter becomes much more frequent when patients are taking multiple medications with many times-per-day dosing schedules. This is also not the reason for providing a nitrate-free period every day in patients taking long-term nitrates. Educational Objective: Patients taking daily maintenance nitrates need to have a nitrate-free period every day to avoid tolerance to the drug.

A 60-Year-Old Caucasian Male Is Diagnosed with Exertional Angina