Question

GF, a 63-year-old man with a history of hypertension, diabetes, and hypercholesterolemia, begins to develop episodes of chest pain with exertion. One week after his first episode, a bout of chest pain occurs while he is mowing the lawn. Twenty minutes after the onset of his pain, GF takes two of his wife’s sublingual nitroglycerin tablets. Within a few minutes, he feels much better. GF feels so well that he decides to take one of the sildenafil (Viagra®) pills that a friend had previously offered to him. A few minutes after taking sildenafil, he feels flushed, develops a throbbing headache, and senses his heart racing. Upon standing, GF becomes light-headed and faints. He is taken immediately to the emergency department, where he is found to have severe hypotension. He is quickly placed in a supine position with his legs raised and monitored until he regains consciousness. The physician considers administering an α-adrenergic agonist, such as phenylephrine, but the rapid improvement in GF’s blood pressure after he is placed in a supine position suggests that pharmacologic intervention is unnecessary. After GF recovers, his physician discusses with him the dangers of taking medications without a prescription and, specifically, the risk of concurrent administration of organic nitrates and sildenafil.

Questions

What is the mechanism by which sublingual nitroglycerin acts so quickly to relieve chest pain? What are the common adverse effects of nitroglycerin?

How can sildenafil and organic nitrates interact to precipitate severe hypotension?

Are non-nitrate antihypertensives, such as calcium channel blockers, also contraindicated for men taking sildenafil?

How can the mechanisms of action of drugs be used to predict possible drug–drug interactions or lack of interactions?

Answer 1

1. What is the mechanism by which sublingual nitroglycerin acts so quickly to relieve chest pain?

Sublingual nitroglycerine is rapidly absorbed and metabolized to nitric oxide, which dilates systemic veins and epicardial arteries, decreasing myocardial oxygen demand and increasing myocardial oxygen supply.

2. What are the common adverse effects of nitroglycerin?

Headache

3. How can sildenafil and organic nitrates interact to precipitate severe hypotension?

Both agents promote vasodilation

4. Are non-nitrate antihypertensives, such as calcium channel blockers, also contraindicated for men taking sildenafil?

The concomitant use of sildenafil l and different classes of antihypertensive agents such as (beta-blockers, alpha-blockers, diuretics, ACE inhibitors, calcium antagonists) may lead to additive but not to potentiating blood pressure decreases.

5. How can the mechanisms of action of drugs be used to predict possible drug-drug interactions or lack of interactions?

The term drug-drug interactions refer to the influence of one drug upon another, e.g., where a second drug stimulates catabolism of the first drug, thereby reducing the efficacy of the first drug, or where a second drug inhibits catabolism of the first drug, thereby increasing its efficacy (or increasing its toxicity).

6. How can the mechanisms of action of drugs be used to predict possible drug-drug interactions or lack of interactions?

interactions can occur at the level of drug action, Examples such as the combination of verapamil, a calcium channel blocker, and a beta-blocker. Both slow the heart rate by different mechanisms, and the combination is relatively contraindicated because heart block can result. Because of this interaction, many textbooks and computer programs warn against concomitant use of any beta-blocker and any calcium channel blocker. This creates a great deal of confusion and distrust of drug interaction warnings because most health care providers know that drugs in these two classes are often employed successfully and safely in patients with hypertension.