12.02.2 Drugs to Treat an Attack of Typical Angina

The group of drugs used to treat an attack of angina are the nitrovasodilators (nitroglycerin and isosorbide dinitrate), which are used sublingually to get a quick effect (relief of attack). The nitrovasodilators mimic the effect of endogenous nitric oxide (NO). Nitric oxide stimulates guanylate cyclase, leading to increased intracellular cGMP, which promotes the relaxation of smooth muscle including vascular smooth muscle (Figure 12.2.3). The nitrovasodilators release nitric oxide, which has the same effect as the endogenous NO.

Figure 12.2.3 Nitrovasodilators (Copyright QUT, Sheila Doggrell)

Normal coronary arteries are dilated by nitrovasodilators. Diseased coronary arteries have lost their elasticity, and are difficult to dilate. Thus, nitrovasodilators only cause a small dilation of diseased coronary arteries, and this alone does not explain the benefit of nitrovasodilators in typical angina. Nitrovasodilators end an angina attack by causing venodilation (dilation of veins) (Figure 12.2.4). Venodilation leads to pooling of the blood in the veins, which reduces venous return, which (in turn) reduced the work done by the heart, and reduces the oxygen demand (Figure 12.2.4). This does not improve the function of the coronary arteries, but rather reduces the oxygen demand of the heart to level that can be met by the diseased coronary arteries.

Figure 12.2.4 Mechanism of nitrovasodilators (Copyright QUT, Sheila Doggrell)

Nitroglycerin has extensive first pass liver metabolism, which means it is not active after oral administration. Nitroglycerin is used as a sublingual tablet or spray to avoid first pass liver metabolism. The other advantage of sublingual over oral is that it is a faster way to provide the nitroglycerin to the circulation in an attack of typical angina. With sublingual/spray of nitroglycerin, the onset of action is within a minute, and the half-life (t_1/2) is about 3 minutes, and this is ideal for the treatment of typical angina. Nitroglycerin can also be used in the prevention of an attack of angina, where patches or ointment are used for the prevention of angina attacks.

Isosorbide mononitrate is a nitrate that is resistant to first pass liver metabolism. This means that it active after oral administration and has a longer half-life (3-6 hours) than nitroglycerin. Thus, after nitroglycerin has ended the attack of angina, isosorbide mononitrate can be used to prevent a further attack of angina.