10.03.3 Nitric Oxide and Angina

Nitric oxide (NO) is a neurotransmitter and a local chemical mediator. As a local chemical mediator, NO relaxes blood vessels. There are a group of drugs that mimic NO by releasing NO, and the group is known as nitrovasodilators. Examples of nitrovasodilators are nitroglycerin and isosorbide-5-mononitrate. Nitrovasodilators release NO, which relaxes blood vessels, and is useful in the treatment and prevention of angina, which is due to diseased coronary arteries. As diseased coronary arteries are difficult to dilate, nitrovasodilators have little effect on diseased coronary arteries. Nitrovasodilators end an angina attack by causing venodilation, and reducing the workload on the heart, and this will be discussed further under Systematic Pharmacology.

As discussed previously (eChapter 1), nitroglycerin undergoes extensive first pass liver metabolism, and cannot be used orally. Rather, nitroglycerin is used as a sublingual tablet or spray (faster) in an attack of angina, and starts to work within a minute, but is only effective for a short time as has a t_1/2 of about 3 minutes. For a longer effect, and to prevent an anginal attack, nitroglycerin patches or ointment are used.

Isosorbide-5-mononitrate is the only nitrate developed to date, that has no significant first pass liver metabolism, and can be used orally. Isosorbide-5-mononitrate is used orally to prevent an angina attack.