Vasodilators & the Treatment of Angina Pectoris
heart disease is one of the most common cardiovascular disease in developed countries,
and angina pectoris is the most common condition involving tissue ischemia in
which vasodilator drugs are used. The name angina
pectoris denotes chest pain caused by accumulation of metabolites resulting
from myocardial ischemia. The organic nitrates, eg, nitroglycerin, are the mainstay of therapy for the immediate relief
of angina. Another group of vasodilators, the calcium channel blockers, is also important, especially for
prophylaxis, and βblockers, which are not
vasodila-tors, are also useful in prophylaxis. Several newer groups of drugs
are under investigation, including drugs that alter myocardial metabolism and
selective cardiac rate inhibitors.
By far the most common cause of angina is atheromatous obstruction of the large coronary vessels (coronary artery disease, CAD). Inadequate blood flow in the presence of CAD results in effort angina, also known as classic angina.However, transientspasm of localized portions of these vessels, which is usually associ-ated with underlying atheromas, can also cause significant myo-cardial ischemia and pain (vasospastic or variant angina). Variant angina is also called Prinzmetal angina. The primary cause of angina pectoris is an imbalance between the oxygen requirement of the heart and the oxygen supplied to it via the coronary vessels. In effort angina, the imbalance occurs when the myocardial oxygen requirement increases, especially during exercise, and coronary blood flow does not increase pro-portionately. The resulting ischemia usually leads to pain. In fact, coronary flow reserve is frequently impaired in such patients because of endothelial dysfunction, which is associated with impaired vasodilation. As a result, ischemia may occur at a lower level of myocardial oxygen demand. In some individuals, the isch-emia is not always accompanied by pain, resulting in “silent” or “ambulatory” ischemia. In variant angina, oxygen delivery decreases as a result of reversible coronary vasospasm.
Unstable angina, an acute coronary syndrome, is said to be pres-ent when episodes of angina occur at rest and when there is an increase in the severity, frequency, and duration of chest pain in patients with previously stable angina. Unstable angina is caused by episodes of increased epicardial coronary artery resistance or small platelet clots occurring in the vicinity of an atherosclerotic plaque. In most cases, formation of labile partially occlusive thrombi at the site of a fissured or ulcerated plaque is the mechanism for reduction in flow. The course and the prognosis of unstable angina are variable, but this subset of acute coronary syndrome is associated with a high risk of myocardial infarction and death and is considered a medical emergency.
In theory, the imbalance between oxygen delivery and myocar-dial oxygen demand can be corrected by decreasing oxygendemand or by increasing delivery (by increasing coronary flow).In effort angina, oxygen demand can be reduced by decreasing cardiac work or, according to some studies, by shifting myocardial metabolism to substrates that require less oxygen per unit of ade-nosine triphosphate (ATP) produced. In variant angina, on the other hand, spasm of coronary vessels can be reversed by nitrate or calcium channel-blocking vasodilators. Lipid-lowering drugs, especially the “statins,” have become extremely important in the long-term treatment of atherosclerotic disease . In unstable angina, vigorous measures are taken to achieve both— increase oxygen delivery and decrease oxygen demand.
A 74-year-old man presents with a history of anterior chest pressure whenever he walks more than one block. The chest discomfort is diffuse, and he cannot localize it; sometimes it radiates to his lower jaw. The discomfort is more severe when he walks after meals but is relieved within 5–10 minutes when he stops walking. Assuming that a diagnosis of stable effort angina is correct, what medical treatments should be implemented to reduce the acute pain of an attack and to prevent future attacks?
CASE STUDY ANSWER
The case described is typical of stable atherosclerotic angina. Treatment of acute episodes should include sublingual tab-lets or sprayed nitroglycerin, 0.4–0.6 mg. Relief of discom-fort within 2–4 minutes can be expected. If anginal episodes are frequent, or to prevent episodes of angina, a β blocker such as metoprolol should be tried first. If contraindications to the use of a β blocker are present, a medium- to long-acting calcium channel blocker such as verapamil, diltiazem, or amlodipine is likely to be effective.