Angina

=HHP621= =**Angina**=

__**Causes of Angina**__ Angina, which is sometimes called angina pectoris, is chest pain that is caused by inadequate [|**coronary blood flow**] to the myocardium. When coronary blood flow cannot deliver sufficient oxygen to support cardiac oxidative metabolism (reduced **oxygen supply/demand ratio**), the myocardium becomes [|**hypoxic**]. This triggers pain receptors within the heart, which lead to the classical presentation of chest pain and the sensation of substernal heaviness or pressure. As described below and in the above figure, coronary blood flow can be decreased by 1) transient constriction of the coronary arteries (i.e., vasospasm), 2) chronic narrowing of a coronary artery (i.e., fixed stenosis) caused by atherosclerosis, or 3) the formation of a blood clot within the vessel lumen (i.e., coronary thrombosis). Angina can also be precipitated by **increased oxygen consumption**, especially if the coronary blood flow is already compromised. Increases in heart rate, contractility (**inotropy**), [|****afterload****] (e.g., elevated arterial pressure, aortic valve stenosis, ventricular dilation), and **preload**, the latter of which stimulates the **Frank-Starling mechanism** to increase the force of cardiac contraction. Decreasing either coronary flow or increasing oxygen demand, or a combination of the two, will decrease the **oxygen supply/demand ratio** and lead to myocardial hypoxia and the stimulation of pain receptors within the myocardium.

__**Types of Angina**__ There are three types of angina: Printzmetal's variant angina, chronic stable angina, and unstable angina. All three forms are associated with a reduction in the oxygen supply/demand ratio.
 * Variant (Printzmetal's) angina** results from coronary vasospasm, which temporarily reduces coronary blood flow (i.e., produces **ischemia** by reducing oxygen supply; "**supply ischemia**"), thereby decreasing the oxygen supply/demand ratio. Enhanced sympathetic activity (e.g., during emotional stress), especially when coupled with a dysfunctional coronary vascular endothelium (i.e., reduced endothelial production of the vasodilators **nitric oxide** and **prostacyclin**) can precipitate vasospastic angina.
 * Chronic stable angina** is caused by a chronic narrowing of coronary arteries due to atherosclerosis. When a coronary artery is narrowed beyond a critical value (**critical stenosis**), the myocardial tissue perfused by the artery will not receive adequate blood flow (i.e., the tissue becomes ischemic and hypoxic), particularly during times of increased oxygen demand (e.g., during physical exertion). The relative ischemia occurs when the oxygen demand increases, so this is referred to as "demand ischemia." This will lead to anginal pain during physical exertion. The pain usually is associated with a predictable threshold of physical activity. Other conditions that cause myocardial oxygen demand to increase, such as a large meal or emotional stress, can also precipitate pain.
 * Unstable angina** is caused by transient formation and dissolution of a blood clot (thrombosis) within a coronary artery. The clots often form in response to plaque rupture in atherosclerotic coronary arteries; however, the clot may also form because diseased coronary artery endothelium is unable to produce nitric oxide and prostacyclin that inhibit platelet aggregation and clot formation. When the clot forms, coronary flow is reduced, leading to a reduction in the oxygen supply/demand ratio ("**supply ischemia**"). If the clot completely occludes the coronary artery for a sufficient period of time, the myocardium supplied by the vessel may become infarcted (**acute myocardial infarction**) and become irreversibly damaged.

__**Therapeutic Use and Rationale**__ **Angina** results from a reduction in the [|oxygen supply/demand ratio]. Therefore, in order to alleviate the pain, it is necessary to improve this ratio. This can be done either by increasing blood flow (which increases oxygen delivery or supply), or by decreasing **oxygen demand** (i.e., by decreasing myocardial oxygen consumption). Pharmacologic interventions that block coronary vasospasm (coronary vasodilators) or inhibit clot formation are used to treat **variant and unstable angina**, respectively. These drugs act by increasing coronary blood flow and oxygen supply, or by preventing vasospasm and clot formation, and associated decreases in blood flow. Drugs that reduce myocardial oxygen demand are also given to patients with these two forms of angina to reduce oxygen demand and thereby help to alleviate the pain. Drugs that reduce myocardial oxygen demand are commonly used to prevent and treat episodes of ischemic pain associated with fixed stenotic lesions (i.e., **chronic stable angina**). Some of these drugs reduce oxygen demand by decreasing heart rate (decreased chronotropy) and contractility (decreased [|inotropy]), while other drugs reduce [|afterload] and or [|preload] on the heart. Afterload and preload reducing drugs act by dilating peripheral arteries and veins. Direct vasodilation of the coronary arteries is ineffective as a therapeutic approach and may actually worsen the ischemia by producing [|coronary vascular steal]
 * Antianginal Drugs**

__**Classes of Drugs Used to Treat Angina**__ Classes of drugs used in the treatment of angina and myocardial infarction are given below. Clicking on the drug class will link you to the page describing the pharmacology of that drug class. > - calcium-channel blockers > - beta-blockers > > - anticoagulants > - anti-platelet drugs >
 * **Vasodilators** (dilate arteries and veins)
 * - nitrodilators
 * Cardioinhibitory drugs (reduce heart rate and contractility)
 * - calcium-channel blockers
 * Anti-thrombotic drugs (prevent thrombus formation)