What Is an Antianginal?

Antianginal drugs mainly reduce myocardial oxygen consumption by dilating blood vessels, slowing heart rate, and reducing left ventricular end-diastolic volume; by expanding coronary arteries, promoting collateral circulation, opening and promoting blood redistribution, and increasing myocardial oxygen supply; by promoting Lipid metabolism is transformed into glucose metabolism to improve myocardial metabolism and inhibit platelet aggregation and thrombosis. Commonly used drugs are nitrates, beta receptor blockers, calcium channel blockers, antiplatelet drugs, and angiotensin I converting enzyme inhibitors.

Including nitrates, beta blockers, calcium antagonists:

Antianginal drugs nitrates

Nitroglycerin (nitroglycerin) is a representative drug of nitrates, because it has the advantages of fast onset, affirmative effect, convenient use, economy, etc., it is the most commonly used drug for the prevention and treatment of angina pectoris. Nitroglycerin is orally affected by the effects of the first pass, etc., and the bioavailability is only 8%. Therefore, it is clinically administered topically under the tongue or ointment (ointment or film).

Pharmacological effects of antianginal drugs

The basic effect of nitroglycerin is to relax smooth muscle, but the selectivity to different tissues and organs is different, so that it has the most significant effect on vascular smooth muscle. Because nitroglycerin expands the systemic and coronary vessels, it has the following effects:

Reduce myocardial oxygen consumption. A small dose of nitroglycerin can significantly dilate venous blood vessels, reduce returning blood volume, reduce intraventricular pressure, reduce ventricular wall tension, shorten ejection time, and reduce myocardial oxygen consumption. A slightly larger dose can also significantly relax arterial blood vessels, reduce the ejection resistance of the heart, thereby reducing left ventricular pressure and ventricular wall tension, and reducing myocardial oxygen consumption;

Dilate the coronary arteries and increase blood perfusion in the ischemic area;

Reduce left ventricular filling pressure, increase endocardial blood supply, and improve left ventricular compliance;

Protect ischemic cardiomyocytes and reduce ischemic injury.

Mechanism of antianginal drugs

Nitroglycerin relaxes smooth muscle through the same mechanism of action as endothelium derived relaxing factor (EDRF, NO) without relying on vascular endothelial cells. Therefore, blood vessels with lesions in the endothelium can still play a role. . Nitroglycerol releases NO in the smooth muscle cells through the catalysis of glutathione transferase. The combination of NO with Fe2 + in the active center of soluble guanylate cyclase can activate guanylate cyclase, increase the content of cGMP in cells, and then activate cGMP-dependent protein kinase, reducing intracellular Ca2 + release and external Ca2 + influx. Decreased intracellular Ca2 + dephosphorylates myosin light chains and relaxes vascular smooth muscle. Nitroglycerin is also involved in the vasodilator effect of PGI2 and cell membrane hyperpolarization. In addition, nitroglycerin inhibits platelet aggregation and adhesion by producing NO, which is also beneficial to the treatment of coronary heart disease.

Clinical application of antianginal drugs

Sublingual nitroglycerin can quickly relieve various types of angina. Medications can also prevent attacks before they are expected to occur. For patients with acute myocardial infarction, multi-venous administration can not only reduce myocardial oxygen consumption, increase blood supply to the ischemic area, but also inhibit platelet aggregation and adhesion, thereby reducing the scope of infarction. In addition, because nitroglycerin can reduce the pre- and post-load of the heart, it can also be used for the treatment of heart failure. It can also relax pulmonary blood vessels, reduce pulmonary blood vessel resistance, improve pulmonary ventilation, and is used for patients with acute respiratory failure and pulmonary hypertension.

Precautions for antianginal medicine

Most of the adverse reactions are caused by its vasodilating effect, such as flushing of the skin on the cheeks, pulsatile headache, and elevated intraocular pressure. Large doses can occur with orthostatic hypotension and syncope. Excessive dose can reduce blood pressure excessively, coronary artery perfusion pressure is too low, and can reflexively excite sympathetic nerves, increase heart rate, strengthen myocardial contractility, but can increase oxygen consumption and aggravate angina. Overdose also causes methemoglobinemia, manifested as vomiting, cyanosis and so on.
Nitroglycerin can be tolerated for about 2 weeks of continuous application. The dose size, frequency of administration, route of administration, and dosage form all affect the development of drug resistance. Large doses or frequent repeated application easily lead to tolerance. Cross-tolerance between different types of nitrates, tolerance after 1 to 2 weeks of withdrawal
Similar drugs include isosorbide dinitrate and isosorbide mononitrate. Their effects and mechanisms are similar to nitroglycerin, but the effect is weaker, the action is slower, and the effect is longer. It is mainly used orally for the prevention of angina pectoris and long-term treatment of heart failure after myocardial infarction.

Antiangina pectoris beta receptor antagonist

-adrenergic receptor antagonists can reduce the number of angina pectoris attacks, improve ischemic electrocardiogram, increase patient exercise tolerance, reduce myocardial oxygen consumption, improve ischemic area metabolism, and reduce the scope of myocardial infarction. Has been used as a first-line treatment of angina pectoris.

Antianginal effect

1. Beta-receptor antagonists that reduce myocardial oxygen consumption can reduce myocardial oxygen consumption by antagonizing beta receptors and weakening myocardial contractility, slowing down myocardial fiber shortening, slowing heart rate, and lowering blood pressure. However, its inhibition of myocardial contractility can increase ventricular volume and prolong ventricular ejection time, leading to increased myocardial oxygen consumption, but the overall effect is still to reduce myocardial oxygen consumption.

2. Improving the blockade of -receptors in the coronary ischemic region of the myocardial ischemia, the increase in blood vessel tension between the non-ischemic and ischemic regions promotes blood flow to the compensated dilated ischemic region, thereby increasing blood flow in the ischemic region. Secondly, because the heart rate is slowed, the diastolic period is relatively extended, which is conducive to the flow of blood from the epicardial blood vessels to the ischemic endocardium. In addition, it can also increase the collateral circulation in the ischemic area and increase the blood perfusion in the ischemic area.

In addition, this class of drugs can inhibit the activity of lipolytic enzymes and reduce the content of free fatty acids in the myocardium due to antagonistic beta receptors; improve the uptake and utilization of glucose in the ischemic region of the myocardium, improve glucose metabolism and reduce oxygen consumption; Dissociation increases tissue oxygenation.

Clinical application of antianginal drugs

Beta-receptor antagonists are stable angina pectoris that is insensitive to nitrates or has poor curative effects, which can reduce the number of attacks. It is especially suitable for those with arrhythmia and hypertension. Long-term use of beta-blockers can shorten the ischemic time in patients with asymptomatic angina pectoris with only ischaemic ECG changes. Beta-blockers can also reduce the incidence and mortality of angina pectoris in patients with myocardial infarction.

Coronary spasm-induced variant angina pectoris should not be used. It is also effective for myocardial infarction and can reduce the scope of the infarct area, but it should be used with caution because it inhibits myocardial contractility. -receptor antagonists and nitrates are used in combination, and drugs with a similar action time should be used. Generally, propranolol and isosorbide nitrate are used in combination. Beta-receptor antagonists can counteract the accelerated reflex heart rate and increase myocardial contractility caused by nitrates. Nitrate can reduce the increase of ventricular volume and prolonged ventricular ejection time caused by beta-receptor antagonists. Synergistically reduce oxygen consumption, reduce dosage, and reduce side effects.

-receptor antagonists are generally suitable for oral administration. Due to large individual differences in dosage, the dosage should be gradually increased from a small amount. -receptor antagonists should be gradually reduced when discontinued, such as sudden discontinuation can lead to increased angina and / or induce myocardial infarction. It should not be applied to patients with cardiac insufficiency, bronchial asthma, past history of asthma and bradycardia. It also affects blood lipids after long-term application. This class of drugs is contraindicated in patients with dyslipidemia.

Angina pectoris calcium antagonist

Calcium channel blockers are commonly used drugs for the prevention and treatment of angina pectoris, especially for angina pectoris.

Antianginal effect

1. Calcium channel blockers that reduce myocardial oxygen consumption can reduce myocardial contractility, slow heart rate, relax vascular smooth muscle, reduce blood pressure, and reduce heart load, thereby reducing myocardial oxygen consumption.
2. Diastolic coronary vessels This class of drugs has a dilating effect on the larger transport vessels and small resistance vessels in the coronary arteries, especially on the vessels that are in a spasm state, which has a significant anti-spasm effect, thereby increasing blood perfusion in the ischemic area. It can also increase collateral circulation and improve blood and oxygen supply in the ischemic area.
3 Ca2 + channel blockers that protect ischemic cardiomyocytes protect myocardial cells by inhibiting external calcium influx and reducing the Ca2 + overload of ischemic cardiomyocytes. It can reduce the scope of infarction in patients with acute myocardial infarction.
4 Inhibition of platelet aggregation unstable angina pectoris is related to platelet adhesion and aggregation, and reduced coronary blood flow. Most acute myocardial infarctions are also caused by ruptured atherosclerotic plaques and localized thrombus formation that suddenly blocks coronary arteries. Calcium channel blockers block Ca2 + influx, reduce Ca2 + concentration in platelets, and inhibit platelet aggregation.

It has been reported that calcium channel blockers also promote the production and release of endogenous NO by vascular endothelial cells.

Clinical application of antianginal drugs

Calcium channel blockers have the following advantages in treating angina:

Calcium channel blockers have a strong role in expanding coronary arteries, and variant angina pectoris is the best indication;
Calcium channel blockers are more suitable for patients with myocardial ischemia and bronchial asthma because of their role in relaxing bronchial smooth muscle;
Calcium channel blockers have a weaker effect on inhibiting myocardium, especially nifedipine also has a stronger function of expanding peripheral blood vessels, reducing peripheral resistance, and strengthening myocardial contractility after reflex, which can partially offset the inhibitory effect on myocardium. Thus less induce heart failure;
-receptor antagonists are contraindicated in patients with myocardial ischemia and peripheral vasospasm disease, and calcium channel blockers are suitable for the treatment of such patients due to the expansion of peripheral blood vessels. Commonly used calcium channel blockers for antiangina pectoris include nifedipine, verapamil, diltiazem zhuo, perhexiline, and piramide. Because calcium channel blockers have a significant effect on relieving coronary spasm, they have a significant effect on variant angina pectoris and are also effective on stable angina pectoris and acute myocardial infarction.

Calcium channel blockers and -receptor antagonists are used in combination, especially nifedipine and -receptor antagonists are safer. The combination of the two can play a synergistic role in reducing myocardial oxygen consumption. -receptor antagonists can eliminate Reflex tachycardia caused by calcium channel blockers, the latter of which can counteract the vasoconstrictive effect of the former. Clinically proven to be most suitable for angina pectoris with hypertension and significantly increased heart rate during exercise.

Antianginal Pills Other Drugs

Carvedilol 1, 2, and receptor blockers have certain antioxidant effects, so they can be used for the treatment of angina pectoris, cardiac insufficiency, and hypertension.
Modol (molsidomine) metabolites act as donors of NO, releasing NO, and acting similarly to nitrates. Sublingual administration or spray inhalation is more effective for patients with stable angina pectoris or myocardial infarction with high filling pressure.
Nicorandil is a K + channel activator, which both activates K + channels of vascular smooth muscle cell membranes, promotes K + outflow, hyperpolarizes the cell membrane, inhibits Ca2 + influx, and releases NO to increase cGMP production in vascular smooth muscle cells. Role. It can dilate coronary blood vessels and reduce the damage of Ca2 + overload on ischemic cardiomyocytes. It is mainly suitable for variant angina pectoris and chronic stable angina pectoris, and it is not easy to produce tolerance. Similar drugs include pinacidil and cromakalim. ^[1]