2. Increase coronary blood flow and improve oxygenation of the myocardium can be achieved by expansion of the coronary vessels. This is usually the result of direct exposure to substances on vascular smooth muscle. In particular, this type of action are characterized by means of oppressing current of calcium ions into the muscle cells we have ¬ (verapamil). Furthermore, antianginal agents may in to the accumulation in the myocardium endogenous substances (e.g., adenosine). According to this principle operates dipyridamole. However, the known drugs that eliminate the reflex spasm of the coronary vessels (validol). Draws attention to the possibility of eliminating coronary spasm of blood vessels due to the oppression koronarosuzhivayuschih reflexes (central WIDE links such reflections block nitroglycerin, morphine). One of the most important factors governmental increasing coronary blood flow is the reduction in diastolic ventricular wall stress (decrease extravasal compression vessel disease). Vasodilatation of the heart may also be secondary associated with changes in metabolic processes. It is shown that the coronary vessels expand with an increase in myocardial oxygen demand, which is observed with the introduction of aminophylline. Strengthening of collateral blood circulation in the heart of is also one of the very desirable effects of drugs used for angina.

3. Based on these principles, there is the following classification of antianginal agents: 1. Decreasing the myocardial oxygen demand and increasing oxygen delivery to the myocardium: A. Organic nitrates - nitroglycerin, sustak, trinitrolong, nitrong, Erin, nitrosorbid, isosorbide mononitrate B. Means calcium channel blocking L-type - nifedipine, verapamil V. Activators of potassium channels - pinacidil, nicorandil G. Different tools - amiodarone 2. Decreasing the myocardial oxygen demand: A. β-blockers - propranolol, talinolol, metoprolol B. bradycardic agents - alinidin, falipamil 3. Tools that increase oxygen delivery to the myocardium: A. koronarorasshiryayuschego means myotropic action - dipyridamole B. Means of reflex action, eliminating coronary spasm - validol

4. Pharmacotherapy of angina is complex. In this disease, the following groups of drugs: - Means normalizing the disturbed balance between the need of the heart for oxygen and its delivery; - Cardioprotective agents; - Means of preventing thrombosis; - Lipid-lowering agents; - Psychotropic drugs. Decreasing the myocardial oxygen demand and improve its blood supply This means a group comprising organic nitrates, calcium channel blockers, potassium channel activators and amiodarone. a) organic nitrates Among the agents for the treatment of angina include various preparations containing nitroglycerin.

5. Nitroglycerin is representative of nitrate (and nitric acid ester of glycerol). The mechanism of its therapeutic action of a number of components. Long believed that the basis of its action is an increase in coronary blood flow due to direct myotropic koronarorasshiryayuschego action. However, cannulation of the coronary sinus in patients with angina showed that the administration of sublingual nitroglycerin almost does not increase coronary blood flow, although large vessels and expanded. However, nitroglycerin, injected directly into the left coronary artery, many patients increased blood flow in the coronary sinus, but did not eliminate angina caused by stress. Subsequent administration of nitroglycerin in the vein gave the desired effect. These data suggest that the antianginal effect of nitroglycerin is strongly associated with noncardiac his influence. The main reason for removing an angina attack is to reduce venous nitroglycerin, as well as blood pressure and venous return, respectively, reducing the resistance to blood flow and ultimately lowering the pre-and afterload. In turn, this leads to a reduction of the heart and its oxygen requirements. Under these conditions, the current level of blood flow and oxygenation is quite adequate and the state hypoxia persists. According to the sensitivity of blood vessels to nitroglycerin they are in the following order: the veins> arteries> arterioles and capillaries WIDE sphincters. With respect to the mechanism of relaxation of vascular smooth muscle by shown that nitroglycerin acts as an endothelial relaxing factor (N0). In the body of nitroglycerin (and other nitrates) released nitric oxide, which are formed from S-nitrosothiols. These compounds activate cytosolic soluble guanylate cyclase. The latter causes reduction content of free cytosolic Ca2 +. All this leads to the relaxation of vascular smooth muscle.

6. It is important that nitroglycerin improves blood flow to the ischemic myocardium teaching. This is due to several effects. Thus, the decrease in diastolic ventricular wall stress improves blood flow to parts of subendocardial infarction. The positive role played already marked the expansion of large coronary vessels. Especially beneficial importance for their expansion on the site of occlusion. In addition, it was found that nitroglycerin improves collateral circulation, and blocks the central WIDE links reflexes that cause narrowing of the coronary vessels. Nitroglycerin also expands blood vessels of the brain, internal organs, retina. As myotropic antispasmodic action, it reduces the tonus of smooth muscle organs (gastrointestinal tract, bronchioles, etc.). Of the adverse effects it can cause reflex tachycardia (compensatory response associated with a fall in blood pressure), head pain, and dizziness. These effects are particularly pronounced after the first for quantities of the drug. The intensity of headache subsequently decreases and it is no longer occur. However, the ability to eliminate the effects of angina persists. In the application of nitroglycerin, especially if it's overdose perhaps excessive reduction of blood pressure up to the collapse. Getting used to nitroglycerin arises only in the event of an extended continuous use (for example, intravenous infusion of addiction develops within 24 hours). For occasional use of the drug is not IME a practical value.

7. Fast and short-acting nitroglycerin is used for the relief of angina attacks have emerged. It is usually administered sublingual tablets or capsules (containing an oil solution of the past nitroglycerin; dental capsule to be crushed), or as an alcoholic solution (1-2 drops on a piece of sugar). Nitroglycerin is rapidly absorbed (the action starts his 2-3 min) and eliminates (suppresses) angina. There is also a formulation for intravenous administration of nitroglycerin, which is used for emergency indications the ineffectiveness of other drugs (as well as in myocardial infarction). Furthermore, available nitroglycerin sprays for inhalation. To prevent strokes used drugs nitroglycerin width of prolonged action. Created special microencapsulated and his other dosage forms that provide a gradual absorption. One such drug is sustak - nitroglycerin slowly dissolving tablet which is taken orally. The action begins after 10-15 minutes and lasts for a few hours (about 4 hours). Side effects are less pronounced than when nitroglycerin. Analogical for the duration of action (3-4 h) is trinitrolong. It is applied in the form of a polymer plate on the gum. More nitrong prolonged effect (7-8 hr). Take it into tablets. Long-term effect has 2% nitroglycerin ointment. The effect occurs in 15-30 minutes and lasts up to 5 hours Isafavor as nitroglycerin patches. It should be borne in mind that the application of plasteal with nitroglycerin, ensuring a constant supply of the drug in the organism, addiction develops quickly - for 8-24 h, thus leaving a patch are not more than 12 hours (usually 8 - 10 hours), and then make an interval of 12 hours is ensured preservation efficiency nitrogli cerinum in said dosage form. Addictive, as well as for drug dence may occur in the military and employees of pharmaceutical companies working with nitroglycerin.

8. For long-acting nitrates relation also nitrosorbid (isosorbide dinitrate), Erin (pentaerythrytyl tetranitrate, nitropenton), and isosorbide mono-nitrate (monocinque). Their efficiency is somewhat less than the depot formulations of nitroglycerin. If ingestion occurs after about 30 minutes and lasts 1-4 hours drugs bind to plasma proteins. Side-effects are similar to those of nitroglitseri ni over, but less pronounced. Subject to dyspeptic symptoms. With prolonged use there is addictive. Observed cross- pref circuiting to nitrates. b) Funds blocking calcium channels (calcium antagonists) To the calcium channel blockers of L-type, used for angina include nifedipine (fenigidin), verapamil, diltiazem, amlodipine (normodipin) and other drugs. The basic principle of action is that they disturb the penetration of calcium ions from the extracellular space into the muscle cells of the heart and blood vessels through the slow calcium channels (L-Ch). The effectiveness of these agents (e.g., verapamil) with angina due to the fact that they reduce the heart and coronary blood vessels extend, i.e. reducing the oxygen demand of the heart while improving its delivery.

9. Minimal entry of calcium ions into myocardial cells reduces energy phosphate bonds to mechanical work of the heart. The force of heart contractions and decreased heart function. Accordingly, reduced oxygen demand of the heart. Reducing heart work is also connected with the extension of the peripheral arteries and lowering blood pressure (down resistance of blood flow and consequently decreases the afterload on the heart). Heart rate under the influence of calcium channel blockers alter ambiguous. This is due to the fact that the latter have a direct negative chronotropic effect on the heart, which to some extent offset by any reflex tachycardia that occurs in response to the hypotensive effect of drugs. Antianginal effect of calcium channel blockers expressed also provided increased coronary vessels (resulting in reduction of calcium ion influx into vascular smooth muscle) that enhances delivery of oxygen to the heart. Calcium channel blockers improve subendocardial flow and possibly increasing the collateral circulation. Nifedipine (fenigidin, Justice, korinfar) causes marked expansion of the coronary blood vessels, lowers blood pressure. At the heart has a slight negative inotropic effect, but it is compensated reflex tachycardia and therefore not shown. As a result, the basis for the anti-anginal effect of nifedipine is the expansion of the coronary vessels. The main use of the drug - treatment of angina India, as well as hypertension. Antiarrhythmic activity of nifedipine and expressed little interest in practice is not. The drug is well absorbed from the gastrointestinal tract. The effect is 15-20 minutes, reaching a maximum after 1-2 hours and lasts 6-8 hours Approximately 90% of the drug binds to plasma proteins. Excreted by the kidneys. Apply it in and sublingual. Side effects: headache, reflex tachycardia, edema, sometimes skin rashes, fever.

10. In regulation of the cardiovascular system are of great importance not only calcium L-type channels, but transient T-type channels. The latter are the voltage dependent calcium channels. At the heart of them are located in the sinoatrial and atrioventricular nodes, as well as in Purkinje fibers. Calcium T-type channels play a role in activation sinus pacemaker, i.e. generating a heartbeat. Furthermore, they are important for the regulation of the conductivity in the atrio-ventricular node. In the contractile ventricular myocardium T-channels is almost defined and it does not significantly affect its function. In this case, the main role played by L-channels. In vessels calcium channels are L-or T-type, the activation of which enhances entry of calcium ions into smooth muscle cells, which leads to their reduction. Calcium T-type channels are also found in the thalamus in various secretory cells and other tissues. It was possible to create a drug (mibefradil), mainly blocking calcium T- channels (especially the blood vessels). Sensitivity to L-channels 20-30 times smaller than T channels. The main effects of the drug - governmental extension of coronary and peripheral vessels. From this follow two indications for its application NIJ - as antianginal and antihypertensive agent. However, the practically use of the drug was stopped, as it raises a number of serious side effects. However, a further search for effective and safe blockers of calcium T-channels is of great interest.

11. c) potassium channel activators Drugs in this group (pinacidil, nicorandil, etc.) open potassium channels. In this case, the smooth muscle cells of the ions, which leads to hyperpolarization. Against this background, voltage-calcium channels are opened and thus the intracellular content of calcium ions decreases. As a result of vascular smooth muscle tone is reduced. One of the first drugs of this group is pinacidil. It causes dilation of coronary and peripheral vascular disease. Reduces afterload. Increases the heart rate. Content decreases in plasma cholesterol and triglycerides. The frequency of side effects significantlying that limits the application of pinacidil monotherapy. Of the adverse effects observed swelling, headache, palpitations, tachycardia, hypertrichosis, etc. Sometimes the shape is indicated for vasospastic angina and heart failure. Significant anti-anginal efficacy of the nicorandil. It activates potassium channel, and moreover, is a donor N0 (nitratopodobnoe action). Dilates coronary vessels. Lowers the tone of the arteries and veins, thereby reducing post-and preload on the heart. Increases the frequency of cardiac cuts. It is used for stable and vasospastic angina India, with arterial hypertension. Of the side effects may be pro-arrhythmic effect, headache (often), dizziness, palpitations, dyspepsia, etc. It is suggested in the presence of potassium channel activators cardioprotective action. d) Various means have antianginal activity Amiodarone is used as an anti-anginal and anti-arrhythmic agent.

12. Decreasing the myocardial oxygen demand a) β-blockers The main representatives of this group are β-blockers. Antianginal effect was primarily due to their block β-adrenergic receptors of the heart and the elimination of adrenergic influences. This is a decrease in the frequency and strength of heart contractions. After the heart is reduced, and therefore the drops of myocardial oxygen demand. The hypotensive effect of β-blockers also promotes unloading of the heart. Coronary blood flow does not improve and may even several to deteriorate. Thus arose in angina imbalance between the demand for oxygen and its delivery is eliminated by reducing myocardial oxygen demand. Pharmacotherapeutic specific importance is the effect of β- blockers on the central nervous system, manifesting itself in the form of an anxiolytic effect. For the treatment of angina pectoris using β-blockers indiscriminate (Inderal) and β1- adrenergic blockers (talinolol, metoprolol, atenolol). Highly desirable combination of β-blockers with nitrates, as it eliminates a number of adverse effects of drugs of each group. b) bradicapdic drugs A new class of antianginal agents are the so-called bradikapdic drugs. Their distinctive feature is that, in certain doses, they significantly reduce the heart rate (and thus oxygen demand of the heart) with virtually no impact on other indicators of cardiac and hemodynamic parameters. Bradycardia associated with a direct inhibitory effect of substances on the automatism of the sinus node (slow phase 4). Contractile activity of the heart is not changed. This group includes drugs that dilate the coronary vessels or eliminating coronary spasm. Their mechanisms of action are different. They may be related to a direct effect on vascular smooth muscle is mediated via either humoral or neurogenic effect.

13. It should be noted that dipyridamole has an inhibitory effect on platelet aggregation, which has a positive effect on the microcirculation in the myocardium. Use the drug for angina without signs of atherosclerosis of the coronary vessels. Occlusion of the coronary branch atheromatous plaque dipyridamole does not improve oxygen delivery to the ischemic zone, but may even worsen its blood supply. This is due to the fact that in the ischemic myocardium small coronary vessels are maximally dilated (compensatory reactions to hypoxia). If you enter dipyridamole, will dilation of arterioles and collaterals in the unchanged portion of the myocardium and this further reduces the flow of blood and oxygen to the ischemic area (a so-called "steal syndrome"). Given this characteristic action dipiridamole, it is sometimes used to detect latent coronary insufficiency. In general, dipyridamole has a low antianginal activity. Take it inside. Of the side effects observed dyspepsia, headache, and hypotension. b) Due to the reflex action that address coronary spasm Such preparation is validol. It is a 25-30% solution of menthol menthyl ester of isovaleric acid. Efficiency Walid low as antianginal agents. The drug is prescribed for the relief of angina at the first attack, and in light of its forms. A few drops on a piece of validol sugar pill or capsule formulations is placed under the tongue (to complete resorption). Irritating the mucous hull of the mouth, he reflexively improves coronary blood flow. If after 2-3 minutes the pain persists, it can be assumed that validol not valid and must be replaced nitroglycerin.

14. Cardioprotective drugs A promising direction in the treatment of coronary heart disease is the creation of cardioprotective medications that increase the stability of cardiomyocytes to ischemia. One of the drugs in this group is the trimetazidine (preduktal), which provides a direct effect on cardiac myocytes in the ischemic and normalizing their energy balance. Importantly, it cardiotrop action at the cellular level is not accompanied by any effect on systemic hemodynamics. The drug prevents ischemia occurs when a reduction of ATP in cardiomyocytes. This keeps the energy resources of the cells, normalizes the function of ion channels and ion kinetics, respectively. On the basis of experimental data suggests that one of the mechanisms cardioprotective action of trimetazidine is its inhibitory effect on the long-chain isoform of the enzyme 3-ketoacyl CoA thiolase, resulting in suppressed the oxidation of fatty acids. Against this background, the oxidation of glucose goat is activated, which has a beneficial effect on myocardial function. Over the past few years, a new dosage form of trimetazidine (preduktal MW), characterized by a long duration of action, and providing a stable concentration of the substance during the day. The latter would favorably affect its antiischemic efficiency. The usual drug administered 3 times a day, preduktal MB - 2 times, which is much more convenient. The drug is rapidly and almost completely absorbed from the digestive trackt. Approximately half of the dose is metabolized in the liver. E protein C plasma binds slightly (about 1%). Displayed trimetazidine and its metabolites in the kidneys.

15. The drug is well tolerated and virtually no side effects. Clinical studies TMZ angina, coronary artery bypass operations and other states show the feasibility of its use in myocardial ischemia alone or in combination with other antianginal agents. OTHER FUNDS USED TO treat angina Note that in the treatment of angina, among the above drugs are used substances from other pharmacological groups with different mechanism of action. For example, in this condition for a broad received the funds, preventing thrombosis. These include antiplatelet agents (acetylsalicylic acid, ticlopidine, abciximab, eptifibatide, etc.) and anticoagulants (heparin). An important role is also played by lipid-lowering agents (statins) that inhibit the development of atherosclerosis in the coronary and other vessels. Given that the majority of patients with coronary insufficiency observed more or less marked psychoneurotic disorders, in many cases it is advisable the appointment of psychotropic drugs (antidepressants, anxiolytics). Medicines used in myocardial infarction In myocardial infarction, especially if it is complicated by cardiogenic shock, use a range of therapeutic agents. Thus, to eliminate pain with opioid analgesics (fentanyl, morphine, promedol), and means for nitrous oxide anesthesia. Good anesthetic effect is neuroleptanalgesia (Talamonal). Due to the fact that the myocardial infarction is usually When spasm of arterioles and tissue ischemia may be useful α-blockers (phentolamine, chlorpromazine in small doses). For the prevention of thrombosis appropriate use of anticoagulants (heparin, etc.) and antiplatelet agents. In the presence of fresh thrombus administered fibrinolytic agents (eg, streptokinase). using a variety of symptomatic agents, proofreaders acid-base status, plasma expanders, etc. Selection of the necessary preparations in each case is determined by the patient.