Organic nitrates were introduced into clinical practice in the 19th century. In 1879 an article was published by Dr. Murrel, who proposed the use of nitroglycerin to eliminate angina attacks.
Given the significant prevalence of coronary disease, the relevance of the considered medications is very high today. Until now, nitroglycerin and other drugs created on its basis, as well as drugs close to them, isosorbide mono- and dinitrate, are considered the most effective antianginal drugs.
The antianginal effect of organic nitrates is associated with an increase in the supply of oxygen to the heart muscle and, at the same time, with a decrease in its need for it.
Mechanism of action
Despite such a long experience of use, the mechanism of antianginal andThe vasodilating effect of nitrates has been established relatively recently. It consists in the myotropic and neurotropic effects of the main components.
When ingested, the NO group is separated from the nitrate molecule, similar to the endothelial relaxing factor. It activates guanylate cyclase, which leads to an increase in the levels of cyclic guanosine monophosphate, the accumulation of which contributes to the development of myosin dephosphorylation and a decrease in the penetration of calcium ions into cells, resulting in relaxation of the smooth muscles of the vascular walls. This can also be noted in the urinary, respiratory tract, digestive tract. By acting on the structures of the brain, nitrates contribute to the blocking of the central sections of coronary reflexes, and the weakening of the sympathetic control of the cardiovascular system.
It is known that starch is an organic substance. Lime water and silver nitrate are not.
Antianginal efficacy of nitrates
For antianginal effectiveness, not only short-term and intermittent expansion of coronary vessels and increased blood flow through them are important, but also hemodynamic unloading of the heart muscle, which leads to a weakening of the heart and its oxygen needs. As a result of the expansion of the veins, the return of venous blood to the organ is limited (decrease in preload, pressure inside the ventricles, tension in their walls), and the expansion of the arteries reduces the level of resistance to cardiac output (decrease in afterload, resistance to cardiac output, flowenergy and myocardial oxygen consumption).
Beneficial effect on myocardial trophism
In addition, organic nitrates have a beneficial effect on myocardial trophism, the activity of respiratory enzymes, electrolyte metabolism, increase the electrical stability of the heart muscle, preventing the development of arrhythmias. Of great importance is also the property of these substances to lower pressure, due to which they are used in case of left ventricular failure.
Medications
Medical substances close to organic nitrates (sodium nitroprusside, nitrites, molsidomine) also have a nitrooxidergic effect.
They have well-known differences in pharmacokinetic parameters and indications for use (nitroglycerin is used mainly to eliminate angina attacks, other medicines to prevent their development). Adverse reactions of individual medical products are mainly due to the mechanism of action common to the entire category of these drugs, and therefore are very similar.
Classification of organic nitrates
All such medicines fall into four main categories:
- nitroglycerin preparations;
- drugs based on isosorbide dinitrate;
- drugs of isosorbide mononitrate;
- nitrate-like drugs.
Medicines based on nitroglycerin have a long period of action. These include:"Sustonit", "Sustak", "Nitrong", "Trinitrolong", "Nitroderm".
Medicines based on isosorbide dinitrate have a short period of action.
The group of organic nitrates includes such medications as Iso-Mik, Nitrosorbide and Isodinit.
Medications based on isosorbide mononitrate have long-term effectiveness, and their list includes drugs such as Monocinque Retard, Mono Mac Depot.
Nitrate-like drugs include Molsidomin, Amyl nitrite and sodium nitroprusside.
How is organic nitrate used for hypertension?
Treatment of arterial hypotension
A decrease in blood pressure of more than 15 mmHg is of great clinical importance. Art. from entry level. The disease is due to the pronounced vasodilating effect of nitrates. With a significant decrease in blood pressure, it is possible to reduce the blood supply to all organs, including the heart. To prevent the development of severe hypotension, the use of nitroglycerin in a sitting or lying position with legs elevated is recommended.
Intake of this substance in a standing position can provoke fainting and weaken the antianginal effect, since a sharp decrease in blood flow contributes to a decrease in coronary blood flow. In such cases, steal syndrome may occur, which is an increase in ischemia of the heart muscle, especially inpatients with stenosing widespread atherosclerosis of the coronary vessels.
A sharp drop in pressure can provoke an organic nitrate preparation based on sodium nitroprusside, which is used intravenously in the development of hypertensive crises, pulmonary edema, preeclampsia, dissecting aortic aneurysm, eclampsia, as well as controlled hypotension during surgical interventions.
Contraindications
This adverse reaction causes such contraindications to the use of nitroglycerin and other organic nitrates as arterial hypotension with systolic pressure less than 90 mm Hg. Art., and diastolic - less than 60 mm Hg. Art.; shock, collapse.
Drug Interactions
The ability of organic nitrates to lower blood pressure is enhanced when combined with other vasodilating drugs, alcohol, narcotic analgesics. Separately, it is necessary to note their incompatibility with sildenafil ("Viagra"). This drug also acts through nitric oxide and potentiates vasodilating effects with profound hypotension and even death.
Side effects of organic nitrates
Nitrates can cause the following negative effects:
- Orthostatic collapse. Most often, this side effect provokes nitroglycerin. The mechanism of this pathological condition is associated with a decrease in venous return to the heart, which reduces the level of blood supply to the brain.brain when taking a vertical position. Therefore, after taking the drug, the patient must do it slowly and carefully.
- Tachycardia, which is the main side effect of organic nitrates and has baroreflex effects, which is to reduce the parasympathetic control of heart contractions in response to the relaxation of the vascular walls. Tachycardia is sometimes especially pronounced with self-treatment with nitrates. In cases of their simultaneous use with drugs that cause bradycardia: calcium channel blockers from the category of phenylalkylamines ("Verapamil"), β-blockers and dihydropyridines ("Amlodipine", "Nicardipine", etc.) - this side symptom is leveled.
- Bradycardia, which is a rather rare side effect that sometimes occurs with intravenous injections of nitroglycerin against the background of a strong decrease in pressure. The main reason for this pathological condition is to increase the tone of the vagus nerve. Atropine may be used to correct this phenomenon.
- Headache is a symptom that often occurs after taking organic nitrates. This reaction can last from 20 minutes to several hours, be accompanied by dizziness, have a pulsating character, especially in patients with cerebral atherosclerosis. Cephalgia is associated with the negative effect of organic nitrates on cerebral hemodynamics. The consequence of this is a decrease in blood flow in the brain, oxygen starvation of the brain, an increase in intracranial pressure, expansion of the walls of the veins inside the skull,which causes pain.
- Increased intraocular pressure, which is an intermittent side symptom of nitrates. In this regard, glaucoma is considered a contraindication for their use.
Medication dosages
"Nitroglycerin" is used as follows:
- capsules with 1% oil solution at a dose of 0.001 and 0.0005 g;
- tablets 0.0005 g;
- aerosol for sublingual use - 0.0004g;
- alcohol solution - 1-2 drops per sugar.
To prevent angina attacks, long-acting oral tablets are used - Nitrong, Nitrogranu-long, Sustak forte. The list of organic nitrates is quite extensive. After taking these medicines, the action of the main element begins after 120 minutes and lasts about 6 hours. These funds are also used according to the transdermal therapeutic system - special patches ("Deponit"), which are glued to the skin for 12 hours (the patch releases 0.0005 g of the substance per day).
Isosorbide dinitrate is administered sublingually, its effect develops after 3-5 minutes, when administered orally - after 15-30 minutes. The dosage is one tablet once, further use is determined by the therapy regimen established by the specialist. Despite the widespread use of this medication in modern medical practice, its use is best coordinated with a doctor, inwith a pronounced clinical effect and possible adverse reactions.
