Organic nitrates were introduced into clinical practice in the 19th century. In 1879, an article was published by Dr. Murrell, who proposed the use of nitroglycerin to eliminate angina attacks.
Given the significant prevalence of coronary disease, the relevance of the medications under consideration 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 and vasodilating effects 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 promotes the development of myosin dephosphorylation and a decrease in the penetration of calcium ions into the cells, as a result of which smooth muscle relaxation of the vascular walls is observed. This can also be noted in the urinary, respiratory tract, digestive tract. By acting on the structure of the brain, nitrates help to block the central sections of coronary constriction reflexes, and weaken the sympathetic control of the cardiovascular system.
Organic matter is known to be starch. Calcareous 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, the tension of their walls), and the expansion of arteries reduces the level of resistance to cardiac output (decrease in afterload, resistance to cardiac output, energy consumption and oxygen consumption by the myocardium).
Favorable effects on myocardial trophism
In addition, organic nitrates favorably affect myocardial trophism, the activity of respiratory enzymes, electrolyte metabolism, and increase the electrical stability of the heart muscle, preventing the development of arrhythmia. The ability of these substances to lower the pressure is also of great importance, due to which they are used in case of insufficiency of the left ventricle.
Medications
Medical substances close to organic nitrates (sodium nitroprusside, nitrites, molsidomin) also have a nitroxergic effect.
They have well-known differences in pharmacokinetic parameters and indications for use (nitroglycerin is mainly used to eliminate angina attacks, other medicines to prevent their development). Adverse reactions of individual medical devices are mainly due to the general mechanism of action for 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;
- isosorbide dinitrate medications;
- isosorbide mononitrate preparations;
- nitrate-like medicines.
Nitroglycerin-based medicines have a long period of action. These include: Sustonit, Sustak, Nitrong, Trinitrolong, Nitroderm.
Isosorbide dinitrate-based drugs have a short period of action.
The group of organic nitrates includes such medications as Izo-Mik, Nitrosorbide and Izodinit.
Medicines based on isosorbide mononitrate are characterized by long-term effectiveness, and their list includes drugs such as Monochinque Retard, Mono Mack Depot.
Nitrate-like medicines include Molsidomin, Amylnitrite and sodium nitroprusside.
How are organic nitrates used for hypertension?
Treatment of arterial hypotension
Of great clinical significance is a decrease in pressure of more than 15 mm Hg. Art. from entry level. The disease is due to the pronounced vasodilating effect of nitrates. With a significant decrease in blood pressure, a decrease in blood supply to all organs, including the heart, is possible. To prevent the development of severe hypotension, the use of nitroglycerin in a sitting or lying position with raised legs is recommended.
Taking this substance in a standing position can provoke a swoon and a weakening of the antianginal effect, since a sharp decrease in blood flow helps to weaken the coronary blood flow. In such cases, the occurrence of a robbery syndrome is possible, which is an increase in cardiac muscle ischemia, especially in patients with stenotic widespread atherosclerosis of the coronary vessels.
A sharp decrease in pressure can provoke a preparation of organic nitrates based on sodium nitroprusside, which is used intravenously in the development of hypertensive crises, pulmonary edema, preeclampsia, exfoliating 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, such as arterial hypotension with a systolic pressure of less than 90 mm Hg. Art., and diastolic - less than 60 mm RT. st .; shock, collapse.
Drug interaction
The ability of organic nitrates to lower pressure is enhanced if they are combined with other vasodilating drugs, alcohol, narcotic analgesics. Separately, it is necessary to note their incompatibility with sildenafil ("Viagra"). This medicine also acts through nitric oxide, and potentiation of vasodilating effects with deep hypotension and even death occurs.
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 when taking a vertical position. Therefore, after taking the drug, the patient needs to do this slowly and carefully.
- Tachycardia, which is the main side effect of organic nitrates and has baroreflex effects, which consists in lowering the parasympathetic control of heart contractions as a response to 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-adrenergic blockers and dihydropyridines (Amlodipine, Nicardipine, etc.) - this side symptom is leveled.
- Bradycardia, which is a rather rare side effect that sometimes occurs with intravenous injection of nitroglycerin against a background of a strong decrease in pressure. The main reason for this pathological condition is to increase the tone of the vagus nerve. Atropine can 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 a 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, increased intracranial pressure, expansion of the walls of the veins inside the skull, which is the cause of pain.
- Increased intraocular pressure, which is an intermittent side effect of nitrates. In connection with this contraindication for their use is considered glaucoma.
Dosage of medicines
Nitroglycerin is used as follows:
- capsules with 1% oil solution at a dose of 0.001 and 0.0005 g;
- tablets of 0.0005 g;
- aerosol for sublingual use - 0.0004 g;
- alcohol solution - 1-2 drops per sugar.
To prevent angina attacks, tablets of prolonged exposure for oral administration are used - “Nitrong”, “Nitrogran-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 agents are also used in the transdermal therapeutic system - special plasters ("Deponit"), which are glued onto the skin for 12 hours (the patch releases 0.0005 g of substance per day).
Isosorbide dinitrate is administered sublingually, its action develops after 3-5 minutes, with oral administration - after 15-30 minutes. The dosage is one tablet once, further use is determined by the treatment regimen established by a specialist. Despite the widespread use of this medication in modern medical practice, its administration is best coordinated with the doctor, due to the pronounced clinical effect and possible adverse reactions.