Instructions Nitroglycerin sublingual tablets 0.0005 g container No. 40
Composition
active ingredient: 1 sublingual tablet contains nitroglycerin 2% on lactose, equivalent to nitroglycerin 0.5 mg;
Excipients: lactose monohydrate, pregelatinized starch, microcrystalline cellulose, croscarmellose sodium, calcium stearate.
Dosage form
Sublingual tablets.
Main physical and chemical properties: single-layer tablets of round shape, with flat upper and lower surfaces, beveled edges, with a line, white or white with a creamy tint. Marbling is allowed on the surface of the tablets. A relatively homogeneous structure is visible on the break under a magnifying glass.
Pharmacotherapeutic group
Vasodilators used in cardiology. Organic nitrates.
ATX code C01D A02.
Pharmacological properties
Pharmacodynamics.
Nitroglycerin is a peripheral vasodilator with a predominant effect on peripheral vessels.
Nitroglycerin acts directly on smooth muscle, mainly of venous and arterial vessels, via the nitrate receptor located in the smooth muscle membrane of the vascular wall. Nitroglycerin is enzymatically converted in smooth muscle to nitric oxide (NO), which stimulates soluble guanylate cyclase, which is responsible for the formation of cyclic guanosine-3'5'-monophosphate (cGMP), which is a mediator of relaxation.
It affects the processes of central regulation of vascular tone and cardiac activity. It promotes the release of catecholamines in the brain and heart, which leads to central inhibition of sympathetic and vasomotor tone, indirect sympathomimetic action on the myocardium, and changes in the conformation of the troponin-tropomyosin complex. The nature and intensity of the action of nitroglycerin on the heart and peripheral vessels depends on the interaction of central and peripheral processes. Inhibition of vasoconstrictor reflexes on the coronary vessels, which is the result of central inhibition of pain impulses, helps to relieve attacks of pain in angina. The antianginal effect of nitroglycerin is due to the normalizing effect on electrolyte metabolism and myocardial energy, namely: on key indicators of the respiratory chain - the ratio of oxidized and reduced forms of nicotinamide coenzymes, the activity of NAD-dependent dehydrogenases. Affects cardiac activity and systemic hemodynamics. Under the influence of nitroglycerin, retrograde blood flow increases due to the expansion and increase in the number of functioning collaterals. Indirect sympathomimetic action, as well as the accumulation of cyclic AMP in the myocardium, lead to an increase in its contractility. In addition, nitric oxide effectively inhibits both aggregation and adhesion of platelets. Reduction of peripheral resistance and reduction of venous return are effects associated with S3 relaxation of vascular smooth muscle, reduction of pre- and afterload on the heart. Venous dilation leads to a decrease in the amount of blood entering the heart, a decrease in preload, and arterial dilation leads to a decrease in total peripheral resistance and a decrease in afterload, which ultimately results in easier heart work and improved coronary circulation.
There is a redistribution of blood circulation in the myocardium in favor of the ischemic focus, the ionotropic function of the myocardium is enhanced. The end-diastolic pressure in the left ventricle and the size of the heart decrease, which improves the blood supply to the subendocardial area of the myocardium that is most vulnerable to ischemia. The weakening of peripheral venous and arterial resistance and the pressure of filling the heart with blood contributes to a decrease in energy expenditure by the left ventricle and the need for oxygen by the myocardium. The pressure in the pulmonary capillaries decreases, which necessitates the appointment of nitroglycerin in myocardial infarction with pulmonary edema, as well as in heart failure. With ischemic hypokinesia of individual areas of the myocardium, its contractility is restored. Meningeal vessels dilate, vessels of internal organs constrict, pressure in the pulmonary artery system decreases due to vasodilation and systemic effect of nitroglycerin. Nitroglycerin relaxes smooth muscles of the bronchi, biliary tract, digestive tract and urinary tract. In experimental studies, no teratogenic or toxic effects on the embryo were detected.
Pharmacokinetics.
Nitroglycerin, taken sublingually, is absorbed by the mucous membrane and enters mainly the systemic circulation. 60-75% of the dose taken is absorbed. 2-4 minutes after administration, the maximum concentration in the blood plasma is reached - 2.3 μg / l, by the 8th minute - it decreases by 50% and after 20 minutes nitroglycerin is almost not detected in the blood. It is rapidly metabolized in the liver. Nitroesters of polyhydric alcohols are quickly denitrated. Denitrated metabolites, such as 1,2- and 3,4-dinitrates, are weaker and have a longer half-life compared to nitroglycerin. The half-life of nitroglycerin is almost 30 minutes. The cleavage of nitro groups occurs sequentially both through the formation of inorganic nitrites and with the formation of nitrates. Alcohols, aldehydes and organic acids are formed from the organic part of the nitroester molecule. 4 hours after the drug is used, nitroesters (the initial product) are almost not detected. They are most actively metabolized in the liver, kidneys and blood. Nitroesters are broken down in two ways: by glutathione-dependent reductase, which is localized mainly in the soluble fraction of hepatocytes, and by an enzyme that does not require reduced glutathione. The drug is metabolized primarily in the arteriovenous vascular bed, diffuses into smooth muscle cells, where it is converted to nitric oxide. A small part of the drug, mainly under the influence of glutathione-S reductase, is biotransformed in the liver to di-, mononitrates and glycerol. When taken orally, most of the drug is metabolized in the liver (the "first-pass" effect). A significant part of the dinitrate and mononitrate forms conjugates with glucuronic acid. Excretion of nitroglycerin metabolites occurs mainly by the kidneys, some metabolites are excreted through the lungs with exhaled air. The total clearance of nitroglycerin is 25-30 liters.
The half-life is 4-5 minutes. The half-life of metabolites is 4 hours.
Indication
Angina pectoris (for relief of angina attacks and short-term prevention).
Contraindication
Hypersensitivity to nitrates and auxiliary components of the drug; cerebral ischemia, hemorrhagic stroke, cerebral hemorrhage, increased intracranial pressure, recent head injury, bradycardia (less than 50 beats/min), arterial hypotension (systolic blood pressure below 90 mm Hg), shock, collapse, hypertrophic obstructive cardiomyopathy, aortic stenosis, conditions accompanied by a decrease in left ventricular filling pressure (acute myocardial infarction, isolated mitral stenosis, constrictive pericarditis), cardiac tamponade, toxic pulmonary edema, angle-closure glaucoma with high intraocular pressure, simultaneous use of phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, tadalafil, vardenafil),
Interaction with other medicinal products and other types of interactions
When used simultaneously with other vasodilators, antihypertensives, ACE inhibitors, "slow" calcium channel blockers, diuretics, tricyclic antidepressants, MAO inhibitors, ethanol and ethanol-containing drugs, beta-blockers, procainamide, quinidine, novocainamide, the hypotensive effect of nitroglycerin is enhanced.
Phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil) - simultaneous use of nitroglycerin with these drugs is contraindicated, as there is a potential risk of uncontrolled arterial hypotension and life-threatening cardiovascular complications.
Atropine and other drugs that have M-cholinolytic effects may reduce the effect of nitroglycerin due to reduced secretion and bioavailability of the drug.
Use with dihydroergotamine may lead to an increase in its plasma concentration and an increase in blood pressure (due to increased bioavailability of dihydroergotamine).
When used simultaneously with heparin, the anticoagulant effect of the latter may be reduced (after discontinuation of the drug, a significant decrease in blood clotting is possible, which may require a reduction in the dose of heparin).
Phenobarbital activates the metabolism of nitrates in the liver. Alpha-adrenomimetics, histamine, pituitrin, corticosteroids, CNS stimulants, bee venom, snake venom, sunlight reduce the antianginal effect of nitroglycerin. Salicylates increase the level of nitroglycerin in the blood, barbiturates accelerate its metabolism. Donors of sulfhydryl groups (captopril, acetylcysteine, unitiol) restore reduced sensitivity to nitroglycerin.
Application features
It is necessary to take the drug with caution, comparing the risk and benefit, in the following cases: uncontrolled hypovolemia, patients with heart failure with normal or low pulmonary artery pressure, severe anemia, hyperthyroidism, severe renal and/or hepatic failure (risk of developing methemoglobinemia).
It should be used with caution in patients with severe cerebral atherosclerosis, elderly patients. During the treatment period, alcohol consumption is not allowed; visiting baths, saunas, and hot showers are contraindicated.
To nitroglycerin, as to other organic nitrates, with frequent use, addiction (tolerance) may develop, which requires an increase in dosage. With prolonged use of Nitroglycerin, to prevent the development of tolerance, intermittent administration of the drug during the day (with an interval of 10-12 hours) or simultaneous administration of calcium antagonists, ACE inhibitors or diuretics is recommended. If necessary, when tolerance develops, sometimes it is necessary to temporarily discontinue the use of nitroglycerin (for several days) and replace it with antianginal agents of other pharmacotherapeutic groups.
Before using the drug for the first time, you should consult a doctor!
Be sure to inform your doctor about any previous reactions to medications in this group.
When taking nitroglycerin, a significant decrease in blood pressure and dizziness may occur when suddenly moving to a vertical position from a lying or sitting position; when using alcohol, or when performing physical exercises in hot weather.
If blurred vision or dry mouth persists or is significantly severe, treatment should be discontinued.
The severity of headache when taking the drug can be reduced by reducing its dose and/or taking validol at the same time.
The risk of developing methemoglobinemia, manifested by cyanosis and a change in blood color, increases with prolonged uncontrolled use of nitroglycerin, taking high doses of the drug in patients with liver failure. If methemoglobinemia develops, nitroglycerin must be urgently canceled and the antidote - methylthioninium chloride (methylene blue) must be used. If further use of nitrates is necessary, monitoring of the methemoglobin content is mandatory.
The drug contains lactose, therefore patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not use the drug.
Use during pregnancy or breastfeeding
The use of nitroglycerin during pregnancy or breastfeeding is contraindicated.
The ability to influence the reaction speed when driving or working with other mechanisms
When driving vehicles and mechanisms that require increased attention, it should be remembered that taking nitroglycerin may lead to a decrease in reaction speed.
Method of administration and doses
Apply to adults.
When prescribing the drug for the first time, it is necessary to study its effect on blood pressure. Monitoring the effectiveness of Nitroglycerin should be carried out by heart rate and blood pressure.
It should be taken immediately at the first symptoms of an angina attack.
Immediately after the onset of pain, place 1 tablet under the tongue and keep in the mouth until completely dissolved, without swallowing. The usual dose of the drug is 1 tablet under the tongue. If there is no antianginal effect within 3-5 minutes, you need to take 1 more tablet of Nitroglycerin.
If there is no therapeutic effect after taking 2-3 tablets, you should call a doctor.
With frequent attacks of angina, it is advisable to use prolonged-acting drugs.
Tolerance to sublingual forms of nitroglycerin rarely develops, but if it does occur in some patients, the dose of the drug should be gradually increased, bringing it to 2-3 tablets.
Children
There is no experience with the use of the drug in children, therefore it is not recommended for use in this age group of patients.
Overdose
Symptoms: decreased blood pressure (below 90 mm Hg) with orthostatic dysregulation, headache, severe dizziness, fainting, palpitations, nausea and vomiting, shortness of breath, severe weakness, drowsiness, increased body temperature, feeling of heat, arterial hypotension, increased sweating, chills.
When using high doses (more than 20 mcg/kg) - collapse, cyanosis of the lips, nails or palms, methemoglobinemia, dyspnea and tachypnea.
Treatment: place the patient in a horizontal position, elevate the legs, in severe cases prescribe plasma substitutes, sympathomimetics, oxygen, and in case of methemoglobinemia - methylene blue.
Side effects
From the side of the central nervous system: blurred vision, "nitrate" headache (especially at the beginning of the course of treatment, decreases with prolonged therapy), dizziness and feeling of weakness, anxiety, psychotic reactions, inhibition, disorientation.
From the cardiovascular system: decreased blood pressure, reflex tachycardia, rarely (especially in case of overdose) - orthostatic collapse, cyanosis, methemoglobinemia, facial flushing.
On the part of the digestive tract: dry mouth, nausea, vomiting, abdominal pain.
On the part of the immune system: allergic reactions, including skin rashes, urticaria, itching; hyperemia of the skin, pallor, anaphylactic shock.
Others: excitability, visual impairment, exacerbation of glaucoma, hypothermia, feeling of heat, respiratory distress, weakness.
Sometimes, with a sudden decrease in blood pressure, an increase in angina symptoms may occur (paradoxical "nitrate" reactions).
Expiration date
2.5 years.
Storage conditions
Store in original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
20 or 40 sublingual tablets in a container; 1 container in a pack.
Vacation category
Without a prescription.
Producer
Technolog PJSC.
Address
20300, Ukraine, Cherkasy region, Uman city, Stara Prorizna Street, building 8.
