Instructions for Nitroglycerin 0,5 mg 40 pills
Pharmacological properties:
Nitroglycerin is an agent of the group of organic nitrates, mainly a venous dilator. Nitrates are able to release nitric oxide from their molecule, which is a natural endothelial relaxing factor - a mediator of direct activation of guanylate cyclase. An increase in the concentration of cGMP leads to relaxation of smooth muscle fibers, mainly venules and veins. It has an antianginal and antispasmodic effect, relaxes smooth muscle cells of the walls of vessels, bronchi, digestive tract, bile tract and ureters. When in/in administration causes a decrease in preload on the heart due to expansion of peripheral veins. Reduces blood flow to the right atrium, helps reduce pressure in the small circulation and regression of symptoms during pulmonary edema, reduces post-load, myocardial oxygen demand (due to reduced preload, post-load and ventricular wall tension due to decreased heart volume).
It promotes the redistribution of coronary blood flow in the area with reduced circulation. It has a central inhibitory effect on the sympathetic tone of the vessels, inhibiting the vascular component of the formation of pain syndrome. It causes the expansion of meningeal vessels, which explains the appearance of a specific "nitrate" headache. With prolonged or frequent use of nitrates of prolonged action, the development of tolerance is possible. After a break in treatment, the sensitivity to nitrates is restored. In order to prevent the development of tolerance, it is recommended to observe a daily interval in the intake of nitrates (8-12 hours), preferably at night. In most patients, such therapy is more effective than continuous treatment. When sublingual forms are used, the angina attack is stopped after 1.5 minutes, the hemodynamic and antianginal effect is preserved up to 30 minutes. Retard tablets can prevent the development of angina attacks.
Nitroglycerine is rapidly and completely absorbed from the surface of the mucous membranes and through the skin. When ingested, bioavailability is not more than 10% compared to Nitroglycerine administered sublingual (effect of primary passage through the liver). With sublingual, buccal and in/in administration, presystemic metabolism is excluded, and the active substance enters the systemic bloodstream directly. With sublingual administration at a dose of 0.5 mg, bioavailability is almost 100%, the maximum concentration in blood plasma is noted after 5 minutes.
Up to 60% of Nitroglycerine binds to blood plasma proteins. It is quickly metabolized with the participation of nitrate reductase, with the formation of di- and mononitrates (only isosorbide-5-mononitrate is active), the final metabolite is glycerol. Excreted in urine as metabolites. The total clearance is 25-30 l/min, the half-life is 4-5 min. If the half-life is introduced, the half-life is 1-3 min, the total clearance is 30-78 l/min. The active substance is rapidly metabolized in the liver by glutathione reductase acting on organic nitrates. In addition, Nitroglycerine metabolizes in erythrocytes using enzymatic reactions occurring with the participation of sulfhydryl radicals, as well as when interacting with reduced hemoglobin.
Indications:
IHD — angina, including in the post-infarction period; for intravenous administration-acute period of myocardial infarction (including complicated by acute left ventricular failure), unstable and post-infarction angina, pulmonary edema, controlled arterial hypotension during surgical interventions to reduce bleeding in the operating field, occlusion of the central retinal artery.
Application:
Inward, sublingual, in/in. Elimination of angina pectoris. Sublingual (a tablet or capsule with a p-rom is kept under the tongue until completely resorbed, without swallowing), immediately after the onset of pain - 0.5-1 mg per appointment. If necessary, in order to achieve a faster effect, the capsule should be immediately disassembled, the capsule can be repeated after 30-40 minutes.
Usually, the antianginal effect manifests itself after 0.5-2 minutes, in some cases during 4-5 minutes. In the absence of antianginal action, another 0.5 mg of nitroglycerin should be prescribed for the first 5 minutes. In the absence of a therapeutic effect after 2-3 times of administration, the probability of developing myocardial infarction should be taken into account.
When using 1% Nitroglycerine in order to stop the attack, 2-3 drops of p-ra are applied to a small piece of sugar and kept in the mouth without swallowing until completely resorbed. The duration of action after sublingual reception is about 45 minutes.
With frequent attacks of angina pectoris, it is advisable to prescribe prolonged forms of nitrates. If an attack of angina develops against the background of treatment with prolonged forms of nitrates, it is necessary to sublingual take nitroglycerin to stop an acute attack. Tolerance to sublingual forms of nitroglycerin does not develop often, however, with its development in some patients, the dose has to be gradually increased, bringing it to 2-3 tablets.
Prolonged nitroglycerin intended for prevention of angina pectoris is ingested by drinking water before meals. In light cases - 0.0029-0.0058 g 2-3 times a day. In more severe cases - 0.0052-0.01 g 2-3 times a day. The maximum daily dose is 0.0348 g. Due to the fact that the bioavailability of nitroglycerin from retard tablets is low, it is recommended to take 1-3 tablets at a time regularly 3-4 times during the day or periodically 30-40 minutes before the expected physical activity. With insufficient therapeutic effect, the dose can be gradually increased (but not more than 2 tablets per 1 take), and after the therapeutic effect, it can be reduced.
Aerosol for sublingual use: for stopping an attack of angina pectoris - 0.4-0.8 mg, pressing the dosing valve, preferably in a sitting position, when holding breathing at intervals of 30 s; then close your mouth for a few seconds. If necessary - repeated administration, but not more than 1.2 mg during 15 minutes. To prevent an attack - 0.4 mg 5-10 minutes before the load. In acute left-ventricular insufficiency, developing pulmonary edema - 1.6 mg or more in a short period of time.
Treatment with nitroglycerin for IV administration should be carried out by individually determining the rate of administration of p-p. It is introduced through an automatic dispenser or through a conventional infusion system.
When using a system of polyvinyl chloride tubes, the active substance is absorbed and losses on the walls of the tubes are up to 60% (it is advisable to use polyethylene and glass tubes).
R-r is quickly destroyed in the light, so vials and the transfusion system need to be shielded with a light-proof material. Usually, infusion p-p is used with a concentration of 100 μg/ml: concentrated p-p is diluted with 0.9% sodium chloride prom or 5% dextrose prom and introduced in/in dropwise at an initial rate of 5 μg/min. The rate of administration can be increased every 3-5 minutes by 5 μg/min (depending on the effect, HR, central venous pressure and systolic BP, which can be reduced by 10-25% of the initial, but should not be lower than 90 mm Hg).
If the therapeutic effect is not achieved at the administration rate of 20 μg/min, the administration rate can be increased by 10-20 μg/min. When a response occurs (in particular, a decrease in BP), a further increase in the infusion rate is not carried out or is carried out at longer intervals. In order to achieve a good effect, the administration rate of 0.01% of nitroglycerin is usually not more than 100 μg/min (1 ml/min). In the absence of an effect due to the use of nitroglycerin at lower doses and at an acceptable BP level, the administration rate of 0.01% p-p can reach 300-400 μg/min (3-4 ml/min). A further increase in the rate of infusion is impractical. The duration of application is determined by clinical indications and can be 2-3 days.
Contraindications:
Hypersensitivity to nitroglycerin; for in/in administration (relative contraindications) - hemorrhagic stroke, traumatic brain injury, increased intracranial pressure, cardiac tamponade, constrictive pericarditis, hypovolemia (must be scorrigated before using nitroglycerin).
Side effects:
- Dizziness, "nitrate" headache
- tachycardia
- skin hyperemia
- heat sensation
- decreased BP
- rarely (mainly in overdose)
- orthostatic collapse, cyanosis; feeling dry in the mouth, nausea, vomiting, abdominal pain;
- rarely (mainly in overdose) - anxiety, psychotic reactions, retardation, disorientation; rarely - allergic reactions (cutaneous itching, rash); local reactions for transdermal use: hyperemia and itching of the skin, burning, allergic contact dermatitis;
- blurred vision,
- general weakness,
- hypothermia,
- methemoglobinemia.
Overdose:
Manifested by a decrease in BP (below 90 mm Hg. Art.), orthostatic reactions, reflex tachycardia, headache, dizziness, drowsiness, feeling heat, nausea, vomiting, with a significant overdose (more than 20 mg/kg) - collapse, cyanosis, methemoglobinemia, dyspnea and tachypnea. When overdose symptoms develop, further administration is stopped, the patch is removed.
Lower the head end of the bed and raise the patient's legs. As a rule, BP is normalized within 15-20 minutes after the cessation of nitroglycerin administration, then it is possible to continue administration after re-establishing the infusion rate.
Phenylephrine, epinephrine and other vasoconstrictors can be used to correct BP. In case of methemoglobinemia, depending on the severity, ascorbic acid 1 g is prescribed inside or in the form of sodium salt IV; v/v methylene blue 0.1-0.15 ml/kg 1% p-ra (up to 50 ml), oxygenotherapy, hemodialysis, blood exchange transfusion.
