Nitroglycerine

General characteristics. Structure:

Active ingredient: 10 mg of mix of nitroglycerine with glucose (dextrose) in 1 ml of solution.

Excipients: sodium chloride, potassium dihydrophosphate, water for injections.

Pharmacological properties:

Pharmacodynamics. Venodilatiruyushchy means from group of nitrates. Nitrates are capable to release from the molecule the nitrogen oxide which is the natural endothelial running-down factor - a mediator of direct activation of guanylate cyclase. Increase in concentration of a cyclic guanozinmonofosfat leads to relaxation of smooth muscle fibers (preferential venules and veins). Has anti-anginal and spasmolytic effect, relaxes smooth muscles of vascular walls, bronchial tubes, digestive tract, biliary tract, ureters. At intravenous administration causes bystry reduction of preload of heart due to expansion of peripheral veins.

Reduces inflow of blood to the right auricle, promotes pressure decrease in a "small" circle of blood circulation and regression of symptoms at a fluid lungs, reduces an afterload, the need of a myocardium for oxygen (due to decrease in preloading, an afterload and tension of walls of ventricles in connection with reduction of volume of heart). Promotes redistribution of a coronary blood-groove in the area with reduced blood circulation.

Exerts the central braking impact on a sympathetic tone of vessels, oppressing a vascular component of formation of a pain syndrome. Causes expansion of brain vessels, than the headache at its use speaks.

At prolonged or frequent use of nitrates of the prolonged action development of tolerance to drug (easing of therapeutic effect) is observed. After a break sensitivity is recovered. For the purpose of prevention of emergence of tolerance it is recommended to observe daily, preferably night "beznitratny interval" during 8-12 h. At most of patients such therapy is more effective, than continuous treatment.

Pharmacokinetics. It is quickly metabolized with the participation of nitrate reductase, with education of di - and mononitrates (only isosorbide-5-mononitrate is active), a final metabolite - glycerin. It is removed by kidneys in the form of metabolites. The general clearance makes 25-30 l/min.

At intravenous administration an elimination half-life — 1-3 min., the general clearance of 30-78 l/min.

Indications to use:

Acute myocardial infarction (including complicated by an acute left ventricular failure); unstable and postinfarction stenocardia; fluid lungs; the managed hypotension during operative measures for the purpose of reduction of bleeding in a surgery field.

Route of administration and doses:

Intravenous administration of nitroglycerine has to be carried out with individual selection of rate of administering of drug. Solution is entered via the automatic doser or through usual system for intravenous injections. The automatic doser allows to enter even not divorced 0,1% solution with exact dosing of a rhythm of introduction and the general dose. Introduction through usual system for transfusion of liquids provides the choice of an exact dose by calculation of number of drops. When using system of tubes from polyvinylchloride active agent is absorbed, and losses on walls of tubes make up to 60% (reasonablly to use polyethylene and glass tubes). Solution quickly collapses on light therefore bottles and system for transfusion need to be shielded lightproof material.

Usually use infusion solution with concentration of 100 mkg/ml: strong solution is parted by 0,9% with solution of sodium of chloride or 5% dextrose solution (it is not necessary to use other solvents).

Solution is entered intravenously kapelno, with an initial speed of 5 mkg/min. It is possible to increase rate of administering each 3-5 min. by 5 mkg/min. (depending on therapeutic effect, heart rate, the central venous pressure and systolic arterial pressure which can be reduced by 10-25% from initial, but should not be lower than 90 mm hg). If at rate of administering of 20 mkg/min. the therapeutic effect is not gained, the further gain of rate of administering has to make 10-20 mkg/min.

At emergence of response (in particular, lowerings of arterial pressure) further increase in speed of infusion is not carried out or carried out through more long intervals of time.

For achievement of good effect rate of administering of 0,01% of Solution Nitroglycerini usually does not exceed 100 mkg/min. (1 ml/min.). In the absence of effect of smaller doses and tolerance level of arterial pressure rate of administering of 0,01% of solution can reach 300 mkg/min. (3 ml/min.). Further increase in speed is inexpedient.

Duration of treatment is defined by clinical indications and can make 2-3 days.

Nitroglycerine for intravenous administration if necessary can repeatedly be entered, through any periods.

Features of use:

Use at pregnancy and during feeding by a breast. Use of nitroglycerine at pregnancy and during feeding by a breast perhaps if the potential advantage of treatment for mother surpasses risk for a fruit or the child.

At an acute myocardial infarction or an acute heart failure it is necessary to apply only on condition of careful observation of the patient. For prevention of increase of attacks of stenocardia it is necessary to avoid sharp cancellation.

For prevention of an undesirable lowering of arterial pressure follows individually and methodically correctly (see above) to select drug rate of administering.

The lowering of arterial pressure can be observed not only during selection of rate of administering of nitroglycerine, but also later, against the background of originally stabilized arterial pressure. Therefore control of arterial pressure it is necessary to carry out at least 3-4 times an hour throughout all time of infusion of nitroglycerine.

Development of tolerance to nitroglycerine, and also development of group tolerance to nitrates is possible (reduction of efficiency of medicine at the previous therapy by other nitrates).

For obtaining desirable hemodynamic effect higher dose can be required by the patients undergoing earlier treatment by organic nitrates (isosorbide dinitrate, isosorbide-5-mononitrate).

Solution for intravenous administration contains a dextrose that needs to be considered when using at patients with a diabetes mellitus.

During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From cardiovascular system: tachycardia, a dermahemia, heat, a lowering of arterial pressure, a heart consciousness, unpleasant feelings behind a breast; orthostatic collapse, cyanosis. At the expressed lowering of arterial pressure developing of paradoxical bradycardia and strengthening of symptoms of stenocardia is possible.

From digestive tract: dryness of a mucous membrane of an oral cavity, nausea, vomiting, abdominal pain.

From the central nervous system: dizziness, headache, uneasiness, psychotic reactions, block, disorientation, syncope.

Allergic reactions: skin rash, itch.

Local reactions: dermahemia, skin itch, burning, allergic contact dermatitis.

Others: sight illegibility, weakness, hypothermia, methemoglobinemia.

Interaction with other medicines:

Simultaneous use of nitroglycerine with vazodilatator, hypotensive medicines, inhibitors of the angiotensin-converting enzyme (ACE), beta adrenoblockers, blockers of "slow" calcium channels, procaineamide, tricyclic antidepressants, monoamine oxidase inhibitors, diuretics, and also ethanol strengthens hypotensive effect.

At a concomitant use with sildenafily, and also with other inhibitors of phosphodiesterase there can be a sharp lowering of arterial pressure.

Appointment with dihydroergotamine can lead to increase in its concentration in blood and to increase in arterial pressure (increase in bioavailability of dihydroergotamine).

Against the background of quinidine and procaineamide there can be an orthostatic collapse.
Co-administration of nitroglycerine and heparin reduces efficiency of the last (after drug withdrawal the heparin dose decline can be required).

Contraindications:

Hypersensitivity to nitroglycerine and other organic nitrates, the isolated mitral stenosis, an aortal stenosis, a subaortal stenosis, cardiogenic shock, a toxic fluid lungs, an acute disorder of blood circulation (shock, a vascular collapse), a hypovolemia, heavy arterial hypotension (systolic arterial pressure ≤ 90 mm hg), the cardiac tamponade, chronic cardial compression, diseases proceeding with the increased intracranial pressure, a hematencephalon, heavy anemia, age up to 18 years (efficiency and safety are not established).

In connection with considerable hypotensive action and the expressed side effects (a faint, a myocardial infarction), medicines for treatment of erectile dysfunction (phosphodiesterase inhibitors) should not be used against the background of therapy by drugs of group of nitroglycerine.

With care. A hypertrophic subaortic stenosis, atherosclerosis, an acute myocardial infarction with the low pressure of filling of a left ventricle, recently postponed head injury, closed-angle glaucoma, a heavy renal failure, a liver failure (risk of development of a methemoglobinemia), a thyrotoxicosis, a diabetes mellitus.

Overdose:

Symptoms: the expressed lowering of arterial pressure (it is lower than 90 mm hg) with orthostatic dysregulation, reflex tachycardia, a headache; the adynamy, dizziness, the increased drowsiness, feeling of heat, nausea, vomiting can develop; at use in high doses (more than 20 mg/kg) — a collapse, cyanosis, a methemoglobinemia, диспноэ and a tachypnea; at very high doses increase in intracranial pressure is possible.

Treatment: at intravenous administration — stop further introduction. It is necessary to lower the head end of a bed and to raise the patient's legs. As a rule, arterial pressure at the same time is normalized within 15-20 min. after the termination of administration of nitroglycerine, then it is possible to continue introduction, after repeated selection of speed of infusion. For correction of arterial pressure use of Phenylephrinum and other vasoconstrictors is possible.

At a methemoglobinemia, depending on severity, are appointed: ascorbic acid - 1 g in or intravenously (in the form of sodium salt); oxygenotherapy, hemodialysis, exchange hemotransfusion.

Storage conditions:

In the cool, protected from light place, far from fire. Storage of solution in the opened ampoule is not allowed. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Concentrate for preparation of solution for infusions of 1 mg/ml in ampoules on 10 ml. On 10 ampoules with the application instruction, a knife ampoule or the scarificator ampoule (if necessary) in a pack from a cardboard. On 5 or 10 ampoules in a blister strip packaging. A blister strip packaging without covering. On 1 or 2 blister strip packagings with the application instruction, a knife ampoule or the scarificator ampoule (if necessary) in a pack from a cardboard.