Nitroglycerine

General characteristics. Structure:

Active ingredient: 1 mg of nitroglycerine [as a part of mix with a 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 (tsGMF) 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 (in) introduction renders 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 meningeal vessels, than the headache at its use speaks.

Pharmacokinetics. Getting to a system blood stream, 60% communicate proteins of a blood plasma. Vysokolipofilen, has the large volume of distribution (1,2-3,3 l/kg). It is quickly metabolized in a liver glutationreduktazy, influencing organic nitrates, with education of di - and mononitrates, a final metabolite - glycerin. It is removed by kidneys in the form of metabolites.

The general clearance makes 30-78 l/min, the elimination half-life - Besides, in erythrocytes happens 1-3 min. metabolism of nitroglycerine by means of the enzymatic reactions occurring with the assistance of sulphhydryl radicals and also at interaction to the recovered hemoglobin.

Indications to use:

Acute myocardial infarction (including complicated by acute LZh insufficiency), unstable and postinfarction stenocardia, a fluid lungs, the managed hypotension during operative measures for the purpose of reduction of bleeding in a surgery field.

Route of administration and doses:

Treatment has to be carried out with individual selection of speed to administrations of drug. Solution is entered via the automatic doser or through инфузомат, the rates of administering allowing to enter solution with exact dosing and the general dose.

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 of the poured liquid, for this purpose Solution Nitroglycerini is previously parted by 0,9% with solution of sodium of chloride or 5% solution of a dextrose (glucose) - it is not necessary to use other solvents - to concentration of 0,01% of nitroglycerine.

Selection of a dose and rate of administering is carried out individually taking into account the arterial pressure (AP), the heart rate (HR), the central venous pressure, an ECG and other indicators.

When using system of tubes from polyvinylchloride active agent is absorbed, and losses on walls of tubes make from 40 to 80% (reasonablly to use polyethylene and glass tubes).

Solution quickly collapses on light therefore bottles and system for transfusion need to be shielded lightproof material.

Storage of solution in the opened ampoule is not allowed.

The spilled solution from an ampoule needs to be neutralized strong alkali.

The mode of dosing and the recommended concentration

1,0 ml = to 20 drops

Initial rate of administering of solution of 0,5-1 mg/h, the maximum speed makes 8-10 mg/h. Duration of treatment is defined by clinical indications and can make of several hours to 2-3 days.

Features of use:

Pregnancy and lactation. Use at pregnancy and during feeding by a breast has to be carried out under medical control 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 clinical observation of the patient.

Against the background of intravenous administration of nitroglycerine perhaps considerable decrease in the ABP and emergence of dizziness upon sharp transition to vertical position from situation "lying" or "sitting"; hot weather, and also strengthening of stenocardia (at sharp decrease in the ABP) and myocardium ischemia up to a myocardial infarction and sudden death (paradoxical nitrate reactions). For prevention of undesirable decrease in the ABP the rule to select drug rate of administering follows individually and methodically. Decrease in the ABP can be observed not only during selection of rate of administering of nitroglycerine, but also is later against the background of the stabilized ABP. Therefore control of the ABP it is necessary to carry out at least 3-4 times an hour throughout all time of infusion of nitroglycerine.

At frequent use without intervals, free from use, the accustoming demanding increase in a dose can develop.

Higher dose can be required by the patients undergoing earlier treatment by organic nitrates (for example, isosorbide dinitrate, isosorbide mononitrate).

Expressiveness of a headache against the background of use of nitroglycerine can be reduced by decrease in its dose and/or simultaneous reception of mentolosoderzhashchy medicines.

If the illegibility of sight or dryness in a mouth remains and is expressed strongly, treatment has to be stopped.

At treatment of patients with the accompanying insulin-dependent diabetes mellitus it is necessary to consider that Solution Nitroglycerini contains a dextrose.

Side effects:

From cardiovascular system: weakness, a dermahemia, tachycardia, a heart consciousness, the expressed decrease in the ABP, unpleasant feelings behind a breast, an orthostatic collapse, cyanosis.

At the expressed decrease in the ABP developing of paradoxical bradycardia and strengthening of symptoms of stenocardia, feeling of heat, dryness of a mucous membrane of an oral cavity is possible.

From the alimentary system: nausea, vomiting, abdominal pain.

From the central nervous system: concern, uneasiness, psychotic reactions, faint, dizziness, "nitrate" headache, block, general weakness, disorientation.

Allergic reactions: skin rash, itch.

Local reactions: dermahemia, burning, dermatitis.

Others: sight illegibility, hypothermia, methemoglobinemia.

Interaction with other medicines:

Simultaneous use with vazodilatator, antihypertensives, inhibitors of an angiotensin-converting enzyme (APF), beta adrenoblockers, blockers of "slow" calcium channels, procaineamide, tricyclic antidepressants, monoamine oxidase inhibitors (MAO), phosphodiesterase-5 inhibitors, and also ethanol, strengthens hypotensive effect.

Against the background of quinidine and procaineamide the orthostatic collapse is possible.

Use with dihydroergotamine can lead to increase in its content in blood and lead to increase in the ABP (increase in bioavailability of dihydroergotamine).

Simultaneous intravenous administration of the fabric plasminogen activator (FPA) and nitroglycerine can accelerate clearance of TAPAS from a blood plasma due to strengthening of a hepatic blood-groove.

Simultaneous use of nitroglycerine and heparin reduces efficiency of the last (after drug withdrawal perhaps essential decrease in indicators of coagulability of blood that can demand a heparin dose decline).

Simultaneous use of nitroglycerine and sapropterin increases risk of development of arterial hypotension, in a consequence of potentiation sapropteriny synthesis of additional amount of nitrogen oxide.

Contraindications:

- hypersensitivity to drug and other organic nitrates;

- the isolated mitral stenosis, an aortal stenosis, a subaortal stenosis;

- cardiogenic shock;

- toxic fluid lungs;

- acute disorder of blood circulation (shock, collapse);

- an uncontrollable hypovolemia with a normal or low pulmonary pressure at patients with heart failure;

- arterial hypotension (at the systolic ABP the state hg can aggravate less than 90 mm, having caused paradoxical bradycardia and attacks of stenocardia);

- cardiac tamponade, chronic cardial compression;

- the diseases which are followed increase in intracranial pressure (including a craniocereberal injury, a hematencephalon);

- the expressed anemia;

- a concomitant use, phosphodiesterase-5 inhibitors (sildenafit, vardenafit, tadalafit);

- age up to 18 years (efficiency and safety are not established).

With care: atherosclerosis, an acute myocardial infarction with the low pressure of filling, a left ventricle, a hypertrophic subaortic stenosis, a heavy renal and/or liver failure, a thyrotoxicosis, closed-angle glaucoma, a diabetes mellitus.

Overdose:

Symptoms: the expressed decrease in the ABP (less than 90 mm hg), with orthostatic dysregulation, reflex tachycardia, the pulsing headache; the adynamy, dizziness, the increased drowsiness, feeling of heat, nausea, vomiting and diarrhea can develop; at use of high doses (more than 20 mg/kg) - a collapse, cyanosis, a methemoglobinemia, an asthma and a tachypnea. At very high doses increase in intracranial pressure is possible.

Treatment: stop further administration of drug. It is necessary to lower a bed-head and to raise the patient. As a rule, the ABP at the same time is normalized within 15-20 minutes after the termination of administration of drug, then it is possible to continue introduction after repeated selection of speed of infusion.

In case of the expressed decrease in the ABP and/or shock compensation of volume of the circulating blood has to be made; in exceptional cases for maintenance of blood circulation it is possible to enter Norepinephrinum (noradrenaline) and/or a dopamine.

Depending on severity it is offered to apply the following antidotes in case of a methemoglobinemia:

1. Ascorbic acid: 1 g in or intravenously.

2. Oxygen therapy, hemodialysis, exchange hemotransfusion.

Storage conditions:

In the place protected from light, far from fire, at a temperature from 5 to 25 °C. To store in the place, unavailable to children. A period of validity - 3 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, 1 mg/ml. Packaging: in ampoules on 2, 5 and 10 ml. On 5 ampoules place in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished or papers with a polymeric covering (or without foil and paper with a polymeric covering). On 1, 2 or on 10 blister strip packagings together with a knife ampoule or the scarificator and the application instruction place in a pack from a cardboard. When using ampoules with notches, rings and points the scarificator or a knife ampoule do not put.