Nitromintum

General characteristics. Structure:

Aerosol hypoglossal dosed 1 dose - nitroglycerine of 0,4 mg
excipients: ethanol; propylene glycol  
in the aerosol cans with the portioning device containing 1% of solution (active agent of 8 g) on 10 g; in a box 1 cylinder containing 180 doses.
Description of a dosage form

Colourless or almost colourless transparent solution without deposit.

Pharmacological properties:

Pharmacological action - anti-anginal, vasodilating, venodilatiruyushchy.

Pharmacokinetics. Nitromintum an aerosol is quickly and completely soaked up from an oral cavity in a system blood stream. Bioavailability at sublingual reception makes 100% since "primary" hepatic degradation of drug is excluded. Cmax in a blood plasma is reached in 4 min. Linkng with blood proteins — 60%. 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 Cl makes 25–30 l/min. After administration of drug under the T1/2 language makes 2,5–4,4 min. of a blood plasma. The circulating nitroglycerine is strongly connected with erythrocytes and collects in walls of vessels. The main way of removal of nitroglycerine — excretion of metabolites with urine, less than 1% of the entered dose is allocated in not changed look.

Pharmacodynamics. Effects of nitroglycerine are caused by its ability to release the nitrogen oxide which is the natural endothelial running-down factor from the molecule. Nitrogen oxide increases intracellular concentration of a cyclic guanozinmonofosfat that prevents penetration of calcium ions into smooth muscle cells and causes their relaxation. Relaxation of unstriated muscles of a vascular wall causes vasodilatation that reduces venous return to heart (preloading) and resistance of a big circle of blood circulation (afterload). It reduces load of heart and reduces the need of a myocardium for oxygen.
Expansion of coronary vessels improves a coronary blood stream and promotes its redistribution in the area with reduced blood circulation that increases delivery of oxygen in a myocardium. Reduction of venous return leads to filling pressure decrease, improvement of blood supply of subendocardial layers, pressure decrease in a small circle of blood circulation and regression of symptoms at a fluid lungs.
Nitroglycerine exerts the central braking impact on a sympathetic tone of vessels, oppressing a vascular component of formation of a pain syndrome. Nitroglycerine also relaxes smooth muscle cells of bronchial tubes, urinary tract, a gall bladder, bilious channels, a gullet, a small and large intestine, and also their sphincters.
Action of Nitromintum begins quickly, the effect develops within 1–1,5 min. and about 30 min. last.

Indications to use:

- stenocardia (stopping and prevention of attacks, including before an exercise stress);
- an acute left ventricular failure (as auxiliary therapy).

Route of administration and doses:

Sublingual. Before the first use of a cylinder it is necessary to fill a dispensing pump by removal of a protective cap and pressing the dosing valve several times before emergence of an aerosol. After a long break in use of a cylinder there can be a need for a pump refill. When using the cylinder should be held vertically, the spraying head up. Each pressing the dosing valve releases 1 dose (0,4 mg of nitroglycerine) in the form of an aerosol from the cylinder supplied with the mechanical pump. It is not necessary to stir up a cylinder before the use.
For stopping of an attack of stenocardia — 0,4–0,8 mg (1–2 doses), pressing the dosing valve, it is desirable in situation "sitting", at breath holding with intervals in 30 with; after that it is necessary to close a mouth for several seconds. If necessary — repeated introduction, but no more than 1,2 mg (3 doses) within 15 min.
For the prevention of development of an attack — 0,4 mg (1 dose) in 5–10 min. prior to loading.
At an acute left ventricular failure, the developing fluid lungs — 1,6 mg (4 doses) and more for a short period at strict control of a condition of blood circulation (the GARDEN has to be> 100 mm of mercury.). At insufficient therapeutic effect the same dose can be repeated in 10 min.
Change of the mode of dosing at use of drug for elderly patients is not required.

Features of use:

Nitromintum strengthens removal of catecholamines and vanilinmindalny acid with urine.
The use of alcoholic beverages during use of drug is strictly forbidden.
Influence on driving of motor transport and the work requiring special attention
In an initiation of treatment it is necessary to abstain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions. Further extent of restrictions is defined individually for each patient.

Side effects:

From cardiovascular system: dizziness, headache, tachycardia, heat, decrease in the ABP; seldom (especially at overdose) — an orthostatic collapse, cyanosis.
From the alimentary system: dryness in a mouth; seldom — nausea, vomiting, abdominal pain.
From TsNS: weakness; seldom — uneasiness, psychotic reactions, block, a disorientation.
Allergic reactions: seldom — skin rash, an itch.
Local reactions: a dermahemia, burning under language.
Others: seldom — a sight illegibility, a hypothermia, a methemoglobinemia.

Contraindications:

hypersensitivity to organic nitrates;
shock;
collapse;
age up to 18 years (lack of sufficient clinical data).

With care:
the acute circulatory unefficiency which is followed by the expressed arterial hypotension (the GARDEN <90 mm of mercury.);
orthostatic hypotension;
hemorrhagic stroke;
acute myocardial infarction and chronic heart failure with the low filling pressure of a left ventricle;
hypertrophic cardiomyopathy;
heavy renal and/or liver failure;
heavy anemia and thyrotoxicosis;
alcohol intoxication;
 epilepsy;
CHMT;
intracranial hypertensia;
closed-angle glaucoma (risk of increase in intraocular pressure);
migraine.

Use at pregnancy and feeding by a breast

Use of Nitromintum at pregnancy and during breastfeeding demands careful comparison of risk and advantage and has to be carried out under strict medical observation. Nitroglycerine excretion in breast milk is not established.

Overdose:

Symptoms: a headache, decrease in the ABP, orthostatic hypotension, reflex tachycardia, dizziness, face reddening, vomiting and diarrhea, an adynamy, the increased drowsiness, feeling of heat. Extremely high doses (more than 20 mg/kg) lead to a methemoglobinemia, cyanosis, диспноэ and a tachypnea, to an orthostatic collapse.
Treatment: in mild cases — transfer of the patient in situation "lying" with the raised legs. In hard cases it is necessary to apply the general methods of treatment of intoxication and shock (completion of OTsK, introduction of noradrenaline and/or dopamine, etc.). Use of adrenaline is contraindicated!
At development of a methemoglobinemia it is possible to apply the following antidotes and methods of treatment:
1) vitamin C — 1 g in the form of sodium salt inside or in/in;
2) methylene blue in/in in a dose to 50 ml of 1% of solution;
3) toluidine blue in/in, the first dose — 2–4 mg/kg, then repeatedly on 2 mg/kg;
4) oxygenotherapy, hemodialysis, hemotransfusion (exchange).

Storage conditions:

Period of validity 3 years. List B.: In the place protected from light, far from heat sources, at a temperature of 15-25 °C. Drug is flammable and explosive! The empty cylinder is impossible bromate in fire! It is forbidden to store and apply near naked flame and during smoking!

Issue conditions:

According to the recipe

Packaging:

The aerosol hypoglossal dosed 0,4 mg / a dose. On 10 g of solution (180 doses) in lithographed metal (from aluminum) the cylinder supplied with a dispensing pump with a raspylitelny head. 1 cylinder is packed into a cardboard pack.