Mononitrosid

General characteristics. Structure:

International and chemical names: Isosorbіde mononіtrate; 1,4:3,6-диангидро-D-глюситола-5-нитрат;основные physical and chemical properties: tablets on 20 mg of white color, a ploskotsilindrichesky form, with a facet; tablets on 40 mg of white color, a ploskotsilindrichesky form, with a facet and risky; structure: 1 tablet contains 20 or 40 mg of isosorbide of mononitrate; excipients: lactose, starch corn, calcium stearate.

Pharmacological properties:

Pharmacodynamics. Drug represents a product of metabolism of nitroglycerine and isosorbide of dinitrate. Anti-anginal means from group of organic nitrates, a peripheral vazodilatator with the prevailing influence on venous vessels which mechanism of action is connected with formation of nitrogen oxide (an internal cause of a relaxation) in the presence of cysteine or other tiolsoderzhashchy connections. Nitrogen oxide, stimulating activity of guanylate cyclase, promotes accumulation of tsGMF and relaxation of unstriated muscles of vessels. The phlebectasia leads to reduction of venous capacity and preload of a myocardium, and arteries – to decrease in the general peripheric vascular resistance, pulmonary pressure and reduction of postload of heart. At the same time end diastolic pressure decreases, coronary circulation improves, blood supply of the most impressionable to ischemia of the subendocardial site of a myocardium improves. Weakening of peripheric venous and arterial resistance promotes reduction of expenses of energy, need of a myocardium for oxygen and recovery of sokratitelny activity of a myocardium in the conditions of heart failure and ischemia. At patients with heart failure and an ischemic disease drug increases cordial emission, tolerance to an exercise stress, reduces weight and frequency of attacks of stenocardia. Drug expands brain vessels, narrows vessels of internals, weakens unstriated muscles of bronchial tubes, the digestive channel, zhelche-and urinary tract. Isosorbide mononitrate promotes transition of hemoglobin to a methemoglobin and can worsen oxygen transport; suppresses aggregation and adhesion of thrombocytes.

Pharmacokinetics. Drug is completely soaked up after intake. Does not give in to presistemny metabolism at the first passing through a liver. Communication with blood proteins makes about 4%. The maximum concentration of drug in blood is reached through 2 – 4 – 6 hours. Anti-anginal action is registered in 45 – 90 minutes, lasts to 8 – 10 – 16 – 20 – 24 hours. The average period during which therapeutic concentration (not less than 100 mg/ml) contains makes till 17 o'clock. There is a direct dependence of concentration of drug in blood from the applied drug dose. Drug turns in kidneys where isosorbide and 2 glucuronide isosorbide-5-mononitrate is formed. The insignificant quantity – with excrements is excreted preferential by kidneys almost only in the form of metabolites (2% in not changed look). The elimination half-life for isosorbide of mononitrate makes 6,5 – 12 – 16 hours.

Indications to use:

Prevention of attacks of stenocardia. Treatment of chronic heart failure (as a part of a combination therapy), pulmonary hypertensia.

Route of administration and doses:

To accept 1 – 2 time a day on 1 tablet. Average daily doses make 20 – 40 – 100 mg/days. The maximum daily dose makes 120 mg, in case of emergency the dose can be raised to 120 – 240 mg of 1 times a day. It is necessary to swallow of a tablet entirely, washing down with a small amount of liquid. Duration of treatment and a dose is defined by portability of drug and achievement of therapeutic effect.

Features of use:

At long-term use of drug tolerance can develop, however drug withdrawal for 6–7 days recovers its efficiency. For prevention of development of tolerance breaks between purpose of drug have to make not less than 6-8 hours. Mononitrosid in tablets is not suitable for treatment of a bad attack of stenocardia. Administration of drug can lead to temporary decrease in content of oxygen in an arterial blood (anoxemia) because of relative redistribution of a blood-groove in the hypoventilated segments of lungs (the hypoventilated alveolar sites). It can serve as the reason of insufficient blood supply of heart (ischemia) at patients with disturbance of blood supply of coronary vessels of heart.
With care apply at patients with the expressed cerebral atherosclerosis, disturbances of cerebral circulation, at tendency to orthostatic hypotension, at heavy anemia, at patients of old age, and also at a hypovolemia and the expressed abnormal liver functions and kidneys. To periodically control the arterial pressure and the electrocardiogram at patients with the expressed atherosclerosis of coronary vessels and vessels of a brain. Reduction of end diastolic pressure (pulmonary capillary pressure) should not be lower than 1,4 kPa (12 mm of mercury.), – it is lower than 8 kPa of diastolic pressure (60 mm of mercury.), and system arterial pressure – lower than 1/3 from initial. During treatment not to allow alcohol intake. Can reduce the speed of psychomotor reactions that should be considered at control of vehicles or at occupations other potentially dangerous types of activity. Care when performing physical exercises in connection with strengthening of orthostatic hypotensive effects is necessary.
Pregnancy and lactation. Use of drug during pregnancy and in the period of a lactation perhaps only in case the expected advantage for mother exceeds potential risk for a fruit or the child.
There is no experience of use of drug for treatment of children.

Side effects:

From the central nervous system: a sight illegibility, a headache (in particular at the beginning of a course of treatment, at long therapy decreases), dizziness and feeling of weakness, motive concern.
From cardiovascular system: arterial hypotension, including orthostatic, feeling of heat, reflex tachycardia, hyperemia of the person. Sometimes, at a sharp lowering of arterial pressure, strengthening of symptoms of stenocardia (paradoxical "nitrate" reactions) can be observed.
From a digestive tract: dryness in a mouth, nausea, vomiting.
Allergic reactions: in some cases – an enanthesis, an itch; inflammatory diseases of skin (exfoliative dermatitis).

Interaction with other medicines:

At simultaneous use of Mononitrosid with other vazodilatator, APF inhibitors, blockers of calcium channels, β-adrenoblockers, diuretics, tricyclic antidepressants, MAO inhibitors, viagra (sildenafily), opioid analgetika, ethanol and etanolsoderzhashchy drugs hypotensive action amplifies. With β-adrenoblockers, blockers of calcium channels and APF inhibitors observe strengthening, and with sympathomimetics (noradrenaline, a phenylephine hydrochloride), oppression of anti-anginal action; with dihydroergotamine – increase in its concentration in plasma is possible. Use of drug against the background of reception of quinidine or a novokainamid can cause an orthostatic collapse. At use with heparin decrease in anticoagulating action is possible. Atropine and other drugs which possess M-holinoblokiruyushchim action (этацизин, an Ethmosinum) can reduce Mononitrosid's effect. Donators of sulphhydryl groups (captopril, Acetylcysteinum, Unithiolum) recover reduced sensitivity of an organism to drug.

Contraindications:

Shock, collapse, arterial hypotension (systolic arterial pressure is lower than 100 mm of mercury., diastolic arterial pressure is lower than 60 mm of mercury.), an acute myocardial infarction with the low filling pressure of a left ventricle, a hypertrophic subaortic stenosis, increase in intracranial pressure (including at a hemorrhagic stroke, after the postponed head injury), a closed-angle form of glaucoma with high intraocular pressure, hypersensitivity to nitrates, simultaneous use with viagra (sildenafily), a toxic fluid lungs.

Overdose:

Symptoms: a headache, nausea, vomiting, hypotension, feeling of heat or a fever, the increased sweating, диспноэ, increase in intracranial pressure (brain symptoms up to development of spasms and a coma), a methemoglobinemia (cyanosis and a tachypnea).
Treatment: to transfer the patient to horizontal position (legs raise higher than the level of the head), to wash out a stomach if there passed a little time, to apply plasma substitutes, sympathomimetics, oxygen. For elimination of a methemoglobinemia drug of the choice is methylene blue.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 25 °C. A period of validity – 2 years.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging, on 3 or 4 planimetric packagings in a pack.