Isoketum spray doser. fl. 15 ml

Pharmacological properties

Pharmacodynamics. isosorbide dinitrate causes relaxation of unstriated muscles of vessels that conducts to a vazodilatation. at the same time both peripheral arteries, and veins relax. such effect promotes venous "pooling" of blood and reduces venous return to heart; thus the ventricular end diastolic pressure and volume (preloading) decreases. action on an artery, and at use of the highest doses — on arterioles — leads to decrease in system vascular resistance (afterload). it, in turn, facilitates cardiac performance.

Influence as on before - and leads an afterload to further reduction of consumption by oxygen heart.

Isosorbide dinitrate also causes redistribution of a blood-groove to subendocardial departments of heart in case coronary circulation is partially complicated by atherosclerotic defeats. Such influence is probably explained by selection dilatation of large coronary vessels. The dilatation of collateral arteries caused by nitrates can improve perfusion of a poststenotichny myocardium. Besides, nitrates counteract emergence and eliminate a coronary spasm.

At patients with stagnant heart failure nitrates improve a hemodynamics at rest and at loading. This positive effect is reached owing to a number of pathogenetic mechanisms, including improvement of valve regurgitation (thanks to reduction of a ventricle) and reduction of need of a myocardium for oxygen.

Owing to reduction of oxygen requirement and increase in its receipt injury of a myocardium in a heart attack. Thus, use of isosorbide of dinitrate can be useful to patients which transferred a myocardial infarction.

Influence on other systems of bodies are included by relaxation of muscles of bronchial tubes and also muscles of a GIT, bilious and urinary tract. There are also messages about relaxation of unstriated muscles of a uterus.

action Mechanism

It is similar to all organic nitrates, isosorbide dinitrate works as the donor of nitrogen oxide (NO). Nitrogen oxide causes relaxation of unstriated muscles of vessels by stimulation of a guanililtsiklaza and further increase in concentration of intracellular tsGMF. Thus the tsGMF-dependent protein kinase is stimulated and thereof phosphorylation of proteins in a cell of an unstriated muscle changes. It, in turn, causes dephosphorylation of easy chains of myosin and decrease in a contractilnost.

Pharmacokinetics. After injection in an oral cavity active agent — isosorbide dinitrate — is very quickly soaked up. Effect of medicament begins in 1–3 min. after use, the C _max in blood plasma is reached for 3–6 min. T _½ makes 30–60 min. For 90–120 min. the concentration in blood plasma is restored to initial level. Isosorbide dinitrate is metabolized with formation of isosorbide-2-mononitrate and isosorbide-5-mononitrate with T _½ which make according to 1.5-2 h and 4–6 h. Both metabolites have pharmacological activity.

At use in an oral cavity of isosorbide dinitrate passes fast metabolism in a liver thanks to what much higher bioavailability — 60–100% (is reached at oral administration — 15–30%).

Indication

is Appointed the adult:

• for prevention and treatment of attacks of stenocardia;
• in an acute myocardial infarction;
• in acute left ventricular heart failure.

Use

Drug is appointed only the adult. for dispersion in an oral cavity. the dose has to be adapted to specific features of the patient.

For stopping of an attack of stenocardia or before physical or emotional activity which can cause an attack needs to inject medicament into an oral cavity 1–3 times with an interval between injections of 30 pages.

Single dose for the termination of an attack of stenocardia can be raised (to 3 injections) only according to the recommendation of the doctor.

In an acute myocardial infarction or an acute heart failure is begun with 1–3 injections. In case of lack of effect for 5 min. it is possible to make 1 more injection. If in the next 10 min. the improvement does not occur, it is possible to repeat use of spray under careful control of the ABP.

described tolerance (decrease in efficiency) and also cross tolerance with other medicaments of nitrate group (decrease in effect in case of the previous therapy by other nitrate). To prevent decrease or loss of effect, it is necessary to avoid frequent administration of medicament in high doses.

Instruction for use

Before the first use of medicament needs to be pressed several times the spray, sending splashes to air, the uniform cloudlet of spray will not be created yet. Now medicament is ready to use.

If after the last use of medicament passed 1 days, the first raspryskivaniye should be made in air, in order to avoid use of an incomplete dose.

At use a bottle needs to be held vertically, the spray up.

closely to a mouth and, having pressed the spray, to inject solution into a mouth thus:

• to make a deep breath;
• to hold the breath;
pressing
• spray, to inject solution into a mouth (at the same time there can be an easy burning in language);
• to close a mouth and throughout the following 30 with to breathe only through a nose.

Solution should not be inhaled. For a guarantee of faultless action it is necessary to press the spray continuously up to the end and again to release. From time to time it is necessary to check operation of the spray, especially at long non-use.

On the label of a bottle from below put an arrow. If liquid level in a bottle reaches the upper edge of an arrow, it is recommended to get a new bottle of drug. However, further use is possible too until in slightly inclined bottle the end of a tube still is shipped in liquid.

Drug is contraindicated to

Contraindication

• hypersensitivity to isosorbide to dinitrate, other nitrate compounds or other components of drug;
• acute vascular insufficiency (shock, vascular collapse);
• cardiogenic shock, at impossibility of correction of end diastolic pressure of a left ventricle by means of the appropriate measures;
• profound arterial hypotension (systolic arterial blood pressure of 90 mm Hg.);
• a hypertrophic subaortic stenosis;
• chronic cardial compression;
• to a cardiac tamponade.

during therapy by nitrates cannot apply FDE inhibitors (for example sildenafit — see INTERACTIONS).

Side effects

In an initiation of treatment quite often the headache (nitrate headache) which usually disappears in several days and does not demand medicament withdrawal can arise.

from a cardiovascular system: often — reflex tachycardia, at the first use or at increase in a dose noted sharp decrease in the ABP and/or at change of position of a body; sometimes, at considerable decrease in the ABP, the expressiveness of symptomatology of stenocardia can increase; collapse can develop (which sometimes is followed by bradyarrhythmia (delay of pulse) and a short-term loss of consciousness (syncope).

from a GIT: sometimes — nausea, vomiting; very seldom — heartburn.

General disturbances: the feeling of weakness, easy burning is always on the lips after injection of medicament in an oral cavity.

from nervous system: sometimes — a headache; often — dizziness, drowsiness, feeling of heat.

from skin and hypodermic fabric: sometimes — erubescence and allergic reactions (for example rash); in some cases there was exfoliative dermatitis. Very seldom the Quincke's disease, Stephens's syndrome — Johnson can develop.

! At use of organic nitrates there are data on development of heavy hypotensive reactions which were followed by nausea, vomiting, feeling of concern, pallor and the raised potovydeleniye.

Use of medicament can cause a temporary anoxemia because of relative redistribution of a blood-groove in alveolar zones with hypoventilation. At persons with an ischemic heart disease it can lead to a temporary hypoxia of a myocardium.

Special instructions

can use Drug with extra care and at careful observation of the doctor at:

• lowered arterial blood pressure, for example in an acute myocardial infarction, dysfunction of a left ventricle (left ventricular failure); it is necessary to avoid decrease in systolic arterial blood pressure of 90 mm Hg.;
• aortal and/or mitral stenosis;
• orthostatic dysfunction;
• diseases which are followed by increase in intracranial pressure (though further increase in pressure happens only at administration of nitroglycerine in high doses);
• at use of Isoketum the tolerance to other medicaments containing nitrates can develop.

Caution: solution contains 85 about. alcohol %.

hits of solution in eyes.

that administration of medicaments containing FDE inhibitors is forbidden to them (for example sildenafit) in connection with risk of emergence of an attack of stenocardia.

Use during pregnancy and feeding by a breast. In pilot studies on animals the teratogenic effect of isosorbide of dinitrate is not revealed. Drug can be used during pregnancy only in urgent cases and it is exclusive when the advantage for the woman exceeds possible risk for a fruit.

Drug can probably get into breast milk therefore in need of use of medicament during this period the feeding by a breast should be stopped.

Children. Do not apply.

Ability to influence speed of response at control of vehicles and in operating time with mechanisms. Drug can reduce speed of response therefore it is necessary to refrain from control of vehicles or work with mechanisms for the period of treatment. Such effect amplifies at alcohol intake.

Interaction

Hypotensive effect of medicament can amplify at simultaneous use with other vasodilators, such as blockers of β-adrenoceptors, blockers of calcium channels, vazodilatator, etc., ethanol, neuroleptics and tricyclic antidepressants.

At the combined use with FDE inhibitors (for example with sildenafily which is applied in erectile dysfunction) effect of medicament so amplifies that it can lead to cardiovascular complications, life-threatening.

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Overdose

Symptoms: sharp decrease hell to level systolic hell of 90 mm Hg.; pallor; the strengthened potovydeleniye; weak filling of pulse; tachycardia; dizziness (including orthostatic reactions at change of position of a body); headache; weakness; nausea; vomiting; diarrhea.

Concerning the patients accepting other nitrates it was reported about methemoglobinemia cases. At biotransformation of isosorbide of dinitrate nitrite ions which can induce a methemoglobinemia and cyanosis with the subsequent tachypnea, feeling of alarm, a loss of consciousness and cardiac arrest are released. It is impossible to exclude a possibility of development of such side reaction at dinitrate isosorbide overdose.

to increase in intracranial pressure which sometimes leads to emergence of cerebral symptoms.

Treatment: to stop medicament use; in case of arterial hypotension to give to the patient horizontal position with the hung head and the lower extremities raised higher than the level of the head; to provide intake of oxygen; to increase the volume of the circulating blood plasma; to carry out special antishock therapy (the patient has to be in intensive care unit).

Special measures: increase in the ABP if it is very low; additional use of Norepinephrinum or other vasoconstrictors; do not recommend to apply epinephrine in such situation (the negative effect over positive prevails).

Treatment of a methemoglobinemia: recovery therapy with vitamin C, methylene blue or toluidine blue — for choice, oxygen use (if necessary), IVL, blood transfusion (if necessary). The hemodialysis is inefficient.

At emergence of symptoms of an apnoea or blood circulation are immediately undertaken by resuscitation measures.

Storage conditions

At a temperature not above 25 °C.