Izo-Mik sublingual spray 1.25 mg/300 doses 15 ml.

Description

Izo-Mik spray Composition
active substance: isosorbide dinitrate;

1 dose of spray contains isosorbide dinitrate isosorbide dinitrate aqueous (in terms of 100% isosorbide dinitrate) – 1.25 mg;

excipients: macrogol-400; ethanol 96%.

Izo-Mik spray Dosage form

Sublingual spray is dosed.

Basic physical and chemical properties: transparent colorless liquid with an alcohol smell.

Izo-Mik spray Pharmacotherapeutic group

Vasodilators used in cardiology. Organic nitrates. ATX code C01D A08.

Pharmacological properties

Pharmacodynamics.

Isosorbide dinitrate causes vascular smooth muscle to relax, leading to vasodilation. At the same time both peripheral arteries, and veins relax. This effect promotes venous “pulping” of blood and reduces venous return to the heart; thus reducing ventricular end-diastolic pressure and volume (preload). The effect on the arteries, and at higher doses on the arterioles leads to a decrease in systemic vascular resistance (postload). This, in turn, facilitates the work of the heart.

The effect on both preload and postload leads to a further reduction in cardiac oxygen consumption.

Isosorbide dinitrate also causes redistribution of blood flow to the subendocardial parts of the heart when coronary circulation is partially complicated by atherosclerotic lesions. This effect is probably due to the selective dilatation of large coronary vessels. Dilatation of collateral arteries caused by nitrates may improve poststenotic myocardial perfusion. In addition, nitrates counteract the appearance and eliminate coronary spasms.

In patients with congestive heart failure, nitrates improve hemodynamics at rest and during exercise. This positive effect is due to a number of pathogenetic mechanisms, including improved valvular regurgitation (by reducing the ventricle) and reducing myocardial oxygen demand.

Due to the decrease in oxygen demand and increase in its supply, nitrates limit myocardial damage during a heart attack. Thus, the use of isosorbide dinitrate may be useful for patients who have suffered a myocardial infarction.

Effects on other organ systems include relaxation of the muscles of the bronchi, as well as the muscles of the digestive tract, bile and urinary tract. There have also been reports of uterine smooth muscle relaxation.

Mechanism of action.

Like all organic nitrates, isosorbide dinitrate acts as a nitric oxide (NO) donor. Nitric oxide relaxes vascular smooth muscle by stimulating guanylyl cyclase and further increasing the concentration of cyclic intracellular guanosyl monophosphate (cGMP). This stimulates cGMP-dependent protein kinase and alters the phosphorylation of proteins in smooth muscle cells. This, in turn, causes dephosphorylation of myosin light chains and reduced contractility.

Pharmacokinetics.

After spraying in the mouth, the active substance – isosorbide dinitrate is absorbed very quickly. The effect of the drug begins in 1-3 minutes after application, the maximum concentration in blood plasma is reached within 3-6 minutes. The half-life is 30-60 minutes. Within 90-120 minutes, the concentration in blood plasma returns to baseline. Isosorbide dinitrate is metabolized to form isosorbide-2-mononitrate and isosorbide-5-mononitrate with half-lives of 1.5-2 hours and 4-6 hours, respectively. Both metabolites have pharmacological activity.

When used in the oral cavity isosorbide dinitrate undergoes rapid metabolism in the liver, resulting in a much higher bioavailability – 60-100% (when administered orally – 15-30%).