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Pharmacological properties


Mechanism of action. Like all organic nitrates, isosorbide dinitrate (ISDN) acts as a nitric oxide (NO) donor. NO leads to relaxation of vascular smooth muscle by stimulation of guanylate cyclase and a subsequent increase in the concentration of intracellular cGMP. In this way, cGMP-dependent protein kinase is stimulated; as a result, phosphorylation of various proteins in the smooth muscle cell changes. In turn, this leads to dephosphorylation of the light chains of myosin and a decrease in contractility.

Pharmacodynamic effect. ISDN causes relaxation of the smooth muscles of blood vessels, which leads to vasodilation. Varicose veins promotes venous deposition of blood and reduces venous return to the heart; thus, the ventricular end diastolic pressure and volume are reduced (preload).

The effect on the arteries, and at higher doses on the arterioles, leads to a decrease in systemic vascular resistance (afterload). This, in turn, improves heart function.

The effect on both pre- and afterload leads to a decrease in heart oxygen consumption.

In addition, ISDN causes a redistribution of blood flow to the subendocardial parts of the heart under conditions of atherosclerotic lesions. The latter effect is probably due to the selective dilatation of large coronary vessels. Dilatation of collateral arteries caused by nitrates can improve myocardial perfusion in vascular stenosis. 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 develops as a result of a number of mechanisms, including a decrease in valvular regurgitation (by reducing ventricular dilatation) and a decrease in myocardial oxygen demand.

An increase in oxygen supply while reducing the need for it to the heart muscle reduces the area of ​​myocardial damage. Thus, isosorbide dinitrate may be useful for patients with myocardial infarction.

Influence on other organ systems includes relaxation of the bronchial muscles, gastrointestinal muscles, as well as the muscles of the biliary and urinary tract; the relaxation effect of the smooth muscles of the uterus has been reported.

Pharmacokinetics In the digestive tract, ISDN is released slowly from the sustained release tablet over the course of several hours. The onset of the drug in 15-30 minutes, the time to reach Cmax - from 15 minutes to 1-2 hours. Absorption of the active substance is high. Binding to plasma proteins - 30%.

The effect of the first passage is higher with oral administration.

ISDN is metabolized in the liver to form isosorbide-2-mononitrate (T½ - 1.5–2 h) and isosorbide-5-mononatrate (T½ - 4-6 hours). Both metabolites have pharmacological activity.

Bioavailability. The relative bioavailability of Dicor long when administered orally is about 80% compared to that of isosorbide dinitrate in the form of tablets that do not have a prolonged action. After the first passage through the liver, bioavailability is 15–30%.


Prevention and long-term treatment of angina pectoris.


Dicor long 20 mg: 1 tablet 2 times a day (equivalent to 40 mg of isosorbide dinitrate). the second / next dose should be taken no earlier than 6-8 hours after taking the first dose. with increased demand for nitrates, the daily dose can be increased to 1 tablet 3 times a day with an interval of 6 hours.

Dicor long 40 mg: 1 tablet 1 time per day (equivalent to 40 mg of isosorbide dinitrate). With increased demand for nitro drugs, the daily dose can be increased to 1 tablet 2 times a day (equivalent to 80 mg of isosorbide dinitrate). The second / next dose should be taken no earlier than 6-8 hours after taking the first dose.

Dicor long 60 mg: 1 tablet 1 time per day (equivalent to 60 mg of isosorbide dinitrate). With increased demand for nitrates, the daily dose can be increased to 1 tablet 2 times a day (equivalent to 120 mg of isosorbide dinitrate). The second / next dose should be taken no earlier than 6-8 hours after taking the first dose.

The maximum daily dose is 120 mg. The duration of the course of treatment is determined individually. The drug is intended for prolonged use, you can not abruptly stop.

Elderly patients. There is no evidence of a need for dose changes for elderly patients.

Pediatric population. The safety and effectiveness of isosorbide dinitrate for children have not been established to date.

Mode of application. Swallow the tablets without chewing, with a sufficient amount of liquid (for example, a glass of water).

Treatment should begin with low doses, gradually increasing them to the maximum effective. The duration of the course of treatment is determined by the doctor.


  • Hypersensitivity to isdn, other nitrate compounds or other components of the drug; acute vascular insufficiency (shock, vascular collapse); cardiogenic shock (if appropriate measures do not support a sufficient level of final diastolic pressure); severe arterial hypotension (systolic hell 90 mm RT. Art.); hypertrophic obstructive cardiomyopathy; constrictive pericarditis; cardiac tamponade; severe anemia; bleeding, severe hypovolemia (ISD, reducing venous return, can provoke syncope); during nitrate therapy, phosphodiesterase inhibitors cannot be used (e.g. sildenafil, see interactions); during nitrate therapy, you cannot use a soluble guanylate cyclase stimulant - riotsiguat (see interactions).

Side effects

The frequency of side effects can be defined as very often (≥1 / 10), often (≥1 / 100, 1/10), infrequently (≥1 / 1000, 1/100), rarely (≥1 / 10,000, 1/1000 ), very rarely (1/10 000), unknown (cannot be determined from the available data).

When using the drug, the following side effects are possible.

From the nervous system: very often - headache ("nitrate" headache); often - dizziness, drowsiness.

From the cardiovascular system: often - tachycardia; infrequently - increased symptoms of angina pectoris.

From the vascular system: often - orthostatic hypotension; infrequently - vascular collapse (sometimes accompanied by bradyarrhythmia and loss of consciousness); unknown - hypotension.

From the digestive tract: rarely - nausea, vomiting; very rarely - heartburn.

On the part of the skin and subcutaneous tissue: infrequently - allergic skin reactions (eg rash), hot flashes; very rarely - angioedema, Stevens-Johnson syndrome; unknown - exfoliative dermatitis.

General disorders: often - asthenia.

When using organic nitrates, severe hypotensive reactions have been reported, accompanied by nausea, vomiting, a feeling of anxiety, pallor, and increased sweating.

During therapy with the drug, temporary hypoxemia may occur due to the relative redistribution of blood flow into the alveolar zones with hypoventilation. In particular, in patients with coronary artery disease, this can lead to myocardial hypoxia.

Increasing the dose and / or changing the interval between doses can lead to a decrease in effectiveness or lack of effect.

Reporting suspected adverse reactions. Reporting suspected adverse reactions after drug registration is important. This allows continuous monitoring of the benefit / risk of this drug. Health care providers should report all suspected adverse reactions through the national reporting system.

special instructions

The drug should be used with caution and under close medical supervision with:

  • with low filling pressure, including acute myocardial infarction in case of dysfunction of the left ventricle (left ventricular failure). It is necessary to maintain a pressure of at least 90 mm Hg. st .;
  • with aortic and / or mitral stenosis;
  • with orthostatic dysfunction;
  • in diseases associated with increased intracranial pressure (an increase is possible. To date, such symptoms have been observed only after iv administration of high doses of nitroglycerin).

The drug should not be used to eliminate acute attacks of angina pectoris.

It describes the development of tolerance (decreased effectiveness), as well as cross tolerance to other drugs of the nitrate type (a decrease in the effect if the patient has previously taken a different nitrate). To prevent a decrease or loss of effect, long-term use at high doses (120 mg / day) should be avoided.

Patients on maintenance therapy should be advised that they should not take drugs that contain PDE inhibitors (e.g. sildenafil, tadalafil, vardenafil), because of the risk of developing uncontrolled arterial hypotension. ISDN therapy should not be discontinued for the administration of drugs containing PDE inhibitors (e.g. sildenafil, tadalafil, vardenafil), for an increased risk of an angina attack (see CONTRAINDICATIONS and SPECIAL INSTRUCTIONS).

Due to the fact that the drug contains lactose, it cannot be prescribed to patients with rare genetic diseases, such as galactose intolerance, Lapps hereditary lactase deficiency, glucose-galactose malabsorption.

Use during pregnancy and lactation

Pregnancy. Studies of reproductive toxicity in animals using isosorbide dinitrate in doses toxic to adults have not revealed evidence of toxic effects on the fetus. However, adequate and well-controlled studies in pregnant women are not available.

Given that animal studies cannot always predict the effect on humans, the drug should be used during pregnancy only if absolutely necessary and under the constant supervision of a doctor.

Lactation. It is not known whether isosorbide dinitrate passes into breast milk, therefore it is not recommended to be prescribed to women during lactation.

Fertility. There is no evidence of the effect of isosorbide mononitrate on human fertility.

Children. Do not use in children.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Even if used as directed, the drug can affect the reaction rate when driving vehicles or working with other mechanisms. This effect is enhanced by alcohol.


The antihypertensive effect of the drug can be enhanced when used with antihypertensive drugs (for example, β-adrenergic receptor blockers, diuretics, calcium channel blockers, apf inhibitors), vasodilators, antipsychotics, tricyclic antidepressants, as well as with alcohol.

The hypotensive effect of the drug is enhanced while taking PDE inhibitors (such as sildenafil, tadalafil, vardenafil), which can lead to life-threatening cardiovascular complications (see CONTRAINDICATIONS and SPECIAL INDICATIONS). Do not use isosorbide dinitrate simultaneously with PDE inhibitors (such as sildenafil, tadalafil, vardenafil).

The use of the drug Dicor long with riotsiguatom, a soluble stimulant of guanylate cyclase, is contraindicated (see CONTRAINDICATIONS), since the simultaneous use of these drugs can lead to arterial hypotension.

Patients recently treated with PDE inhibitors (e.g. sildenafil, vardenafil, tadalafil) should not use isosorbide dinitrate to treat acute conditions.

There are reports that the simultaneous use of the drug with dihydroergotamine can lead to an increase in the concentration of dihydroergotamine in the blood and, thus, enhance its effect.

Sapropertin (tetrahydrobiopterin, BH4) Is a cofactor of nitric oxide synthetase. With caution, it is recommended to use preparations containing saproterin simultaneously with any vasodilators, the mechanism of action of which is also associated with an effect on nitric oxide metabolism or which are also classic donors of nitric oxide (including nitroglycerin, isosorbide dinitrate (ISDN), isosorbide mononitrate (ISMN) )).


Symptoms: decreased hell ≤90 mm Hg. Art., pallor of the skin, increased sweating, a weak pulse, tachycardia, dizziness (including orthostatic reactions when changing the position of the body), headache, weakness, nausea, vomiting, diarrhea.

Cases of methemoglobinemia have been reported for patients taking other nitrates. During the biotransformation of ISDN, nitrite ions are released that can induce methemoglobinemia and cyanosis, followed by tachypnea, anxiety, loss of consciousness and cardiac arrest. The possibility of this adverse reaction in case of an overdose of ISDN cannot be ruled out.

Excessive doses can increase intracranial pressure, which sometimes causes cerebral symptoms.

General measures: stop using the drug.

General measures that are used in case of arterial hypotension caused by nitrates: give the patient a horizontal position with his head bowed at a low head; provide oxygen; increase bcc; carry out special anti-shock therapy (the patient should be in the intensive care unit).

Special measures: there is no specific antagonist of the vasodilating effect of ISDN. Since arterial hypotension, which develops with an overdose, is the result of venodilation and arterial hypovolemia, therapy should be aimed at increasing bcc (see General measures). Sometimes it is enough to give the patient a horizontal position. Sometimes an IV infusion of 0.9% sodium chloride solution (or a similar solution) is required. The use of adrenaline (INN - epinephrinum) in this situation is not recommended (the negative effect prevails over the positive).

Treatment of methemoglobinemia: restorative therapy with vitamin C, methylene blue or toluidine blue - to choose from; oxygen therapy (if necessary); Mechanical ventilation, exchange blood transfusion (if necessary); hemodialysis (if necessary).

Resuscitation measures: in case of signs of respiratory arrest or blood circulation, resuscitation measures are immediately applied.

Storage conditions

At a temperature not exceeding 30 ° C in the original packaging.

Tags: Isosorbide dinitrate