Isosorbide dinitrate

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Available since: 2019-09-19

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Clinical Pharmacology

Peripheral vasodilator with a predominant effect on the venous vessels. Antianginal agent. The mechanism of action is associated with the release of the active substance nitric oxide in the smooth muscles of the vessels. Nitric oxide causes the activation of guanylate cyclase and increases the level of cGMP, which ultimately leads to relaxation of smooth muscles. Under the influence of isosorbide dinitrate, arterioles and precapillary sphincters relax to a lesser extent than large arteries and veins. This is partly due to reflex reactions, as well as the less intense formation of nitric oxide from the molecules of the active substance in the walls of arterioles.

The action of isosorbide dinitrate is mainly associated with a decrease in myocardial oxygen demand due to a decrease in preload (dilation of peripheral veins and a decrease in blood flow to the right atrium) and afterload (decrease in OPS), as well as direct coronary dilating. It promotes the redistribution of coronary blood flow in the area with reduced blood supply.

Increases exercise tolerance in patients with coronary artery disease, angina pectoris. In heart failure, it helps to relieve the myocardium by reducing preload. Reduces pressure in the pulmonary circulation.

Indications

For oral administration, sublingually, buccal: relief and prevention of angina attacks, rehabilitation treatment after myocardial infarction. Chronic heart failure (as part of combination therapy), some forms of pulmonary hypertension, pulmonary heart (as part of combination therapy).

For injection into the oral cavity: the relief and prevention of strokes; as a means of emergency care in acute myocardial infarction and acute left ventricular failure in the prehospital phase. Prevention and treatment of coronary artery spasm using a cardiac catheter.

For iv administration: acute myocardial infarction, incl. complicated by acute left ventricular failure; unstable angina; pulmonary edema.

For skin use: prevention of strokes.

Composition

Active islands: isosorbide dinitrate 10 mg;
Auxiliary Islands: sugar, potato starch, calcium stearate

Isosorbide dinitrate is marketed under different brands and generic names, and comes in different dosage forms:

Brand name	Manufacturer	Country	Dosage form
			pills
Cardiket	UCB Pharma	Belgium	pills
Izoket			ampoules

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Dosage and Administration

For ingestion, a single dose is 10-120 mg, the frequency of administration is 1-5 times / day, depending on the indication and the dosage form used.

With sublingual or buccal administration, a single dose is 5–10 mg, the frequency of administration depends on the indications and the patient’s response to treatment.

When injected into the oral cavity, use 1-3 doses with an interval of about 30 seconds on the background of breath holding. In acute myocardial infarction and acute heart failure, the initial dose is 1-3 injections. If there is no improvement after 5 minutes, the injection can be repeated under the condition of constant monitoring of blood pressure and heart rate. For the prevention of coronary spasm in the case of catheterization, 1-2 doses should be applied immediately before the procedure.

With the / in the introduction of the dosing regimen depends on the clinical situation and the dosage form used.

For cutaneous application, the initial dose is 1 g at night, at bedtime, and if necessary in the morning.

The duration of treatment is determined in each case individually.

Adverse reactions

Since the cardiovascular system: dizziness, headache, tachycardia, transient facial flushing, sensation of heat, arterial hypotension; in some cases - increased angina attacks (paradoxical reaction).

On the part of the digestive system: nausea, vomiting, the appearance of a slight burning sensation of the tongue, dry mouth.

From the side of the central nervous system and peripheral nervous system: drowsiness, blurred vision; rarely - cerebral ischemia and collapse.

Allergic reactions: skin rash.

Contraindications

Severe arterial hypotension (systolic blood pressure less than 100 mm Hg, diastolic blood pressure less than 60 mm Hg), collapse, shock, acute myocardial infarction with severe arterial hypotension, hypertrophic obstructive cardiomyopathy, constrictive pericarditis, heart swelling, constrictive pericarditis, cardiac swelling, hypertrophic obstructive cardiomyopathy, constrictive pericarditis, cardiac arterial hypotension, hypertrophic obstructive cardiomyopathy, constrictive pericarditis, cardiovascular hypotension , conditions associated with increased intracranial pressure (including hemorrhagic stroke, head injury), angle-closure glaucoma, simultaneous administration of sildenafil (PDE inhibitor), increased sensitivity to nitrate .

Drug interactions

At simultaneous use with adsorbents, the knitting and enveloping means absorption of isosorbide dinitrate decreases.

With the simultaneous use of antihypertensive drugs, peripheral vasodilators, calcium channel blockers, beta-blockers, antipsychotics (neuroleptics), tricyclic antidepressants, PDE inhibitors, ethanol may increase the hypotensive effect.

With simultaneous use of anticholinergic agents, memory and attention disorders in elderly patients are possible.

With simultaneous use with sympathomimetic agents, the antianginal effect of isosorbide dinitrate may be reduced.

With simultaneous use with dihydroergotamine may increase the concentration and enhance the action of dihydroergotamine.

With simultaneous use with norepinephrine, the therapeutic effect of norepinephrine is reduced.

With simultaneous use with sildenafil there is a risk of severe arterial hypotension and myocardial infarction.

Pregnancy and Lactation

The use of isosorbide dinitrate during pregnancy and lactation (breastfeeding) is possible only if the intended benefit to the mother outweighs the potential risk to the fetus or child.

Special instructions

It is used with caution in patients with impaired cerebral circulation, with aortic and / or mitral stenosis; in patients prone to orthostatic hypotension; in elderly patients. During the period of treatment, especially in the case of a gradual increase in dose, control of blood pressure and heart rate is necessary.

During the period of treatment to prevent the use of alcohol.

Influence on ability to drive motor transport and control mechanisms

During the period of treatment it is not recommended to drive vehicles or engage in other potentially hazardous activities, because with regular use, isosorbide dinitrate reduces the ability to concentrate and the speed of psychomotor reactions.