Isosorbide dinitrate

Ischemic heart disease is considered one of the most common cardiac pathologies. Angina pectoris, heart failure, asthma attacks, edematous syndrome - this is an incomplete list of common conditions, often manifestations of IHD. To effectively combat dangerous pathology, it is customary to use a remarkable anti-angiogenic agent - isosorbide dinitrate, which belongs to the class of nitrates and is an active substance of many cardiac preparations.

In this article we will talk about the drug of the same name, named in accordance with the active substance "Isosorbide dinitrate".

[1], [2], [3], [4],

Indications Isosorbide dinitrate

As already mentioned, the main indication for the use of isosorbide dinitrate, under whatever name the drug is produced, is ischemic heart disease, which is often called the hungry heart syndrome. But different manifestations of pathology may require the use of different forms of the drug, which is used both for long-term medical treatment, and for rapid removal of dangerous symptoms.

Thus, the administration of conventional long-acting tablets and capsules, sublingual tablets and TTC films is advisable in the following cases:

• to reduce the intensity of angina attacks (pressing or compressive pain, and burning behind the sternum in the heart),
• for the prevention of the above-described conditions associated with a lack of blood supply to the heart muscle,
• for the treatment of CHF (chronic or congestive heart failure), when this drug is prescribed as part of various measures for the treatment of the disease,
• for the treatment of arterial hypertension as one of the manifestations of IHD,
• for the treatment of certain types of pulmonary hypertension, characterized by increased pressure in the pulmonary artery system,
• in the composition of multicomponent therapy of pathology, in which the right heart is enlarged (enlarged) due to diseases of the broncho-pulmonary system ("pulmonary heart"),
• for rehabilitation after myocardial infarction.

A solution for intravenous infusion or slow injection is used in situations that are life-threatening for the patient, such as:

• pulmonary edema,
• acute stage of myocardial infarction,
• complication of IHD, threatening the development of myocardial infarction, called unstable angina in medical practice.

The use of a spray (inhalation route of administration of the drug) is justified if an ambulance outside the hospital is required:

• at an acute stage of a myocardial infarction on a background of left ventricular failure,
• for the prevention and treatment of angina attacks,
• as a therapeutic and prophylactic agent for spasm of the heart arteries during the study of blood vessels with the help of a cardiac catheter.

In acute heart failure, "Isosorbide dinitrate" is often used to widen the lumen in the vessels and improve the coronary circulation.

[5], [6]

Release form

Treatment with isosorbide dinitrate is just the case when nitrates (nitric acid salts) do not harm health, but rather allow it to be strengthened. The chemical formula of the active substance is representable as C ₆ H ₈ N ₂ O ₈.

Nitrocontaining substance itself has the appearance of a white powder, which lacks both smell and taste. The powder is practically insoluble in water. To dissolve it, use acetone, alcohol or ether.

For convenience of use, taking into account the indications for use, the medicine for ischemic heart disease is produced in several forms. Traditional release forms, such as tablets, capsules and concentrate (the powder from which the solution used for injections and droppers are prepared) exist in parallel with the special ones: sublingual spray and TTC (drug film that is attached to the gum).

Conventional tablets may contain 5, 10 or 20 mg of active ingredient. The package contains 20 or 50 tablets. Sublingual tablets (they should not be swallowed, but kept under the tongue until completely dissolved) contain 5 mg of isosorbide dinitrate.

Prolonged forms of the drug (tablets and capsules with a prolonged action) contain 20, 40, 60 and even 120 mg of the active ingredient.

Concentrate for the preparation of the solution in vials contains 10 mg of the active ingredient in 1 ml volume.

Spray and aerosol for spraying under the tongue contain 300 doses of cardiac medication (300 sprays), with each dose containing 1.25 mg of isosorbide dihydrate.

[7], [8], [9]

Pharmacodynamics

"Isosorbide dinitrate" is considered one of the most effective tools used to treat ischemia of the heart and relief of angina attacks. Such recognition is due to its active substance, which has the following properties:

• expansion of the lumen of the vessels (vasodilating effect),
• decrease in the need of the main cardiac muscle in oxygen (anti-angiogenic effect),
• general coronary dilatory action.

Expansion of coronary and peripheral vessels is due to a decrease in the tone of the vessels and the relaxation of their muscular walls, which is impossible without the participation of nitric oxide. The drug increases the concentration of NO ₂  in the muscle tissue of the vessels (arteries and veins).

Antianginal action of the drug is due to three factors:

• reduction of peripheral resistance of blood vessels (postload),
• the expansion of peripheral veins, as a result of which the blood flow to the right atrium decreases (preload),
• expansion of coronary vessels.

Thus, "Isosorbide dinitrate" reduces the load on the heart muscle (myocardium) in the failure of its functions. It also promotes the expansion of the blood vessels of the heart and ensures normal nutrition and oxygen saturation of areas with a disturbed blood supply to the blood.

Isosorbide dinitrate is able to reduce blood pressure in a small circle of circulation. And this, in turn, is a necessary measure to prevent pulmonary edema.

[10], [11], [12], [13]

Pharmacokinetics

Improving coronary and peripheral blood circulation, the drug still has no effect on the frequency of contractions of the heart muscle. Only in rare cases there is a slight increase in heart rate. In addition to expanding the heart vessels, the drug promotes dilatation of the vessels of the brain and lungs, improving cerebral and pulmonary circulation.

The speed of the onset of the effect of taking the drug depends on the form of release of the drug. Although they all have sufficient speed. For example, the action of sublingual tablets can be noticed after 3-5 minutes. Ordinary and prolonged tablets give effect after 15-20 minutes, although some circumstances can slow the onset of the therapeutic effect to 30-40 minutes.

In case of spraying the spray into the oral cavity, the therapeutic effect can be seen after half a minute (due to the rapid absorption of the drug into the blood through the mucous membrane), which is very important in situations requiring urgent measures. At the same time, a once-sprayed dose is sufficient for a period of up to 2 hours.  

The metabolism of the active substance occurs in the liver, as a result of which monosodium isosorbide is formed. The medicine is excreted from the body through the kidneys.

The half-life of the drug also depends on the form of release. For the injection solution, it is about 20 minutes, for conventional tablets - 4 hours, for sublingual - 1 hour, etc.

[14], [15], [16], [17], [18]

Dosing and administration

"Isosorbide dinitrate" is a cardiac drug that can be used in any effective and convenient way: by mouth, washing the tablets with water, placing a sublingual tablet under the tongue or spraying into this area a spray at the prescribed dosage, fixing a special medicinal film on the gum or behind the cheek, and also using intravenous injections or droppers.

Tablets for oral administration are usually taken orally in whole, squeezed with enough liquid, it is recommended to do this an hour before meals or, in extreme cases, a couple of hours after it.

If necessary, to relieve an attack of angina pectoris can be chewed and swallowed after the pain syndrome subsides. For this purpose, tablets 5 and 10 mg are used. A tablet with a higher dosage will have to be divided.

Prevention of angina attacks begins with a dosage of 10 mg. Take the pill will have 4 to 5 times a day.

If the indicated dosage turns out to be insufficiently effective, on the 4th-5th day of therapy with the drug, the daily dosage is increased (from 60 to 120 mg as much as possible). The frequency of taking the drug depends on the type of tablets: regular tablets - 3-4 times a day, retard - from 1 to 3 times a day.

Treatment of CHF symptoms is carried out using conventional tablets with a dosage of 10 and 20 mg. Multiplicity of reception in this case can be from 3 to 4 times a day.

The maximum single dose for sublingual tablets and buccal films is 10 mg. Multiplicity of admission is established by the attending physician based on the diagnosis and condition of the patient.

Using a sublingual spray involves injecting into the oral cavity from 1 to 3 doses of the formulation. Injections should be carried out with an interval of half a minute and a delay in breathing at the time of manipulation.

The use of the spray as an emergency for acute infarction or CHF is carried out at the same dosage, the only time that if the first dose of the drug has not brought relief, after 5 minutes, the injection of the drug can be repeated. The next use of the spray is possible after 10 minutes. Usually this is enough to relieve the life-threatening symptoms.

When performing a coronary examination using a catheter, the patient is injected into the patient under the tongue 1 or 2 doses of the drug in the form of a spray. This is necessary to prevent spasm of the blood vessels of the heart.

Dosage for intravenous infections or infusions can vary greatly in each case. The effective dose is determined by the attending physician, however, as well as the duration of therapy with the drug "Isosorbide dinitrate".

[24], [25], [26], [27]

Use Isosorbide dinitrate during pregnancy

The use of Isosorbide dinitrate during pregnancy is not prohibited, but it should only be taken after a preliminary consultation with a specialist doctor and in the doses indicated. You can apply the drug and during breastfeeding, but just in case it is better at this time to transfer the baby to nutritional milk formula.

Contraindications

The preparation based on isosorbide dinitrate is undesirable and even dangerous to apply in the following situations:

• if the patient is diagnosed with a stably low blood pressure,
• shock state,
• a sharp drop in blood pressure, characterizing the onset of collapse,
• a neglected stage of pericarditis, in which the inflammation and thickening of the leaves of the cardiac membrane (pericardium) causes compression of the heart (constrictive pericarditis),
• thickening of the interventricular muscle, which leads to a violation of coronary blood flow (obstructive HCMC),
• with craniocerebral injuries,
• patients with a diagnosis of "hemorrhagic stroke,
• at high rates of intracranial pressure,
• if acute myocardial infarction is observed against a background of low blood pressure,
• accumulation of fluid in the cavity of the heart shell, which in cardiology is called a cardiac tamponade,
• If pulmonary edema is caused by a toxic factor,
• glaucoma is of the closed type,
• hypersensitivity to the components of the dosage form,
• an allergic reaction to organic nitrates.

The drug should be used under the supervision of a doctor with a narrowing of the mitral orifice and aortic stenosis, with low blood pressure, impaired cerebral circulation, liver failure, in old age. The drug is not used in pediatrics.

[19], [20], [21], [22]

Side effects Isosorbide dinitrate

Individual reaction of the body to taking the drug "Isosorbide dinitrate" can be different. Some patients tolerate therapy with the drug well, while others may experience some side effects. Among such unpleasant manifestations are:

• mild to moderate headaches,
• change in skin color on the face (noticeable redness),
• dizziness,
• decrease in blood pressure indicators (sometimes to critical levels)
• increased heart rate, or heart rate (more than 90 beats per minute),
• tides to the head, accompanied by a feeling of heat,
• unpleasant sensations in the mouth, due to the dryness of the mucous membranes,
• burning sensation in the area of the tongue (most often at its tip),
• minor nausea,
• temporary deterioration of vision,
• general weakness and fatigue,
• skin rashes caused by an allergic reaction to the drug.

Sometimes, against the background of therapy with the drug at fairly low pressures, there may be an increase in the morbid manifestations of angina pectoris. In very rare cases, taking the drug is accompanied by the development of ischemia (oxygen starvation) of the brain. 

[23]

Overdose

The safe use of various forms of the heart drug "Isosorbide dinitrate" implies a clear compliance with the instructions of the doctor in terms of dispensing the drug and the frequency of its administration. In case of taking high doses of medication and unreasonably prolonged treatment, an overdose may occur with a drug that will have its unpleasant symptoms.

Symptoms of an overdose of isosorbide dinitrate include strengthening some side effects of the drug, such as headaches and dizziness, visual and stool disorders, dyspeptic disorders, weakness, the development of collapse against a background of a sharp decrease in pressure.

But there may be other symptoms that are not characteristic of this medicine. If there are signs of oxygen starvation of body tissues (anoxia), episodes of fainting, an increase in body temperature, cyanosis of the lips and nails, diagnosed convulsions, dyspnea, a decrease in heart rate and intracranial pressure is an excuse to take action to eliminate the effects of drug overdose.

First aid is to wash the stomach. Then, measures are taken to eliminate the above-described symptoms at home or in the hospital.

If the oxygen starvation of tissues is observed against the background of an increase in the level of methemoglobin, this indicates the development of methemoglobinemia. In this situation, emergency care involves intravenous administration of a solution of methylene blue. The dosage is determined on the basis of the following ratio: 1 kg or 2 mg of solution is taken per kilogram of body weight of the patient.

[28], [29], [30], [31]

Interactions with other drugs

The drug therapy should be carried out strictly taking into account the drug interaction of Isosorbide dinitrate with other drugs, in order to ensure good effectiveness of the drug and prevent unpleasant consequences associated with worsening of the patient's health after simultaneous reception of various medications.

For example, with the simultaneous administration of Isosorbide dinitrate and alpha-adrenoblocker Dihydroergotamine, plasma concentrations and effects of the latter may increase, which is fraught with the development of overdose symptoms.

If the background of taking Isosorbide dinitrate is performed with cholinetic means, especially in the elderly, there is a decrease in memory and attention in patients.

Adsorbents, astringents and enveloping agents reduce absorption (absorbability) of the drug in the peroral and sublingual modes of administration.

Drugs related to groups of peripheral vasodilators, beta-adrenoblockers, tricyclic antidepressants, calcium channel blockers and taken in parallel with isosorbide dinitrate, contribute to lowering blood pressure. The same can be said about neuroleptics, drugs for lowering blood pressure, PDE inhibitors and ethyl alcohol.

Anti-angiogenic effect of the drug is markedly reduced when taken in parallel with sympathomimetics.

Isosorbide dinitrate is undesirable to be taken simultaneously with the alpha-adrenomimetic "Norepinephrine", since such therapy reduces the effect of the latter.

But the parallel treatment of erection "Sildenafil" significantly increases the likelihood of myocardial infarction and collapse.

[32]

Storage conditions

The effectiveness and safety of any medication, including Isosorbide dinitrate, may be affected by non-compliance with the storage conditions of the drug. In this case, the storage requirements are few:

• the temperature is within the room temperature,
• protected from the sun, moisture and childish curiosity is a secluded place.

Compliance with such uncomplicated conditions will help prevent premature spoilage of the drug, as well as save your health and your relatives.

[33], [34]

Special instructions

During therapy with isosorbide danatrate preparations, it must be taken into account that these drugs have a negative effect on the reaction rate, so it is better to refuse for a while driving a car and performing activities requiring increased attention.

If the drug has to take a long time, every 3-5 weeks, you need to do a 4-day break, which will prevent addiction to the drug and reduce the therapeutic effect.

If there is a need for an increase in the dose, this should be done gradually, while constantly monitoring the indices of pressure and pulse. 

[35], [36]

Shelf life

The shelf life of the drug in its native packaging without damage to the protective shell varies from 3 to 5 years, depending on the form of release, and sometimes the name. But we need to take into account that opening the package, we reduce this period, which must be noted in the instructions for the use of a particular drug. 

[37], [38]