Isosorbide dinitrate

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

In this article we will talk about the drug of the same name, named according to the active substance “Isosorbide dinitrate”.

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

Indications Isosorbide dinitrate

As already mentioned, the main indication for the use of isosorbide dinitrate, no matter what name the drug is released under, is coronary heart disease, which is often called the hungry heart syndrome. But various manifestations of the pathology may require the use of different forms of the drug, which is used both for long-term therapeutic effects and for the rapid relief of dangerous symptoms.

Thus, taking regular tablets and prolonged-release capsules, sublingual tablets and TTS films is advisable in the following cases:

• to reduce the intensity of angina attacks (pressing or squeezing pain, as well as a burning sensation behind the breastbone in the heart area),
• to prevent the above-described conditions associated with insufficient 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 to treat the disease,
• for the treatment of arterial hypertension as one of the manifestations of coronary heart disease,
• for the treatment of certain types of pulmonary hypertension, characterized by elevated pressure in the pulmonary artery system,
• as part of a multicomponent therapy for a pathology in which there is an expansion (enlargement) of the right sections of the heart due to diseases of the bronchopulmonary system (“pulmonary heart”),
• for rehabilitation after myocardial infarction.

The solution for intravenous infusions or slow injections is used in such life-threatening situations for the patient as:

• pulmonary edema,
• acute stage of myocardial infarction,
• a complication of coronary heart disease that threatens the development of myocardial infarction, called unstable angina in medical practice.

The use of a spray (inhalation route of drug administration) is justified if emergency care outside a hospital is required:

• in the acute stage of myocardial infarction against the background of left ventricular failure,
• to prevent and treat angina attacks,
• as a therapeutic and prophylactic agent for spasm of the cardiac arteries during examination of the vessels using a cardiac catheter.

In acute heart failure, Isosorbide dinitrate is often used to expand the lumen of blood vessels and improve coronary circulation.

[ 5 ], [ 6 ]

Release form

Treatment with isosorbide dinitrate is exactly the case when nitrates (salts of nitric acid) do not harm health, but on the contrary, allow you to strengthen it. The chemical formula of the active substance is represented as C ₆ H ₈ N ₂ O ₈.

The nitro-containing substance itself is a white powder that has no smell or taste. The powder is practically insoluble in water. Acetone, alcohol or ether are used to dissolve it.

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

Regular tablets may contain 5, 10 or 20 mg of the active substance. 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.

Extended-release forms of the drug (long-acting tablets and capsules) contain 20, 40, 60 and even 120 mg of the active substance.

The concentrate for the preparation of a solution in vials contains 10 mg of the active component in 1 ml of volume.

The spray and aerosol for sublingual spray contain 300 doses of cardiac medicine (300 sprays), with each dose containing 1.25 mg of isosorbide dinitrate.

[ 7 ], [ 8 ], [ 9 ]

Pharmacodynamics

"Isosorbide dinitrate" is considered one of the most effective drugs used to treat cardiac ischemia and relieve angina attacks. The drug owes this recognition to its active substance, which has the following properties:

• expansion of the lumen of blood vessels (vasodilating effect),
• reducing the need of the main heart muscle for oxygen (antianginal effect),
• general coronary dilating effect.

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

The antianginal effect of the drug is due to three factors:

• reduction of peripheral vascular resistance (afterload),
• dilation of peripheral veins, resulting in a decrease in blood flow to the right atrium (preload),
• expansion of coronary vessels.

Thus, "Isosorbide dinitrate" reduces the load on the heart muscle (myocardium) in case of its insufficient functions. It also promotes the expansion of the heart vessels and ensures normal nutrition and oxygen saturation of areas with impaired blood supply as a result of the disease.

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

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

Pharmacokinetics

While improving coronary and peripheral circulation, the drug does not affect the heart rate. Only in rare cases is a slight increase in heart rate observed. In addition to dilating the heart vessels, the drug promotes dilation of the brain and lung vessels, improving cerebral and pulmonary circulation.

The speed of the onset of the effect from taking the drug depends on the form of release of the drug. Although they all have sufficient speed of action. For example, the effect of sublingual tablets can be noticed after 3-5 minutes. Regular and prolonged tablets give an effect after 15-20 minutes, although some circumstances can slow down 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 single sprayed dose is enough for a period of up to 2 hours.

The active substance is metabolized in the liver, resulting in the formation of isosorbide mononitrates. The drug is excreted from the body through the kidneys.

The half-life of the drug also depends on the form of release. For an injection solution, it is about 20 minutes, for regular 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: orally, by washing down the tablets with water, by placing a sublingual tablet under the tongue or spraying a spray in the prescribed dosage into this area, by attaching a special medicinal film to the gum or behind the cheek, as well as by intravenous injections or droppers.

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

If necessary, to relieve an attack of angina, the tablet can be chewed and swallowed after the pain has subsided. Tablets of 5 and 10 mg are used for this purpose. The tablet with a higher dosage will have to be divided.

Prevention of angina attacks begins with a dosage of 10 mg. You will have to take the tablets 4 to 5 times a day.

If the indicated dosage is not effective enough, on the 4th-5th day of therapy with the drug, the daily dosage is increased (from 60 to 120 mg maximum). 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 regular tablets with a dosage of 10 and 20 mg. The frequency of administration in this case can be from 3 to 4 times a day.

The maximum single dose for sublingual tablets and transbuccal films is 10 mg. The frequency of administration is determined by the attending physician based on the diagnosis and the patient's condition.

The use of a sublingual spray involves injecting 1 to 3 doses of the composition into the oral cavity. Injections should be done at intervals of half a minute and holding your breath during the manipulation.

The use of the spray as emergency aid for acute infarction or CHF is carried out in the same dosage, the only point is that if the first dose of the drug does not bring relief, after 5 minutes the injection of the drug can be repeated. The next use of the spray is possible after 10 minutes. This is usually enough to relieve life-threatening symptoms.

When conducting a coronary vessel examination using a catheter, 1 or 2 doses of the drug are first sprayed under the patient's tongue. This is necessary to prevent spasm of the heart vessels.

The dosage for intravenous infections or infusions may vary greatly in each individual case. The effective dose is determined by the attending physician, 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 its use should only occur after prior consultation with a specialist doctor and in the doses indicated by him. The drug can also be used during breastfeeding, but just in case, it is better to transfer the baby to nutritious milk formulas at this time.

Contraindications

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

• if the patient is diagnosed with persistently low blood pressure,
• state of shock,
• a sharp drop in blood pressure, characterizing the onset of collapse,
• advanced stage of pericarditis, in which inflammation and thickening of the layers of the heart membrane (pericardium) causes compression of the heart (constrictive pericarditis),
• thickening of the interventricular muscle, which leads to disruption of coronary blood flow (obstructive HCM),
• in case of traumatic brain injury,
• patients diagnosed with hemorrhagic stroke,
• with high intracranial pressure,
• if acute myocardial infarction is observed against the background of low blood pressure,
• accumulation of fluid in the cavity of the heart membrane, which in cardiology is called cardiac tamponade,
• if pulmonary edema is caused by a toxic factor,
• closed-angle glaucoma,
• hypersensitivity to the components of the dosage form,
• allergic reaction to organic nitrates.

The drug should be used under the supervision of a physician in case of mitral stenosis and aortic stenosis, low blood pressure, cerebrovascular accidents, liver failure, and in old age. The drug is not used in pediatrics.

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

Side effects Isosorbide dinitrate

Individual reactions to the drug "Isosorbide dinitrate" may vary. Some patients tolerate the drug therapy well, while others may experience some side effects. Among such unpleasant manifestations, the following can be distinguished:

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

Sometimes, against the background of drug therapy at fairly low pressure readings, an increase in painful manifestations of angina may be observed. In very rare cases, taking the drug is accompanied by the development of ischemia (oxygen starvation) of the brain.

[ 23 ]

Overdose

Safe use of various forms of the cardiac drug "Isosorbide dinitrate" implies strict adherence to the doctor's instructions in terms of dosage of the drug and frequency of its administration. In case of taking high doses of the drug and unjustifiably long-term treatment, an overdose of the drug may occur, which will have its own unpleasant symptoms.

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

But other symptoms not typical for this medicine may also appear. If signs of oxygen starvation of body tissues (anoxia) appear, episodes of fainting, an increase in body temperature, cyanosis of the lips and nails are diagnosed, convulsions, shortness of breath, decreased pulse rate and intracranial pressure are observed - this is already a reason to take measures to eliminate the consequences of an overdose of the drug.

First aid consists of gastric lavage. Then measures are taken to eliminate the above-described symptoms at home or in hospital.

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

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

Interactions with other drugs

Therapy with the drug 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 deterioration of the patient's health after the simultaneous use of various drugs.

For example, when taking Isosorbide dinitrate and the alpha-adrenergic blocker Dihydroergotamine simultaneously, the plasma concentration and effect of the latter may increase, which may lead to the development of overdose symptoms.

If therapy with cholinetic agents is carried out against the background of taking Isosorbide dinitrate, especially in elderly people, a decrease in memory and attention is observed in patients.

Adsorbents, astringents and enveloping agents reduce the absorption of the drug when administered orally and sublingually.

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

The antianginal effect of the drug is significantly reduced when taken in parallel with sympathomimetics.

It is not advisable to take isosorbide dinitrate simultaneously with the alpha-adrenergic agonist Norepinephrine, since such therapy reduces the effect of the latter.

However, parallel treatment of erectile dysfunction with Sildenafil significantly increases the likelihood of developing myocardial infarction and collapse.

[ 32 ]

Storage conditions

The effectiveness and safety of any drug, including Isosorbide dinitrate, may be affected by failure to comply with the storage conditions of the drug. In this case, there are few storage requirements:

• temperature within room temperature,
• a secluded place protected from the sun, moisture and children's curiosity.

Compliance with such simple conditions will help prevent premature deterioration of the drug, and will also protect your health and the health of your family.

[ 33 ], [ 34 ]

Special instructions

During therapy with isosorbide danatrate, it is necessary to take into account that these drugs have a negative effect on reaction speed, so it is better to temporarily refrain from driving a car and performing activities that require increased attention.

If the drug has to be taken for a long time, a 4-day break should be taken every 3-5 weeks, which will prevent addiction to the drug and a decrease in the therapeutic effect.

If there is a need to increase the dose, this should be done gradually, while constantly monitoring blood pressure and pulse rates.

[ 35 ], [ 36 ]

Shelf life

The shelf life of the drug in its original packaging without damage to the protective shell ranges from 3 to 5 years, depending on the form of release, and sometimes the name. But it should be taken into account that by opening the package, we reduce this period, which must be noted in the instructions for use of a specific drug.

[ 37 ], [ 38 ]