"Nitroglycerin", solution for injection: instructions for use

A little history

The ability of nitroglycerin to have a beneficial effect on human health was first noticed by the English doctor D. Merrill, observing workers involved in the production of explosives. It was this doctor who subsequently established the fact that nitroglycerin can be used as a medicine intended to eliminate spasms of the heart vessels.

The ability of this remedy to quickly help with angina pectoris has been established, thus, it was experimentally. Actually, the mechanism of action of nitroglycerin on the human body, unfortunately, was not studied for a long time. Scientists conducted such studies only at the end of the last century.

Today, the drug “Nitroglycerin” is considered one of the most effective drugs used to quickly help patients with acute attacks of angina. The analgesic effect when using this medicine occurs almost instantly.

Compound

The drug "Nitroglycerin" can be produced in different forms. In most cases, patients take it in tablets. However, very often this medicine is supplied to the market in the form of an alcoholic concentrated liquid for injection in ampoules of 2-10 ml or bottles of 50-500 ml.

The recipe for preparing Nitroglycerin solution is quite simple. This drug was once produced in very limited quantities. Only a few people could use it for emergency treatment of heart attacks. Today this medicine is available in absolutely all pharmacies and clinics. If necessary, purchasing this drug, at least in tablets, will not be difficult.

The main active ingredient of this product is, of course, nitroglycerin itself. 1 ml of this substance contains 10 mg. Also, the solution of the drug “Nitroglycerin” includes an additional substance such as ethanol.

special instructions

Drinking alcohol during therapy is prohibited.

In case of severe blurred vision or dry mouth, you should stop taking nitroglycerin.

When using the drug, a significant decrease in blood pressure and dizziness may be observed in the event of a rapid transition from a “sitting” or “lying” position to an upright position, performing physical exercise, as well as when drinking alcohol.

Reducing the dose of the drug or simultaneous use of validol can help reduce the severity of headaches that occur during treatment.

Patients with diabetes mellitus should remember that the solution for intravenous administration contains dextrose.

It is necessary to avoid abrupt withdrawal of the drug due to the threat of increased frequency of angina attacks.

The spray must not be inhaled!

During the period of therapy, it is recommended to refrain from driving vehicles and operating other complex mechanisms.

The therapeutic doses indicated in the instructions should not be exceeded.

1 tablet of sublingual Nitroglycerin contains 2.65 H10-3 XE (bread units).

During therapy, a significant decrease in blood pressure and the development of dizziness are possible with a sudden transition to a vertical position from a lying or sitting position, as well as in hot weather, when doing physical exercise or drinking alcohol.

If blurred vision or dryness of the oral mucosa persists or becomes significant, treatment should be interrupted.

According to the instructions, Nitroglycerin, like other organic nitrates, can be addictive (in this case, an increase in dosage will be required).

The severity of headache during therapy can be reduced by reducing the dose of the drug and/or simultaneous administration of validol.

For frequent attacks of angina, it is recommended to use long-acting nitroglycerin medications.

While using Nitroglycerin, drinking alcoholic beverages is strictly prohibited.

The sublingual spray contains alcohol, which is important for nursing and pregnant women, patients with functional liver disorders, epilepsy, traumatic brain injuries and other diseases of the central nervous system, as well as alcohol abuse.

The infusion solution contains glucose (dextrose), which should be taken into account in patients with diabetes.

In acute heart failure or acute myocardial infarction, Nitroglycerin should be used only under the condition of careful clinical monitoring of the patient's condition.

To prevent an increase in angina attacks, it is recommended to avoid abrupt withdrawal of the drug.

To prevent an unwanted decrease in blood pressure, the rate of administration of the Nitroglycerin infusion solution must be selected individually. A decrease in blood pressure can be observed not only when selecting the rate of solution administration, but also later, against the background of initially stabilized blood pressure (monitoring should be carried out at least 3-4 times per hour throughout the entire infusion time).

Patients previously treated with organic nitrates (isosorbide-5-mononitrate, isosorbide dinitrate) may require a higher dose to obtain the desired hemodynamic effect.

When using Nitroglycerin, care must be taken when driving vehicles and performing potentially dangerous types of work that require increased concentration and rapid psychomotor reactions.

While taking nitroglycerin, there may be a significant decrease in blood pressure and the appearance of dizziness during a sudden transition to a vertical position from a “lying” or “sitting” position, when drinking alcohol, doing physical exercise, and in hot weather. Nitroglycerin, like all organic nitrates, develops addiction with frequent use and requires increasing the dose.

When driving vehicles and operating machinery that require increased attention, it should be borne in mind that taking nitroglycerin can lead to a decrease in the speed of motor and mental reactions.

The severity of headache while taking nitroglycerin can be reduced by reducing its dose and/or simultaneous administration of validol.

Side effects

Nitroglycerin helps very well with heart attacks and angina. However, this remedy, unfortunately, can have many side effects. Quite often, for example, after an injection of a Nitroglycerin solution, patients begin to experience a headache. This happens due to the dilation of blood vessels in the brain.

Headache in patients after injection of this drug indicates that the drug has begun to work. In most cases, this side effect occurs in those people who have not previously used Nitroglycerin in any form. Usually this unpleasant phenomenon goes away over time and patients no longer experience such a side effect.

Also, when using Nitroglycerin for treatment, patients may experience:

• hyperemia of the skin;
• tachycardia;
• feeling of heat;
• nausea and vomiting;
• arterial hypotension.

Sometimes patients, after taking this drug, begin to experience severe unreasonable anxiety or develop some other psychotic reaction. In some cases, patients may also be allergic to the components of the drug.

Alcohol compatibility

Nitroglycerin is most often prescribed to patients with coronary artery disease, which develops against the background of an unhealthy lifestyle and bad habits. Therefore, the issue of compatibility of the drug with alcoholic beverages becomes relevant.

The main effect of Nitroglycerin is based on lowering blood pressure through various mechanisms. Alcoholic drinks have a similar effect: drinking even a small amount of vodka helps to expand the lumen of the arteries and veins (characteristic signs of redness of the skin, a feeling of warmth).

Simultaneous use has an “explosive” effect - a sharp drop in blood pressure, which impairs blood flow to the internal organs and, first of all, to the brain. An additional inhibitory effect on the central nervous system prevents the activation of compensatory mechanisms.

Is it possible to die when consumed with alcohol?

The use of Nitroglycerin simultaneously (or with an interval of less than 2 hours) with alcoholic beverages is accompanied by a high risk of deterioration of systemic hemodynamics and the general condition of a person.

A lethal outcome occurs when taking a high dose of Nitroglycerin and alcohol, which is determined for each person separately depending on the state of the liver enzyme system. Chronic alcoholism leads to dysfunction of the latter, and there is not enough protein in the blood to bind circulating Nitroglycerin.

Such patients may die due to an increase in the concentration of active metabolites of the drug and an increase in the hypotensive effect of ethanol.

Does the medicine have contraindications?

Unfortunately, not all people can use Nitroglycerin injection solution for heart attacks, like any other medicine. First of all, an allergy to its components may be a contraindication to the use of this product. Such reactions manifest themselves mainly as skin itching and rash. If such symptoms occur, use of the drug should, of course, be discontinued.

Also contraindications to the use of this drug are:

• collapse;
• shock;
• arterial hypotension;
• hypertrophic obstructive cardiomyopathy;
• acute infarction with severe arterial hypotension;
• toxic pulmonary edema;
• cardiac tamponade;
• constrictive pericarditis;
• increased intracranial pressure;
• intraocular pressure in glaucoma.

In addition, Nitroglycerin is not prescribed to patients with hypersensitivity to nitrates.

Indications and contraindications for the use of nitroglycerin

Nitroglycerin is used very widely. Almost every elderly patient suffering from periodic heart pain carries with him tablets or a spray of this drug, which can be taken immediately as soon as an attack is felt. The effect occurs very quickly, pain is relieved, and heart function improves. The main reason for using nitroglycerin is coronary heart disease. The drug is used for:

• Paroxysms of angina pectoris (pain in the heart) and to prevent them;
• Recovery in the post-infarction period.

Intravenous administration of nitroglycerin is necessary in the following cases:

1. Acute myocardial infarction;
2. Angina pectoris resistant to other types of treatment;
3. Post-infarction and unstable angina;
4. Acute left ventricular failure with pulmonary edema;
5. Controlled hypotension, which is established during surgical interventions to reduce the volume of blood loss;
6. Thrombosis of the central retinal artery.

In addition to cardiac pathology, indications for the use of nitroglycerin may include acute pancreatitis, attacks of biliary colic, dyskinesia of the esophagus and intestines, and impaired motility of the gallbladder.

There are also contraindications to taking nitroglycerin. Among them:

• Individual intolerance;
• Concomitant use of phosphodiesterase inhibitors (sildenafil);
• Severe hypotension;
• Lactose and galactose intolerance caused by hereditary causes;
• Cardiac hemotamponade;
• Adhesive pericarditis.

Nitroglycerin should be prescribed with caution:

1. Patients with cerebral hemorrhages, increased intracranial and intraocular pressure;
2. With congestive heart failure, when the pressure in the left ventricle is very low;
3. For anemia;
4. Hyperfunction of the thyroid gland;
5. Pathologies of the liver and kidneys;
6. Valvular heart defects;
7. Tendency to hypotension.

It is better to refrain from taking nitroglycerin for pregnant women and nursing mothers. Its safety in children and adolescents has not been established, so nitroglycerin is not usually used before the age of 18.

The listed contraindications apply to all dosage forms of nitroglycerin. In addition, long-acting drugs are contraindicated for people with increased intestinal and gastric motility and impaired absorption, and intravenous administration of nitroglycerin is prohibited for traumatic brain injuries, severe atherosclerosis, shock, hemotamponade of the pericardium and pericarditis, toxic pulmonary edema.

The instructions for use of nitroglycerin contain a large amount of information regarding not only the mechanism of action, but also possible adverse reactions, complications during treatment, drug interactions, which the patient should be aware of, therefore, after prescribing this medicine, it is better to immediately read the instructions and follow the recommendations of your doctor

Adverse reactions from the use of nitroglycerin occur in the cardiovascular, nervous system, and digestive organs. Often, while taking nitroglycerin, patients complain of dizziness, headaches, and tachycardia, which is associated with rapid vasodilation. These effects develop most often and usually disappear within 10-20 minutes from the moment of administration. To restore blood supply to the brain vessels and eliminate headaches, it is better to take a horizontal position, lowering your head and slightly raising your legs. Less commonly, nausea, dry mouth, and dyspepsia are possible.

In case of an overdose of the drug, symptoms from the nervous system appear: the patient is agitated, disoriented, may be inhibited, and in rare cases it can lead to psychosis. Severe intoxication with nitroglycerin is accompanied by collapse, bluish skin, breathing problems, and methemoglobin appears in the blood, causing hypoxia.

The likelihood of such effects dictates the need to strictly follow the prescribed dosage and regimen of nitroglycerin. Very rare, but still not excluded, allergic reactions and local negative manifestations - itching, burning, redness of the skin, dermatitis.

If adverse reactions develop during intravenous infusions, they are stopped immediately. If skin products are used, they should be removed (ointments, patches). Taking into account the expansion of cerebral vessels and possible fainting, the patient is placed with his legs elevated and his head slightly lowered. Normal blood pressure is usually restored within 15-20 minutes.

For methemoglobinemia caused by an overdose of nitroglycerin, ascorbic acid and oxygen therapy are indicated; for acute renal failure against this background, hemodialysis is necessary. In rare cases, doctors are forced to resort to blood transfusions.

Can it be used during pregnancy?

It is permissible to take this drug while carrying a child. However, this medicine should be used in this case exclusively under the supervision of the attending physician. The same rule should be followed when using the solution during lactation.

Also, only for health reasons, this drug can be used to provide emergency care to patients:

• with epilepsy;
• having liver problems;
• children.

In all these cases, it is necessary to use minimal doses of the medicine.

In what cases should it be taken with caution?

Sometimes the doctor has to weigh the benefits of using this drug and the possible harm from it. This happens if the patient has, for example, problems such as:

• constrictive pericarditis;
• severe anemia;
• cardiac tamponade;
• atherosclerosis;
• recent head injury;
• cerebral hemorrhage;
• severe renal failure;
• acute infarction with low left ventricular filling pressure;
• liver diseases;
• thyrotoxicosis.

What are the consequences of an overdose

This medicine should be taken strictly according to the instructions. Overdoses of Nitroglycerin solution should not be allowed under any circumstances. Otherwise, the patient may experience:

• tachycardia;
• arterial hypotension;
• headache;
• feeling of heat;
• syncope.

With an overdose of Nitroglycerin solution, patients also often experience a significant increase in intracranial pressure. In this case, the patient may experience confusion and various types of neuralgic disorders. An overdose within a few hours leads to ethanol intoxication.

Due to methemoglobinemia, if Nitroglycerin is used incorrectly, the patient may develop hypoxia, and subsequently:

• cyanosis;
• coma;
• metabolic acidosis;
• convulsions;
• vascular collapse.

Overdose

Symptoms of an overdose of Nitroglycerin are: nausea, vomiting, increased drowsiness, severe weakness, asthenia, severe dizziness, headache, seizures, feeling hot, shortness of breath, reflex tachycardia, decreased blood pressure (below 90 mm Hg), accompanied by orthostatic dysregulation . Taking the drug in high doses (more than 20 mg/kg) can lead to the development of tachypnea, dyspnea, cyanosis, collapse, and methemoglobinemia.

If signs of overdose occur, you should immediately put the patient in a horizontal position, raising his legs, and also seek medical help.

Help with overdose

Arterial hypotension in case of overdose should be eliminated by reducing the rate or completely stopping the administration of the drug. In severe cases, the patient should be placed in a horizontal position. If arterial hypotension is associated with bradycardia, the patient may also be prescribed Dopamine and Atropine.

For methemoglobinemia, patients are required to receive intravenous methylene blue solution. Its dosage should be equal to 1-2 mg per kilogram of body weight.

Instructions for use

Use Nitroglycerin solution only for intravenous injections. With this method of use, the medication acts as quickly as possible. In order to provide emergency assistance to a patient if necessary, you need to take a Nitroglycerin solution and inject it into a vein using an infusion pump or automatic DLV-1. The rhythm of intake into the body and the amount of this medicine should be dosed as accurately as possible.

Sometimes this drug can also be given using a regular fluid infusion system. In this case, the exact dose is selected by counting drops per minute. A 0.1% solution of “Nitroglycerin” is diluted with 5% glucose or sodium chloride (9 parts) to a concentration of 0.01%.

In each specific case, the selection of the dosage of “Nitroglycerin” is carried out by the attending physician on an individual basis, depending on:

• blood pressure indicators;
• ECG;
• venous pressure;
• number of heartbeats.

The initial rate of administration of this drug is usually 0.5-1 mg/hour. The maximum is 8-10 mg/h. The duration of administration depends on the patient’s condition and can range from several hours to 3 days.

The use of intravenous nitroglycerin in emergency cardiology

Nitroglycerin preparations have been used in medicine for more than 100 years, but interest in this group of drugs has not waned. New beneficial effects of nitroglycerin are regularly discovered, expanding the possibilities of its clinical use. Since 1879, when it was first used to relieve an attack of angina, nitroglycerin has remained one of the main agents for the treatment of coronary artery disease. In 1970, nitroglycerin was first used to treat heart failure and acute myocardial infarction. In 1978, it was shown that stimulation of guanylate cyclase, leading to the accumulation of cyclic guanazine-3',5'-monophosphate in the smooth muscle cells of the vascular wall, causing vasodilation, occurs after the metabolism of nitroglycerin into nitric oxide (NO). In 1998, a group of scientists (RF Furchgott, LJ Ignarro and F. Murad) was awarded the Nobel Prize for elucidating the physiological role of NO (endothelium-dependent relaxation factor), including its regulatory effect on vascular tone. NO deficiency is observed in coronary heart disease, arterial hypertension and heart failure and appears to be of great importance in their pathogenesis. Thus, new data allow us to consider nitroglycerin in these diseases as a replacement therapy drug.

The advantages of nitroglycerin also include a variety of dosage forms, which allows for their rational choice for various diseases and for different categories of patients. An important place in the treatment of emergency conditions in cardiology belongs to the dosage form for intravenous infusion.

Nitroglycerin infusion, stabilized with ethyl alcohol and propylene glycol, appeared on the international pharmaceutical market in the early 1980s. The main indications for its use are:

• unstable angina, refractory to treatment with standard antianginal drugs;
• myocardial infarction;
• acute left ventricular failure;
• controlled hypotension during surgery;
• monitoring blood pressure during perioperative hypertension that occurs during intubation, anesthesia, during skin incision, during extracorporeal circulation and immediately after surgery.

The effectiveness of intravenous nitroglycerin in unstable angina has been studied in small studies [1-3]. Their results show that under the influence of the drug, the vast majority of patients experience a decrease in the frequency of episodes of pain at rest and their intensity. In one study, 63% of patients receiving nitroglycerin infusions experienced complete pain relief [1]. The use of intravenous nitroglycerin is recommended in patients without contraindications (for example, hypotension or taking sildenafil less than 24 hours before the start of therapy) in whom three sublingual 0.4 mg tablets of the drug were ineffective [4].

It has been shown that the effectiveness of nitroglycerin in unstable angina increases with the simultaneous use of N-acetylcysteine, but the frequency of side effects also increases [5].

For unstable angina caused by coronary artery restenosis in patients undergoing angioplasty, intravenous nitroglycerin was superior in effectiveness to intravenous heparin [6]. In this study, 200 patients hospitalized with unstable angina within six months of angioplasty (without stenting) were randomized into four groups. The first group received intravenous heparin, the second - intravenous nitroglycerin, the third - both drugs, the fourth - placebo. The primary endpoint of angina recurrence was observed in 75% of patients receiving placebo or heparin and in 42% of patients in both groups receiving nitroglycerin.

There is convincing experimental and clinical evidence that intravenous infusions of nitroglycerin lead to a reduction in the area of ​​myocardial infarction and improve regional cardiac function [7, 8]. It has been suggested that nitroglycerin may prevent left ventricular remodeling observed after large transmural infarctions [7]. Moreover, numerous studies conducted in the “pre-thrombolytic era” (see Table 1) revealed a significant decrease under the influence of intravenous nitroglycerin in the incidence of complications of myocardial infarction and mortality both during the first 14 days and in the next 3-12 months [7— 9]. In a meta-analysis of 2042 patients, mortality in patients receiving intravenous nitrate infusions during the acute stage of myocardial infarction decreased by 35% (95% CI, 28 to 49%; P < 0.001) [9]. Moreover, nitroglycerin was superior to sodium nitroprusside in this indicator (45% versus 23%).

However, the large clinical trial GISSI-3 did not confirm the ability of nitroglycerin, when added to standard therapy, including thrombolytic agents, to have a significant effect on mortality in patients with myocardial infarction [15]. In this study, which included 19,394 patients, a 24-hour nitroglycerin infusion was given on the first day, followed by a nitroglycerin patch (10 mg/day) for the next six weeks. After six weeks, there was a trend toward decreased mortality in the study group (6.52%) compared to the control group (6.92%), but the difference was not statistically significant. The results of this study may be considered controversial, since about 50% of patients in the control group also received nitrates in the first two days after a heart attack.

Another large clinical trial (58,050 patients) of ISIS-4 did not show a reduction in mortality with another nitrate, oral isosorbide mononitrate [16]. However, this work suffers from the same methodological shortcomings as GISSI-3.

Currently, most experts consider the routine use of nitrates in the acute period of myocardial infarction inappropriate. However, they agree that intravenous infusion of nitroglycerin in the first 24-48 hours is certainly indicated for patients with persistent myocardial ischemia, left ventricular failure and arterial hypertension. In patients with heart failure and extensive transmural myocardial infarction, oral or topical nitrates can be continued, but early intravenous nitroglycerin is recommended for safety reasons. The absence of contraindications for intravenous administration of nitroglycerin allows its use not only in a hospital setting, but also at the prehospital stage - in an ambulance.

The greater safety of the injection form of nitroglycerin compared to other nitrates in urgent situations is due to the peculiarities of its pharmacokinetics: rapid (within 2-3 minutes) onset of action, short half-life (1-4 minutes), which allows you to quickly stop the effect of the drug in case of development of undesirable effects. reactions, the ability to control the strength of the effect by titrating the dose and changing the rate of administration. In some countries, such as the United States, nitroglycerin is the only nitrate approved for intravenous administration.

The effect of nitroglycerin on hemodynamics (decrease in capillary wedge pressure in the lungs, systolic blood pressure, increase in stroke volume, decrease in load on the heart) determines its particularly beneficial effect on patients with impaired left ventricular function and congestive heart failure. In contrast, in patients with right ventricular infarction, hypovolemia, or hypotension, the risk of nitrate use outweighs the potential benefit [17].

A recently completed study showed the beneficial effect of combined intravenous nitroglycerin and verapamil before thrombolytic therapy in patients with ST elevation myocardial infarction [18]. This combination, administered immediately after hospitalization, resulted in restoration of myocardial perfusion and improvement in clinical status and ECG parameters in 36 of 101 patients participating in the study. Researchers believe that the beneficial effect of this combination is due to the elimination of coronary vasospasm, reduction of platelet aggregation and improvement of collateral blood flow, and therefore it is considered a promising additional method for the treatment of ST-elevation myocardial infarction.

Intravenous nitroglycerin is considered the drug of choice to reduce afterload in patients with congestive heart failure and pulmonary edema. Unlike sodium nitroprusside, it does not cause the “steal” phenomenon, and its use is associated with a significantly lower risk of developing methemoglobinemia. The beneficial effect of the drug on hemodynamic parameters has been shown in congestive heart failure in children with a congenital heart defect - left-to-right shunting [19].

Intravenous nitroglycerin has been successfully used to relieve hypertensive crises, primarily in patients with myocardial infarction, unstable angina, left ventricular failure and patients who have undergone coronary artery bypass surgery.

Intravenous infusions of nitroglycerin are widely used in the intra- and postoperative periods for various types of surgical interventions. The drug improves hemodynamic parameters, prevents myocardial ischemia and allows effective control of blood pressure. In patients with acute hypertension during coronary artery surgery, nitroglycerin infusion led to a decrease in systolic and diastolic blood pressure and a decrease in ST segment depression on the ECG [20]. Intravenous administration of nitroglycerin at a dose of 100 mcg/min 12 hours after elective coronary stenting, according to a double-blind, placebo-controlled study, caused a decrease in the incidence of small necrotic changes in the myocardium caused by microembolism, coronary vasospasm or microcirculatory disorders. In patients suffering from angina pectoris, nitroglycerin in doses of 90-100 mcg/min significantly reduced the frequency of episodes of myocardial ischemia during laryngoscopy, intubation and in the intraoperative period [21, 22].

The speed and short duration of the effect of nitroglycerin are due to its advantages over sodium nitroprusside during cesarean sections [23]. Intravenous nitroglycerin can effectively control blood pressure in pregnant women during laryngoscopy and endotracheal intubation and does not have a negative effect on fetal respiration and blood pressure [23].

The relaxing effect of injectable nitroglycerin on extravascular smooth muscle allows its use in other areas of medicine, for example, in patients with portal hypertension in combination with vasopressin or prokinetics [24, 25]. Its effectiveness when used as a tocolytic agent is currently being studied [26].

The tolerability, frequency and severity of side effects of intravenous nitroglycerin largely depend on its correct use. When administering the drug, careful monitoring of blood pressure and heart rate should be carried out. The initial rate of administration should be 5-10 mcg/min. Subsequently, under the control of blood pressure, the rate of administration can be increased every 5-10 minutes by 5-10 mcg/min until the desired hemodynamic or clinical effect is obtained. In this case, systolic blood pressure should not be reduced by more than 10% from the initial level in patients with normotension and by more than 30% in patients with hypertension. Heart rate should not increase by more than 10 beats/min. The minimum acceptable level of systolic blood pressure is 90 mm Hg. Art., maximum heart rate - 110 beats/min. Systolic pressure readings are below 90 mm Hg. Art. or average pressure below 80 mm Hg. Art. are unacceptable due to the high risk of worsening coronary insufficiency and deterioration of cerebral perfusion. In this case, the nitroglycerin infusion should be suspended.

The optimal and maximum doses of the drug have not been established. In most patients, an adequate therapeutic effect is observed in the dose range from 50 to 200 mcg/min. Patients with inferior infarction are especially sensitive to low doses of nitroglycerin. In addition, inferior infarction is often combined with right ventricular infarction, which is associated with a high risk of severe hypotension [17], and therefore special care is required when titrating doses in these patients.

The duration of infusion for extensive myocardial infarction, heart failure, and persistent ischemia is usually 24-48 hours. With an infusion duration of more than 48 hours, tolerance may develop, but it can often be overcome by increasing the dose or rate of administration. Sensitivity is restored 10-14 hours after stopping the infusion.

If there is no therapeutic effect at an injection rate of 200 μg/ml, nitroglycerin is recommended to be discontinued or replaced with another vasodilator [10]. The drug should also be discontinued if bradycardia and hypotension occur. Emergency measures in this situation: elevate the patient's lower limbs and quickly administer fluid and atropine. With the development of reflex tachycardia (more than 100 beats/min), you can reduce the dose of nitroglycerin or prescribe medications that slow down the heart rate.

The drug is contraindicated in patients with systolic blood pressure below 90 mmHg. Art. (mean blood pressure below 60 mm Hg) and heart rate less than 50 beats/min, hypovolemia, constrictive pericarditis or pericardial tamponade, severe renal or liver failure, increased intracranial pressure. It is also not recommended for use in patients with tachycardia. Due to the risk of collapse, caution should be used when prescribing intravenous nitroglycerin to patients with aortic stenosis and reduced left ventricular output.

When used correctly, serious side effects from injectable nitroglycerin are rare. These include methemoglobinemia, which is a consequence of the interaction of nitrite ion and hemoglobin and leads to disruption of oxygen transfer by hemoglobin. This complication is more often observed in children. In rare cases, intoxication may occur due to the presence of nitroglycerin in commercial preparations for intravenous administration of ethyl alcohol (up to 5%). The most common side effects are headache, upper body flushing and dizziness.

One should remember the clinically significant interaction of intravenous nitroglycerin with heparin, which entails inhibition of the anticoagulant effect of the latter and the need to increase its dose [27]. In this case, after stopping the nitroglycerin infusion, bleeding may develop. Nitroglycerin solution cannot be mixed with any other medications. When administering it, avoid plastic infusion systems containing polyvinyl chloride, which actively absorbs nitroglycerin and can lead to significant losses of the drug and a dose-dependent decrease in its hemodynamic activity [28].

Thus, nitroglycerin for intravenous administration is a highly effective and fairly safe drug in many urgent situations.

On the Russian pharmaceutical market you can find several foreign preparations of nitroglycerin for intravenous administration of foreign origin. Unfortunately, their widespread use is limited due to high prices. However, in the near future, the domestic drug “Nitroglycerin solution 0.1% for injection No. 10” should appear on the Russian pharmaceutical market. At the beginning of 2003, the drug was tested in the emergency cardiology and cardiac intensive care departments of City Clinical Hospital No. 1 named after. N. I. Pirogova, City Clinical Hospital No. 7, City Clinical Hospital No. 13, City Clinical Hospital No. 15, City Clinical Hospital No. 23, City Clinical Hospital No. 59, Scientific and Practical Center for Interventional Cardioangiology. Based on feedback from cardiologists, the chief cardiologist of the Moscow Department of Health, prof. D. G. Ioseliani made the following conclusion:

• the drug is effective in the treatment of patients with acute coronary pathology and chronic heart failure;
• the drug is pyrogen-free;
• the drug does not cause allergic reactions;
• the drug is comparable in action to imported analogues (isoket, nitromac, nitropol, perlinganite);
• The drug is available in a convenient dosage.

The domestic drug “Nitroglycerin solution 0.1% for injection No. 10” was recommended for use in cardiology departments, cardiac intensive care units and intensive care units of medical institutions in Moscow, as well as specialized specialized cardiological institutions.

The advantages of the domestic drug, along with a significantly lower price compared to foreign analogues, also include greater safety due to the absence of alcohol in its composition (the drug is an aqueous, not an alcoholic solution) and a reduced glucose content.

Literature

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20. Kaplan JA, Dunbar RW, Jones EL. Nitroglycerin infusion during coronary artery surgery. Anesthesiology 1976; 45:14-21.
21. Coriat P, Daloz M, Bousseau D, et al. Prevention of intraoperative myocardial ischemia during noncardiac surgery with intravenous nitroglycerin. Anesthesiology 1984;61: 193.
22. Fusciardi J, Godet G, Barnard JM, et al. Role of fentanyl and nitroglycerin in prevention of myocardial ischemic associated with laryngoscopy and tracheal intubation in patients undergoing operations of short duration. Anesth Analg 1986; 65:617-24.
23. Snyder SW, Wheeler AS, James FM III. The use of nitroglycerin to control severe hypertension of pregnancy during caesarian section. Anesthesiology 1979;51:563-4.
24. Saraya A, Sarin SK.Effects of intravenous nitroglycerin and metoclopramide on intravariceal pressure: a double-blind, randomized study. Am J Gastroenterol 1993;88:1850-3.
25. Westaby D, Gimson A, Hayes PC, Williams R. Haemodynamic response to intravenous vasopressin and nitroglycerin in portal hypertension. Gut 1988;29:372-7.
26. Morgan PJ, Kung R, Tarshis J. Nitroglycerin as a uterine relaxant: a systematic review. J Obstet Gynaecol Can 2002;24:403-9.
27. Gonzalez ER, Jones HD, Graham S, Elswick RK. Assessment of the drug interaction between intravenous nitroglycerin and heparin. Ann Pharmacother 1992;26:1512-4.
28. Mutch WA, Culligan JD, Cote DD, Thomson IR. Hemodynamic effects of intravenous nitroglycerin: importance of the delivery system. Anesth Analg 1982;61:927-32.

D. V. Privalov City Clinical Hospital No. 51, Moscow

Interaction with other drugs

The hypotensive effect of Nitroglycerin, in which the patient experiences low blood pressure, may increase when taken simultaneously with:

• morphine and other vasodilators;
• ACE inhibitors;
• beta blockers;
• neuroleptics;
• Viagra;
• diuretics;
• tricyclic antidepressants;
• analgesics;
• ethanol

The use of Nitroglycerin in combination with procainamide or quinidine can lead to the development of orthostatic collapse in the patient. The effect of using this drug is reduced by medications such as Atropine and drugs that have an M-anticholinergic effect.

When treated with Nitroglycerin, the patient should definitely stop drinking alcohol. This drug is used in the form of a solution, of course, usually in a hospital setting.

Directions for use and doses

The dosage regimen is set individually, depending on the clinical response and systolic blood pressure.

An infusion solution containing 100 mcg/ml nitroglycerin is usually used. This solution is prepared by diluting 1 ampoule of Nitroglycerin, concentrate for infusion 10 mg/ml (= 20 mg nitroglycerin) in 200 ml of 0.9% sodium chloride solution, 5% glucose solution or isotonic glucose-saline solution to obtain a solution concentration of 100 μg/ ml. Higher concentrations can be used, but not more than 400 mcg/ml.

Infusion systems should be made of polyethylene (PE), polypropylene (PP), polytetrafluoroethylene (PTFE) or glass. Nitroglycerin is absorbed by materials made from polyvinyl chloride (PVC) and polyurethane (PU), which requires increasing its dose.

With intravenous administration of nitroglycerin, a pronounced hemodynamic effect is observed. Therefore, the drug is used only in a hospital setting, constantly monitoring the functions of the cardiovascular system. Systolic blood pressure should not decrease by more than 10-15 mmHg. in normotensive patients, no more than 5 mm Hg.

Sublingual.

Nitroglycerin is recommended to be taken as prescribed by a doctor.

The tablet is kept under the tongue until completely absorbed, without swallowing, immediately after pain occurs - 0.5–1 mg per dose. In many patients with stable angina, the effect occurs with a smaller dose (1/2–1/3 tablet), therefore, if the pain goes away quickly, it is recommended to spit out the remainder of the tablet that has not had time to dissolve.

Typically, the antianginal effect appears within 0.5–2 minutes; 75% of patients note improvement within the first 3 minutes, and another 15% within 4–5 minutes. If there is no antianginal effect, during the first 5 minutes you need to take 1 more tablet. nitroglycerin. In the absence of a therapeutic effect after taking 2-3 tablets.

you need to call a doctor immediately. Duration of action after sublingual administration is about 45 minutes. For frequent attacks of angina, it is customary to prescribe long-acting nitroglycerin medications. Tolerance to sublingual forms of nitroglycerin develops infrequently, however, if it occurs in some patients, the dose of the drug must be gradually increased, bringing it to 2-3 tablets.

Drug analogues

In case of heart attacks, many people are helped with the use of Nitroglycerin solution. In Latin this drug is called Nitroglycerinum. But of course, if necessary, some other medicine with a similar effect can be used for the same purpose.

You can replace Nitroglycerin, for example, with drugs such as:

• "Nitrocor".
• "Dikor Long."
• "Nitrogranulong".
• "Nitrosorbitol".

The products “Nitrocor” and “Nitrogranulong” are synonymous with this medication, since they contain the same active substance. Both of these drugs are used in emergency cases to relieve pain due to heart problems.

The active ingredient of Nitrosorbitol is isosorbitol dinitrate. This medicine is available in the form of tablets and solution. For attacks, only the second option of this drug can be used. Nitrosorbitol tablets act too slowly.

The product "Dikor Long" is not an absolute analogue of "Nitroglycerin". It is used mainly only for the prevention of attacks. One of the features of this medicine is that it is able to unload the heart muscle. Unfortunately, this medication acts slowly, and therefore cannot be used in emergency cases.

Pharmacological properties

Pharmacodynamics

Nitroglycerin is a peripheral vasodilator, preferentially affecting the venous vessels. Its effect is mainly due to a decrease in myocardial oxygen demand due to a decrease in preload (decreased blood flow to the right atrium and dilation of peripheral venous vessels) and afterload (decreased total peripheral vascular resistance).

Nitroglycerin is capable of releasing nitric oxide from its molecule, which is a natural endothelial relaxing factor. The compound increases the concentration of cyclic guanosine monophosphatase inside the cell, which prevents the penetration of calcium ions into smooth muscle cells and provokes their relaxation.

Relaxation of the smooth muscles of the vascular wall leads to vasodilation, which reduces the load on the heart and the myocardium’s need for oxygen. Dilation of the coronary vessels helps improve coronary blood flow and its redistribution to areas characterized by reduced blood circulation, which stimulates the transport of oxygen to the myocardium.

A decrease in venous return causes a decrease in pressure in the pulmonary circulation and filling pressure, improvement in blood supply to the subendocardial layers and regression of symptoms characteristic of pulmonary edema. Nitroglycerin is characterized by a central inhibitory effect on the sympathetic tone of blood vessels and suppression of the vascular component responsible for the formation of pain.

The use of sublingual forms usually makes it possible to stop an attack of angina within 1.5 minutes after oral administration, and the antianginal effect lasts for 30–60 minutes.

Pharmacokinetics

Nitroglycerin is quickly and almost completely absorbed from the surface of the mucous membranes of the oral cavity. When taken sublingually, it immediately penetrates the systemic bloodstream. The bioavailability of the drug is 100%, since primary hepatic degradation of the substance is excluded. The maximum concentration of nitroglycerin in the blood plasma is determined after 4-5 minutes.

The drug has a very large volume of distribution (1.2‒3.3 l/kg). The degree of binding to plasma proteins is 60%. Nitroglycerin is excreted in the urine in the form of metabolites (less than 1% of the dose taken is excreted unchanged), the total clearance is 25–30 l/min (with infusion administration - up to 78 l/min).

Pharmacodynamics. Nitroglycerin is an antianginal drug from the group of peripheral vasodilators with a predominant effect on venous vessels. The mechanism of action is associated with the release of the active substance nitric oxide (NO) in vascular smooth muscle. Nitric oxide causes activation of guanylate cyclase and increases the level of cGMP, which leads to relaxation of smooth muscle cells in the walls of blood vessels. Under the influence of nitroglycerin, arterioles and precapillary sphincters relax to a lesser extent than large arteries and veins.

The antianginal effect of nitroglycerin is associated mainly with a decrease in myocardial oxygen demand due to a decrease in preload (dilation of veins and a decrease in blood flow to the right atrium) and afterload (reduction in total peripheral vascular resistance). Promotes the distribution of coronary circulation in ischemic areas of the myocardium.

Pharmacokinetics. The effect is observed 1-2 minutes from the start of glyceryl trinitrate infusion and lasts 3-5 minutes.

The volume of distribution of glyceryl trinitrate is 3.3 ± 1.2 l/kg. At a serum concentration of 50 - 500 mcg/l, 60% of nitroglycerin binds to blood plasma proteins.

Metabolism of nitroglycerin occurs primarily in the liver under the influence of glutathione reductase. In addition, spontaneous hydrolysis and inorganic breakdown of nitroglycerin occurs in the blood serum. The metabolites are predominantly water-soluble, partially or completely freed from nitrogen, and are further metabolized to glucuronides and excreted in urine or bile. Enterohepatic recirculation is not observed.

The pharmacokinetics of nitroglycerin is complex and depends on the individual characteristics of patients. Fluctuations are due, for example, to primary metabolism through the liver, a large volume of distribution, concentration in the vessel walls, significant differences in concentrations in arteries and veins, hydrolysis in the blood serum and variable concentrations in the blood plasma. Plasma clearance of nitroglycerin during continuous infusion is 230 ± 9 ml/min/kg.

Reviews about the medicine

For the most part, people experiencing heart problems praise the drug Nitroglycerin. Judging by the reviews, it helps with attacks very well. However, most patients still advise taking this medicine only when it is really necessary. Nitroglycerin actually has a lot of side effects.

For example, this medicine can lower blood pressure to critical limits. Therefore, it is worth using it, and especially in the form of an alcohol solution intravenously, only during a severe attack. If heart problems are not too serious, most patients still advise relieving pain with the use of milder drugs, for example, the same Corvalol.

Precautionary measures

A patient who is prescribed nitroglycerin tells the attending physician in detail about all the medications he is taking in order to avoid unwanted interactions. The simultaneous use of nitroglycerin and other vasodilators, blood pressure pills, diuretics, some groups of antidepressants, antiarrhythmic drugs, beta blockers increases the hypotensive effect of nitroglycerin.

Nitroglycerin and alcohol are also incompatible things due to the risk of severe hypotension, so you should categorically avoid drinking any alcohol-containing drinks, especially since heart problems, which are an indication for taking nitroglycerin, themselves do not go well with drinking alcohol.

Hot rooms and high ambient temperatures contribute to the dilation of peripheral blood vessels, so taking nitroglycerin in such conditions may be accompanied by hypotension.

Tablets of nitroglycerin do not need to be chewed, since sudden penetration of the entire dose into the bloodstream at once can provoke a severe headache. To prevent this effect, you can take validol and menthol under the tongue at the same time.

Patients with acute cardiac pathology usually require heparin. In this case, it is worth remembering that nitroglycerin reduces the blood-thinning effect of heparin, therefore, if the doctor is forced to prescribe them simultaneously, he will strictly monitor hemostasis indicators.

Nitroglycerin preparations in the form of buccal plates should not be used in cases of stomatitis, periodontitis, or the presence of removable dentures, since these circumstances complicate the absorption of the active substance.

Uncontrolled, long-term use of nitrates without a break creates the preconditions for the formation of drug resistance. This is especially likely when using a patch or ointment, when the medicine is actually present in the blood constantly. Drug resistance makes treatment ineffective, requiring an increase in the dose of the drug taken. To avoid such negative aspects, doctors recommend taking breaks every day - removing the patch at night, for example.

It is worth recalling once again that nitroglycerin in any form should be prescribed by a specialist; you can take it yourself only if an accurate diagnosis and cause of chest pain have been established, and a cardiologist or therapist has already prescribed a specific dosage and dosage form. In this case, each patient is warned about the maximum amount of the drug at one time, upon reaching which, if there is no effect, a doctor must be immediately called.

Other forms of release

In addition to tablets and concentrated liquid for injection, this drug can be produced in the form of a spray or oil solution. “Nitroglycerin” of all these types, in any case, judging by the reviews, helps with angina very well.

In the form of an oil solution, this medicine is supplied to the market in capsules. This form of it can be found on sale very often today. Of course, if you wish, you can also take an oil solution of Nitroglycerin from the pharmacy. This form does not help with heart problems as quickly as alcohol injection. However, judging by the reviews, it can be considered quite effective.

If a patient at a pharmacy decides to take an oil solution of Nitroglycerin, he, of course, also needs to know how to use it. In this case, the medication capsule is placed under the tongue during an attack. The tablets of this remedy are supposed to be taken in exactly the same way.

Some people are also interested in how to make an oil solution of Nitroglycerin. The recipe for this medicine is actually quite simple. The drug in this form does not contain any complex components. For example, one of its components is regular vegetable oil. However, for your home medicine cabinet it is, of course, worth purchasing ready-made capsules containing such a medicine. Of course, only an industrial drug manufactured in compliance with all required technologies can be guaranteed to help with a heart attack. Experiments in this case can have more than sad consequences.

Dosage forms and features of taking nitroglycerin

Nitroglycerin can be prescribed intravenously or in the form of tablets, sprays, or patches. A solution of the drug is used for intravenous administration. Administration of the medicine through the skin or mucous membrane of the gums is considered very effective. To do this, use drops, tablets, sprays that are taken under the tongue.

Nitroglycerin should be taken as soon as pain appears, or even as a preventative measure if the patient has to exercise or perform activities that provoke heart pain. In the first case, the number of tablets can reach up to three; in the second, it is usually enough to take just one. The onset of the effect is judged by the reduction and disappearance of pain; monitoring of blood pressure and pulse is mandatory.

The modern pharmacological market offers a wide selection of both forms and names of nitrate-containing drugs. Analogues of regular nitroglycerin in tablets - nitrocardin, nitrocor, long-acting nitrates - sustak mite, sustak forte, nitrogranulong. A common aerosol containing nitroglycerin is nitromint, the spray is called nitrospray, plates for buccal use are trinitrolong, patches are deposit 10 and nitropercutene TTC.

To absorb the medicine through the blood vessels of the skin, a special patch soaked in nitroglycerin is prescribed. Tablets can be sublingual, acting quite quickly, but prolonged forms are also available, designed for long-term effects.

The dosage, dosage form and regimen are determined by the pathology for the treatment of which the cardiologist prescribes nitroglycerin - angina pectoris, heart attack, hypertensive crisis, etc.

taking nitroglycerin under the tongue

During an attack of heart pain, take a tablet or capsule of nitroglycerin under the tongue until it dissolves; the average dose for a pain attack is 0.5-1 milligram. If the first tablet does not work, it is recommended to take the next one no earlier than half an hour later. If the pain has passed, but the tablet still has not dissolved, it can and even should be removed from the mouth.

In most patients, the pain is relieved within the first few minutes after taking nitroglycerin, but if after 5 minutes the heart still hurts, then you can add half a milligram of the drug. The maximum number of tablets per attack is up to three. If they do not work, you need to immediately call an ambulance, because the pain may indicate a myocardial infarction.

For frequently recurring episodes of angina, it is more advisable to prescribe long-acting forms of nitroglycerin, but if an acute attack develops against this background, the patient needs to additionally take nitroglycerin under the tongue.

Nitrates for preventive purposes are prescribed in the form of long-acting tablets (extended-release). They are taken orally with water before meals. The dosage of nitroglycerin is 2.9 mg, up to two tablets per dose, the frequency of use is 3-4 times a day. In case of severe pathology, the dosage of the drug can be increased to 5.2 mg.

Long-acting nitrates act more slowly, most of them are inactivated in the liver, so the effectiveness is lower than that of “sublingual” drugs. With regular use, the maximum number of tablets per dose should not be more than two.

Films or drops that penetrate the oral mucosa are much more effective. Drops are instilled under the tongue, the film is glued to the gum. These drugs are indicated both for eliminating a painful attack and for preventing angina pectoris (during periods of physical activity, for example).

Transdermal patches with nitroglycerin ensure a uniform and long-term release of the drug into the bloodstream through the skin. They are indicated for patients with chronic circulatory failure after heart attack. It is advisable to begin treatment with them in a hospital setting, and when the maximum effective dose is reached, the patient is sent home.

In addition to patches, penetration of the drug through the skin is achieved by using an ointment, which is applied to an area of ​​the body that is devoid of hair and the possibility of friction with clothing.

nitroglycerin spray

Spray and aerosols are popular and convenient forms of using nitroglycerin. They are used for attacks of pain in the heart, as well as for incipient or developed pulmonary edema. In a sitting position, the patient needs to make 1-2 presses on the bottle dispenser, while holding his breath. After the drug enters the oral cavity, the effect occurs within a few minutes.

The maximum dose of a spray or aerosol for a painful attack is 3 presses, for pulmonary edema - up to four. To prevent an attack of pain before physical activity, the patient can take one dose of the drug.

Intravenous administration of nitroglycerin is indicated for myocardial infarction and other severe forms of coronary heart disease. It is important to carefully calculate the rate of administration of the drug, otherwise side effects cannot be avoided. If you use a special dispenser, it is possible to use even undiluted nitroglycerin, because the device itself will calculate at what intervals and in what quantity it should be administered to the patient. When using a regular dropper, the doctor calculates the number of drops per unit of time.

Treatment by intravenous infusion can be carried out for 2-3 days; repeated administration of nitroglycerin is not prohibited if necessary. During administration, the doctor must monitor blood pressure levels to prevent severe hypotension.

Nitroglycerin is often taken not only for angina attacks, but also for high blood pressure in combination with other antihypertensive drugs. This is especially justified for chest pain and shortness of breath against the background of a hypertensive crisis. The dosage of the drug is the same as for angina pectoris - up to three tablets with an interval of 5-10 minutes. If the pain does not go away, the pressure continues to be high, you must immediately call an ambulance.