Concentrate for solution for infusion Nitroglycerin is used for the following indications:
- Severe and prolonged pain of ischemic origin in the heart area, associated with myocardial infarction or unstable angina.
- Failure of the pumping function of the heart and pulmonary edema associated with acute myocardial infarction.
- Hypertension associated with open heart surgery and other surgical procedures.
- Ensuring controlled arterial hypotension during surgical interventions.
Contraindications
Hypersensitivity to nitroglycerin and other nitro compounds. Hypovolemia, severe arterial hypotension (systolic pressure <90 mmHg), acute myocardial infarction localized in the right ventricle, increased intracranial pressure (due to head injury or cerebral hemorrhage), cardiac tamponade, hypertrophic obstructive cardiomyopathy, constrictive pericarditis, angle-closure glaucoma, toxic pulmonary edema, anemia, acute vascular insufficiency (shock, vascular collapse).
Sildenafil. Concomitant use of the phosphodiesterase type 5 inhibitor sildenafil, since sildenafil potentiates the hypotensive effect of nitrates (the interval between doses should be at least 48 hours).
Nitroglycerin
In acute myocardial infarction or acute heart failure, it should be used only with careful clinical monitoring of the patient.
To prevent an increase in angina attacks, abrupt withdrawal should be avoided.
If the patient is known to be taking phosphodiesterase-5 inhibitors, drug therapy is contraindicated. Patients receiving therapy with the drug should be warned not to take phosphodiesterase-5 inhibitors (for example, sildenafil, tadalafil, vardenafil).
Against the background of intravenous administration of the drug, a significant decrease in blood pressure and the appearance of dizziness may occur during a sharp transition from the “lying” or “sitting” position to the “standing” position; hot weather, as well as increased angina (with a sharp decrease in blood pressure) and myocardial ischemia up to myocardial infarction and sudden death (paradoxical nitrate reactions). To prevent an undesirable decrease in blood pressure, the rate of drug administration should be individually and methodically selected correctly. A decrease in blood pressure can be observed not only during the period of selecting the rate of drug administration, but also later against the background of stabilized blood pressure. Therefore, blood pressure monitoring should be carried out at least 3-4 times per hour throughout the entire infusion time.
It is possible to develop tolerance and cross-tolerance to other drugs of the nitrate group with long-term use, especially in high doses. Patients previously treated with organic nitrates (eg, isosorbide dinitrate, isosorbide-5-mononitrate) may require a higher dose.
If blurred vision persists or is severe, treatment should be discontinued.
In patients with severe liver failure and severe renal failure, dose adjustment is required depending on the severity of the disease (especially when using high doses), it is recommended to start with the lowest possible dose. Careful monitoring of the patient is necessary.
Hypoxemia
Caution should be exercised when used in patients with arterial hypoxemia due to severe anemia (including glucose-6-phosphate dehydrogenase (G6PD)-induced deficiency) because the metabolism of nitroglycerin is reduced in such patients.
Caution is also required when used in patients with hypoxemia and impaired ventilation/perfusion due to pulmonary disease or heart failure; as well as in patients with angina pectoris, myocardial infarction or cerebral ischemia, with airway disorders (especially alveolar hypoxia).
Under these conditions, vasoconstriction occurs in the lungs in order to shift the perfusion of the area of alveolar hypoxia to the part of the lung with better ventilation (Euler-Lillestrand reflex). As a potent vasodilator, nitroglycerin may interfere with this protective vasoconstriction and consequently lead to increased perfusion of poorly ventilated areas, worsening venous-perfusion imbalances, and a further decrease in arterial partial pressure of oxygen.
Methemoglobinemia
The development of methemoglobinemia has been reported after use of the drug. Treatment of methemoglobinemia with methylene blue is contraindicated in patients with glucose 6-phosphate dehydrogenase or methemoglobin reductase deficiency.
Overdose
Symptoms: arterial hypotension, tachycardia, feeling of heat, hyperemia, headache, rapid heartbeat, fainting. Increased intracranial pressure, which can lead to confusion and neurological disorders. An overdose over several hours can lead to ethanol intoxication.
Treatment. Excessive hypotension can be corrected by reducing the rate of drug infusion or stopping its administration. In case of severe arterial hypotension, the patient should be placed in a horizontal position with the head of the bed lowered. For arterial hypotension associated with bradycardia, the use of atropine and dopamine is indicated. Hypoxia caused by methemoglobinemia can cause cyanosis, metabolic acidosis, coma, convulsions, and vascular collapse. For methemoglobinemia, a solution of methylene blue (1-2 mg/kg body weight) is administered.
A pronounced and rapid anti-ischemic effect, an equally pronounced and rapid effect on hemodynamics, “controllability” and safety - all these characteristics of nitroglycerin (NTG) have long ensured its role as one of the main drugs used to treat exacerbations of coronary heart disease (CHD; table. 1). The purpose of this report is to analyze current recommendations for the use of intravenous NTG in the treatment of patients with acute coronary syndromes (ACS).
Mechanism of action: antianginal, hemodynamic and other effects of NTG
The mechanism of action of NTG and other nitrates is closely related to one of the main vasoactive substances in the body - nitric oxide. Essentially, all nitrates should be considered as exogenous sources. Nitric oxide, by activating the enzyme guanylate cyclase, helps to increase the content of cyclic guanidine monophosphate (cGMP) in cells, a universal intracellular messenger that causes relaxation of smooth muscle structures.
The antianginal effect of NTG is based on multiple physiological reactions associated with both its direct effect on coronary blood flow and changes in a number of hemodynamic characteristics. By causing dilatation of both normal and atherosclerotic arteries, increasing blood flow in collaterals, NTG improves coronary circulation and promotes blood redistribution in favor of the ischemic zone. IGT causes both predominantly venous and arterial dilatation. By dilating the peripheral veins, NTG reduces the level of preload, which, in turn, reduces the tension of the left ventricle and its oxygen demand. By dilating peripheral arteries, NTG reduces afterload.
The indicated vascular effects of NTG (especially when administered intravenously) should be complemented by a beneficial effect on the parameters of the coagulation system, aggregation of blood platelets, and rheological properties of blood.
NTG in the treatment of ACS from the perspective of evidence-based medicine
Meta-analysis by S. Yusuf et al. [10] 10 small randomized studies performed in the period preceding the widespread use of thrombolytic therapy in the treatment of acute myocardial infarction (MI), and including a total of about 2000 patients, showed a fairly pronounced (35%) reduction in mortality in patients who received early intravenous administration NTG. The most serious (and large) controlled studies of nitrates in acute MI were performed in the early 90s. last century – GISSI-3 [2] and ISIS-4 [3]. They already provided for the use of thrombolytic agents. In fact, both studies, covering about 80 thousand patients, compared the effectiveness of 2 strategies - routine (“all in the absence of contraindications”) and selective (“according to indications”) use of nitrates in the treatment of acute MI. In this regard, the “traditional interpretation” of their result, as evidence that nitrates have no effect on the survival of patients with MI, does not seem entirely correct. It is probably more acceptable to conclude that there is no advantage to routine use of nitrates over selective use, since a significant proportion of patients randomized to the “control group” naturally received nitrates when necessary. There have been no significant studies of nitrates in unstable angina and non-ST elevation MI (non-ST elevation ACS). Thus, the use of NTG and other nitrates in patients with ACS, as modern guidelines unanimously note, is based mainly on “pathophysiological premises and clinical experience” [4].
Indications for starting intravenous administration of NTG in patients with ACS
Intravenous infusion of NTG in ACS with ST segment elevation
Indications for starting intravenous infusion of NTG in patients with MI are presented in Table 2 and correspond to the main provisions of existing practical guidelines [5]. Situations in which NTG infusion within the first 24-48 hours is effective include cases of anterior major MI; MI complicated by heart failure and recurrent ischemia; as well as MI occurring against the background of high blood pressure (BP). Infusion of NTG can be continued for more than 48 hours if stagnation in the pulmonary circulation and early post-infarction angina persists. There are no concerns limiting the routine use of NTG in all cases of MI in the absence of contraindications, as well as (more than 48 hours) in cases of extensive anterior MI complicated by heart failure.
Intravenous infusion of NTG for ACS without ST segment elevation
The need for intravenous administration of NTG in cases of ACS without ST elevation (Table 3) is largely determined by the presence of clear indications. As a rule, it is advisable in patients with high coronary risk - with recurrent angina attacks, despite adequate treatment, as well as in cases of congestive heart failure.
Contraindications to starting intravenous infusion of NTG
Conditions in which the use of intravenous NTG may be associated with a potential risk (Table 2) include arterial hypotension with a systolic blood pressure level below 90 mm Hg. Art., bradycardia (heart rate less than 50 per minute) or, on the contrary, severe tachycardia. Contraindications should also include cases of right ventricular MI that occurs with significant hemodynamic disturbances. Nitrates within the next 24 hours are unsafe for patients who have taken sildenafil (Viagra). The last warning is due to the mechanism of action of sildenafil, which blocks phosphodiesterase and thereby promotes excessive accumulation of cGMP in cells. This can lead to the development of uncontrolled arterial hypotension with all the ensuing consequences.
Dosing of intravenous NTG, development of tolerance
If necessary, the administration of NTG can be started with an intravenous bolus of 12.5-25 mcg. The initial infusion rate is usually 10 mcg/min. At intervals of 3-5 minutes, monitoring the patient’s condition, the infusion rate is increased by 10 mcg/min until individual criteria for optimal dosing are achieved. These include: elimination of ischemic symptoms, reduction of systolic blood pressure by 10% (10-15 mm Hg) in normotensive patients and by 25-30% in patients with high blood pressure. The criterion for optimal dosing of NTG in congestive heart failure is, as a rule, the blood pressure level. There is no information on the maximum permissible doses of NTG, although in practice doses exceeding 200 mcg/min are usually not used. If the symptoms of ischemia are not eliminated by increasing the rate of NTG administration, then the criterion for stopping further increase in the dose is the blood pressure level.
The development of tolerance to IGT becomes clinically significant one day after the start of continuous infusion. In an ACS situation, it usually does not pose a big problem and can be overcome by escalating the dose of the administered drug. If longer-term use of nitrates is necessary, conditions should be created for their intermittent use, using alternative treatment options.
Side effects of intravenous NTG and discontinuation of its infusion
The most common side effects of intravenous infusion of NTG are hypotension and headache. Methemoglobinemia, as a rule, has only theoretical significance: it has been shown that even long-term (2-4 weeks) administration of NTG at 300-400 mcg/h does not lead to an increase in the content of methemoglobin in the blood [6]. The most serious side effect of IGT is considered to be arterial hypotension. A pronounced decrease in blood pressure upon administration of even minimal doses of NTG may be one of the clinical manifestations of right ventricular myocardial infarction.
If necessary, an attempt is made to gradually reduce the infusion rate (especially in patients receiving large doses of the drug) with subsequent cessation of the administration of NTG. Rapid withdrawal of IGT in some cases can provoke repeated ischemic episodes.
IGT and right ventricular myocardial infarction
Typical disorders that develop with significant lesions of the right ventricular myocardium are characterized by dilatation of its cavity, a decrease in right ventricular output, a decrease in left ventricular preload, left ventricular filling pressure, cardiac output, circulating blood volume and systemic blood pressure. Due to the above circumstances, a further decrease in preload with the introduction of NTG, as well as diuretics, can contribute to the aggravation of hemodynamic disorders, frequent arterial hypotension, and even lead to the development of shock. The basis for the treatment of shock that complicates the course of right ventricular myocardial infarction is volume-replenishment therapy and the use of dobutamine. With combined dysfunction of the left and right ventricles, NTG infusion may be added to treatment with dobutamine; in this case, manipulations of administered drugs should be carried out under the control of central hemodynamic parameters using a “floating” Swan-Ganz catheter. The maximum pumping function of the heart is usually observed when the pressure increases (“jamming”) to 20 mm Hg. Art.
NTG in the treatment of patients with cardiogenic shock
Dopamine and/or dobutamine, drugs that stimulate the contractile function of the heart and have a pressor effect, form the basis of pharmacotherapy for cardiogenic shock. Carefully monitored infusion of NTG may be required if there is a need to further reduce left ventricular filling pressure, increase cardiac output, or when pulmonary congestion is associated with the use of pressor agents.
Conclusion
Summarizing all of the above, we can conclude that in the absence of clearly defined contraindications and correct use, including compliance with all necessary precautions, intravenous NTG can be actively used in the treatment of various forms of ACS, incl. THEM.
An important advantage of NTG for intravenous administration over other nitrates is its greater safety, determined by the pharmacokinetics of this drug (rapid onset of action, short half-life), which makes it possible to very quickly stop the effect of NTG if adverse events develop. In addition, this provides the ability to regulate the strength of the therapeutic effect of NTG. Due to its good “controllability,” intravenous NTG in the early stages of acute coronary disorders should be given preference over its other formulations (sublingual, tablets, aerosol).
Tolerance that develops with prolonged NTG infusion is usually easily overcome by increasing the dosage or rate of administration.
There are a number of imported intravenous nitroglycerin preparations on the Russian drug market, but their widespread clinical use is limited by the price factor. The situation changed for the better after the domestic drug “Nitroglycerin solution 0.1% for injection No. 10” entered the market. At the beginning of this year, the drug underwent clinical testing in a number of Moscow clinics and, according to experts, turned out to be effective in patients with acute coronary pathology and chronic heart failure. Domestic intravenous nitroglycerin was not inferior to foreign analogues (Izoket, Nitromac, etc.) and was characterized by high safety.
Note!
Description of the drug Nitroglycerin conc. d/r-ra d/inf. 10mg/ml amp. 2ml No. 10 on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.
Nitroglycerin 0.1% 10ml n10 solution for injection
Release form
Tablets, capsules and sublingual drops.
Compound
Capsules and tablets of 0.5 mg nitroglycerin.
Drops 10 mg/ml.
Package
20, 40 pcs.
pharmachologic effect
NITROGLYCERIN is a peripheral vasodilator with a predominant effect on venous vessels. Antianginal agent. The mechanism of action is associated with the release of the active substance nitric oxide in the smooth muscles of blood vessels. Nitric oxide causes activation of guanylate cyclase and increases cGMP levels, which ultimately leads to smooth muscle relaxation. Under the influence of nitroglycerin, 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 active substance molecules in the walls of arterioles.
The effect of nitroglycerin 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 (decreased peripheral vascular resistance). Promotes the redistribution of coronary blood flow into ischemic subendocardial areas of the myocardium. Increases exercise tolerance in patients with coronary artery disease and angina pectoris. In heart failure, it helps to unload the myocardium mainly by reducing preload. Reduces pressure in the pulmonary circulation.
Indications
IHD: angina pectoris (treatment, prevention), vasospastic angina (Prinzmetal), unstable angina, spasm of the coronary arteries during coronary angiography, acute coronary syndrome, acute myocardial infarction, acute left ventricular failure (cardiac asthma, interstitial and alveolar pulmonary edema), chronic heart failure, controlled arterial hypotension during surgical procedures, prevention of hypertensive reactions during endotracheal intubation, skin incisions, sternotomy, occlusion of the central retinal artery, esophageal dyskinesia, functional cholecystopathy, acute pancreatitis, biliary colic, spastic intestinal dyskinesia.
Contraindications
Hypersensitivity, severe hypotension, collapse, myocardial infarction with low end-diastolic pressure in the left ventricle and/or severe hypotension (systolic blood pressure below 90 mmHg) or collapse, right ventricular infarction, bradycardia less than 50 beats/min, primary pulmonary hypertension, cerebral hemorrhage, head injury, increased intracranial pressure, cerebral ischemia, cardiac tamponade, toxic pulmonary edema, severe aortic stenosis, conditions accompanied by a decrease in end-diastolic pressure in the left ventricle (isolated mitral stenosis, constrictive pericarditis), angle-closure glaucoma, pregnancy, breastfeeding.
Directions for use and doses
Orally, sublingually, buccally, intravenously, transdermally, cutaneously.
Relief of angina pectoris. Sublingually (the tablet or capsule is kept under the tongue until completely absorbed, without swallowing), immediately after the onset of pain - 0.5-1 mg per dose. If necessary, to achieve a faster effect, the capsule should be immediately crushed with teeth; the capsule can be repeated after 30-40 minutes. In many patients with stable angina, the effect occurs with a smaller dose (1/2-1/3 tablets), 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, another 0.5 mg of nitroglycerin should be taken during the first 5 minutes. If there is no therapeutic effect after taking 2 tablets, you should immediately call a doctor. Duration of action after sublingual administration is about 45 minutes.
For frequent attacks of angina, it is advisable to prescribe prolonged forms of nitrates. If an angina attack develops during treatment with long-acting nitrates, nitroglycerin must be taken sublingually to stop the acute attack. 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.
To prevent angina pectoris, take it orally with water before meals. In mild cases - 1-2 tablets of 2.9 mg 2-3 times a day. In more severe cases - 1-2 tablets of 5.2 mg 2-3 times a day. The maximum daily dose is 34.8 mg. Due to the fact that the bioavailability of nitroglycerin from retard tablets is low, it is recommended, if well tolerated, to take 1-3 tablets at a time regularly 3-4 times a day or periodically, 30-40 minutes before the expected physical activity. If the therapeutic effect is insufficient, the dose can be gradually increased (but not more than 2 tablets per dose), and after the onset of a therapeutic effect, it can be reduced.
1% solution for sublingual use: relief of an attack - 1-2 drops sublingually or 2-3 drops applied to a small piece of sugar and keep it in the mouth, without swallowing, until completely absorbed.
Buccal: a plate with a selected dose of nitroglycerin is glued to the oral mucosa, usually in the upper gum area above the canines or small molars. To do this, simply press the plate with your finger against the oral mucosa for a few seconds. The action occurs almost immediately and lasts 3-4 hours or more. To prevent angina attacks, 1 mg films are used for 1-1.5 hours, and 2 mg films are used for 2-3 hours. If it is necessary to increase the flow of nitroglycerin into the blood (including during intense walking, climbing several floors), you should lick the film 2-3 times with your tongue without moving it from its place. If physical activity exceeds the period of resorption of the film, it is necessary to stick a new one on the opposite side of the gum.
Use during pregnancy and breastfeeding
Information not described.
Side effects
From the nervous system and sensory organs:
headache, dizziness, feeling of fullness in the head, weakness, restlessness, psychotic reactions, blurred vision, exacerbation of glaucoma.
From the cardiovascular system and blood (hematopoiesis, hemostasis):
flushing of the face, palpitations, hypotension, incl. orthostatic, collapse, methemoglobinemia.
From the gastrointestinal tract:
dry mouth, nausea, vomiting, diarrhea,
From the skin:
cyanosis, skin hyperemia.
Allergic reactions:
itching and burning, allergic contact dermatitis (when using transdermal forms).
Other:
hypothermia, feeling of heat, paradoxical effects - an attack of angina, ischemia up to the development of myocardial infarction and sudden death; development of tolerance.
special instructions
The drug contains dextrose (glucose), which must be taken into account when used in patients with diabetes.
In acute myocardial infarction or acute heart failure, it should be used only under the condition of careful clinical monitoring of the patient.
To prevent an increase in angina attacks, abrupt withdrawal should be avoided.
To prevent an undesirable decrease in blood pressure, the rate of drug administration should be individually and methodically correct (see above). A decrease in blood pressure can be observed not only during the period of selecting the rate of nitroglycerin administration, but also later, against the background of initially stabilized blood pressure. Therefore, blood pressure monitoring should be carried out at least 3-4 times per hour throughout the entire duration of nitroglycerin infusion.
Patients previously treated with organic nitrates (isosorbide dinitrate, isosorbide-5-mononitrate) may require a higher dose to obtain the desired hemodynamic effect.
The severity of headache while taking nitroglycerin can be reduced by reducing its dose or by simultaneously taking validol.
If blurred vision or dry mouth persists or is severe, treatment should be discontinued.
While taking nitroglycerin, a significant decrease in blood pressure and the appearance of dizziness with a sharp transition to a vertical position from a “lying” or “sitting” position are possible, as well as increased angina pectoris with a sharp decrease in blood pressure, ischemia, up to the development of myocardial infarction and sudden death (paradoxical nitrate reactions ).
Interaction
Salicylates increase the level of nitroglycerin in plasma, barbiturates accelerate metabolism. Nitroglycerin reduces the pressor effect of adrenergic agonists and the anticoagulant effect of heparin (with intravenous administration). Antihypertensive, antiadrenergic drugs, vasodilators, sildenafil citrate, calcium antagonists, tricyclic antidepressants, MAO inhibitors, ethanol, quinidine and procainamide enhance the hypotensive and systemic vasodilating effects. Methionine, N-acetylcysteine, ACE inhibitors and salicylates increase antianginal activity. Unithiol restores reduced sensitivity to nitroglycerin. Dihydroergotamine, m-anticholinergics, alpha-adrenomimetics, histamine, pituitrin, corticosteroids, stimulants of the central nervous system and autonomic ganglia, bee and snake venoms, excessive insolation reduce the vasodilatory and antianginal effects.
Overdose
Symptoms:
pronounced decrease in blood pressure (below 90 mm Hg) with orthostatic dysregulation, reflex tachycardia, headache, asthenia, dizziness, increased drowsiness, feeling of heat, nausea, vomiting may develop when using high doses (more than 20 mg/kg) - collapse, cyanosis, methemoglobinemia, dyspnea and tachypnea.
Treatment:
stop further administration. The head of the bed should be lowered and the patient's legs should be raised. As a rule, blood pressure normalizes within 15-20 minutes after stopping the administration of nitroglycerin, then administration can be continued after reselecting the infusion rate.
In case of severe hypotension and/or shock, volume replacement should be performed; To correct blood pressure, it is possible to use phenylephrine and other vasoconstrictors. The use of epinephrine (adrenaline) and similar substances is contraindicated!
Depending on the severity, the following antidotes are suggested in cases of methemoglobinemia:
1. Ascorbic acid 1 g orally or as sodium salt intravenously
2. Methylthioninium chloride (methylene blue) up to 50 ml of 1% solution i.v.
3. Oxygen therapy, hemodialysis, exchange blood transfusion.
Best before date
3 years. Do not use after the expiration date indicated on the package.
Storage conditions
In a place protected from light and out of reach of children, away from fire, at a temperature of 5°C to 25°C.
