Sustak Forte instructions for use of the drug

Release form, packaging and composition of the drug Clinical-pharmacological group Pharmaco-therapeutic group Pharmacological action Indications for use Method of administration and doses Side effects Contraindications for use Use in children Special instructions Drug interactions

Registration Certificate Holder:

KRKA-RUS, LLC (Russia)

ATX Code:

C01DA02

Active substance:

nitroglycerin (glyceryl trinitrate)

Dosage form:

Sustak Forte

pharmachologic effect

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 glyceryl trinitrate, 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 (glyceryl trinitrate) 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 OPSS). 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 for use

For sublingual and buccal use: relief and prevention of angina attacks; as an emergency medicine for acute myocardial infarction and acute left ventricular failure at the prehospital stage.

For oral administration: relief and prevention of angina attacks, rehabilitation treatment after myocardial infarction.

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

For cutaneous use: prevention of angina attacks.

Directions for use and doses

The method of administration and dosage regimen of a particular drug depend on its release form and other factors. The optimal dosage regimen is determined by the doctor. The compliance of the dosage form of a particular drug with the indications for use and dosage regimen should be strictly observed.

Use sublingually, buccally, orally, cutaneously, intravenously. The dose and treatment regimen are set individually, depending on the indications, the specific clinical situation, and the dosage form used.

Buy Ripart Forte synovial fluid prosthesis 15 mg/ml 3 ml No. 1 in pharmacies

product name

“Medicine for replacing synovial fluid RIPART®, volumes 1 ml, 2 ml, 3 ml, RIPART® Forte, volumes 1 ml, 2 ml, 3 ml and RIPART® Long, volumes 1 ml, 2 ml, 3 ml” (hereinafter referred to as text - Means for replacing synovial fluid).

Type of contact with the human body: constant contact with the internal environment of the body.

This product is sterile. For single use.

Conditions of use: in clinics, hospitals and other medical institutions by qualified medical personnel trained in the technique of injecting synovial fluid replacement agents.

Application area

The product is used for administration to replace synovial fluid in case of joint damage, to eliminate pain and improve joint mobility. The agent for replacing synovial fluid is used for osteoarthritis and other degenerative-dystrophic, traumatic and post-traumatic changes in the joints: knee, hip and other large joints, as well as as an aid in orthopedic surgery.

The medical device is used in traumatology, orthopedics, and sports medicine.

Product characteristics

The synovial fluid replacement product is a sterile, colorless and transparent viscous solution of highly purified sodium hyaluronate, obtained by biofermentation. The product contains sodium hyaluronate in a concentration of 10 mg/ml (RIPART® synovial fluid replacement agent), 15 mg/ml (RIPART® Forte synovial fluid replacement agent) and 20 mg/ml (RIPART® Long synovial fluid replacement agent), sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium chloride 0.9% solution for infusion.

Sodium hyaluronate is the sodium salt of hyaluronic acid, a glycosaminoglycan formed by groups representing D-glucuronic acid and N-acetyl-D-glucosaminodisaccharide. It is widely present in the extracellular matrix in both animals and humans. The molecular weight of sodium hyaluronate used in the manufacture of the synovial fluid replacement agent must be at least 3 MDa.

Sodium hyaluronate belongs to a small group of substances that are the same for all living organisms. Sodium hyaluronate is a natural polysaccharide that is part of all tissues of the body, and sodium hyaluronate is found in especially high concentrations in synovial fluid and skin. The synovial fluid replacement agent consists of biosynthetically produced and purified sodium hyaluronate. Sodium hyaluronate in the body is a natural component of synovial fluid, which in joints serves as a lubricant for cartilage and ligaments, and is also an shock absorber. It is known that synovial fluid in affected joints has lower viscosity and elasticity than synovial fluid in healthy joints. Injecting sodium hyaluronate into a joint to restore viscosity and elasticity can reduce pain and restore joint mobility.

The composition of the synovial fluid replacement agent ensures the restoration of viscoelastic properties and the transition of the viscous properties of the solution into elastic (elastic) in the range of shear rates from 0.5 to 2.5 Hz, which corresponds to the range of movements from walking to running.

Main technical characteristics and materials used in manufacturing

Table 1. Main technical characteristics of the product

Table 2 - Materials used in the manufacture of the product

Information about the presence of a medicinal product, materials of animal and (or) human origin in a medical product

The synovial fluid replacement product contains the following drugs:

- sodium hyaluronate; - sodium chloride, solution for infusion 0.9%;

Materials of animal and (or) human origin are not contained in this medical product.

Sterility

The product is supplied sterile. Sterilization parameters: steam sterilization method in accordance with the requirements of GOST R ISO 17665-1.

Repeated sterilization of the product is prohibited. Reuse is prohibited.

Indications, contraindications, warnings, precautions, side effects

Indications for use:

— Osteoarthritis and other degenerative-dystrophic, traumatic and post-traumatic changes in joints: knee, hip and other joints. — As an aid in orthopedic surgery. — For use in patients who have increased physical activity and regularly load the damaged joint.

Contraindications:

— Do not use in patients suffering from hypersensitivity (allergy) to products containing sodium hyaluronate. — It is prohibited to inject the Synovial Fluid Replacement Agent into the joint of patients who have infectious or skin diseases in the area where the injection is intended.

Warnings:

To prepare the skin, it is prohibited to simultaneously use disinfectants containing quaternary ammonium salts, since sodium hyaluronate may form a precipitate in their presence.

Intravascular administration is prohibited due to the possibility of systemic adverse side effects. It is prohibited to use the product to replace synovial fluid during intraocular surgery.

Precautionary measures:

— The safety and effectiveness of injection of this product in parallel with other intra-articular injections have not been studied. — Efficacy has been established only if the minimum recommended course of treatment is followed. — The synovial fluid replacement agent should be used with caution in patients with signs of impaired venous or lymphatic drainage in the lower extremities. — For bilateral treatment, separate syringes should be used for each knee or hip joint. — Local anesthetics should not be used if the patient is known to be allergic or hypersensitive to local anesthetics. — X-ray-guided hip injections should not be performed using radiocontrast agents if the patient is known to be allergic or hypersensitive to radiocontrast agents. — STERILE CONTENTS. The pre-filled syringe is intended for single use. The contents of the syringe must be used immediately after the container is opened. Any unused amount of Synovial Fluid Replacement Agent should be discarded. — It is necessary to check the expiration date and the integrity of the individual packaging (syringe) before using the medical product. Do not use after the expiration date, or if the packaging is open or damaged.

Side effects:

The synovial fluid replacement agent is well tolerated. Possible side effects include short-term pain at the injection site, a feeling of heat, bruising, redness and/or swelling. As a rule, such reactions disappear without a trace within 2-3 days and do not in any way affect the effectiveness of treatment. Cases of allergic and anaphylactic reactions are rare. If precautions are not taken during intra-articular administration, septic arthritis may occur in very rare cases.

Risks of use:

The manufacturer has determined the risks for the patient associated with the occurrence of each type of hazardous factors and the occurrence of their consequences. The parameters for reducing risks when applying measures to prevent the occurrence of conditions for the manifestation of hazardous factors or the occurrence of their consequences are calculated.

It has been established that after the implementation of risk control measures, no new risks arise, and the overall residual risk is considered acceptable; The production risks do not change depending on the composition and type of packaging of a medical product.

Patient Information

- As with any invasive procedures performed on the joints, the patient is advised to avoid any physical exertion, as well as prolonged (lasting for more than 1 hour) activities associated with bearing weight loads (this applies, for example, to jogging and tennis) within 48 hours after intra-articular injection of the product. — The safety and effectiveness of use of the drug for replacing synovial fluid in women during pregnancy and lactation, as well as in children under 18 years of age, has not been established.

Recommendations for a medical specialist

The volume of synovial fluid replacement agent administered depends on the size of the joint. The physician is responsible for determining the applicable volume and must ensure that the joint is not overloaded.

A course of treatment with RIPART® synovial fluid replacement agent usually requires a cycle of procedures consisting of 3-5 injections (with an interval of 1 week).

A course of treatment with RIPART® Forte, a synovial fluid replacement agent, usually requires a cycle of procedures consisting of 1-3 injections (with an interval of 1 week).

A course of treatment with RIPART® Long, a synovial fluid replacement agent, usually requires a cycle of procedures consisting of 1-2 injections (with an interval of 1 week).

The amount of sodium hyaluronate injected into the joint during the procedure is determined according to tables 3, 4 and 5. The choice of dosage is at the discretion of the attending physician.

Table 3. For RIPART® Synovial Fluid Replacement Agent

Table 4. For Synovial Fluid Replacement Agent RIPART® Forte

Table 5. For Synovial Fluid Replacement Agent RIPART® Long

If necessary, the course can be repeated.

The decision on the applicability of a repeated course is made by the attending physician.

Procedure for working with a medical device

1. The synovial fluid replacement agent is administered intra-articularly once. Subcutaneous administration of lidocaine or a similar local anesthetic may be recommended prior to administration of the synovial fluid replacement agent. 2. Do not use Synovial Fluid Replacement Product if the blister pack is opened or shows signs of damage. Do not use the product after the expiration date indicated on the packaging. 3. When preparing for use and during the actual use of a medical device, strict adherence to aseptic rules is required. 4. If necessary (if present), remove joint effusion before administering Synovial Fluid Replacement Agent. 5. It is necessary to remove the screw cap of the syringe and the cap of the needle tip in compliance with all the rules of asepsis. Introduction Means for replacing synovial fluid into the joint must be carried out using an appropriately sized needle (selected based on the size of the joint). The needle is not included in the product packaging.

Inject the required volume of synovial fluid replacement into each joint. If there is a doctor's order that involves injection into several joints, a separate syringe must be used for each joint.

The synovial fluid replacement product is a DISPOSABLE MEDICAL DEVICE (REPEATED USE IS PROHIBITED).

Conditions of use, storage and transportation

The medical device is used indoors at an ambient temperature of 2°C to 25°C.

Transportation must be carried out by all types of transport, in closed vehicles, in accordance with the rules for the carriage of goods in force for this type of transport.

The synovial fluid replacement agent must be transported in the manufacturer's packaging at a temperature of 2°C to 25°C and a relative humidity of 30 to 75% without moisture condensation.

The synovial fluid replacement product must be stored in the manufacturer's packaging, protected from direct sunlight, heat and freezing, at a temperature from 2°C to 25°C and relative humidity from 30 to 75% without moisture condensation.

Biodegradation of a medical device in the patient’s body

The protective film formed after the introduction of the synovial fluid replacement agent retains its elastic properties for 6 months.

After 6 months, the synovial fluid replacement agent breaks down under the influence of a group of tissue enzymes called hyaluronidases into decomposition products: oligosaccharides and low molecular weight hyaluronates, which are subsequently excreted from the body through natural metabolic pathways.

Removal or replacement Synovial fluid replacement agents are not possible because it is inseparably mixed with the synovial fluid of the joint.

Medical product packaging

The synovial fluid replacement product is individually packaged as a syringe. Next, 1 syringe is packaged in a single-barrier polymer contour cell packaging, hermetically sealed with laminated paper or multilayer combined paper-based material. Next, single-barrier polymer contour blister packaging 1 pc. Packed in a cardboard box. Instructions for use included 1 piece.

Disposal Information

The medical device must be disposed of after use or expiration date, as well as if the integrity of the packaging is damaged, in accordance with the local legislation of the consumer’s country.

Disposal of used syringes must be carried out in accordance with SanPiN 2.1.7.2790-10 for class B waste (epidemiologically hazardous waste).

Unused medical products with an expired expiration date or with damaged packaging, as well as blister packaging, cardboard packs and shipping containers are disposed of in accordance with SanPiN 2.1.7.2790-10 for class A waste (epidemiologically safe waste, similar in composition to solid household waste) .

Guarantees

The manufacturer guarantees that the quality of the product meets the requirements of the technical specifications, subject to the conditions of use, integrity of packaging, transportation and storage conditions in accordance with the manufacturer’s instructions for use.

The warranty period when stored in packaging is 3 years from the date of production (packaging).

After the warranty period expires, the product must be disposed of.

Side effect

From the cardiovascular system:

dizziness, headache, tachycardia, skin hyperemia, feeling of heat, arterial hypotension; rarely (especially with overdose) - collapse, cyanosis.

From the digestive system:

nausea, vomiting.

From the side of the central nervous system:

rarely (especially in case of overdose) - anxiety, psychotic reactions.

Allergic reactions:

rarely - skin rash, itching.

Local reactions:

slight itching, burning, redness of the skin.

Other:

methemoglobinemia.

Side effects of the drug Sustak

They are dose-dependent and are mainly a consequence of the vasodilatory effect of nitroglycerin. Possible headache, arterial hypotension, reflex tachycardia, flushing of the facial skin, dizziness and peripheral edema. Transient nausea and vomiting may occur. Methemoglobinemia is extremely rare when the recommended dosage regimen is followed. Allergic reactions occur infrequently, mainly in the form of skin reactions. Side effects can be largely prevented by gradually increasing the dose. The need to discontinue the drug arises only in case of severe side effects.

Contraindications for use

Shock, collapse, arterial hypotension (systolic blood pressure <100 mm Hg, diastolic blood pressure <60 mm Hg), acute myocardial infarction with severe arterial hypotension, hypertrophic obstructive cardiomyopathy, constrictive pericarditis, cardiac tamponade, toxic pulmonary edema, increased intracranial pressure (including with hemorrhagic stroke, after a recent head injury), closed-angle glaucoma with high intraocular pressure, increased sensitivity to nitrates.

special instructions

Use with caution in patients with severe cerebral atherosclerosis, cerebrovascular accidents, with a tendency to orthostatic hypotension, with severe anemia, in elderly patients, as well as with hypovolemia and severe impairment of liver and kidney function (parenteral). With long-term use, the development of tolerance is possible to the action of nitrates. To prevent the occurrence of tolerance, it is recommended to observe a 10-12-hour break in their use during each 24-hour cycle. If an attack of angina occurs during the cutaneous use of nitroglycerin (glyceryl trinitrate), it should be stopped by taking glyceryl trinitrate under the tongue. During the treatment period, do not allow drinking alcohol. Impact on the ability to drive vehicles and operate machinery

Glyceryl trinitrate may reduce the speed of psychomotor reactions, which should be taken into account when driving vehicles or engaging in other potentially hazardous activities.

The role of nitrates in the treatment of coronary heart disease at the present stage

Nitrates are one of the “oldest” groups of drugs used in cardiology: nitroglycerin was used to relieve angina attacks back in 1879. For a long time, nitrates were used only in the form of dosage forms with a short duration of action. Since the mid-twentieth century, long-acting drugs have also become available. There have been lively debates about the effectiveness of the latter and the advisability of their use for a long time, but some problems associated with the administration of long-acting nitrates have not yet been resolved.

Classification of nitrates and their mechanism of action

Nitrates vary in their chemical structure. Currently, three drugs are used: nitroglycerin (or glyceryl trinitrate), isosorbide dinitrate and isosorbide-5-mononitrate. These drugs are usually called organic nitrates. Their mechanism of action is the same: as a result of complex biochemical reactions, all these drugs are converted into nitric oxide (NO), a substance that is the so-called endothelial relaxing factor. The differences between the three nitrates mentioned above lie only in the duration of their effect: nitroglycerin has the shortest duration of action (15-20 minutes), isosorbide dinitrate, prescribed in regular tablets, lasts 3-5 hours, isosorbide-5-mononitrate, prescribed in regular tablets , - 5-7 hours. Long-acting dosage forms of the same drugs have a longer-lasting effect.

Nitrates easily penetrate through any mucous membrane, as well as through the skin, so they are produced in numerous dosage forms: tablets under the tongue, tablets or plates for application to the gums, aerosols, tablets and capsules for oral administration, various forms for application to the skin, solutions for intravenous administration.

It is convenient to classify nitrates by duration of action. Conventionally, they are divided into drugs with a short duration of action (up to 1 hour), which include primarily nitroglycerin tablets for administration under the tongue and aerosols of nitroglycerin and isosorbide dinitrate, drugs with a moderately prolonged action (from 1 to 6 hours), which include regular tablets isosorbide dinitrate, isosorbide-5-mononitrate, nitroglycerin, drugs with significantly prolonged action (more than 6 hours), such as special tablets and capsules of isosorbide dinitrate and isosorbide-5-mononitrate (Olycard 40 retard), as well as transdermal dosage forms of nitroglycerin and isosorbide dinitrate .

Indications for the use of nitrates

Nitrates have a distinct antianginal, or, more precisely, anti-ischemic effect, that is, the ability to prevent the occurrence of myocardial ischemia or reduce its severity. Therefore, these drugs are used to treat all types of angina: stable angina, unstable angina, variant angina. Nitrates have no effect on the course of coronary heart disease, so prescribing them for preventive purposes is pointless. A number of studies (in particular, ISIS-4 - Fourth International Study of Infarct Survival [1]) have shown that nitrates do not have any effect on the prognosis of life in patients with a high risk of complications, for example, in patients who have suffered a myocardial infarction. To improve the life prognosis in such patients, other drugs are used, primarily β-blockers. There is still no data regarding whether nitrates affect the long-term prognosis of life in patients with stable angina pectoris.

Previously, nitrates were actively used to treat congestive heart failure, but now, after the widespread introduction of angiotensin-converting enzyme inhibitors, their role in the treatment of this disease has significantly decreased. Nitrates continue to be actively used in the acute phase of myocardial infarction, but their ability to influence the extent of the infarction has not been proven.

Nitrates compared with other antianginal drugs

Nitrates, along with β-blockers and calcium antagonists, are part of the main antianginal drugs. In terms of the severity of the antianginal effect, they are at least not inferior to calcium antagonists and β-blockers, and according to some data, even superior to them. Thus, in the course of the CIAP study (Cooperative Study of Antianginal Drugs), conducted in patients with coronary artery disease with stable angina pectoris of the 2nd-3rd functional class, the task was to select the most effective antianginal drug for each of the patients participating in the study. To evaluate the result, tests with dosed physical activity were used. It was shown that for 27% of patients the most effective antianginal drugs are nitrates, for 19% - calcium antagonists, for 11% of patients - β-blockers. In other cases, the effectiveness of different groups of drugs was approximately the same [2].

It is convenient to combine nitrates with β-blockers, as well as with the so-called pulse-reducing calcium antagonists - verapamil and diltiazem. However, the combination of nitrates with dihydropyridine calcium antagonists not only does not provide any benefits, but even increases the risk of side and undesirable effects.

How can a practitioner monitor the effectiveness of nitrate therapy?

The effect of nitrates is manifested by an improvement in exercise tolerance, accompanied by a decrease in signs of myocardial ischemia. Therefore, the best way to objectify the effect of nitrates (as well as other antianginal drugs) is to conduct tests with dosed physical activity (on a treadmill or bicycle ergometer) against the background of the action of the drugs and compare the results obtained with those indicators that occurred before the prescription of nitrates. However, practice shows that such tests are carried out quite rarely.

There is also an indirect sign that allows one to evaluate the effect of nitrates: it has been shown that effective doses of these drugs cause a decrease in systolic blood pressure by 15-20 mm Hg. Art. Therefore, the doctor can easily assess the effectiveness of their action by measuring systolic blood pressure before prescribing the nitrate and then during the period when the effect of the drug should be maximum (that is, 5-10 minutes after taking short-acting dosage forms or 1-2 hours after taking drugs long-acting forms).

Contraindications to the administration of nitrates

There are few contraindications to the use of nitrates. According to the official recommendations of the American Heart Association, hypertrophic obstructive cardiomyopathy is a relative contraindication to the prescription of nitrates (nitrates in this disease can increase the degree of obstruction of the left ventricular outflow tract and the severity of mitral regurgitation and thereby cause presyncope or syncope). Nitrates can have the same effect on patients with severe aortic stenosis [3].

Nitrates are used with caution in patients with low blood pressure (BP), however, there are no clear recommendations regarding the lower limit of blood pressure at which the use of nitrates is contraindicated. Taking nitrates is not recommended for increased intracranial pressure. Glaucoma, contrary to previously held opinion, is not a contraindication to the use of nitrates.

Problems arising during treatment with nitrates

Side effects of nitrates are few. First of all, these include headache, which occurs in more than half of patients when taking nitrates for the first time. If you continue to take nitrates, the intensity of the headache usually decreases significantly or disappears altogether. However, in some patients, even with regular intake of nitrates, the headache persists, and all attempts to “accustom” such patients to the action of nitrates end in failure. These patients, apparently, should not be prescribed long-acting nitrates at all, limiting themselves to taking short-acting dosage forms. It is most convenient to use nitrate aerosols for this purpose (for example, nitroglycerin aerosol - nitromint).

With regular use of nitrates, their effect can weaken significantly, and sometimes even disappear; in such cases, they talk about the development of addiction (or tolerance) to nitrates. The severity of addiction to nitrates varies from patient to patient, but on average the likelihood of developing tolerance is directly proportional to the length of time the drug remains in the body.

Accustoming to nitrates is a reversible phenomenon. After nitrates are removed from the body, sensitivity to them is soon restored. The principle of intermittent administration of nitrates is based on this pattern, which provides for the creation of a so-called “period free from the action of nitrates” during the day. It is believed that in order for addiction to nitrates not to develop, the duration of this period during the day should be 6-8 hours.

The disadvantage of intermittent administration of nitrates is the inability to maintain therapeutic effectiveness for 24 hours (although in most patients this is not necessary, see below). In addition, during the period free from the action of nitrates, the development of the so-called rebound syndrome is possible, which develops in response to the rapid disappearance of the drug from the body and is a special case of withdrawal syndrome. When using long-acting dosage forms of nitrates prescribed orally, rebound syndrome usually does not develop, since the concentration of the drug in the body in this case decreases quite smoothly.

How to prescribe nitrates in the clinic

In order to maximize the beneficial effects of nitrates and reduce the risk of side and undesirable effects, these drugs are prescribed differentially, taking into account the severity of coronary artery disease and the characteristics of its course in a particular patient [4]. “Routine” prescription of nitrates (1 tablet 3 times a day), often practiced to this day, does not allow their therapeutic properties to be fully realized and is fraught with the development of complications.

In order to identify the need to prescribe nitrates and develop a specific regimen for their administration, it is necessary to determine whether the patient has angina and identify its functional class. For this purpose, a survey according to the standard scheme is used [3]. To document myocardial ischemia, it is advisable to perform an exercise test.

If a patient, even with proven coronary artery disease (for example, having previously suffered a myocardial infarction), does not have angina pectoris and there are no signs of myocardial ischemia during dosed physical activity, then there is no need for regular use of nitrates. It is advisable for such patients to have short-acting nitrates with them (it is most convenient to use nitrates in aerosol form for this) in case of anginal pain.

In the presence of angina, whenever possible, nitrates are prescribed intermittently to minimize the risk of addiction. For mild angina (functional class 1 or 2), when attacks occur predictably, only during physical activity, nitrates are prescribed in the form of dosage forms of short or moderately prolonged action and only in cases where a situation arises that can provoke an attack of angina. . Forms of drugs with a rapid onset of action are suitable for this - aerosols of nitroglycerin (for example, the previously mentioned drug nitromint) or isosorbide dinitrate, dosage forms of nitroglycerin for application to the gums, regular tablets of isosorbide dinitrate (nitrosorbide). The advantage of nitrate aerosols is also their ease of use, as well as the good preservation of the drug that these dosage forms provide.

For more severe angina, when attacks occur more often, with less physical activity, and also at rest, nitrates are prescribed in the form of long-acting dosage forms, and, if possible, they also try to create a period during the day free from the effects of nitrates. For angina pectoris of the 3rd functional class, nitrates are used in such a way as to ensure a constant effect throughout the day. To do this, prescribe either regular tablets of isosorbide dinitrate and isosorbide-5-mononitrate 3-4 times a day, or (which is more convenient) tablets of isosorbide dinitrate and isosorbide-5-mononitrate (Olycard 40 retard) of significantly prolonged action once a day in the morning.

For angina pectoris of the 4th functional class, nitrates must be prescribed in such a way as to ensure a constant effect of the drug throughout the day. For this purpose, dosage forms of isosorbide dinitrate or isosorbide-5-mononitrate (Olycard 40 retard) of significantly prolonged action are prescribed 2 or even 3 times a day. It should be remembered that with this method of prescribing nitrates, the risk of developing addiction to them is especially high.

Conclusion

Thus, the role of nitrates in the treatment of patients with coronary artery disease is still high, but only a differentiated approach to their administration, based on the ability to correctly diagnose and knowledge of clinical pharmacology, will help achieve the desired result.

S. Yu. Martsevich, Doctor of Medical Sciences, Professor of the State Research Center for Preventive Medicine of the Ministry of Health of the Russian Federation, Moscow

Literature

1. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: A randomized factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction // Lancet. 1995; 345:669-685.
2. Metelitsa VI, Kokurina EV, Martsevich SY Individual choice and long-term administration of the antianginal drugs for secondary prevention of ischemic heart disease: problems, new approaches // Sov. Med. Rev. A. Cardiology. 1991; 3: 111-134.
3. ACC/AHA/ACP-ACIM Guidelines for the management of patients with chronic stable angina. A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines // J. Amer. Coll. Cardiol. 1999; 33: 2092-2198.
4. Martsevich S. Yu. Debuts of coronary heart disease: diagnostic and treatment strategy // Cardiovascular therapy and prevention. 2002; 1: 76-83.

Some statistics

According to a Comcon study conducted in October 2001, more than 60% of Russian clinic physicians prescribe menthol-containing drugs to relieve an attack of angina. Moreover, 42% of doctors consider such therapy highly effective. At the same time, leading foreign and domestic cardiologists consider such therapy not only ineffective, but also dangerous. Since the appointment of such therapy ultimately leads to a delay in the elimination of acute ischemia and may be the reason for its transition to an irreversible form - myocardial infarction. At the present stage, the drug of choice for the treatment of an attack of angina is nitroglycerin in aerosol form.

Olicard 40 retard in the treatment of angina pectoris

Olicard 40 retard is the only domestic mononitrate.

Olycard 40 retard is presented in a unique galenic form - capsules containing microspheres with gradual release of the active substance, which ensures a long-term therapeutic effect and the absence of tolerance.

Drug interactions

When used simultaneously with vasodilators, ACE inhibitors, calcium channel blockers, beta-blockers, diuretics, tricyclic antidepressants, MAO inhibitors, ethanol, ethanol-containing drugs, the hypotensive effect of glyceryl trinitrate may be enhanced. When used simultaneously with beta-blockers, calcium channel blockers, the antianginal effect is enhanced When used simultaneously with sympathomimetics, it is possible to reduce the antianginal effect of glyceryl trinitrate, which, in turn, can reduce the pressor effect of sympathomimetics (as a result, arterial hypotension is possible). With the simultaneous use of drugs with anticholinergic activity (including tricyclic antidepressants, disopyramide ) hyposalivation and dry mouth develop. There is limited evidence that acetylsalicylic acid, used as an analgesic, increases the concentration of nitroglycerin (glyceryl trinitrate) in the blood plasma. This may be accompanied by an increase in the hypotensive effect and headaches. A number of studies have observed a decrease in the vasodilating effect of nitroglycerin (glyceryl trinitrate) during long-term therapy with acetylsalicylic acid. It is believed that it is possible to enhance the antiplatelet effect of acetylsalicylic acid during the use of nitroglycerin (glyceryl trinitrate). With simultaneous use with nitroglycerin, the effect of acetylcholine, histamine, norepinephrine is reduced. Against the background of intravenous administration of nitroglycerin, the anticoagulant effect of heparin may be reduced. With simultaneous use, it is possible to increase the bioavailability of dihydroergotamine and reduce the antianginal effect of nitroglycerin (glyceryl trinitrate). With simultaneous use with novocainamide, an increase in the hypotensive effect and development of collapse. When used simultaneously with rizatriptan, sumatriptan, the risk of developing coronary artery spasm increases; with sildenafil - the risk of developing severe arterial hypotension and myocardial infarction; with quinidine - orthostatic collapse is possible; with ethanol - severe weakness and dizziness.

Sustak forte

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 2-3 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.

Transdermal: treatment begins with the application of one TTC 5 patch (0.2 mg/h) per day. To maintain therapy, the daily dose can be increased by attaching an additional patch (0.2 mg/h) and/or TTC 10 (0.4 mg/h). The maximum daily dose is the application of 2 TTC 10 patches (0.8 mg/hour). For CHF, it is recommended to begin and carry out treatment in a hospital setting until the patient is transferred to the required maintenance dose. The optimal dose should be determined (taking into account the clinical response and possible side effects). In this case, you should strictly monitor the appearance of signs of overdose (decreased blood pressure and tachycardia).

Cutaneously (ointment): the initial dose is 2.5 cm of ointment. If the effect is insufficient, the dose is gradually increased to 5-10 cm. The maximum single dose is 15 cm. The ointment is used 2-3 times a day. The prescribed amount of ointment is squeezed onto the dosing paper scale, the paper is attached tightly to a hairless area of ​​skin (in the area of ​​the upper chest, abdomen, outer thigh).

Aerosol, spray for sublingual use: to relieve an attack of angina - 0.4-0.8 mg (1-2 doses), pressing the dosing valve, preferably in a sitting position, while holding your breath at intervals of 30 seconds; After this, you should close your mouth for a few seconds. If necessary, repeat administration, but not more than 1.2 mg (3 doses) over 15 minutes. To prevent the development of an attack - 0.4 mg (1 dose) 5-10 minutes before exercise. In case of acute LV failure, developing pulmonary edema - 1.6 mg (4 doses) or more in a short period of time (under strict medical supervision).

IV administration of nitroglycerin should be carried out with individual selection of the rate of administration of the drug. The solution is administered through an automatic dispenser or through a conventional IV system. The automatic dispenser allows you to administer even an undiluted 0.1% solution with precise dosing of the rhythm of administration and the total dose. Administration through a conventional fluid transfusion system ensures precise dosage selection by counting the number of drops. When using a polyvinyl chloride tube system, the active substance is absorbed and losses on the tube walls are up to 60% (it is advisable to use polyethylene and glass tubes). The solution quickly degrades in light, so the vials and transfusion system must be shielded with light-proof material.

Typically, an infusion solution with a concentration of 100 mcg/ml is used: the concentrated solution is diluted with 0.9% NaCl solution or 5% dextrose solution (other solvents should not be used). The solution is administered intravenously at an initial rate of 5 mcg/min. The rate of administration can be increased every 3-5 minutes by 5 mcg/min (depending on the effect and response of heart rate, central venous pressure and systolic blood pressure, which can be reduced by 10-25% of the original, but should not be lower than 90 mm Hg .st.). If no therapeutic effect is obtained at an injection rate of 20 mcg/min, a further increase in the injection rate should be 10-20 mcg/min. If a response occurs (in particular, a decrease in blood pressure), a further increase in the infusion rate is not carried out or is carried out at longer intervals.

To achieve a good effect, the rate of administration of a 0.01% nitroglycerin solution usually does not exceed 100 mcg/min (1 ml/min). If there is no effect from lower doses and the blood pressure level is acceptable, the rate of administration of a 0.01% solution can reach 300 mcg/min (3 ml/min). Further increase in speed is not advisable.

The duration of treatment is determined by clinical indications and can be 2-3 days.

Nitroglycerin for intravenous administration, if necessary, can be re-administered at any time intervals.