Angioprotectors: what are they, list of drugs with angioprotective action

Vascular pathologies are represented by a large group of diseases. According to statistical estimates, it is these disorders that more often become the direct cause of death of patients (for example, a stroke or heart attack as such leads to death, but the provocateur is stenosis or blockage of a vessel supplying cardiac or cerebral structures).

Angioprotectors are drugs aimed at correcting blood properties, strengthening vascular walls, increasing their elasticity and tissue regeneration.

There are many groups of these drugs and even more specific names. The mechanisms of influence are different, and therefore the effect is always different.

It is permissible to combine several pharmaceutical types of drugs to achieve a greater therapeutic result. However, it will not be possible to work out the scheme on your own. Rather, a person will achieve the opposite effect and aggravate the process.

The need to use medications in this broad group is determined by the course of pathologies of the cardiovascular system; it is also permissible to use medications for preventive purposes.

It is absolutely necessary to take it in the postoperative period. There are many questions, the answer can only be given by a specialist in vascular surgery or cardiology (often a whole council of doctors is required).

Mechanism of action

As already mentioned, there are several subgroups within the described category of pharmaceuticals.

They differ fundamentally in all respects except one - the effect on blood vessels or blood properties.

Since medications have different effects, it makes sense to use them in various safe combinations to achieve the greatest effect.

• Blood thinning. Restoring its normal fluidity and rheological properties.

The so-called anticoagulation mechanism. Plays one of the key roles after a stroke, heart attack, or injury. Because it does not allow formed cells to stick together and form blood clots.

Medicines with this mechanism are actively used both in the treatment and prevention of diseases.

• Correction of microcirculation. Achieved by regulating the tone of small vessels. Many products of this type are used in the postoperative period.
• Phlebotonic mechanism. Based on the ability to activate the functioning of vascular valves. Normally, blood moves in one direction and does not return.

This occurs through a complex system of muscle structures also called valves. If they do not work enough, blood stagnation occurs or, even worse, reverse flow occurs (relatively rare).

Ischemia (insufficient blood supply) of tissues follows, the normal elasticity of the artery or vein is disrupted, and degenerative processes occur in its wall. Fragility is detected.

A classic case known to many is varicose veins. This is how it develops. The same goes for hemorrhoids. Phlebotonics make the valves work, this is their main property.

• Vasodilation. Relief of spasm or stenosis. By biochemical means, the lumen of the arteries or veins increases, and a stable normalization of blood flow is achieved.

In parallel with this, a decrease in pressure is possible. Such an effect is not always desirable, therefore it is necessary to evaluate the factors separately, based on specific data.

• Metabolic mechanism. Some medications speed up metabolic processes, which allows for better tissue nutrition.

Strictly speaking, angioprotectors have such an effect relatively rarely. We are talking about combined complex medications with a whole group of beneficial effects.

The mechanisms are different, and therefore the scope of application of certain drugs will be different.

Microcirculation correctors for external use

If varicose veins affect only superficial veins, then external treatment using ointment and gel forms of drugs is recommended. In the initial stage, this may be enough; in the future, local remedies are combined with the internal use of venotonics.

Lyoton 1000

It is a gel, 1 g of which contains 1000 IU of heparin. Once absorbed into the skin, it helps reduce swelling, inflammation, and increased blood clotting. Prescribed for varicose veins and its complications - phlebitis, thrombosis, after surgical treatment of blood vessels. It is also used for injuries and sprains, soft tissue bruises, and hematomas.

Troxevasin

The drug contains rutoside, a derivative of vitamin P. The main therapeutic effects are:

• tones and protects the venous wall,
• relieves inflammation and pain in the legs,
• inhibits the release of blood from vessels into tissues,
• prevents platelet fixation on the vessel wall.

Indicated for soft tissue injuries associated with injury or surgery to resolve swelling, improve venous and lymphatic outflow, thrombo- and periphlebitis, dermatitis with varicose veins.

Venitan

It is produced on the basis of extract from horse chestnut seeds. It has an anti-inflammatory and tonic effect on the venous network, tightens the vascular walls, and prevents fluid from accumulating in the tissues in the form of edema. Helps with night cramps, pain and heaviness in the legs, itching associated with venous insufficiency. Safe for pregnant women, used for injuries to muscles and ligaments in sports medicine.

We recommend reading the article about the treatment of cerebral atherosclerosis. From it you will learn about the disease and complex therapy, the choice of drugs and symptomatic therapy.

And here is more information about the treatment of varicose veins with drugs.

Angioprotectors are prescribed to strengthen the vascular wall, improve blood circulation and tissue nutrition in case of venous insufficiency, inflammation or damage to blood vessels. They can be used topically or internally. Many drugs are based on plants, so patients report minimal side effects during treatment.

For optimal effect, it is recommended to use original medications for oral use and external agents.

You can only choose drugs for the vessels of the head with your attending physician, since they may have a different spectrum of action, and also have side effects and contraindications. What are the best drugs for dilating blood vessels and treating veins?

Treatment of cerebral atherosclerosis, drugs for which are prescribed exclusively by a doctor, is carried out comprehensively. What is included in a home first aid kit?

Retinal atherosclerosis occurs due to cholesterol deposits or other unfavorable changes in the blood vessels of the eyes. The treatment is complex - medications, vitamins, laser coagulation. Traditional methods won't hurt either.

There are not so many methods for strengthening the veins and blood vessels in the legs. For this purpose, folk remedies, medications are used and the patient’s lifestyle is changed.

Antiplatelet agents

The basis of the effect of using this group of drugs is the ability to thin the blood and prevent the formation of blood clots, which reduces the load on blood vessels and prevents the development of emergency conditions (primary or after surgery).

Attention:

The drugs must be used with extreme caution; in some combinations they can cause bleeding.

They are absolutely not suitable for use without medical supervision.

Heparin

Quite an old drug with a pronounced effect, but its duration hardly reaches several hours.

Therefore, the medication is especially actively used in inpatient settings for patients in a complex condition, with stroke, heart attack, thrombosis.

It has a lot of side effects and is used in the form of injections. Not suitable for course purposes due to risks - this is a first aid remedy.

There are also more modern and safer analogues with a long lasting effect. For example, Clexane or Fraxiparine.

Aspirin and analogues

Unlike Heparin, modern names of antiplatelet drugs based on acetylsalicylic acid are suitable for long-term use over many years.

The essence is the same blood thinning.

Among the effective analogues of simple Aspirin are Magnicor, Plavix, Plagril, Cardiomagnil and others. They are more effective, but also have different degrees of safety.

The question of prescribing a specific medication remains at the discretion of the specialist. It is necessary to take into account concomitant diseases and contraindications.

According to statistics, constant use of drugs from this subgroup helps reduce the risk of heart attack and stroke by almost 60%.

Tissue respiration stimulants

For this purpose, the enzyme preparation Cytochrome C , which is produced from the heart muscle of cows. The active substance is a participant in the act of tissue respiration and can accelerate oxidative reactions. Known as one of the components of Katachrom drops.

The drug is prescribed as an intramuscular injection of 5 ml. Before starting the course, a test is performed, the frequency of daily injections is 1 or 2. The duration of treatment is up to 20 days.

A test is required before each treatment course. With its help, the individual sensitivity of the patient is determined. As a test, 0.1 ml of Cytochrome C is injected into the skin and observed for half an hour. If redness, itching or allergic rashes occur, individual intolerance is indicated and the appointment is cancelled.

Preparations for normalizing microcirculation

Angioprotectors of this group have the ability to dilate blood vessels, reduce the likelihood of oxidation of the walls of blood supplying structures, and make it possible to reduce their fragility.

In the system, this makes it possible to reduce the risks of emergency conditions several times.

It has been proven that patients taking drugs to improve microcirculation have good disease dynamics.

In total, two subgroups can be distinguished in this category.

Pentoxifylline and drug analogues

Pentoxifylline has pronounced pharmacological activity with a relatively low likelihood of side effects.

Suitable for long-term use in high dosages. The ideal regimen involves a 2-3 week course of intravenous drip infusion with a transition to the tablet form after.

The drug should not be taken if you have severe heart disease.

One of the main advantages, which sometimes even tips the scales when choosing a medication, is the low cost of Pentoxifylline.

Although there are more effective, safer analogues, including long-acting ones (Vazonit, which is drunk once a day).

Foreign analogues have proven high efficiency, it is more than that of the original medicine (Trental and others).

Prostaglandins

New generation of microcirculation stimulators. Pentoxifylline cannot compare with them in terms of duration and severity of the effect. Names: Vazaprostan, Ilomedin, Alprostan, etc.

However, there is one huge disadvantage behind this - while the efficiency is tens of times higher, you will have to spend a lot of money. The price starts from 5 thousand rubles, there are also more expensive options.

Not everyone can afford such treatment, especially since prostaglandins are not included in the special list, which is why they are not prescribed even under federal benefits.

Phlebotonics

Mainly affect veins. The effect on the arteries is minimal or non-existent.

Angioprotective therapy in this case is aimed at relieving varicose veins or eliminating the manifestations of hemorrhoids.

The mechanism of action is to stimulate the work of special vascular valves, which help move blood forward and prevent stagnation.

List of the most popular drugs:

• Detralex. It is a rather expensive angioprotective agent, but clinical data indicate its high effectiveness. Used twice a day. It allows not only to stimulate the work of venous valves, but also to increase the elasticity of the walls of blood vessels. Does not affect the rheological properties of blood (its fluidity). Therefore, it requires use in the system, except in rare cases.
• Venarus. If Detralex is a foreign development, then this name is of domestic origin. There are no fundamental differences between them. These are structural analogues. Therefore, you can use one or the other of your choice. There is no information about lower therapeutic effectiveness. At the same time, the low price of Venarus compared to Detralex is an undoubted advantage.
• Phlebodia. There is also no fundamental difference other than cost. However, the medicine has a long-lasting effect. It must be taken once a day.
• Troxerutin. Against the background of mass loud advertising calling for the purchase of this or that medicine, effective and affordable medicines go unnoticed. These include the phlebotonic Troxerutin.

It is relatively cheap and highly effective. But it requires three times a day, which may be inconvenient for busy people. Otherwise, there is again no fundamental difference.

The most popular titles are presented. There are others too. Moreover, not only in tablets, but also in creams and ointments.

Angioprotectors

These are substances that help normalize the permeability of vascular walls, reduce swelling of vascular tissue, and accelerate metabolic processes in the vascular wall. The angioprotective effect is fully possessed by: vitamin P, anti-inflammatory non-steroidal drugs, as well as the following medications.

Doxium, the main substance of which is a special form of calcium dobesylate, necessary for strengthening the walls of blood vessels. This drug is needed to increase capillary resistance, improve blood microcirculation, and stimulate drainage function in lymphatic vessels. It thins the blood and slightly reduces platelet aggregation, which has a beneficial effect on the condition of the retinal tissue. Does not have any effect on microaneurysms and does not significantly penetrate the blood-brain barrier.

The tablet form of the drug is prescribed at the rate of 0.75-1.0 g per day, which is 3-4 tablets, which are drunk after meals. The course of treatment is quite long and can last a year or a year and a half.

Among the negative aspects of taking the drug, experts note dyspepsia and allergic skin rashes. This is a reason to reduce the dose or completely cancel it. Not prescribed during pregnancy.

Ascorbic acid is a drug for normalizing the permeability of the capillary wall, improving redox reactions, and regulating carbohydrate metabolism. In addition, ascorbic acid helps reduce cholesterol levels in the blood, accelerate tissue regeneration, and stimulate the production of steroid hormones. This property of the drug is very important if a course of steroid therapy is necessary.

Prescribed in injections or tablets. Dosage for tablets: 0.05-0.1 g up to 5 times daily, with intramuscular administration of a 5% solution - 2.0 ml No. 20-30. Intravenous injections in the same dose are also possible, although it must be taken into account that in the case of thrombosis, thrombophlebitis or increased blood clotting, they are contraindicated.

Flavonoid Rutin is a drug that reduces capillary fragility and permeability (especially in combination with ascorbic acid). Together with it, it is a participant in redox reactions and slows down the action of hyaluronidase.

The daily dose of Rutin is usually 0.1 g, prescribed in combination with ascorbic acid. Ascorutin tablets are mass produced, including rutin with ascorbic acid and glucose. The therapeutic course involves taking them 4 pieces per day. It has no contraindications or side effects.

Troxevasin (venoruton) is a drug with an action close to rutin. Regulates capillary permeability, fights swelling and tissue inflammation. In capsules, prescribed one at a time with meals, for a course of 2-4 weeks.

Divascan is a hemostatic drug that reduces microvascular permeability. Available in tablets, which are prescribed one three times a day. Patients with diabetic retinopathy or intraocular hemorrhages are recommended to take without interruption for at least two years.

Dicynone (etamsylate) is a substance that increases the content of high molecular weight mucopolysaccharides in the capillary wall, which increases their stability and normalizes permeability. The drug has the property of improving microcirculation, normalizing platelet adhesion, and has a hemostatic effect without promoting the formation of blood clots.

Prescribed orally or intramuscularly. The daily dose in tablets is 1.5-2.0 g, duration of administration is 2-3 months. IM injections are prescribed for 10-14 days; they can be combined with subcutaneous administration of this drug at a dose of 0.5 ml.

To prevent bleeding during surgical interventions, Dicynon is administered intramuscularly before and after surgery if there is a risk of postoperative bleeding.

The drug is prescribed with caution to patients with thrombosis and embolism. There are no side effects.

Prodectin (parmidin) is an angioprotector drug whose action is aimed at restoring microcirculation. It helps reduce platelet aggregation, activates fibrinogenesis, and improves the condition of the vascular endothelium. Prodectin has a pronounced anti-sclerotic effect and accelerates the disappearance of signs of intoxication.

Its intake is 4 tablets daily (1.0 g), for a course of up to 6 months.

Side effects include nausea, occasionally allergic skin rashes, and headache. When the dosage is reduced or the drug is discontinued, all phenomena disappear. Contraindications for use are liver disease.

Emoxipine helps reduce blood viscosity, reduce the permeability of vessel walls, and resolve hemorrhages. It is a retinoprotector and antioxidant, protects the retina from the negative effects of bright light (laser coagulation, sunburn). It is prescribed for hemorrhages, retinopathy, complicated myopia, retinal dystrophies, thrombosis of its veins, light or radiation burns of the eyes, and glaucoma. It is also a component of complex treatment for laser coagulation.

Prescribe one injection into the eye (subconjunctival, retrobulbar, parabulbar) of a 1% solution in a dosage of 0.5 ml every day for 10-15 days. If necessary, the course of treatment is extended to 30 days and repeated several times a year. Sometimes the drug is used in the form of eye drops.

Its side effects may include: itching, burning, pain, related to allergic reactions. They are relieved by using corticosteroids. Sometimes during injections, compaction of the orbital tissue is observed, which subsequently resolves on its own.

Means for increasing the lumen of arteries

The mechanism is based on the ability to biochemically dilate blood vessels, normalize blood flow and reduce the load on arteries and capillaries. The effect is always complex.

These medications are also called nitro group donors. Typical names that can be found on pharmacy shelves are Tivomax, Tivertin.

Method of administration: intravenous, drip. Not suitable for prolonged use.

The maximum possible continuous course is 14 days. Then take a break of 2 weeks and, if necessary, repeat the scheme. It is possible to use medications in children over 3 years of age, which is important.

Side effects are relatively rare. And if they do occur, they are easily tolerated and do not require a revision of the therapeutic course.

The same applies to contraindications. Among these, the manufacturer names an allergic reaction to medication components.

It should be added that the drugs are used with caution in case of a polyvalent (multiple) response to various medications.

The cost is low, so this type of angioprotective therapy is available to most people.

Metabolic drugs

Combined mechanism. They affect the condition of blood vessels on the one hand, on the other hand they have the ability to normalize metabolic processes in affected tissues, accelerate the utilization of glucose, increase the amount of energy produced, and prevent ischemic and hypoxic processes.

Among the names, the key place belongs to Actovegin.

The medicine is suitable for use in different categories of patients. There are minimal contraindications and virtually no side effects, although variations are possible.

It is quite expensive, but long courses are not required. The optimal regimen is parenteral (injection) administration in large doses in the first few days, reducing concentrations as you progress.

It is important to note. Metabolic angioprotective agents increase the nutrition of all tissues without exception, including abnormal ones.

Therefore, such drugs cannot be used if there are brain tumors. It doesn't matter whether they are malignant or benign. There are high risks of continued growth.

Application

Let's consider several situations in which drugs included in the group of angioprotectors are used:

• Treatment of vascular lesions that occur in diabetes mellitus, rheumatological diseases, widespread atherosclerosis. Vitamin-based medications are often used for these diseases. Their mechanism of action is poorly understood, but it is believed that they inhibit the synthesis of hyaluronidase. As is known, this enzyme is present in every source of inflammation. This class of angioprotectors reduces the permeability of the vascular wall and reduces swelling.
• Blockage of the vascular lumen. The cause of this condition may be the appearance of atherosclerotic plaques or changes in blood composition. In this case, antiplatelet agents and drugs that change the ability of cells to stick together and form blood clots can serve as angioprotectors. In addition, substances that affect cholesterol and antispasmodics are used.
• Peripheral circulatory disorders. In this case, angioprotectors are agents that increase the resistance of surrounding tissues to a lack of oxygen. Antioxidants are also used to suppress the large formation of free radicals. Often used antioxidants are vitamin C and E. Mexidol and hypoxen, which are specially synthesized on the basis of vitamins, have a specific antioxidant effect.
• Consequences of cerebrovascular accident and ischemic heart disease. In this case, the above drugs are often used. If they are prescribed at the right time, it is possible to reduce the affected area near the blocked vessel and increase the resistance of cells to insufficient oxygen supply.
• Damage to the venous bed. Angioprotectors in this situation include venotonic medications, antithrombotic drugs and vasodilators. The most popular drugs used to treat vein lesions are solutions based on horse chestnut extract and their chemical analogues.

Indications

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It is clear to say in which cases medications should not be used. Because the list of groups is large, the mechanisms are different. We need to proceed from this.

The average list of readings looks like this:

• Atherosclerosis. Including obliterating, affecting the lower extremities.
• Angiopathy of diabetic origin.
• Coronary heart disease, cardiac dysfunction, including against the background of poor nutrition in the coronary arteries.
• Cerebrovascular insufficiency. Trophic (nutrition) disorders of the brain.
• Hemorrhoids, varicose veins (predominant indications for the use of phlebotonics).
• Tendency to form blood clots as a result of impaired blood flow (it becomes thick).
• Increased fragility of blood vessels.
• High probability of aneurysm formation (objective indicators, especially if they are combined with complicated heredity).

What diseases affect blood vessels?

Vascular function is most affected by:

• atherosclerosis,
• rheumatism,
• diabetes mellitus,
• kidney damage,
• varicose veins,
• trophic ulcers,
• obliterating endarteritis.

This is not a complete list of vascular pathologies. If diseases primarily affect the arteries, the veins suffer the consequences. For example, with coronary atherosclerosis, circulatory failure develops, which leads to venous stagnation. And inflammation of the veins contributes to thrombophlebitis and can be complicated by cardiac embolism with subsequent entry of a blood clot into vital arteries.

Microcirculation is provided by the smallest vessels - capillaries. They depend on the pressure in the arterial and venous knee. Lack or overflow of blood leads to failure of capillary blood flow and tissue hypoxia.

Ensuring the necessary tone of the muscular lining of the artery guarantees a proper response to any nerve impulses

Contraindications

Since the list of drugs is wide, it is necessary to proceed from specific recommendations for refusal of use, depending on the group of medications.

Preparations to improve microcirculation:

• Severe heart disease.
• Recent hemorrhagic stroke.
• Tendency to bleed.
• Age over 60-65 years.

Vasodilators, metabolic drugs, phlebotonics:

• Intolerance to the components of the drug.
• Polyvalent allergic reaction (with caution, not a strict contraindication).

Anticoagulants are not used if there is a tendency to develop bleeding, because they can provoke dangerous hemorrhagic complications.

A general contraindication for all medications without exception, and not only those described, is an allergic reaction to the drug. But it can be discovered experimentally.

It is recommended to start with the minimum dosage unless there is reason to the contrary. Otherwise, it is better to carry out therapy in a hospital setting. This will allow you to react in time and revise the course if necessary.

Medicines for external use

The list of drugs should be supplemented with angioprotectors that have the proper pharmacological effect during the local treatment of diseases. Angioprotective drugs in the form of ointments, gels and creams for external application:

• Heparin ointment.
• Procto-Glivenol.
• Hepatrombin.
• Proctosan.
• Venitan.
• Lyoton gel.
• Venorutinol.
• Proctosedyl.
• Essaven.
• Troxevasin.

The drug Indovazin deserves special attention. This product is available in the form of a gel for external application and contains troxerutin in combination with indomethacin. The combined composition helps to provide a pronounced anti-inflammatory and angioprotective effect, eliminates pain. The gel can be used in severe cases of the disease.

For the treatment of hemorrhoids and anal fissures, the following angioprotector can be prescribed:

• Anestezol.
• Posterized.
• Nigepan.
• Relief.
• Proctosan.
• Ultraproct.
• Procto-Glivenol.
• Proctosedyl.

Side effects

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Undesirable effects also depend on the type of medication. If you look at the list on average, you get the following picture:

• Anemia. Decreased hemoglobin concentration in the blood.
• Allergic reactions of varying severity. From urticaria and skin itching to attacks of bronchial asthma, Quincke's edema and even anaphylactic shock. Fortunately, such dangerous phenomena are rare.
• Headache. Minor, but quite long lasting. Up to several hours. With long-term treatment, the side effect disappears on its own; no special help is required.
• Noise in ears.
• Nose bleed.
• Rhinitis.
• Dyspeptic phenomena. Including nausea, vomiting, diarrhea, constipation, heartburn, belching in various combinations. If such side effects persist, it makes sense to reconsider the course of treatment.
• Bronchospasm.
• Hematuria. Excretion of blood in the urine.

There are also more serious complications such as stroke, heart attack, acute heart or kidney failure.

However, these are extremely rare cases and such emergency conditions develop due to the joint negligence of the doctor and the patient.

Modern venotonic drugs: possibilities of clinical pharmacology and pharmacotherapy

According to generalized data from epidemiological studies, chronic venous diseases (CVD) in different countries affect 35–60% of the working population [1].

According to large studies assessing venous insufficiency conducted in Russia in 2004, it was shown that 67% of women and 50% of men have chronic diseases of the veins of the lower extremities [2].

According to a multicenter study in 2007, which included 3,788 women aged 18 to 65 years exposed to those risk factors for the development of CVD that are associated with modern life features (physical inactivity, obesity), external signs of CVD were absent in only 23.1% of women, with In this case, more than half of Russian women (52.1%) suffer from various forms of chronic venous disease with the development of varicose veins of the saphenous veins, edema and trophic disorders [3].

Thus, the development of drugs for the treatment of chronic venous disease is currently an urgent problem.

Depending on the stage of the disease, both conservative and surgical treatment methods may be recommended for the treatment of CVD. Clinical experience shows that only 10% of patients with chronic venous pathology require surgical treatment, while the rest need conservative measures aimed at improving venous outflow from the lower extremities [4]. For a number of patients, treatment methods such as the use of compression stockings and pharmacotherapy will play a leading role.

The main indications for pharmacotherapy of CVD, according to the recommendations of the Russian Association of Phlebologists, are [5]:

1) the presence of subjective symptoms of CVD (C0S-C6S according to CEAP, see classification of CVD below); 2) CVI (C3-C6 according to CEAP); 3) pain and other manifestations of pelvic venous congestion syndrome; 4) prevention of hypostatic and premenstrual edema; 5) prevention and treatment of undesirable (side) events after surgical interventions on the venous system of the lower extremities.

Classification of CVD:

• C0 - no visible or palpable signs of CVD;
• C1 - telangiectasia or reticular veins;
• C2 - varicose saphenous veins;
• C3 - edema;
• C4 - trophic changes in the skin and subcutaneous tissues: a - hyperpigmentation and/or varicose eczema; b — lipodermatosclerosis and/or white skin atrophy;
• C5 - healed venous ulcer;
• C6 - open (active) venous ulcer.

Basic pharmacotherapy for CVD includes phlebotropic drugs (venoactive drugs, phleboprotectors, venotonics). This is a large, diverse group of biologically active substances obtained by processing plant raw materials or chemical synthesis, combined by pharmacological and clinical effects [5].

According to a 2005 meta-analysis, venotonics are effective at all stages of CVD, from initial to severe with severe trophic disorders. In some cases, venotonics can replace elastic compression [6].

The main mechanism of action of venotonics is associated with an increase in venous tone against the background of inactivation of norepinephrine, improvement of the rheological properties of blood and a positive effect on endothelial function [7].

Of the main venotonics, the most studied g-benzopyrones are flavonoids and preparations based on diosmin [8].

The angioprotective effect of bioflavonoids became known back in 1937, and since that time drugs from this series have been studied.

Preparations based on diosmin have been used for the treatment of chronic venous insufficiency, lymphedema and hemorrhoids for 30 years. Diosmin, along with its capillary-protective effect, has anti-inflammatory, antioxidant and antimutagenic properties [7].

Initially, when studying the pharmacokinetics of diosmin in healthy volunteers, it was revealed that its lipophilic aglycone, diosmetin, was detected in plasma [8]. Subsequently, it was shown that diosmin is metabolized by intestinal microflora to diosmetin, which increases its absorption. In this case, part of the drug is metabolized by bacteria of the cecum with the formation of hippuric and benzoic acids. The bioavailability of the drug after oral administration is approximately 40–57.9%.

The maximum concentration in blood plasma is achieved 5 hours after administration. The drug accumulates in all layers of the wall of the vena cava and saphenous veins of the lower extremities, to a lesser extent in the kidneys, liver and lungs and other tissues. The volume of distribution of the drug is 62.1 l. The maximum selective accumulation of diosmin and/or its metabolites in the wall of venous vessels is observed 9 hours after administration and persists for 96 hours.

While in the bloodstream, diosmetin interacts with proteins, primarily albumin.

Diosmin is rapidly metabolized in the liver. The main metabolite is hydroxyphenylpropionic acid. Diosmin metabolites are excreted primarily by the kidneys in the form of conjugates with glucuronic acid. Approximately 79% of taken diosmin is excreted by the kidneys, 11% by the intestines, and 2.4% is excreted by the bile. Enterohepatic circulation of the drug is noted. After taking radiolabeled diosmin, approximately 86% of the drug is excreted by the kidneys and intestines within 48 hours.

Diosmin preparations are produced both in granules and in film-coated tablet dosage form, however, ultrasonic micronization is important to increase the bioavailability of the drug [9]. This was demonstrated in a study on healthy volunteers when they received labeled forms of micronized and non-micronized diosmin [10].

The results of numerous clinical trials indicate that in the early stages of the disease (C0S-C2S) all phlebotropic drugs have a good therapeutic effect on subjective symptoms, but not external manifestations (telangiectasia, varicose veins of the reticular and saphenous veins) of CVD. However, when conducting pharmacotherapy of early stages of chronic venous disease, preference should be given to phlebotropic drugs, the effectiveness and safety of which have been proven in randomized controlled clinical trials [5].

It should be noted that the maximum volume of clinical and preclinical studies is carried out, as a rule, by the developer and manufacturer of a new, original drug, which requires quite large investments to carry out all stages of bringing the original drug into wide clinical practice. After the expiration of the patent protection of the original drug, as a rule, generic drugs appear. Since the manufacturer of generic drugs can rely on already conducted studies of the original (reference) drug, the production of a generic drug costs the manufacturer much less, which allows increasing the availability of the drug while maintaining the quality of their production.

For generic drugs, it is mandatory to conduct a bioequivalence study, which shows the comparability of pharmacokinetics and comparative bioavailability of the original and generic drugs. This study gives grounds to talk about comparable clinical efficacy and safety of the reference and generic drugs.

Currently, several drugs with the international nonproprietary name (INN) “diosmin” in oral dosage form in the form of tablets are registered and in circulation in Russia, for many of which clinical studies, including multicenter studies, have been conducted.

For the Russian drug with the INN: “diosmin”, trade name Phlebofa, a comparative clinical study was conducted with the reference drug [11–15]. The reference drug has proven its effectiveness in CVD [11–13] and in the treatment of hemorrhoids [14, 15].

As a result of comparative clinical studies of Phlebofa drugs (main group) and the reference drug (control group), 60 patients of both sexes aged 18 to 70 years with chronic venous insufficiency of varying severity were studied. During treatment, a significant improvement was revealed in both groups, which was manifested in a decrease in malleolar volume (p = 0.023 for the main and p = 0.0001 for the control group), a decrease in the diameter of the common femoral vein after treatment during the Valsalva maneuver (p < 0. 0001 and p = 0.005), a decrease in systemic venous pressure (p = 0.001 and p = 0.01), an improvement in quality of life indicators (p = 0.0001 and p = 0.0001) and a significant improvement in the total score on the clinical severity rating scale VSCC disease (p = 0.002 and p = 0.0013) [16].

Thus, the reproduced Russian-made drug Phlebofa showed comparable results during a bioequivalence study, and comparable data on clinical efficacy were noted during clinical trials in patients with CVD.

Conclusion

Treatment of patients suffering from chronic venous insufficiency involves the use of effective and safe medications.

The drug Phlebofa is a high-quality generic domestic drug with a unique production technology and can be used to treat patients with chronic hepatitis A along with other drugs based on semi-synthetic diosmin. The use of generic drugs with proven effectiveness, safety, quality and a positive pharmacoeconomic profile makes it possible to provide all patients in need with highly effective and affordable drugs.

Literature

1. Sturov N. Chronic venous insufficiency of the lower extremities: epidemiology, pathogenesis, clinical picture and principles of therapy // Doctor. 2008, No. 4, p. 22–24.
2. Shevchenko Yu. L., Stoyko Yu. M. Fundamentals of clinical phlebology. 2013.
3. Zolotukhin I. A. Chronic venous diseases in women: results of the Russian screening study DEVA // Consilium Medicum. 2008; 08: 128–131.
4. Karalkin A.V., Gavrilov S.G., Kirienko A.I. The effectiveness of compression hosiery “TONUS ELAST” in the treatment of varicose veins of the lower extremities // RMJ. 2007. No. 12. P. 977.
5. Russian clinical guidelines for the diagnosis and treatment of chronic venous diseases, 2013.
6. Ramelet A.-A., Boisseau M.R., Allegra C., Nicolaides A. et al. Veno-active drugs in the management of chronic venous disease. An international consensus statement: current medical position, prospective views and final resolution // Clin Hemorheol Microcirc. 2005; 33 (4): 309–319.
7. Bogachev V. Yu. et al. Bioflavonoids and their significance in angiology // Focus on diosmin. 2013, no. 1, 19.
8. Klimova E. A. Chronic venous insufficiency and methods of its treatment // Breast cancer. 2009. No. 12. P. 828.
9. Cova D., De Angelis L., Giavarini F., Palladini G., Perego R. Pharmacokinetics and metabolism of oral diosmin in healthy volunteers // Int J Clin Pharmacol Ther Toxicol. 1992 Jan; 30 (1): 29–33.
10. Garner RC et al. Comparison of the Absorption of Micronized (Daflon 500® mg) and Nonmicronized 14 C diosmin Tablets After Oral Administration to Healthy Volunteers by Accelerator Mass Spectrometry and Liquid Scintillation Counting // J Pharm Sci. 2002 Jan; 91(1):32–40.
11. Batchvarov I. et al. One-year diosmin therapy (600 mg) in patients with chronic venous insufficiency — results and analysis // J Biomed Clin Res. 2010, vol. 3, no. 1.
12. Maksimovic ZV et al. Medicamentous treatment of chronic venous insufficiency using semisynthetic diosmin - a prospective study // Acta Chir Iugosl. 2008; 55 (4): 53–59.
13. Vakhratyan P. E., Gavrilenko A. V., Kim E. A. Results of complex treatment of patients with varicose veins of the lower extremities // Angiology and Vascular Surgery. 2008, vol. 14, no. 4.
14. Kecmanovic D. et al. Phlebodia (diosmine): a role in the management of bleeding nonprolapsed hemorrhoids // Acta Chir Iugosl. 2005; 52 (1): 115–116.
15. Logutova L. S., Petrukhin V. A., Akhvlediani K. N. et al. The effectiveness of angioprotectors in the treatment of pregnant women with placental insufficiency // Russian Bulletin of Obstetrician-Gynecologist. 2007, vol. 7, no. 2, p. 45–48.
16. Shumilina M.V. et al. Open comparative randomized clinical study of the effectiveness and safety of the drug phlebof in the treatment of chronic venous insufficiency of the lower extremities // Clinical Physiology of Blood Circulation. 2014, no. 1, p. 61–67.

M. V. Zhuravleva, Doctor of Medical Sciences, Professor S. Yu. Serebrova, Doctor of Medical Sciences, Professor A. B. Prokofiev, Doctor of Medical Sciences, Professor T. M. Ponomarenko E. Yu. Demchenkova, Candidate of Medical Sciences G. I Gorodetskaya1

FSBEI HE First Moscow State Medical University named after. I. M. Sechenova Ministry of Health of the Russian Federation, Moscow

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