Agapurin

Agapurin is a pentoxifylline-based drug. The drug belongs to the metabolites of the xanthine, purine group and is aimed at correcting and improving microcirculation in various vascular pathologies. As an active vasodilator, Agapurin significantly improves the rheological properties of blood, dilates coronary arteries, tones muscles, and can increase the level of ATP in the body's cells.

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Indications Agapurina

Pentoxifylline as the main active ingredient of Agapurin and its analogues was first synthesized in the 70s of the last century. Germany is considered the originator of the drug, German manufacturers are considered one of the most effective drugs, although drugs containing pentoxifylline, produced in other countries, are not inferior in quality or in the effectiveness of the impact on microcirculation and rheological parameters of the blood.

Main indications for use:

1. Anticoagulant effect, significant reduction in blood viscosity
2. Angioprotective effect
3. Activation of blood flow, increase in blood fluidity
4. Improvement of all rheological parameters of blood
5. Increased ATP levels in erythrocytes and leukocytes, resulting in improved plasticity
6. Activation of cytokine production (cytoprotective effect)
7. Smooth muscle relaxation
8. Dilation of pulmonary vessels
9. Increasing the tone of the diaphragm
10. Prevention of tissue hypoxia

Nosologies for which Agapurin is indicated:

• Vestibular disorders
• Otosclerotic pathologies
• Retinal vascular occlusions
• Retinal arterial occlusion
• Spasm of the retinal arteries
• Diseases of the inner ear
• Cerebrovascular pathologies and their consequences
• Atherosclerosis, including atherosclerosis of the extremities
• Raynaud's syndrome
• Peripheral angiopathies, including diabetic angiopathies
• Thromboangiitis obliterans
• Varicose veins of the lower extremities, including those accompanied by ulceration
• Gangrene
• Paresthesia
• Frostbite
• Intermittent claudication
• Cerebral circulatory disorder (ischemia)
• Discirculatory encephalopathy
• Trophic tissue disorders (ulcers, consequences of thrombophlebitis)
• Acrocyanosis
• Post-stroke conditions
• Headache associated with ischemic disorders
• Memory loss
• IHD – ischemic heart disease
• Neuroinfections of viral etiology
• Sepsis
• Conditions after myocardial infarction
• Impotence associated with vascular disorders
• BA – bronchial asthma
• COPD - chronic obstructive pulmonary disease.

It should be noted that this medicine has many analogues, which are also developed on the basis of pentoxifylline. The attending physician can choose the medicine depending on the indications. Among the analogues, the following drugs are most in demand:

• Arbiflex
• Vazonite
• Pentamon
• Pentoxifylline
• Mellinorm
• Eskom
• Trental
• Flexital

Indications for use may be varied, sometimes contradicting the instructions and contraindications, for example, during pregnancy. A limited period of taking the drug may be due to an urgent need that exceeds the risk of side effects, when the benefits and effectiveness of pentoxifylline significantly exceed its potential complications. In addition, the properties of the drug are constantly being studied, since Agapurin is considered a relatively "young" drug. It is likely that the list of its indications will soon be significantly expanded and many diseases associated with circulatory failure will receive a new method of effective treatment.

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Release form

The medicine is available in tablet and injection form, in different dosages, which are indicated for various vascular pathologies depending on the severity of the disease. As a rule, if the disorders are diagnosed as severe, intravenous or intramuscular injections of Agapurin are prescribed, maintenance therapy or treatment of chronic diseases involves taking the medicine in tablet form.

Release form:

• Injection solution - ampoules of 5 milliliters, 5 ampoules in a package
• Tablets in a dosage of 100 milligrams, 60 tablets in a bottle
• Tablets - 400 milligrams of active ingredient - 10 tablets in a blister, 2-10 blisters in the original packaging
• Tablets - 600 milligrams of pentoxifylline, 10 tablets per blister, 2 to 10 blisters per package
• Agapurin retard - 400, 600 milligrams of active substance, 10 tablets in a blister, 2 blisters in a package

The composition includes the following components:

• Pentoxifylline (100, 400, 600 mg)
• : Lactose monohydrate (lactose monohydrate, milk sugar)
• Talc
• Cornstarch
• Magnesium stearate (magnesium stearate, stearic acid)
• Silicium dioxide colloidal (silicon dioxide colloidal)
• Carmellose sodium, glycerol (sodium carmellose)
• Sucrose
• Methylparaben (methylparaben in minimal quantity)
• Gummi arabicum (acacia gum)
• Titanium Dioxide (titanium dioxide)
• Microcrystalline cellulose

Pharmacodynamics

The pharmacological action is due to the activity of pentoxifylline in relation to adenosine (purinergic) receptors P1 and P2. The active substance of the drug blocks them, causing inhibition of PDE (phosphodiesterase) - an enzyme capable of detaching nucleotides from the DNA polynucleotide chain. As a result, cyclic adenosine monophosphate (cAMP) begins to accumulate in platelets, the rate of platelet aggregation decreases, the elasticity of erythrocytes increases significantly and the level of viscosity and thickness of the blood decreases. Thus, the pharmacodynamics of Agapurin is aimed at vasodilation, reducing the level of aggregation, activating microcirculation, and concentrating ATP in the external environment. The drug mainly acts in capillaries and small vessels, where the rheological properties of the blood improve, and due to its inflow, the supply of oxygen to tissues becomes more intense.

Pharmacodynamics:

• Anti-inflammatory effect
• Cytoprotective effect
• Activation of blood microcirculation
• Blood flow oxygenation (CNS, extremities)
• Prevention of myocardial hypoxia
• Increased tone of the intercostal, scalene muscles and diaphragm - respiratory muscles
• Activation of collateral blood flow
• Prevention or reduction of idiopathic (night) seizures
• Increased ATP concentration and significant improvement in bioelectrical parameters of the central nervous system

Pharmacokinetics

Agapurin has a high absorption rate. Pharmacokinetics is characterized by almost complete absorption in the digestive tract (up to 95%). The active ingredient combines with the protein structures of erythrocytes (membranes), the biotransformation process occurs in erythrocytes and liver cells. Almost all pentoxifylline is excreted in the form of intracellular metabolism products, in the form of metabolites. Metabolic products formed by the liver are divided into metabolite I (1-5-hydroxyhexyl-3,7-dimethylxanthine) and metabolite V (1-3-carboxypropyl-3,7-dimethylxanthine), these compounds are concentrated in blood plasma and eliminated from the body during defecation and urination (metabolite V with urine up to 95%). No more than 2% of the active ingredient is excreted in pure form - in the form of pentoxifylline. The excretion time does not exceed 4 hours after the first dose. It should be taken into account that Agapurin can be excreted in breast milk, therefore it is not prescribed during lactation or breastfeeding is replaced with artificial mixtures. Also, the normal pharmacokinetics of the drug can be disrupted in severe nephropathology, given the maximum excretion of the drug by the kidneys.

Dosing and administration

The regimen and dosage depend on the nosology and severity of the disease. There can be no universal prescriptions in this sense, however, there are general recommendations, which are given below.

Method of administration and dosage by form:

1. Tablet form. The medicine is taken after meals, the tablet should be taken without chewing, with a large volume of liquid (water)
2. The intake should be determined by the regimen - the tablet is taken at the same time of day.
3. The initial dose of the drug is 200 milligrams three times a day.
4. If side effects occur, the dose is reduced in the same way as the regimen - 100 mg 2 times a day. After 3-4 days, 100 mg can be taken three times a day.
5. The maximum daily dose should not exceed 1200 milligrams.
6. Agapurin retard (prolonged-release drug) is taken less frequently - 1-2 times a day, depending on the indications
7. Injections can be administered either intramuscularly or intravenously:

• Intramuscularly 100 mg 102 times a day without the use of a solvent
• Intravenously - the drug is diluted in 250 or 500 ml of sodium chloride (as an option in a glucose solution - 5%). The method of administration is slow, not higher than 150 milliliters per hour. The maximum daily dose of injection Agapurin is 2 ampoules.
• Intra-arterial drip administration – the ampoule is dissolved in 20 or 50 mg of sodium chloride. The administration should be slow, 10 minutes per ampoule. The maximum daily dose is 3 ampoules per day.
• The duration of the course of treatment depends on the clinical picture of the disease and the expected therapeutic effect.

These recommendations are not dogma and cannot be considered a direct recommendation for the use of the drug. The method of administration and dosage are determined by the attending physician in accordance with the patient's condition and the indications of the diagnosed vascular pathology.

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Use Agapurina during pregnancy

According to the instructions, use during pregnancy is not recommended. However, in clinical obstetric practice, there are often cases when the expectant mother may still be prescribed a drug containing pentoxifylline. During gestation, various circulatory disorders are possible, and these conditions are very dangerous for fetal development. In such cases, the attending physician faces the question of the ratio of side effects for the mother and threats to the baby. One of the most dangerous conditions is gestosis, which develops in the second trimester due to venous congestion or blockage of capillaries. The process begins with swelling, then kidney dysfunction occurs, protein appears in the urine, headaches and even convulsions. Also dangerous is FPN - fetoplacental insufficiency, accompanied by spasms of the vascular system of the placenta and fetal hypoxia.
Use during pregnancy in such cases is not only acceptable, but also necessary, since the drug is able to restore normal microcirculation and blood circulation in general. Prescribing the drug helps to activate blood flow, reduce the risk of platelet aggregation (sticking together), and improve the rheological properties of blood. Vasodilation ensures proper blood supply to tissues and neutralizes the potential threat of fetal hypoxia. Such prescriptions are justified, since the benefits to the mother and baby significantly exceed all possible side effects of pentoxifylline.

It is prescribed with caution to pregnant women with a history of gastric ulcer or duodenal ulcer, as well as to those who have a low level of blood clotting. Also, the drug should be discontinued at the end of pregnancy to avoid the risk of bleeding during the birth process. In general, Agapurin, as well as its analogues, is quite widely used in gynecological and obstetric practice as an effective vasodilator that does not have a pathological effect on fetal development.

Contraindications

Like other effective vasodilator drugs, Agapurin has its own specific contraindications.

Contraindications for use:

• Individual intolerance to methixanthines, including pentoxifylline
• Gestation period, breastfeeding
• Children, teenagers, young people under 18 years of age
• Any bleeding
• Retinal hemorrhages (bleeding into the retina)
• Myocardial infarction, acute infarction
• Porphyria
• Hemorrhagic stroke
• Arrhythmia
• Coronary atherosclerosis in the acute stage
• Cerebral atherosclerosis in the acute stage
• Hypotension (risk of significant drop in blood pressure)
• Hemorrhagic diathesis
• Renal pathologies in which creatinine clearance is less than 30 ml/minute

The following conditions are not direct contraindications for use, but they must be taken into account to avoid complications:

• Chronic heart failure
• GU – gastric ulcer
• History of duodenal ulcer
• Renal failure
• Hepatitis
• Recent surgery (blood loss)
• Diabetes (therapy requires dosage adjustment)

Agapurin does not affect psychomotor reactions and does not influence concentration, memory, coordination of movements or the psyche.

Side effects Agapurina

Taking Agapurin is rarely accompanied by undesirable effects, however, they are worth mentioning in order to avoid complications.

Side effects may manifest themselves in the form of the following symptoms:

• A sharp decrease in blood pressure (hypotension)
• Tachycardia
• Bleeding, including internal
• Hypoglycemia
• Arrhythmia
• Transient headache, spasms
• Increased nervous excitability
• Sleep disturbance
• Scotoma (blind spot in the visual field)
• Hyperhidrosis (excessive sweating)
• Rarely - allergic reactions in the form of rash, hives, skin irritation, itching
• Edema in kidney pathology
• Rarely - convulsive syndrome
• Dizziness
• Increased fragility of nails
• Decreased appetite, nausea
• With prolonged use, exacerbation of cholecystitis (cholestatic hepatitis) is possible.
• Thrombocypenia

Side effects are rare, with proper use of the drug, according to the doctor's recommendations, such situations are noted only in 3 cases per 1000 patients. However, caution is necessary when prescribing to patients with myocardial infarction, low blood pressure, nephropathology and hepatitis, as well as elderly patients.

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Overdose

Overdose manifests itself in the form of side effects - bleeding, nausea, vomiting, dizziness, hypotension, hypoglycemia, allergic reaction, less often - convulsions. As a rule, these cases are associated with either an excess of the drug dosage or in the case of excessively frequent use. The most serious threat is an overdose accompanied by anaphylaxis and convulsions.

How does an overdose manifest itself?

• Dizziness
• Lowering blood pressure
• Hyperemia of the skin
• Tachycardia
• Drowsiness, weakness
• Elevated body temperature
• Hypoglycemia
• Loss of consciousness
• Symptoms of internal bleeding (vomiting blood)
• Chills
• Tonic-clonic seizures

These conditions require immediate medical attention, since it is almost impossible to remove the drug at home, there is no specific antidote to it. The only thing that can be done at home is to wash the stomach and take any enterosorbent. The same actions are carried out in hospital conditions, in addition to them, the patient is shown symptomatic therapy, which relieves severe symptoms. The patient should also be under constant supervision of a doctor who monitors all vital functions, especially breathing and blood pressure.

Intoxication caused by overdose can be avoided by strictly following the recommendations of the attending physician; if the regimen and dosage are not exceeded, the risk of complications is reduced to a minimum.

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Interactions with other drugs

Drug interactions are due to its pharmacodynamics, the drug is able to activate any antihypertensive agent, vasodilators, synthetic amines (ganglionic blockers). Thus, all drugs that can affect blood clotting, when taken simultaneously, enhance their effect, causing a synergistic effect. Direct and indirect anticoagulants, drugs containing valproic acid, some types of antibiotics, especially cephalosporins in combination with Agapurin can provoke undesirable side effects, this must be taken into account when prescribing such drugs.

Interactions with other drugs:

1. Increased efficiency:

• In combination with thrombolytics
• When taking antihypertensive drugs simultaneously
• In combination with insulin or other hypoglycemic drugs in tablet form
• When administered concomitantly with cephalosporins (cefoperazone, cefamandole, cefotetan)
• In combination with PVC-valproates (Depakine, Valparine, Convulex)

1. Use with caution with the following drugs:

• In combination with cimetidine, the level of the active substance (pentoxifylline) in the blood plasma may increase
• Simultaneous use of Agapurin and other purines, xanthines can provoke side effects from the nervous system (increased nervous excitability)
• In combination with anti-asthmatic drugs (theophylline), side effects typical of phosphodiesterase inhibitors may develop - nausea, diarrhea, headache, epileptoid conditions

Since Agapurin quickly activates the action of drugs intended to reduce blood pressure, it is necessary to ensure that such a combination of drugs does not provoke a sharp jump in blood pressure (hypotension). In addition, long-term use of xanthines can potentiate the effect of hypoglycemic drugs, as well as insulin, in such cases, it is recommended to correct antidiabetic treatment and constantly monitor blood sugar levels to avoid hypoglycemia. When Agapurin and thrombolytics are prescribed simultaneously, PT (prothrombin time) and PTI (prothrombin index) should be constantly measured to prevent the risk of hemorrhage, hemorrhage.

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Storage conditions

Medicines in any form are stored according to the procedure regulated by special orders of the Ministry of Health. The conditions and terms of storage are determined by List B, intended for pharmacies. This list includes a group of drugs classified as potent, such drugs are stored separately from other medications. The group includes almost all analgesics, cardiac drugs, vasodilators such as Agapurin, sulfonamides, drugs containing alkaloids, hormones and many other drugs.

Storage conditions and periods for drugs from list B:

• Separate cabinet, home medicine cabinet
• Protection from light
• Moisture protection
• Store in original factory packaging
• Air temperature not higher than +20 degrees
• Place inaccessible to children

Shelf life

The shelf life depends on the amount of the main active ingredient and the form of the drug, as a rule, the shelf life does not exceed 5 years. The expiration date is indicated on the factory packaging, after which it is not recommended to take the medicine, even if the drug is not used completely.

Shelf life depending on the form of the drug:

• Tablets (100 and 400 mg) - shelf life up to 5 years
• Tablets (600mg) – shelf life up to 4 years
• The injection solution is stored for no more than 3 years.

Agapurin is one of the most reliable and effective drugs that helps to significantly improve the condition of patients with chronic arterial insufficiency, obliterating atherosclerosis of the lower extremities, as well as other pathologies accompanied by impaired blood microcirculation and cerebrovascular pathology. This is a promising drug, the properties of which continue to be studied, resulting in an expanding list of indications for its use every year. Positive reviews of the drug from doctors and patients indicate the effectiveness of Agapurin and its real positive effect on blood microcirculation, subject to compliance with the rules of administration, regimen and the required dosage.