Agapurin

Agapurin is a drug based on pentoxifylline. The drug refers to metabolites from the group of xanthines, purines and is aimed at correcting and improving microcirculation in various vascular pathologies. As an active vasodilator Agapurin significantly improves rheological properties of blood, dilates coronary arteries, tones muscles, is able to increase the level of ATP in the cells of the body.

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Indications of the agapurina

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

The main indications for use:

1. Anticoagulant effect, a significant decrease in the level of blood viscosity
2. Angioprotective effect
3. Increased blood flow, increased blood fluidity
4. Improvement of all rheological parameters of blood
5. Increase in the level of ATP in erythrocytes, leukocytes, as a result - improve their plasticity
6. Activation of cytokine production (cytoprotective action)
7. Relaxation of smooth muscles
8. Expansion of the vessels of the lungs
9. Increase the tone of the diaphragm
10. Prevention of tissue hypoxia

Nosology, which shows the reception of Agapurin:

• Vestibular disorders
• Otosclerotic pathologies
• Occlusion of the vessels of the retina
• Retinal artery occlusion
• Spasm of the arteries of the retina
• Diseases of the inner ear
• Cerebrovascular pathologies and their consequences
• Atherosclerosis, including atherosclerosis of the extremities
• Raynaud's syndrome
• Peripheral angiopathies, including diabetic angiopathies
• Obliterating thromboangiitis
• Varicose veins of the lower extremities, including those accompanied by ulceration
• Gangrene
• Paresthesia
• Frostbite
• Intermittent claudication
• Violation of cerebral circulation (ischemia)
• Encephalopathy
• Trophic tissue disorders (ulcers, consequences of thrombophlebitis)
• Acrocyanosis
• Post-stroke states
• Headache associated with ischemic impairment
• Memory loss
• IHD is ischemic heart disease
• Neuroinfection of viral etiology
• Sepsis
• Conditions after myocardial infarction
• Impotence associated with vascular disorders
• Asthma - asthma
• COPD is a chronic obstructive pulmonary disease.

It should be noted that this medicine has many analogues, which are also developed based on pentoxifylline. Depending on the indications, a doctor can choose a medicine. Among the analogues the most popular are such drugs:

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

Indications for use can be various, sometimes conflicting instructions and contraindications, for example, in pregnancy. The limited duration of the medication can be caused by an acute need, exceeding the risk of side effects, when the benefit and effectiveness of pentoxifylline significantly exceeds 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 his testimony will soon be significantly expanded and many diseases associated with circulatory failure will receive a new way of effective treatment.

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Release form

The drug is available in tableted and injectable form, in a different dosage, which is indicated for various vascular pathologies, depending on the severity of the disease. Typically, if the violations are diagnosed as severe, injections of Agapurin are given intravenously or intramuscularly, maintenance therapy or treatment of chronic diseases presupposes taking the drug in tablet form.

Form of issue:

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

The structure includes such components:

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

Pharmacodynamics

The pharmacological action is due to the activity of pentoxifylline against adenosine (purineergic) receptors P1 and P2. The active substance of the drug blocks them, provoking the inhibition of PDE (phosphodiesterase), an enzyme capable of detaching nucleotides from the polynucleotide chain of DNA. As a result, cyclic adenosine monophosphate (cAMP) begins to accumulate in the platelets, the platelet aggregation rate decreases, the elasticity of erythrocytes increases significantly and the level of viscosity and blood density decreases. Thus, the pharmacodynamics of Agapurin is aimed at vasodilatation, reduction of the level of aggregation, activation of microcirculation, and concentration of ATP in the external environment. Basically, the action of the drug occurs in the capillaries and small vessels, it is there that the rheological properties of the blood improve, and due to its influx, the supply of tissues with oxygen becomes more intensive.

Pharmacodynamics:

• Anti-inflammatory effect
• Cytoprotective effect
• Activation of blood microcirculation
• Oxygenation of blood flow (CNS, limbs)
• Prevention of myocardial hypoxia
• Increase in the tone of the intercostal, staircases and diaphragm - respiratory musculature
• Activation of collateral blood flow
• Prevention or reduction in the frequency of idiopathic (nocturnal) seizures
• An increase in the concentration of ATP and a significant improvement in the bioelectric 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%). Active active substance comes into contact with protein structures of erythrocytes (membranes), the process of biotransformation takes place in erythrocytes and liver cells. Almost all pentoxifylline is released in the form of intracellular metabolism products, in the form of metabolites. The 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 removed from the of the body during bowel movements and urination (metabolite V with urine up to 95%). Not more than 2% of the active ingredient is excreted in its pure form - in the form of pentoxifylline. The elimination time does not exceed 4 hours after the first administration. It should be noted that Agapurin is able to excrete with breast milk, so during lactation it is not prescribed or is replaced by breastfeeding with artificial mixtures. Also, the normal pharmacokinetics of the drug may be disrupted in severe nephropathology, given the maximum excretion of the drug by the kidney.

Dosing and administration

The regimen and dosage depend on the nosology and severity of the disease. There can not be universal appointments in this sense, nevertheless there are general recommendations, which are given below.

Method of administration and dose by forms:

1. Tablet form. The medicine is taken after a meal, a tablet to drink without chewing, squeezed with a large volume of liquid (water)
2. Reception should be determined by the regimen - the tablet is drunk at the same time of day
3. The initial dose of the drug is 200 milligrams three times a day
4. With the appearance of side effects, the dose decreases in the same way as the regimen - 100 mg 2 times and in knocking. After 3-4 days, 100 mg can be taken thrice a day
5. The maximum daily dose should not exceed 1200 milligrams
6. Agapurin retard (prolonged drug) is taken less often - 1-2 times a day, depending on the indications
7. Injections can be administered both intramuscularly and 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 solution of glucose - 5%). The method of administration is slow, not exceeding 150 milliliters per hour. The maximum daily dose of Agapurin injection is 2 ampoules
• Intraarterial drip injection - the ampoule is dissolved in 20 or 50 ml of sodium chloride. The introduction should be slow, on the ampoule - 10 minutes. The maximum daily dose is 3 ampoules per day
• The length of the course of treatment depends on the clinical picture of the disease and the expected therapeutic effect

These recommendations are not a dogma and can not be considered a direct recommendation to use the medication. The method of application and dose is determined by the attending physician in accordance with the patient's condition and indications of a diagnosed vascular pathology.

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Use of the agapurina during pregnancy

According to the instructions, use during pregnancy is not recommended. However, in clinical obstetric practice, it is not uncommon for a future mother to prescribe a drug containing pentoxifylline. During the gestation period, various blood circulation abnormalities are possible, and these conditions are very dangerous for the development of the fetus. In such cases, before the attending physician the question arises of the correlation of side effects for the mother and the threats to the baby. One of the most dangerous conditions is gestosis, which develops in the second trimester because of venous congestion or blockage of capillaries. The process begins with puffiness, then there is kidney dysfunction, there is a protein in the urine, headaches and even cramps. Also FPN is a fetoplacental insufficiency, accompanied by spasms of the vascular system of the placenta and hypoxia of the fetus.
Use during pregnancy in such cases is not only permissible, but also necessary, since the drug is able to restore normal microcirculation and blood circulation as a whole. The purpose of the drug helps to activate blood flow, reduce the risk of platelet aggregation (adhesion), improve the rheological properties of blood. Expansion of the vessels allows to ensure proper blood supply to tissues and neutralize the potential threat of fetal hypoxia. Such appointments are justified, since the benefits to the body of the mother and the baby greatly exceed all the possible side effects of pentoxifylline.

Be wary appoint pregnant women who have a history of YaBZ or duodenal ulcer, as well as those who have a low level of coagulation. Also, the drug should be discontinued at the end of the pregnancy period to avoid the risk of bleeding during the birth process. In general, Agapurin, as well as its analogs, is widely used in gynecological and obstetrical practice as an effective vasodilator, which does not have a pathological effect on fetal development.

Contraindications

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

Contraindications:

• Individual intolerance to methixantins, including pentoxifylline
• Gestational period, breastfeeding
• Children, teenagers, young people under 18 years of age
• Any bleeding
• Retinal bleeding (retinal hemorrhage)
• Myocardial infarction, acute myocardial infarction
• Porphyria
• Hemorrhagic stroke
• Arrhythmia
• Coronary atherosclerosis in the acute stage
• Cerebral atherosclerosis in the acute stage
• Hypotension (risk of a significant drop in blood pressure)
• Hemorrhagic diathesis
• Kidney pathology in which creatinine clearance is less than 30 ml / min

The following conditions are not direct contraindications to use, however, it is necessary to take into account to avoid complications:

• Chronic heart failure
• JAW - peptic ulcer disease
• Duodenal ulcer in anamnesis
• Renal insufficiency
• Hepatitis
• The recently transferred surgical intervention (blood loss)
• Diabetes (therapy requires adjustments based on dosage)

Primer Agapurina does not affect psychomotor reactions and does not affect the concentration of attention, memory, coordination of movements and psyche.

Side effects of the agapurina

Admission of Agapurin is rarely accompanied by undesirable manifestations, nevertheless they are worth mentioning, in order to avoid complications.

Side effects can manifest themselves in the form of such symptoms:

• A sharp drop in blood pressure (hypotension)
• Tachycardia
• Bleeding, including internal
• Hypoglycaemia
• Arrhythmia
• Transient headache, spasms
• Increased nervous excitability
• Sleep disturbance
• Scotoma (blind spot in sight)
• Hyperhidrosis (increased sweating)
• Rarely - allergic reactions in the form of rash, urticaria, skin irritation, itching
• Edema in kidney pathology
• Rarely - convulsive syndrome
• Dizziness
• Increased brittleness of nails
• Decreased appetite, nausea
• With prolonged admission, an exacerbation of cholecystitis (cholestatic hepatitis)
• Thrombocytopenia

Side effects are rare, with proper medication, according to the doctor's recommendations, such situations are noted only in 3 cases for every 1000 patients. However, caution is necessary in the appointment of 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 - seizures. As a rule, these cases are associated with the excess of either the dosage of the drug, or in case of too frequent admission. The most serious threat is overdose, accompanied by anaphylaxis and seizures.

How is overdose manifested?

• Dizziness
• Reduction of blood pressure
• Hyperemia of the skin
• Tachycardia
• Drowsiness, weakness
• Increased body temperature
• Hypoglycaemia
• Loss of consciousness
• Symptoms of internal bleeding (vomiting with an admixture of blood)
• Chills
• Tonic-clonic convulsions

 These conditions require immediate medical attention, since it is almost impossible to withdraw the medicine at home, there is no specific antidote to it. The only thing you can do at home is to wash the stomach and take any enterosorbent. The same actions are carried out and in hospital, in addition to them, the patient is shown symptomatic therapy that relieves severe symptoms. Also, the patient must be under the constant supervision of a physician, who monitors all vital functions, especially for breathing and arterial pressure.

To avoid intoxication caused by overdose, it is possible, with the help of clear observance, the recommendation of the attending doctor, if the regimen and dose of intake is not exceeded, the risk of complications is minimized.

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Interactions with other drugs

Drug interaction is due to its pharmacodynamics, the drug is able to activate any antihypertensive agent, vasodilators, synthetic amines (ganglion blockers). Thus, all drugs capable of influencing blood coagulability, with simultaneous admission, strengthen their action, causing a synergy effect. Direct and indirect anticoagulants, preparations containing valproic acid, certain types of antibiotics, especially cephalosporins in combination with Agapurin, can provoke unwanted side effects, this must be taken into account when prescribing such medications.

Interactions with other drugs:

1. Increased efficiency:

• In combination with thrombolytics
• With the simultaneous use of antihypertensive drugs
• In combination with insulin or other hypoglycemic drugs in tablet form
• With concurrent administration with cephalosporins (cefoperazone, cefamandol, cefotetan)
• In combination with PVK - valproate (Depakin, Valparin, Convulex)

1. Prescribe with caution with such drugs:

• In combination with cimetidine, the level of the active substance (pentoxifylline) in the blood plasma can increase
• Simultaneous administration 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 characteristic of phosphodiesterase inhibitors can occur-nausea, diarrhea, headache, epileptoid conditions

Since Agapurin rapidly activates the effect of drugs designed to reduce blood pressure, it must be ensured that such a combination of drugs does not provoke a sharp jump in blood pressure down (hypotension). In addition, long-term use of xanthines can potentiate the effect of hypoglycemic drugs, as well as insulin, in such cases, recommended correction of antidiabetic treatment and constant monitoring of blood sugar in order to avoid hypoglycemia. With the simultaneous administration of Agapurin and thrombolytics, PTV (prothrombin time) and PTI (prothrombin index) should be continuously monitored to prevent the risk of hemorrhage and hemorrhage.

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Storage conditions

The medicine in any form is stored according to the order, regulated by special orders of the Ministry of Health. The terms and conditions of storage are determined by list B, intended for pharmacy institutions. This list includes a group of drugs classified as strong, such drugs are stored separately from other medicines. The group includes virtually all analgesics, cardiac drugs, vasodilators, such as Agapurin, sulfonamides, drugs containing alkaloids, hormones and many other drugs.

Conditions and terms of storage of drugs from list B:

• Separate cupboard, home first aid kit
• Protection from light
• Protection against moisture
• Storage in original original packaging
• Air temperature not above +20 degrees
• A place inaccessible to children

Shelf life

The shelf life depends on the amount of the main active ingredient and the form of the preparation, as a rule, the shelf life does not exceed 5 years. The deadline for the final sale date is indicated on the original packaging, after that the drug should not be taken, even if the drug is not used completely.

Shelf life, depending on the form of the preparation:

• Tablets (100 and 400 mg) - shelf life up to 5 years
• Tablets (600 mg) - shelf life up to 4 years
• Solution for injection 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, with obliterating atherosclerosis of the lower extremities, as well as in other pathologies accompanied by impaired microcirculation and cerebrovascular pathology. This is a promising drug, the properties of which continue to be studied, which results in an expanding list of indications to its purpose every year. Positive feedback about the drug from doctors and patients speaks about the effectiveness of Agapurin and its real positive effect on blood microcirculation, provided that the rules of admission, treatment and the correct dosage are observed.