Agrenox

Agrenoks refers to a group of drugs that have the ability to affect the rheological characteristics of the blood. According to the classification, this drug is an inhibitor of the adhesion of platelets without the content of heparin in it. Pharmacotherapeutic group of the drug is a means of affecting the circulatory system and the hemopoiesis. 

The drug is widely used for the treatment of diseases, the pathogenesis of which is associated with an increased level of thrombus formation in the circulatory system. In addition, Agrenoks is used to prevent and treat complications of acute and chronic pathological conditions.

Despite the high effectiveness of this drug, it is necessary to consider the likelihood of adverse reactions. Before taking Agrenox should take into account contraindications, and dosage is prescribed exclusively by a doctor.

The drug, with observance of dosages and duration of administration, is well tolerated and does not cause side reactions associated with overdose or features of each component, including the influence of the main active substance.

[1], [2],

Indications of the agrenox

Indications for use Agrenoks include preventive and curative measures. Due to the ability of the drug to prevent the adhesion of platelets and the formation of conglomerates, it is widely used in pathological conditions, the genesis of which is based precisely on this property of platelets.

Of acute conditions should be identified transient ischemic attack of the brain, a pathogenetic explanation of its development is the occlusion of a thrombus lumen of a blood vessel. Depending on the size of the thrombus, clinical manifestations may differ.

Thus, with a slight closure of the lumen, there is a decrease in blood flow in a certain vessel, which feeds the site of the brain. As a result, dizziness and headaches are possible. However, as the process progresses and further occlusion of the lumen appears, a more pronounced clinic with loss of consciousness and a violation of certain functions in the body.

Indications for use Agrenoks are also used in ischemic stroke, when the nature of the acute condition is confirmed with the help of special instrumental techniques. In addition, the drug is used for prophylactic purposes in people who already have a history of strokes. Indications are due to the ability of Agrenox to reduce thrombosis.

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Release form

The form of release determines the mode of application of the medicinal product. Thus, Agrenoks is available in the form of capsules, which ensures the delivery of their contents to the stomach, bypassing the process of splitting in the oral cavity.

One capsule of the drug consists of dipyridamole with a gradual release in the volume of 200 mg and acetylsalicylic acid - 0.025 g. In addition, the capsule has some auxiliary components: gelatin, hypromelosum, dimethicone 350, glyceryl triacetate, methacrylate copolymer (type B), titanium dioxide (E 171 ), acacia, microcrystalline cellulose and many others.

All these components are capsules with extended activity. The encapsulated form of the release prevents the effect of saliva enzymes on the main active ingredients. The drug is produced in polypropylene tuba with a different amount: 30 and 60 capsules in each.

Each capsule consists of gelatin of a firm consistency and is divided into two lids: one - red opaque, and the second - with a shade of milky color. The filling of the capsule is represented by granules of yellow color and a tablet. The latter has a round biconvex shape with a shell with flat edges.

[4], [5]

Pharmacodynamics

Pharmacodynamics Agrenoks is due to several biochemical mechanisms associated with acetylsalicylic acid and dipyridamole.

Acetylsalicylic acid has the ability to interfere with the synthesis of thromboxane A2, which serves as an activator of the adhesion of platelets and spasm of blood vessels. This mechanism is based on the blocking of cyclo-genase in platelets.

Dipiradamol affects several mechanisms. It is able to inhibit the absorption of the formed elements of the blood and endothelial cells of adenosine. Reduction of activity of this process occurs on 80% under condition of observance of therapeutic dosage, not exceeding 2 mcg / ml. 

As a result, there is an increase in the amount of adenosine, which affects the receptor apparatus of platelets A2, which in turn activates the synthesis of adenylate cyclase and increases the cAMP content in platelets.

As a result of these reactions, there is a decrease in the rate of adhesion of platelets in response to the effect of their activation factor, collagen and adenosine diphosphate.

Reducing the adhesion of platelets increases their life expectancy, resulting in the normalization of their number. In addition, dipiridamol is able to dilate the vessels, since it has vasodilator activity.

Pharmacodynamics Agrenoks with dipyridamole reduces the activity of thrombocyto genesis due to subepithelial structures by increasing the content of the protective mediator.

Thus, the combined effect of dipyridamole and acetylsalicylic acid provides inhibition of aggregation, activation and gluing of platelets.

[6], [7]

Pharmacokinetics

The pharmacokinetics of Agrenox is caused by the pathogenetic effects of dipyridamole and acetylsalicylic acid.

Absorption of dipyridamole provides a bioavailability of the drug of about 70%. The maximum concentration of active substance in the bloodstream falls on the period - 2-3 hours after taking 400 mg (200 mg twice) - this is a daily dose.

Pharmacokinetics Agrenoks with gradual release does not change from food intake. The distribution of dipyridamole is observed in many organs due to its high lipophilicity. The active phase of distribution when administered intravenously does not differ from oral administration.

Dipyridamole can penetrate insignificantly through the blood-brain and transplacental barriers. The active substance is transported in a complex with blood proteins. Metabolism mostly occurs in the liver due to its formed complex with glucuronic acid with the formation of mono- and diglucoronides.

The process of deducing dipyridamole is divided into two phases. The predominant half-life is 40 minutes, and the final half-life is 13 hours. Repeated use of the drug does not cause its accumulation in the body.

Another component of Agrenox is acetylsalicylic acid, when used orally, quickly absorbed in the gastrointestinal tract. The maximum content in the blood is reached after 30 minutes, subject to taking 50 mg twice.

Acetylsalicylic acid is transformed into salicylate, which combines with albumin and is transported to all organs and tissues, including those that enter the breast milk, the structure of the central nervous system, and the fetal tissue. The concentration of salicylate is rapidly decreasing, and its metabolism occurs with the help of specific esterases.

The elimination of almost 100% of acetylsalicylic acid occurs in the metabolized form of the kidneys. The unaltered form of this substance with increasing dose is allocated in a larger volume.

[8],

Dosing and administration

Agrenox is taken regardless of the meal twice a day. There should be a certain interval between the medications of the remedy, therefore Agrohnox is used in the morning and in the evening.

In order for the contents of the capsule to be delivered to the stomach unchanged, the capsule must be swallowed whole, without chewing it. To facilitate the administration of Agrenox, the capsule is filled with a glass of water.

The way of application and the dose for each person should be selected individually, as some people may have the appearance of cephalgia at the beginning of therapy with Agrenox. To reduce the occurrence of side effects, it is necessary to reduce the dosage taken and leave one capsule per day, preferably at bedtime. In the morning, take a small dose of acetylsalicylic acid.

However, it should be remembered that in order to obtain the desired result, it is necessary to follow the method of application and dose, therefore, once the headache ceases to disturb, it is recommended to resume the dosage in two capsules. The duration of the therapeutic course is determined individually, based on the severity of the disease and the presence of concomitant pathology.

[12], [13], [14], [15]

Use of the agrenox during pregnancy

The use of Agrenox during pregnancy is limited due to the lack of data on its use in this period. Due to the content of acetylsalicylic acid in this medication, it can have a negative effect on the fetus.

Taking the drug after the second trimester of pregnancy can provoke the premature birth of a premature baby, the appearance of intracranial hemorrhages in the substance and space of the fetal brain, as well as the birth of a dead fetus or the onset of death in the first hours after birth.

Based on the above, the use of Agrenox during pregnancy in the 3rd semester of pregnancy should be prohibited due to the negative effect of the drug on the fetus in the form of a cardiovascular pathology - closure of the arterial duct.

Studies have not been conducted on pregnant women using this medication, so its use should not be recommended at this time. In addition, in case of conception of the fetus during the administration of Agrenox, the pregnant woman should be warned about the possible pathological effect of the drug on the fetus.

As for the period of breastfeeding, the main active ingredients of the drug - dipyridamole and salicylates - can penetrate into breast milk. As a result, the use of Agrenox in this period is not recommended.

Contraindications

Contraindications to the use of Agrogenx are based on the individual characteristics of the organism and the presence of concomitant pathological conditions. From the genetic intolerance of Agrenox components, it is worth noting allergic reactions to dipyridamole and acetylsalicylic acid, as well as additional components. It is not recommended to use the drug in the third semester of pregnancy and in childhood.

Contraindications to the use of Agrogenx also include certain diseases, for example, ulcerative lesions of the stomach and duodenal mucosa, the pathology of the coagulated system of blood - hemophilia, hemorrhagic diseases or diathesis, which can be complicated by bleeding.

Due to the presence of acetylsalicylic acid in the drug, it is not recommended to take it for people with allergic diseases - bronchial asthma or polyps in the nasal cavity.

Renal, hepatic and heart failure in the stage of decompensation are contraindications to the appointment of Agrenox. In addition, simultaneous administration of this drug with methotrexate in a dosage greater than 15 mg / week is not recommended.

[9], [10]

Side effects of the agrenox

All the side effects of Agrenox are divided according to violations in certain systems of the body. From the side of the circulatory and lymphatic systems, one should single out a decrease in the level of platelets, red blood cells in the blood. In addition, due to constant bleeding in the stomach cavity, it is possible to develop iron deficiency anemia.

The immune system can respond to the drug with a hypersensitivity reaction with the appearance of rashes, severe bronchospasm, angioedema or urticaria.

 Side-effects Agrenoks caused by the nervous system, manifested by hemorrhages in the tissue or space of the brain, cephalalgia, dizziness, similar to migraine.

Bleeding is possible in the eyes, nasal cavity, organs of the gastrointestinal tract, skin, as well as difficulties in stopping it during surgical operations or other manipulations.

The cardiovascular system can respond to Agrenox by increasing heart rate, fainting, lowering blood pressure, or feeling "hot".

The gastrointestinal tract can manifest a reaction to the drug with nausea, vomiting, bowel movement and pain in the abdomen. Myalgia is a symptom of the defeat of the musculoskeletal system. 

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Overdose

Overdose of the drug is more evident in the clinical symptoms of excessive accumulation of dipyridamole. This is due to the fact that the capsule contains 200 mg of dipyridamole and only 0.025 g of acetylsalicylic acid. As a result, overdose can be expressed by hot flushes, increased sweating, nervousness and general weakness.

In addition, pain can be felt behind the sternum, a decrease in blood pressure and increased heart rate.

Overdosage with acetylsalicylic acid is less intense, but still there is dizziness, frequent shallow breathing, digestive disorders, tinnitus (especially in old age), decreased visual and auditory perception and loss of consciousness. In the case of taking a large dose, hyperthermia is possible with an increase in temperature to 39 degrees, as well as symptoms of hypovolemia. The lack of fluid in the body contributes to the development of life-threatening conditions.

However, these clinical manifestations can occur only in a small number of cases in view of the small quantitative composition of acetylsalicylic acid in one capsule of Agrenox.

When symptoms of an overdose occur, symptomatic treatment should be performed. It includes gastric lavage, the administration of xanthine derivatives (aminophilin), which can reduce the severity of overdose. The remaining methods to accelerate the removal of the drug have no special significance, since Agrogenx is transformed in the liver and tissues, which causes its long-term content in the body.

Interactions with other drugs

Interactions Agrenoks with other drugs are based on the enhancement or inhibition of certain therapeutic effects simultaneously taking drugs.

Acetylsalicylic acid is able to increase the activity of anticoagulants, antithrombotic agents, valproic acid and phenytoin, which may increase the likelihood of side effects.

The combination with non-steroidal anti-inflammatory drugs (paracetamol and ibuprofen), hormones and alcohol can provoke complications from the digestive system. Acetylsalicylic acid enhances the effect of drugs that reduce blood sugar, as well as the toxic properties of methotrexate, especially in dosages above 15 mg / week.

This acid inhibits the activity of prostaglandins and leads to a decrease in renal blood flow with a further retention of fluid and salts. As a result, the therapeutic effect of beta-blockers and diuretics (spironolactone) may decrease.

Dipyridamole is able to increase the concentration of adenosine in the blood, so the dosage of the latter should be reviewed. Joint use with warfarin does not lead to the development of complications, including bleeding, to a greater extent than warfarin alone.

Dipyridamole enhances the activity of drugs, the mechanism of action of which is based on a decrease in blood pressure, and inhibits the effect of anticholinesterase inhibitors, which are used in malignant myasthenia gravis.

Interactions Agrenoks with other drugs in the dosage of acetylsalicylic acid more than 3 g / day can lead to a decrease in the therapeutic effect of ACE inhibitors due to the effect of acid on the reaction of converting renin to angiotensin. 

The simultaneous use of acetylsalicylic acid and acetazolamide can provoke an increase in the concentration of the latter in the blood and the development of side effects. 

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Storage conditions

Agrénox storage conditions, like any other drug, imply compliance with certain rules that include temperature, humidity and the absence of direct sunlight on the package of the drug.

The temperature of the room where the medicinal product is stored should not exceed 30 degrees. In addition, it is necessary to monitor the integrity of the drug package.

The manufacturer worried about children who can get to Agrenox and take a large dosage or the capsule will be able to close the lumen of the upper respiratory tract, so the bottle has a special lid. As a result, only by applying force, you can open it.

The storage conditions of Agrenox ensure the safety of the indicated therapeutic properties for a certain period of time. The date of the last day of taking the drug is also indicated on the outer carton and inner vial. Thanks to such packaging, the active substance is not affected by environmental factors.

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Shelf life

The expiry date is information about the preparation, which is mandatory for each drug. It represents a certain period of time, which has a specific date for the last reception. During this period, the manufacturer of the drug guarantees the doubt of the main therapeutic properties provided that the above storage conditions are met.

The shelf life of Agrenox is 3 years. After the end of this period, it is forbidden to use the drug, as it can not only lose its medicinal properties, but also have a negative effect on the body with varying intensity.

Agrenoks is a proven effective drug based on dipyridamole and acetylsalicylic acid. Due to their combination, this agent has an antithrombotic effect. It is achieved by preventing aggregation of platelets in the bloodstream. Its therapeutic property is used for therapeutic and preventive purposes with transient ischemic attacks or ischemic strokes.

[21], [22], [23]