Dipyridamole - instructions for use, dose, side effects, contraindications

Influences both primary and secondary aggregation of platelets. It inhibits their adhesion, potentiates the anti-aggregation effect of prostacyclin. In the mechanism of action, the inhibition of phosphodiesterase and the increase in the content of cAMP in platelets are essential, which leads to inhibition of their aggregation. In addition, the release of prostacyclin by endothelial cells is stimulated, thromboxane A2 is inhibited. It has a vasodilating effect on coronary vessels by inhibiting adenosine deaminase (this property is used for conducting pharmacological tests), inhibiting the reverse capture of adenosine by erythrocytes (possibly,by affecting a special nucleoside transporter in the cell membrane) and increasing its concentration in the blood. Adenosine stimulates adenylate cyclase and, in turn, increases the cAMP content in platelets. Along with this, it affects the smooth muscles of the vessels and prevents the release of catecholamines.

As an anti-aggregation agent is often used in combination with acetylsalicylic acid. It inhibits the adhesion of platelets in the vessels and, to a lesser extent, aggregation. Antiaggregation effect occurs at a plasma concentration of 0.1 μg / ml. Dose-dependent extends the abnormally shortened lifetime of thrombocytes. Expands coronary arteries, especially unchanged, causes the phenomenon of intercoronary stealing. Dipyridamole stress-echocardiography in the diagnosis of coronary heart disease in patients with angiographically unchanged coronary arteries is highly sensitive in combination with high specificity (91 and 83%, respectively); the sensitivity of this test is higher in multivessel lesions in patients with well developed collaterals and in patients with reduced regional myocardial perfusion.Normalizes venous outflow, reduces the incidence of deep vein thrombosis in the postoperative period. Improves microcirculation in the retina of the eye, renal glomeruli. Reduces the resistance of cerebral vessels, is effective for dynamic disorders of cerebral circulation. It has a preventive effect on the thrombosis of implants and venous coronary shunts (in combination with anticoagulants). In combination with acetylsalicylic acid prevents the formation of thrombotic overlays on the prostheses of the heart valves. According to the angiographic study, the combination of acetylsalicylic acid with dipyridamole slows the progression of peripheral atherosclerosis. In obstetric practice, corrects placental blood flow, prevents dystrophic changes in the placenta (with the threat of preeclampsia), eliminates hypoxia of the fetal tissues and promotes the accumulation of glycogen in them. It is an inducer of interferon and has a modulating effect on the functional activity of the interferon system; increases non-specific antiviral resistance to viral infections.

Pharmacokinetics:After oral administration, it is rapidly absorbed from the digestive tract.Bioavailability is 37-66%. C_max - 75 minutes. Binding to plasma proteins is 91-99% (mainly with albumin and acid alpha₁glycoprotein). Quickly penetrates into the tissue. Pharmacokinetics two-phase - in the first phase the half-life period is approximately 40 minutes; in the second phase - about 10 hours Metabolized mainly in the liver, 20% of the drug is included in enterohepatic circulation. Excreted with bile in the form of monoglyukuronide and a small amount of diglucuronide. Renal elimination is negligible. Cumulation is possible (mainly with impaired liver function).

Indications:Prevention of arterial and venous thrombosis, including after the operation of prosthetic heart valves; prevention of occlusion of stents and aortocoronary shunts (in combination with acetylsalicylic acid); treatment and prevention of cerebral circulation disorders by ischemic type; encephalopathy; disorders of microcirculation of any genesis (as part of complex therapy); chronic obliterating diseases of the vessels of the lower extremities, especially in the presence of risk factors (arterial hypertension,smoking); primary and secondary prevention of coronary heart disease, especially with intolerance to acetylsalicylic acid; prevention of placental insufficiency in a complicated pregnancy; treatment and prevention of DIC syndrome in children with infectious toxicosis and septicemia; prevention and treatment of influenza and ARVI; perfusion scintigraphy with exercise, dipyridamole stress-echocardiography.

ICD-10

VI.G90-G99.G93.4 Encephalopathy, unspecified

IX.I20-I25.I25 Chronic ischemic heart disease

IX.I60-I69.I63 Cerebral infarction

IX.I60-I69.I67.9 Cerebrovascular disease, unspecified

IX.I70-I79.I73.9 Peripheral vascular disease, unspecified

IX.I70-I79.I74.9 Embolism and thrombosis of unspecified arteries

IX.I80-I89.I82.9 Embolism and thrombosis of unspecified vein

XX.Y83-Y84.Y83.8 Other Surgery

Contraindications:Hypersensitivity, acute myocardial infarction, unstable angina, widespread stenosing coronary artery atherosclerosis, subaortic stenosis of the aorta, decompensated chronic heart failure, arterial hypotension, collapse, severe arterial hypertension,severe disorders of the heart rhythm, hemorrhagic diathesis, chronic obstructive pulmonary diseases, diseases with an increased risk of bleeding (including peptic ulcer and duodenal ulcer), liver failure, chronic renal failure.

Carefully:

To reduce the dyspeptic phenomena are taken with milk.

If coronary steal syndrome occurs, an aminophylline is indicated to improve intracardiac blood flow.

Pregnancy and lactation:

Application in pregnancy and breastfeeding is possible if the intended benefit for the mother exceeds the potential risk to the fetus and the baby (penetrates into breast milk).

The action category for fetus by FDA is B.

Dosing and Administration:

Inside, intravenously. The dose is selected individually, depending on the indications, the severity of the disease and the individual reaction of the patient and is 50-600 mg per day when administered.

For diagnostic purposes, 300-400 mg directly during stress echocardiography or 45 minutes before the injection of the radiopharmaceutical.

Side effects:

From the nervous system and sensory organs: weakness, dizziness, headache, sensation of ear congestion, noise in the head.

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): palpitations, tachycardia, bradycardia, blood flow to the face, coronary steal syndrome (with doses more than 225 mg per day), lowering blood pressure (especially with rapid intravenous administration), thrombocytopenia, changes in the functional properties of platelets, bleeding, increased bleeding.

On the part of the digestive system: nausea, vomiting, diarrhea, epigastric pain.

Allergic reactions: skin rash, hives.

Other: arthritis, myalgia, rhinitis.

Overdose:

Symptoms: short-term reduction in blood pressure and tachycardia.

Treatment: symptomatic therapy, including the administration of vasopressor agents.

Interaction:Antacids reduce C_max dipyridamole due to decreased absorption. Acetylsalicylic acid and indirect anticoagulants increase the effect, heparin increases the risk of hemorrhagic complications. When combined with clopidogrel, the risk of bleeding increases.With simultaneous application with fludarabine, the effects of fludarabine are likely to decrease. Dipyridamole increases the plasma concentration and cardiovascular effects of adenosine. Dipyridamole may interfere with the anticholinesterase effect of cholinesterase inhibitors, therefore potentially exacerbating the course myasthenia gravis. Do not mix in one syringe dipyridamole with other drugs (precipitation may occur).

Special instructions:Not recommended for children and adolescents under 12 years of age (safety and efficacy not determined).

Instructions

Dipyridamole (Dipyridamolum)