Vinpocetine + Indapamide + Metoprolol + Enalapril - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Included in the formulation

Vinpocetine-Acry®

pills inwards

AKRIKHIN HFK, JSC Russia

АТХ:

C.07.F.B.02 Metoprolol in combination with other antihypertensive agents

Pharmacodynamics:

Vinpocetine

It inhibits phosphodiesterase, decreasing the rate of cAMP cleavage, thereby increasing the metabolism of neurons. Promotes the utilization of glucose, increases the amount of dopamine and norepinephrine, activating the adenylate cyclase.

Has vasodilating and antiaggregatory effects, improving the blood supply to the brain. Slightly lowers blood pressure.

Indapamide

Diuretic, a derivative of sulfonamide. Inhibits the reabsorption of sodium in the renal tubules, increases the excretion of sodium and chlorine, enhancing diuresis. Selectively blocks "slow" calcium channels, reduces the overall peripheral resistance of blood vessels, increases the elasticity of the walls of the arteries by reducing the reactivity of the vascular walls to norepinephrine and angiotensin II, enhancing the synthesis of prostaglandins, dilating blood vessels. Has no effect on the metabolism of lipids and carbohydrates.

Metoprolol

Selective β₁-blocker, which does not have internal sympathomimetic activity. Has antihypertensive, antiarrhythmic and antianginal action. In therapeutic doses does not affect the tone of peripheral arteries.

Reduces the effect of catecholamines on the heart muscle, thereby reducing the heart rate, minute and shock volumes of blood within 24 hours.

Eliminates the effects of arrhythmogenic factors: tachycardia, arterial hypertension, increased content of cyclic AMP.

Antianginal action is due to a decrease in myocardial oxygen demand with prolonged diastole and improved perfusion of the heart muscle.

Enalapril

Angiotensin-converting enzyme inhibitor. Prodrug: active metabolite - enalaprilate. Blocking the conversion of angiotensin I in angiotensin II, resulting in a decrease in the release of norepinephrine from the endings of sympathetic fibers, the vasoconstrictor effect, the secretion of aldosterone by the adrenal cortex and increases the bradykinin content by reducing its inactivation by the angiotensin-converting enzyme.

Bradykinin stimulates B₂-cinin receptors of the vascular endothelium, which leads to the rapid release of prostacyclin and other vasodilating substances that cause relaxation of smooth muscles.

Reduces the overall peripheral resistance of blood vessels, without affecting the heart rate. Reduces the aggregation of platelets, improves blood flow of ischemic areas of the heart muscle. With prolonged use there is a decrease in hypertrophy of the left ventricle of the heart.

Pharmacokinetics:

Vinpocetine

After oral administration, up to 70% is absorbed in the gastrointestinal tract. The maximum concentration in the blood plasma is reached after 1 hour. The connection with plasma proteins is 66%. Penetrates through the blood-brain and placental barrier, is found in breast milk.

Metabolism in the liver.

The half-life is 4.8-5 hours. Elimination by the kidneys.

Indapamide

After oral administration, the empty stomach is completely absorbed in the gastrointestinal tract. The maximum concentration in the blood plasma is reached after 1 hour. The connection with plasma proteins is 79%. Therapeutic effect develops 1-2 hours after the start of the procedure.

Penetrates through the blood-brain and placental barrier, excreted in breast milk. Do not cumulate.

Metabolism in the liver.

The half-life is 18 hours. Elimination by the kidneys and with feces in the form of metabolites.

Metoprolol

The maximum concentration is achieved in 2-4 hours.

It binds to plasma proteins up to 16%. Poorly penetrates the blood-brain barrier, penetrates the placenta.

The half-life is 3-7 hours. Partially metabolized in the liver, eliminated by the kidneys: 5% unchanged and 95% - in the form of metabolites. When hemodialysis is not excreted from the blood plasma.

Enalapril

After oral administration, fasted to 60% is absorbed in the gastrointestinal tract. The maximum concentration in the blood plasma is achieved in 1-2 hours. The connection with plasma proteins is 50-60%.

Therapeutic effect develops 1 hour after the start of the treatment, reaches a maximum after 4-6 hours and persists for 24 hours. Metabolism in the liver, hydrolyzed to the active metabolite enalaprilata.

The half-life of enalaprilate is 11 hours. Elimination by the kidneys and with feces. Removed during hemodialysis.

Indications:

It is used for the treatment of arterial hypertension I and II severity in patients older than 45 years.

ICD-10

IX.I10-I15.I10 Essential [primary] hypertension

Contraindications:

Vinpocetine

Age to 18 years, pregnancy and lactation, increased intracranial pressure, hemorrhagic stroke.

Indapamide

Hypokalemia, anuria, severe renal and hepatic insufficiency, acute disturbance of cerebral circulation, individual intolerance.

Metoprolol

Cardiogenic shock, atrioventricular blockade of II-III degree, bradycardia, chronic cardiac insufficiency, resistant to the action of cardiac glycosides, bronchial asthma, renal and hepatic insufficiency.

Enalapril

Porphyria, individual intolerance.

Age to 18 years, pregnancy and lactation, individual intolerance.

Carefully:

Systemic diseases of connective tissue, stenocardia, renovascular hypertension, advanced age, hypersensitivity. Chronic bronchitis with an asthmatic component, obliterating arterial diseases, atrioventricular blockade of the 1st degree, disturbance of the water-electrolyte balance.

Pregnancy and lactation:

Recommendations for the FDA - Category D without teratogenicity. Not applicable in pregnancy and lactation.

Dosing and Administration:

Inside, on an empty stomach, 1 tablet 1 time per day in the morning. If necessary, the dose can be increased to 3 tablets with an interval of 8 hours.

The highest daily dose: 3 tablets.

The highest single dose: 1 tablet.

Side effects:

Vinpocetine

Central and peripheral nervous system: drowsiness, dizziness, headache, weakness.

The cardiovascular system: arterial hypotension, tachycardia, lengthening of the interval QT.

Digestive system: heartburn, dry mouth.

Dermatological reactions: Hyperhidrosis.

Allergic reactions.

Indapamide

Central and peripheral nervous system: headache, asthenia, nervousness, depression, irritability, anxiety, paresthesia.

Respiratory system: pharyngitis, sinusitis, cough, sometimes - rhinitis.

The cardiovascular system: arrhythmias, orthostatic hypotension, palpitation.

Digestive system: anorexia, dry mouth, gastralgia, vomiting, constipation, diarrhea, pancreatitis.

Dermatological reactions: hemorrhagic vasculitis.

Sense organs: visual disturbances, conjunctivitis.

urinary system: nocturia, polyuria.

Reproductive system: decreased potency and libido.

Allergic reactions.

Metoprolol

Central and peripheral nervous system: dizziness, insomnia, asthenia.

Respiratory system: shortness of breath, rarely - bronchospasm

The cardiovascular system: bradycardia, atrioventricular blockade, cold extremities.

Hematopoietic system: neutropenia, thrombocytopenia.

Sense organs: "dry eye syndrome", transient visual impairment.

The digestive system: indigestion, diarrhea, or constipation.

Reproductive system: lowering the potency.

Dermatological reactions: Hyperhidrosis.

Allergic reactions.

Enalapril

Central and peripheral nervous system: cerebral ischemia, headache, dizziness, anxiety, confusion, paresthesia.

Hemopoietic system: anemia, leukopenia, thrombocytopenia, rarely - eosinophilia.

Respiratory system: dry cough, bronchospasm, dyspnea, rhinorrhea, pharyngitis, dysphonia.

The cardiovascular system: hyperkalemia, hyponatremia, orthostatic hypotension, syncope, tachycardia, angina pectoris, myocardial infarction.

Digestive system: nausea, cholestatic jaundice, constipation, dry mouth.

urinary system: hypercreatininaemia, proteinuria, increased urea levels, development or progression of chronic renal failure.

Dermatological reactions: onycholysis, alopecia.

Reproductive system: decreased potency.

Allergic reactions.

Overdose:

Vinpocetine

Increased side effects.

Treatment is symptomatic.

Indapamide

Drowsiness, dizziness, confusion, respiratory depression. Patients with cirrhosis develop hepatic coma.

Treatment is symptomatic.

Metoprolol

Pronounced bradycardia, arterial hypotension.

Treatment: intravenously 1-2 mg atropine, 2.5 μg / kg dobutamine, intravenously bolus 10 mg glucagon, intravenously drip 10-20 μg isoprenaline at a rate of not more than 5 μg / min.

Enalapril

Pronounced decrease in blood pressure, electrolyte imbalance, bradycardia, cardiovascular shock, renal failure.

Treatment: intravenous epinephrine, blood substitution solutions, hydrocortisone, angiotensin injection II, hemodialysis.

Interaction:

Vinpocetine

Strengthens the effect of antihypertensive drugs.

With simultaneous use with anticoagulants, the risk of hemorrhagic complications increases.

Indapamide

By reducing the excretion in the urine increases the concentration of lithium ions, which increases the risk of developing nephrotoxic action.

Cardiac glycosides, saluretics, mineralo- and glucocorticoids, amphotericin B (with intravenous administration), tetracosactide, laxatives increase the state of acidosis.

With simultaneous use with calcium preparations, hypercalcemia develops.

Reduces the hypotensive effect of glucocorticosteroids, non-steroidal anti-inflammatory drugs, sympathomimetics, tetracosactide.

Strengthens the hypotensive effect baclofen.

With the simultaneous use of iodine-containing contrast agents, dehydration develops.

Antipsychotic drugs and antidepressants strengthen the hypotensive effect, which can lead to orthostatic collapse.

Reduces the effect of indirect anticoagulants by increasing the concentration of coagulation factors, due to increased production of liver and reducing the volume of circulating blood.

Strengthens the effect of nondepolarizing muscle relaxants.

Metoprolol

Increases the concentration of ethanol in the blood and lengthens its excretion.

Potentiates the effect of lidocaine in systemic application.

Negative dromo-, foreign, chromotropic influences are intensified with simultaneous admission with amiodarone, anesthetics, antiarrhythmics, digoxin, diltiazem, verapamil.

Increases the bioavailability of metoprolol together with cimetidine.

Enalapril

Strengthens the hypoglycemic action of insulin and oral hypoglycemic drugs.

Enhances the toxic effects of lithium preparations.

Sodium chloride, non-steroidal anti-inflammatory drugs reduce the hypotensive effect of perindopril.

With simultaneous use with potassium-sparing diuretics (amiloride, triamterene, spironolactone), products with a high content of potassium develops hyperkalemia.

When used simultaneously with cytostatics, allopurinol, systemic glucocorticosteroids, procainamide, immunosuppressants increase the risk of developing leukopenia.

With simultaneous use with drugs for general anesthesia and for local anesthesia, it is possible to develop arterial hypotension.

Special instructions:

During surgical interventions during the treatment with enalapril, it is possible to develop arterial hypotension, which should be corrected by the introduction of a sufficient amount of fluid.

Indapamide can give a positive result in the conduct of doping control.

In the treatment it is not recommended to drive vehicles and work with moving mechanisms.

Instructions

Vinpocetine + Indapamide + Metoprolol + Enalapril (Vinpocetinum + Indapamidum + Metoprololum + Enalaprilum)