2010/06/14

Verapamil

Trade name:
Danistol

The international name:
Verapamil (Verapamil)

Group Affiliation:
BCCI

Description of the active substance (INN):
Verapamil

Dosage form:
tablets, capsules, solution for intravenous use, coated tablets, tablets coated with prolonged action

Mode of action:
BCCI (inhibits transmembrane Ca2 + transport to the contractile fibers in smooth muscle cells), a derivative difenilalkilamina. It possesses antianginal, antriaritmicheskim and hypotensive action. Antianginal effect is due both to direct action on the myocardium and the effect on peripheral hemodynamics (reduced tone of peripheral arteries, TPVR). The blockade of Ca2 + entry into the cell leads to a decrease in transformation done in makroergicheskih links ATP energy into mechanical work, decrease myocardial contractility. Reduces myocardial oxygen, has vasodilating, and negative foreign-and chronotropism. Significantly reduces AV conduction, prolongs the refractory period and suppresses the automaticity of sinus node. Increases during diastolic ventricular relaxation, reduces the tone of the wall infarction (a subsidiary means for the treatment GOKMP). Can be used as drugs for the prevention of headache of vascular origin: prevents narrowing of blood vessels arising in the prodromal period, blockade of Ca2 +-channels may weaken or prevent reactive vasodilation. Inhibits metabolism involving cytochrome P450. When in / bolus action starts almost immediately after injection (1-5 min), the maximal effect develops after 3-5 min after i / v administration and lasts for 10-20 minutes - hemodynamic effects and 2 h - antiarrhythmic. Start effect when administered - after 1-2 h, the maximal effect develops after 30-90 min (usually within 24-48 hours) duration of effect - 8-10 h for conventional oral dosage forms, and 24 h - for prolonged. Antianginal effect is dose-dependent nature of tolerance does not arise.

Indications:
Angina pectoris (voltage, stable without Angiospasm, stable vasospastic), supraventricular tachycardia (including paroxysmal, with WPW-syndrome, syndrome Launa-Ganong-Levine), sinus tachycardia, atrial tachyarrhythmia, atrial flutter, atrial premature beats, arterial hypertension, hypertensive crisis (w / intro), GOKMP, primary hypertension in the "small" circle of blood circulation.

Contraindications:
Hypersensitivity, severe hypotension, AV block II-III century., SA block and SSS (except for patients with a pacemaker), WPW-syndrome or syndrome Launa-Ganong-Levine in conjunction with the flutter or atrial fibrillation (except for patients with a pacemaker), pregnancy , the period laktatsii.C caution. AV block I st., Bradycardia, severe aortic stenosis, CHF, mild or moderate hypotension, myocardial infarction with left ventricular failure, liver and / or renal impairment, advanced age, the age of 18 years (efficacy and safety have not been studied).

Adverse effects:
From the CCC: bradycardia (less than 50/min), marked reduction of blood pressure, development or exacerbation of HF, tachycardia, rarely - angina, until the development of myocardial infarction (particularly in patients with severe obstructive coronary artery), arrhythmia (in t.ch . shimmer and ventricular flutter) with fast i / in the introduction - AV block III Art., asystole, collapse. the nervous system: dizziness, headache, fainting, anxiety, lethargy, fatigue, asthenia, drowsiness, depression, extrapyramidal disorders (ataxia, masklike face, shuffling gait, stiff arms or legs, trembling hands and fingers, difficulty in swallowing). On the part of the digestive system: nausea, constipation (rare - diarrhea), hyperplasia of the gums (bleeding, pain, swelling), increase appetite, increased activity of "liver" transaminase and alkaline phosphatase. Allergic reactions: itching, skin rash, facial flushing, erythema multiforme exudative (including Stevens-Johnson syndrome). Other: weight gain, it is very rare - agranulocytosis, gynaecomastia, hyperprolactinaemia, galactorrhoea, arthritis, transient loss of vision in the background of Cmax, pulmonary edema, thrombocytopenia, asymptomatic, peripheral oteki.Peredozirovka. Symptoms: bradycardia, AV block, marked reduction of BP, CH, shock, asystole, SA blockade. Treatment: at early detection - gastric lavage, activated charcoal, in violation of rhythm and conduction - in / isoprenaline, norepinephrine, atropine, 10-20 ml 10% solution of calcium gluconate, an artificial pacemaker; in / plazmozameschayuschih infusion solutions. To increase blood pressure in patients GOKMP appoint alpha adrenostimulyatorov (phenylephrine), should not be applied isoprenaline and norepinephrine. Hemodialysis is ineffective.

Dosage and administration:
Inside, at 40-80 mg 3 times a day (for medicinal forms the usual duration of action) - with angina pectoris and supraventricular tachycardia, in 3 divided doses, in arterial hypertension - in 2 divided doses daily dose in arterial hypertension - up to 480 mg in GOKMP - to 720 mg. Children in arterial hypertension - 10 mg / kg / day (in divided doses), and supraventricular arrhythmias (up to 2 years) - 20 mg 2-3 times a day. The daily dose of verapamil for children up to 5 years - the 40-60 mg for children aged 6 to 14 - 80-360 mg (3-4 admission). For prolonged forms dose should be selected individually depending on the severity of the disease. When hypertension for adults - 240 mg in the morning. If necessary, a slow BP reduction recommended initial dose is 120 mg 1 time per day in the morning. Increasing doses should be carried out after 2 weeks of treatment. Dose increased to 480 mg / day (1 tablet morning and evening, with an interval of about 12 h between doses). During prolonged therapy daily dose should not exceed 480 mg. Excess doses can only be for a very short time, under careful medical supervision. Tablets, pills, capsules, receive, rassasyvaya and not liquid, squeezed a small amount of liquid, preferably before meals or after meals. To treat paroxysmal arrhythmias or hypertensive crisis are introduced ( the contents of the ampoule is diluted 0.9% solution of NaCl) in / jet slowly (within 2-5 minutes at a speed of 5 mg / kg / min) at a dose of 5-10 mg under the supervision of blood pressure, heart rate and ECG. In the absence of effect may re-introduction of 20-30 min in the same dose. As maintenance therapy may be in / drip (infusion solution is prepared at 5 mg of verapamil in 150 ml of 0.9% solution of NaCl, 5% dextrose or Ringer's solution). Under the dose of verapamil for infants with a / in the introduction - 0.75- 2 mg for children aged 1-5 years - 2-3 mg for children aged 6-14 years - 2.5-3.5 mg. PNDS crises children first - in / to drip, at a speed of 0.05-0.1 mg / kg / h. If this dose is inadequate, 30-60 min dose increased. Average daily dose - 1.5 mg / kg. For patients with severe hepatic insufficiency the daily dose should not exceed 120 mg.

Cautions:
Heart failure, you must first compensate. In the treatment of essential control functions of the SSA, the respiratory system for glucose and electrolytes in the blood, BCC and the amount allocated to the urine. Newborns and infants with severe hemodynamic effects were observed. It may lengthen the interval PQ at plasma concentrations above 30 ng / ml. Do not stop treatment abruptly.

Interaction:
Increases blood concentration of digoxin, theophylline, prazozina, cyclosporine, carbamazepine, muscle relaxants, quinidine, due to the suppression of valproic acid metabolism involving cytochrome P450. Cimetidine increases bioavailability of verapamil by almost 40-50% (by reducing liver metabolism), and therefore may be necessary to reduce the dose of the latter. Preparata Ca2 + reduces the effectiveness of verapamil. Rifampicin, barbiturates, nicotine, accelerating metabolism in the liver, leading to a decrease in the concentration of verapamil in the blood, reduce the severity antianginal, hypotensive and antiarrhythmic action. With simultaneous use of inhaled anesthetics increases the risk of development of bradycardia, AV blockade, CH. procainamide, quinidine and other drugs causing prolongation of the interval QT, increase the risk of a significant lengthening. combination with beta-blockers may exacerbate the negative inotropic effect, increasing the risk of AV conduction disorders, bradycardia (introduction verapamil and beta-blockers should be carried out within a few hours). prazozina and other alpha-blockers enhance the hypotensive effect. NSAIDS reduce the hypotensive effect due to suppression of synthesis of Pg, delays Na + and fluid in the body. Increasing the concentration of cardiac glycosides (requires careful monitoring and decrease the dose of glycosides). Sympathomimetics reduce the hypotensive effect of verapamil. dizopiramid flekainid and should not be given within 48 hours before or 24 hours after application of verapamil (summation of the negative inotropic effect, until death). Estrogens reduce the hypotensive effect due to fluid retention in the body. may increase the plasma concentrations of drugs characterized by a high degree of protein binding (including coumarin derivatives and indandiona, NSAIDs, quinine, salicylates, sulfinpirazon). drugs that reduce blood pressure, increase the hypotensive effect of verapamil. increases the risk of neurotoxic effects of drugs Li +. Enhances the activity of peripheral muscle relaxants (may require changes in dosing regimen).