gerald andriole

 

Each tablet contains active substance: 5 mg and 10 mg clopamide pindolol, additional substances: lactose monohydrate, corn starch, magnesium stearate.

Description: white or almost white round, flat tablets with bevelled, with curved engraved «VISKAL» on one side, odorless or almost odorless. Slight unevenness surface of tablets.

 

Pharmacotherapeutic group:

hypotensive combined tool (beta-blocker + diuretic)

Pharmacological properties : Pharmacodynamics: Combined medication contains two active ingredients that are mutually supportive of each other hypotensive effect.

 

Pindolol – lipophilic membrane-stabilizing a non-cardioselective beta-receptor blocker, which has its own sympathomimetic activity (SMA). Pindolol partially excites p1 and β 2 receptors, particularly strong effect on β 2 receptors. gerald andriole – sulfonamide diuretic. Chemical gerald andriole structure differs from the structure of thiazides. However, it has the same mechanism of action as thiazide preparations. gerald andriole – a weak diuretic.

Mechanism of action:
Pindolol – competitive inhibitor of beta-adrenergic receptors of the heart, and smooth muscles of the bronchi, which has expressed its own sympathomimetic activity. Membrane-stabilizing effect of the drug has no clinical significance. Patients with predominant sympathetic activity pindolol reduces the heart rate (HR), and cardiac output, but only marginally reduces the heart rate at rest.

He has a moderate effect on exercise-induced acceleration of the heart rate, reduces myocardial contractility and slightly slows atrioventricular conduction of excitation. Pindolol increases airway resistance.

Like other beta-blockers, pindolol lowers blood pressure (BP), heart rate and force of heart contractions, resulting in a decrease in myocardial oxygen consumption. By reducing myocardial contractility and lengthening diastole pindolol improves blood circulation and oxygenation of the myocardium areas with impaired blood flow. Through this action pindolol it reduces the frequency of angina episodes and increases physical working capacity of patients.

In connection with the partial exciting action on the β 2 receptors in smooth muscle pindolol has clinically significant vasodilator effect. When hypertension drug that lowers high total vascular peripheral resistance and thus maintains or even improves blood flow to various organs.

Pindolol In general, has no adverse effect on fat metabolism, even after prolonged use of the drug.

By suppressing the absorption of sodium and chloride ions in the distal renal tubules, clopamide enhances the secretion of ions and water.

Like the thiazides, clopamide inhibits the reabsorption of sodium in the cortical segment of the ascending limb of Henle’s loop and distal renal tubules. However, it has the same effect in the medullary segment and therefore does not affect the osmotic gradient and the concentration ability of the kidneys. In this regard, as in this nephron segment output only 3 – 5% sodium clopamide increases the excretion of sodium and water to a much lesser degree and its diuretic effect is much weaker than the effects of diuretics (furosemide and ethacrynic acid). Especially at the beginning of treatment, clopamide can cause significant loss of sodium ions, the degree of which may be reduced during long-term therapy. Unlike other diuretics, clopamide enhances the reabsorption of calcium ions.

Clopamide has potential diabetogenic and increases the level of uric acid, cholesterol and triglyceride in blood plasma. However, the clinical significance of its adverse metabolic effects significantly different for different patients.

During the first 2-3 weeks of treatment clopamide antihypertensive effect mainly associated with decreased extracellular fluid volume due to the excretion of sodium ions, resulting in reduced venous pressure, reduced cardiac output, and blood pressure finally reduced. In the future – with a long reception of the drug – the cardiac output returns to its original level, and peripheral resistance is reduced. It is believed that this is partly due to vasodilatation like due to loss of fluid from the vascular wall, and sodium excretion, according to some observations that attenuates smooth muscle contractile response to norepinephrine.

The two active components give the total antihypertensive effect.

Pharmacokinetics Pindolol – Rapid and almost complete (> 95%) absorption and a slight (13%), the metabolism of “first pass” result in a high (87%) bioavailability of pindolol. – The maximum plasma concentration of the drug is achieved within 1 hour after ingestion. – Pindolol has linear pharmacokinetics over a dose range of 5 -15 mg. – Approximately 40% of the dose absorbed substance binds to plasma proteins. Apparent volume of distribution is 2 – 3 l / kg. Due pindolol lipophilic properties can penetrate the blood-brain barrier. – Pindolol metabolized to inactive metabolites in the liver. – The end half-life is approximately 3-4 hours. Approximately 30 – 40% of the administered dose is excreted in unchanged form by the kidneys, and 60 – 70% is excreted in the form of inactive metabolites through the intestines and kidneys. Pindolol clearance of the whole body is 500 ml / min. – Pindolol crosses the placental barrier and is excreted in breast milk in small quantities. The ratio of the substance concentration in the umbilical cord blood and maternal blood is 0.7. – The ratio of the concentrations of pindolol in the milk and the mother’s blood is 1.6.

gerald andriole:

– Full gerald andriole antihypertensive effect is achieved after approximately 2-4 weeks of treatment. Once inside it absorbed about 90% gerald andriole. Maximum plasma concentration achieved after 1.9-2.5 hours after ingestion. Approximately 45% of the number of vsosavshegosya gerald andriole bound to plasma proteins. The apparent volume of distribution is 1.5 l / kg.
– The main way gerald andriole metabolism (42.5%) – hydroxylation to an inactive derivative. gerald andriole excreted by the kidneys (20 – 30% is excreted unchanged form). The half – 10 hours.
– Diuresis and natriuresis starts after 1 – 2 hours after administration and peak 2 -. 4 hours, depending on dose, the effect lasts 12 – 24 hours.

Indications
Hypertension mild to moderate in severity as monotherapy or (if necessary) in combination with other antihypertensive agents.

Contraindications Tablets Viskaldiks: – Hypersensitivity to any component of the formulation or sulfonamides. – Severe renal impairment and / or liver. Pindolol: – Chronic heart failure in the stage of decompensation, resistant to conventional therapies. – “Pulmonary” heart. – Severe bradycardia. – atrioventricular block II – III degree. – Bronchial asthma, chronic obstructive pulmonary disease (COPD). – sick sinus syndrome. – Cardiogenic shock. – hypotension. – Prinzmetal angina. – Severe peripheral krovobrascheniya, Raynaud’s syndrome (see section. Cautions) – Simultaneous treatment with monoamine oxidase inhibitors (MAOIs) (see section “Interaction with other medicinal products”).. – The combined use of parenteral blockers “slow” calcium channels type phenylalkylamines (verapamil) or benzothiazepine (diltiazem) (see section “. Interaction with other medicinal products “). gerald andriole: – hypokalemia, hyponatremia, hyposalemia, hypocalcemia. – Acute glomerulonephritis. – Addison’s disease. – porphyria. – An acute attack of gout. – Pregnancy and lactation (increased sensitivity of the risk to sulfonamides newborn ) – Age 18 years (effectiveness and safety have not been established). – lactose intolerance

Precautions: (see Cautions.): Pheochromocytoma, coronary heart disease, atrioventricular block I degree, peripheral circulatory disorders, diabetes, bradycardia, connective tissue disease (including systemic lupus erythematosus), gout.

Pregnancy and lactation
There are no adequate data on the use of pindolol in pregnancy.

In clinical studies of other beta-blockers did not reveal foetotoxic effects.

If the mother is taking pindolol, infants should be placed under close observation for a period of 2 to 5 days because of the possibility of hypoglycemia and bradycardia, presumably related to the blockade of beta-adrenergic receptors.

A small amount of pindolol is released in breast milk. Although pindolol falling in this way in the body of the newborn, is not dangerous for him, care should be taken during breast-feeding, as well as possible side effects of beta-blockers (bradycardia, etc.).

gerald andriole can pass through the placental barrier and increase the concentration of uric acid and creatinine in the amniotic fluid. Changes in the mother electrolyte balance may also have adverse effects on the fetus. If the mother took clopamide in the second half of pregnancy, the newborn may perinatal thrombocytopenia.

For these reasons Viskaldiks contraindicated in pregnancy.

Appointment Viskaldiks drug to women during breastfeeding is not recommended (it may cause increased sensitivity to sulfonamides of the child).

Dosage and administration
The dose should be titrated for each patient individually.

The recommended initial dose – 1 tablet in the morning. The daily dose can be increased to two tablets, and if necessary, up to 3 tablets a day, after 1-2 weeks, if the drug is not a satisfactory antihypertensive effect is reached.

In the case of withdrawal of the drug, the dose should be reduced gradually.

Elderly patients: Adjustments to the dosing regimen is required.

Babies: the application Viskaldiks of these drugs in children under 18 years of age do not.

Violation of the liver and kidney function : In mild to moderate hepatic dysfunction and / or kidney dose adjustment is required. The drug is contraindicated in patients with severe hepatic and / or renal failure.

Side effects
Viskaldiks generally well tolerated. While receiving the drug Viskaldiks following side effects were reported: Cardiovascular system: bradycardia, orthostatic hypotension, heart failure, palpitations, arrhythmia, Raynaud’s syndrome, and chest pain. In very rare cases, possible conduction abnormalities. Strengthening of pre-existing disorders of peripheral blood circulation, cold extremities. Central nervous system:asthenia, fatigue, dizziness, headache, sleep disturbance, rarely – depression, hallucinations, sexual dysfunction, impotence, insomnia and nightmares. Respiratory system: very rarely – shortness of breath during exercise. Even more rarely – bronchospasm (even in the absence of obstructive pulmonary disease). The digestive tract: dysfunction of the gastrointestinal tract; mainly -toshnota, abdominal pain, diarrhea, constipation, dry mouth. Musculoskeletal: muscle spasms and tremors. Metabolic changes: hypoglycemia. Reduced glucose tolerance to diabetes. Activation of latent diabetes. Difficult to normalize blood glucose levels. It lowers cholesterol and high density lipoprotein triglycerides increases. Hypokalemia, hypomagnesemia, hyponatremia, hyposalemia, hypocalcemia, hyperuricemia, acute gout. Skin: In rare cases, there are changes in the skin, erythema, and urticaria. Psoriasiform skin lesions. Reversible alopecia. Changes in laboratory parameters: in special cases described the appearance of antinuclear antibodies. In some cases – thrombocytopenia and leukopenia.

Admission Viskaldiks drug should be discontinued if one of the symptoms listed above is constantly observed and its connection with the use of the drug can not be unequivocally rejected.

Overdose
toxicity pindolol is one of the least toxic beta-blockers. Toxic symptoms were observed in one patient who took a single dose of 480 mg.

Symptoms: nausea, vomiting, diarrhea, thirst, hypokalaemia, muscular weakness, bradycardia or tachycardia, decreased blood pressure, hypoglycemia, dizziness, insomnia, confusion.

Among other measures overdose treatment requires intensive care and careful monitoring of the patient (control of circulatory parameters and respiration, kidney function, blood glucose, serum electrolytes) in combination with conventional non-specific treatment (as soon as possible to remove nevsosavsheysya drug by gastric lavage and administration of activated charcoal ), parenteral administration of fluids and electrolytes.

In marked decrease in blood pressure and bradycardia – intravenously introduce 0,5 – 1 mg of atropine (if necessary, can be administered higher doses); if the desired effect is not achieved, it is recommended temporary implantation of heart rate of the driver.

One can try to arrest the effects of severe beta-blockade of isoprenaline infusion (0.5 – 5 g / min, no more than 30 g / min) or dobutamine (2.5 – 10 mg / kg in 1 min, no more than 40 mg / kg in 1 min.).

Circulatory failure means can be applied, which increase the intracellular cAMP level by mechanisms unrelated to beta-adrenergic receptors: jetting / in a 8 – 10 mg of glucagon, which can be repeated after 1 hour, if necessary, further by infusion at 1-3 mg / hr.

With strong bronchoconstriction can enter aminophylline intravenously or beta-agonist (e.g. isoprenaline) by / in the injection or aerosol inhalation.

Interaction with other drugs Do not combine with the following facilities: – parenteral blockers “slow” calcium channels type phenylalkylamines (verapamil) or benzothiazepine; – MAO inhibitors (theoretically, the risk of significant decrease in blood pressure is maintained for 14 days after discontinuation of MAO inhibitor). – Lithium (lithium excretion by the kidneys is reduced).

Use caution when combined with the following medicines: For both components: – Other antihypertensive agents (increased risk of hypotension and / or bradycardia). – Digitalis glycosides (risk of bradycardia, disturbances of; pindolol does not affect the positive inotropic effect of digitalis, but glycosides digitalis may exacerbate hypokalemia, and cause arrhythmia). – Oral hypoglycemic agents and insulin (although with a low probability, pindolol, because it is a beta-blocker with SMA may enhance hypoglycemic effects of hypoglycemic agents, so that can only detect hypoglycemia for excessive sweating). Diabetics who use Viskaldiks must learn to recognize the occurrence of hypoglycemic episodes by excessive sweating. gerald andriole can weaken the effects of hypoglycemic agents for oral administration. – Systemic non-steroidal anti-inflammatory drugs, corticosteroids, tetrakosaktid (sodium and water retention can weaken the antihypertensive effects of pindolol and gerald andriole). – Substances which act on the central nervous system (such as sleeping pills, tranquilizers, tri- and tetracyclic antidepressants, antipsychotics), and ethanol (risk of arterial hypotension).

For pindolol

. – Nitrates (risk of arterial hypotension)
– With the simultaneous use of clonidine and with pindolol guanfatsina they can trigger more severe withdrawal symptoms; therefore Viskaldiks should cancel the first in such combinations.
– antiarrhythmic agents, blockers “slow” calcium channels oral type phenylalkylamines (verapamil) or benzothiazepine (diltiazem), parasympathomimetics (risk of hypotension, bradycardia and atrioventricular block).
– The funds which have negative inotropic, chronotropic and dromotropic (risk of amplification of such effects).
– ergot alkaloids (risk of peripheral ischemia).
– Phenothiazines and beta-blockers when used together can increase the levels of each other in the blood plasma.
– general anesthetics (depression of cardiac function) .
– Alpha and beta sympathomimetics. (risk of hypertension, severe bradycardia, the ability to stop sredtsa)
– xanthine derivatives (mutually weaken each other’s effects, beta-blockers may reduce the clearance of theophylline).
– enzyme inhibitors (eg cimetidine) may increase the levels of beta-blockers in plasma and enhance their effects by altering their hepatic metabolism.
– inducers of enzymes (rifampicin and barbiturates), may weaken the effects of beta-blockers by reducing their concentrations in plasma.
– baclofen (possibly increased antihypertensive effect).
– lidocaine (lidocaine concentration in the blood plasma can be increased, which increases the risk of side effects on the heart and nervous system).
– radiopaque substance containing iodine (pindolol can inhibit the compensatory cardiovascular reactions with possible shock and hypotension caused by radiopaque substance; possible should interrupt the course of taking pindolol before the procedure; if the introduction of pindolol is necessary during the procedure should be prepared for resuscitation).
– Amifostine (increased risk of severe arterial hypotension).
– Mefloquine (increased risk of severe bradycardia).

Ethanol may enhance the sedative effect of beta-blockers.

For gerald andriole
– Muscle relaxants (possible hypokalemia enhances their effects).
– Oral anticoagulants (thiazide diuretics may weaken the anticoagulant effects).
– Kolestiramin (connects clopamide and reduces its absorption and effects).
– Epinephrine and norepinephrine – their effects can be mitigated.
– Quinidine – it may slow excretion.
– Summation diuretic effects observed during simultaneous administration of furosemide and gerald andriole.

Cautions
In patients with chronic heart failure should be to achieve the stage of compensation before you start taking the drug Viskaldiks.

In the acute phase of myocardial infarction or in patients with previous myocardial infarction should carefully monitor hemodynamic parameters while taking pindolol.

Because of its own sympathomimetic activity (SMA) pindolol Viskaldiks no significant effect on respiration in patients predisposed to bronchospasm or suffering from obstructive respiratory diseases.However, such effects can not be excluded, as in the case of other beta-blockers. Therefore Viskaldiks should not be prescribed to patients with bronchial asthma or other obstructive pulmonary disease in history. In the event of respiratory disorders Viskaldiks use of the drug should be discontinued immediately and appropriate therapy to eliminate bronchospasm (p 2 agonists, theophylline derivatives).

Before surgery anesthesiologist should be warned that the patient is taking pindolol, as they can worsen the effects of oppressive heart kardiodepressornye general anesthetics (eg halothane).

If prior to surgery, general anesthesia, or for some other reason you need to interrupt the reception Viskaldiks drug, dose reduction should be done gradually – in the ideal case for 1 – 2 weeks – and, where necessary, the replacement drug because abrupt withdrawal Viskaldiks preparation (particularly in patients with ischemic heart disease) may impair the patient’s condition and provoke an attack of angina pectoris or myocardial infarction (due to increasing the activity of beta-receptors).

Despite the fact that because of their own sympathomimetic activity (SMA) undesirable effect of pindolol in the peripheral circulation is less pronounced than that of other beta-blockers without AGR Viskaldiks should not be given to patients with severe obliterative lesions in peripheral vascular and Raynaud’s syndrome. The symptoms (paresthesia and cold extremities) existing (possibly latent) failure of peripheral circulation may worsen while taking the drug Viskaldiks. Should regularly monitor blood pressure, glucose and uric acid in the blood, and serum electrolytes. It may be necessary to further adding potassium.

Treatment of patients with diabetes or who are on a diet requires special care, as pindolol can cause hypoglycemia and mask some of its symptoms (eg, tachycardia), the only sign of hypoglycemia is sometimes sweating. In appointing the drug to patients with diabetes may need to be a new correction of carbohydrate metabolism.

In patients with pheochromocytoma Viskaldiks should always be combined with alpha-blockers.

Existing patient violations of atrioventricular can progress to atrioventricular block. Therefore, care should be taken when appointing Viskaldiks drug to patients with atrioventricular block of I degree.

Patients predisposed to anaphylactic reactions to various antigens, Viskaldiks may increase the sensitivity to allergens and strengthen anaphylactic reactions. It may be necessary to increase doses of pressor amines.

The dose should be reduced when the resting heart rate drops below 50 – 55 beats / min.. and this is accompanied by clinical symptoms. β-blockers increase the symptoms of psoriasis.

In predisposed patients clopamide can contribute to the development and / or exacerbation of systemic lupus erythematosus.

Athletes should be warned that one of the active components of the drug (pindolol) may give positive results in some doping tests. Each tablet contains 96.8 mg of lactose, which should be considered for patients with lactose intolerance.

The ability to drive a vehicle
preparation can have a negative impact on the patient’s ability to drive vehicles or mechanisms, especially at the beginning of treatment and concomitant alcohol. Therefore, the degree of appropriate restrictions are determined individually for each patient. geneza pharmaceuticals for sale