Tenochek, tablets 28 pcs

Tenochek is a combined antihypertensive drug.

Pharmacodynamics

The effect is due to the action of two components – a beta1-adrenoblocker (atenolol) and a “slow” calcium channel blocker, (amlodipine).

The fixed combination of Atenolol and Amlodipine is considered the most effective combination when considered from the perspective of metabolic and hemodynamic interaction of drugs. Amlodipine administration leads to dilatation of arterioles, manifested by reflex tachycardia. This is one of the main side effects of Amlodipine.

The increase in heart rate leads to increased myocardial oxygen demand, which is undesirable for patients with coronary heart disease. As a selective blocker of β₁-adrenergic receptors, Atenolol levels out the reflex tachycardia caused by Amlodipine administration. Clinical studies in recent years have demonstrated a favorable effect of therapy with “slow” calcium channel blockers on the blood lipid spectrum, which helps to reduce the risk of cardiovascular outcomes. The complementary mechanism of action of Amlodipine which decreases general peripheral vascular resistance and Atenolol which reduces cardiac output results in more pronounced hypotensive effect and better tolerability in comparison with Amlodipine and Atenolol monotherapy, improving efficiency/side effect ratio.

Atenolol: has antianginal, hypotensive and antiarrhythmic effects. It does not have membrane stabilizing and intrinsic sympathomimetic activity. Reduces stimulation by catecholamines of cAMP and ATP formation, reduces intracellular Ca²⁺ flow. In the first 24 hours after oral administration, against a background of decreased cardiac output, there is a reactive increase in total peripheral vascular resistance, the severity of which gradually decreases over 1-3 days. Hypotensive effect is associated with decreased cardiac output, decreased activity of the renin-angiotensin system, barocereceptor sensitivity and influence on the central nervous system. The hypotensive effect is manifested by a decrease in systolic and diastolic blood pressure, a decrease in stroke and minute volumes. In medium therapeutic doses, it has no effect on peripheral arterial tone. The hypotensive effect lasts for 24 hours and with regular administration is stabilized by the end of 2 weeks of treatment.

The antianginal effect is determined by decreasing myocardial oxygen demand as a result of decreasing heart rate (prolongation of diastole and improvement of myocardial perfusion) and contractility and decreasing myocardial sensitivity to sympathetic innervation. It decreases the heart rate at rest and during physical activity. By increasing ventricular muscle fiber tension and left ventricular end diastolic pressure, it may increase myocardial oxygen demand, especially in patients with chronic insufficiency. Antiarrhythmic action is manifested by suppression of sinus tachycardia and is associated with the elimination of arrhythmogenic sympathetic effects on the cardiac conduction system, inhibition of heterogeneous automatism, reduction of the rate of excitation spread through the sinoauricular node and prolongation of the refractory period. Inhibits impulse conduction in antegrade and, to a lesser extent, in retrograde direction through the atrioventricular node and along accessory pathways.
Increases survival of patients who had myocardial infarction (reduces the frequency of ventricular arrhythmias and attacks of angina pectoris).

In therapeutic concentrations it has no effect on beta-2-adrenoreceptors; in contrast to non-selective beta-adrenoborcators it has less significant effect on the smooth muscle of the bronchi and peripheral arteries and on lipid metabolism. It slightly reduces the vital capacity of the lungs, practically does not weaken the bronchodilator effect of isoproterenol. When taken more than 100 mg per day it may have beta-2-adrenoblocking effect. The negative chronotropic effect appears 1 hour after intake, reaches a maximum after 2-4 hours and lasts up to 24 hours. Amlodipine: a dihydropyridine derivative. It has antihypertensive, atnyanginal, antispasmodic and vasodilator effects. It blocks entry of calcium ions through cell membranes into myocardial and vascular smooth muscle cells.

The mechanism of hypotensive action is caused by direct relaxant effect on smooth muscles of blood vessels.
Antiinflammatory effect of the drug is due to, firstly, its ability to dilate peripheral arterioles which leads to decrease of total peripheral vascular resistance. Decrease of heart load leads to decrease of myocardial oxygen demand. Secondly, under the action of the drug, due to the expansion of the coronary arteries, the flow of oxygen to the myocardium increases (especially in vasospastic angina pectoris). Amlodipine has no adverse effect on metabolism and blood plasma lipids, has antiatherosclerotic, antithrombotic activity, increases glomerular filtration rate, has a weak natriuretic effect. In diabetic nephropathy it does not increase the severity of microalbuminuria.

Pharmacokinetics

Athenololol: After oral administration the drug is quickly absorbed from the gastrointestinal tract – approximately 50% of the oral dose. Fat solubility is poor, bioavailability is 40-50%, time to reach maximum plasma concentration after oral administration – 2-4 hours. It penetrates poorly through the blood-brain barrier, passes in small amounts through the placental barrier and into breast milk. Binding with blood plasma proteins is 6-16%.

It is practically unmetabolized in the liver. The elimination half-life is 6-9 hours (it increases in elderly patients). Excreted by kidneys through glomerular filtration (85-100% unchanged). Impaired renal function is accompanied by prolongation of T_&frac; and cumulation, with creatinine clearance below 35 mg/min/1.73 m² , T_&frac; is 16-27 hours, with clearance below 15 mg/min over 27 hours (dose reduction required). It is excreted during hemodialysis.

Amlodipine: After oral administration amlodipine is rapidly absorbed from the gastrointestinal tract by 90%, the maximum concentration of the drug in blood is observed after 6-12 hours. The equilibrium concentration of the drug in blood plasma is reached after 7-8 days after its continuous administration.

The drug has high volume of distribution – about 20 l/kg; bioavailability is 60-65%, compliance with blood plasma proteins is high – more than 95%. T_½ of the drug is 35-45 hours. It is metabolized mainly in liver with formation of inactive metabolites. Less than 10% of the dose taken orally is excreted unchanged, about 60% is excreted by the kidneys as inactive metabolites; 20-25% is excreted as metabolites in the bile and intestine, as well as with the breast milk. It penetrates through the blood-brain barrier.

Indications

Arterial hypertension; prevention of angina attacks

Active ingredient

Composition

1 tablet contains the active ingredients:

How to take, the dosage

Ingestion with the required amount of liquid.

In case of arterial hypertension and angina pectoris, the dose is 1 tablet daily.

If necessary, the daily dose can be increased to 2 tablets daily.

The maximum daily dose is 2 tablets.

Interaction

In concomitant use of atenolol and insulin (or other oral hypoglycemic agents), it masks the symptoms of hypoglycemia. When concomitant use with antihypertensive agents of other groups the hypotensive effect is increased. The hypotensive effect is weakened by estrogens (sodium retention).

The simultaneous use of atenolol and cardiac glycosides increases the risk of bradycardia and atrioventricular conduction disorders. Simultaneous use of atenolol with reserpine, methyldopa, clonidine, verapamil may result in marked bradycardia. Patients taking atenolol and clonidine concomitantly should be discontinued clonidine only after several days after stopping treatment with atenolol. When concomitant use of atenolol with derivatives of ergotamine, xanthine its effectiveness decreases.

Simultaneous use with lidocaine may decrease its excretion and increase the risk of its toxic effects.

The use together with phenothiazine derivatives, increases the serum concentration of each drug.

Phenytoin when administered by IV, means for general anesthesia increase the severity of the cardiodepressant effect of atenolol. Concomitant use with MAO inhibitors is not recommended. Allergens used for immunotherapy or allergen extracts for skin tests and iodine-containing radiopaque agents for IV administration increase the risk of severe systemic allergic reactions or anaphylaxis.

Inhaled general anesthesia agents (hydrocarbon derivatives) increase the risk of depressed myocardial function and markedly reduced BP. Amiodarone increases the risk of bradycardia and inhibits AV conduction. Cimetidine increases the plasma concentration of atenolol (inhibits metabolism).

Longens the effect of nondepolarizing myorelaxants, anticoagulation effect of coumarins.

Special Instructions

Patient monitoring should include monitoring of HR and BP (daily at the beginning of treatment, then once every 3-4 months), control of blood glucose concentration in diabetic patients (once every 4-5 months). In elderly patients it is recommended to monitor kidney function (once every 4-5 months).

The patient should be trained in the method of heart rate calculation and instructed to consult a physician if the heart rate is less than 50/min. In thyrotoxicosis, the drug may mask certain clinical signs of hyperthyroidism (e.g., tachycardia). Abrupt withdrawal in patients with thyrotoxicosis is contraindicated, since it may exacerbate the symptoms. Unlike non-selective beta-adrenoblockers, it practically does not increase insulin-induced hypoglycemia and does not delay recovery of blood glucose concentration to normal levels.

In patients with coronary heart disease (CHD), abrupt withdrawal of the drug may increase the frequency or severity of anginal attacks, so discontinuation in CHD patients should be done gradually. Dose selection in patients with decompensated heart failure (compensated) also requires special attention.

Particular attention is necessary in cases in which surgical intervention under general anesthesia is required. Administration of the drug should be discontinued 48 hours before the surgical intervention. As an anesthetic, a prepasate with the possible minimum negative inotropic effect should be chosen. If used concomitantly with clonidine, Tenocek should be discontinued several days before clonidine in order to avoid “withdrawal” of the latter.

The severity of allergic reactions may increase and the lack of effect of conventional doses of epinephrine against a background of a history of aggravated allergy. Drugs that reduce catecholamines (e.g., reserpine) may increase the effect of beta-adrenoblockers, so patients taking such combinations of drugs should be under constant medical supervision for marked BP reduction or bradycardia. In elderly patients with marked bradycardia (less than 50 bpm), marked BP decrease (systolic BP below 100 mmHg, AV blockade, bronchospasm, ventricular arrhythmias, severe hepatic and renal impairment, the dose should be reduced or treatment should be stopped. In case of development of depression caused by taking the drug – it is recommended to discontinue therapy.

If intravenous verapamil administration is necessary, it should be done at least 48 hours after Tenocek administration.
When using atenolol, tear fluid production may decrease, which is important for patients who use contact lenses. Treatment should not be abruptly interrupted because of the risk of severe arrhythmias and myocardial infarction. Withdrawal is done gradually, reducing the dose over 2 weeks or more (reduce the dose by 25% every 3 to 4 days).

The drug should be discontinued before testing blood and urine concentrations of catecholamines, vanillylmindalic acid; antinuclear antibody titers. The effectiveness of beta-adrenoblockers is lower in smokers.

Tenochek should not be abruptly withdrawn in patients with coronary heart disease.

Impact on ability to drive and operate machinery

Tenochek should be prescribed with caution for motor vehicle drivers and those who operate machinery because of possible decreased attention span.

Contraindications

Side effects

The drug is usually well tolerated by patients, however, in some cases the following side effects may occur:

Overdose

Symptoms: marked bradycardia, atrioventricular block of II-III degree, increasing symptoms of heart failure, marked BP decrease, bronchospasm, hypoglycemia.

Treatment: in marked bradycardia intravenous injection of 1 ml of 0.1% solution of atropine sulfate is indicated. In case of II and III degree AV blockade, isoprenaline may be administered in 5 mg tablet under the tongue (repeat administration in 2-4 hours, if necessary), or intravenous drops or slow-flow drug administration in a dose of 0.5-1 mg. In case of bronchospasm beta2-adrenomimetics are indicated. To restore vascular tone – application of vasoconstrictors (in the absence of contraindications for their use); to eliminate the effects of calcium channel blockade – intravenous administration of calcium gluconate.

Pregnancy use

Pregnant women should prescribe Tenocek only in cases when the benefit to the mother exceeds the potential risk to the fetus.

Tenocek is excreted with breast milk, so during lactation it should be taken only in exceptional cases with great caution.