Alotendin

Alotendin is a complex antihypertensive drug (β-blocker and calcium ion antagonist). It blocks the passage of calcium ions through the membrane L-channels into the cells of smooth muscle cardiovascular fibers.

As a result, a direct relaxing effect develops in relation to smooth vascular muscles, leading to a decrease in blood pressure. At the same time, the drug attenuates ischemia associated with angina pectoris, reducing energy consumption and tissue demand for oxygen. In addition, the medication blocks β-adrenergic receptors, reducing cardiac function and the oxygen demand of the heart. [1]

Indications Alotendin

It is used to treat a stable form of chronic angina pectoris , as well as with increased blood pressure.

Release form

The release of the medication is realized in the form of tablets - 7 pieces inside a cell plate (4 or 8 plates inside a box) or 10 pieces inside a blister pack (3 or 9 packs inside a pack).

Pharmacodynamics

Amlodipine is a calcium ion antagonist. The principle of its hypotensive effect is associated with a direct relaxing effect on smooth vascular muscles. The antianginal effect develops according to the following principles:

• expansion of peripheral arterioles, which reduces systemic peripheral resistance (afterload volume). In this case, the heart rate does not change; there is a weakening of the cardiac load, which reduces the energy consumption of the myocardium and its oxygen demand;
• dilatation of the main coronary arteries with arterioles in healthy and ischemic areas of the myocardium. Due to this, the volume of oxygen entering the myocardium increases in persons with variant angina pectoris.

In people with increased blood pressure, 1-time use of amlodipine per day leads to a clinically significant decrease in blood pressure values over a period of 24 hours. The slow onset of exposure to the substance does not allow a sharp decrease in blood pressure indicators. [2]

In persons with angina pectoris, the substance prolongs the general period of receiving physical activity until the development of angina pectoris, and also prolongs the period until a significant depression of the ST segment appears. In addition, amlodipine reduces the frequency of angina attacks and the need for nitroglycerin.

The component does not lead to the appearance of negative metabolic symptoms or changes in plasma lipids, which makes it possible to use the drug in people with gout and AD, as well as diabetics.

Bisoprolol is a selective β1-adrenergic receptor blocker, without ICA. In addition, it does not have significant membrane stabilizing activity.

Blocks the activity of β1-adrenergic receptors and reduces the effect of catecholamines on them. It has an antianginal and antihypertensive effect.

The hypotensive effect develops with a decrease in cardiac output, weakening of sympathetic stimulation of peripheral vessels and suppression of renal renin release processes.

The antianginal effect occurs when the action of β1-adrenergic receptors is blocked, due to which the oxygen demand of the myocardium decreases - due to the negative inotropic and chronotropic effects. In this way, bisoprolol weakens or eliminates the manifestations of ischemia.

The drug reaches the maximum therapeutic effect after 3-4 hours from the moment of oral administration. Often, the maximum hypertensive effect develops after 2 weeks of taking Alotendin.

Pharmacokinetics

Amlodipine.

After applying therapeutic dosages, the substance is well absorbed, reaching the blood Cmax after 6-12 hours. Eating food does not change the bioavailability values of amlodipine - it is in the range of 64-80%. The indicator of the distribution volume is about 21 l / kg. In vitro tests have shown that approximately 93-98% of circulating amlodipine undergoes protein synthesis.

With intrahepatic metabolic processes, metabolites that do not have therapeutic activity are formed. Unchanged amlodipine is excreted in urine (10%) and feces (20-25%); in the form of metabolites, 60% is excreted.

The term plasma half-life is within 35-50 hours, due to which the drug can be used once a day.

Bisoprolol.

Up to 90% of the substance is absorbed inside the gastrointestinal tract. The severity of the 1st intrahepatic passage is rather low (about 10%), the bioavailability index is 90%. The term plasma half-life is within 10-12 hours, which provides a drug effect for 24 hours with a single drug intake per day.

The distribution volume is 3.5 l / kg. Protein synthesis is 30%.

Excretion of bisoprolol is carried out in 2 ways. 50% of the drug during intrahepatic metabolic processes is converted into inactive metabolites, then excreted through the kidneys. The remaining 50% (unchanged substance) is excreted by the kidneys.

Dosing and administration

Alotendin must be taken orally. The size of the standard serving for elevated blood pressure values is 1 tablet per day. In the absence of the required effect, the dosage can be increased to taking a 10/10 mg tablet 1-fold per day.

• Application for children

The medication is not used in pediatrics.

Use Alotendin during pregnancy

There is no information regarding the safety of using Alotendin during pregnancy and hepatitis B. It should be prescribed only in situations where it is not possible to use a safer analogue.

Tests with the participation of animals revealed the development of a negative effect of drugs in relation to reproductive function.

Contraindications

Among the contraindications:

• severe intolerance to amlodipine and dihydropyridines;
• extremely low blood pressure;
• shock state (also cardiogenic shock);
• obstruction affecting the outflow tract of the left ventricular tract (for example, a pronounced form of aortic stenosis);
• unstable angina;
• in the period of 8 days from the moment of the development of the most acute stage of myocardial infarction;
• active form of heart failure or manifestations of decompensation;
• 2-3rd degree of AV block;
• SSSU;
• sinoatrial blockade;
• severe stage of asthma;
• having a severe form of occlusion in the area of peripheral arteries;
• untreated pheochromocytoma;
• a metabolic type of acidosis.

Side effects Alotendin

The main side effects:

• disorders of the blood system and lymph: thrombocyto- or leukopenia;
• metabolic problems: hyperglycemia;
• mental disorders: mood lability, insomnia, depression, anxiety and confusion;
• neurological lesions: drowsiness, dysgeusia, dizziness, syncope, hypertonicity and tremor, and besides this, paresthesia, cephalalgia, hypesthesia, extrapyramidal symptoms and polyneuropathy;
• disorders associated with the organs of perception: visual disorders, including diplopia;
• problems with hearing and labyrinth function: development of ear ringing (tinnitus);
• cardiac disorders: myocardial infarction, increased heart rate and arrhythmia (also bradycardia, tachycardia and atrial flutter);
• vascular lesions: a decrease in blood pressure, hot flashes and vasculitis;
• respiratory disorders: cough, dyspnea and runny nose;
• digestive problems: vomiting, intestinal motility disorder, abdominal pain, xerostomia, nausea and constipation / diarrhea. In addition, hepatitis, jaundice, pancreatitis, gastritis, cholestasis, gingival hyperplasia and an increase in liver enzymes;
• epidermal symptoms: rash, urticaria, purpura, Quincke's edema, alopecia, pruritus, skin discoloration and exanthema. In addition, photosensitivity, hyperhidrosis, SS, exfoliative dermatitis and erythema polyform;
• lesions affecting ODA: arthralgia, pain in the back and muscles, swelling of the legs and muscle cramps;
• disorders in the urogenital system: nocturia, increased urination and urinary disorders;
• reproductive problems: impotence, gynecomastia and psoriasis;
• others: fatigue, increase / decrease in weight, swelling and pain in the sternum.

Overdose

Overdose signs: tachycardia, dizziness, prolonged decrease in blood pressure, bradycardia and AV block.

It is necessary to carry out procedures that support the activity of the CVS, monitor the BCC indicators, diuresis, lung and heart function, and also carry out symptomatic measures. Dialysis performance is very low.

Interactions with other drugs

Amlodipine.

The substance must be carefully combined with nitrates of a prolonged type of influence, NSAIDs, diuretics, β-adrenergic receptor blockers, nitroglycerin taken sublingually, antibiotics and hypoglycemic drugs taken orally.

The effect of other medicines on amlodipine.

Drugs that slow down the activity of CYP 3A4.

The use of the drug together with moderate or powerful inhibitors (azole antimycotics, protease inhibitors, diltiazem or verapamil and macrolides (for example, clarithromycin or erythromycin)) can provoke a significant increase in amlodipine exposure, which increases the likelihood of hypotension. The clinical effect of these changes may be more pronounced in the elderly. Clinical monitoring of the patient's condition and dosage adjustment may be necessary.

It is forbidden to consume grapefruit juice or grapefruit during therapy with amlodipine, since in some people this can cause an increase in the bioavailability of the substance, which is why the antihypertensive effect is potentiated.

Medicines that induce the action of CYP 3A4.

There is no data on the effect of CYP 3A4 inducers on amlodipine. When combining the drug with St. John's wort or rifampicin, it is possible to reduce the plasma level of amlodipine, which is why such combinations are used very carefully.

Dantrolene infusion.

After intravenous administration of dantrolene and verapamil, the animals experienced fatal ventricular fibrillation, as well as collapse of the CVS associated with hyperkalemia.

Due to the risk of hyperkalemia, persons with a tendency to malignant hyperthermia, as well as in the treatment of this disease, should stop using Ca channel blockers (amlodipine).

The effect of amlodipine on other drugs.

The antihypertensive effect of amlodipine enhances the hypotensive effect of other antihypertensive substances.

Tacrolimus.

When combined with amlodipine, there is a possibility of an increase in the blood values of tacrolimus, but the pharmacokinetics of this interaction could not be fully determined.

To avoid the development of toxic effects of tacrolimus, it is necessary to constantly monitor its blood parameters and adjust the dosage, if necessary.

Cyclosporine.

For kidney transplants using amlodipine, consider monitoring cyclosporine and lowering the dose if necessary.

Simvastatin.

The combination of multiple doses of amlodipine (10 mg) with 80 mg of simvastatin caused an increase in the exposure of the latter by 77% (in comparison with the administration of simvastatin alone). People taking amlodipine should limit the daily dosage of simvastatin to 20 mg.

Bisoprolol.

It is forbidden to use in combination.

Calcium antagonists (verapamil, as well as diltiazem (less active)) negatively affect blood pressure, AV conduction and contraction. When using verapamil by persons using β-adrenergic receptor blockers, there may be a significant decrease in blood pressure values and the development of AV blockade.

Hypertensive substances with a central type of activity (methyldopa, rilmenidine with clonidine and moxonidine) in combination with bisoprolol slow down the heart rate, vasodilation and decrease the cardiac output. With a sharp withdrawal of the drug, the likelihood of a withdrawal syndrome in the form of an increase in blood pressure values increases.

Substances that must be carefully combined with bisoprolol.

Dihydropyridine Ca-antagonists (eg, nifedipine) may increase the likelihood of HF and lower blood pressure.

Class I antiarrhythmic drugs (eg, quinidine, propafenone with disopyramide, flecainide, and phenytoin with lidocaine) increase the negative effects of myocardial inotropic activity and AV conduction.

Class III antiarrhythmic drugs (eg, amiodarone) can increase exposure relative to AV conduction.

When combined with parasympathomimetics, the AV conduction period can be prolonged, which increases the likelihood of bradycardia.

Local substances containing elements that block β-adrenergic receptors (eye drops used in the treatment of glaucoma) are able to supplement the systemic activity of bisoprolol.

Oral hypoglycemic drugs and insulin potentiate the antidiabetic effect. Due to the blockade of β-arenoreceptors, masking of the signs of hypoglycemia may occur.

Use together with SG prolongs AV conduction and lowers heart rate.

Administration in combination with NSAIDs weakens the hypotensive effect.

Use with β-sympathomimetics (dobutamine or isoprenaline) can reduce the effects of both drugs.

Sympathomimetics, which activate the activity of α- and β-adrenergic receptors (including norepinephrine with epinephrine), increase blood pressure. This effect is more likely with the introduction of non-selective β-adrenoreceptor blockers.

Ergotamine derivatives exacerbate peripheral blood flow disorders.

Barbiturates, tricyclics, phenothiazines and other antihypertensive substances increase the likelihood of lowering blood pressure values.

Derivatives of carbohydrates and substances for inhalation anesthesia (halothane, chloroform, methoxyflurane and cyclopropane), when combined with drugs that block β-adrenergic receptors, increase the likelihood of suppressing myocardial activity and the occurrence of antihypertensive symptoms.

The effect of non-depolarizing blockers of neuromuscular transmission is potentiated and prolonged by the action of drugs that block the activity of β-adrenergic receptors.

Mefloquine increases the likelihood of bradycardia.

MAOIs (except MAOI-B) potentiate the antihypertensive effect of drugs that block β-adrenergic receptors and increase the likelihood of a hypertensive crisis.

Storage conditions

Alotendin is required to be stored at temperatures within 15-30 ° C.

Shelf life

Alotendin can be used within a 5-year term from the date of manufacture of the therapeutic.

Analogs

An analogue of the medication is the drug Sobikombi.