Alotendine

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

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

Indications Alotendine

It is used to treat stable forms of chronic angina, as well as elevated blood pressure.

Release form

The drug is released 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:

• dilation of peripheral arterioles, which reduces systemic peripheral resistance (afterload volume). In this case, the heart rate does not change; the cardiac load is weakened, 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 volumes of oxygen entering the myocardium increase in people with variant angina.

In people with elevated blood pressure, a single daily dose of amlodipine results in a clinically significant reduction in blood pressure over a 24-hour period. The slow onset of action of the substance prevents a sharp decrease in blood pressure. [ 2 ]

In people with angina, the substance prolongs the total period of physical activity before the development of an angina attack, and also prolongs the period before the appearance of significant ST-segment depression. In addition, amlodipine reduces the frequency of angina attacks and nitroglycerin requirement.

The component does not lead to the appearance of negative metabolic symptoms or changes in plasma lipid indices, which allows the drug to be used in people with gout and bronchial asthma, 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-adrenoreceptors and reduces the influence exerted on them by catecholamines. 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-adrenoreceptors is blocked, which reduces the oxygen demand of the myocardium - due to the negative inotropic and chronotropic effect. In this way, bisoprolol weakens or eliminates the manifestations of ischemia.

The drug achieves its 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 administration of therapeutic doses, the substance is well absorbed, reaching the blood Cmax value after 6-12 hours. Food intake does not change the bioavailability values of amlodipine – it is within 64-80%. The distribution volume is about 21 l/kg. In vitro tests have shown that approximately 93-98% of circulating amlodipine undergoes protein synthesis.

Intrahepatic metabolic processes result in the formation of metabolites that do not have therapeutic activity. Unchanged amlodipine is excreted in urine (10%) and feces (20-25%); 60% is excreted in the form of metabolites.

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

Bisoprolol.

Up to 90% of the substance is absorbed inside the gastrointestinal tract. The expression of the first intrahepatic passage is quite low (about 10%), the bioavailability index is 90%. The plasma half-life is within 10-12 hours, which ensures the medicinal effect for 24 hours with 1-time administration of the drug per day.

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

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

Dosing and administration

Alotendin should be taken orally. The standard dose for elevated blood pressure is 1 tablet per day. If the desired effect is not achieved, the dosage can be increased to taking a 10/10 mg tablet once per day.

• Application for children

The drug is not used in pediatrics.

Use Alotendine during pregnancy

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

Animal tests have shown that the drug has negative effects on reproductive function.

Contraindications

Among the contraindications:

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

Side effects Alotendine

Main side effects:

• disorders of the blood and lymph system: thrombocytopenia or leukopenia;
• problems with metabolic processes: hyperglycemia;
• mental disorders: mood lability, insomnia, depression, anxiety and confusion;
• neurological lesions: drowsiness, dysgeusia, dizziness, syncope, hypertonia and tremor, as well as paresthesia, cephalgia, hypoesthesia, extrapyramidal symptoms and polyneuropathy;
• disorders associated with the organs of perception: visual disturbances, including diplopia;
• problems with hearing and labyrinth function: development of ear ringing (tinnitus);
• Cardiological disorders: myocardial infarction, increased heart rate and arrhythmia (also bradycardia, tachycardia and atrial flutter);
• vascular lesions: decreased blood pressure, hot flashes and vasculitis;
• respiratory disorders: cough, dyspnea and runny nose;
• Digestive problems: vomiting, intestinal peristalsis disorder, abdominal pain, xerostomia, nausea and constipation/diarrhea. In addition, hepatitis, jaundice, pancreatitis, gastritis, cholestasis, gingival hyperplasia and increased liver enzymes;
• Epidermal symptoms: rash, urticaria, purpura, Quincke's edema, alopecia, itching, changes in skin tone and exanthema. In addition, photosensitivity, hyperhidrosis, SJS, exfoliative dermatitis and erythema multiforme;
• lesions affecting the musculoskeletal system: arthralgia, pain in the back and muscles, swelling of the legs and muscle cramps;
• disorders of the urogenital system: nocturia, frequent urination and urinary disorders;
• problems with reproductive function: impotence, gynecomastia and psoriasis;
• Others: fatigue, weight gain/loss, swelling and pain in the chest area.

Overdose

Signs of overdose: tachycardia, dizziness, prolonged decrease in blood pressure, bradycardia and atrioventricular block.

It is necessary to perform procedures that support the activity of the cardiovascular system, monitor the indices of the blood volume, diuresis, lung and heart function, and also carry out symptomatic measures. The effectiveness of dialysis is very low.

Interactions with other drugs

Amlodipine.

The substance should be combined with caution with prolonged-release nitrates, NSAIDs, diuretics, β-adrenergic receptor blockers, sublingual nitroglycerin, antibiotics and orally administered hypoglycemic drugs.

Effects of other drugs on amlodipine.

Agents that inhibit CYP 3A4 activity.

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

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

Medicines that induce CYP 3A4 action.

There are no data on the effect of CYP 3A4 inducers on amlodipine. When combining the drug with St. John's wort or rifampicin, a decrease in the plasma level of amlodipine is possible, which is why such combinations should be used with great caution.

Dantrolene infusions.

Following intravenous administration of dantrolene and verapamil, fatal ventricular fibrillation and CV collapse associated with hyperkalemia were observed in animals.

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

The effect of amlodipine on other drugs.

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

Tacrolimus.

When combined with amlodipine, there is a potential for increased blood levels of tacrolimus, but the pharmacokinetics of this interaction have not been fully determined.

To avoid the development of toxic effects of tacrolimus, its blood levels should be constantly monitored and the dosage adjusted if necessary.

Cyclosporine.

For kidney transplant recipients using amlodipine, consideration should be given to monitoring cyclosporine levels and reducing the dosage if necessary.

Simvastatin.

Combining multiple doses of amlodipine (10 mg) with 80 mg of simvastatin resulted in a 77% increase in simvastatin exposure (compared to simvastatin alone). People taking amlodipine should limit their daily simvastatin dose to 20 mg.

Bisoprolol.

It is prohibited to use in combination.

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

Hypertensive agents with a central type of activity (methyldopa, rilmenidine with clonidine and moxonidine) in combination with bisoprolol slow the heart rate, vasodilation and reduce the cardiac output. With abrupt withdrawal of the drug, the likelihood of withdrawal syndrome in the form of increased blood pressure increases.

Substances that should be combined with caution with bisoprolol.

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

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

Class III antiarrhythmic drugs (eg, amiodarone) may increase their effects on AV conduction.

When combined with parasympathomimetics, the period of AV conduction may 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.

Orally administered hypoglycemic drugs and insulin potentiate the antidiabetic effect. Due to the blockade of β-arenoceptors, the signs of hypoglycemia may be masked.

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

Administration in combination with NSAIDs weakens the hypotensive effect.

Use with β-sympathomimetics (dobutamine or isoprenaline) may weaken the effect of both drugs.

Sympathomimetics that activate the activity of α- and β-adrenoreceptors (including norepinephrine and epinephrine) increase blood pressure. This effect is more likely when non-selective β-adrenoreceptor blockers are administered.

Ergotamine derivatives cause exacerbation of peripheral blood flow disorders.

Barbiturates, tricyclics, phenothiazines and other antihypertensive agents increase the likelihood of a decrease in blood pressure values.

Carbohydrate derivatives and inhalational anesthetics (halothane, chloroform, methoxyflurane, and cyclopropane) when combined with beta-adrenergic blocking drugs increase the likelihood of myocardial suppression and the development of antihypertensive symptoms.

The effect of non-depolarizing neuromuscular transmission blockers is potentiated and prolonged by agents 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 hypertensive crisis.

Storage conditions

Alotendin must be stored at temperatures between 15-30°C.

Shelf life

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

Analogues

An analogue of the drug is Sobicombi.