Adelphan - instructions for use, reviews, analogs and form of release (Ezidrex tablets) medicines for the treatment of hypertension and depression in adults, children and pregnancy. Composition and interaction with alcohol
In this article, you can read the instructions for using the drug Adelphane. Presented are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors of specialists on the use of Adelfan in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Adelfan in the presence of existing structural analogues. Use to treat hypertension and reduce blood pressure in adults, children,as well as during pregnancy and lactation. Composition and interaction of the drug with alcohol.
Adelphane - is a combination of antihypertensive components that have different points of application and mutually complementary antihypertensive effects of each other.
Reserpine causes depletion of the catecholamine depot in the endings of postganglionic sympathetic nerves and in the central nervous system. As a result, the ability to deposit catecholamines is disrupted for a fairly long period of time. Depletion of catecholamine stocks leads to impairment of impulse transmission in the endings of sympathetic nerves, which in turn leads to a decrease in the tone of the sympathetic nervous system (the activity of the parasympathetic nervous system does not change). Thus, reserpine reduces the elevated blood pressure and heart rate. In addition, reserpine causes sedation. Reserpine also depletes the reserves of other neurotransmitters, incl. serotonin, dopamine, neuropeptides and adrenaline in the central and peripheral neurons. These effects of reserpine may play a role in the realization of its pharmacological effects and antihypertensive effects.
After taking reserpine, its antihypertensive effect develops slowly; The maximum effect is achieved only after 2-3 weeks and is maintained for a long time.
Dihydralazine sulfate is an arterial vasodilator, reduces the tone of the smooth muscles of arterial vessels (predominantly arterioles) and reduces OPSS. The mechanism of this action at the cellular level remains unclear. In a greater degree, the vascular resistance decreases in the vessels of the heart, brain, kidneys and other internal organs and to a lesser extent in the vessels of the skin and skeletal muscles. If the decrease in blood pressure is not of a pronounced nature, the blood flow in the enlarged bloodstream generally increases. The predominant expansion of arterioles, rather than venules, reduces the severity of orthostatic hypotension and contributes to an increase in cardiac output.
Vascular expansion, leading to a reduction in blood pressure (mostly diastolic than systolic), is accompanied by a reflex increase in heart rate, stroke volume and cardiac output. Reflex increase in heart rate and cardiac output can be leveled by combining dihydralazine with reserpine, which suppresses the sympathetic nervous system.
Hydrochlorothiazide - thiazide diuretic - acts in the cortical segment of the Henle loop and the distal sections of the renal tubules. It inhibits the reabsorption of chloride and sodium ions (due to antagonistic interaction with the transport enzyme NaCl) and enhances the reabsorption of calcium ions (the mechanism is unknown). An increase in the amount and / or rate of intake of sodium and water ions into the cortical segment of the collecting tubes leads to an increase in the secretion and excretion of potassium and hydrogen ions.
In patients with normal renal function, an increase in diuresis is observed after a single application of hydrochlorothiazide at a dose of 12.5 mg. The increase in urinary excretion of sodium and chlorine and a slightly less pronounced increase in potassium -urease depend on the dose of hydrochlorothiazide. After taking the medication, diuretic and natriuretic effects start within 1-2 hours, peak at 4-6 hours, and last for 10-12 hours. Diuresis caused by thiazides first leads to a decrease in the volume of circulating plasma, cardiac output, and systemic blood pressure. It is possible to activate the renin-angiotensin-aldosterone system. With long-term use of hydrochlorothiazide, the maintenance of the hypotensive effect is provided, probably, due to the reduction in OPSS.Cardiac output returns to baseline values, a small decrease in plasma volume and an increase in plasma renin activity persist.
Composition
Reserpine + Dihydralazine sulfate (hydrated) + auxiliary substances.
Reserpine + Dihydralazine sulfate (hydrated) + Hydrochlorothiazide + auxiliary substances (Adelphan Ezidrex).
Pharmacokinetics
Reserpine is rapidly absorbed after ingestion.
Dihydralazine is rapidly absorbed after oral administration. In the blood plasma, dihydralazine is mainly in the form of unchanged dihydralazine and hydrazone substances formed as a result of the metabolism of the basic substance. Approximately 10% of dihydralazine is in the blood plasma in the form of hydralazine.
Hydrochlorothiazide after intake is absorbed by 60-80%. Changes in absorption due to food intake are not clinically important.
Hydrochlorothiazide accumulates in erythrocytes.
Reserpine is metabolized in the intestine and liver. The main metabolites are methyl reserpate and trimethoxybenzoic acid. Dihydralazine is metabolized to a large extent by oxidation (with the formation of hydrazones) and acetylation. Hydrochlorothiazide is metabolized to a very small extent.Its only metabolite found in trace amounts is 2-amino-4-chloro-M-benzenedisulfonamide.
During the first 96 hours after ingestion, 8% of the reserpine dose is excreted by the kidneys, mainly in the form of metabolites, and 62% through the intestine, mostly unchanged.
After oral administration, about 46% of the dose of dihydralazine taken is withdrawn within 24 hours, mainly in the form of metabolites, mainly through the intestine. About 0.5% of the dose is detected in the urine as an unchanged substance.
In patients with normal renal function, the excretion of hydrochlorothiazide is almost exclusively performed by the kidneys. In general, 50-75% of the dose taken internally is excreted in the urine unchanged.
Indications
- arterial hypertension.
Forms of release
Pills.
Instructions for use and dosing regimen
The drug is taken with food and washed down with water.
The dose of the drug should be selected individually. Treatment begins with the appointment of a minimal dose, which can be gradually (not more often than every 2-3 weeks) to increase, depending on the patient's response to treatment. The daily dose is usually 1-3 tablets. The maximum daily dose is 3 tablets. The frequency of taking the drug is 2-3 times a day.
If adequate blood pressure control can not be achieved, the treatment should be reviewed and, possibly, switched to a drug of another pharmacological group (beta-blocker, slow calcium channel blocker, ACE inhibitor).
In elderly patients, as well as in patients with impaired hepatic function, a single dose of the drug or an interval between its prescriptions should be established with caution, taking into account the required clinical response to treatment and tolerability.
Side effect
- dry mouth;
- increased secretion of gastric juice;
- increased salivation;
- nausea, vomiting;
- diarrhea;
- increased appetite;
- ulcer formation;
- gastrointestinal bleeding;
- sinus bradycardia;
- edema;
- arrhythmias;
- pain behind the sternum, suggesting angina pectoris;
- orthostatic hypotension;
- flushes of blood to the face;
- fainting;
- heart failure;
- disorders of cerebral circulation;
- edema of the nasal mucosa;
- dyspnea;
- nose bleed;
- dizziness;
- depression;
- irritability;
- nightmarish dreams;
- increased fatigue;
- extrapyramidal disorders (including parkinsonism);
- headache;
- alarm status;
- violation of concentration of attention;
- stupor;
- violation of orientation;
- cerebral edema;
- violation of potency and ejaculation;
- dysuria;
- glomerulonephritis;
- increase in body weight;
- decreased body weight;
- increased secretion of prolactin;
- galactorrhea;
- gynecomastia;
- swelling of the mammary glands;
- blurring of vision;
- hyperemia of the conjunctiva;
- lacrimation;
- hearing impairment;
- eczema;
- itching;
- decreased libido;
- anemia, thrombocytopenia.
Contraindications
- depression (currently or in history);
- Parkinson's disease;
- epilepsy;
- electroconvulsive therapy;
- peptic ulcer of the stomach and duodenum in the phase of exacerbation;
- ulcerative colitis;
- pheochromocytoma;
- concomitant or recent treatment with MAO inhibitors;
- systemic lupus erythematosus (idiopathic);
- severe tachycardia and heart failure on the background of high cardiac output (including with thyrotoxicosis);
- heart failure due to mechanical obstruction (including the presence of aortic or mitral stenosis or constrictive pericarditis);
- isolated right ventricular failure due to pulmonary hypertension ("pulmonary" heart);
- anuria, marked renal failure (creatinine clearance less than 30 ml / min);
- liver failure;
- refractory hypokalemia, hyponatremia, hypercalcemia;
- hyperuricemia with clinical manifestations;
- pregnancy;
- children under 18 years of age (efficacy and safety not established);
- hypersensitivity to reserpine and related substances, dihydralazine or other hydrazinophthalazines, hydrochlorothiazide or other sulfonamide derivatives.
Application in pregnancy and lactation
Adelphan is contraindicated in pregnancy for the following reasons.
Reserpine, in the case of its appointment before childbirth, can cause a pronounced drowsiness in the newborn, swelling of the nasal mucosa and anorexia. The effect of thiazide diuretics, incl. hydrochlorothiazide, resulted in the fetus and newborn thrombocytopenia. Since thiazide diuretics do not prevent the onset and do not affect the severity of the manifestations of toxicosis of pregnant women (edema, proteinuria, hypertension), they should not be prescribed for this indication.
Reserpine, dihydralazine and hydrochlorothiazide penetrate into breast milk. Reserpine in a newborn baby may cause the reactions described above. Hydrochlorothiazide can inhibit lactation. It is not recommended to use Adelfan during lactation.
There have been no studies to study the influence of Adelphan on reproductive performance in animals.
special instructions
Patients who underwent myocardial infarction should not be prescribed dihydralazine until the stabilization period is over after myocardial infarction. As with the administration of any antihypertensive drugs with a pronounced hypotensive effect, special care should be taken when administering Adelphan to patients with coronary and cerebral atherosclerosis. In these cases, a sharp decrease in blood pressure should be avoided. this can lead to a decrease in blood flow. The following precautions apply not only to each component alone, but also to the preparation of Adelphan as a whole.
Since reserpine increases motility and secretion in the digestive tract, caution should be exercised when it is used in patients with peptic ulcer of the stomach and duodenum in anamnesis, as well as in patients with erosive gastritis and cholelithiasis. Care should also be taken in patients with heart failure, sinus bradycardia, conduction disorders, as well as in patients who have recently undergone myocardial infarction.
Care should be taken in patients with suspected coronary artery disease. Dihydralazine-induced tachycardia can lead to an attack of angina and changes in the ECG, indicating myocardial ischemia. In some cases, the connection of myocardial infarction with the intake of dihydralazine was not excluded.
Adelfan should be avoided (especially if used with potassium or with potassium-sparing diuretics) for patients taking ACE inhibitors. As with the use of other thiazide diuretics, caution should be exercised in patients with diabetes mellitus and gout.
When signs of depression appear, the drug should be immediately discontinued, since there is a risk of suicidal actions. Depression caused by reserpine (especially when using Adelfan in high doses) can be severe enough to provoke suicidal actions. It can persist for several months after drug withdrawal.
The use of dihydralazine can lead to a delay in sodium and water in the body and, consequently, the development of edema and a decrease in diuresis.
It is required to systematically monitor the condition of patients with impaired liver function, given the possibility of the occurrence of rare but serious side effects of dihydralazine on the part of the liver. It should also be taken into account that even minor violations of the water-electrolyte balance caused by the thiazide diuretic can provoke hepatic coma, especially in patients with cirrhosis of the liver. At present, there are few reports of cases of lupus-like syndrome associated with the intake of dihydralazine. The mild forms of this syndrome are manifested by arthralgia, sometimes accompanied by fever and skin rashes; with the withdrawal of the drug, these symptoms pass by themselves. In more severe cases, the clinical picture is similar to that of systemic lupus erythematosus; complete disappearance of symptoms can be achieved only with long-term treatment of SCS. The frequency of this syndrome is directly related to the dose and duration of treatment. In this regard, for the duration of maintenance therapy is recommended to use the minimum effective dose.
During treatment with dihydralazine, it seems advisable to determine the antinuclear factor in the blood plasma every 6 months. In the case of detection of an antinuclear factor, it is necessary to systematically determine its titers. If clinical manifestations of lupus-like syndrome develop, the drug should be immediately withdrawn. Reserpine should be discontinued at least 7 days before electroconvulsive therapy.
The cancellation of reserpine before the operation is not a guarantee that during the operation there will be no instability of hemodynamics. It is important to warn an anesthesiologist that the patient is taking reserpine, and took this into account when administering the patient. There are cases of a decrease in blood pressure in patients receiving drugs rauwolfia. During the surgical intervention in patients receiving dihydralazine, there may be a marked decrease in blood pressure.
Against the background of hydrochlorothiazide, hypokalemia develops. Hypokalemia can increase the sensitivity of the myocardium or strengthen the heart's response to the toxic effects of digitalis preparations. The risk of hypokalemia is increased with cirrhosis of the liver, rapidly developing diuresis, inadequate intake of potassium with food, concomitant therapy with GCS,stimulants of beta2-adrenergic receptors or ACTH. With the purpose of timely detection of possible electrolyte balance disturbances it is necessary to determine the electrolyte content in the plasma at the beginning of treatment and at certain intervals during the treatment.
Nonspecific manifestations of violations of electrolyte balance, observed in a number of cases, were dry mouth, thirst, weakness, drowsiness, anxiety, muscle aches and cramps, muscle weakness, decreased blood pressure, oliguria, tachycardia, nausea.
Thiazide diuretics cause a decrease in calcium excretion. Several patients who received long-lasting thiazide diuretics had pathological changes in the parathyroid gland, accompanied by hypercalcemia and hypophosphatemia. In the case of hypercalcemia, additional tests are needed to clarify the diagnosis. There were no complications that are usually associated with hyperparathyroidism, such as the formation of kidney stones, bone resorption, peptic ulcers.
Thiazide diuretics cause an increase in urinary excretion of magnesium, which can lead to hypomagnesemia.
When used in high doses, thiazide diuretics can cause a decrease in glucose tolerance and lead to an increase in plasma concentrations of cholesterol, triglycerides and uric acid.
The use of reserpine affects the results of the determination in urine of 17-ketosteroids and 17-hydroxycorticosteroids by a colorimetric method, leading to an underestimation of these results.
Impact on the ability to drive vehicles and manage mechanisms
Adelfan can disrupt the patient's ability to respond quickly, especially at the beginning of treatment. As with the appointment of other antihypertensive drugs, patients managing vehicles and mechanisms should be warned about the possibility of reducing the speed of psychomotor reactions, and be careful.
Drug Interactions
The hypotensive effect of Adelphan is enhanced by the simultaneous administration of other antihypertensive drugs: guanethidine, alpha-methyldopa, beta adrenoblockers, vasodilators, slow calcium channel blockers, ACE inhibitors.
A number of interactions associated with individual components of the drug are also possible.
Reserpine
It is necessary to abolish MAO inhibitors at least 14 days before starting reserpine therapy.If it is necessary to administer MAO inhibitors to a patient receiving reserpine, MAO inhibitors should be given at least 14 days after the withdrawal of reserpine. With simultaneous application of reserpine and MAO inhibitors, hyperactivity, hypertensive crisis are possible.
Reserpine increases the depressing effect on the central nervous system alcohol, funds for general anesthesia, some antihistamines, barbiturates and tricyclic antidepressants. Reserpine weakens the action of levodopa. The simultaneous use of reserpine and tricyclic antidepressants can reduce the hypotensive effect of reserpine.
Reserpine should be discontinued a few days before the scheduled surgery to avoid excessive BP reduction during general anesthesia. The administration of reserpine in combination with antiarrhythmic drugs or digitalis preparations can lead to sinus bradycardia.
Reserpine may enhance the effects of epinephrine (adrenaline) or other sympathomimetic agents (Caution should be exercised while the use of antitussives, nasal drops, eye drops).
Dihydralazine sulfate
The simultaneous use of tricyclic antidepressants, neuroleptics, as well as ethanol-containing drugs (as well as alcohol) can enhance the hypotensive effect of dihydralazine. The administration of dihydralazine shortly before or shortly after administration of diazoxide may cause a marked decrease in blood pressure.
Hydrochlorothiazide
With the simultaneous use of hydrochlorothiazide and lithium preparations, it is possible to increase the concentration of lithium in the blood, so in this case, a systematic control of the level of lithium in the blood is necessary. In cases where lithium preparations cause polyuria, hydrochlorothiazide can cause a paradoxical antidiuretic effect. Hydrochlorothiazide can enhance the effects of nondepolarizing muscle relaxants.
The hypokalemic effect caused by diuretics can be enhanced with simultaneous application of GCS, ACTH, amphotericin, carbenoxolone. Hypokalemia and hypomagnesemia (undesirable effects of thiazide diuretics) can contribute to the development of cardiac arrhythmias in patients receiving cardiac glycosides.
When using hydrochlorothiazide in patients with diabetes mellitus, it may be necessary to adjust the doses of insulin and oral hypoglycemic drugs.
Simultaneous administration of NSAIDs (incl.indomethacin) can weaken the diuretic, natriuretic and antihypertensive effects of hydrochlorothiazide. There are some reports of impaired renal function in predisposed patients.
The absorption of hydrochlorothiazide is disturbed in the presence of anion-exchange resins. The absorption of hydrochlorothiazide from the digestive tract with simultaneous single application of colestyramine and colestipol decreases by 85% and 43%, respectively, due to binding to these compounds.
The simultaneous use of thiazide diuretics (including hydrochlorothiazide) may increase the risk of Allopurinol hypersensitivity reactions, increase the risk of side effects of amantadine, increase the hyperglycemic effect of diazoxide, reduce renal excretion of cytotoxic agents (including cyclophosphamide, methotrexate) and intensify their myelosuppressive effect.
Anticholinergic drugs (including atropine, biperiden) can increase the bioavailability of hydrochlorothiazide, which is associated with a decrease in motor activity of the gastrointestinal tract and the rate of gastric emptying.
Simultaneous intake of hydrochlorothiazide with vitamin D or calcium preparations can lead to an increase in the level of calcium in the blood.
With the simultaneous use of hydrochlorothiazide and cyclosporine, the risk of developing hyperuricemia and gout increases.
There are reports of the development of hemolytic anemia with simultaneous administration of hydrochlorothiazide and methyldopa preparations.
Analogues of the drug Adelphan
Structural analogs for the active substance:
- Adelphan Ezidrex.
Similar medicines:
Other medicines:
- Essentiale - instructions for use, reviews, analogs and forms of release (injections in ampoules for intravenous injection of H, capsules or tablets Forte H) a drug for the treatment of necrosis and cirrhosis in adults, children and pregnancy. Composition
- Centrum - instructions for use, analogs, reviews and release forms (tablets, chewable Junior Pro, Materna, children's, Silver, lutein) medication for the treatment of hypovitaminosis in adults, children and pregnancy. Composition of vitamins
- Goldline - instructions for use, analogs, reviews and release forms (capsules or tablets 10 mg and 15 mg) drugs for the treatment of obesity and weight loss in adults, children and pregnancy. Composition