More info
Active ingredients
Methyldopa
Release form
Pills
Composition
Active ingredient: Methyldopa sesquihydrate. Concentration of active ingredient (mg): 250
Pharmacological effect
Dopegyt (methyldopa) - a drug that has a hypotensive effect, belongs to the central α2-adrenostimulyatory. The hypotensive effect of the drug is due to its ability to reduce the heart rate and the minute volume of blood, as well as reduce the total peripheral vascular resistance. In the CNS, Dopegyt forms a metabolite - α-melitnorepinephrine, which stimulates postsynaptic α2-adrenoreceptors of the medulla oblongata, which leads to inhibition of sympathetic impulses and a decrease in vascular tone. Dopegyt has the ability to reduce OPSS, cause orthostatic hypertension, reduce the tissue concentration of dopamine, serotonin and epinephrine (by inhibiting the enzyme dopa-decarboxylase), and inhibit plasma renin activity. Dopegyt causes an increase in renal blood flow. The drug on dopaminergic nerve endings contributes to the replacement of endogenous dopamine ("false neurotransmitter"). Prolonged use of Dopegyt can lead to regression of left ventricular hypertrophy with an increase in collagen in the heart muscle. The first dose of the drug in some cases may cause short-term hypertension. The hypotensive effect Dopegita during exercise is less pronounced. Dopegyt is able to delay the excretion of water and sodium ions, slow down the sinus rhythm, increase the activity of baroreceptors, which explains the development of refractoriness with long-term treatment. For the drug Dopegyt characterized by "withdrawal." Dopegyt may cause sedation. The severity of sedation decreases after 2-3 weeks from the start of therapy with the drug. After oral administration of the drug after 4-6 hours there is a maximum decrease in blood pressure, which persists for 1-2 days. The hypotensive effect in the first days of treatment gradually increases. About 50% of the drug is absorbed from the digestive tract. In the mucous membrane of the gastrointestinal tract, metabolism begins (as a result of the formation of ortho-sulfonated derivatives). The maximum concentration of the drug in the plasma is observed after 2.5 - 6 hours, which corresponds to the time of onset of the maximum hypotensive effect. In the liver, the formation of conjugates with sulfates. The ability to bind to plasma proteins reaches 20%. Dopegyt enters the CNS through the blood-brain barrier.In the central nervous system, part of the dose taken (about 10%) is decarboxylated and β-hydroxylated to methyldopamine and methylnoradrenaline. The half-life of the drug - 2 hours. Dopegyt is excreted by the kidneys, for the most part - unchanged. A small part of the drug is excreted in the urine in the form of orthosulfate conjugates. Removal from the body is of a bioexponential nature: in patients with normal kidney functions, phase 1 takes 100-120 minutes (at this time 90% of the drug is excreted), phase 2 of oral elimination takes about 2 hours. In patients with severe chronic renal failure, drug withdrawal slows down (in the first phase, only 50% of the drug is eliminated). In patients with liver disease metabolism slows down. Renal clearance is about 130 ml / min. , with prolonged use, the drug is cumulated.
Pharmacokinetics
The absorption of methyldopa from the gastrointestinal tract is approximately 50%. After oral administration, the bioavailability of methyldopa is about 25%. The maximum concentration of the drug in the blood plasma is determined after 2–3 hours. Communication with plasma proteins is less than 20%. The metabolism of the active substance is intense. Methyldopa is metabolized primarily in the liver. The active metabolite, methyldopa-alpha-methylnoradrenaline, is formed in the adrenergic neurons of the central nervous system. There are also some other methyldopes that are excreted by the kidneys. Approximately two thirds of the absorbed methyldopa excreted by the kidneys in unchanged form, as well as in the form of sulfate compounds. The rest of the drug is excreted through the intestines (also in an unchanged condition). Removal of methyldopa has a biphasic character. With preserved renal function, the half-life of the drug is 1.8 ± 0.2 hours. The active substance is completely excreted from the body within 36 hours. Methyldopa is removed from the body by dialysis. A six-hour hemodialysis session results in the elimination of approximately 60% of the absorbed dose, whereas as a result of a 20-30 hour peritoneal dialysis, approximately 22–39% of the drug is removed. Methyldopa penetrates the placental barrier and is excreted in breast milk.Patients with impaired renal function: With impaired renal function, the excretion of methyldopa slows down in proportion to the severity of renal failure. In severe renal failure (without hemodialysis), the half-life of the drug is increased by about 10 times.
Indications
Arterial hypertension.
Contraindications
Dopegyt is contraindicated in patients with hemolytic anemia, hypersensitivity, acute hepatitis, renal insufficiency, hepatic insufficiency, cirrhosis of the liver, systemic connective tissue diseases, depression, parkinsonism, pheochromocytoma, severe coronary atherosclerosis, acute myocardial stroma, a symptomatic manifesto, a symptomatic manifesto, a pronounced myocardial stroke, a symptomatic manifestation, a symptomatic heart attack, a symptomatic heart attack, a symptomatic heart attack, a symptomatic heart attack, a pronounced myocardial myocardial syndrome, a symptomatic manifestation, a pronounced coronary atherosclerosis, an acute myocardial stroma, a morphic syndrome, a symptomatic syndrome, a symptomatic heart disease, a symptomatic heart attack and MAO inhibitors. Caution should be exercised in the appointment of the drug Dopegyt during lactation and in patients with a history of hepatitis, diencephalic syndrome, acute left ventricular failure.
Precautionary measures
European and Russian recommendations for the treatment of hypertension consider methyldopa as a first-line drug in the treatment of hypertension in pregnant women, because it is characterized by better safety and does not cause unwanted reactions in the mother and fetus. Extreme caution is required when prescribing Dopegita to patients with hepatic porphyria or their close relatives. In the process of treatment, control of liver function and the picture of peripheral blood is necessary. Before starting treatment with Dopegite, the number of blood corpuscles should be investigated, and during the first 6-10 weeks of therapy a direct Coombs test should be performed, which should then be repeated every six months or a year. A positive Coombs test may be present in 10–20% of patients receiving this drug, especially after taking more than 1 g of Dopegyt daily for six months or one year. Less than 5% of these patients may develop hemolytic anemia. In this case, it is absolutely necessary to immediately discontinue Dopegita. After discontinuation of the drug hemolytic anemia stops. If this does not happen, the use of GCS or analysis of other possible causes of hemolytic anemia is required.If hemolytic anemia is caused by Dopegyt, the patient should not receive this drug in the future. A positive Coombs test becomes negative a few weeks or months after discontinuation of the drug. By itself, the presence of a positive Coombs test or its appearance in a patient is not a contraindication to Dopegite therapy. If the Coombs test becomes positive during treatment with Dopegite, hemolytic anemia should be established and the degree of clinical significance of the Coombs positive test should be established. For example, in addition to the positive direct Coombs test, there is less often a positive indirect Coombs test that can affect blood cross-compatibility. If necessary, blood transfusions to patients receiving Dopegyt should be performed by direct and indirect Coombs tests. In the absence of hemolytic anemia, only the direct Coombs test is usually positive. The direct Coombs test itself does not affect blood typing or cross-compatibility. If the indirect Coombs test is also positive, consultation with a hematologist or transfusiologist is necessary. During the first 6-12 weeks of treatment, as well as in the event of fever of unknown etiology, liver function monitoring should be carried out. When changing the activity of hepatic transaminases or the presence of jaundice should suggest the occurrence of hypersensitivity reactions, in which there is cholestasis, damage to the liver cells or hepatitis. In very rare cases, deadly liver necrosis can occur. Therefore, when the activity of liver enzymes changes or the onset of symptoms of liver failure, the course of treatment with Dopegite should be stopped immediately. Such patients in the future can not be prescribed Dopegyt. Patients with a medical history or liver dysfunction in the history of this drug should be prescribed with extreme caution. Very rare cases of agranulocytosis and thrombocytopenia may occur during treatment. Usually they pass after Dopegyt is canceled. Some patients may develop swelling or weight gain while taking Dopegite; in these conditions, diuretics should be prescribed. Dopegitum treatment cannot be continued with an increase in edema or the development of symptoms of heart failure.Methyldopa is displayed during dialysis. Therefore, after this procedure, blood pressure may increase. Since methyldopa has fluorescence at the same wavelength as catecholamines, high concentrations of catecholamines can be detected in the urine, which prevents the diagnosis of pheochromocytoma. However, methyldopa does not affect the measurement results of the IUD (vanillyl almond acid). Patients receiving Dopegyt should reduce the dose of drugs for general anesthesia. If arterial hypotension occurs during general anesthesia, vasoconstrictor agents may be administered to correct it. Adrenergic receptors remain sensitive to treatment with methyldopa. In patients with severe bilateral lesion of the cerebral vessels, involuntary choreoathetotic movements may rarely occur. During the reception Dopegita should avoid taking alcoholic beverages.
Use during pregnancy and lactation
The results of clinical studies revealed no signs of damage to the newborn or fetus when using the drug in the second and third trimesters of pregnancy. However, it is recommended to prescribe the drug Dopegyt to pregnant women only under strict indications.
Dosage and administration
The drug Dopegyt requires individual dosing. Dopegyt is prescribed for adults, orally, in the initial dosage of 250 mg in the evening (in the first two days). Over the next every two days, a single dose is increased by 250 mg until the optimal hypotensive effect is achieved (as a rule, it is noted upon reaching a daily dose of 1 g divided into 2-3 doses). First of all, it is recommended to increase the evening dose in order to reduce the sedative effect. The maximum daily dosage of the drug Dopegyt - 2 g. When combined therapy with other antihypertensive drugs, the maximum daily dose of Dopegita should not exceed 500 mg. The dose of the drug is gradually reduced after reaching a stable hypotensive effect to the level of the minimum effective dosage. Patients with impaired renal function is recommended to reduce a single dose of the drug. The initial daily dosage of Dopegita for children is 10 mgkg, divided into 2-4 doses.The maximum daily dosage of the drug Dopegyt for children should not exceed 65 mgkg. For elderly patients it is recommended to prescribe the initial dosage of the drug 125 mg once or twice a day. The maximum daily dose for elderly patients is 2 g, divided into 2 doses.
Side effects
When Dopegita is used, the appearance of: lethargy, drowsiness, lethargy, facial nerve palsy, parkinsonism, paresthesia, spontaneous chorioathetoid movements, staggering during walking, dizziness, headache. Orthostatic hypertension, peripheral edema, bradycardia, hyperemia of the upper half of the body, exacerbation of the phenomena of heart failure, increased angina, in rare cases - pericarditis, myocarditis. Glossalgia, dryness of the oral mucosa, vomiting, nausea, diarrhea, colitis, hepatotoxicity, pancreatitis, jaundice, increased activity of hepatic transaminases. Leukopenia, hemolytic anemia, agranulocytosis, thrombocytopenia. Arthralgia, myalgia. Galactorrhea, gynecomastia, hyperprolactinemia. Reduced libido, reduced potency, amenorrhea. Fever, rash, exanthema, toxic epidermal necrolysis (Lyell's syndrome). Inflammation of the salivary glands, nasal congestion. Positive direct Coombs test (when taking the drug for more than 6 months at a daily dosage of> 1 g).
Overdose
In case of an overdose of Dopegyt, the development of severe arterial hypotension, weakness, severe bradycardia, drowsiness, tremor, lethargy, dizziness, flatulence, constipation, diarrhea, vomiting, nausea, intestinal atony may be possible. Overdose treatment: shortly after ingestion - flush the stomach and stimulate vomiting in order to reduce the amount of the absorbed drug. It is advisable to control the BCC, heart rate, electrolyte balance, the functions of the kidneys, intestines and brain. The introduction of sympathomimetic drugs (epinephrine) is allowed if necessary.
Interaction with other drugs
The combination of the drug with MAO inhibitors can lead to increased side effects: hypotension or hypertensive crisis with psychomotor agitation. The combination with tricyclic antidepressants can reduce the hypotensive effect of the drug and provoke the appearance of headaches, tachycardia, agitation.Combined use with levodopa can lead to increased anti-Parkinsonian effect, which is caused by inhibition of peripheral decarboxylation of levodopa under the action of methyldopa and an increase in the concentration of levodopa in the central nervous system. In cases where inhibition of decarboxylation predominates in the central nervous system, a decrease in the anti-Parkinsonian effect of levodopa occurs. The combination of Dopegita with drugs that contain levodopa + carbidopa, can lead to the development of orthostatic hypotension. In such cases, patients are advised to be in a horizontal position for 1-2 hours after taking the drugs. The combination of dopegita with haloperidol leads to an increased likelihood of developing dementia; a combination with digoxin in elderly patients may lead to an increased likelihood of developing SSS. To increase the hypotensive effect of the drug, it is advisable to combine it with diuretics, hydralazine and nifedipine. Simultaneous administration of the drug with β-blockers may lead to the development of orthostatic hypotension. Simultaneous administration with adrenergic agonists, indomethacin and other NSAIDs leads to a decrease in the severity of the hypotensive effect of the drug. The combination of Dopegita with anxiolytics (tranquilizers) enhances the hypotensive effect of the drug. Alkalization of urine during the treatment with methyldopa leads to an increase in its action, acidification of urine to a decrease in action. The drug should be stopped 7-10 days prior to general anesthesia in order to avoid the development of a collaptoid state. Medicines for general anesthesia (sodium thiopental or halothane) should be carefully prescribed to patients taking methyldopa. Use of diethyl ether is contraindicated. Dopegyt increases the hepatotoxicity of oral contraceptives and lithium salts. The drug is incompatible with reserpine. Care should be taken when combining Dopegita with quinidine, neuroleptics, acetazolamide and procainamide.
special instructions
In some cases, hemolytic anemia may develop during therapy. When symptoms of the disease appear, hematocrit and hemoglobin concentration must be determined. When confirming the diagnosis, it is necessary to additionally assess the degree of hemolysis.With the development of hemolytic anemia, dopegite is discontinued. With prolonged therapy, a positive Coombs test can be determined. If this phenomenon did not occur during the first year of Dopegyt administration, further detection is unlikely. Rarely, this disorder is observed in patients taking the drug in a daily dose of less than 1 g. If a positive direct Coombs test is detected while taking the drug, it is necessary to exclude the patient from hemolytic anemia and determine the clinical significance of this phenomenon. In rare cases, when Dopegita is used, reversible leukopenia and granulocytopenia may occur. As a rule, after stopping treatment, the number of granulocytes returns to normal. In some patients, fever develops during the first 21 days of therapy, which in rare cases is accompanied by eosinophilia or increased activity of hepatic transaminases. In addition, the use of Dopegita may be accompanied by the development of jaundice, which appears during the first 2-3 months of therapy. In some cases, cholestasis and fatal necrotic hepatitis may develop. If an unexplained fever occurs, it is recommended to determine the activity of hepatic transaminases and complete blood count with a leukocyte formula. With the development of jaundice, fever, or with increased activity of hepatic transaminases, therapy should be stopped immediately. If the appearance of these symptoms is associated with hypersensitivity to the active substance of the drug, then after discontinuation of Dopegyt the fever disappears, and functional liver tests return to normal values. It is not recommended to resume therapy in such patients. Patients with liver pathology in the history of Dopegyt should be taken with extreme caution. In some patients, peripheral edema and weight gain are observed during therapy. These side effects are easily eliminated with diuretics. If symptoms of heart failure appear and edema increases, therapy should be discontinued. Patients receiving Dopegyt may require lower doses of anesthetics. With the development of hypotension during general anesthesia, therapy with vasopressors should be used.In case of bilateral lesion of cerebral vessels (cerebrovascular disease), Dopegyt administration may be accompanied by involuntary choreoathetotic movements. In this case, therapy is stopped. The drug should be used with great caution in the treatment of patients with hepatic porphyria and their close relatives. Dopegyt can affect the results of measuring the concentration of uric acid, creatinine and aspartate aminotransferase in serum. It is also possible to obtain false-positive results of the determination of the content of catecholamines in the urine by the fluorescent method, which may complicate the diagnosis of pheochromocytoma. Alcohol should not be consumed during therapy. Reception Dopegita may be accompanied by sedative effects, which, as a rule, are transient in nature and develop at the beginning of therapy or with an increase in the dose taken. In this case, patients should not perform work that requires increased attention, for example, to drive vehicles or machinery.