Methyldopa (Methyldopa)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
Read on
Clinical and pharmacological group: & nbsp

Alpha-adrenomimetics

Included in the formulation
  • Dopegit®
    pills inwards 
    EGIS ZAO Pharmaceutical Plant     Hungary
  • Methyldopa
    pills inwards 
    R-PHARM, CJSC     Russia
    • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    ONLS

    АТХ:

    C.02.A.B   Methyldopa

    Pharmacodynamics:

    A selective agonist of postsynaptic α2Αadrenoreceptors of the ventrolateral region of the medulla oblongata responsible for tonic and reflex control of the sympathetic nervous system, false neurotransmitter, renin inhibitor. Has antihypertensive effect.

    Pharmacokinetics:

    Prodrug. Connection with plasma proteins <20%, sulfated metabolite ∼30-70%. Biotransformation in neurons to the active substance - α-methylnoradrenaline, in the liver (sulfation, pronounced effect of "first passage" through the liver). The half-life is 1.7 h, with chronic renal failure 4-6 h. It is excreted by the kidneys (50-70% in the form of conjugates, 25% unchanged), unabsorbed part - with feces. It is removed during hemodialysis and peritoneal dialysis.

    Indications:

    Arterial hypertension of mild and moderate severity.

    ICD-10

    IX.I10-I15.I15   Secondary Hypertension

    IX.I10-I15.I10   Essential [primary] hypertension

    Contraindications:

    · Individual intolerance.

    · Hemolytic anemia.

    · Acute hepatitis and cirrhosis.

    · Hepatic and / or renal insufficiency.

    · Collagenoses.

    · Parkinsonism.

    · Depression.

    · Pheochromocytoma.

    · Acute myocardial infarction.

    · Pronounced coronary atherosclerosis and atherosclerosis of cerebral vessels.

    · Simultaneous administration of monoamine oxidase inhibitors, levodopa.

    Carefully:

    · Acute left ventricular failure.

    · Chronic heart failure.

    · Diencephalic syndrome.

    · Porphyria.

    · Lactation.

    Pregnancy and lactation:

    FDA recommendation category B. Application during pregnancy is possible (according to strict indications). Use with caution in the period of breastfeeding (methyldopa penetrates into breast milk).

    Dosing and Administration:

    Inside, starting with 250 mg in the evening, increasing every 2 days by 250 mg (average daily dose of 1 g in 2-3 divided doses). To reduce the severity of sedation, first increase the evening dose. The maximum daily dose of 2 g (when combined with other antihypertensive drugs - not more than 500 mg per day).

    Intravenously drip for 30-60 minutes 250-500 mg per 100 ml of 5% dextrose. Elderly, the initial dose of 125 mg 1-2 times a day, the maximum daily dose of 2 g in 2 divided doses.

    Side effects:

    Side effects occur in 60% of patients, most of which are transient (reversible).

    Peripheral edema> 10%.

    A rise in body temperature occurs in 1-10% of cases in the first 3 months of treatment, often accompanied by eosinophilia and changes in functional liver samples, due to immunological reaction or hypersensitivity. It is necessary to cancel and not resume methyldopa.

    Headache and changes in mental state (drowsiness, depression - 3.6%, anxiety, nightmares, unusually bright dreams) arise in 1-10% of cases.

    Dry mouth develops in 9% of patients, the salivary glands can become inflamed.

    With a positive Coombs test (10-20%), you should abolish methyldopa and do not resume taking.

    Colitis, cholestasis, hepatitis (rarely fatal necrosis of the liver) (if functional liver tests, hepatitis or jaundice are to be reversed, do not resume methyldopa), pancreatitis, diarrhea, nausea, or vomiting.

    Autoimmune hemolytic anemia occurs in <5% of Coombs positive individuals (0.2% of patients receiving methyldopa), probably due to methyldopa suppression of T suppressors and induction-T suppressors and induction of disturbances in the reticuloendothelial system.You must cancel, do not resume reception.

    Possible development of reversible leuko- or granulocytopenia, thrombocytopenia, requiring urgent discontinuation of the drug.

    Myocarditis, aggravation of angina, paradoxical increase in blood pressure (for intravenous administration), sinus bradycardia, orthostatic hypotension.

    Lupus-like syndrome and the appearance of antinuclear antibodies are observed in 13% of patients (in 3.8% of persons with AH who did not receive methyldopa).

    Decreased libido, hyperprolactinaemia, paresthesia, chorea, choreiform irregularities, nasal congestion, darkening of urine in contact with air (decomposition of methyldopa and metabolites).

    Overdose:

    When an overdose occurs hypotension, drowsiness, bradycardia, dizziness, constipation or diarrhea, nausea, vomiting, flatulence, raspiranie in the stomach.

    With a recent oral intake, it is necessary to rinse the stomach, artificially induce vomiting. Treatment is symptomatic: hemodialysis is used, peritoneal dialysis.

    Interaction:

    Alcohol, drugs, depressing the central nervous system - intensifying the oppressive effect.

    Anticoagulants (derivatives of coumarin and indanedione) - increased anticoagulant effect.

    Bromocriptine - increasing prolactin concentration in the blood and counteracting the effects of bromocriptine.

    Haloperidol - disorientation, slowing or hindering the processes of thinking.

    Other drugs that reduce blood pressure, as well as fenfluramine - enhance the effect of methyldopa.

    Iron sulfate and gluconate - a decrease in the absorption of methyldopa by 60-70%.

    Monoamine oxidase inhibitors, including furazolidone, procarbazine and selegiline, - increased excitability, headache, arterial hypertension, hallucinations.

    Lithium - increase in lithium toxicity.

    Levodopa - weakening of the antiparkinsonian effect of levodopa, mutual enhancement of toxicity with the development of psychosis.

    Sympathomimetics - weakening of hypotensive effect of methyldopa, probable potentiation of pressor effects.

    Tricyclic antidepressants, NSAIDs, especially indomethacin, anorexigenic agents, with the exception of fenfluramine, estrogens - a weakening of the effect of methyldopa.

    Special instructions:

    During the treatment is not recommended the use of alcohol. Patients taking methyldopa should refrain from potentially dangerous activities requiring increased attention, rapid psychomotor reactions.

    Instructions
    Up