Doparine

Each film-coated tablet contains: Methyldopa (as sesquihydrate) 250 mg.
Methyldopa, the L-isomer of alpha-methyldopa is levo-3(3,4-dihydroxyphenyl)-2-methylalanine. Its empirical formula is C₁₀H₁₃NO₄ with a molecular weight of 211.22.
It is sparingly soluble in water, very soluble in 3N hydrochloric acid; slightly soluble in alcohol; practically insoluble in either.

Pharmacology: Pharmacokinetics: Methyldopa is variably and incompletely absorbed after oral administration, apparently by an amino-acid active transport system. The mean bioavailability has been reported to be about 50%. It is extensively metabolized and is excreted in urine mainly as unchanged drug and the O-sulfate conjugate. It crosses the blood-brain barrier and is decarboxylated in the CNS to active alpha-methylnoradrenaline.
The elimination is biphasic with a half-life of about 1.7 hours in the initial phase; the second phase is more prolonged. Clearance is decreased and half-life prolonged in renal impairment. Plasma protein binding is reported to be minimal. Methyldopa crosses the placenta; small amounts are distributed into breast milk.

Methyldopa is an antihypertensive drug that is thought to have a predominantly central action. It is decarboxylated in the Central Nervous System to alpha-methyladrenaline which is thought to stimulate alpha 2 adrenoceptors resulting in a reduction in sympathetic tone and a fall in blood pressure. It may also act as false neurotransmitter, and have some inhibitory actions on plasma renin activity. Methyldopa reduces the tissue concentrations of dopamine, noradrenaline, adrenaline, and serotonin.
Methyldopa is used in the management of hypertension. Although other drugs with fewer adverse effects are generally preferred, methyldopa may however be the drug of choice for hypertension in pregnancy. When given with thiazide diuretics edema and tolerance with methyldopa therapy may be reduced.

Adult: Initial dose of 250 mg of methyldopa two to three times daily for 2 days. Adjusted thereafter with maximum dose of 3 g daily or as prescribed by the physician.
For maintenance dose, 500 mg to 2 g daily or as prescribed by the physician.
Elderly: Initial dose of 125 mg twice daily. Dose may be increased gradually if necessary but should not exceed 2 g daily or as prescribed by the physician.

Methyldopa should be used with caution in patients impaired renal or hepatic function or history of haemolytic anaemia, liver disease, or depression. It should not be given to patients with active liver disease or depression and it is not recommended for phaeochromocytoma.
Patients taking methyldopa may produce a positive response to a direct Coomb's test reaction will aid cross-matching.
Methyldopa may cause sedation. Affected patient is not advisable to drive or operate machinery.

Adverse effects of methyldopa are mostly consequences of its pharmacological action. Drowsiness is common, especially on initial and following an increase in dosage. Dizziness and light-headedness may be associated with postural hypotension. Methyldopa is frequently associated with fluid retention and oedema, which responds to diuretics but may rarely progress to heart failure. Angina pectoris may be aggravated. Bradycardia, syncope and prolonged carotid sinus hypersensitivity have been reported. The mental neurological effects of methyldopa have been included impaired concentration and memory, mild psychoses, depression, disturbed sleep and nightmares, paraesthesias, Bell's palsy, involuntary choreoathetotic movements and parkinsonism.
Methyldopa may produce gastrointestinal disturbances such as nausea and vomiting, diarrhea, constipation, and rarely pancreatitis and colitis. A black or sore tongue, and inflammation of the salivary glands have occurred, and dry mouth is quite common. A positive Coomb's Test may occur in 10 to 20% of all patients in prolonged therapy but only small proportion may develop haemolytic anemia. Other hypersensitivity effects have included myocarditis, fever, eosinophilia. And disturbances of liver function, rashes, lichenoid and granulomatous eruptions, toxic epidermal necrolysis, flu-like syndrome, nocturia; uraemia, nasal congestion and retroperitoneal fibrosis.
Hyperprolactinaemia may occur, with breast enlargement or gynaecomastia, galactorrhoea and amenorrhoea. Hepatitis may develop particularly in the first 2 to 3 months therapy and is generally reversible in discontinuation but fatal hepatic necrosis as occurred. Antinuclear antibodies may develop and cases of lupus-like syndrome have been reported. Methyldopa may occasionally cause urine to darken on exposure to the air because of the breakdown of the drug or its metabolites.
Treatment of Adverse Reactions: Withdrawal of methyldopa or reduction in dosage causes the reversal of many side-effects. If overdosage occurs, activated charcoal may be given or the stomach may be emptied by lavage. Treatment is largely symptomatic, but if necessary, intravenous fluid infusion may be given to promote urinary excretion, and vasopressors given cautiously. Severe hypotension may respond to placing the patients in the supine with the feet raised.

The hypotensive effects of methyldopa are potentiated by diuretics, other antihypertensives, and drug with hypotensive effects. However, there have been reports of paradoxical antagonism of the hypotensive effects by tricyclic antidepressants, antipsychotics, and beta blockers. Sympathomimetics may also antagonize the hypotensive effects.
There may be an interaction between methyldopa and MAOI's. Patient care is required if they are given concomitantly. Caution is also needed with entacapone since it might inhibit the metabolism of methyldopa.
Patient receiving methyldopa may require lower doses of general anaesthetics.

Store at temperature not exceeding 30°C.

Other Antihypertensives

C02AB01 - methyldopa (levorotatory) ; Belongs to the class of methyldopa, centrally-acting antiadrenergic agents. Used in the treatment of hypertension.

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