Basic Profile / Key Facts
Drug Category
- Adrenergic alpha-Agonists
- Antihypertensive Agents
- Sympatholytics
Dosage Forms
- Liquid for injection
- Tablets for oral use (125 mg, 250 mg, or 500 mg)
Indications
For use in the treatment of hypertension.
Pharmacology
Methyldopa is an aromatic-amino-acid decarboxylase inhibitor in animals and in man. Only methyldopa, the L-isomer of alpha-methyldopa, has the ability to inhibit dopa decarboxylase and to deplete animal tissues of norepinephrine. In man the antihypertensive activity appears to be due solely to the L-isomer. About twice the dose of the racemate (DL-alpha-methyldopa) is required for equal antihypertensive effect. Methyldopa has no direct effect on cardiac function and usually does not reduce glomerular filtration rate, renal blood flow, or filtration fraction. Cardiac output usually is maintained without cardiac acceleration. In some patients the heart rate is slowed. Normal or elevated plasma renin activity may decrease in the course of methyldopa therapy. Methyldopa reduces both supine and standing blood pressure. Methyldopa usually produces highly effective lowering of the supine pressure with infrequent symptomatic postural hypotension. Exercise hypotension and diurnal blood pressure variations rarely occur.
Mechanism of Action
Although the mechanism of action has yet to be conclusively demonstrated, the antihypertensive effect of methyldopa probably is due to its metabolism to alpha-methylnorepinephrine, which then lowers arterial pressure by stimulation of central inhibitory alpha-adrenergic receptors, false neurotransmission, and/or reduction of plasma renin activity. Methyldopa has been shown to cause a net reduction in the tissue concentration of serotonin, dopamine, norepinephrine, and epinephrine.
Absorption
Absorption from the gastrointestinal tract is variable but averages approximately 50%.
Toxicity
The oral LD50 of methyldopa is greater than 1.5 g/kg in both the mouse and the rat. Symptoms of overdose include bloating, constipation, diarrhea, dizziness, extreme drowsiness, gas, light-headedness, nausea, severely low blood pressure, slow heartbeat, vomiting, and weakness.
Biotrnasformation / Drug Metabolism
Hepatic, extensively metabolized. The known urinary metabolites are: a-methyldopa mono-0-sulfate; 3-0-methyl-a-methyldopa; 3,4-dihydroxyphenylacetone; a-methyldopamine; 3-0-methyl-a-methyldopamine and their conjugates.
Contraindications
Contraindicated in patients with active hepatic disease, such as acute hepatitis and active cirrhosis with liver disorders previously associated with methyldopa therapy; with hypersensitivity to any component of these products; and in patients on therapy with monoamine oxidase (MAO) inhibitors.
Drug Interactions
When methyldopa is used with other antihypertensive drugs, potentiation of antihypertensive effect may
occur. Patients should be followed carefully to detect side reactions or unusual manifestations of drug
idiosyncrasy.
Patients may require reduced doses of anesthetics when on methyldopa. If hypotension does occur during
anesthesia, it usually can be controlled by vasopressors. The adrenergic receptors remain sensitive during treatment
with methyldopa.
When methyldopa and lithium are given concomitantly the patient should be carefully monitored for
symptoms of lithium toxicity. Read the circular for lithium preparations.
Several studies demonstrate a decrease in the bioavailability of methyldopa when it is ingested with
ferrous sulfate or ferrous gluconate. This may adversely affect blood pressure control in patients treated with
methyldopa. Coadministration of methyldopa with ferrous sulfate or ferrous gluconate is not recommended.
Monoamine oxidase (MAO) inhibitors: See CONTRAINDICATIONS.
Drug/Laboratory Test Interactions
Methyldopa may interfere with measurement of: urinary uric acid by the phosphotungstate method, serum
creatinine by the alkaline picrate method, and SGOT by colorimetric methods. Interference with spectrophotometric
methods for SGOT analysis has not been reported.
Since methyldopa causes fluorescence in urine samples at the same wave lengths as catecholamines,
falsely high levels of urinary catecholamines may be reported. This will interfere with the diagnosis of
pheochromocytoma. It is important to recognize this phenomenon before a patient with a possible pheochromocytoma is
subjected to surgery. Methyldopa does not interfere with measurement of VMA (vanillylmandelic acid), a test for
pheochromocytoma, by those methods which convert VMA to vanillin. Methyldopa is not recommended for the treatment of
patients with pheochromocytoma. Rarely, when urine is exposed to air after voiding, it may darken because of
breakdown of methyldopa or its metabolites.
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