Apo-Methyldopa - General Information
An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.
Pharmacology of Apo-Methyldopa
Apo-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. Apo-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. Apo-Methyldopa reduces both supine and standing blood pressure. Apo-Methyldopa usually produces highly effective lowering of the supine pressure with infrequent symptomatic postural hypotension. Exercise hypotension and diurnal blood pressure variations rarely occur.
Apo-Methyldopa for patients
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.
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.
Additional information about Apo-Methyldopa
Apo-Methyldopa Indication: For use in the treatment of hypertension.
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. Apo-Methyldopa has been shown to cause a net reduction in the tissue concentration of serotonin, dopamine, norepinephrine, and epinephrine.
Drug Interactions: Carteolol Possible hypertensive crisis
Nadolol Possible hypertensive crisis
Oxprenolol Possible hypertensive crisis
Penbutolol Possible hypertensive crisis
Pindolol Possible hypertensive crisis
Propranolol Possible hypertensive crisis
Sotalol Possible hypertensive crisis
Timolol Possible hypertensive crisis
Terbutaline Increased arterial pressure
Salbutamol Increased arterial pressure
Pseudoephedrine Increased arterial pressure
Procaterol Increased arterial pressure
Pirbuterol Increased arterial pressure
Phenylpropanolamine Increased arterial pressure
Orciprenaline Increased arterial pressure
Phenylephrine Increased arterial pressure
Norepinephrine Increased arterial pressure
Methoxamine Increased arterial pressure
Metaraminol Increased arterial pressure
Mephentermine Increased arterial pressure
Isoproterenol Increased arterial pressure
Iron Iron decreases the absorption of dopa derivatives
Levodopa Apo-Methyldopa increases the effect and toxicity of levodopa
Lithium Signs of increased lithium levels without increase with this combination
Dobutamine Increased arterial pressure
Dopamine Increased arterial pressure
Ephedra Increased arterial pressure
Ephedrine Increased arterial pressure
Epinephrine Increased arterial pressure
Fenoterol Increased arterial pressure
Entacapone Entacapone increases the effect and toxicity of sympathomimetics
Haloperidol Apo-Methyldopa increases haloperidol effect or risk of psychosis
Food Interactions: Avoid alcohol.
No iron, zinc or fluoride within 2 hours of taking this medication.
May take Vitamin D.
Avoid natural licorice.
Increase dietary intake of magnesium, folate, vitamin B6, B12, and/or consider taking a multivitamin.
Generic Name: Methyldopa
Synonyms: Alphamethyldopa; Alpha medopa; AMD; L-Methyl Dopa; Methyldopa anhydrous; Methyldopate; Methyldopate HCL; Mk. b51
Drug Category: Adrenergic alpha-Agonists; Antihypertensive Agents; Sympatholytics
Drug Type: Small Molecule; Approved
Absorption: Absorption from the gastrointestinal tract is variable but averages approximately 50%.
Toxicity (Overdose): 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.
Protein Binding: Low (less than 20%).
Biotransformation: 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.
Half Life: The plasma half-life of methyldopa is 105 minutes.
Dosage Forms of Apo-Methyldopa: Tablet Oral
Chemical IUPAC Name: (2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid
Chemical Formula: C10H13NO4
Methyldopa on Wikipedia: https://en.wikipedia.org/wiki/Methyldopa
Organisms Affected: Humans and other mammals