HYDOPA (Methyldopa Tablets)
Methyldopa is an aromatic-amino-acid decarboxylase inhibitor in animals and in man. Only methyldopa, the L-isomer of α-methyldopa, has the ability to inhibit DOPA decarboxylase and to deplete animal tissue of norepinephrine. In man the antihypertensive activity appears to be due to 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 rennin activity may decrease in the course of methyldopa therapy.
Although mechanism of action has yet to be conclusively demonstrated, the resultant hypertensive effect is most likely due to the drugs action on the CNS. Methyldopa is decarboxylated to α-methyl norepinephrine, in the CNS, where it is thought that it stimulate the central inhibitory α-adrenergic receptors, leading to a reduction in sympathetic tone leading to a fall in total peripheral resistance and blood pressure. It may also act as a false neurotransmitter and have some inhibitory actions on plasma rennin activity. Reduction in plasma rennin activity, tissue concentration of dopamine, as well as the inhibition of both central and peripheral norepinephrine, epinephrine and serotonin production may also contribute to the drug’s antihypertensive effect although this is not a major mechanism of action. This is done through the inhibition of the decarboxylation of dihdroxyphenylamine (DOPA), the precursor of norepinephrine and of 5-hydroxytryptophan (5-HTP); the precursor of serotonin in the CNS and in most peripheral tissues.
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. On oral administration the effects of methyldopa reach a maximum in 4 to 6 hours following a single dose, although the maximum hypertensive effect may not occur until the second or third day of continuous treatment, some effect is usually apparent for 48 hours after its withdrawal.
Hydopa Tablets are administered by the oral route in the treatment of severe hypertension and is primarily indicated in conditions like hypertension, hypertension in pregnancy, hypertension emergencies, primary hypertension, renal hypertension and can also be given in adjunctive therapy as an alternative drug of choice in Postmenopausal flushing. It reduces the standing and to a lesser extent the supine blood pressure.
Dosage and administration
Initiation of therapy in adults: The usual starting dosage of methyldopa is 250mg two or three times a day in the first 48 hours. The daily dosage then may be increased or decreased, preferably at intervals of not less than two days, until adequate response is achieved. To minimize the sedation, start dosage increases in the evening. By adjustment of dosage, morning hypotension may be prevented without sacrificing control of afternoon blood pressure. When methyldopa is given to patients on other antihypertensives, the dose of these agents may need to be adjusted to effect a smooth transition. When methyldopa is given with antihypertensive other than thiazides, the initial dosage of methyldopa should be limited to 500mg daily in divided doses, when methyldopa is added to thiazide the dosage of thiazide need to be changed.
Maintenance therapy in adults: the usual daily dosage of methyldopa is 500mg to 2g in two to four doses. Although occasional patients have responded to higher doses, the maximum recommended daily dosage is 3g. once an effective dosage range is attained, a smooth blood pressure response occurs in most patients in 12 to 24 hours. Since methyldopa has a relatively short duration of action, withdrawal is followed by return of hypertension usually within 48 hours. This is not complicated by an overshoot of blood pressure. Occasionally tolerance may occur usually between the second and third month of therapy.
Adding diuretic or increasing the dosage of methyldopa frequently will restore effective control of blood pressure. A thiazide may be added at any time during methyldopa therapy and is recommended if therapy has not been started with a thiazide or if effective control of blood pressure cannot be maintained on 2g of methyldopa daily or if it is necessarily to reduce the side effects due to administration of large doses of methyldopa. This will also reduce oedema that sometimes occurs with methyldopa therapy and the development of tolerance. Methyldopa is largely excreted by the kidney and patients with impaired renal function may respond to smaller doses. Syncope iin older patients may be related to an increased sensitivity and advanced arteriosclerotic vascular disease. This may be avoided by lower doses.
Treatment of pediatrics: initial dosage is based on 10mg/kg of body weight daily in two to four doses. The daily dosage is increased or decreased until adequate response is achieved. The maximum dosage is 65mg/kg or 3g daily, whichever is less.
The adverse effects associated with methyldopa include; drowsiness, dizziness, lightheadedness, nausea, vomiting, headache, weakness, fatigue, decreased libido, impaired concentration and memory, mild psychoses, depression, disturbed sleep and nightmares, paraesthesias, bell’s palsy and Parkinsonism. Other adverse effects include fluid retention and oedema which responds to diuretics, angina pectoris may be aggravated, bradycardia and syncope.
Precautions and warnings
- The patient should have hemoglobin, hemocrit and ESR assessed before and during methyldopa therapy because of the risk of the hemolytic anemia. Hydopa Tablets should be used with caution in patients with impaired kidney or liver function or in patients with a history of hemolytic anaemia or liver disease.
- It is advisable to make periodic blood counts and to perform liver-function test at intervals during the first 6 to 12 weeks of treatment or if the patients develops an unexplained fever. Patients taking methyldopa mmay produce a positive response to a direct Combs’ test.
- Care is also advisable in patients withParkinsonism, cardiovascular insufficiency and mental depression.
- Hydopa Tablets should not be given to patients with active liver disease or autoimmune disease or phaeochromocytoma. Methyldopa has been reported to aggravate porphyria
- Lower doses of general anesthetics may be required in patients taking methyldopa. The hypotensive effects of methyldopa are enhanced by thiazide diuretics and other antihypertensive agents but may be antagonized by sympathomimetics or tricyclic antidepressants. Care is required if methyldopa is given to patients receiving monoamine oxidase inhibitors.
- Hydopa Tablets may cause sedation, impaired physical coordination and/or reduced mental alertness usually transient, during the initial period of therapy or whenever the dose is increased. The patient should be warned not to drive or operate machinery if sedated.
Pregnancy and lactation
Methyldopa should be used during pregnancy only if clearly needed.
Methyldopa appears in breast milk, therefore caution should be exercised when methyldopa is given to a nursing woman.
Methyldopa is contraindicated in conditions like hepatic disease, hypersensitivity and postural hypotension
Methyldopa is known to interact with other drugs like Aldesleukin, Amantadine, Apomorphine, Cabergoline, Chlorpromazine HCL, Disipramine HCL, Diazoxide, Doxepin HCL, Fluphenazine, Furazolide, Gastodene, Haloperidol, Iron salts, Levodopa, Lithium. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.
Overdose and treatment
Methyldopa (alpha-methyldopa) can cause profound hypotension when ingested in sufficient quantity by a suicidal patient. The effect is more marked upon the blood pressure when the patient is standing. Treatment of hypotension should include placing the patient in the recumbent position, administering fluids intravenously and vasopressors where indicated. Other symptoms of overdose include bloating, constipation, diarrhea, dizziness, extreme drowsiness, gas, light-headedness, nausea, slow heartbeat, vomiting and weakness