Overview
Methyldopa is a centrally-acting antihypertensive agent used primarily for the management of hypertension. It works by stimulating central alpha-adrenergic receptors, leading to reduced sympathetic outflow and lowering of blood pressure. It has been used for decades and is considered safe during pregnancy.
Mechanism of Action
Methyldopa is metabolized to alpha-methylnorepinephrine in the brain, which acts as an agonist at central alpha-2 adrenergic receptors. This stimulation inhibits sympathetic outflow from the brainstem, resulting in decreased peripheral vascular resistance and reduced blood pressure without significantly affecting cardiac output.
Indications
- Hypertension
Common Doses
- 250 mg
- 500 mg
Dosage
Initial adult dosage is 250 mg two to three times daily for first 48 hours, then titrated at intervals of at least 2 days. Maintenance dose typically ranges from 500 mg to 2 g daily in divided doses, with maximum recommended dose of 3 g daily. Pediatric dosing based on 10 mg/kg/day in divided doses, up to maximum of 65 mg/kg/day or 3 g daily.
Contraindications
- Active hepatic disease (acute hepatitis, active cirrhosis)
- Previous liver disorders associated with methyldopa therapy
- Hypersensitivity to any component
- Concurrent therapy with monoamine oxidase (MAO) inhibitors
Side Effects
- Sedation (especially during initiation)
- Orthostatic hypotension, bradycardia, edema
- Hepatitis, abnormal liver function tests
- Positive Coombs test, hemolytic anemia
- Nausea, constipation, dry mouth
- Headache, dizziness, weakness
- Parkinsonism, depression, nightmares
- Nasal stuffiness, rash
- Gynecomastia, impotence, lactation
Interactions
- Potentiation of antihypertensive effects with other antihypertensives
- Reduced bioavailability when taken with ferrous sulfate or ferrous gluconate
- Increased risk of lithium toxicity with concurrent use
- MAO inhibitors contraindicated
- Reduced anesthetic requirements during surgery
Counseling Points
- Take exactly as prescribed, do not stop abruptly
- Rise slowly from sitting/lying position to prevent dizziness
- Report fever, yellowing of skin/eyes, unusual fatigue, or dark urine immediately
- Avoid iron supplements within 2 hours of methyldopa dose
- Sedation may occur initially but usually improves with continued use
- Regular blood pressure monitoring required