Usage
- Methyldopa is primarily prescribed for the treatment of hypertension (high blood pressure), especially in patients who are pregnant or have chronic kidney disease. It is considered safe to use during all trimesters of pregnancy and during breastfeeding. However, it is no longer a first-line treatment for most other patients with hypertension.
- Pharmacological Classification: Centrally acting antihypertensive, adrenergic receptor agonist (specifically, alpha-2 adrenergic receptor agonist).
- Mechanism of Action: Methyldopa is converted to alpha-methylnorepinephrine in the central nervous system. Alpha-methylnorepinephrine stimulates central alpha-2 adrenergic receptors, leading to a decrease in sympathetic outflow, reduced peripheral vascular resistance, and lowered blood pressure.
Alternate Names
- International Nonproprietary Name (INN): Methyldopa
- Other Names: Methyldopate hydrochloride (IV formulation)
- Brand Name: Aldomet
How It Works
- Pharmacodynamics: Methyldopa lowers blood pressure by decreasing peripheral vascular resistance while having little effect on heart rate or cardiac output. It does not usually reduce glomerular filtration rate or renal blood flow. It has sedative effects related to its central mechanism of action.
- Pharmacokinetics:
- Absorption: Methyldopa is well-absorbed orally. Peak plasma concentrations occur in 3-6 hours.
- Metabolism: It is extensively metabolized in the liver. The active metabolite, alpha-methylnorepinephrine, is responsible for its antihypertensive effect.
- Elimination: Primarily excreted in the urine, both as unchanged drug and metabolites. The elimination half-life is about 2 hours.
- Mode of Action: Methyldopa’s metabolite, alpha-methylnorepinephrine, acts as an agonist at central alpha-2 adrenergic receptors in the brainstem. Stimulation of these receptors inhibits sympathetic outflow from the central nervous system to the heart and blood vessels.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Alpha-2 adrenergic receptor agonist, reduces sympathetic outflow.
- Elimination Pathways: Renal excretion.
Dosage
Standard Dosage
Adults:
- Initial: 250 mg orally 2-3 times a day for the first 48 hours.
- Maintenance: 500 mg to 2 g orally daily, divided into 2-4 doses.
- Maximum: 3 g orally daily.
Children:
- Initial: 10 mg/kg orally daily, divided into 2-4 doses.
- Maximum: 65 mg/kg or 3 g daily, whichever is less.
- Pediatric Safety Considerations: Monitor for hypotension and sedation.
Special Cases:
- Elderly Patients: Start with a lower dose (e.g., 125 mg twice daily) and titrate slowly. Maximum dose: 2 g/day. Monitor closely for syncope.
- Patients with Renal Impairment: Adjust dosage frequency based on creatinine clearance (CrCl). CrCl < 15 mL/min: every 12-24 hours. CrCl 15-50 mL/min: every 8-12 hours.
- Patients with Hepatic Dysfunction: Contraindicated in active hepatic disease. Use with caution in patients with a history of liver problems.
- Patients with Comorbid Conditions: Use with caution in patients with severe cerebrovascular disease, depression, or those undergoing surgery.
Clinical Use Cases
- Intubation: No specific dosage adjustments.
- Surgical Procedures: May require dosage adjustments of concomitant antihypertensive agents.
- Mechanical Ventilation: No specific dosage adjustments.
- Intensive Care Unit (ICU) Use: No specific dosage adjustments.
- Emergency Situations: Hypertensive emergency: 250-500 mg IV every 6 hours up to a maximum of 1 g every 6 hours or 4 g/day. Switch to oral administration once blood pressure is controlled.
Dosage Adjustments
- Adjust dosage based on patient response, renal/hepatic function, and concomitant medications.
- May need lower doses in elderly patients and those with renal impairment.
Side Effects
Common Side Effects
- Sedation, drowsiness
- Headache
- Dizziness, lightheadedness
- Dry mouth
- Edema (swelling)
- Nausea, vomiting, diarrhea
Rare but Serious Side Effects
- Hepatotoxicity (liver damage)
- Hemolytic anemia
- Depression
- Drug-induced lupus
- Myocarditis
Long-Term Effects
Adverse Drug Reactions (ADR)
- Hepatotoxicity, hemolytic anemia, and drug-induced lupus.
Contraindications
- Active liver disease (acute hepatitis, active cirrhosis)
- History of methyldopa-induced liver disorders
- Hypersensitivity to methyldopa
- Concurrent use of monoamine oxidase inhibitors (MAOIs)
- Pheochromocytoma
Drug Interactions
- MAOIs: Concomitant use is contraindicated.
- Other Antihypertensives: Additive hypotensive effects. Monitor blood pressure closely.
- Lithium: Increased risk of lithium toxicity.
- Tricyclic Antidepressants: Enhanced hypotensive effects.
- CNS Depressants: Increased sedation.
- Iron Supplements: May decrease methyldopa absorption.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B (oral) and C (IV). Generally considered safe for use during pregnancy, but benefits must outweigh risks.
- Breastfeeding: Methyldopa is excreted in breast milk in low concentrations. Generally considered safe for use during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Stimulates central alpha-2 adrenergic receptors, reducing sympathetic outflow and blood pressure.
- Side Effects: Sedation, headache, dizziness, dry mouth, edema. Serious side effects include liver damage, hemolytic anemia, and depression.
- Contraindications: Active liver disease, hypersensitivity, MAOI use.
- Drug Interactions: MAOIs, other antihypertensives, lithium, tricyclic antidepressants.
- Pregnancy & Breastfeeding: Generally considered safe.
- Dosage: Initial: 250 mg orally 2-3 times daily; maintenance: 500 mg-2 g daily.
- Monitoring Parameters: Blood pressure, liver function tests, complete blood count (CBC), particularly during the first 6-12 weeks of treatment.
Popular Combinations
- Hydrochlorothiazide: Combined in a single tablet for enhanced antihypertensive effect.
Precautions
- General Precautions: Monitor liver function and CBC.
- Specific Populations: See dosage adjustments for elderly and patients with renal impairment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Methyldopa?
A: Adults: Initial dose is 250 mg orally 2-3 times a day, increasing to a maintenance dose of 500 mg-2 g daily divided into 2-4 doses. Children: Initial dose is 10 mg/kg/day in 2-4 divided doses. Maximum daily dose: 65 mg/kg or 3g, whichever is less.
Q2: What are the common side effects of Methyldopa?
A: Common side effects include drowsiness, headache, dizziness, dry mouth, and edema.
Q3: Is Methyldopa safe to use during pregnancy?
A: Yes, generally methyldopa is considered safe for use during pregnancy, but the benefits must outweigh the risks.
Q4: What are the contraindications for using Methyldopa?
A: Contraindications include active liver disease, history of methyldopa-induced liver problems, and concurrent use of MAOIs.
Q5: How does Methyldopa work to lower blood pressure?
A: It works by stimulating central alpha-2 adrenergic receptors, which reduces sympathetic outflow and lowers peripheral vascular resistance.
Q6: What are the serious side effects of Methyldopa that require medical attention?
A: Serious side effects include liver damage (hepatotoxicity), hemolytic anemia, and depression. Seek immediate medical attention if these occur.
Q7: Does Methyldopa interact with other medications?
A: Yes, it can interact with other antihypertensives, MAOIs, lithium, and tricyclic antidepressants.
Q8: Can tolerance develop to Methyldopa?
A: Yes, tolerance may develop, usually between the second and third month of therapy.
Q9: What should patients be monitored for while taking Methyldopa?
A: Blood pressure, complete blood count (CBC), and liver function tests.
A: Methyldopate hydrochloride.
