Methyldopa – A Safe Antihypertensive for Pregnancy and Chronic Hypertension

 

Introduction:

*Methyldopa* is a *centrally acting antihypertensive drug*, primarily used in the treatment of *high blood pressure*, especially in *pregnant women*. It has been used safely for decades and is recommended as a *first-line therapy for gestational hypertension and preeclampsia*.

Mechanism of Action:

Methyldopa is a *prodrug* that gets converted in the brain to *alpha-methylnorepinephrine*, which stimulates *central alpha-2 adrenergic receptors*, resulting in:

- Reduced sympathetic outflow from the CNS

- Decreased heart rate and cardiac output

- Lowered peripheral vascular resistance

→ Overall *reduction in blood pressure*

Pharmacokinetics:

- *Absorption*: ~50% orally bioavailable  

- *Onset*: 4–6 hours  

- *Peak effect*: 6–8 hours  

- *Half-life*: ~1.5–2 hours (but effect lasts longer)  

- *Metabolism*: Liver  

- *Excretion*: Primarily via kidneys (urine)

Pharmacodynamics:

- Lowers both *systolic and diastolic* BP  

- No significant effect on renal blood flow  

- Causes *less reflex tachycardia* compared to other antihypertensives  

- Safe for long-term use in *pregnancy*

Indications:

- *Chronic hypertension*  

- *Hypertension in pregnancy* (including preeclampsia)  

- *Resistant hypertension* as add-on therapy  

- Pediatric hypertension (under supervision)

Contraindications:

- Active *liver disease*  

- History of *methyldopa-induced liver dysfunction*  

- *Depression*  

- Concurrent use with *MAO inhibitors*  

- *Pheochromocytoma*

Side Effects:

*Common:*

- Drowsiness, fatigue

- Dry mouth

- Headache

- Nasal congestion

*Less Common:*

- Orthostatic hypotension

- Weight gain

- Sexual dysfunction

*Serious (Rare):*

- Hemolytic anemia (Coombs positive)

- Hepatotoxicity

- Depression

- Parkinsonism-like symptoms

Dosage:

- *Initial dose (adult)*: 250 mg *2–3 times daily*  

- Can be titrated every 2 days up to *2000–3000 mg/day* (divided doses)  

- *Maintenance*: 500–2000 mg/day  

- *In pregnancy*: Often used at *250–500 mg twice daily*

*Note:* Monitor *LFTs and CBC* in long-term use.

Brand Names:

- *Aldomet* (original brand)  

- *Dopamet*  

- *Methyldopar*  

- *Methylpres*  

- *Dopegyt*  

- *Alphadopa*

Price:

- *Pakistan*: PKR 10–30 per 250 mg tablet  

- *India*: INR 3–10 per tablet  

- *International*: 0.50–2 per tablet (generic)

Conclusion:

*Methyldopa* remains a *trusted and safe option* for managing hypertension, especially in *pregnant women* where other drugs may pose risks. Though newer agents exist, its *long track record of safety*, particularly in obstetrics, secures its place in modern clinical practice. Monitoring is essential for long-term use due to potential *liver and hematological effects*.