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*.

Amlodipine – A Powerful Calcium Channel Blocker for Hypertension and Angina

 

Introduction:

*Amlodipine* is a widely prescribed *calcium channel blocker (CCB)* used in the treatment of *hypertension*, *angina pectoris*, and *coronary artery disease*. Belonging to the *dihydropyridine class*, it works by relaxing blood vessels, making it easier for the heart to pump blood and reducing chest pain caused by ischemia.

Mechanism of Action:

Amlodipine *inhibits the influx of calcium ions* through *L-type calcium channels* in:

- *Vascular smooth muscle* → causing *vasodilation*

- *Cardiac muscle* → reduced oxygen demand

This leads to:

- *Lowered blood pressure*

- *Improved oxygen delivery* to the myocardium

- *Reduction in anginal symptoms*

Pharmacokinetics:

- *Absorption*: ~60–90% orally bioavailable  

- *Onset*: 6–12 hours  

- *Peak concentration*: 6–12 hours post-dose  

- *Half-life*: 30–50 hours (allows once-daily dosing)  

- *Metabolism*: Hepatic (CYP3A4)

- *Excretion*: Mainly via urine

Pharmacodynamics:

- *Selective vasodilation* of peripheral arterioles  

- Minimal effect on heart rate or myocardial contractility  

- Effective in all age groups, especially in *elderly* and *Afro-Caribbean* patients

Indications:

- *Primary Hypertension* (first-line)  

- *Stable and Vasospastic Angina*  

- *Coronary Artery Disease (CAD)*  

- *Hypertensive emergencies* (as part of combination therapy)  

- *Raynaud’s phenomenon* (off-label)

Drug of Choice For:

- *Elderly patients with isolated systolic hypertension*  

- *Pregnant women* (with caution; not first-line)  

- *Patients with angina & hypertension co-existence*  

- *Black patients with hypertension*

Contraindications:

- Hypersensitivity to Amlodipine or other dihydropyridines  

- Severe *aortic stenosis*  

- *Cardiogenic shock*  

- Unstable heart failure (use with caution)

Side Effects:

*Common:*

- Peripheral *edema* (ankles, feet)  

- Headache  

- Flushing  

- Fatigue  

- Dizziness

*Less Common:*

- Palpitations  

- Nausea  

- Abdominal pain  

- Sleep disturbances

*Rare:*

- Gingival hyperplasia  

- Liver enzyme elevation  

- Allergic reactions

Dosage:

- *Adults (Hypertension/Angina)*:

  - *Starting dose*: 5 mg once daily

- *Max dose*: 10 mg once daily  

- *Elderly or hepatic impairment*: Start at 2.5 mg daily  

- *Children (6–17 years)*: 2.5–5 mg once daily

Brand Names:

- *Norvasc* (Pfizer – original brand)  

- *Amlopres*  

- *Amlodac*  

- *Amlovas*  

- *Amlogard*  

- *Cardvas*  

- *Istin*

Price:

- *Pakistan*: PKR 5–20 per 5 mg tablet  

- *India*: INR 2–15 per tablet  

- *International*: 0.10–1 per tablet (generic)

Conclusion:

Amlodipine is one of the *most effective and well-tolerated antihypertensives*, offering *24-hour blood pressure control* and *angina relief* with once-daily dosing. Its long half-life, affordability, and efficacy make it a popular choice for both primary care and cardiology settings.