Methyldopa is a prodrug which is metabolized to the active agent, alpha-methylnorepinephrine.

Alpha-methylnorepinephrine acts in the brain, inhibiting adrenergic outflow from the brainstem. Inhibition of sympathetic outflow results in a decrease in blood pressure.

Methyldopa produces no change in cardiac output in younger patients, but in older patients a decline in cardiac output results from reduced heart rate and stroke volume. The reduction in stoke volume occurs due to increased venous pooling (decreased preload).

Since renal blood flow and function is maintained during methyldopa treatment, methyldopa maybe valuable in managing hypertensive patients with renal insufficiency.

Adverse Effects:

• Dry Mouth

• Reduced libido

• Parkinsonian signs

• Hyperprolactinemia (gynecomastia, galactorrhea)

• Bradycardia (in patients with SA nodal abnormality)

• Hepatoxicity (avoid in patients with hepatic disease)

• positive Coombs' test (20%)\

• 1-5% of those with postive Coombs' develop hemolytic anemia (requiring immediate discontinuation of the drug)