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Methyldopa

Methyldopa or alpha-methyldopa (brand names Aldomet, Apo-Methyldopa, Dopamet, Novomedopa) is a centrally-acting antiadrenergic antihypertensive medication. more...

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Methyldopa is approximately 50% absorbed from the gut; it is metabolized in the intestines and liver; its metabolite alpha-methylnorepineprine acts in the brain to stimulate alpha-adrenergic receptors decreasing total peripheral resistance. It is excreted in urine.

Methyldopa, in its active metabolite form, leads to increased alpha-2 receptor-mediated inhibition of SNS (centrally and peripherally), allowing PSNS tone to increase. Such activity leads to a decrease in total peripheral resistance (TPR) and cardiac output.

All drugs in this class can cause "rebound" hypertension due to an up-regulation of alpha-2 receptors while under the influence of the drug. If the drug is abruptly withdrawn, the "original" as well as "new" receptors become available and cause a severe reaction to the "normal" SNS activity (which is usually in excess). In other words, the SNS typically releases more norepinephrine (NE) than is needed to activate receptors (leading to a sustained response), and extra receptors leads to an over-response (in this case mediated by alfa-2 receptors leading to vascular smooth muscle constriction = rebound hypertension).

When introduced it was a mainstay of antihypertensive therapy, but its use has declined, with increased use of other classes of agents. One of its important present-day uses is in the management of pregnancy-induced hypertension, as it is relatively safe in pregnancy compared to other antihypertensive drugs.

Side effects (some of these are serious and need to be reported to a physician)
A possible side-effect of methyldopa is breast enlargement in men (gynecomastia). Hyper-prolactinaemia. Many patients report orthostatic hypotension, which tends to improve over time. Skin rashes. Bruising. Low white blood cells. Thrombocytopenia (Low platelets). Haemolytic anaemia: the direct Coombs test may become positive. Tiredness. Depression. Impotence.

This list is not complete.
Side effects are usually fewer if the dose is less than 1 gm per day.

Read more at Wikipedia.org


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