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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 If the drug is abruptly withdrawn, the "original" as well as "new" receptors become available and cause a severe reaction to the "normal" SNS activity (which is usually in excess).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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Methyldopa a Safe Antihypertensive During Pregnancy
From OB/GYN News, 6/1/01 by Bruce Jancin

VAIL, COLO. -- Methyldopa is an old and frequently overlooked agent that, in the setting of hypertension in pregnancy, is suddenly transformed into first-line therapy, Dr. Jill Davies said at a conference on obstetrics and gynecology sponsored by the University of Colorado.

"Aldomet [methyldopa] is a category B medication. It has the longest safety record for treatment of hypertension in pregnancy. So even though outside of pregnancy it's not even close to being considered a first-line agent, we still consider it first-line therapy in pregnancy because of its safety record," said Dr. Davies of the university.

The most problematic class of antihypertensive agents in pregnancy are the angiotensin-converting enzyme inhibitors. They are particularly teratogenic and have been linked to congenital skull defects, oligohydramnios, nephrotoxicity, intrauterine growth retardation, hypoplastic lungs, and increased perinatal mortality.

[beta]-blockers, while not teratogenic, have been associated with ill effects on the fetus, most commonly intrauterine growth retardation. Of course, hypertensive patients are already predisposed to fetal growth restriction due to their underlying blood pressure disorder. However, [beta]-blockers have also been linked to growth retardation when prescribed as antiarrhythmic agents in normotensive pregnant women.

"This makes sense because [beta]-blockers lower the blood pressure systemically, which lowers uterine perfusion pressure, Dr. Davies noted.

COPYRIGHT 2001 International Medical News Group
COPYRIGHT 2001 Gale Group

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