Methyldopa clinical effects

Depletion of peripheral amines probably accounts for much of the beneficial antihypertensive effect of reserpine, but a central component cannot be ruled out. The effects of low but clinically effective doses resemble those of centrally acting agents (eg, methyldopa) in that sympathetic reflexes remain largely intact, blood pressure is reduced in supine as well as in standing patients, and postural hypotension is mild. Reserpine readily enters the brain, and depletion of cerebral amine stores causes sedation, mental depression, and parkinsonism symptoms. 

Clinical studies on Catapresan have been reported which indicate that a reliable and substantial lowering of blood pressure can be obtained upon oral administration in divided doses of 225-1350 7 of the drug to hypertensive patients. The effects can be seen in cases of primary and secondary, benign or malignant hypertension . The degree of pressure reduction attainable was about the same as that from a-methyldopa . Side effects encountered were dryness of the mouth and sedation, particularly at higher doses. ... 

As a result of this search, a number of new compounds with interesting properties have been developed. These include bretylium tosylate (2), guanethidine (14), methyldopa [3-(3,4-dihydroxyphenyl)alanine] (18), and pargyline (11). All these compounds produce a more selective inhibition of the sympathetic nervous system, although each differs somewhat one from the other, in both primary mode of action and clinical effects. Of these compounds, guanethidine has received the most extensive therapeutic trial and clinical acceptance. 

Cyclazenin (l-(2-gxianidinoethyl)-l,2,3,6-tetrahydro-4-picoline) was clinically effective in some cases where other agents failed However persistent side effects—parotid pain and orthostatic hypotension in particular—may limit its usefulness In combination with methyldopa efficacy was increased and side effects reduced ... 

LITHIUM CENTRALLY ACTING ANTI HYPERTENSIVES 1. Methyldopa may reduce the effect of antidepressants 2. Case reports of lithium toxicity when co-ingested with methyldopa. It was noted that lithium levels were in the therapeutic range 1. Methyldopa can cause depression 2. Uncertain at present 1. Methyldopa should be avoided in patients with depression 2. Avoid co-administration if possible if not, watch closely for clinical features of toxicity and do not rely on lithium levels... 

Activated charcoal will adsorb methyldopa and should be considered in patients with substantial recent ingestions. Standard supportive therapies, such as support of airway, breathing, and circulation, should be utilized as clinically necessary. Administration of vasopressors may be required for patients experiencing profound cardiovascular effects. Hemodialysis is of theoretical value if standard therapies fail. 

Amino Acid Enzyme Inhibitors - A comparative clinical study of the antihypertensive effects elicited by intravenous injection of a-methyldopa and a-methyl-m-tyrosine has shown, contrary to previous reports, that the latter agent has a longer duration of action in essential hypertonia and also a more pronounced orthostatic effect.2S... 

Garratty G, Amdt P, Prince HE, Shulman lA (1993) The effect of methyldopa and procainamide on suppressor cell activity in relation to red cell autoantibody production. Br J Haematol 84 310-315 Gottschall JL, Elliot W, Lianos E, McFarland JG, Wolfmeyer K, Aster RH (1991) Quinine-induced immune thrombocytopenia associated with hemolytic uremic syndrome a new clinical entity. Blood 77 306-310... 

It is perhaps difficult to challenge the evidence supporting a methyldopa-in-duced effect for both types of hepatoxicity, but there is not sufficient data, either clinical or experimental, to indicate that the syndromes are the result of hypersensitivity mechanisms. 

These findings eventually led to the first trials in man [166], in which methyldopa proved to be an effective antihypertensive agent. Since then, several thousand papers have been published on the pharmacology and clinical use of this compound. 

New clinical studies have confirmed previous reports of effective antihypertensive action with a low incidence of side effects aivi no impairment of renal hemodynamicsIn cases of poor control with ST 155 alone, combination with methyldopa or guanethidine gave good results without orthostatic or renal problems J ... 

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