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PubMed1988

Methyldopa-induced syndrome of inappropriate antidiuretic hormone secretion and bone marrow granulomatosis.

A case of an elderly man who developed severe hyponatremia and bone marrow granulomatosis while taking methyldopa is described. The hyponatremia was found to be due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Bone marrow biopsy revealed granulomas. A MEDLINE search of the English literature was done, yielding only one previous report of methyldopa-induced bone marrow granulomatosis and no previous reports of methyldopa-induced SIADH.

Aged↗
PubMed1980

Differential effects of alpha-methyldopa, clonidine and hydralazine on norepinephrine and epinephrine synthesizing enzymes in the brainstem nuclei of spontaneously hypertensive rats.

Repeated administrations of clonidine to spontaneously hypertensive rats (SHR) markedly lowered dopamine beta-hydroxylase (DBH) activity in the locus coeruleus (LC) and increased it in the spinal intermediolateral cell column (IML), while alpha-methyldopa tended to lower the enzyme activity in the medullary nucleus tractus solitarii (NTS) and A1 cell areas. Clonidine-induced inhibition of 3H-norepinephrine binding to crude cerebral membranes of SHR or Kyoto Wistar rats (KWR) as a measure of alpha-receptor agonist activity was 7 times greater than that of (+/-)alpha-methyl-(+/-)-norepinephrine. Clonidine and hydralazine significantly lowered phenylethanolamine N-methyltransferase (PNMT) activity elevated in the nucleus hypothalamicus posterior (NHP) of SHR to the level of KWR, and both drugs or alpha-methyldopa consistently increased PNMT in the nucleus paraventricularis (NPA). Peripherally active hydralazine also increased PNMT activity in the NTS, and antagonized the activity elevated in the A1 cell area of SHR to the level of KWR. In conclusion, clonidine selectively lowers DBH activity in the LC, while alpha-methyldopa appears to decrease the enzyme activity in the medullary NTS and A1 cell areas, suggesting different sites of action of both drugs. The decreased DBH activity in these nuclei may be related to stimulation of respective alpha-noradrenergic receptors. Elevating effects of all three drugs on PNMT activity in the NPA may be due to decreased baroreceptor afferent impulses to the nucleus after a fall in blood pressure.

Animals↗
PubMed1988

Comparison between the effects of urapidil and methyldopa on left ventricular hypertrophy and haemodynamics in humans.

In a randomised double-blind study the effects on left ventricular mass (LV mass) and cardiac haemodynamics of urapidil, an antihypertensive agent with a vascular postsynaptic alpha 1-blocking action and a central antihypertensive effect, were compared with those of methyldopa in 29 patients with essential hypertension. During a 3-month period, urapidil was initially given at 120 mg/day and increased to 180 mg/day if a satisfactory antihypertensive response was not achieved. Methyldopa was started at 100 mg/day and increased to 1500 mg/day if an adequate blood pressure response was not achieved. Echocardiographic measurements were obtained at baseline and after 12 weeks' active treatment. The frequency rates of responders (DBP less than 95 mm Hg) on urapidil and methyldopa were 54% and 62%, respectively, after 12 weeks. In the group as a whole there was a nonsignificant tendency for decreased LV mass on both active drugs. However, the haemodynamic changes were difficult to interpret because of baseline differences between the 2 treatment groups.

Adult↗
PubMedDate not supplied

Noneffect of methyldopa on urine glucose tests.

Methyldopa has been reported to cause a false-positive urine glucose test by the copper reduction method (Clinitest). We investigated the effect of methyldopa on urine glucose tests in 30 patients by comparing commonly used glucose oxidase methods to Clinitest. The results of our study indicate that methyldopa does not interfere with the copper reduction method for urine glucose determination.

Copper↗
PubMed1981

Histologic follow-up of alpha-methyldopa-induced liver injury.

Alpha-methyldopa-induced liver injury was studied in six patients by clinical, biochemical, histologic, and morphometric methods. The patients, all women, developed hepatic injury after long-term therapy lasting 2 to 8 years. Withdrawal of the drug resulted in improvement of the symptoms. Hepatitis with fibrosis and moderate to severe fatty accumulation was seen in most of the liver biopsies at onset of symptoms. Follow-up ranged from 7 to 24.5 months, at the end of which the liver function test results were in the normal range. A second liver biopsy showed significant decrease in fatty infiltration. Three patients showed a decrease in lipid content from moderate to mild or normal and two other patients from severe to moderate. A 73-year-old patient had chronic aggressive hepatitis with massive necrosis of the parenchyma after 8 years of therapy, and follow-up biopsy 12 months later showed cirrhosis. In this study alpha-methyldopa withdrawal resulted in a reduction of lipid and fibrous trabeculae content, possibly caused by alpha-methyldopa-induced derangement of liver function.

Aged↗
PubMed1978

Sympathetic nervous function and renin activity in hypertensives on long term drug treatment with propranolol, methyldopa or bendrofluazide.

Plasma noradrenaline and plasma renin activity were measured as indices of sympathetic activity and renin angiotensin system in similar groups of hypertensive patients receiving either propranolol, bendrofluazide or methyldopa. Plasma renin activity was similar in the propranolol and methyldopa groups and significantly lower (p less than 0.01) in both these groups than the diuretic treated subjects. Plasma noradrenaline was significantly lower (p less than 0.01) on methyldopa than either propranolol or bendrofluazide. These different effects on the renin angiotensin system and the sympathetic nervous system of these drugs may be relevant in the choice of long term therapy in hypertension.

Adult↗
PubMed1984

The involvement of central alpha adrenoceptors in the antihypertensive actions of methyldopa and clonidine in the rat.

The antihypertensive effects of methyldopa and clonidine result from agonist activity at alpha adrenoceptor sites within the brain. Methyldopa is converted enzymatically to alpha-methylnoradrenaline in noradrenergic neurones in rat brain and replaces the natural transmitter, noradrenaline. Radioligand receptor studies show that alpha-methylnoradrenaline differs from noradrenaline in being much more selective (70 times) for the alpha 2 subclass of adrenoceptors than noradrenaline and it is likely that the antihypertensive action of methyldopa results from selective activation of alpha 2 adrenoceptors by alpha-methylnoradrenaline in the nucleus tractus solitarius and the anterior hypothalamus. Radioligand studies also show that clonidine is a selective alpha 2 adrenoceptor agonist although it probably interacts with alpha 1 adrenoceptors at higher concentrations. With regard to a withdrawal syndrome after cessation of clonidine treatment, the cardiovascular and behavioural components can now be characterised in a rat model. The components include increases in basal blood pressure and heart rate, as well as increases in cardiovascular reactivity and also increases in rapid eye movement (REM) sleep, body shakes and tremor which is reminiscent of an opiate withdrawal syndrome. Increased central noradrenergic activity is involved in this syndrome and alpha 1 and alpha 2 adrenoceptors mediate opposing effects on the REM sleep rebound component.

Animals↗
PubMed2002

Methyldopa versus no drug treatment in the management of mild pre-eclampsia.

OBJECTIVES: To evaluate the efficacy of methyldopa in the treatment of mild pre-eclampsia, to prevent its progress and to investigate its effect on the pregnancy outcomes. DESIGNS: Randomised clinical trial. SETTING: Wad Medani Hospital in the central Sudan. SUBJECTS: Seventy primigravidae with single, alive baby of 28-36 weeks gestational age suffering from true mild pre-eclampsia were enrolled. The patients were randomised in two groups, treatment group who received methyldopa 750-4000 mg/day (n=34) and a control group who received no treatment (n=36). All the (treatment and control) patients were drug followed as in-patients till the delivery, seen with their babies on the days 7, 42 after the delivery. MAIN OUTCOMES MEASURES: The outcomes examined were, rise of the diastolic blood pressure to 110 mm Hg or more, occurrence of imminent eclampsia or the eclampsia, if the maturity could be achieved, occurrence of intrauterine growth retardation, abruptio placentae, mode of delivery, birth weight, placental weight, perinatal death, Apgar score and referral of the babies to the pediatrician. RESULTS: Three out of 34 (8.8%) of the treatment group had a rise in the diastolic blood pressure of 110 mm Hg, 18/36 (50%) of the control had a rise in the diastolic blood pressure of 110 mmHg (p < 0.05). Three out of thirty four (8.8%) of the treatment group developed imminent eclampsia, while 10/36 (27.8) of the control group developed imminent eclampsia (p < 0.05). The maturity was achieved in 82.3% and 88.8% of the treatment and the control, respectively (p > 0.05). There were ten (14.2%) perinatal deaths, four of them in the treatment group, while six in the control (p > 0.05). There was no difference regarding birth weight, occurrence of intrauterine growth retardation, placental weight, mode of delivery, Apgar score, referral of the babies to the paediatrician. No patient developed eclampsia or abruptio placenta; there was no maternal death in both groups. CONCLUSION: Methyldopa can prevent the progress of the mild pre-eclampsia to severe pre-eclampsia, without affecting the maturity, birthweight or the neonatal outcomes.

Abruptio Placentae↗
PubMed1975

Effects of guanethidine and methyldopa on a standardized test for renin responsiveness.

A standardized test for renin responsiveness, employing the dual stimulus of upright posture and the loop diuretic furosemide, was applied to 19 hypertensive patients in the untreated state and during therapy with the antihypertensive agents guanethidine and methyldopa. During therapy with guanethidine, 6 of 10 patients with "low-renin essential hypertension" experienced elevations of plasma renin activity to levles ordinarily diagnostic of "normal-renin" hypertension (P less than 0.05), whereas methyldopa had no significant effect on plasma renin activity in either "low-renin" or "normal-renin" patients. It is suggested that methyldopa has a negligible influence on renin responsiveness when stimulated under the above conditions and that it may be used during assessment of plasma renin activity in hypertensive patients whose blood pressure is too severely elevated for temporary withdrawal of therapy.

Adult↗
PubMedDate not supplied

A comparative evaluation of metoprolol and methyldopa in the management of pregnancy induced hypertension.

Thirty patients matched for age, parity, socioeconomic status and severity of pregnancy induced hypertension (PIH) were randomly allocated to treatment with metoprolol or methyldopa. The average fall in diastolic blood pressure was significant in the group treated with metoprolol as compared with the methyldopa group (p less than 0.01). There were 3 perinatal deaths in the methyldopa group and 1 in the metoprolol group; the mean birth weight of the babies was higher in cases treated with metoprolol. The results suggest metoprolol to be more efficacious with regard to control of hypertension and fetal outcome in cases of pregnancy induced hypertension.

Adult↗
PubMed2003

Methyldopa supplement for resistant essential hypertension: a prospective randomized placebo control crossover study.

BACKGROUND: Resistant hypertension is an important public health problem, its prevalence varies between 30 to 50 per cent. However, there is no definite recommendation for the treatment of resistant hypertension (HT). MATERIAL AND METHOD: A prospective randomized placebo control crossover study in resistant HT was designed to compare safety and efficacy between methyldopa 250 mg twice daily and placebo using ambulatory blood pressure monitoring. RESULTS: 87 from 1,112 cases (7.82%) from the hypertension clinic of Vajira Hospital were found to have clinical resistant HT and 40 cases were accepted to enrolled in the study. 23 cases of true resistant HT proceeded to the treatment phase of the study and all of them completed the study. Methyldopa reduced systolic blood pressure (BP) from 153.67 to 135.23 mmHg, or -18.44 mmHg (95% confidence interval 15.13-21.75). Diastolic BP was reduced from 86.42 to 74.90 mmHg, or -11.52 mmHg (95% confidence interval 9.41-13.63). CONCLUSION: The addition of methyldopa to the optimal medical therapy contributed to the improvement of BP control among patients with resistant HT.

Adult↗
PubMed2005

Cyclic voltammetric study of alpha-methyldopa at carbon paste electrode.

The cyclic voltammetric behaviour of alpha-methyldopa at a silicon oil carbon paste electrode has been reported. This allowed the development of a quantitative method to determine alpha-methyldopa in LiCl, KCl, NaCl, HCl, H2SO4 and CH3COOH as supporting electrolytes. For qualitative characteristics, alpha-methyldopa showed an ECC mechanism in terms of electron transfer reaction (placing it in DPI zone) at carbon paste electrode. The values of transfer coefficients alpha and beta were determined. The larger DeltaEp values were obtained due to the use of unmodified carbon paste electrode (CPE) has decreased the rate of electron transfer at the surface of the test electrode. The first order rate constant values (ko) were within 0.10-7.78 +/- 0.1x10(-3) s(-1). Adsorption of analyte was also determined at CPE using repeated scan method.

Antihypertensive Agents↗
PubMed1990

Evaluation of the efficacy and safety of enalapril plus hydrochlorothiazide plus methyldopa vs standard triple therapy in the treatment of moderate to severe hypertension: results from a multicentre study.

We report the results of a randomized, double-blind, parallel group multicentre study in 120 patients with moderate to severe hypertension, comparing two different types of antihypertensive treatment: a) the standard 'triple therapy' with hydrochlorothiazide, propranolol and hydralazine, and b) the combination of an ACE inhibitor, enalapril with hydrochlorothiazide (HCTZ) and methyldopa. The two regimens caused similar degrees of blood pressure reductions. The only significant difference between the two groups was heart rate due to the bradycardiac effect of propranolol in the group treated with the standard 'triple therapy'. Only 3.4% of patients receiving the regimen of enalapril, HCTZ and methyldopa were withdrawn from the study for adverse reactions, against 10% of patients on HCTZ, propranolol and hydralazine. Four cases of hypokalaemia in the enalapril group and 19 in the propranolol group were reported: so enalapril seemed to ameliorate the hypokalaemic effect of HCTZ. The overall analysis of the study results shows that the treatment based on enalapril, HCTZ and methyldopa is as efficient and better tolerated than the established regimen of HCTZ, propranolol and hydralazine.

Blood Pressure↗
PubMedDate not supplied

[Changes in left ventricular function and structure in hypertensive patients treated with methyldopa and urapidil].

In a randomized cross-over and double-blind trial twenty mild-to-moderate hypertensives (11 males, 9 females, mean age 48.4 +/- 7.6 years) were receiving methyldopa (250 mg b.i.d.) or urapidil (30 mg b.i.d.) for 7 weeks and then treated with alternative drug for additional 7 weeks, separated by one week of wash-out period. Both antihypertensives induced significant reduction (P less than 0.01) in systolic and diastolic arterial pressure, while no significant changes (P greater than 0.20) in the body weight and the heart rate were observed. The echocardiographic features of left ventricular hypertrophy (LVH) did not decrease significantly (P greater than 0.05) on either drug, except for the left ventricular posterior wall thickness (LVPWd), which decreased on methyldopa from 10.4 +/- 1.3 to 9.8 +/- 1.4 mm (P less than 0.05). The drugs under study did not change significantly the echocardiographic indices of left ventricular function. Echocardiography resulted to be more sensitive in detecting LVH than electrocardiography. It is concluded that methyldopa might successfully reduce LVH, while direct and indirect vasodilators (such as urapidil) are less effective.

Adult↗
PubMed1975

Extemporaneous preparation of methyldopa in two syrup vehicles.

The stability of methyldopa in two extemporaneous syrup preparations was studied. Film-coated methyldopa tablets were triturated and incorporated into (1) unpreserved Syrup USP and (2) an equal mixture of simple syrup containing 0.5% citric acid and 0.2 N hydrochloric acid, in concentrations of 50 mg/ml. The preparations were stored in the dark, for 14 days at 5 C and 25 C. Samples were analyzed spectrophotometrically for methyldopa content at various intervals. Both preparations were stable under the conditions studied.

Biological Availability↗
PubMed1987

[Effectiveness of alpha-methyldopa in complex ventricular extrasystole by inhibition of central sympathetic activity].

Twelve patients (11 men, 1 woman) suffering from coronary heart disease, with a mean age of 59 +/- 9 years, were examined before and after 2 weeks of treatment with alpha-methyldopa by means of a 24-hour ECG. Statistical evaluation of the 24-hour analysis of ventricular arrhythmias revealed a decrease of the ventricular extrasystoles from 1605 +/- 2088 to 385 +/- 291 (p less than 0.01). A similar result was also found for couplets, which decreased significantly from 25 +/- 46 to 1.0 +/- 1.5 after treatment with alpha-methyldopa. Statistical evaluation of the maximal grade of arrhythmias according to Lown's classification showed a significant improvement in the Lown grades from 4.2 to 3.2 in all patients (p less than 0.001). Ventricular tachycardia, present in 5 of 12 patients, were prevented in all cases by alpha-methyldopa.

Cardiac Complexes, Premature↗
PubMedDate not supplied

Ketanserin in mild to moderate hypertension in the elderly: a double-blind study versus methyldopa.

In a double-blind study of 30 elderly patients with mild to moderate essential hypertension, the antihypertensive effects of ketanserin and methyldopa were compared. The patients were randomly assigned to receive 20 mg of ketanserin or 250 mg of methyldopa twice daily for two weeks; the dose was then doubled for the rest of the three-month period. Two of the ketanserin group dropped out of treatment, one because of psychic depression, the other because of epigastric pain. After three months of therapy with ketanserin, systolic blood pressure decreased in a dose-dependent manner from 190 +/- 20 to 175 +/- 20 mmHg (P less than 0.05) and diastolic blood pressure from 106 +/- 8 to 91 +/- 9 mmHg (P less than 0.001). Blood pressure was reduced to 160/90 mmHg or less in eight of the 13 ketanserin patients and in five of the 15 methyldopa patients. In both groups heart rate and body weight remained constant. No orthostatic hypotension or hypertensive rebound after ketanserin withdrawal was recorded. It is concluded that 40 mg of ketanserin twice daily can control hypertension in the elderly.

Adult↗
PubMedDate not supplied

Evaluation of succinimidoethyl and pivaloyloxyethyl esters as progenitors of methyldopa in man, rhesus monkey, dog, and rat.

The succinimidoethyl (Sm) and pivaloyloxyethyl (P) esters of methyldopa were evaluated as progenitors of the latter. Experiments in spontaneously hypertensive (SH) rats and humans demonstrated that a radioactive dose of progenitor was well absorbed. The metabolism of these progenitors appeared to be comparable in the SH rat; the urinary excretion of [3H]methyldopa was similar after oral administration of [3H]Sm or [3H]P. In humans the levels of [3H]methyldopa were higher in the urine following administration of [3H]P. Apparently Sm was more resistant than P to extrahepatic esterase action in man (and dog). In man the catechol nucleus of Sm was apparently conjugated prior to hydrolytic cleavage to release conjugated [3H]methyidopa. The progenitors possessed similar antihypertensive properties in the SH rat but preliminary results in humans suggested that Sm possessed less antihypertensive potency than P.

Adult↗