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PubMed1992

Effects of methyldopa on umbilical and placental artery blood flow velocity waveforms.

OBJECTIVE: To identify the effects of methyldopa on umbilical and placental artery Doppler velocity waveforms in mild preeclamptic and chronic hypertensive women with blood pressure below 160/110 mmHg. METHODS: Twenty-two normotensive, 11 untreated mild preeclamptic, 14 treated mild preeclamptic, 29 untreated chronic hypertensive, and 14 treated chronic hypertensive women were studied. Methyldopa was begun if the blood pressure remained higher than 140/90 mmHg after 24 hours of hospitalization. The pulsatility index (PI) was measured on days 0 and 7. RESULTS: Blood pressure decreased significantly with methyldopa in chronic hypertensive women only (P < .05). The PI did not vary in the umbilical artery in the five groups, or in the placental artery in normotensive, untreated preeclamptic, and untreated chronic hypertensive women. The PI decreased significantly in treated preeclamptic and chronic hypertensive women (P < .05). Birth weight was similar in the hypertensive groups. CONCLUSION: Methyldopa decreases placental vascular resistance in mild preeclamptic and chronic hypertensive women.

Adult↗
PubMed1991

Colorimetric assay of methyldopa bulk drug and tablets as its Fe(III) complex.

A new colorimetric method for the determination of methyldopa is described. The method is based on the reaction of methyldopa with ferric chloride in the pH range of 3.0-3.5 and producing a water soluble (1:2) brown complex with maximum absorbance at 423 nm. The conditional stability constant of the complex at the optimum pH 3.0 and ionic strength 0.4 M, is found to be 10(7.5). Beer's low is obeyed up to 6 mmol/l methyldopa concentration. The RSD of the method is 0.708-1.226%. The proposed method was found to be suitable for the accurate and reproducible analysis of methyldopa bulk drug and tablets which is pointed by high recovery values 99.20-99.79%.

Colorimetry↗
PubMed1990

Animal model of anxiety: the effect of methyldopa in the genetically hypertensive non-obese rats of Koletsky type and in the rats of Wistar strain.

The experiments were carried out in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats which were developed by Koletsky; the experiments were performed in the both sexes. The behavior of control and methyldopa treated rats were traced in the holeboard and in the elevated plus-maze. In the control animals when compared to the normotensive rats of both sexes, the genetically hypertensive rats of both sexes show elevated aversion towards open space and height (when the number of visits of centre and open arms is considered), elevated locomotor-exploratory activity and reduced rate of habituation of the latter activity; the genetically hypertensive males than show reduced percentage of time spent head dipping relative to the normotensive males. Methyldopa decreases locomotor-exploratory activity and increases intra-session rate of habituation of the latter activity in the both strains of rats. This drug shows in the first session decrease in the normotensive males and increase in the genetically hypertensive rats of both sexes the percentage of time spent head dipping. Methyldopa shows in the first session increase in the number of entries in centre and in open arms in elevated plus-maze solely in the genetically hypertensive rats of both sexes. When time spent in centre and in open arms of the elevated plus-maze is taken into consideration, methyldopa shows in the normotensive males decrease and in the genetically hypertensive males increase.

Animals↗
PubMed1990

[Fatal toxic hepatitis in pregnancy. A discussion of the role of methyldopa].

The authors report a case of toxic hepatitis in a woman of 22 years of age in the third trimester of her first pregnancy treated by methyldopa for hypertension of pregnancy which was diagnosed at 33 weeks of amenorrhoea. The prodromal symptoms were mild and consisted of nausea, vomiting and rise in temperature and this phase was associated with febrile jaundice without pruritus and it was only associated with coagulation disorders in the third stage of labour. This was a case of mixed cytolytic hepatitis (ASAT x 3N) and cholestasis (x 1.5N). The outcome was fatal. The patient died three days after delivery following haematemesis and renal failure as well as hepatic encephalopathy. The main diagnostic feature was acute hepatic stasis in spite of the absence of pruritus and the presence of a raised temperature after hematolytic, viral and obstructive causes had been eliminated. Histology confirmed that there was toxic hepatitis. This aetiology was suggested by the timing of the symptoms after MD (methyldopa) had been taken. Elkington described methyldopa hepato-toxicity in 1969. Fatal cases in the literature were in patients who were over 40 years of age. Methyldopa is used in pregnant women because of its safety as far as the fetus is concerned. Mechanism by which it causes toxic hepatitis is a combination of abnormal metabolism (the cytochrome P450 chain produces an antigen) and an immune reaction in response to this antigen and these explain why such severe and potentially fatal forms of the condition exist.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Methyldopa-related convergence insufficiency.

A case report of convergence insufficiency related to the use of methyldopa is presented. Methyldopa is a systemic antihypertensive agent. It has sympatholytic properties which lower blood pressure by decreasing peripheral vascular resistance. The proposed effects of methyldopa on binocular vision are reduced accommodative convergence and increased demand on fusional convergence. These effects would create a susceptibility to convergence insufficiency. To my knowledge, an association between methyldopa and convergence insufficiency has not been previously reported.

Accommodation, Ocular↗
PubMed1988

Methyldopa hypersensitivity can mimic acute toxic enterocolitis.

The most widely known hypersensitivity reaction of methyldopa, a drug commonly used in the treatment of hypertension, is seroconversion to a positive result of a direct Coombs' test that may lead to a hemolytic anemia. The authors report a case of an infrequently noted, but serious, hypersensitivity reaction to methyldopa, manifesting primarily as acute toxic enterocolitis. A 63-year-old woman was admitted to hospital and underwent aggressive and prolonged investigation of enterocolitis. Withdrawal of methyldopa gave immediate relief of intestinal problems. Rechallenge precipitated a return of symptoms within 14 hours. It is recommended that periodic blood counts and liver function tests be done on patients treated with methyldopa for hypertension. If any abnormalities are noted the drug should be discontinued.

Acute Disease↗
PubMed1978

Antihypertensive activity of alpha-methyldopa on a twice daily regimen in comparison to metoprolol. A multi-centre controlled clinical trial.

1. The antihypertensive effects of alpha-methyldopa and metoprolol have been compared in 110 patients (fifty-one males and fifty-nine females) with previously untreated essential hypertension (sixty-eight WHO stage 1 and forty-two WHO stage 2). 2. After 2 weeks of placebo, the patients were randomly allocated to treatment with either of the two drugs: alpha-methyldopa up to 500 mg b.i.d. and metroprolol up to 200 mg b.i.d. for 6 weeks. Periodical clinical, biochemical, haematological, radiological and electrocardiographical measurements were performed. 3. The average reduction in blood pressure produced by the two drugs was comparable. 4. In general, side-effects were few and tolerable: mainly bradycardia in the metoprolol group and dizziness and drowsiness in the alpha-methyldopa group. 5. The plasma renin activity was significantly reduced in the metoprolol but not in the alpha-methyldopa group.

Adult↗
PubMed1978

Oxprenolol slow-release with cyclopenthiazide-KCl compared with methyldopa in the treatment of essential hypertension. A multicentre general practice trial.

Two hundred and thirty-eight patients with essential hypertension from 39 general practice centres were treated in a double-blind trial with either oxprenolol 160 mg in a slow-release (SR) formulation with cyclopenthiazide 0,25 mg and potassium chloride 600 mg given once daily, or methyldopa 250 mg 3 times daily. After a 2-week placebo washout period, each patient was treated for 10 weeks. Both treatments significantly reduced blood pressure. Oxprenolol SR plus cyclopenthiazide-KCl was shown to possess significantly superior antihypertensive activity to methyldopa. Pulse rate, as expected, was significantly decreased by the beta-blocker and virtually unaffected by methyldopa. The overall incidence of side-effects was low. The incidence of sleepiness and dry mouth was significantly higher in the methyldopa group, and erythema in the oxprenolol group. The principle of general practitioners conducting multi-centre double-blind trials for research purposes, on drugs which are predominantly given to ambulatory patients, has been established for the first time in South Africa. Virtually no difficulty was encountered in getting patients' consent in the general practice milieu.

Adult↗
PubMed1979

A comparative study of methyldopa and labetalol in the treatment of hypertension.

1 Twenty patients with essential hypertension completed a double-blind, dose-tritrated, cross-over comparison of methyldopa and labetalol. 2 Average lying BPs (systolic/diastolic) were reduced by 28/15 mmHg with methyldopa and by 23/15 mmHg with labetalol. 3 Average standing BPs (systolic/diastolic) were reduced by 29/14 mmHg with methyldopa and by 29/15 mmHg with labetalol. 4 Both lying and standing heart rates were reduced with labetalol. 5 It is concluded that the antihypertensive properties of labetalol and methyldopa are similar but that larger patient populations are needed to study the relative incidence of subjective adverse effects.

Blood Cell Count↗
PubMed1979

Patterns of hepatic injury induced by methyldopa.

Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.

Adult↗
PubMed1966

The long-term effectiveness of methyldopa in hypertension.

A trial of methyldopa in hypertension was conducted in 60 patients for a mean time of 9.4 months. Initially, four different dosages of methyldopa were studied and blood pressure was significantly lowered in the supine and standing positions. Standing blood pressure was significantly reduced more than supine. An average of 5.2 visits passed before maintenance blood pressure was obtained. There was no significent evidence of deterioration during the duration of this study. Side effects were mild. Only two patients voluntarily requested discontinuance of this study. Tolerance to the drug occurred and approximately 50 per cent of the patients no longer had a significant blood pressure reduction to methyldopa alone by the end of the study. Methyldopa appears to be a significant addition to the drug therapy of hypertension.

Female↗
PubMed1977

Methyldopa and renal stones: a retrospective study.

A possible association between treatment with methyldopa and the occurrence of renal stones was sought by retrospectively comparing 54 hypertensive patients with calculi detected by X-ray examination with a control group matched for age and sex. Treatment with methyldopa was equally frequent in both groups. There was a significant excess of methyldopa use in a subgroup of 16 patients with bilateral calculi, but the drug could be the primary cause of stone formation in, at most, four of these patients. If methyldopa does cause renal stones, it is probably an uncommon event, but precipitation of the drug from the urine may worsen a tendency to stone formation, which will lead to a higher incidence of bilateral calculi.

Female↗
PubMed1981

Intracellular inhibition of catalase by alpha-methyldopa.

The effect of preincubation with alpha-methyldopa on catalase-dependent decomposition of H2O2 was studied in isolated rat hepatocytes. A direct assay of catalase function was obtained by measurement of O2 production under anaerobic conditions following additions of H2O2. Both the total O2 produced and the maximal O2 concentration attained were decreased by preincubation with alpha-methyldopa. The results demonstrate that alpha-methyldopa-induced formation of Compound II is associated with loss of intracellular catalase activity. These results indicate that the hepatotoxicity of alpha-methyldopa may be related to an increased sensitivity to oxidative injury due to inhibited catalase function.

Animals↗
PubMed1984

Haemodynamic changes in peripheral arterial circulation during antihypertensive treatment with captopril, methyldopa and indapamide.

Structural changes in resistance vessels of the lower limbs have been detected in early stages of arterial hypertension. In these patients it might be important to reduce blood pressure by drugs which do not impair peripheral blood flow. Twenty-four patients with arterial hypertension, without target organ damage were randomly given a placebo, 50 mg captopril, 500 mg methyldopa or 2.5 mg indapamide and their blood pressure, arterial blood flow and peripheral resistance were measured at baseline and at the peak action of the antihypertensive treatment. Significant decreases in blood pressure and peripheral resistance have been induced by a single oral dose of captopril and methyldopa: a concomitant significant increase in peripheral blood flow to the lower limbs was also observed during methyldopa treatment. No acute effect was observed on the placebo or on indapamide: the latter induced a decrease in blood pressure and in peripheral resistance along with an increase in arterial blood flow during long-term treatment after four weeks of therapy. Our observations seem to support the usefulness in hypertensive patients with concomitant lesions in the peripheral arterial tree of antihypertensive agents such as methyldopa and indapamide which increase blood flow and reduce peripheral resistance while lowering high blood pressure.

Adult↗
PubMed1983

A comparative study of metoprolol and methyldopa in the treatment of hypertension.

The efficacy of metoprolol, a new cardioselective beta-blocking drug, was compared with that of methyldopa in patients with mild to moderate essential hypertension in a long-term study. A total of 25 patients received metoprolol in a maximum dose of 200 mg once daily; 30 patients received 500 mg methyldopa twice a day. Both groups of hypertensive patients had similar blood pressure upon entering the study (methyldopa: 182/110 mmHg; metoprolol: 180/110 mmHg). Two years after continuing therapy the blood pressures were similar (methyldopa: 142/90 mmHg; metoprolol: 145/90 mmHg). The great difference between the two drugs was the incidence and severity of side effects, here metoprolol offered a definite advantage.

Adult↗
PubMed1980

Long term comparative study of guanfacine and alpha-methyldopa in essential hypertension.

The hypotensive action of guanfacine and alpha-methyldopa has been compared in 30 patients wth moderate essential hypertension. After 2 weeks of placebo treatment, the patients were randomly allocated to a 12 week treatment with either of the two drugs. The treatment was started with guanfacine, 1 mg twice daily p.o., or alpha-methyldopa, 250 mg three time a day p.o. This dose of guanfacine was able to induce a satisfactory control of blood pressure in all patients while the dose of alpha-methyldopa was gradually increased to a predetermined maximum daily dose (2 g) in those patients with unsatisfactory blood pressure control, i.e., systolic blood pressure above 160 mmHg and diastolic above 95 mmHg. Then the two treatments were dicontinued for one week. Both drugs induced a significant reduction of systolic and diastolic blood pressure. However, guanfacine induced a more marked decrease in systolic blood pressure after the 14th day of treatment while the reduction of diastolic blood pressure was significantly higher only at the end of the final wash-out period, thus indicating a longer lasting effect of guanfacine as compared to alpha-methyldopa. Two patients treated with guanfacine developed dryness of the mouth and three of those in the alphamethyldopa group complained of excessive sedation.

Age Factors↗
PubMed1982

Chlorpromazine interactions with guanethidine and alpha-methyldopa: effects on arterial pressure control and heart rate in renovascular hypertensive rats.

The ability of chlorpromazine to impair the anti-hypertensive effectiveness of guanethidine or alpha-methyldopa was evaluated in one-kidney, one clip and two-kidney, one clip renovascular hypertensive rat models. Subacute blood pressure studies were conducted using chronically hypertensive rats receiving guanethidine (50 mg/kg/day) or alpha-methyldopa (100 mg/kg/day). Incremental doses of chlorpromazine (1, 3 and 10 mg/kg/day) for five consecutive days per dose were added to the antihypertensive regimen. Chlorpromazine (10 mg/kg/day) reversed the antihypertensive effect of guanethidine equally in both hypertensive models but did not alter guanethidine-induced bradycardia. Chlorpromazine did not impair the hypertensive effectiveness of alpha-methyldopa in either hypertensive rat model. These findings demonstrate the utility of the renovascular hypertensive rat models studied for investigating cardiovascular drug interactions with guanethidine and document the interactive potential of chlorpromazine with guanethidine or alpha-methyldopa in these hypertensive models.

Animals↗
PubMed1981

Sinus node dysfunction caused by methyldopa and digoxin.

Symptomatic sinus bradycardia developed in two patients while they were taking methyldopa and digoxin. In one patient, bradycardia did not occur with either digoxin or methyldopa alone. The other patient, who had never taken methyldopa alone, did not demonstrate bradycardia with digoxin alone. In each patient, normal sinus node function was demonstrated after methyldopa and digoxin therapy was discontinued. Both patients continued to receive digoxin without recurrence of bradycardia.

Aged↗