SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The effect of pretreatment with clonidine, methyldopa and propranolol, and of atropine was studied in mice on acute toxicity of fenitrothion, the active ingredient of TIK-20. Atropine significantly decreased and propranolol somewhat decreased the fenitrothion induced death in mice. Clonidine and methyldopa somewhat increased the percentage mortality due to fenitrothion.
The antihypertensive efficacy of acute treatment with the serotonin receptor antagonist, ketanserin, in women with preeclampsia has been recently documented. The purpose of this study was to determine the safety and efficacy of chronic ketanserin treatment in a group of 20 hypertensive pregnant women: 10 received daily oral doses of ketanserin (20-80 mg), and 10 were treated with oral alpha-methyldopa (500-2000 mg). This study includes (a) patients with a sustained elevation of systolic blood pressure higher than 159 mm Hg and/or diastolic blood pressure higher than 99 mm Hg at bed rest, and (b) hypertensive patients with systolic blood pressure higher than 140 mm Hg or diastolic blood pressure higher than 90 mm Hg with superimposed symptoms such as headaches, stomach aches, and neurological disturbances. A significant and comparable decrease in blood pressure was noted in both groups, in relation with pretreatment levels; no adverse affects were observed in mother or fetus from the ketanserin and alpha-methyldopa groups.
1. Methyldopa was administered to hypertensive patients in association with two different inhibitors of dopa decarboxylase, one of which, carbidopa, scarcely penetrates the central nervous system while the other, benserazide, penetrates the central nervous system when given in high doses. 2. The evidence suggests that in man, as in animals, the predominant action of methyldopa is mediated by the formation of methyldopamine and methyl-nor-adrenaline within the brain.
1. During acute injection of alpha-methyldopa there is a reduction in the blood pressure within a period of a few hours and a modest reduction in the cardiac output, sometimes due to a modest decrease in heart rate. Frequently the total peripheral resistance is decreased. In contrast, acute injection of beta-blockers induces a marked decrease in heart rate and cardiac output, a compensatory increase in the total peripheral resistance and no decrease in the blood pressure. 2. During long-term use alpha-methyldopa frequently reduces the total peripheral resistance and the reduction in cardiac output is usually modest, at rest as well as during exercise. The beta-blockers reduce the blood pressure, but induce a marked decrease in cardiac output and heart rate. The total peripheral resistance is little affected compared to the pre-treatment level.
Micro-injection of methyldopa into the area of the midline B3 serotonin cell group in the ventral medulla of spontaneously hypertensive rats, stroke-prone strain (SHRSP), caused a fall in blood pressure of 30-40 mmHg, maximally 2-3 h after administration. This hypotension was abolished by the selective serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) injected intracerebroventricularly, but it was not affected by intraspinal injection of 5,7-DHT to produce a selective lesion of serotonin nerves descending into the spinal cord, or by injection of 5,7-DHT into the median forebrain bundle, one of the main ascending pathways from the B3 serotonin cells. It seems likely that the midline serotonin B3 cells in the medulla contribute to the hypotensive action of methyldopa through a projection restricted to the caudal brainstem.
Direct within-patient comparisons of the effects of centrally acting sympathetic inhibitors and beta-blockers on blood pressure (BP) of the elderly have not been done. In the present study, 32 elderly hypertensive patients were treated with a diuretic. Methyldopa (500 mg/d) (16 patients, subgroup A) or slow-release oxprenolol (80 mg/d) (subgroup B) was added as a second-step antihypertensive agent for a period of eight weeks, after which the second-step agents were switched, respectively, for another period of eight weeks. In subgroup A the supine BP dropped from 193/99 to 169/93 mm Hg and the standing BP from 183/100 to 163/92 mm Hg, whereas in subgroup B the supine BP fell from 190/103 to 182/97 mm Hg and the standing BP from 187/101 to 172/95 mm Hg. After switching the drugs, the respective BP values were 177/91 and 170/95 mm Hg and 170/90 and 156/89 mm Hg. In the doses given, methyldopa therapy is more effective than oxprenolol therapy in lowering the BP of elderly hypertensive patients.
Bioavailability of alpha-methyldopa from a film coated tablet Dopegyt (EGIS Pharmaceutical Works, Budapest, Hungary) and from Aldometil (MSD, Sharp and Dohme GmbH, Munich, FRG) containing 250 mg of effective substance, was investigated in a crossover study in six patients with mild hypertension having normal renal and liver functions. Alpha-methyldopa was determined in plasma by fluorometry. There was no difference in the pharmacokinetic parameters calculated (Cl, Vd, AUC, t1/2) indicating that the two preparations are bioequivalent.
Control of hypertension (ie, reduction of blood pressure to less than or equal to 160/90 mmHg) in 40 mild to moderate hypertensives not responding adequately to hydrochlorothiazide was achieved by the addition of guanfacine (once daily) or methyldopa (twice daily) in a 16-week, double-blind, parallel-group trial. Control occurred after two weeks (at 1 mg/day) in 50% of the guanfacine-treated patients and in most patients within four to six weeks of treatment. The final mean doses were 2.5 mg/day of guanfacine or 763 mg/day of methyldopa. Sixteen patients maintained control of hypertension with continued guanfacine therapy for one year.
Though drug fever from methyldopa is well known, to my knowledge fever and hypotension simulating septic shock have never been described in this country as a syndrome resulting from methyldopa therapy. Three such cases are presented here, all proved on rechallenge. They erroneously accounted for almost 6% of all cases of septic shock at St Elizabeth Medical Center in the last ten years.
1 Nineteen pregnant patients whose mean arterial pressure (MAP) was persistently greater than or equal to 103.3 mmHg were given labetalol or methyldopa. 2 Singificant falls (P less than 0.001) in BP only occurred in the group treated with labetalol, and daily BP control was better in this group. 3 Two severely hypertensive patients were successfully treated with intravenous labetalol. 4 There was a higher incidence of spontaneous labour in the labetalol group and a significant difference (P less than 0.05) in the Bishop score of the cervix between the two groups. 5 There were no apparent detrimental effects on the foetus antenatally, during labour or post partum. 6 Slight breathlessness in one patient treated with labetalol was the only side-effect observed but drowsiness, headache and postural hypotension were reported in patients receiving methyldopa.
Five patients with hypertension died as a result of myocarditis. Three were treated with methyldopa and hydrochlorothiazide, two with methyldopa alone. Their ages ranged from 30 to 71 years. In all instances death occurred suddenly, and myocarditis was not suspected clinically. The inflammatory changes in the hearts of these patients were most consistent with a hypersensitivity reaction. Additionally, there was hepatitis consistent with hypersensitivity in four of the cases.
Efficacy and dosage data were analyzed for patients who received methyldopa up to 4.5 years. A prompt initial response to methyldopa was observed, and the blood pressure reduction was maintained throughout the follow-up period. Mean dosage rose modestly during this time.
Tolerability data recorded during long-term administration of methyldopa are presented here. Since diuretics and other antihypertensive agents were frequently coadministered with methyldopa, no attempt was made to assign possible drug relationships for any particular adverse effect. The most common clinical adverse effects among the entire study population were drowsiness and dizziness. Impotence was reported by 16% of 258 men.
The antihypertensive effect of debrisoquine (20 mg/day), methyldopa (100 mg/day) and propranolol (160 mg/day) was compared to that obtained with a placebo in a controlled trial carried out by a group of 14 internists. Forty-eight patients with uncomplicated essential hypertension were included. Mefruside (25 mg/day) was first given alone for 6 weeks ("open phase" of the trial) and to this diuretic was then added in double-blind fashion and randomized sequence a placebo or an active drug. Each of the 4 blind phases lasted 4 weeks. At the end of the "open phase", blood pressure in seated position averaged 168/111 +/- 19.6/13.5 mm Hg (mean +/- SD). A significant blood pressure decrease was observed after 4 weeks of treatment with the placebo as well as with the investigated compounds. With the placebo blood pressure was reduced to 158/102 +/- 19.6/13.5 mm Hg (p less than 0.001). The magnitude of the additional blood pressure decrease induced by the active drugs was relatively small and varied from 4 (debrisoquine) to 10 mm Hg (methyldopa, p less than 0.01) for the systolic and from 3 (debrisoquine, p less than 0.05) to 5 mm Hg (propranolol, p less than 0.05) for the diastolic. The percentage of patients with systolic pressure of less than or equal to 140 mm Hg and with diastolic pressure of less than 90 mm Hg during administration of either drug was not greater than 40 to 20% respectively. Propranolol appeared to be better tolerated than the other antihypertensive agents. These rather disappointing blood pressure results suggest that the efficacy of antihypertensive agents in private practice cannot be extrapolated from studies carried out in specialized hypertension clinics.
In a double-blind, cross-over, placebo-controlled study the efficacy of a new antihypertensive agent, guanfacine, was compared that of with methyldopa. Guanfacine was more effective in controlling blood pressure than methyldopa, but it induced a slightly higher incidence of side-effects.
An open-label clinical trail comparing the effectiveness of the combination of methyldopa with hydrochlorothiazide in low doses with that of hydrochlorothiazide therapy alone was conducted in 21 elderly patients with isolated systolic hypertension. The combination therapy reduced the systolic blood pressure to levels markedly lower than those measured at baseline and after two weeks of hydrochlorothiazide therapy. Standing blood pressure fell from a mean of 166/90 mmHg at baseline to a mean of 164/88 mmHg after two weeks of hydrochlorothiazide treatment and to a mean of 132/80 mmHg after 16 weeks of treatment with hydrochlorothiazide and methyldopa. Side effects were mild, and there were no significant changes in laboratory findings.
The effects of methyldopa, a central alpha 2-agonist, and bromocriptine, a dopaminergic drug, on negative pressure breathing-induced diuresis were studied in the dog. Methyldopa (20 mg/kg i.v. during 20 min) or bromocriptine (0.3 mg/kg i.v.) suppressed the diuretic reflex without changing blood pressure. Since negative pressure breathing-induced diuresis is mainly due to an inhibition of vasopressin secretion, it is suggested that central alpha 2-adrenoceptors and dopaminergic receptors play an inhibitory role in mediating vasopressin release to non osmotic stimuli.
Methyldopa (200 and 400 micrograms/ml) induced an increase in the responsiveness of guinea-pig ileum to ACh after incubation for 1 hr 15 min. However, no such effect was observed in the case of frog rectus abdominis muscle. It is suggested that methyldopa influences receptor mechanisms associated with cholinergic muscarinic but not nicotinic receptors.