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European Journal of Clinical... Aug 1975The plasma concentrations of free alpha-methyldopa and methyldopa sulphate conjugate were measured in 7 hypertensive patients with normal renal function following... (Comparative Study)
Comparative Study
Plasma concentration of alpha-methyldopa and sulphate conjugate after oral administration of methyldopa and intravenous administration of methyldopa and methyldopa hydrochloride ethyl ester.
The plasma concentrations of free alpha-methyldopa and methyldopa sulphate conjugate were measured in 7 hypertensive patients with normal renal function following alpha-methyldopa (1 g) orally. Five of these patients subsequently received alpha-methyldopa ethyl ester (250 mg) (methyldopate) intravenously and two further patients received 250 mg of alpha-methyldopa intravenously. After oral administration a large amount of total plasma alpha-methyldopa was present as sulphate conjugate. There were wide interindividual differences in the ratio of free: conjugated alpha-methyldopa in plasma (ratio at 4 hours ranged from 3.73-0.83) suggesting that individual differences in the extent of sulphate conjugation may occur. There was no close correlation between the degree of conjugation and the fall in arterial pressure. At all time intervals examined, plasma concentrations were higher following intravenous alpha-methyldopa than alpha-methyldopate. The plasma concentration of alpha-methyldopa (free and esterified) 60 minutes after i.v. alpha-methyldopate was 1.7+/-0.3 mug/ml while at the same time after the same dose of methyldopa by the same route the mean concentration was 5.9 mug/ml. Although small amounts of sulphate conjugate were detected after i.v. alpha-methyldopate, insignificant quantities of conjugate were found after i.v. alpha-methyldopa. The average fall in mean arterial pressure was 27 mm/Hg following i.v. alpha-methyldopa but only 2.7 mm Hg following alpha-methyldopate. These results suggest that sulphate conjugation of alpha-methyldopa occurs in the gastrointestinal tract during absorption. Hydrolysis of alpha-methyldopa ethyl ester does not appear to be instantaneous and pharmacokinetic differences between the ester and free alpha-methyldopa have been demonstrated.
Topics: Administration, Oral; Adult; Aged; Biotransformation; Blood Pressure; Female; Humans; Hypertension; Infusions, Parenteral; Male; Methyldopa; Middle Aged; Sulfates
PubMed: 1233238
DOI: 10.1007/BF00562310 -
Urology Feb 1977Fifty patients with neurogenic bladder dysfunction were treated with methyldopa (Aldomet). The preliminary results that are presented suggest a beneficial action in...
Fifty patients with neurogenic bladder dysfunction were treated with methyldopa (Aldomet). The preliminary results that are presented suggest a beneficial action in patients with upper neuron lesions. The probable mechanism of the drug's action is discussed.
Topics: Adrenergic Fibers; Autonomic Fibers, Postganglionic; Humans; Methyldopa; Motor Neurons; Sympathetic Nervous System; Urinary Bladder; Urinary Bladder, Neurogenic
PubMed: 841787
DOI: 10.1016/0090-4295(77)90197-2 -
The New Zealand Medical Journal Aug 2009Drug-induced haemolytic anaemia is a commonly encountered clinical situation. Methyldopa-induced haemolytic anaemia, once the most common cause of drug induced...
Drug-induced haemolytic anaemia is a commonly encountered clinical situation. Methyldopa-induced haemolytic anaemia, once the most common cause of drug induced haemolysis, is now rarely seen due to decline in its use. We report a case of methyldopa induced immune haemolytic anaemia in a young woman where the diagnosis was initially missed. The major mechanisms of drug induced immune haemolysis and unique characteristics of methyldopa induced haemolysis are also outlined.
Topics: Adult; Anemia, Hemolytic, Autoimmune; Antihypertensive Agents; Autoantibodies; Female; Humans; Methyldopa
PubMed: 19829392
DOI: No ID Found -
British Journal of Pharmacology Jul 19881. The effects of i.v. administration of alpha-methyldopa (MD) on rat pupil diameter were investigated. All experiments were carried out in rats in which vagosympathetic...
1. The effects of i.v. administration of alpha-methyldopa (MD) on rat pupil diameter were investigated. All experiments were carried out in rats in which vagosympathetic nerve trunks were sectioned bilaterally at the cervical level. 2. In anaesthetized rats MD produced a marked dose-related increase in pupil diameter. The onset of pupillary response to MD was gradual and reached maximal levels 2-3 h after administration. 3. Pretreatment with alpha 2-adrenoceptor antagonists yohimbine (1.5 mg kg-1, i.v.) or idazoxan (0.5 mg kg-1, i.v.) blocked the pupillary response to MD. In contrast, the alpha 1-antagonists prazosin (1.0 mg kg-1, i.v.) and phenoxybenzamine (1.5 mg kg-1, i.v.) did not significantly alter the pupillary effects of MD. 4. Selective enzymatic blockade with 3-hydroxy-benzyl-hydrazine (NSD-1015; 25 mg kg-1, i.p.), a dopa-decarboxylase inhibitor, as well as bis (4-methyl-homopiperazinyl-thiocarbonyl) disulphide (FLA-63, 5.0 mg kg-1, i.p.), a dopamine-beta-hydroxylase inhibitor, prevented the mydriatic effect of MD. 5. The above findings support the hypothesis that MD produces a clonidine-like CNS mydriasis in the rat. This effect appears to be mediated primarily by the MD metabolite, alpha-methylnoradrenaline. 6. These results indicate that MD produces mydriasis in the rat by a CNS action. The mydriatic action of MD appears to be produced by its metabolite alpha-methylnoradrenaline which in turn stimulates CNS postsynaptic alpha 2-adrenoceptors.
Topics: Adrenergic alpha-Antagonists; Animals; Biogenic Monoamines; Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; Central Nervous System; Enzyme Inhibitors; Hydrazines; Male; Methyldopa; Pupil; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha
PubMed: 2902894
DOI: 10.1111/j.1476-5381.1988.tb11594.x -
American Journal of Obstetrics and... Jan 1995A case of hepatotoxicity in a multiparous Native woman, who was begun on a regimen of methyldopa for control of chronic hypertension, is described. The patient was first...
A case of hepatotoxicity in a multiparous Native woman, who was begun on a regimen of methyldopa for control of chronic hypertension, is described. The patient was first seen for clinical evidence of hepatotoxicity approximately 3 weeks after initiation of treatment. At presentation the aspartate aminotransferase level was 1800 IU/L and alanine amniotransferase was 2415 IU/L. There was also a significant prolongation of clotting time, which required therapy. Resolution of symptoms occurred after cessation of the medication. Although methyldopa is considered to have a wide margin of safety in the treatment of chronic hypertension in pregnancy, potentially serious adverse effects can occur. It is important to monitor serum aminotransferase levels after initiation of methyldopa therapy.
Topics: Adult; Chemical and Drug Induced Liver Injury; Female; Humans; Hypertension; Methyldopa; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Transaminases
PubMed: 7847544
DOI: 10.1016/0002-9378(95)90123-x -
European Journal of Clinical... 1988In a group of ten hypertensive patients, the effects of methyldopa administration in two different formulations on serum prolactin (PRL) were studied. A single oral dose... (Clinical Trial)
Clinical Trial Comparative Study
In a group of ten hypertensive patients, the effects of methyldopa administration in two different formulations on serum prolactin (PRL) were studied. A single oral dose of normal release methyldopa significantly increased serum prolactin levels, peak concentrations occurring 3 to 6 h after drug administration. On the contrary, administration of sustained release methyldopa at the same dose was only followed by slight and not significant fluctuations in prolactin plasma levels. Both formulations produced a significant decrease of systolic and diastolic blood pressures, without significant differences between sustained and normal release methyldopa effects.
Topics: Adult; Aged; Blood Pressure; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Hypertension; Male; Methyldopa; Middle Aged; Prolactin; Radioimmunoassay
PubMed: 3203713
DOI: 10.1007/BF01046712 -
The Medical Journal of Australia May 1986The clinical features and laboratory findings of 78 cases of methyldopa fever are reported. This drug reaction masqueraded as a variety of acute infectious diseases...
The clinical features and laboratory findings of 78 cases of methyldopa fever are reported. This drug reaction masqueraded as a variety of acute infectious diseases including septicaemia, meningitis, hepatitis and gastroenteritis, occurred within five weeks of starting the drug and appeared to be unrelated to its dosage. Eosinophilia and skin rashes were conspicuous by their absence. In the majority of patients, symptoms were relieved within 48 hours of the withdrawal of the drug. Sixty-one per cent of patients had biochemical evidence of liver damage but jaundice was uncommon. This pattern of mild hepatotoxicity in patients with early febrile reactions to methyldopa contrasts with the later more serious viral hepatitis-like illness due to the drug.
Topics: Adult; Aged; Chemical and Drug Induced Liver Injury; Female; Fever; Humans; Liver Diseases; Liver Function Tests; Male; Methyldopa; Middle Aged
PubMed: 3713591
DOI: 10.5694/j.1326-5377.1986.tb112322.x -
British Journal of Pharmacology May 1972
Topics: Animals; Aromatic Amino Acid Decarboxylase Inhibitors; Disulfiram; Hydrazines; Hypertension; Methyldopa; Rats; Thiocarbamates
PubMed: 5041485
DOI: No ID Found -
Acta Obstetricia Et Gynecologica... 2007alpha-Methyldopa is a classic antihypertensive agent, used routinely in the treatment of pregnancy-induced hypertension. However, only a few data are available about its...
BACKGROUND
alpha-Methyldopa is a classic antihypertensive agent, used routinely in the treatment of pregnancy-induced hypertension. However, only a few data are available about its direct uterotropic effect. Accordingly, the aim of the present study was to investigate the direct effects of alpha-methyldopa on the myometrial adrenergic functions in rat.
METHODS
The effects of alpha-methyldopa on the sympathetic transmission in the non-pregnant, early pregnant and late-pregnant myometrium were investigated by a superfusion technique. Myometrial samples from control and alpha-methyldopa-treated (200 mg/kg i.p. for 7 days) non-pregnant, 7-day and 21-day pregnant rats were saturated with [(3)H]noradrenaline, and the liberation evoked by electric field stimulation was determined. The contractility responses to alpha- and beta-adrenergic stimulation were additionally characterised by generating concentration-response curves of myometrial rings to noradrenaline and terbutaline in the same arrangement. The changes in the density and affinity of the adrenergic receptors (alpha(2) and beta(2)) were investigated by a radioligand binding technique.
RESULTS
The treatment with alpha-methyldopa substantially decreased both the [(3)H]noradrenaline uptake and release in both the non-pregnant and early pregnant uterus, while treatment-dependent changes were observed at term only in the uptake capacity. The contractility response to exogenous alpha-sympathomimetics was higher in the group treated in early pregnancy, and a decreased terbutaline-induced relaxation was observed in the non-pregnant state and at term. The treatment resulted in increased affinity for alpha(2) receptors in early pregnancy, while K(d) for beta(2) was increased at term.
CONCLUSIONS
Our experimental data suggest that besides its antihypertensive effect, alpha-methyldopa may influence the adrenergic transmission of the pregnant uterus. Our results indicate that the agent decreases the efficacy of beta(2)-adrenergic agonists at term pregnancy and increases the response to alpha-sympathomimetics in early pregnancy.
Topics: Animals; Disease Models, Animal; Female; Hypertension, Pregnancy-Induced; Injections, Intraperitoneal; Methyldopa; Myometrium; Norepinephrine; Pregnancy; Rats; Rats, Sprague-Dawley; Sympatholytics; Uterine Contraction
PubMed: 17653886
DOI: 10.1080/00016340701463830 -
British Medical Journal Apr 1973The interaction between methyldopa and levodopa was studied in 18 patients with Parkinsonism. Together they produced a fall in blood pressure in doses which when given... (Clinical Trial)
Clinical Trial
The interaction between methyldopa and levodopa was studied in 18 patients with Parkinsonism. Together they produced a fall in blood pressure in doses which when given alone had no effect or only a slight hypotensive effect. Severe hypotension never occurred. It is reasonable to give methyldopa to hypertensive patients on levodopa but the regimen should be initiated in hospital.
Topics: Blood Pressure; Clinical Trials as Topic; Dihydroxyphenylalanine; Drug Synergism; Humans; Methyldopa; Parkinson Disease
PubMed: 4573316
DOI: 10.1136/bmj.2.5858.90