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Introduction. There are three groups of disorders during pregnancy: disorders specific for pregnancy that resolve spontaneously or soon after delivery, acute hepatic disorders coinciding with pregnancy, and chronic disorders. Drug-induced liver disease prevails among women and it is estimated to be a leading cause of acute liver injury. Drug-induced hepatitis is rare in pregnancy with only a few cases reported in literature. Alpha-methyldopa is one of the commonly used drugs in pregnancy that could cause hepatotoxicity with different clinical presentations and possible adverse effects on normal course of pregnancy. Case outline. We reported a rare case of hepatotoxicity caused by alpha-methyldopa in 26 gestational weeks pregnancy in a 35-year-old patient admitted because of jaundice and elevated liver function tests. She had been using antihypertensive drug, alpha-methyldopa, from 12th gestational week, and no other medication or supplementation was recorded. Ultrasound of the abdomen excluded obstruction or any other abnormalities. Autoimmune panel was done. Biochemical analyses were indicative of toxic acute liver injury caused by alpha-methyldopa according to values of transaminase. After 13 days, patient was discharged recovered from the hospital. Conclusion. Diagnosis of alpha-methyldopa hepatotoxicity is challenging since the low incidence, unpredictability, diverse symptomatology and absence of specific biomarkers. That is why timely diagnosis is crucial for the well-being of both future mother and child.

Introduction : Anacardium occidentale Linn. 1753 (Anacardiaceae) est une plante très utilisée en médecine traditionnelle en Afrique de l’Ouest pour le traitement de diverses pathologies, notamment cardiovasculaires. L’objectif de cette présente étude est d’évaluer l’effet hypotenseur de l’extrait aqueux de Anacardium occidentale. Matériel et méthodes : Le matériel biologique de cette étude est constitué d’écorces de tronc de Anacardium occidentale et de lapins de l’espèce Oryctolagus cuniculus (Leporideae) pesant en moyenne deux (2) kilogrammes. L’extrait aqueux d’écorces de tronc de Anacardium occidentale (ANO) est obtenu après macération dans deux (2) litres d’eau distillée de cinquante (50) grammes de poudre de plante. Le filtrat obtenu est évaporé sous vide à 70°C grâce à un évaporateur Rotavapor de type "Bucchi" et lyophilisé. L’enregistrement de la pression artérielle de lapin est effectué grâce à un manomètre de LUDWIG, comprenant un tube en U contenant du mercure dont l’un des cathéters est relié à la carotide mise à nu du lapin. Les variations de la pression carotidienne du lapin sont transmises à la colonne de mercure et sont transcrites à l’aide d’un stylet inscripteur, sur un cylindre recouvert de papier enduit de noir de fumée et tournant à vitesse constante. Résultats et discussion : ANO, à des doses comprises entre 2,5.10-4 g/kg P.C et 6,2.10-2 g/kg P.C., provoque une hypotension soutenue dose-dépendante semblable à celle induite par l’acétylcholine de 5,6.10–7 à 5,5.10–4 g/kg de PC. Ces résultats sont en accord avec ceux de TCHIKAYA et al. (2003) qui ont travaillé dans les mêmes conditions expérimentales sur le même extrait aqueux. Ces effets pharmacologiques sont comparables à ceux de l’acétylcholine, une substance hypotensive (FURCHGOTT et VANHOUTTE, 1989), dont l’atropine, antagoniste compétitif des récepteurs cholinergiques de type muscarinique (GEROVA et al., 2005), n’a pas d’effet important sur les propriétés hypotensives de ANO. Les substances hypotensives contenues dans cet extrait brut ne seraint donc pas des substances cholinomimétiques de type muscarinique. Les effets hypotenseurs de notre extrait aqueux étant totalement inhibés par la chlorpromazine, un antipsychotique (BORDET, 2004), ANO pourrait avoir une action centrale comme la clonidine et l’alpha-métyldopa (DE CORT et al., 2004). De par ses effets sur le système nerveux central, cet extrait brut pourrait inhiber le système orthosympathique et provoquer chez l’animal entier c'est-à-dire chez le lapin une cardioinhibition et une vasodilatation induisant ainsi un effet hypotenseur. Cela justifierait ainsi l’utilisation de cette plante dans le traitement de l’hypertension artérielle.

INTRODUCTION: there is variance in both the types and combinations of antihypertensive drugs used for managing pre-eclampsia in the postpartum period. Knowledge of the most common and suitable single or combination antihypertensive drug therapies in the postpartum period will minimize harmful effects, promote adherence to medications, overcome any fears that lactating mothers may have about these drugs and will assist in healthcare planning.

Introduction: there is variance in both the types and combinations of antihypertensive drugs used for managing pre-eclampsia in the postpartum period. Knowledge of the most common and suitable single or combination antihypertensive drug therapies in the postpartum period will minimize harmful effects, promote adherence to medications, overcome any fears that lactating mothers may have about these drugs and will assist in healthcare planning. Objective: to determine the types of antihypertensive drug therapies used in managing pre-eclampsia with severe features (sPE) in the postpartum period in a regional hospital in South Africa. Methods: fifty consecutively presenting pregnant women with sPE were followed up prospectively from the pre-delivery period (within 48 hours before delivery) until day 3 postpartum. The antihypertensive drug therapies administered to the participants were observed. Their blood pressures were measured daily at 04: 00, 08: 00, 14: 00 and 22: 00 hours. Results: nifedipine was the commonest rapid-acting agent used for severe hypertension. Prepartum, 9 different combinations of antihypertensive drugs were prescribed; alpha-methyldopa was the commonest single long-acting agent used. Postpartum, the number of different drug combinations administered were 15, 18, 22 and 16 on days 0, 1, 2 and 3 respectively. Alpha-methyldopa was the commonest single agent used on postpartum days 0 - 2 while hydrochlorothiazide was the most frequently used single agent on postpartum day 3. Postpartum, the commonest combination therapy was alpha-methyldopa and amlodipine on day 0; alpha-methyldopa and amlodipine as a regimen as well as alpha-methyldopa, amlodipine and hydrochlorothiazide as another regimen on day 1; alpha-methyldopa and amlodipine on day 2; and many amlodipine-based regimens on day 3. Conclusion: a variety of antihypertensive drug combinations were used in the postpartum period indicating the need for standardised guidelines; however, detailed studies are required to evaluate their efficacies completely. [ABSTRACT FROM AUTHOR]

Background: Prenatal period is a critical developmental phase that is sensitive to hormonal disruption by natural and/or exogenous hormones. Some pharmaceuticals frequently prescribed and used safely during pregnancy are shown to interact with the developmental programming of fetus, resulting in endocrine-related adverse effects., Objective: In this research, we aimed to determine the endocrine disrupting potential of paracetamol, indomethacin, alpha-methyldopa and pantoprazole which are frequently prescribed pharmaceuticals during pregnancy., Methods: In vitro aromatase inhibitory, estrogen receptor (ER) agonist/antagonist (E-Screen assay) and hormone biosynthesis modulatory effects (H295R steroidogenesis assay) of the selected pharmaceuticals were evaluated. Furthermore, their effects on viability of MCF-7/BUS and H295R cells were also evaluated by MTT assay., Results: None of the pharmaceuticals affected H295R cell viability. Only indomethacin reduced MCF-7/BUS cell viability at 100µM and 300µM. Among the tested pharmaceuticals, only paracetamol and indomethacin showed aromatase inhibitory activity with IC 50 values of 14.7 x 10 -5 M and 57.6 x 10 -5 M, respectively. Moreover, indomethacin displayed a biphasic ER agonist effect. ER antagonist effects of indomethacin and pantoprazole were confirmed by performing two stepped E-Screen assay. After the partial validation of the H295R steroidogenesis assay with forskolin and prochloraz, the effects of pharmaceuticals on synthesis of testosterone (T) and estradiol (E2) levels were tested. Alpha-methyldopa increased E2 at all tested concentrations and T at 1.48 and 4.4µM. Contrarily other tested pharmaceuticals did not affect steroidogenesis., Conclusion: Present data suggest that all tested pharmaceuticals may have potential endocrine disrupting effect, which should be considered when used in pregnancy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A multicentre study of 6-10 weeks duration was performed in 60 ambulant hypertensive patients aged over 60 years to compare the efficacy of methyldopa and propranolol with particular reference to the occurrence of cold extremities and sleep disturbances. Blood pressure was effectively controlled by both drugs being reduced from a mean of 180/108 mmHg to 161/93 with methyldopa and 180/108 to 162/94 with propranolol. More patients treated with methyldopa (74%) achieved the target diastolic blood pressure of 95 mmHg or below compared with those treated with propranolol (58%). Side effects were more frequent in the propranolol group necessitating the withdrawal of four patients from the study. Only one patient on methyldopa was withdrawn. The incidence of cold extremities was significantly greater with propranolol. The occurrence of sleep disturbances was similar in both groups. In this group of elderly patients methyldopa was better tolerated than propranolol. [ABSTRACT FROM AUTHOR]

The clinical picture and drug metabolism in 36 consecutive patients with alpha-methyldopa - induced hepatic injury were investigated. The diagnosis was based on case history and biochemical, histological and follow-up studies after withdrawal the drug. Alpha-methyldopa-induced liver damage was found to occur in two phases, acutely within months and chronically within years after beginning treatment. Differences were also found in clinical symptoms and the results of liver tests on the patients if they were divided on the basis of the time factor. Drug metabolism was impaired in patients with alpha-methyldopa-induced liver damage, as indicated by low cytochrome P-450 level in liver biopsies and prolonged antipyrine elimination rate from plasma. Disappearance of the symptoms and normalisation of the liver tests after drug withdrawal occurred faster in patients with an acute type of hepatotoxicity than in subjects with delayed onset of the symptoms. The occurrence of hepatotoxicity in four members of a family suggests a genetic disposition to alpha-methyldopa-induced hepatic injury. The occurrence of two phases of liver damage suggests that a possible mechanism for acute hepatotoxicity might be an allergic reaction to metabolic intermediates produced during breakdown of alpha-methyldopa in the liver. For cases of delayed onset the cause might be increasing damage to microsomal liver protein due to covalent binding during long-term exposure to the drug. [ABSTRACT FROM AUTHOR]

In a single-blind study, the dopa-decarboxylase inhibitor benserazide (375 mg/day for 3 days and 750 mg/day for further 3 days) and a placebo were given orally in combination with individually effective doses of alpha-methyldopa (mean 1.5 g/day) to 3 hospitalized patients with essential hypertension. Alpha-methyldopa (α-MD) alone lowered blood pressure from 165/107 to 136/93 mm Hg (P<0.05). Benserazide did not alter the hypotensive effect of α-MD, although the decarboxylation of α-MD was markedly reduced, as shown by the urinary excretion of alpha-methyldopamine (α-MDA). During administration of α-MD alone, the ratio α-MD/α-MDA in urine of the 3 patients was 8:1, 7:1 and 22:1, respectively. When benserazide 375 mg/day was added the ratio rose to 31:1, 31:1 and 35:1; the ratio was 37:1, 18:1 and 46:1 at the higher dose of inhibitor. In a double-blind crossover study the effect on blood pressure of 3 weeks of treatment with α-MD (mean 1.75 mg/day), benserazide (375 mg/day), placebo and their combinations were compared in 5 hypertensive subjects. Again, benserazide did not influence the antihypertensive action of α-MD. To study whether benserazide entered the CNS, a single oral dose ofC-benserazide of 125 mg was given to 2 patients who were to undergo diagnostic lumbar puncture. Two hours after intake of the labelled drug, when radioactivity in blood had reached a maximum, the concentration of radioactivity in spinal fluid was less than 1% of the plasma level. Thus, the antihypertensive action of α-MD was not influenced by oral doses of the decarboxylase inhibitor benserazide. The results suggest that benserazide in doses up to 750 mg/day does not affect central decarboxylation of α-MD and that this antihypertensive agent lowers blood pressure by a central action. [ABSTRACT FROM AUTHOR]

The hypotensive actions of metoprolol and alpha-methyldopa have been compared in 37 men with previously untreated essential hypertension; 36 belonged to stage 1 and 1 to stage 2 of the WHO classification. After four weeks of placebo treatment the patients were randomly allocated to treatment with either of the two drugs. Treatment was started with metoprolol 75 mg daily or alpha-methyldopa 375 mg and was doubled after eight weeks. Satisfactory blood pressure control was defined as systolic blood pressure below 160 mm Hg and diastolic below 95 mm Hg. The patients were examined every four weeks and in those with unsatisfactory control the dose was gradually increased up to a maximum daily dose of metoprolol 450 mg or alpha-methyldopa 2250 mg. The trial lasted for 24 weeks after randomization. Five patients dropped out of the study. After six months, satisfactory blood pressure control was recorded in 16 out of 17 patients and 14 out of 15 patients treated with metoprolol and alpha-methyldopa, respectively. The average reduction in blood pressure produced by the two drugs was comparable. One patient in the alpha-methyldopa group developed drug exanthema and two patients a positive Coombs' test. Other side effects were few and did not differ between the two compounds. [ABSTRACT FROM AUTHOR]

Alpha-methyldopa is one of the most widely prescribed antihypertensive agents used during pregnancy. Despite its known potential hepatotoxicity, there have been only a few reports describing hepatotoxicity with the use of this drug during pregnancy. We report here a new case of acute hepatitis in a pregnant woman related to the use of alpha-methyldopa, and briefly review the literature on alpha-methyldopa-induced hepatotoxicity in pregnancy. [ABSTRACT FROM AUTHOR]

Background: The treatment of cocaine toxicity is an important subject for emergency physicians. We investigated the effects of dexmedetomidine, moxonidine and alpha-methyldopa on acute cocaine toxicity in mice., Objectives: The aim of this study was to evaluate the effects of dexmedetomidine, moxonidine and alpha-methyldopa in a mouse model of acute cocaine toxicity., Materials and Methods: We performed an experiment consisting of four groups (n = 25 each). The first group received normal saline solution, the second group received 40 µg/kg of dexmedetomidine, the third group received 0.1 mg/kg of moxonidine and the fourth group received 200 mg/kg of alpha-methyldopa, all of which were intraperitoneally administered 10 minutes before cocaine hydrochloride (105 mg/kg). All animals were observed for seizures (popcorn jumping, tonic-clonic activity, or a loss of the righting reflex) and lethality over the 30 minutes following cocaine treatment., Results: The ratio of animals with convulsions was lower in all treated groups when compared to the control (P < 0.001). Furthermore, 68% (n = 17) of animals in the dexmedetomidine group, 84% (n = 21) of the alpha-methyldopa group, 92% (n = 23) of the moxonidine group and 100% (n = 25) of the control group showed evidence of seizure activity (P = 0.009). Cocaine-induced lethality was observed in 12% (n = 3) of the dexmedetomidine group, 48% (n = 12) of the alpha-methyldopa group, 52% (n = 13) of the moxonidine group, and 72% (n = 18) of the control group (P < 0.001). All treatments prolonged the time to seizure, which was longest in the dexmedetomidine group (P > 0.05). In addition, the time to lethality was also longer in the same group (P < 0.001)., Conclusions: The present study provides the first experimental evidence in support of dexmedetomidine treatment for cocaine-induced seizures. Premedication with dexmedetomidine reduces seizure activity in a mouse model of acute cocaine toxicity. In addition, while dexmedetomidine may be effective, moxonidine and alpha-methyldopa did not effectively prevent cocaine-induced lethality.