Comparative analysis of high dose methyldopa and low dose methyldopa with nifedipine in terms of blood pressure in cases of pregnancy induced hypertension

Objective: Comparison between Methyldopa and combination of Methyldopa and Nifedipine in terms of mean change in blood pressure in pregnancy induced hypertension. Material and methods: This randomized controlled was conducted at Depart Obstetrics and Gynecology DHQ Okara. Total 80 women with pregnancy induced hypertension having age range from 20-40 years and with gestational age 20-40 weeks were selected. Results: Mean age of the patients was 30.81 ± 5.670 years, mean age of patients of group A was 31.50 ± 5.809 years and mean age of group B was 30.13 ± 5.515 years. Mean gestational age was 30.17 ± 5.981 weeks, mean gestational age of patients of group A was 29.70 ± 6.329 weeks and mean gestational age of patients of group B was 6.329 ± 5.650 weeks. In group A, mean diastolic blood pressure was decrease from 101.2250 ± 4.97938 to 84.5000 ± 3.26599 and in group B from 107.7750 ± 7.18434 to 82.5000 ± 2.25320. Comparison of mean decrease in diastolic blood pressure between group A (High dose Methyldopa) and group B (Low dose Low dose Methyldopa with Nifedipine) was done. Mean decrease in diastolic blood pressure in group A was 16.72 ± 3.935 and in group B was 25.28 ± 6.876. Statistically significant difference of mean decrease in diastolic blood pressure between the both groups was noted with p value 0.000. Conclusion: Results of this study showed that Low dose Methyldopa with Nifedipine combination is more effective as compared to High dose Methyldopa to reduce diastolic blood pressure in pregnant women suffering from pregnancy induced hypertension.

Study of labetalol vs. methyldopa in treatment of pregnancy induced hypertension

Background: Hypertension is a common medical problem encountered during pregnancy and is associated with increased risk of adverse outcomes. Objective of this study was to compare efficacy and safety of Labetalol and Methyldopa in controlling blood pressure in patients with PIH and pre-eclampsia.Methods: A comparative, prospective observational, single centre study conducted from November 2015 to November 2017 in women with PIH at Indira Gandhi Government Medical College, Nagpur. Group A included 100 patients treated with Labetalol while Group B included 100 patients who were given Methyldopa. Response in lowering of BP was assessed over a period of 7 days.Results: Labetalol treated group of patients showed significant fall from 143.50±7.30mmHg/101.30±3.93 (sytolic/diastolic) on 1st day to 126.10±5.49 mmHg/87.40±5.62 mmHg (sytolic/diastolic) on day 7, while systolic/diastolic BP in methyldopa group on 1st day was 145.20±7.17 mmHg/101.60±4.20 mmHg which was reduced to 129.20±4.86 mmHg/90.50±3.30 mmHg on day 7. Author found that MAP in Labetalol group reduced from 115.226±4.17 mmHg to 100.17±4.43 mmHg on day 7 while in Methyldopa group had MAP on admission 115.99±4.38 mmHg and on day 7 it reduced to 103.27±2.99mmHg which is highly significant.Conclusions: Labetalol controls systolic and diastolic blood pressure more rapidly and effectively than Methyldopa. Safety profile and adverse effects of Labetalol and Methyldopa are similar to each other.

Labetalol o alfa-metildopa oral en el tratamiento de la hipertensión severa en preeclámpticas / Oral labetalol or alpha-methyldopa in the treatment of severe hypertension in preeclamptic patients

Objetivo. Comparar la eficacia del labetalol oral con alfa-metildopa oral en el tratamiento de la hipertensión severa en preeclámpticas. Diseño. Estudio de casos y controles. Institución. Hospital Central "Dr. Urquinaona", Maracaibo, Venezuela. Participantes. 200 preeclámpticas que fueron asignadas al azar para ser tratadas con labetalol oral (grupo A) o con alfa-metildopa oral (grupo B). Principales medidas de resultado. Eficacia del tratamiento de la hipertensión, tasa de persistencia de la hipertensión y efectos adversos relacionados con el uso de los fármacos. Resultados. No se encontraron diferencias entre los grupos con relación a edad materna, edad gestacional al momento de la inclusión en el estudio e índice de masa corporal (p = ns). Tampoco se observaron diferencias estadísticamente significativas en los valores de presión arterial sistólica, diastólica y media entre los grupos (p = ns). Se observó que las pacientes tratadas con labetalol oral presentaron valores significativamente más bajos de presión arterial sistólica, diastólica y media comparadas con las pacientes tratadas con alfa-metildopa oral (p < 0,0001). Ninguna paciente en el grupo A presentó persistencia de la hipertensión comparado con 17 pacientes en el grupo B (p < 0,0001). El síntoma más común en el grupo A fue la cefalea y en el grupo B, las náuseas, que mostraron ser significativamente más frecuentes (p = 0,006). Conclusión. El labetalol oral fue más efectivo que la alfa-metildopa en el tratamiento de la hipertensión severa en preeclámpticas.

Objective: To compare the efficacy of oral labetalol with oral alpha-methyldopa in the treatment of severe hypertension in preeclamptic patients. Design: Case-control study. Institution: Hospital Central "Dr. Urquinaona", Maracaibo, Venezuela. Participants: 200 preeclamptic patients who were randomly assigned to be treated with oral labetalol (group A) or with oral alpha-methyldopa (group B). Main outcome measures: Hypertension treatment efficacy, rate of persistence of hypertension and adverse effects related to drug use. Results: There were no differences between groups regarding maternal age, gestational age at the time of inclusion, and body mass index (p = ns). There were also no statistically significant differences in systolic, diastolic and mean arterial pressure between groups (p = ns). We observed that patients treated with oral labetalol had significantly lower values of systolic, diastolic and mean arterial pressure compared to patients treated with oral alphamethyldopa (p < 0.0001). No patient in group A had persistent hypertension, while 17 patients in group B did present it (p < 0.0001). The most common symptom in group A was headaches; in group B, nausea was significantly more frequent (p = 0.006). Conclusion: Oral labetalol is more effective than alpha-methyldopa in the treatment of severe hypertension in preeclamptic patients.

Prescripción de metildopa en el tratamiento de pacientes con enfermedad hipertensiva en el embarazo / Methyldopa prescription in patients with hipertensive disease during pregnancy

Se realizó un estudio descriptivo y transversal, de utilización de medicamentos, de tipo indicación-prescripción, de 67 gestantes con enfermedad hipertensiva en el embarazo, atendidas en el Hospital Materno Sur Mariana Grajales Coello de Santiago de Cuba, desde julio de 2015 hasta junio de 2016, con vistas a caracterizar la prescripción de metildopa en estas pacientes. En la casuística predominó el uso de este fármaco en las pacientes que tenían situaciones asociadas con las formas más graves de la enfermedad, tales como la edad avanzada, la nuliparidad y el antecedente de hipertensión arterial. Las principales dificultades correspondieron a la combinación de medicamentos con riesgo de interacciones con la metildopa y al empleo de esta a dosis elevadas

A descriptive cross-sectional indication-prescription study of medications use, of 67 pregnant women with hipertensive disease during pregnancy, assisted in Mariana Grajales Coello Southern Maternal Hospital was carried out in Santiago de Cuba, from July, 2015 to June, 2016, aimed at characterizing methyldopa prescription in these patients. The use of this medicine prevailed in the case material in patients that had situations associated with the most serious forms of the disease, such as advanced age, nonpariity and hypertension history. The main difficulties corresponded to the combination of medicines with risk of methyldopa interactions and its use at a high dose

A comparative randomized controlled parallel group study of efficacy and tolerability of labetalol versus methyldopa in the treatment of mild preeclampsia.

Background: The objective of the current study was to compare the efficacy and tolerability of labetalol versus methyldopa in the treatment of mild preeclampsia. Methods: We carried out a prospective randomized controlled parallel group study on 100 outpatients of Obstetrics and Gynaecology Department of Government Medical College, Patiala, a tertiary care teaching hospital. Pregnant patients (20-40 weeks gestational age) newly diagnosed with blood pressure (BP) of ≥140/90 mm Hg were included in the study. All patients with systolic BP (SBP) ≥160 mm Hg and diastolic BP (DBP) ≥110 mm Hg after 20 weeks of gestation, history of hypertension, renal diseases, diabetes mellitus, epilepsy, and thyroid diseases were excluded from the study. After taking the informed consent, 50 patients each were randomized to either of the two treatment arm-oral labetalol or oral methyldopa. Difference in the BP measurements at the time of admission and at the time of delivery were analyzed by applying paired t-test. For intergroup analysis, we applied independent t-test using SPSS version 16. A p<0.05 was regarded as significant. Results: Both methyldopa and labetalol cause significant fall in SBP, DBP and mean arterial pressure (MAP) in their groups (p<0.001). However, when we compared both groups it was labetalol, which causes significant fall in MAP as compared to methyldopa (p<0.001). The incidence of adverse effects like hypotension, headache, and sedation were also less in labetalol group. Conclusion: Labetalol has an upper edge over methyldopa in control of BP during pregnancy with minimal adverse effects.

Development of a HPLC/MS/MS methodology for determining 3-O-methyldopa in human plasma and its application in a bioequivalence study

A simple, sensitive and specific HPLC/MS/MS methodology was developed and it was validated for determining 3-O-methyldopa, the major metabolite of dopamine, in human plasma. The separation was achieved on Atlantis T3 C18 analytical column (5 μm; 150 x 4.6 mm i.d.) using a mobile phase consisted of a solution of water and methanol (85:15, v/v) and containing formic acid 0.05 %. The extraction from the analyte and the internal standard sample was performed using a simple protein plasma precipitation with perchloric acid. The detection was conducted on a triple quadrupole tandem mass spectrometer with a positive multiple reaction monitoring mode (MRM). The monitored fragmentation transitions were m/z212.0  m/z 166.0 for 3-O-methyldopa and m/z 227.10  m/z 181.0 for carbidopa (internal standard).The calibration curves were linear in the range of 50–4000 ng/mL for 3-O-methyldopa. The methodology presented a good precision and accuracy in accordance to the criteria for biomedical analysis. And it was successfully applied to the bioequivalence study of two formulations levodopa + benserazide (200 + 50mg) in plasma samples from healthy human volunteers, following the ANVISA guidelines...

Development and validation of a simple spectrophotometric method for the determination of methyldopa in both bulk and marketed dosage formulations

A simple, precise, sensitive, rapid, specific and economical spectrophotometric method was developed to determine methyldopa (MTD) content in bulk and pharmaceutical dosage formulations. The proposed method was based on the formation of a colored product from the nitrosation reaction of MTD with sodium nitrite in an acid medium. The resultant nitroso derivative species reacts further with sodium hydroxide and is converted it into a more stable compound. This yellow nitrosation product exhibited an absorption maximum at 430 nm. Beer's Law was obeyed in a concentration range of 6.37 to 82.81 μg mL-1 MTD with an excellent coefficient of determination (R 2 = 0.9998). No interference was observed from common excipients in formulations. The results showed the method to be simple, accurate and readily applied for the determination of MTD in pure form and in pharmaceutical preparations. The analytical results obtained for these products using the proposed method are in agreement with those of the Brazilian Pharmacopoeia procedure at a 95% confidence level.

Desenvolveu-se método espectrofotométrico simples, preciso, sensível, rápido, específico e econômico para a determinação do teor de metildopa (MTD) em matéria-prima e em formulações farmacêuticas. O método proposto baseia-se na formação de um produto colorido resultante da reação de nitrosação da MTD com nitrito de sódio em meio ácido. A espécie resultante (nitroso derivado) reage com hidróxido de sódio e é convertida a um composto mais estável de cor amarela. Este produto exibiu máximo de absorção a 430 nm. A lei de Beer foi obedecida na faixa de concentração de 6,37 a 82,81 μg mL-1 de MTD com excelente coeficiente de determinação (R 2 = 0,9998). Não se observou interferência de excipientes comumente encontrados em formulações farmacêuticas comerciais. Os resultados demonstraram que o método proposto apresenta simplicidade, excelentes precisão e exatidão e pode ser aplicado para a determinação de MTD na sua forma pura e em preparações farmacêuticas. Os resultados analíticos obtidos pelo método proposto estão de acordo com aqueles obtidos pelo método oficial descrito na Farmacopéia Brasileira, a um nível de confiança de 95%.

Labetalol - An Emerging First-line Drug for Pregnancy-induced Hypertension.

Research questions: To study labetalol as a first-line drug for hypertension in pregnancy and endorse its superiority over alpha-methyldopa. Settings: Dept. of Obstetrics and Gynecology, Bharati Vidyapeeth Medical College and Hospital, Pune. Study design and methodology: Patients with diastolic blood pressure recorded above 100 mmHg have been admitted and administered labetalol 100 mg twice-daily orally, the dose escalating to 1.2 g/day. The control of pressures and side effects have been noted. Results: Labetalol is instrumental in causing a sustained and smooth fall in blood pressure and is free of the side effects of alpha-methyldopa. Conclusion: Thus, labetalol supercedes alpha-methyldopa as a first-line drug for hypertension in pregnancy.

Comparative evaluation of antihypertensive drugs in the management of pregnancy-induced hypertension.

Background: Pregnancy-induced hypertension is associated with various adverse fetal and maternal outcomes. The use of anti-hypertensive drugs in pregnancy is controversial. We conducted a prospective study to evaluate the comparative effectiveness and safety of nifedipine, methyldopa and labetalol monotherapy in patients with pregnancy-induced hypertension. Methods: A total of 60 pregnant women with blood pressure of 140/90 mm Hg or more with ≥1+ proteinuria between 20 and 38 weeks of gestation were randomly allocated to receive nifedipine (n=20), methyldopa (n=20) or labetalol (n=20). Blood pressure was measured at 0, 6, 24, 48 and 72 h of initiation of antihypertensive drugs. Patients were also followed up for development of adverse drug effects during this period. Results: Antihypertensive treatment with methyldopa was associated with reduction in systolic blood pressure (SBP) by 50 mmHg and diastolic blood pressure (DBP) by 30 mmHg at 72 h. For the same period treatment with nifedipine was associated with reduction in SBP by 54 mmHg and DBP by 30 mmHg. Treatment with labetalol was associated with reduction in SBP by 70 mmHg and DBP by 36 mmHg at 72 h. Conclusions: Labetalol was more effective than methyldopa and nifedipine in controlling blood pressure in patients with pregnancy-induced hypertension while methyldopa and nifedipine are equally effective in controlling blood pressure.

Different culture media containing methyldopa for melanin production by Cryptococcus species / Avaliação de diferentes meios de cultura contendo metildopa para a produção de melanina por espécies de Cryptococcus

INTRODUCTION: Melanin production by species of Cryptococcus is widely used to characterize C. neoformans complex in mycology laboratories. This study aims to test the efficacy of methyldopa from pharmaceutical tablet as a substrate for melanin production, to compare the production of melanin using different agar base added with methyldopa, and to compare the melanin produced in those media with that produced in Niger seed agar and sunflower seed agar by C. neoformans, C. laurentii, and C. albidus. Two isolates of each species, C. neoformans, C. laurentii, and C. albidus, and one of Candida albicans were used to experimentally detect conditions for melanin production. METHODS: The following media were tested: Mueller-Hinton agar (MHA), brain and heart infusion agar (BHIA), blood agar base (BAB), and minimal medium agar (MMA), all added with methyldopa, and the media Niger seed agar (NSA) and sunflower seed agar (SSA). RESULTS: All isolates grew in most of the culture media after 24h. Strains planted on media BAB and BHIA showed growth only after 48h. All isolates produced melanin in MMA, MHA, SSA, and NSA media. CONCLUSIONS: Methyldopa in the form pharmaceutical tablet can be used as a substrate for melanin production by Cryptococcus species; minimal medium plus methyldopa was more efficient than the BAB, MHA, and BHIA in the melanin production; and NSA and SSA, followed by MMA added with methyldopa, were more efficient than other media studied for melanin production by all strains studied.

INTRODUÇÃO: A produção de melanina por espécies de Cryptococcus é uma característica amplamente utilizada em laboratórios de micologia para caracterização do complexoC. neoformans. O objetivo deste estudo foi verificar a eficácia da metildopa na forma farmacêutica de comprimido, como substrato para a produção de melanina por Cryptococcus, comparar diferentes bases de meios de cultura acrescidas de metildopa para produção de melanina e comparar o pigmento produzido nestes meios com o produzido em ágar Níger e ágar girassol por C. neoformans, C. laurentii e C. albidus. MÉTODOS: Foram testados dois isolados de cada uma das espécies, C. neoformans, C.laurentii e C.albidus, e um de C. albicans para avaliar a produção de melanina nos meios de cultura ágar Müeller-Hinton (MH), ágar brain heart infusion (BHI), ágar base sangue (BS), meio mínimo (MM), todos acrescidos de metildopa, e ainda ágar girassol e ágar Níger. RESULTADOS: Todos os isolados cresceram na maioria dos meios após 24h. O crescimento nos meios BS e BHI somente ocorreu após 48h. Todos os isolados produziram melanina nos meios MM, MH, girassol e Niger. CONCLUSÕES: A metildopa de origem farmacêutica pode ser utilizada como substrato para a produção de melanina por espécies de Cryptococcus; o MM acrescido de metildopa mostrou-se mais eficiente na produção de melanina do que os meios BS, MH e BHI; ágar girassol e ágar Níger seguidos de MM acrescido de metildopa foram os mais eficientes na produção de melanina pelos isolados estudados.

Tratamento da pré-eclâmpsia baseado em evidências / Pre-eclampsia treatment according to scientific evidence

As síndromes hipertensivas na gestação merecem especial destaque no cenário da saúde pública mundial. Atualmente, respondem como terceira causa de mortalidade materna no mundo e primeira no Brasil. Do ponto de vista prático, a pré-eclâmpsia continua sendo uma síndrome que leva a graves repercussões maternas e fetais, conhecendo-se ainda pouco sobre sua etiologia. Atualmente, tem-se discutido a melhor terapêutica para os quadros de pré-eclâmpsia em diversos momentos do ciclo gravídico-puerperal, visando sempre à redução de altos índices de morbimortalidade materna e fetal. O parto, considerando-se a fisiopatologia do evento, representa a melhor forma de tratamento. O uso de sulfato de magnésio é recomendado em todos os casos de pré-eclâmpsia grave e eclâmpsia para prevenção e tratamento das crises convulsivas. Da mesma forma, o tratamento dos picos hipertensivos é recomendado. Hidralazina, nifedipina e labetalol têm sido as drogas mais utilizadas com essa finalidade, mas seu uso dependente da familiaridade do médico assistente. A corticoterapia antenatal está indicada sempre que existe risco iminente de prematuridade entre a 24º e 34º semana. Em contrapartida, não há evidências suficientes para recomendar repouso e administração de expansores plasmáticos de rotina, assim como há necessidade urgente de ensaios clínicos randomizados para determinar se o tratamento anti-hipertensivo de manutenção nas gestantes apresenta benefícios ou riscos para mães e fetos, em todas as formas clínicas da doença, em particular nos casos de pré-eclâmpsia pura.

Hypertensive disorders in pregnancy deserve special attention in the setting of global public health. Currently, they represent the third cause of maternal mortality in the world and first in Brazil. From a practical standpoint, pre-eclampsia remains a syndrome that leads to serious repercussions on maternal and fetal mortality and its etiology is not well known. Currently, the best treatment for forms of pre-eclampsia is being discussed at different times in pregnancy and puerperium, with the objective to reduce the high rates of maternal and fetal morbidity and mortality. Considering the pathophysiology of the event, anticipation of delivery is the best treatment for pre-eclampsia. The use of magnesium sulfate is recommended in all cases of severe pre-eclampsia and eclampsia for prevention and treatment of seizures. Likewise, treatment of hypertensive crises is recommended. Hydralazine, nifedipine and labetalol have been the most commonly used drugs for this purpose, but their use depends on the familiarity of the treating physician. Antenatal corticoid therapy is indicated whenever there is an imminent risk of preterm delivery between 24 and 34 weeks. In contrast, there is insufficient evidence to recommend bed rest and routine plasma volume expansion, and there is an urgent need for randomized clinical trials to determine whether maintenance antihypertensive treatment in pregnant women has benefits or risks for mothers and fetuses in all clinical forms of disease, particularly in cases of pure pre-eclampsia.

Anemia hemolítica secundaria a metildopa / Hemolytic secondary anemia to methyldopa

Se presentó el caso de una paciente de sesenta y dos años, hipertensa esencial desde hace veinte años. Después de recibir tratamiento con metildopa, dos gramos diarios durante cuatro meses, presenta anemia hemolítica y trombocitopenia, con prueba de Coombs directa positiva. Se discutieron los mecanismos fisiopatológicos posibles, y se reseñaron las drogas capaces de producir esta enfermedad, así como los mecanismos de acción de la metildopa y los efectos hematológicos adversos.

A case of a sixty two year-old patient, essential hypertensive for twenty years is presented. After receiving treatment with methyldopa, two daily grams during four months, showed hemolytic anemia and thrombocytopenia, with the positive direct Coombs´test. Possible physiopathologic mechanisms were discussed, the drugs able to produce this disease, the action mechanisms of methyldopa and the hematologic side effects were pointed out.

Does 3-O-Methyldopa(3-OMD) Inhibit the Binding of Levodopa to Plasma Protein / 대한정신약물학회지

OBJECTIVE: We determined the influence of 3-OMD in the protein binding of levodopa to estimate the effect of 3-OMD on the penetration of levodopa into brain. METHOD: P-glycoprotein in the brain may serve to limit drug penetration into the brain. Because it is not available as an experimental substance, but has similar binding properties with alpha 1 acid glycoprotein(AGP), we used AGP in this study. Additionally, we used blood plasma to see the affinity of plasma binding of levodopa. The final concentration of chemicals used in this study were 125, 250, 500, 1000, 2000, 4000 microgram/l for levodopa and 0, 1250, 5000, 10,000 microgram/l for 3-OMD, 1 mg/l for AGP. The free fraction of levodopa in blood plasma and AGP were separated by ultrafiltration method and determined by beta-counter, respectively. RESULTS: We found that levodopa did not bind with AGP, but only 22-24% from 125 microgram/l to 4000 microgram/l of it bound with blood plasma. The addition of 3-OMD to the blood plasma did not significantly change the binding of levodopa. CONCLUSIONS: We can conclude that 3-OMD does not influence the penetration of levodopa into brain. These small amount of the binding does not expect to influence to other drugs on the binding with plasma.