Tratamento farmacológico e intervencionista do sistema nervoso simpático / Pharmacological and interventional treatment of sympathetic system

o sistema nervoso autônomo contribui diretamente para uma série de atividades biológicas e está envolvido em inúmeras doenças. A hiperatividade simpática é um dos vários mecanismos envolvidos na patogênese da hipertensão arterial sistêmica (HAS) primária. A transmissão da informação nervosa através de sinapses é mediada por agentes químicos específicos conhecidos como neurotransmissores, representados pela acetilcolina e pelas catecolaminas. O bloqueio dos receptores pré e pós-sinapse permite que a ação de fárrnacos alcance sua plenitude no controle dos portadores de hiperati vidade simpática. Um percentual significativo de hipertensos são resistentes ao tratamento farrnacológico. A denervação simpática renal surgiu como estratégia terapêutica adjunta no controle de hipertensos resistentes ao tratamento clínico. Nos últimos cinco anos, diversos estudos demonstraram resultados consistentes na redução da pressão arterial. Diversas outras condições clínicas associam-se à hiperatividade do sistema adrenérgico, tais como a insuficiência cardíaca, o diabetes mellitus, a doença renal crônica, a síndrome da apneia e hipopneia obstrutiva do sono e as arritmias cardíacas. Nestes contextos, a redução da atividade simpática renal também mostrou-se ser benéfica em estudos clínicos iniciais. Uma variedade de dispositivos dedicados foram e estão sendo desenvolvidos com o objetivo de ampliar a segurança e a eficácia do método, além de facilitar o procedimento. Estudos multicêntricos, prospectivos, randomizados e controlados em andamento investigam desfechos como mortalidade cardiovascular, infarto agudo do miocárdio e acidente vascular cerebral em longo prazo.

The autonomic nervous system contributes directly to a number of biological activities and is involved in numerous diseases. Sympathetic hyperactivity is one of several mechanisms involved in the pathogenesis of primary hypertension. The transmission through the nerve synapses is mediated by specific chemical agents known as neurotransmitters represented by the acetylcholine and catecholarnine. Blockade of specific pre-and post-synapse receptors allows the treatment of patients with sympathetic hyperactivity. A large proportion of hypertensive patients are resistant to pharmacological treatment. Renal sympathetic denervation emerged as adjunctive therapeutic strategy in controlling hypertension resistant to medical treatrnent. ln the last five years, several studies have shown consistent results in lowering blood pressure. Several other clinica! conditions are associated with hyperactivity of the adrenergic system such as heart failure, diabetes mellitus, chronic kidney disease, obstructive sleep apnea, polycystic ovary syndrome and cardiac arrhythrnias. ln these contexts, the reduction in renal sympathetic activity also proved to be beneficial in initial clinical studies. A substantial variety of dedicated devices have been developed in order to reduce variability between operators, reduce renal artery manipulation, improve vessel contact, reduce radiation exposure and procedure time, and therefore improving safety and efficacy. Mu!ticenter, prospective, randomized, controlled trials are ongoing to investigate long term outcomes such as cardiovascular mortality, acute myocardial infarction and stroke.

Alpha-methyldopa hepatotoxicity in pregnancy

12-week pregnant, 33-year-old African American female, presented with jaundice and change in urine colour. Liver function tests revealed raised transamines and normal alkaline phosphatase. She was started on methyldopa 6 weeks prior to presentation. After initial negative investigations including viral and autoimmune hepatitis, she was given prednisone for methyldopa induced hepatitis. Two weeks later, repeat enzymes revealed normal values. Important clinical and management points related to methyldopa induced hepatotoxicity are discussed

Síndrome de anticuerpos antifosfolipídicos (SAPS) en terapia intensiva obstétrica / Antiphospholipid antibody syndrome in obstetric intensive care

El Síndrome de Anticuerpos Antifosfolipídicos (SAPS) o de Hughes es un estado de hipercoagulabilidad asociado a pérdidas repetidas de embarazo y severas complicaciones obstétricas. La progresiva adquisición de conocimiento en relación con su patogenia ha permitido aplicar terapéuticas que lleve la gestación a término o a una edad gestacional segura donde pueda ser terminada si la conducta médica lo exige, y tambien evitar o en su defecto disminuir la intensidad de las complicaciones maternas. El espectro de transtornos obstétricos graves en este síndrome es variado pero la preeclampsia, el síndrome de HELLP (hemolysis, elevated liver enzymes and low platelets) y los trastornos de la coagulación; particularmente coagulación intravascular diseminada (CID) pueden ser los dominantes, definiendo el ingreso a una unidad de terapia intensiva (UTI). Presentamos el caso de una paciente que fue admitida a UTI por preeclampsia severa y CID. Fue medicada con aspirina, corticoides, heparina no fraccionada (HNF) y apoyo con plasmaféresis teniendo buena evolución, pero lamentablemente feto muerto in útero posterior al evento agudo

Hepatites medicamenteuses a la methyldopa: a propos de 3 cas

Between January 1991 and Janury 1992, we have collected in National Center of Pharmacovigilance, 3 cases of drug-induced hepatitis in which the responsability of Methyldopa was suspected. In 2 cases, we noticed a mixed hepatitis that associate an intense cytolysis, a cholestase and a hepatocellular insufficiency. Cytolysis, cholestase and hepatoceliular insufficiency evolved favouraby after stopping treatment in all cases. The great delay from treatment start [4 months to 5 years] and the previous hepatitis history in all cases, suggested a toxi mechanism for these drug-induced hepatitis. As Mehtyldopa is still used in many countries for its cheaper cost, we must take care before prescribing it by a good research of hepatic antecedents

effect of centrally acting antihypertensive drugs [clonidine and alpha methyl dopa] on the lipoprotein profile in hypertensive subjects without hyperlipoproteinemia

A large number of trials in the treatment of hypertension proved that some antihypertensive drugs have a negative effect in relation to CHD mortality, although most of the complications of hypertension improved much with such a therapy. This negative effect is most probably due to the adverse effects of these drugs on lipids and lipoproteins. The present study aimed to delineate the effect of two centrally acting antihypertensive drugs [clonidine and alpha methyl dopa] on the blood lipids, lipoproteins, and CHD risk ratios. Thirty mild hypertensive patients of different age and sex were selected, and classified into two equal groups. To the first group clonidine was given in a common dose [0.2 mg/day, for 21 days]. To the other group alpha methyl dopa was given in a common dose [250 mg/three times daily for 21 days]. The lipid profile of each patient was determined before and after therapy with both drugs. The study showed that clonidine produced favorable results with respect to blood lipids and lipoproteins, there were 1 no alterations in lipid or lipoprotein indices which would be considered favorable with regard to the probability of developing CHD. The most common improvement was a lowering of the ratio of total cholesterol to HDL-C, a potent predictor of future CHD. While an unfavorable alteration in lipid-lipoprotein concentrations with respect to the risk of coronary heart disease has been noted with alpha methyl dopa therapy especially in patients with hyperlipoproteinemia

A comparative evaluation of metoprolol and methyldopa in the management of pregnancy induced hypertension.

Thirty patients matched for age, parity, socioeconomic status and severity of pregnancy induced hypertension (PIH) were randomly allocated to treatment with metoprolol or methyldopa. The average fall in diastolic blood pressure was significant in the group treated with metoprolol as compared with the methyldopa group (p less than 0.01). There were 3 perinatal deaths in the methyldopa group and 1 in the metoprolol group; the mean birth weight of the babies was higher in cases treated with metoprolol. The results suggest metoprolol to be more efficacious with regard to control of hypertension and fetal outcome in cases of pregnancy induced hypertension.

Lesiones hepáticas por drogas: presentación de 26 casos / Hepatic lesions induced by drugs: report of 26 cases

Se revisaron 2671 biopsias hepáticas entre los años 1972 y 1985 en el Hospital A. Posadas. Hubo 26 pacientes con daño hepático producido por drogas, habiéndose incluido aquellos enfermos con los siguientes criterios: contacto con un fármaco capaz de producir efecto hepatotóxico; cuadro clínico, biológico e histológico compatible con la droga examinada; remisión completa del cuadro al interrumpir la droga; ausencia de otros tóxicos hepáticos. Catorce pacientes mostraron colestasis intrahepática inducida por estrógenos; 5 tuvieron lesiones hepatitis-like debido a: alfametildopa (3), ketoconazol (1) e indometacina (1). Dos presentaron cambios inflamatorios y cambios grasos por tetracloruro de carbono mientras que la fenibutazona produjo una granulomatosis hepática y una hepatitis colestática. Los últimos tres casos fueron lesiones colestáticas después de la administración de clorpromazina allopurinol y penicilina respectivamente. La evolución en 24 pacientes fue excelente después que se retiró la droga. Dos pacientes murieron por complicaciones quirúrgicas ya que fueron operados con el diagnóstico erróneo de colestasis extrahepática

Hypothermia dn alphamethyldopa treatment.

The hypotensive drug alphamethyldopa, an inhibitor of serotonin synthesis, caused significant hypothermia ranging from 33.4 to 34.8 degrees C (t=3.09 at P less than 0.05) in four out of nine hypertensive patients, with evidence of cerebral atherosclerosis. The anti-serotonin effect of alphamethyldopa correlated with statistically significant (t=6.8 at P less than 0.001) fall in the 24 hour urinary 5-hydroxyindoleacetic acid on the third day of the therapy. The possible mode of hypothermic side effect is discussed.