Efeitos endócrinos e metabólicos das drogas antiepilépticas / Endocrine and metabolic effects of antiepileptic drugs

As drogas antiepilépticas (DAE) são utilizadas por um enorme contingente de pessoas em todo o mundo - tanto no tratamento das epilepsias como para outros fins - frequentemente por um longo tempo. Por essas razões, torna-se fundamental o conhecimento sobre os potenciais efeitos adversos desses medicamentos, muitos deles envolvendo vários aspectos hormonais e metabólicos que devem ser do conhecimento do endocrinologista. Nesta revisão, foi abordada a relação das DAE com anormalidades no metabolismo mineral ósseo, balanço energético e peso corporal, eixo gonadal e função tireoideana, além de ter sido revisado o papel terapêutico dessas medicações no tratamento da neuropatia diabética.

The antiepileptic drugs (AED) have been widely used for a great deal of people - in the treatment of epilepsy and other diseases - throughout the world. Continuous and prolonged use of AED may be associated with adverse effects in different systems, including a variety of endocrine and metabolic abnormalities. In this review, the relationship of AED with alterations in bone mineral metabolism, energy balance and body weight, gonadal function and thyroid metabolism was revised, as well as their clinical utility in the treatment of diabetic neuropathy.

Calcium homeostasis in low and high calcium water acclimatized Oreochromis mossambicus exposed to ambient and dietary cadmium.

The effects of cadmium administered via ambient water (10 microg/l) or food (10 microgCd/fish/day) on plasma calcium, corpuscles of Stannius and bony tissues of Oreochromis mossambicus acclimated to low calcium (0.2 mM) and high calcium (0.8 mM) water were studied for 2, 4, 14 and 35 days. In low calcium water acclimated fish, ambient cadmium induced significant hypocalcemia, while the structure and morphometry of type-1 and type-2 cells of corpuscles of Stannius were not affected on day 2 and 4. Subsequently on day 14 and 35, recovery of plasma calcium to normal levels was observed followed by a decrease in corpuscles of Stannius index (CSI), cell size, volume of granular endoplasmic reticulum (p < 0.05) of type-1 cells in both, fish exposed to ambient or dietary cadmium. The type-2 cells were not affected. In high calcium water acclimated fish both, ambient and dietary cadmium caused a significant reduction of plasma calcium levels on day 2 and 4. In these fish, there was a significant transient increase in the size of corpuscles of Stannius on day 4, followed by recovery on day 14 and 35. Ultrastructural observations of corpuscles of Stannius revealed that cadmium did not cause any cellular damage on type- and type-2 cells during 35 days exposure. In low or high calcium water acclimatized tilapia exposed to ambient or dietary cadmium had no effect on the calcium and phosphate composition of the scales, operculum and vertebrae. Thus, it is unlikely that recovery of hypocalcemia was due to the dissolution of calcium from bony tissues. This study also revealed that cadmium does not mediate stimulation of the corpuscles of Stannius gland, and that high Ca2+ water had a protective effect against ambient and dietary cadmium.

Growth and puberty after treatment for acute lymphoblastic leukemia

Nos últimos 20 anos, após o tratamento de pacientes portadores de leucemia linfoblástica aguda, com quimioterapia e radioterapia, houve melhora na taxa de sobrevivência e cura em torno de 70 por cento. Crianças portadoras da doença foram envolvidas em protocolos de tratamento internacionais que visavam melhorar a sobrevida e minimizar os graves e irreversíveis efeitos tardios. A nossa unidade utiliza o protocolo internacional GBTLI LLA-85 e 90, com as drogas metrotexate, citosina, arabinoside, dexametasona e radioterapia .Entretanto, estes tratamentos podem causar insuficiências gonadais e prejuízo no crescimento. PACIENTES E MÉTODO: Os autores analisaram 20 crianças fora de terapia a fim de determinar o papel das várias doses de radioterapia sobre alterações endocrinológicas. Foram divididos em três grupos baseados na profilaxia do sistema nervoso central: o grupo A foi submetido à quimioterapia, o grupo B à quimioterapia mias radioterapia (18Gy) e o grupo C à quimioterapia mais radioterapia (24 Gy). Foram avaliadas as concentrações séricas de LH, FSH, GH e testosterona. Os estudos de imagem incluiram idade óssea, ultrassonografia pélvica, escrotal e ressonância nuclear magnética do crânio. RESULTADOS: Houve diferenças significativas nas respostas do hormônio de crescimento e prejuízo na estatura final (Bayley-Pinneau) entre os dois grupos irradiados e o grupo que não foi irradiado, mas não houve diferenças quando se compararam as doses de radiação utilizadas (18 ou 24 Gy). A previsão da altura final (Bayley-Pinneau) foi menor (p= 0,0071) nos dois grupos tratados com radioterapia. Duas meninas apresentaram puberdade precoce e um menino teve atraso puberal associado a calcificação do epidídimo. CONCLUSÃO: A radioterapia é responsável por efeitos colaterais especialmente quanto ao crescimento e puberdade.

Effect of xylazine on some endocrinological and hematological parameters in heifers under thermoneutral or heat stress conditions

A study was performed to assess the effect of xylazine HCl [0.1 mg/kg of body weight, i.v.] in heifers maintained at thermoneutral [TN, 18C, 42% RH] or heat stress [HS, 33C, 63% RH] conditions. Xylazine injection resulted in a sharp increase [P <0.05] in serum cortisol levels after 15 minutes in both groups. However, cortisol levels gradually declined and reached basal levels after 45 minutes and 3 hours in heifers maintained under TN and HS conditions, respectively. Xylazine administration increased [P <0.05] serum T3 concentrations after 15 and 30 minutes in the thermoneutral and heat-stressed animals, respectively. Serum T3, however, gradually decreased and reached basal values after 3 hours in both groups. The xylazine- treated heifers had lower [P <0.05] red blood cells, hemoglobin and packed cell volume under TN conditions, while higher [P <0.05] values were observed under HS conditions. All the above parameters were greater [P <0.05] in the thermoneutral animals than in the heat- stressed ones either before or after xylazine administration. It is possible than an undesirable interaction occurred between xylazine and the hot environment, thus it is suggested that xylazine should be used cautiously in hyperthermic animals

Drug induced endocrine problems.

Drug induced effects on the various endocrine and metabolic processes constitute a very common differential diagnostic possibility in investigating endocrine disorders. Knowledge of drug-effect is of paramount importance to avoid unnecessary and expensive investigations and treatment. Since most of the effects are type A effects and hence predictable, reduction of dose or modification of therapy is sufficient to reverse the adverse effects.

Effect of period-suppressing danazol therapy on the endocrine profile of pretreatment normally menstruating women

A dose of 400 mg danazol daily for 6 months produced no persistent change in basal levels of serum gonadotrophins. Nevertheless there was an enhanced luteinizing hormone response to exogenous luteinizing hormone releasing hormone. Both oestradiol and sex hormone binding globulin showed a significant secondary rise after an initial marked drop. Prolactin followed the oestradiol trend but dehydroepiandrosterone sulphate showed no significant 'between months' change throughout the study