Bilateral ocular deposit of chlorpromazine / Depósito ocular bilateral de clorpromazina

ABSTRACT Chlorpromazine is a medication widely used in psychiatry for the treatment of psychoses, especially schizophrenia. Since 1964, published articles have been correlating this medication with the appearance of ocular alterations. In this paper, we report the case of a 65-year-old patient with ocular effects due to long-term therapy with chlorpromazine. Biomicroscopy of both eyes presented diffuse granular brown deposits, most prominent at the deep stroma and corneal endothelium level. Also showed anterior subcapsular brown deposits with a stellate pattern in the lens. The total amount exceeds 2.000g (significant for the ocular alterations described) considering the patient's daily dosage of chlorpromazine of 300mg for ten years. After performing complete ophthalmic evaluation and discarding other causes for the ocular deposits, we diagnosed a secondary corneal deposit and cataract due to the use of chlorpromazine. This case reinforces the importance of periodic follow-up with an ophthalmologist for chlorpromazine users to trace ocular changes, heeding the exposure time and its dosage.

RESUMO A clorpromazina é uma medicação muito empregada na psiquiatria para tratamento de psicoses, especialmente em casos de esquizofrenia. Desde 1964 existem artigos publicados que correlacionam o uso dessa medicação com o aparecimento de alterações oculares. Neste trabalho, relatamos o caso de um paciente de 65 anos com efeitos oculares devido à terapia de longo prazo com clorpromazina. A biomicroscopia de ambos os olhos apresentou depósitos granulares difusos e de cor marrom, mais proeminente ao nível do estroma profundo e do endotélio da córnea, além de depósitos castanhos subcapsulares anteriores centrais em um padrão estrelado no cristalino. Considerando a dose diária de clorpromazina de 300mg por 10 anos usada pelo paciente, a quantidade total ultrapassa 2.000g (dose considerada significativa para as alterações oculares descritas). Após avaliação oftalmológica completa e descartado outras causas desses depósitos oculares, foram diagnosticados depósito corneano e catarata secundários ao uso de clorpromazina. O caso apresentado reforça a importância do acompanhamento oftalmolÓgico periÓdico de usuários de clorpromazina para o rastreio de alteraçÕes oculares, atentando-se ao tempo de exposição à droga e à posologia da mesma.

Síndrome Neuroléptico Maligno / Malignant neuroleptic syndrome

El síndrome neuroléptico maligno constituye una complicación infrecuente asociada con el uso de neruolépticos. El cuadro establecido tiene toma de conciencia, rigidez generalizada, disautonomías asociadas con rabdomiólisis con creatinin fosfoquinasa elevada. Se presenta un paciente del sexo masculino de 31 años de edad, con antecedentes de cuadros delirantes alucinatorios a los 7 años, a los 21 y el actual. Los primeros síntomas comenzaron 2 meses antes de su ingreso, con alucinaciones auditivas. Comienza tratamiento con haloperidol; al no mejorar el cuadro psicótico y estar muy agresivo deciden asociarle clorpromazina. Un mes después presenta fiebre y manifestaciones respiratorias. Días después empeora la fiebre, aparece la rigidez axial y la sialorrea. Es trasladado a cuidados intensivos con el diagnóstico de síndrome neuroléptico maligno, comienza tratamiento específico, no obstante fallece a los 3 días. Se concluye que el síndrome neuroléptico maligno es una complicación neurológica infrecuente pero muy grave, con una elevada mortalidad en los casos no tratados de manera precoz

Neurobehavioural study of subchronic administration of oxydemeton-methyl (insecticide and acaricide) in rats.

Oxydemeton-methyl, an organophosphate insecticide and acaricide produced decrease in the exploratory behaviour and prolongation of barbitone sodium induced hypnosis in rats after intermittent aerosol spray inhalational exposure, for 1/2 hour daily for 7 consecutive days, compared to the saline control group. Further, ED50 +/- SEM value for haloperidol induced catalepsy, CD50 +/- SEM value for pentylenetetrazole induced seizure and CI50 +/- SEM value for electroshock (i.e. the dose of haloperidol, PTZ and intensity of electroshock producing catalepsy or positive seizure response in 50% of rats) were significantly decreased after 7 days exposure to oxydemeton-methyl compared to that of saline control group. The study has established the central nervous system depressant effect, extrapyramidal effect and proconvulsant potential of oxydemeton-methyl which is widely used by the agricultural workers in the form of field spray.

Emprego da levomepromazina no bloqueio da arritmia induzida pela adrenalina em cäes anestesiados pelo sevoflurano / The use of levomepromazine to blokade the arrhythmia induced by the epinephrine in dogs anesthetized with sevoflurane

Este experimento objetivou estudar o possível efeito antiarritmogênico da levomepromazina em cäes anestesiados pelo sevoflurano e submetidos a doses crescentes de adrenalina. Para tal, foram empregados 21 animais adultos, machos e fêmeas, sem raça definida e considerados sadios. Os cäes foram separados em dois grupos, sendo um de 11 (G1) e outro de 10 (G2) animais. O G1 recebeu, por via intravenosa, soluçäo salina a 0,9 por cento, na dose de 0,2ml/kg (placebo), seguida 15 minutos após, pela aplicaçäo de tiopental, pela mesma via, na dose suficiente para abolir o reflexo laringotraqueal. Procedeu-se à intubaçäo orotraqueal e iniciou-se a administraçäo de sevoflurano a 2,5V por cento, em circuito anestésico semi-fechado. Decorridos 20 minutos da induçäo anestésica, iniciou-se a administraçäo contínua, por via intravenosa, com emprego de bomba de infusäo, de soluçäo de adrenalina a 2 por cento, em doses crescentes de 1, 2, 3, 4 e 5µg/kg/min (M1 a M5, respectivamente), com incremento da dose a intervalos de 10 minutos. Para o G2, empregou-se a mesma metodologia substituindo-se o placebo por levomepromazina, na dose de 1mg/kg. Foi tomado o traçado eletrocardiográfico, na derivaçäo D2, a partir da induçäo da anestesia. Para efeito estatístico, foi considerado o número total de batimentos cardíacos de origem näo sinusal, coincidentes com cada dose de adrenalina. Os dados numéricos foram submetidos à Análise de Perfil, quando foi possível constatar que as médias do G1 foram crescentes de M1 a M3, diminuindo a partir deste último, até M5. No G2, foi encontrada arritmia ventricular sustentada apenas em M5. Os achados permitiram concluir que a levomepromazina minimiza a arritmia ventricular sustentada, induzida pela adrenalina em cäes anestesiados pelo sevoflurano.

Behavioural alterations in rats induced by single prenatal exposure of haloperidol.

Haloperidol (50 mg/kg, i.p.) treatment was given once to two different groups of pregnant Charles Foster rats on gestational day 9 and 14, these being respectively the critical periods of neural morphogenesis and rapid neural cell proliferation in this species. Pregnant control rats were similarly treated with equal volume of vehicle. The pups born were subjected to open-field exploratory behaviour and elevated plus-maze behaviour tests of anxiety and learned helplessness test of depression at 9 weeks of age. The results indicate that prenatal haloperidol treatment on gestational day 14 induces a significant increase in open-field ambulation and faecal droppings whereas haloperidol treatment on gestational day 9 caused significantly decreased rearing and unaltered ambulation in rat offsprings. Rat offsprings treated with haloperidol on gestational day 9 and 14 also displayed significant anxiogenic behaviour pattern on elevated plus-maze. Significantly increased number of escape failures were observed in learned helplessness tests indicating presence of depression in haloperidol treated rat offsprings. These behavioural alterations were found to be more marked in rat offsprings treated with haloperidol on gestational day 14. The results suggest that prenatal single exposure of high dose of haloperidol during critical period of neural cell proliferation leaves a lasting imprint on offsprings resulting in abnormal emotional state.

Drogas psicotrópicas e coraçäo / Psychotropic drugs and the heart

A moderna Psicofarmacoterapia teve início na década de 1960 e revolucionou o tratamento das doenças mentais. De modo sucessivo e, principalmente no início, empírico, antidepressivos como o diazepam, além do lítio e da carbamazepina foram sendo lançados. Muitas dessas drogas, como os antidepressivos tricíclicos, provocam, mesmo em doses terapêuticas, importantes açöes cardiológicas; eles também interagem, farmacoldinâmica ou farmacocineticamente, com medicamentos usados em Cardiologia. Neste artigo, säo abordados os principais efeitos cardiológicos diretos ou indiretos dos psicofármacos usados na terapêutica psiquiátrica.

Study on the toxic effects of concomitant administration of lithium carbonate and potassium iodide in albino rats

Forty adult albino rats of both sexes were used. They were divided into four equal groups. These groups were control [untreated], Li2 CO3-treated, KI-treated, and combined C03 and KI-treated groups. Li2 CO3-treated group was given 35.5 mg/kg/body weight [1/20, 5%] of the acute oral LD/50 of Li2 CO3 in rats daily, orally, for a period of 8 weeks. Histopathological examination of thyroid glands of this group showed areas of increased activity with cuboidal epithelial lining of thyroid follicles and scanty colloid in their lumina with peripheral vacuolation of the colloid. Biochemical estimation of T3 and T4 of Li2 CO3-treated group showed very highly significant increase in T3 and T4 [P <0.001] compared to the control group. KI-treated group was given 112.5 mg/kg/body weight [1/20, 50%] of the acute oral LD50 of KI [Arena, 1970] after being converted by using Paget and Barnes table [1964], daily, orally, for a period of 8 weeks. Histopathological examination of thyroid glands of this group showed normal thyroid follicles with cuboidal epithelial lining surrounding the colloid, while some areas showed increase in the size of follicles with flattened epithelial lining and appearance of vacuolations in the colloid. Biochemical estimation of T3 and T4 of KI-treated group showed significant increase in T3 [P <0.05] and very highly significant increase in T4 [P <0.001] compared to the control group

Síndrome neuroléptico maligno consecutivo a psicotrópicos y antidepresivos / Malignant neuroleptic syndrome due to psychotropic and antidepressant drugs

Se han estudiado, tres casos clínicos de intoxicación por consumo de neurolépticos que cumplen los criterios diagnósticos del síndrome neurolépticos malignos. Dos de ellos, estuvieron relacionados a la ingesta excesiva de tranilcipromina y trifluoperazina; el tercero, a la asociación de haloperidol y levopromazina. De los tres casos, dos de ellos fallecieron y uno de ellos se puedo efectuar la necropsia; el paciente que sobrevivió presentó síntomas iniciales de síndrome neuroléptico maligno, obteniéndose respuesta favorable al tratamiento. Se revisa el espectro de los síndromes neurolépticos malignos, el diagnóstico diferencial y el esquema de tratamiento

Effects of Antipsychotic Drugs on Cellular lmmunity in Mice

The effects of the two antipsychotic drugs, chlorpromazine and haloperidol, the focus of this study, on cell-mediated immunity in male ICR mice. The peripheral blood WBC count decreased significantly in both cholorpromazine and haloperidol. The absolute lymphocyte count decreased only in the haloperidol-treated groups. The absolute number of thy-1-bearing cells described in both the chlorpromazine and haloperidol groups, the most remarkable effects evidencing itrself in the booster groups of higher dosage chlorpromazine (15 mg/kg), and lower and higher-dosage haloperidol (1 mg/kg and 5 mg/kg). The absolute spleen T-lymphocyte count was decreased significantly in the chlorpromazine higher-dosage booster-dose group and the haloperidol higher-dosage (5 mg/kg) single-dose group and the haloperidol lower and higher-dosage (1 mg/kg and 5mg/kg) booster-dose group. Also, chlorpromazine and haloperidol significantly impaired the in-vitro lymphocyte response to phytohemagglutinin (PHA) and produced a negative reaction of the delayed-hypersensitivity type induced by BCG vaccination. These findings suggest that chlorpromazine and haloperidol suppress the cellular immune responses in mouse.

Effect of alpha-methyl-p-tyrosine on neuroleptic-induced catalepsy in rat.

Pretreatment with alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, was found to increase the intensity of catalepsy induced by haloperidol, chlorpromazine and molindone. The drug probably decreases the synthesis of dopamine and makes less dopamine available for release and to compete with the neuroleptic for the postsynaptic striatal dopamine receptor sites with resultant potentiation of the neuroleptic-induced catalepsy.