RESUMO
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.
Assuntos
Humanos , Masculino , Idoso , Catarata/induzido quimicamente , Clorpromazina/efeitos adversos , Clorpromazina/toxicidade , Córnea/efeitos dos fármacos , Doenças da Córnea/induzido quimicamente , Opacidade da Córnea/induzido quimicamente , Transtornos da Pigmentação/induzido quimicamente , Antipsicóticos/efeitos adversos , Antipsicóticos/toxicidade , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Acuidade Visual , Clorpromazina/administração & dosagem , Clorpromazina/uso terapêutico , Doenças da Córnea/diagnóstico , Opacidade da Córnea/diagnóstico , Lâmpada de Fenda , Microscopia com Lâmpada de FendaRESUMO
OBJECTIVE: The literature has shown that synthetic antipsychotic drugs induce reproductive toxicity, while psychiatric patients treated with traditionally used antipsychotic herbs (Rauwolfia vomitoria) showed no traces of reproductive toxicity. Thus, this study aimed to investigate the expression of CREM, PRM I and II genes in the testes of Wistar rats treated with antipsychotic drugs: chlorpromazine, Rauwolfia vomitoria (RV) and co-administration of reserpine, zinc and ascorbate (RAZ). METHODS: Forty-five adult male Wistar rats with rats with average weight of 180±4.67g were divided into nine groups (A-I) (n=5). Group A was administered saline (control) while rats in Groups B and C received 10 and 20mg/kg body weight (bwt) of chlorpromazine respectively. Groups D and E received 2.5 and 5mg/kg bwt of reserpine, respectively; while Groups F and G received 150 and 300mg/kg bwt of RV leaf extract. Groups H and I received (2.5+5+100) mg/kg bwt and (5+10+200) mg/kg of combination of RAZ, respectively for 56 days. RESULTS: The CREM, PRM I and II genes were significantly downregulated while significant decreased in serum FSH and testosterone concentration were found in the Chlorpromazine- and Reserpine-treated groups. Groups H and I showed a highly significant upregulation of the CREM, PRM I and II genes, and a highly significant increase in serum FSH and testosterone concentrations. CONCLUSION: The study concluded that the HPT-Axis was impaired by chlorpromazine and reserpine, while RV and a combination of RAZ administration enhanced the axis in an animal model. The study recommended that synthetic antipsychotic drugs should be taken with Zinc and Ascorbate in order to help prevent reproductive toxicity associated with antipsychotic drugs. We need further studies in humans to confirm these findings.
Assuntos
Antipsicóticos , Rauwolfia , Animais , Ácido Ascórbico , Clorpromazina/toxicidade , Modulador de Elemento de Resposta do AMP Cíclico , Expressão Gênica , Humanos , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Rauwolfia/genética , Reserpina/toxicidade , Testículo , ZincoRESUMO
The occurrence of pharmaceuticals in the aquatic environment has received increasing attention in recent years, as concerns have risen about their environmental persistence, biological activity and different effects toward nontarget organisms. Considering the magnitude of concentrations (ng L(-1) to mg L(-1)) and their often-specific modes of action, the assessment of physiological responses of exposed aquatic biota may provide significant information regarding the potential ecological consequences of exposure to these contaminants. The present study intended to assess the acute and chronic effects of four pharmaceuticals: acetaminophen, chlorpromazine, diclofenac sodium and propranolol in the cladoceran species Daphnia magna. Parameters such as immobility, total of offspring and rate of population increase were analyzed. Results of acute exposures showed a considerable variability of toxicity among pharmaceuticals, with the following ranking of toxicity: diclofenac (EC50 = 123.3 mg L(-1)) < propranolol (EC50 = 5.531 mg L(-1)) < acetaminophen (EC50 = 2.831 mg L(-1)) < chlorpromazine (EC50 = 1.805 mg L(-1)). The chronic toxicity data showed the exertion of reproductive adverse effects. The compounds chlorpromazine and propranolol caused a significant decrease in fecundity, and the rate of population increase parameter suffered a significant decrease from 0.33 mg L(-1) to 0.128 mg L(-1) onwards, respectively. The levels of exposure to which our test organism was acutely and chronically exposed were above those already reported in the wild. Nevertheless, the extensive production, prescription and release of pharmaceuticals drugs will continue to grow in the future, and consequently their loadings to the environment can result in potential long-term ecological risks to aquatic biota.
Assuntos
Daphnia/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Acetaminofen/administração & dosagem , Acetaminofen/toxicidade , Animais , Clorpromazina/administração & dosagem , Clorpromazina/toxicidade , Diclofenaco/administração & dosagem , Diclofenaco/toxicidade , Relação Dose-Resposta a Droga , Feminino , Propranolol/administração & dosagem , Propranolol/toxicidade , Ratos Wistar , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Poluentes Químicos da Água/administração & dosagemRESUMO
Non-bilayer phospholipid arrangements are three-dimensional structures that can form when anionic phospholipids with an intermediate form of the tubular hexagonal phase II (H(II)), such as phosphatidic acid, phosphatidylserine or cardiolipin, are present in a bilayer of lipids. The drugs chlorpromazine and procainamide, which trigger a lupus-like disease in humans, can induce the formation of non-bilayer phospholipid arrangements, and we have previously shown that liposomes with non-bilayer arrangements induced by these drugs cause an autoimmune disease resembling human lupus in mice. Here we show that liposomes with non-bilayer phospholipid arrangements induced by Mn²âº cause a similar disease in mice. We extensively characterize the physical properties and immunological reactivity of liposomes made of the zwitterionic lipid phosphatidylcholine and a H(II)-preferring lipid, in the absence or presence of Mn²âº, chlorpromazine or procainamide. We use an hapten inhibition assay to define the epitope recognized by sera of mice with the disease, and by a monoclonal antibody that binds specifically to non-bilayer phospholipid arrangements, and we report that phosphorylcholine and glycerolphosphorylcholine, which form part of the polar region of phosphatidylcholine, are the only haptens that block the binding of the tested antibodies to non-bilayer arrangements. We propose a model in which the negatively charged H(II)-preferring lipids form an inverted micelle by electrostatic interactions with the positive charge of Mn²âº, chlorpromazine or procainamide; the inverted micelle is inserted into the bilayer of phosphatidylcholine, whose polar regions are exposed and become targets for antibody production. This model may be relevant in the pathogenesis of human lupus.
Assuntos
Lúpus Eritematoso Sistêmico/metabolismo , Lipossomas Unilamelares/metabolismo , Animais , Anticorpos/sangue , Anticorpos/metabolismo , Anticorpos Monoclonais/metabolismo , Cardiolipinas/química , Cardiolipinas/imunologia , Bovinos , Clorpromazina/toxicidade , Glomérulos Renais/patologia , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Manganês/toxicidade , Camundongos , Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular , Ácidos Fosfatídicos/química , Ácidos Fosfatídicos/imunologia , Fosfatidilcolinas/química , Fosfatidilcolinas/imunologia , Fosfatidilserinas/química , Fosfatidilserinas/imunologia , Procainamida/toxicidade , Pele/patologia , Lipossomas Unilamelares/química , Lipossomas Unilamelares/imunologiaRESUMO
This study presents evidence that chlorpromazine (CPZ) affects human cells and cell membrane molecular models. Human SH-SY5Y neuroblastoma cells incubated with 0.1 mM CPZ suffered a decrease of cell viability. On the other hand, phase contrast microscopy observations of human erythrocytes indicated that they underwent a morphological alteration as 1 microM CPZ changed their discoid normal shape to stomatocytes, and to hemolysis with 1 mM CPZ. X-ray diffraction experiments performed on dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) bilayers, classes of the major phospholipids present in the outer and inner sides of the erythrocyte membrane, respectively showed that CPZ disordered the polar head and acyl chain regions of both DMPC and DMPE, where these interactions were stronger with DMPC bilayers. Fluorescence spectroscopy on DMPC LUV at 18 degrees C confirmed these results. In fact, the assays showed that CPZ induced a significant reduction of their generalized polarization (GP) and anisotropy (r) values, indicative of enhanced disorder at the polar head and acyl chain regions of the DMPC lipid bilayer.
Assuntos
Clorpromazina/toxicidade , Membrana Eritrocítica/efeitos dos fármacos , Modelos Biológicos , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Clorpromazina/química , Dimiristoilfosfatidilcolina/química , Relação Dose-Resposta a Droga , Membrana Eritrocítica/química , Glicerofosfolipídeos/química , Humanos , Bicamadas Lipídicas/química , Masculino , Modelos Moleculares , Estrutura Molecular , Neuroblastoma , Espectrometria de Fluorescência , Testes de Toxicidade , Difração de Raios XRESUMO
Undernutrition during critical periods of development may cause changes in the behavioural responses of rats to centrally acting drugs. In the present study, the effects of undernutrition during suckling on the behavioural responses of 21-days-old rats to chlorpromazine (0, 2.5, 5, 10 and 20 mg/kg) or haloperidol (0, 0.125, 0.25, 0.5, 1 or 2 mg/kg) were examined. Locomotion was assessed at 1 hr 30 min., 4 hr 30 min., 7 hr 30 min, and 10 hr 30 min., and catalepsy was scored at 3 hr, 6 hr and 9 hr after drug administration. Drug was injected on two consecutive days. On day 1, saline-treated undernourished rats showed significantly greater locomotion activity than did normal rats. The neuroleptic-induced inhibition of locomotor activity in undernourished rats was significantly less than that observed in normal rats from 4 hr 30 min. to 10 hr 30 min. (chlorpromazine) or from 7 hr 30 min. to 10 hr 30 min. (haloperidol). On day 2, a similar trend was observed but only in rats injected with 5 mg/kg chlorpromazine or 0.5, 1, and 2 mg/kg haloperidol. On day 1, the catalepsy scores at 3 hr revealed no significant difference between nutritional groups, but at 6 hr undernourished rats responded significantly less to chlorpromazine or haloperidol. On day 2, undernourished rats were less responsive to neuroleptics than normal rats, but the effect was not so evident as observed on day 1. The present results suggest that the behavioural effects of chlorpromazine and haloperidol are less persistent in undernourished rats, possibly due to differences in drug distribution and elimination, when compared to well-nourished rats.
Assuntos
Catalepsia/fisiopatologia , Clorpromazina/toxicidade , Antagonistas de Dopamina/toxicidade , Haloperidol/toxicidade , Locomoção/efeitos dos fármacos , Distúrbios Nutricionais/fisiopatologia , Análise de Variância , Animais , Animais Lactentes , Catalepsia/induzido quimicamente , Clorpromazina/administração & dosagem , Antagonistas de Dopamina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Haloperidol/administração & dosagem , Injeções Subcutâneas , Masculino , Ratos , Ratos Wistar , DesmameRESUMO
Trifluoperazine (TFP) and chlorpromazine (CPZ), two pharmacologically active phenotiazine derivatives, were evaluated for their inhibitory activity on the replication of the arenaviruses Junin (JV), the etiological agent of Argentine hemorrhagic fever, Tacaribe virus and Pichinde virus. Both compounds achieved a concentration-dependent inhibition of viral multiplication at concentrations not affecting cell viability. The 50% inhibitory concentration (IC50) values determined by a virus yield inhibition assay for several strains of JV, including a human pathogenic strain, were in the range of 7.7-23.0 microM and the 90% inhibitory concentration (IC90) fluctuated between 16.6 and 35.2 microM. From time of addition and removal experiments, it can be concluded that CPZ inhibited an early stage in the replicative cycle of JV, probably viral entry. TFP also affected JV penetration when present soon after virus adsorption, and also interfered with a later step of viral maturation when added after 7 h of infection. The expression of viral antigens in the cytoplasm of infected cells was highly reduced in the presence of the compounds, as revealed by immunofluorescence staining, whereas no JV proteins were detected at the cell membrane. The distribution pattern of viral proteins was altered in the few cells exhibiting positive fluorescence after treatment with the phenotiazines. The TFP-induced inhibitory effect on JV multiplication was significantly reversed in the presence of 5 microM calmodulin. These data indicate that TFP and CPZ inhibit JV replication in vitro. Our findings suggest that the integrity of the actin microfilaments may be required for optimal arenavirus multiplication.