Photo-oxidative damage to isolated rat liver mitochondria induced by phenothiazines

Photosensitization is a well-known side-effect of phenothiazines that could involve photochemically promoted oxidative damage to mitochondria, leading to the impairment of metabolic functions and apoptosis. In this work, for the first time, we investigated the effects of photoexcited thioridazine (TR), trifluoperazine (TFP) and fluphenazine (FP) on isolated rat liver mitochondria. Under UV irradiation, the presence of these phenothiazines led to a dose-dependent lack of the respiratory control ratio. These effects were not accompanied by significant swelling and oxidation of protein thiol groups but were accompanied by lipid peroxidation. Lycopene and sorbate, well-known quenchers of singlet oxygen and triplet species, respectively, were ineffective at protecting mitochondrial lipids against the damage promoted by the excited phenothiazines, suggesting that photochemically-produced cation radicals were the pro-oxidant species. Corroborating this proposal, butylated hydroxytoluene (BHT) completely inhibited the lipid peroxidation induced by UV irradiation in the presence of phenothiazines. These novel results make a significant contribution to the understanding of the photochemical properties of phenothiazines in biological systems

Electroconvulsive therapy and intraocular pressure

Psychiatric patients receiving phenothiazine, tricyclic antidepressant and antiparkinsonian drugs for prolonged periods, occasionally develop mydriasis and angle closure glaucoma. Suxamethonium, usually given to modify the convulsion of electroconvulsive therapy [ECT] increases intraocular pressure [IOP] by about 7-8 mmHg, the increase being maximal and having returned to baseline 2 min and 6 mins after injection, respectively. We studied the effects on IOP of an electrically induced convulsion following induction of anesthesia using methohexitone 1 mg. kg [-1] and suxamethonium 0.5 mg. kg [-1] in 21 consecutive cooperative psychiatric patients, all receiving antipsychotropic drugs. IOP was recorded sequentially from before induction of anesthesia to after resumption of spontaneous respiration. Their mean IOP was 15.3 [SD 3.7] mmHg prior to induction of anesthesia, 13.5 [SD 3.5] mmHg after loss of eyelash reflex following injection of methohexitone, 16.1 [SD 2.4] mmHg after cessation of muscle fasciculations induced by suxamethonium, 19.2 [SD 5.6] mmHg after cessation of convulsion and 15.5 [SD 4.4] mmHg following resumption of regular spontaneous respiration. The successive stepwise changes in the mean IOP were all statistically significant [p < 0.001 each change compared with the preceding pressure; paired 't' tests]. These data reveal that the reduction in IOP produced by methohexitone is reversed by the increase in IOP produced by suxamethonium. Collated with the time course of the effects of barbiturates and suxamethomium on IOP, the increase in IOP observed following the induced convulsion was not greater than that expected after suxamethonium alone, suggesting that the induced convulsion during ECT does not pose an ocular hazard to psychiatric patients receiving medications which have iatrogenic glaucomatous potential

Catarata estelar em pacientes näo usuários de fenotiazínicos / Stellar cataract in patients not using phenothiazines

Os autores apresentam um estudo sobre a presença de catarata estelar em um grupo de pacientes ambulatoriais com uma história negativa para o uso de derivados fenotizínicos. Com o encontro de 7 casos em 100, analisam esta frequência em sua distribuiçäo por sexos e faixas etárias, além de compará-la com dados da literatura, concluindo serem os achados concordantes com esta. Comparam ainda tais achados com os de trabalhos nos quais a casuística consistia de pacientes que usavam fenotiazínicos, concluindo que a presença da catarata estelar pode ser considerada altamente sugestiva do uso destas drogas, porém näo patognomônica

Intoxicaciones causadas por neurolépticos y otros fármacos afines / Intoxication caused by neuroleptics and similar drugs

Los neurolépticos (fenotiacinas) y otros medicamentos afines como el haloperidol y la metoclopramida, son causa frecuente de intoxicaciones cuyas principales manifestaciones son síntomas extrapiramidales. En su mayoría las intoxicaciones son de evolución aguda y en casos de grandes sobredosificaciones pueden complicarse con choque, coma y fibrilación ventricular; un signo de mal pronóstico es la hipertermia persistente. Su uso crónico, aún a dosis terapéuticas puede ocasionar discinecias tardías de difícil manejo. Se destaca la utilidad de la difenhidramina para el tratamiento de la intoxicación aguda, administrada inicialmente por vía endovenosa lenta (1 mg/kg/dosis), para una vez remitidos los síntomas, continuar por la vía bucal por un mínimo de 72 horas. La prevención debe dirigirse al uso racional de estos medicamentos y a evitar su uso inadecuado, frecuentemente abuso, derivados de modas terapéuticas

El Piracetam en el Sindrome de abstinencia alcohólica / Piracetam in the Alcoholic withdrawal syndrome

Se efectuó un estudio abierto para apreciar la eficacia del piracetam en el síndorme agudo de la abstinencia alcohólica. Se estudiaron 30 pacientes varones con una edad promedio de 40 años y una crisis reciente de ingestión alcohólica de 17 días en promedio. La mayor parte eran consumidores de bebidas destiladas. 20 de estos pacientes tenían hospitalizaciones previas por alcoholismo; el registro de su respuesta a tratamientos anteriores pudo entonces servir de comparación para evaluar los resultados del tratamiento actual. 18 pacientes tuvieron alucinaciones y 2 desarrollaron un cuadro moderado de delirium tremens. La ansiedad y la agitación, así como los síntomas depresivos, fueron comunes. Durante 5 días, se administraron 9 gramos diarios de piracetam por vía endovenosa, fraccionados en tres dosis, y se evaluaron los signos y síntomas de los sujetos diariamente según una escala de 23 ítems clínicos. Dos pacientes abandonaron el ensayo antes de su fin. La apreciación general de los resultados fué favorable, destacándose la ausencia de somnolencia o letargia y l mayor vitalidad general en comparación con otros tratamientos. Para el quinto día, sólo 12 pacientes presentaban signos y síntomas ligeros de depresión y/o ansiedad. El piracetam parece superar a los fenotiazínicos y tener algunas ventajas sobre los benzadiazepínicos en el tratamiento de estos pacientes