Trypanosoma cruzi: effect of phenothiazines on the parasite and its interaction with host cells

Phenothiazines were observed to have a direct effect on Trypanosoma cruzi and on its in vitro interaction with host cells. They caused lysis of trypomastigotes (50 uM/24 h) and,to a lesser extent, epimastigote proliferation. Treatment of infected peritoneal macrophages with 12.5 uM chlorpromazine or triflupromazine inhibited the infection; this effect was found to be partially reversible if the drugs were removed after 24 h of treatment. At 60 uM, the drugs caused damage to amastigotes interiorized in heart muscle cells. However, the narrow margin of toxity between anti-trypanossomal activity and damage to host cells mitigates against in vivo investigation at the present time. Possible hypothesis for the mechanism of action of phenothiazines are discussed

Suppressive effects of histamine skin reactivity by a nonsedating antihistamine-mequitazine.

The suppressive activity of mequitazine (MQZ) on histamine skin reactivity was evaluated in 29 healthy subjects (age 22-25 years) in a single-blind study. Fifteen subjects received MQZ, at a dosage of 5 mg BID, for 7 days while 14 served as controls. A prick skin test with saline or histamine hydrochloride (1 mg/ml and 10 mg/ml) was performed in duplicate, on both forearms, starting from the baseline day and continuing for 4 days after medication had been discontinued (total of 11 days). The skin-test subject and the reader was unaware of the randomization process. Mean diameters of wheal and flare as well as the skin index scores (after Voorhost) were used in the analysis. Maximal flare suppression (as compared to the baseline values) was observed on day 6 (97% suppression for 1 mg/ml and 54% suppression for 10 mg/ml, p less than 0.01). Suppression of wheal size was significant (19% for 1 mg/ml and 28% for 10 mg/ml) but was not clinically relevant. Suppression of skin index scores was maximal on day 6 (71% for 1 mg/ml and 43% for 10 mg/ml, p less than 0.01). After MQZ had been discontinued, all measurements gradually returned to baseline values and were not different therefrom within 3 days. However, final measurements of wheal and flare were smaller than baseline values (60-94% of baselines). We conclude that MQZ, at the manufacturers's recommended dose of 5 mg BID, significantly suppressed flare size of histamine skin tests and recommend that MQZ be discontinued for at least 3 days prior to performing allergy skin tests.

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