The fetal safety of cetirizine: an observational cohort study and meta-analysis.

Cetirizine, a second-generation antihistamine, is an active metabolite of hydroxyzine used in the treatment of allergies, but the data on fetal safety are inconclusive. Pregnant women who were counselled by the 'Motherisk Program' regarding cetirizine exposure were enrolled in a cohort study and compared with pregnant women counselled for non-teratogenic exposures. The objective was to measure the rate of adverse pregnancy outcomes. Subsequently, we also conducted a meta-analysis of cohort studies that examined the pregnancy outcomes of women exposed to hydroxyzine or cetirizine during pregnancy. In the cohort study, there were no significant differences in the rates of major malformations between the cetirizine exposed and comparison group. In the meta-analysis, cetirizine was not associated with increased teratogenic risk. In contrast, a meta-analysis of cetirizine and hydroxyzine studies showed a marginal association with major malformations. Cetirizine is not associated with a clinically important increase in risk of adverse fetal outcomes.

Opposite effects of GABAA and NMDA receptor antagonists on ethanol-induced behavioral sleep in rats.

The effects of the GABAA receptor antagonists, pentylenetetrazol, bicuculline, and picrotoxin, the glycine antagonist, strychnine, and the NMDA receptor antagonist, memantine, on ethanol-induced behavioral sleep and body temperature were investigated. Pentylenetetrazol, bicuculline, and picrotoxin given prior and following ethanol reduced the behavioral sleep and potentiated the hypothermia caused by ethanol. However, convulsions appeared when bicuculline, but not pentylenetetrazol and picrotoxin, were given following ethanol. After the reversal of unconsciousness in rats without convulsions the animals remained awake throughout the experiments without motor incoordination, hyperexcitability, and sedation, but they were in hypothermia within 12 h. The glycine antagonist, strychnine, given prior or after ethanol had virtually no effect on ethanol-induced behavioral sleep and hypothermia. Ethanol given prior or following strychnine failed to antagonize strychnine-induced convulsions. The NMDA receptor antagonist, memantine, given following ethanol potentiated the behavioral sleep and had virtually no effect on hypothermia induced by ethanol. It is suggested that the ethanol-induced behavioral sleep may be attributed to its ability to enhance the GABAergic mechanisms and to inhibit NMDA-mediated excitatory responses. However, the ethanol-induced hypothermia may be ascribed solely to the facilitation of GABAergic transmission. Further, it is postulated that a bidirectional inhibitory system subserves the regulation of behavioral sleep and convulsions. However, one-way inhibitory system underlies the ethanol-induced hypothermia.