It should be recognised, however, that absorption by the intramuscular route is poor. Diazepam should be given intravenously to patients treated in hospital for OP poisoning, although the intramuscular route is used to administer diazepam outside hospital, such as on the battlefield, when an auto-injector is employed. Although diazepam has a large therapeutic index, there appears to be no place for its routine use in OP poisoning. In severe poisoning, diazepam administration should be considered even before these complications develop. Based on this evidence and pharmacodynamic studies in experimental animals, diazepam should be given to patients poisoned with OPs whenever convulsions or pronounced muscle fasciculation are present. There are numerous case reports of the use of diazepam, generally as an adjunct to other more specific OP antidotes such as atropine and/or pyridinium oximes. In animals experimentally poisoned with OPs, combined treatment with atropine and diazepam significantly lowered lethality compared with atropine treatment alone, indicating a clear beneficial effect. In fact, in one study of large animals, diazepam, given alone, increased lethality. There are no data, either experimental or clinical, demonstrating any clear effect of diazepam alone on lethality in OP poisoning. In addition, case reports suggest that diazepam will also ameliorate muscle fasciculation, a subjectively unpleasant feature of OP pesticide poisoning. Consequently, the use of diazepam is an important part of the treatment regimen of severe OP poisoning as it prevents, or at least reduces the duration of, convulsions. Antihistamines in cough and cold remedies. Selective serotonin reuptake inhibitors (SSRIs) for depression. Animal studies have demonstrated that diazepam prevents and treats convulsions produced by OPs and may prevent the late effects caused by damage to the central nervous system induced by such convulsions. Monoamine oxidase inhibitors (MAOIs) for depression. Although in most series of OP intoxications, convulsions have been relatively uncommon, it is probable that convulsions produce long-term sequelae in the central nervous system by causing structural damage. Although the main site of action of diazepam, as with other benzodiazepines, is at the gamma-aminobutyric acid A (GABAA) receptor, the degree to which the beneficial actions of diazepam in organophosphorus (OP) ester pesticide poisoning are mediated through the GABAA receptor has been a matter of controversy.
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