Diazepam poisoning

Metabolic Effects. Severe metabolic acidosis with high anion gap and hyperglycemia was reported in humans after acute poisoning with endosulfan (Blanco-Coronado et al. 1992 Lo et al. 1995). In five of the six cases reported by Blanco-Coronado et al. (1992), the metabolic acidosis was corrected with gastric lavage with activated charcoal and intravenous sodium bicarbonate and diazepam. No further information regarding metabolic effects in humans after exposure to endosulfan was located. 

A principle of the therapy for acute poisonings with OPC lies in the complex performance of cholinolytics (atropine, scopolamine, aprofene, amisile etc.) with reversible ChE inhibitors (pyridostigmine, proserine etc.) or cholinolytics with tranquillizers (diazepam, fenozepame etc)... 

There is no specific treatment for ingestion of ibotenic acid or muscimol rather, treatment is symptomatic and supportive. Anxiety, hysteria, or convulsions can be treated with sedatives, such as diazepam. This should be done cautiously, however, and with the lowest effective dose because animal studies revealed that respiratory arrest may occur. In severe cases, with prolonged nausea, vomiting, or diarrhea, monitoring of fluid and electrolyte status may be required. Recent cases of muscarine poisonings were reported by Benjamin (1992), and Tupalska-Wilczynska et al. (1997). 

Management of methanol and ethylene glycol poisoning is similar. Symptomatic support of respiration and circulation is augmented by correction of metabolic acidosis with intravenous bicarbonate infusion, and control of seizures with diazepam. Ethanol inhibits the metabolism of methanol and ethylene glycol to the toxic metabolites, and can give time for further treatment. The goal is to maintain blood ethanol concentrations between 100 and 150 mg per decilitre, sufficient to saturate alcohol... 

The benzodiazepines such as diazepam, oxazepam, and temazepam are common causes of acute poisoning, but rarely cause serious toxicity by themselves, even in enormous doses. They can potentiate central nervous system depression from other drugs, including alcohol. 

Treatment of acute nicotine poisoning is largely symptom-directed. Muscarinic excess resulting from parasympathetic ganglion stimulation can be controlled with atropine. Central stimulation is usually treated with parenteral anticonvulsants such as diazepam. Neuromuscular blockade is not responsive to pharmacologic treatment and may require mechanical respiration. 

Abbara et al. performed simultaneous quantification of different antidotes (diazepam, pralidoxime and atropine) typically co-administered for the therapy of anticholinesterase poisoning (Table 5) [44], PK data resulting from i.m. drug injection by means of a bi-compartemental auto-injector were calculated from human plasma concentrations measured by LC-ESIMS/MS with MRM settings. Administration of 2 mg atropine sulphate yielded plasma peak concentrations of about 4 ng/ml 15 min after injection. 

J. Lopez-Herce, et al., Alcohol poisoning following diazepam intravenous infusion. Ann Pharmacol. Ther. 29 632, 1995. 

Hydroxybenzoate preservatives inactivate atropine sulfate in physical mixtures. Atropine can be used for treating acetylcholine poisoning. Organophosphorous pesticides are treated by use of diazepam, phenothiazines, and physostigmine.149... 

Treatment of strychnine poisoning involves an oral administration of an activated charcoal which absorbs any unabsorbed poison within the digestive tract. Unabsorbed strychnine can be removed from the stomach by gastric lavage with tannic acid (strong tea) or potassium permanganate solutions to oxidize strychnine. Seizures are controlled by anticonvulsants, such as phenobarbital or diazepam, along... 

Sket, D., Brzin, M., Vreca, I. (1989). Effect of HI-6 and diazepam on the increase of creatine kinase isoenzymes activity in plasma of atropinized, soman-poisoned rats. Acta Pharm, Jugoslav. 39 151-9. 

Standard therapy of OP poisoning consists of the administration of a combination of atropine, oxime, and diazepam with other supportive measures when necessary. However, the possibility of addition of purified enzymes such as AChE, ChE, CarbE, and A-esterases to this therapeutic scheme has been considered and preliminary experiments in animals have shown much better protective effect after addition of exogenous enzymes. In this respect, protective effects of AChE, ChE, and CarbE are based on formation of covalent conjugates or phosphory-lated enzymes in the stoichiometric ratio 1 1. Capacity for binding of these enzymes is limited by the number of active sites on the enzyme to which OP molecules can be bound. This means that more enzymes have to be administered in order to achieve better detoxification of OPs which may not always be possible due to adverse effects. This can also be infiuenced by differences in the extent of spontaneous reactivation of these enzymes inhibited by OP. 

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