Phenobarbital poisoning with

Death from overdose of barbiturates may occur and is more likely when more than 10 times the hypnotic dose is ingested. The barbiturates with high lipid solubility and short half-lives are the most toxic. Thus the lethal dose of phenobarbital is 6—10 g, whereas that of secobarbital, pentobarbital, or amo-barbital is 2-3 g. Symptoms of barbiturate poisoning include CNS depression, coma, depressed reflex activity, a positive Babinski reflex, contracted pupils (with hypoxia there may be paralytic dilation), altered respiration, hypothermia, depressed cardiac function, hypotension, shock, pulmonary complications, and renal failure. 

In mammals, phenobarbital and phenytoin increase serum ceruloplasmin concentrations (Aaseth and Norseth 1986). Chronic copper poisoning in sheep is exacerbated when diets contain heliotrope plants (Heliotropium sp., Echium spp., Senecio sp.). Aggravated effects of the heliotrope plants include reduced survival and a twofold to threefold increase in liver and kidney copper concentrations when compared to control animals fed copper without heliotropes (Howell et al. 1991). Rats given acutely toxic doses of 2,3,7,8-tetrachlorodibenzo-para-dioxin had elevated concentrations of copper in liver and kidney because of impaired biliary excretion of copper (Elsenhans et al. 1991). Morphine increases copper concentrations in the central nervous system of rats, and dithiocarbam-ates inhibit biliary excretion (Aaseth and Norseth 1986). In human patients, urinary excretion of copper is increased after treatment with D-penicillamine, calcium disodium EDTA, or calcium trisodium diethylenetriamine penta acetic acid (Flora 1991). 

Urine alkalinization is a treatment modality that increases elimination of poisons by the intravenous administration of sodium bicarbonate to produce urine with a pH of more than or equal to 7.5 and must be supported by high urine flow. This technique might be useful for the elimination of drugs with an acid pKa such as salicylates (but not recommended for phenobarbital intoxication for which multiple-dose activated charcoal is better), chlorpropamide, 2,4-dichlorophenoyacetic acid, diflunisal, fluoride, mecoprop, methotrexate. Complications include severe alkalemia, hypokalemia, hypocalcemia and coronary vasoconstriction. 

Changes in plasma pH may also affect the distribution of toxic compounds by altering the proportion of the substance in the nonionized form, which will cause movement of the compound into or out of tissues. This may be of particular importance in the treatment of salicylate poisoning (see chap. 7) and barbiturate poisoning, for instance. Thus, the distribution of phenobarbital, a weak acid (pKa 7.2), shifts between the brain and other tissues and the plasma, with changes in plasma pH (Fig. 3.22). Consequently, the depth of anesthesia varies depending on the amount of phenobarbital in the brain. Alkalosis, which increases plasma pH, causes plasma phenobarbital to become more ionized, alters the equilibrium between plasma and brain, and causes phenobarbital to diffuse back into the plasma (Fig. 3.22). Acidosis will cause the opposite shift in distribution. Administration of bicarbonate is therefore used to treat overdoses of phenobarbital. This treatment will also cause alkaline diuresis and therefore facilitate excretion of phenobarbital into the urine (see below). 

Nonionized lipid-soluble drugs are resorbed and not eliminated. Generally, drugs that are bases are excreted when the urine is acidic, whereas acidic compounds are excreted in greater quantities if the urine is alkaline. For example, in phenobarbital (weak acid pKa of 7.3) poisoning, alkalinization of the urine with sodium bicarbonate is helpful in eliminating the phenobarbital. In amphetamine toxicity, acidification of the urine with ammonium chloride is required (Figure 1.13). 

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... 

Administration of 2-PAM chloride (protopam and pralidoxime) is generally not recommended in carbamate poisoning since it has been shown to interfere with the efficacy of atropine. It was reported that the condition of patients suffering carbaryl-related poisoning deteriorated rapidly following the administration of 2-PAM. Seizure control with diazepam, phenobarbital, or phenytoin may be required. Cardiovascular support and intensive supportive care may be required in serious cases. 

Clinical management is generally symptomatic. Convulsions are usually controlled using diazepam, pentobarbital, or phenobarbital. In some instances, treatment with activated charcoal is effective in increasing the excretion of the pesticide. Cholestyramine has been proven effective in chlordecone poisoning. In severe cases, mechanical maintenance of cardiac function and respiration is necessary. 

Conventional anticonvulsants (e.g., diazepam, phenobarbital, and phenytoin) may be administered to treat pyriminil-induced seizures. Niacinamide has been demonstrated to be an effective antidote in pyriminil poisoning in rats but little information is available regarding its antidotal efficacy in humans. Insulin therapy could be instituted as a preventive measure for possible diabetes mellitus. Orthostatic hypotension due to pyriminil exposure may be treated with conventional mineralocorticoids. 

Drug overdose In a study of 9809 consecutive adults and adolescents with self-poisoning during a 6-month period, there were 474 with non-benzodiazepine antiepileptic drug intoxication [103. The most frequent motivation was intentional intoxication (95.3%). There was no association between antiepileptic drug intoxication and a history of parasuidde, sex, age, or occupation. The most frequent drug involved was carbamazepine ( = 117), followed by phenobarbital ( =77) and sodium valproate ( = 51). 

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