Theodore G. Tong

Phenytoin-Induced Methadone Withdrawal

Methadone-maintained volunteers experienced moderately severe opiate withdrawal symptoms within 3 or 4 days of beginning phenytoin in therapeutic doses. The area under the methadone plasma concentration-time curve decreased while the ratio of the pyrrolidine-to-metabolite excretion in urine to this area increased significantly. This suggests that phenytoin accelerates methadone metabolism. Methadone dosing adjustments should be anticipated when phenytoin is initiated or discontinued in methadone-maintained patients.

Experimental chelation therapy in chromium, lead, and boron intoxication with N-acetylcysteine and other compounds.

The usefulness of N-acetylcysteine (NAC) as a chelating agent was studied for the toxin potassium dichromate, lead tetraacetate, and boric acid. Mature Sprague-Dawley rats were intoxicated with these substances and placed in metabolic cages. Urinary excretion rates of intoxicant and total urine volume were determined during treatment with N-acetylcysteine, calcium EDTA, and/or dimercaptosuccinic acid, N-acetylcysteine proved to be the most effective agent at increasing the excretion of chromium and boron and was also able to reverse the oliguria associated with these toxins. Dimercaptosuccinic acid was most effective at the chelation of lead. NAC did not increase the excretion of lead. We conclude that NAC may be useful in intoxications due to chromate and borate and is effective at reversing the oliguria associated with these intoxicants.

Presystemic metabolism of meperidine to normeperidine in normal and cirrhotic subjects

Plasma concentrations and urinary excretion of meperidine and its metabolite normeperidine were determined after intravenous and oral administration to 11 men; five men had hepatic cirrohosis and six were normal. Systemic clearance of meperidine was smaller and bioavailability and half‐life greater in the cirrhotic patients than in the normal subjects. Plasma concentrations and 24‐hr urinary excretion of normeperidine was lower and persistence of normeperidine in plasma longer in the patients with cirrhosis. The route of administration did not alter the fraction of normeperidine generated from meperidine. The results suggest that in patients requiring repeated meperidine dosage the drug should be taken parenterally rather than orally to allow maximal analgesia and minimal formation of normeperidine. Patients with cirrhosis may be relatively protected from normeperidine toxicity because of impaired formation, but the risk of cumulative toxicity may be greater than in normal subjects because of slower elimination of the metabolite and greater sensitivity to the effects of narcotics on the central nervous system.

Methadone—Disulfiram Interaction During Methadone Maintenance

In an attempt to characterize a possible drug interaction between methadone and disulfiram, 500 mg/day insulfiram was administered orally for seven days to seven subjects on methadone maintenance. Plasma methadone concentrations and urinary excretion of methadone and its pyrrolidine and pyrrolidone metabolites were measured and subjective symptoms of opiate intoxication and abstinence were noted before, during, and after disulfiram administration. Mean trough plasma methadone concentrations and terminal half-lives were lowest and shortest during disulfiram treatment, although this finding was not statistically significant. The ratio of urinary methadone to its pyrrolidine metabolite decreased during disulfiram treatment in all subjects. There is no evidence to support our original hypothesis that disulfiram might inhibit methadone metabolism. In contrast, urinary excretion of the major pyrrolidine metabolite increased relative to excretion of methadone. This suggests enhanced N-demethylation during disulfiram treatment. Disulfiram had no effect on opiate intoxication or abstinence symptoms. Disulfiram may alter methadone disposition, but in this study it was shown that in doses used for management of alcoholism there was no significant interaction between disulfiram and methadone.

Lack of effect of diazepam on methadone metabolism in methadone‐maintained addicts

Four methadone‐maintained subjects were given diazepam (0.3 mg/kg) for 9 days. During the dual drug period, the effects and kinetics of methadone and of its major pyrrolidine metabolite were not altered. These findings indicate that, unlike its effects in rodents, diazepam does not inhibit the metabolism of methadone in man.

Anticholinergic Poisonings Associated with Commercial Burdock Root Tea

AbstractA case of anticholinergic poisoning associated with the consumption of a commerical burdock root tea preparation and confirmed by laboratory analysis in Arizona is reported.A second case of burdock root tea poisoning, confirmed by laboratory determination, has been described. The patient experienced mild anticholinergic symptoms which were caused by an atropine contaminant in the commercial preparation. The estimated dose of atropine involved in this case is 2.28 mg; the usual adult oral dose for antispasmodic activity is 0.3 to 1.2 mg.5 The importance of this finding is evident in the differential diagnosis of any anticholinergic poisoning. Common sources of such toxic symptoms from acute poisoning include phenothiazines, tricyclic antidepressants, and antihistamines. We have been unable to unequivocally ascertain whether the source of atropine in this preparation was the result of contamination from root or vegetable material of some other plant. This discovery of atropine in a commercially avai...

Chest pain and hypoxemia from inhalation of a trichloroethane aerosol product

A 25-year-old man developed severe shortness of breath, constricting chest pressure, chest pain, cough and myalgia following acute exposure to a waterproofing aerosol that contained trichloroethane. He became febrile and developed a small area of atetectasis with significant hypoxemia. Recovery was complete within 36 hours. This experience suggests that casual use of a trichloroethane aerosol with a surface active agent can cause acute pulmonary toxicity. The mechanism of this injury is unknown.

Massive Intoxication with Acetaminophen and Propoxyphene: Unexpected Survival and Unusual Pharmacokinetics of Acetaminophen

A 28-year-old woman ingested an estimated 58 g acetaminophen and 9 g propoxyphene 20 h before hospitalization. Her serum acetaminophen concentration at 22 h was 485 micrograms/mL and declined with an unusually long half-life of 14 h. Hemodialysis for 4 h (started at 36 h) reduced the acetaminophen concentration from 250 to 32 micrograms/mL. The patients complete recovery was remarkable because of the large amounts of drugs ingested, the delayed treatment, and prior exposure to enzyme inducers (known to increase acetaminophen hepatotoxicity). Administration of N-acetylcysteine prevented inorganic sulfate depletion usually caused by acetaminophen and may have increased the formation of acetaminophen sulfate. Some patients eliminate large overdoses of acetaminophen very slowly. Measures to enhance the elimination of this drug and its toxic metabolite by these individuals may be useful even when diagnosis or hospitalization is delayed.

Diazepam kinetics in acute alcohol withdrawal

We performed a within‐subject comparison of the kinetics of diazepam given to 7 alcoholic subjects during acute alcohol withdrawal and again after detoxification. The initial rapid exponential decline of plasma diazepam concentrations (t½α) was more rapid during (0.21 ± 0.03 hr) than after withdrawal (0.44 ± 0.14 hr, p < 0.05). Terminal t½, clearance, and volumes of distribution changed in individual patients, but mean values did not change. Protein binding was less in patients (93.4 ± 2.4%) than in healthy controls (97.0 ± 1.0, p < 0.05). The effects of alcohol withdrawal on diazepam disposition do not explain the high doses of diazepam commonly required to treat the withdrawal.

The Production Model as a Basis for Conducting Economic Evaluations of Regional Poison Control Centers

To identify the significant inputs, activities, and outputs of a regional poison control center, a production model is described and its potential application to the conduct of economic evaluations delineated. The model can help the researcher identify the significant inputs (costs) incurred through the provision of poison control center services. These inputs directly influence the activities that the poison center is capable of undertaking. Activities undertaken by a poison center are intermediate steps between the inputs and outputs, and serve to convert the various inputs into associated outputs. They form the basis for determining the outputs produced by the poison center services. The outputs derived from poison center services provide the conceptual framework for assessing the effectiveness of a poison center in an economic analysis. Also described are potential applications of the production model in conducting poison center cost-effectiveness and cost-benefit analyses.