Utility of acetylcysteine in treating poisonings and adverse drug reactions.

As recognition of the role of free radicals and reactive toxins in the pathogenesis of disease, poisoning, and adverse drug reactions has evolved, interest in the use of acetylcysteine as a modulator of these effects has steadily increased in recent years. Acetylcysteine is commonly thought to serve as a glutathione precursor and consequently can increase or sustain intracellular glutathione which scavenges reactive oxygen species caused by toxins or subsequent tissue injury. At least 10 additional mechanisms of action for acetylcysteine have been demonstrated in various laboratory models, but a unifying framework of its actions is still to be proposed. This paper reviews the current experimental and therapeutic status of acetylcysteine for the treatment of poisonings and adverse drug reactions. Of the 45 potential uses of acetylcysteine that were identified for the treatment of poisonings or adverse drug reactions, 14 of the toxic effects have little support for its use while promising results have been demonstrated for 27 toxicities. Currently, treatment of acute paracetamol (acetaminophen) poisoning is the only widely accepted clinical indication for acetylcysteine as a treatment for poisoning or adverse drug reactions. In many clinical situations acetylcysteine is used empirically utilising modifications of dosage regimens employed for paracetamol poisoning. Often it is difficult to determine the benefit of therapy with acetylcysteine owing to the nature of the toxicity being treated, the use of other therapies, the presence of comorbid conditions, and the small number of patients studied. The diverse and positive nature of the investigations suggest that there is considerable promise in acetylcysteine as a research tool and pharmacological agent.

Problems in assessment of acute melatonin overdose.

Melatonin is sold in the United States as a dietary supplement and is promoted primarily as an aid for insomnia, stress, jet lag, and aging. Cases of acute poisoning have not been reported, partially because of problems in assessment of toxicity. We report the case of a 66-year-old man who became lethargic and disoriented after taking 24 mg melatonin to aid relaxation and sleep the evening before prostate surgery. He recovered uneventfully, and after the scheduled surgery he resumed his regular practice of taking 6 mg melatonin with prescription sedative drugs. Although melatonin is not regulated as a drug, it may interact with benzodiazepines, be antagonized by naloxone and flumazenil, and interact with melatonin receptors in the central nervous system and elsewhere in the body. Melatonin appears to be pharmacologically active and should not be considered a benign agent on overdose.