The widespread use of phenytoin results in frequent accidental and intentional toxicity. Metabolism is enzymatic and can be described by Michaelis-Menten kinetics. This results in an increased half-life in overdose situations and a protracted clinical course which may last a week or more. The primary toxicity is on the central nervous system. The most common initial finding in mild toxicity is nystagmus. As concentrations increase ataxia, decreased coordination, hyper-reflexia, slurred speech and diplopia may develop. Progressive increases result in confusion, lethargy and coma. Various methods tried to increase elimination including dialysis, haemoperfusion, diuresis and plasmaphoresis have been ineffective and are not without risk. Meticulous supportive care including ventilation if necessary should provide a good clinical outcome. Multiple-dose activated charcoal may be helpful in shortening the duration of symptoms.
Presented is a case report of an 80-year-old man with dyspnoea and jaundice who died from autoimmune haemolytic anaemia (AIHA) within 12 hours of arrival at the emergency department. The patient had been taking tolmetin for osteoarthritis. On autopsy he was found to have a superficial gastric adenocarcinoma. A brief presentation on AIHA includes primary (idiopathic) and secondary types. Factors associated with AIHA include nonsteroidal anti-inflammatory drugs (NSAIDs) and gastric carcinoma, although a direct cause cannot be demonstrated. After a discussion of the autoimmune mechanism of drug-associated hemolysis of which methyldopa is the prototype, a review of NSAIDs associated with AIHA is presented. All (18) NSAID cases of immune haemolysis were reviewed to determine which were more likely due to an autoimmune mechanism. These included 3 cases with tolmetin use: one probable and one possibly having an autoimmune basis for haemolysis, while with the third case immune haemolysis was by the drug adsorption mechanism. A review of gastric carcinoma associated with AIHA reveals only 2 previously reported cases. The associations of tolmetin use, as well as gastric carcinoma with AIHA, both rare, are noteworthy but cannot be proven as causative factors with our current level of knowledge and technology.
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