Acute toxicity of pyrazolones

Abstract

Pyrazolone intoxication accounts for most (52 percent) mild analgesic poisonings in West Germany. Severe and fatal intoxication with pyrazolones is, however, rare. In the German literature, only 50 cases have been described in the past 62 years; 80 to 90 percent of these were caused by aminopyrine, which was withdrawn from the West German market in 1978 and replaced by propyphenazone. Up to now, no fatal poisoning with propyphenazone has been reported. However, the signs and symptoms of severe intoxication are similar for both propyphenazone and aminopyrine. The acute toxicity of dipyrone is slightly lower than that of propyphenazone, whereas phenylbutazone and oxyphenbutazone clearly cause less severe reactions. Characteristic symptoms include impaired consciousness progressing to coma, and convulsions. In addition, arrythmia and cardiogenic shock may occur. Severe aminopyrine intoxication may also be complicated by sudden apnea. Liver damage may develop after a latent period of about 24 hours, especially after phenylbutazone and oxyphenbutazone poisoning. Therapy involves supportive measures as well as gastric emptying by emesis or lavage, installation of medical charcoal, and induction of diarrhea or gut lavage. Although exact clinicotoxicologic data on hemoperfusion are not available as yet, distribution volumes, plasma half-lives, and endogenous plasma clearances as well as results of in vitro trials all suggest the efficacy of this procedure. Hemoperfusion with uncoated amberlite XAD-4 resin is, therefore, recommended for patients with severe pyrazolone intoxication.