4-Methylpyrazole may be an alternative to ethanol therapy for ethylene glycol intoxication in man

Abstract

4-Methylpyrazole (4 MP) is a strong inhibitor of alcohol dehydrogenase. Its use in acute ethylene glycol (EG) or methanol intoxication has been suggested in experimental studies about its efficacy and safety. We report three cases of accidental intoxication with ethylene glycol in man treated orally with 20 mg/kg/day of 4 MP. The treatment was maintained until plasma EG concentrations became unmeasurable. The patients were admitted early during the course of the poisoning. Their neurological status was good. A slight metabolic acidosis observed in two cases was easily corrected and did not recur. Renal function remained normal in all cases. No patient underwent hemodialysis. On admission plasma EG concentrations were 24.2 mmol/l, 13 mmol/l and 9.7 mmol/l respectively. Plasma EG half-lives were 14.5, 11.5 and 14.75 hours respectively. Plasma oxalate concentrations and the rate of urine oxalate elimination, determined in two patients, were high on admission but quickly returned to normal. Concerning possible side effects of 4 MP, a skin rash was observed in one patient and a possible eosinophilia in the others. These three cases suggest that 4 MP may decrease the metabolic consequences of EG poisoning in man and may be of therapeutic value when administered early during the course of the intoxication before coma, seizures and organic renal failure have occurred.

The Utility of an Alcohol Oxidase Reaction Test to Expedite the Detection of Toxic Alcohol Exposures

“…1 There may be a prolonged latent period of several to 24 hours during which time the toxic metabolic products are accumulating. 6,19,25 To decrease the resultant morbidity associated with these ingestions, potentially injurious interventions must be initiated before a definitive serum level of a toxic alcohol is reported. In this study we used a currently available test in a novel way to determine whether it might eventually help clinicians to make a rapid analysis, resolve the differential diagnosis, and intervene expeditiously with more specificity than is currently possible in specific toxic alcohol ingestions.…”

“…[9][10][11][12][13][14] The earlier appropriate therapy is initiated for methanol or ethylene glycol ingestions, the better the outcome in preventing the serious consequences of blindness, renal dysfunction, neurotoxicity, acidemia, metabolic acidosis, pancreatitis, and death. [15][16][17] Therapies include altering the toxic alcohol's metabolism with antidotal treatment using ethanol, 8,15,18 fomepizole, 19,20 removal of the alcohols by hemodialysis, 13,18,21,22 supportive care with sodium bicarbonate, 13 and fluid resuscitation, 13 and the administration of adjuvant therapies (thiamine, pyridoxine, and leucovorin 2 ) appropriate to the toxin ingested.…”

Fomepizole in the treatment of acute methanol poisonings: Experience from the Czech mass methanol outbreak 2012-2013

“…5,14 ). Fomepizole (4-methylpyrazole) is another effective antidote with affinity for ADH several thousand times higher than of methanol [15][16][17][18] . There is some evidence for the superiority of fomepizole in the treatment of methanol-poisoning [16][17][18][19][20][21][22] .…”

Synthesis, Antimicrobial and Antioxidant Activities of Sulfone Linked Bis Heterocycles-Pyrazolyl Oxadiazoles and Pyrazolyl Thiadiazole

“…Pyrazoles show a wide variety of pharmacological effects including anti-inflammatory, 1) antiobesity 2) alcohol dehydrogenase inhibitory 3) and phosphodiesterase inhibitory 4) activities. Some bis pyrazoline derivatives are also found with antimicrobial activity.…”

“…[33][34][35] One of the popular methods for the synthesis of 1,3,4-oxadiazoles involves cyclization of diacylhydrazines prepared by the reaction of acyl chlorides and hydrazine. Several cyclodehydrating agents such as Et 2 O · BF 3 , 36) 1,1,1,3,3,3-hexamethyldisilazane, 37) triflic anhydride, 38) phosphorus pentoxide, 39) polyphosphoric acid, 40) thionyl chloride, 41,42) phosphorus oxychloride 43) and sulfuric acid 44) have been used. Recently we have reported the synthesis, antimicrobial and cytotoxic activities of 1,3,4-oxadiazoles and 1,3,4-thiadiazoles.…”