![]() In conclusion, exogenous N-acetylcysteine does not form significant amounts of conjugate with the reactive metabolite of acetaminophen in the rat in vivo but increases glutathione synthesis, thus providing more substrate for the detoxification of the reactive metabolite in the early phase of an acetaminophen intoxication when the critical reaction with vital macromolecules occurs. Animals treated with acetaminophen and N-acetylcysteine excreted 2.7+/-0.8 nmol/min per 100 g of N-acetylcysteine disulfides (measured by high performance liquid chromatography) compared to 0.4+/-0.1 nmol/min per 100 g in rats treated with N-acetylcysteine alone. The victims consumed Tylenol-branded acetaminophen capsules that had been laced with potassium cyanide. N-acetylcysteine produced a marked increase in the biliary excretion of glutathione disulfide from 1.2+/-0.3 nmol/min per 100 g in control animals to 5.7+/-0.8 nmol/min per 100 g. The Chicago Tylenol murders were a series of poisoning deaths resulting from drug tampering in the Chicago metropolitan area in 1982. However, when administered after acetaminophen. N-Acetylcysteine alone did not affect the biliary excretion of glutathione disulfide. Acetaminophen alone depleted intracellular glutathione, and led to a progressive decrease in the biliary excretion of glutathione and glutathione disulfide. Reduction of the benzoquinoneimine by N-acetylcysteine should result in the formation of N-acetylcysteine disulfides and glutathione disulfide via thiol-disulfide exchange. Although the excretion of acetaminophen sulfate increased from 85+/-15 to 211+/-17 mumol/100 g per 24 h after N-acetylcysteine, kinetic simulations showed that increased sulfation does not significantly decrease formation of the toxic metabolite. However, when rats were fasted before the administration of acetaminophen, thereby increasing the stress on the glutathione pool, exogenous N-acetylcysteine significantly increased the formation of the acetaminophen-glutathione adduct from 57 to 105 nmol/min per 100 g. Exogenous N-acetylcysteine did not increase the formation of the N-acetylcysteine and glutathione adducts of acetaminophen in fed rats. N-Acetylcysteine promptly reversed the acetaminophen-induced depletion of glutathione by increasing glutathione synthesis from 0.54 to 2.69 mumol/g per h. After the administration to rats of acetaminophen (1 g/kg) intraduodenally (i.d.) and of -N-acetylcysteine (1.2 g/kg i.d.), the specific activity of the N-acetylcysteine adduct of acetaminophen (mercapturic acid) isolated from urine and assayed by high pressure liquid chromatography averaged 76+/-6% of the specific activity of the glutathione-acetaminophen adduct excreted in bile, indicating that virtually all N-acetylcysteine-acetaminophen originated from the metabolism of the glutathione-acetaminophen adduct rather than from a direct reaction with the toxic metabolite. However, these hypothese have not been tested in vivo, and other mechanisms of action such as reduction of the quinoneimine might be responsible for the clinical efficacy of N-acetylcysteine. It is thought to provide cysteine for glutathione synthesis and possibly to form an adduct directly with the toxic metabolite of acetaminophen, N-acetyl-p-benzoquinoneimine. (1-80) Quick medical attention is critical for adults as well as for children even if you do not notice any signs or symptoms.N-Acetylcysteine is the drug of choice for the treatment of an acetaminophen overdose. Overdose warning: In case of overdose, get medical help or contact a Poison Control Center right away. If pregnant or breast-feeding, ask a health professional before use. These could be signs of a serious condition. fever gets worse or lasts more than 3 days.pain gets worse or lasts more than 5 days in children under 12 years. ![]()
0 Comments
Leave a Reply. |