For acetaminophen overdose

The answer is c. (Hardman, pp 632-633.) Nausea, vomiting, abdominal pain, and diarrhea are early signs of the severe liver toxicity caused by high levels of acetaminophen other symptoms of acetaminophen toxicity include dizziness, excitement, and disorientation. N-acetyl-L-cysteine is the appropriate treatment for acetaminophen overdose. 

Acetylcysteine (Mucomyst) Acetylcysteine is the expectorant prescribed for chronic obstructive pulmonary disease. Acetylcysteine is administered by nebulizer 5 minutes after bronchodilators are administered. Acetylcysteine should not be mixed with other medication. Acetylcysteine is also an antidote for acetaminophen overdose if given within 12 to 24 hours after the overdose. 

Lewisite is the only vesicant with a proven antidote—British anti-lewisite (2,3-dimercaptopropa-nol). Increasing antioxidant levels have been found to be protective against the mustards analog, NAC. NAC, which we have used in our studies with CEES, is immediately clinically available. It is most commonly used for acetaminophen overdose. NAC has a long history of several gram quantities administered in several doses and has minimal adverse reactions. In the case of acetaminophen overdose, it is administered via the oral-gastric route, which increases hepatic GSH levels, and in turn, suppresses inflammatory cytokines (Dambach et al., 2006). Liposome encapsulation of both water- and fat-soluble antioxidants was proven to be more effective in the suppression of OS than the free molecule of NAC. 

Woodhead JL, Howell BA, Yang Y, Harrill AH, Clewell HJ III, Andersen ME, Siler SQ, Watkins PB (2012) An analysis of N-acetylcysteine treatment for acetaminophen overdose using a systems model of drug-induced Uver injury. J Pharmacol Exp... 

Rybolt et al. studied the adsorption of a biomedically active aromatic compound acetaminophen, which is the active constituent of Tylenol, and an aUphalic compound N-acetylcysteine, which is an antidote for acetaminophen overdose on an activated carbon from aqueons solutions at gastric pH 1.2 and intestinal pH 7.0. The adsorption data fitted the Langmuir isotherm equation for both the adsorbates. 

When acetylcysteine is administered for acetaminophen overdosage, the drug is given as soon as the overdosage is discovered. Treatment should begin as soon as possible after overdose and within 24 hours of ingestion. 

Adverse reactions to drugs differ in both type and incidence in the pediatric population. Because of immature metabolic pathways, infants and children may have different metabolic patterns than adults. This at least partially explains why neonates require lower theophylline serum concentrations for the treatment of neonatal apnea and why the incidence of hepatotoxi-city following acetaminophen overdose is much lower in young children than in adults [44,45]. Antibiotic adverse effects unique to the pediatric population may... 

N-Acetylcysteine is used primarily in the treatment of acetaminophen overdose and/or toxicity. It is also nebulized for mucolytic effects and less often used to treat corneal ulcers. It has a very low potential to cause acute toxicity in either animals or humans. 

CNS depression is the most frequently reported clinical effect. The typical overdose patient may present with extreme somnolence that may progress to frank coma. Miosis is usually present unless the individual is acidotic or has suffered hypoxic brain injury. Respiratory depression can occur and may progress to respiratory arrest. Pulmonary edema may be seen. Bradycardia, hypotension, and hyperthermia can develop. Hydrocodone is often combined in products with acetaminophen therefore, patients should be evaluated for hepatotoxicity secondary to acetaminophen overdose. Available opiate immunoassays cross-react unreliably with hydrocodone. Peak therapeutic serum levels are 0.024 mg 1 toxic levels have been reported to reach 0.1-1.3 pgml , but are of little prognostic or therapeutic value. 

Yip L, Dart RC. A 20-hour treatment for acute acetaminophen overdose. N Engl J Med 2003 384 2471-2 (Letter). 

The routine administration of acetylcysteine more than 24 hours after acetaminophen overdose has been proposed. Case reports and animal studies indicate that it is relatively safe and that its use may minimize hepatotoxicity. Although accepted criteria for its use are lacking, it may be considered for patients with fulminant hepatoxicity, when acetaminophen is still measurable in the serum, or when the ingestion was not recognized within 24 hours and liver toxicity is apparent. 

When plasma concentrations are below the nomogram treatment line, there is little risk of toxicity, protective therapy with acetylcysteine is not necessary, and further medical therapy is unnecessary for the acetaminophen overdose. The acetaminophen blood sample should be drawn no sooner than 4 hours after the ingestion to ensure that peak acetaminophen concentrations have been reached. 

Treatment was initiated for paracetamol (acetaminophen) overdose. N-acetyl-L-cysteine is administered orally as follows. A loading dose of 140 mg/kg followed by 17 doses of 70 mg/kg every four hours. The patient was transferred to the intensive care unit. Her liver function tests and serum electrolytes returned to normal values during the next eight days (Table 2). The patient s... 

When reactive metabolites are formed in large amounts (for example, after acetaminophen overdoses) several biochemical events may be triggered which all affect the mitochondria, disrupting the outer mitochondrial membrane and leading to cell death (Fig. 7) (Pessayre et al. 1999 Haouzi et al. 2000). 

Although considered safe at therapeutic doses, at higher doses, acetaminophen produces a centrilobular hepatic necrosis that can be fatal. Acetaminophen poisoning accounts for approximately one-half of all cases of acute liver failure in the United States and Great Britain today (Larson et al. 2005 Ostapowicz et al. 2002) Annually, it accounts for a very high percentage of inquiries to poison control centers and deaths (Litovitz et al. 2002). The direct costs of acetaminophen overdose have been estimated to be as high as US 87 million annually (Bond and Novak 1995). 

Clinical data also support the association of covalent binding and toxicity. Early studies utilized immunoassays to detect adducts in the blood samples of patients with acetaminophen overdose (Hinson et al. 1990). The highest levels of adducts were found in the patients with the most severe toxicity. The recent development of a highly sensitive and specific HPLC-EC assay for detection of acetaminophen protein adducts (3-cysteine-acetaminophen in proteins) has allowed for further... 

Grewal KK, Racz WJ (1993) Intracellular calcium disruption as a secondary event in acetaminophen-induced hepatotoxicity. Can J Physiol Pharmacol 71 26-33 Gujral JS, Knight TR, Earhood A, Bajt ML, Jaeschke H (2002) Mode of cell death after acetaminophen overdose in mice apoptosis or oncotic necrosis Toxicol Sci 67 322-328 Gujral JS, Hinson JA, Earhood A, Jaeschke H (2004) NADPH oxidase-derived oxidant stress is critical for neutrophil cytotoxicity during endotoxemia. Am J Physiol Gastrointest Liver Physiol 287 G243-252... 

---