Overdose acetaminophen

Chronic ethanol use increases the risk of hepatotoxicity when acetaminophen is used in high doses however, acute ingestion of alcohol along with an acetaminophen overdose decreases the toxicity of acetaminophen. 

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... 

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. 

Acetaminophen overdose Initially 140 mg/kg, then 70 mg/kg q4h orally x 17 doses. All 17 doses must be given, even if acetaminophen levels have declined to non-toxic range. 

Kearns GL, Leeder JS, Wasserman GS. Acetaminophen overdose with therapeutic intent. J Pediatr 1998 132(l) 5-8. 

This may be induced in the main by viral infection and by drugs, typically paracetamol (acetaminophen) overdose but occasionally dose independently by antidepressants and antituberculous drugs amongst others (Table 5). 

Mechanism of Action An intratracheal respiratory inhalant that splits the linkage of mucoproteins, reducingtheviscosityof pulmonary secretions.Tiierapeutic Effect Facilitates the removal of pulmonary secretions by coughing, postural drainage, mechanical means. Protects against acetaminophen overdose-induced hepatotoxicity. Pharmacokinetics Protein binding 83% (injection). Rapidly and extensively metabolized in liver. Deacetylated by the liver to cysteine and subsequently metabolized. Excreted in urine. Half-life 5.6 hr (injection). 

Linden CH, Rumack BH Acetaminophen overdose. Emerg Med Clin North Am 1984 2 103. [PMID 6394298]... 

A report on the biomedical application of activated carbon adsorption [600] is also revealing. The authors analyzed the uptakes of an aromatic compound, acetaminophen (active ingredient in Tylenol, pKj = 9.5), and an aliphatic one, (V-acetylcysteine (which provides a protective effect against acetaminophen overdose pKa = 3.3), under both gastric (pH = 1.2) and intestinal (pH = 7.0) conditions. Their results are reproduced in Table 24. 

Lewis RK, Paloucek FP. Assessment and treatment of acetaminophen overdose. Clin Pharm 1991 10(10) 765-74. 

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. 

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. 

Rumack BH, Petersen RG. 1978. Acetaminophen overdose incidence, diagnosis and management in 461 patients. Pediatrics 62(Suppl.) 898-903... 

Smill tein MJ, Knapp GL, Kuhg KW, Rumack BH. Efhcacy of oral N-acetylcysteine in the treatment of acetaminophen overdose Analysis of the national multicenter study (1976-1985). N Engl J Med 1988 319 1557-62. 

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

Treatment decision making (e.g. paracetamol/ acetaminophen overdose)... 

Figure 5. Acetaminophen overdose induces liver necrosis by formation of more hepatotoxin (metabolite A) than can be deactivated by glutathione conjugation (metabolite B). ...

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. 

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. 

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