Acetaminophen

For acetaminophen overdose, the treatment includes N-acetylcysteine. The mechanism for acetaminophen hepatotoxicity is related to its toxic metabolite, N-acetyl-p-benzoquinoneimine (NAPQI). Acetaminophen is primarily metabolized by sulfation and glucuronidation to derivatives that are excreted in urine. However, a small amount of acetaminophen is metabolized by cytochrome P-4502E1 (CYP2E1) to NAPQI. NAPQI is preferentially conjugated with glutathione and excreted as a nontoxic mercapturic acid. When glutathione is depleted, NAPQI covalently binds to cell proteins and ultimately causes hepatic necrosis. Oxidative stress owing to depletion of mitochondrial glutathione and covalent binding to mitochondrial proteins may both contribute. Acetaminophen causes toxicity after single or daily doses of 7.5 g or above because the metabolism pathway using sulfation and glucuronidation is saturated by high doses of acetaminophen, and the surplus is then available to be metabolized by the CYP2E1 pathway. As a result, large amounts of

NAPQI are produced, and once glutathione is depleted, hepatic necrosis occurs. N-Acetylcysteine is a cysteine precursor for glutathione synthesis that replenishes glutathione in hepatocytes. It is noteworthy that therapeutic doses of acetaminophen (< 4 g/24 hours) have been reported to cause liver toxicity. This rare toxicity owing to low-dose acetaminophen probably represents a variant of idiosyncratic drug-induced liver disease in which individual susceptibility is heightened by altered metabolism (eg, induction of CYP2E1 by ethanol, isoniazid, or fasting; by depletion of glucuronic acid or glutathione by fasting; or by altered response of the innate immune system).

Once patients admit to taking acetaminophen at a supratherapeutic dose, a detailed history of the time of consumption and the amount of acetaminophen should be performed. Patients may be asymptomatic or present with minor gastrointestinal symptoms, especially early after acetaminophen ingestion. Liver tests and serum acetaminophen level should be drawn. If the patient presents within 4 hours after drug consumption, gastric lavage should be performed. The use of activated charcoal may also decrease acetaminophen absorption. However, the institution of N-acetylcysteine should not be delayed in patients who admit to recent consumption of more than 7.5 g or 150 mg/kg body weight. However, because estimation of acetaminophen consumed by patients is not always reliable, the serum acetaminophen level is very important. If the patient's acetaminophen level falls above a line between a serum acetaminophen of 200 mg/L at 4 hours after ingestion and 30 mg/L at 15 hours, there is a significant chance of developing severe liver disease (ALT > 1,000). All patients with acetaminophen levels above this line should receive N-acetylcysteine. For high-risk patients, such as chronic alcohol users, malnourished individuals, or those on epileptic medicine, the threshold line is lower, between 100 mg/L at 4 hours and 15 mg/L at 15 hours. Ideally, N-acetylcysteine treatment is given within 8 hours after the acetaminophen overdose. In the past, N-acetylcysteine was not administered beyond 24 hours after acetaminophen ingestion. However, recent data suggest that N-acetylcysteine treatment improves mortality even when it is initiated more than 24 hours after the overdose. For cases of inadvertent overdose who present with overt liver injury, the blood levels and nomogram are not useful. Although there is no proof of efficacy, we recommend using N-acetylcysteine in this setting. In the United States, N-acetylcysteine is given orally because the intravenous (IV) preparation is not available. The standard dose for N-acetylcysteine is 140 mg/kg body weight as a loading dose, followed by 70 mg/kg every 4 hours for 17 doses. In Europe and Canada, the standard dose is 150 mg/kg IV bolus over 15 minutes followed by 50 mg/kg over 4 hours and then 100 mg/kg over 16 hours. The oral preparation has an unpleasant taste and smell and may need to be given with carbonated soda or antiemetic medication. A feeding tube may be needed in patients who cannot tolerate the medication orally. Oral N-acetylcysteine has no serious side effects, but the IV preparation may rarely cause an ana-phylactic reaction.

Constipation Prescription

Constipation Prescription

Did you ever think feeling angry and irritable could be a symptom of constipation? A horrible fullness and pressing sharp pains against the bladders can’t help but affect your mood. Sometimes you just want everyone to leave you alone and sleep to escape the pain. It is virtually impossible to be constipated and keep a sunny disposition. Follow the steps in this guide to alleviate constipation and lead a happier healthy life.

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