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  1. Pharmacology. Acetylcysteine (N-acetylcysteine [NAC]) is a mucolytic agent that acts as a sulfhydryl group donor, substituting for the usual sulfhydryl donor of the liver, glutathione. It rapidly binds (detoxifies) the highly reactive electrophilic intermediates of metabolism, or it may enhance the reduction of the toxic intermediate, NAPQI, to the parent, acetaminophen. It is most effective in preventing acetaminophen-induced liver injury when given early in the course of intoxication (within 8–10 hours), but it may also be of benefit in reducing the severity of acetaminophen and non-cetaminophen-induced liver injury by several proposed mechanisms (improved blood flow and oxygen delivery, modified cytokine production, free radical or oxygen scavenging), even when given after 24 hours. This proposed role of NAC as a glutathione precursor, direct sulfhydryl binding agent, and antioxidant has also been the basis for its investigational use for poisonings from agents that are associated with a free radical or oxidative stress mechanism of toxicity or that bind to sulfhydryl groups. This mechanism coupled with improved renal hemodynamics may prevent contrast-induced nephropathy and provide a rescue from cisplatin and ifosfamide-induced nephrotoxicity. It may be used empirically when the severity of ingestion is unknown or serum concentrations of the ingested drug are not immediately available.

  2. Indications

    1. Acetaminophen overdose.

    2. Case reports of or investigational use in carbon tetrachloride, chloroform, acrylonitrile, doxorubicin, arsenic, gold, amanitin mushroom, carbon monoxide, chromium, cyanide, nitrofurantoin, paraquat, and methyl mercury poisoning.

    3. Pennyroyal oil and clove oil poisoning (case reports). The mechanism of hepatic injury by pennyroyal oil and clove oil is similar to that of acetaminophen, and empiric use of NAC seems justified for any significant pennyroyal oil or clove oil ingestion.

    4. Cisplatin or ifosfamide-induced nephrotoxicity and prevention of contrast-induced nephropathy.

    5. Pyroglutamic aciduria (5-oxoprolinuria).

    6. Non-cetaminophen-induced liver failure.

  3. Contraindications. Known acute hypersensitivity or IgE-mediated anaphylaxis (rare). Anaphylactoid reactions, although similar in clinical effects, may be prevented or ameliorated, as discussed below.

  4. Adverse effects

    1. Acetylcysteine typically causes nausea and vomiting when given orally. If the dose is vomited, it should be repeated. The dose calculation and proper dilution (to 5%) should be verified (this effect may be dose- and concentration-dependent). Use of a gastric tube, slower rate of administration, and strong antiemetic agent (eg, metoclopramide, ondansetron) may be necessary.

    2. Rapid intravenous administration can cause flushing, rash, angioedema, hypotension, and bronchospasm (anaphylactoid reaction). Death (status epilepticus, intracranial hypertension) was reported in a 30-month-old child who accidentally received a massive dose intravenously (2,450 mg/kg over 6 hours, 45 minutes), and fatal bronchospasm occurred in an adult with severe asthma.

      1. Reactions may be reduced by giving the loading dose slowly (over at least 60 minutes) in a dilute (3-4%) solution and by exercising extra caution in patients with asthma (carefully titrate with more dilute solutions and slower infusion rates; pretreat with antihistamines).

      2. An additional risk factor for anaphylactoid reaction may be low serum levels of acetaminophen, whereas high levels may be protective against reactions.

      3. If an anaphylactoid reaction occurs, stop the infusion ...

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