A 20-year-old man is brought to the emergency department after being found confused and somnolent in his apartment. His face and upper body are covered with emesis. The patient was last seen with a normal appearance 4 hours ago. Medical history is significant for excessive alcohol use. Temperature is 36.8 C (98.2 F), blood pressure is 120/88 mm Hg, pulse is 102/min, and respirations are 26/min. The patient is barely rousable and does not answer questions. Cardiopulmonary examination is normal. The abdomen is soft and nontender. There are no focal findings on neurologic examination. Laboratory results are as follows: Acute poisoning is suspected and the patient is given an appropriate antidote. Which of the following is the most likely mechanism of action of the antidote?

Question

A 20-year-old man is brought to the emergency department after being found confused and somnolent in his apartment.  His face and upper body are covered with emesis.  The patient was last seen with a normal appearance 4 hours ago.  Medical history is significant for excessive alcohol use.  Temperature is 36.8 C (98.2 F), blood pressure is 120/88 mm Hg, pulse is 102/min, and respirations are 26/min.  The patient is barely rousable and does not answer questions.  Cardiopulmonary examination is normal.  The abdomen is soft and nontender.  There are no focal findings on neurologic examination.  Laboratory results are as follows:  Acute poisoning is suspected and the patient is given an appropriate antidote.  Which of the following is the most likely mechanism of action of the antidote?

Quizplus · Accepted Answer

11ec160b_3c44_dd87_9249_470b076f1703_MD0001_00 This patient has altered mental status, acute renal failure, anion gap metabolic acidosis (AGMA) with normal glucose and lactate levels, and a markedly elevated osmolar gap. These findings are highly suggestive of toxic alcohol ingestion, likely with ethylene glycol (although methanol ingestion is difficult to rule out in this obtunded patient). Ethylene glycol and methanol are central nervous system depressants found in antifreeze and cleaning solutions, and may be accidentally or intentionally ingested (eg, substitute for ethanol in patients with dependency, suicide attempt). Although the parent alcohols are relatively nontoxic, ethylene glycol and methanol exhibit profoundly toxic effects when metabolized: Ethylene glycol metabolites (eg, oxalic acid, glycolic acid, glyoxylic acid) cause acute kidney injury due to cytotoxicity and crystalline obstruction. Methanol metabolites (eg, formic acid) cause retinal injury that leads to blindness. Fomepizole, a competitive inhibitor of alcohol dehydrogenase, is the preferred agent for treatment of ethylene glycol and methanol toxicity. By inhibiting the first step in alcohol metabolism, fomepizole decreases the conversion rate of the parent alcohols into their toxic metabolites. Alternately, ethanol is sometimes used as a competitive inhibitor, although it is less preferred due to difficulty in dosing. Hemodialysis may be required. (Choice A) Chelators (eg, deferoxamine) bind to heavy metals and form an inert complex that is cleared renally. Heavy metal poisoning often causes gastrointestinal symptoms or neuropsychiatric effects; AGMA (without lactic acidosis) and an elevated osmolar gap are unexpected. (Choice B) Naloxone competitively binds to opioid receptors in the central nervous system and is used to treat opiate overdose. Patients have sedation and respiratory depression but not an osmolar gap; in addition, hypoxia would be expected on arterial blood gas testing. (Choice D) Activated charcoal is used to absorb toxins in the stomach and prevent absorption into the body. It is used for a variety of poisonings (eg, phenobarbital, acetaminophen); however, it does not absorb alcohol. (Choice E) N-acetylcysteine restores hepatic glutathione stores, promoting the enzyme-based detoxification of the toxic acetaminophen metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Acetaminophen toxicity presents with altered mentation and AGMA; however, an elevated osmolar gap is unexpected and patients often develop signs of hepatic failure (eg, jaundice). Educational objective: Ethylene glycol and methanol are toxic alcohols that cause anion gap metabolic acidosis and an elevated osmolar gap. Toxicity occurs after metabolization by alcohol dehydrogenase; fomepizole is a competitive inhibitor of alcohol dehydrogenase and is used for the treatment of acute poisoning. __________ References: Ethylene glycol or methanol intoxication: which antidote should be used, fomepizole or ethanol? (http://www.ncbi.nlm.nih.gov/pubmed/24659589)

A 20-Year-Old Man Is Brought to the Emergency Department After