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Lomotil is a combination product containing diphenoxylate and atropine that is prescribed commonly for symptomatic treatment of diarrhea. Children are especially sensitive to small doses of Lomotil and may develop delayed toxicity after accidental ingestion. Motofen is a similar drug that contains difenoxin and atropine. Loperamide (Imodium) is a nonprescription drug with similar properties.

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  1. Mechanism of toxicity

    1. Diphenoxylate is an opioid analog of meperidine. It is metabolized to difenoxin, which has fivefold the antidiarrheal activity of diphenoxylate. Both agents have opioid effects (See Opiates and Opioids) in overdose.

    2. Atropine is an anticholinergic agent (See Anticholinergics) that may contribute to lethargy and coma. It also slows drug absorption and may delay the onset of symptoms.

    3. Loperamide is a synthetic piperidine derivative that is structurally similar to diphenoxylate and haloperidol. It may produce opioid-like toxicity in overdose.

  2. Toxic dose

    1. Lomotil. The toxic dose is difficult to predict because of wide individual variability in response to drug effects and promptness of treatment. The lethal dose is unknown, but death in children has been reported after ingestion of fewer than five tablets.

    2. Loperamide. A single acute ingestion of less than 0.4 mg/kg is not likely to cause serious toxicity in children older than 1 year of age. Fatalities, abdominal distension, and paralytic ileus have been reported in children younger than 1 year of age after ingestion of 0.6–3 mg/d.

  3. Clinical presentation. Depending on the individual and the time since ingestion, manifestations may be those of primarily anticholinergic or opioid intoxication.

    1. Atropine intoxication may occur before, during, or after opioid effects. Anticholinergic effects include lethargy or agitation, flushed face, dry mucous membranes, mydriasis (dilated pupils), ileus, hyperpyrexia, and tachycardia.

    2. Opioid intoxication produces small pupils, coma, and respiratory arrest, and the onset of these effects often is delayed for several hours after ingestion.

    3. All the antidiarrheals may cause vomiting, abdominal distension, and paralytic ileus.

  4. Diagnosis is based on the history and signs of anticholinergic or opioid intoxication.

    1. Specific levels. Specific serum levels are not available.

    2. Other useful laboratory studies include electrolytes, glucose, and arterial blood gases (if respiratory insufficiency is suspected).

  5. Treatment

    1. Emergency and supportive measures

      1. Maintain an open airway and assist ventilation if necessary (See Airway and Breathing).

      2. Treat coma (See Coma and stupor) and hypotension (See Hypotension) if they occur.

      3. Because of the danger of abrupt respiratory arrest, observe all children with Lomotil or Motofen ingestion in an intensive care unit for 18–24 hours. Similar precautions should be taken for patients with very large ingestions of loperamide.

    2. Specific drugs and antidotes

      1. Administer naloxone, 1–2 mg IV (See Naloxone and Nalmefene), to patients with lethargy, apnea, or coma. Repeated doses of naloxone may be required because its duration of effect (≤1–2 hours) is much shorter than that of the opioids in these products.

      2. There is no evidence that physostigmine (See Physostigmine and Neostigmine) is beneficial for this overdose, although it may reverse signs of anticholinergic poisoning.

    3. Decontamination (See Decontamination). Administer activated ...

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