Drug Toxicity 101

Paracetamol

  • There are various clinical presentations of acetaminophen overdose, including asymptomatic, vague nausea/vomiting, acute liver failure, and even coma. A thorough history, in combination with laboratory data, is crucial for diagnosis.
  • Rule of 150s =>
    • Toxic dose is approximately 150mg/kg
    • Treatment with NAC should be implemented if >150 mg/kg acetaminophen level at 4 hours of presentation
    • The initial dose of IV NAC is 150 mg/kg in the first hour.
  • If you are working in a community hospital, consider transfer to a transplant center early if the patient has evidence of severe toxicity (King’s College criteria) or if there is worsening clinical status despite treatment.

Aspirin

  • Start treatment for aspirin overdose at 40 mg/dL or signs of systemic illness with charcoal (if patient tolerates) and sodium bicarbonate
  • If salicylate levels > 90 mg/dL, AMS, significant organ dysfunction, pH < 7.2, or hemodynamic instability => emergent hemodialysis
  • If possible, avoid intubation! But if intubation is necessary, attempt to match the patient’s minute ventilation!

TCA Toxicity

  • TCA toxicity can present with seizures, tachycardia, hypotension, anticholinergic toxicity, and coma.
  • The most common dysrhythmia is sinus tachycardia but the classic EKG findings include cardiac conduction delays, terminal R wave in aVR, and a widened QRS.
  • Treat initially with IVF resuscitation and sodium bicarbonate when QRS > 100ms or for hemodynamic instability.
  • Last resort therapies for refractory arrhythmias with significant toxicity include lidocaine, magnesium, and intravenous lipid emulsion.

Iron Toxicity

  • Charcoal will NOT be beneficial in iron overdose.
  • Criteria for treatment with deferoxamine are hypotension/shock, CNS symptoms, AG metabolic acidosis, serum iron levels > 500 ug/dl or persistent GI symptoms
  • Deferoxamine has the potential for significant hypotension and pulmonary toxicity. Discuss treatment dosing and duration with your toxicologist.

 

IV Iron

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Indication:

  • Severe iron-deficiency anemia (Hb <9 g/dL) especially if there is ongoing bleeding
  • Rate of bleeding too brisk for oral iron
  • Time-sensitive pressures (eg, an urgent surgical procedure; observational studies of the use of IV iron preoperatively for patients with anemia have shown a reduced rate of red cell transfusion being required)
  • Severe anemia of chronic disease and evidence of iron deficiency (eg, ferritin <30 ug/L)
  • Oral iron being poorly tolerated or the failure of an oral trial
  • Poor oral absorption (due to conditions including gastric bypass, celiac disease, and gastritis)

Dose:

IV iron is given as iron sucrose (brand name Venofer) in an infusion of 300 mg in 250 mL of normal saline over two hours. After IV iron, and with ongoing oral supplementation, a patient’s hemoglobin will start to rise in three to seven days. You can expect a 0.1- to 0.2-point rise in the hemoglobin per day; after two to four weeks, the hemoglobin will have risen 2 to 3 g/dL. Ferrous sulfate (300 mg) contains 60 mg of elemental iron, and one tablet can be taken each night on an empty stomach at least two hours after meals with 500 mg of vitamin C to improve absorption. Patients should be counseled to avoid taking iron with calcium or magnesium supplements as they decrease iron absorption.

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