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Haloperidol (Norodol)

Clinical Effects:

  • USES: Butyrophenones include the typical antipsychotics, droperidol and haloperidol. They are primarily used for treatment of schizophrenia and mood disorders. They are also used as an adjunct in migraines, states of acute psychosis and agitation, and nausea and vomiting. PHARMACOLOGY: In therapeutic doses, butyrophenones are D2 receptor antagonists. Antagonizing D2 neurotransmission is thought to treat the positive symptoms of schizophrenia. It also interferes with other receptors, such as acetylcholine muscarinic receptors (M1 and M2), histamine receptor (H1), and alpha adrenergic receptors. TOXICOLOGY: In overdose, butyrophenones cause CNS depression and sedation. Hypotension can develop from alpha adrenergic blockade. These agents are also antagonists of the delayed rectifier potassium current blockade which can lead to QTc prolongation and possibly torsades de pointes. EPIDEMIOLOGY: With increasing use of atypical antipsychotics, exposure to butyrophenones is less common. Severe toxicity is uncommon and deaths have rarely been reported. MILD TO MODERATE TOXICITY: Mild to moderate toxicity typically consists of CNS depression and sedation. Dystonia may also occur. SEVERE TOXICITY: Severe toxicity includes more profound CNS depression that can lead to coma. However, significant respiratory depression is uncommon in single agent exposures. Other CNS symptoms can develop, such as delirium and agitation, psychosis, and hallucinations; severe agitation can lead to hyperthermia. Seizures and hypotension can also develop. Torsades de pointes may occur. Neuroleptic malignant syndrome (NMS) can occur, characterized by hyperthermia and autonomic dysfunction, muscle rigidity, and altered mental status. ADVERSE EFFECTS: Common adverse effects with therapeutic dosing include hypotension, constipation, xerostomia, extrapyramidal symptoms, somnolence, and blurred vision.

Range of Toxicity:

  • TOXICITY: Adults who have ingested 300 mg haloperidol have experienced life-threatening symptoms, but some have had severe reactions with therapeutic dosing. Toxic concentrations have not been established. THERAPEUTIC DOSE: DROPERIDOL: ADULT: Initial maximum dose is 2.5 mg IM/IV, may repeat 1.25 mg dose based on patient response, caution is advised. CHILD (2 to 12 years): 0.1 mg/kg IV. HALOPERIDOL: ADULT: 0.5 to 5 mg orally 2 or 3 times daily. CHILD (3 to 12 years, 15 to 40 kg): 0.05 to 0.15 mg/kg/day in divided doses, 2 or 3 times daily.
  • Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Supportive care is the mainstay of treatment for butyrophenone toxicity. Evaluate for co-ingestants, intravenous fluids for volume expansion, and benzodiazepines for agitation or delirium. Benztropine or diphenhydramine for acute dystonia. MANAGEMENT OF SEVERE TOXICITY: If CNS depression is severe, intubation and ventilation may be required to protect the airway. Intravenous fluid expansion is initial therapy for hypotension, and vasopressors may also be used if hypotension persists. For agitation and delirium, benzodiazepines should be given. If severe psychomotor agitation and hyperthermia develop, or other signs of NMS, sedation, intubation, and external cooling should be initiated. For QTc prolongation, ensure electrolytes are corrected and monitor for torsades de pointes.
  • Decontamination: PREHOSPITAL: Charcoal can be considered if a large or polypharmacy overdose has occurred. However, the patient should have an alert mental status and be able to take it voluntarily. HOSPITAL: Typically there is no role for lavage. Charcoal can be considered if a large or polypharmacy overdose has occurred. However, the patient should have an alert mental status and be able to take it voluntarily.
  • Airway management: Intubation and ventilation may be needed in a large or polypharmacy overdose when severe CNS depression and coma develop and the patient is unable to protect the airway.
  • Antidote: None
  • Drug-induced dystonia: DYSTONIC REACTION: ADULT: BENZTROPINE: 1 to 4 mg once or twice daily IV or IM (max, 6 mg/day); 1 to 2 mg of the injection will usually provide quick relief in emergency situations, OR DIPHENHYDRAMINE: ADULT: 10 to 50 mg IV at a rate not exceeding 25 mg/minute or deep IM (max, 100 mg/dose; 400 mg/day). CHILDREN: Diphenhydramine: 5 mg/kg/day or 150 mg/m(2)/day IV divided into 4 doses at a rate not to exceed 25 mg/min, or deep IM (max,, 300 mg/day). Not recommended in premature infants and neonates.
  • Monitoring of patient: Monitor vital signs and mental status. Initiate continuous cardiac monitoring and obtain an ECG. Monitor serum electrolytes. Other laboratory tests should be obtained to evaluate for other co-ingestants as needed. Concentrations can be measured, but are typically done at reference laboratories and are not useful in acute care management.
  • Enhanced elimination procedure: There is no role for enhanced elimination, including multidose activated charcoal, hemodialysis, and hemoperfusion, due to large volume of distribution.
  • Patient disposition: HOME CRITERIA: Patients with low dose supratherapeutic ingestions who are asymptomatic or with mild sedation can be watched at home. OBSERVATION CRITERIA: Patients with a deliberate overdose, or who are symptomatic, should be observed in the emergency department for 6 to 8 hours, or until symptoms have resolved. ADMISSION CRITERIA: Patients who have severe toxicity or prolonged toxicity should be admitted until symptoms have resolved. CONSULT CRITERIA: Consult a medical toxicologist or poison center for patients with severe toxicity.
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