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Phenytoin Toxicity Clinical Presentation

  • Author: Charlene Miller, MD; Chief Editor: Asim Tarabar, MD  more...
 
Updated: Apr 25, 2016
 

History

Establish if the toxicity is acute or chronic.

Important historical elements in acute toxicity are as follows:

  • Time of ingestion
  • Co-ingestants
  • Motivation for ingestion (intentional versus accidental)
  • Medications available in the household
  • Paramedics or family members may be able to provide additional information (eg, medications, past medical history)

In chronic toxicity, important historical elements are as follows:

  • Duration of phenytoin use
  • Dosing
  • Frequency
  • Compliance (last dose and missed dose)
  • Recent changes in pharmacotherapy

Important elements for patient query are as follows:

  • When symptoms began
  • Severity of symptoms
  • Exacerbating factors
  • Associated problems
  • Relieving factors
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Physical

See the list below:

  • Phenytoin may cause a febrile reaction, hypotension (during intravenous infusion), or bradycardia.
  • Mouth -Gingival hyperplasia is the most common adverse effect (20%) with long-term use
  • Neurologic
    • Hyperreflexia or hyporeflexia
    • Abnormal gait (bradykinesia, truncal ataxia - Ataxia is very typical with elevated phenytoin levels, and may lead to falls and consequent trauma
    • Respiratory distress
    • Encephalopathy
    • Meningeal irritation with pleocytosis
    • Tremor (intention)
    • Irritability or agitation
    • Confusion
    • Hallucinations
    • Mental status varies from completely normal to the extremes of stupor and coma, particularly if co-ingestants are present
    • Peripheral neuropathy (long-term use)
    • Priapism
    • Urinary incontinence
    • Choreoathetoid movements
    • Dysarthria
    • Dysphagia
    • Seizures (rare)
    • Death (rare)
  • Eyes
    • Nystagmus (horizontal, vertical)
    • Ophthalmoplegia
    • Diplopia
    • Miosis or mydriasis
  • Hypersensitivity reactions (usually 1-4 wk after exposure)
  • Cardiovascular
    • Hypotension, bradycardia[6] , myocardial depression, ventricular fibrillation, asystole, and tissue necrosis[7] all have been associated with the IV formulation.
    • Phlebitis, necrosis, even gangrene
    • "Purple glove syndrome"
      • Distal limb edema, discoloration, and pain after IV administration
      • Usually in elderly and after massive/multiple doses
  • Skin
  • GI/abdomen
    • Right upper quadrant tenderness
    • Hepatomegaly
    • Splenomegaly
    • Nausea
    • Vomiting
    • Hepatitis
  • Metabolic - Osteomalacia and hypothyroidism may result from chronic toxicity

Fetal hydantoin syndrome

Intrauterine exposure to phenytoin may result in the following physical features:

  • Broad nasal bridge
  • Wide fontanelle
  • Low hairline
  • Cleft lip/palate
  • Epicanthal folds
  • Short neck
  • Microcephaly
  • Low-set ears
  • Small or absent nails
  • Hip dislocation
  • Hypoplasia of distal phalanges
  • Impaired growth
  • Congenital heart defects
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Contributor Information and Disclosures
Author

Charlene Miller, MD Consulting Staff, Department of Emergency Medicine, Oakwood Hospital Medical Center

Charlene Miller, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel M Joyce, MD Consulting Staff, Department of Emergency Medicine, Saint Vincent's and Saint Mary's Medical Center

Daniel M Joyce, MD is a member of the following medical societies: American College of Emergency Physicians, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Fred Harchelroad, MD, FACMT, FAAEM, FACEP Attending Physician in Emergency Medicine, Excela Health System

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Lance W Kreplick, MD, FAAEM, MMM Medical Director of Hyperbaric Medicine, Fawcett Wound Management and Hyperbaric Medicine; Consulting Staff in Occupational Health and Rehabilitation, Company Care Occupational Health Services; President and Chief Executive Officer, QED Medical Solutions, LLC

Lance W Kreplick, MD, FAAEM, MMM is a member of the following medical societies: American Academy of Emergency Medicine, American Association for Physician Leadership

Disclosure: Nothing to disclose.

References
  1. Colombo E, Franceschetti S, Avanzini G, Mantegazza M. Phenytoin inhibits the persistent sodium current in neocortical neurons by modifying its inactivation properties. PLoS One. 2013. 8 (1):e55329. [Medline]. [Full Text].

  2. Craig S. Phenytoin poisoning. Neurocrit Care. 2005. 3(2):161-70. [Medline].

  3. McCluggage LK, Voils SA, Bullock MR. Phenytoin toxicity due to genetic polymorphism. Neurocrit Care. 2009. 10(2):222-4. [Medline].

  4. Dorado P, López-Torres E, Peñas-Lledó EM, Martínez-Antón J, Llerena A. Neurological toxicity after phenytoin infusion in a pediatric patient with epilepsy: influence of CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms. Pharmacogenomics J. 2012 May 29. [Medline].

  5. Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol (Phila). 2015. 53 (10):962-1147. [Medline]. [Full Text].

  6. Adams BD, Buckley NH, Kim JY, Tipps LB. Fosphenytoin may cause hemodynamically unstable bradydysrhythmias. J Emerg Med. 2006 Jan. 30(1):75-9. [Medline].

  7. Chokshi R, Openshaw J, Mehta NN, Mohler E 3rd. Purple glove syndrome following intravenous phenytoin administration. Vasc Med. 2007 Feb. 12(1):29-31. [Medline].

  8. Tobler A, Hösli R, Mühlebach S, Huber A. Free phenytoin assessment in patients: measured versus calculated blood serum levels. Int J Clin Pharm. 2016 Apr. 38 (2):303-9. [Medline].

  9. Kiang TK, Ensom MH. A Comprehensive Review on the Predictive Performance of the Sheiner-Tozer and Derivative Equations for the Correction of Phenytoin Concentrations. Ann Pharmacother. 2016 Apr. 50 (4):311-25. [Medline].

  10. Sen S, Ratnaraj N, Davies NA, Mookerjee RP, Cooper CE, Patsalos PN. Treatment of phenytoin toxicity by the molecular adsorbents recirculating system (MARS). Epilepsia. 2003 Feb. 44(2):265-7. [Medline].

  11. [Guideline] Benson BE, Hoppu K, Troutman WG, Bedry R, Erdman A, Höjer J, et al. Position paper update: gastric lavage for gastrointestinal decontamination. Clin Toxicol (Phila). 2013 Mar. 51 (3):140-6. [Medline]. [Full Text].

  12. Dolgin JG, Nix DE, Sanchez J, Watson WA. Pharmacokinetic simulation of the effect of multiple-dose activated charcoal in phenytoin poisoning--report of two pediatric cases. DICP. 1991 Jun. 25(6):646-9. [Medline].

  13. Chan BS, Sellors K, Chiew AL, Buckley NA. Use of multi-dose activated charcoal in phenytoin toxicity secondary to genetic polymorphism. Clin Toxicol (Phila). 2015 Feb. 53 (2):131-3. [Medline].

  14. Ghannoum M, Troyanov S, Ayoub P, Lavergne V, Hewlett T. Successful hemodialysis in a phenytoin overdose: case report and review of the literature. Clin Nephrol. 2010 Jul. 74(1):59-64. [Medline].

  15. Sahoo JN, Gurjar M. Should we do early and frequent charcoal hemoperfusion in phenytoin toxicity?. Indian J Crit Care Med. 2016 Feb. 20 (2):123-5. [Medline]. [Full Text].

  16. De Schoenmakere G, De Waele J, Terryn W, Deweweire M, Verstraete A, Hoste E, et al. Phenytoin intoxication in critically ill patients. Am J Kidney Dis. 2005 Jan;. 45(1):189-92. [Medline].

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