Toxicity, Phenytoin Clinical Presentation

  • Author: Charlene A Miller, MD; Chief Editor: Asim Tarabar, MD   more...
 
Updated: Nov 4, 2010
 

History

Establish if the toxicity is acute or chronic.

  • Intentional overdose
    • Important historical elements
      • Time of ingestion
      • Co-ingestants
      • Motivation for ingestion
      • Medications available in the household
    • Paramedics or family members may be able to provide additional information (eg, medications, past medical history).
  • Chronic toxicity
    • Important historical elements
      • Duration of administration
      • Dosing
      • Frequency
      • Compliance (last dose and missed dose)
      • Recent changes to their pharmacotherapy
    • Important elements for patient query
      • When symptoms began
      • Severity of symptoms
      • Exacerbating factors
      • Associated problems
      • Relieving factors
Next

Physical

  • Phenytoin may cause a febrile reaction, hypotension (during intravenous infusion), or bradycardia.
  • Mouth -Gingival hyperplasia (chronic use), the most common adverse effect (20%)
  • Neurologic
    • Hyperreflexia or hyporeflexia
    • Abnormal gait (bradykinesia, truncal ataxia - Ataxia is very typical presentation for patients with elevated phenytoin levels.
    • 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 (chronic 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[4] , myocardial depression, ventricular fibrillation, asystole, and tissue necrosis[5] 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
  • Other
    • Fetal hydantoin syndrome is manifested by broad nasal bridge, wide fontanelle, low hairline, cleft lip/palate, epicanthal folds, short neck, microcephaly, low-set ears, small or absent nails, dislocated hip, hypoplasia of distal phalanges, impaired growth, and congenital heart defects.
    • Metabolic symptoms may include osteomalacia and hypothyroidism (chronic toxicity).
    • Trauma - Patients suffer from ataxia and consequently falling.
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Contributor Information and Disclosures
Author

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

Charlene A 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

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

Disclosure: Nothing to disclose.

Specialty Editor Board

Lance W Kreplick, MD, MMM, FAAEM, FACEP  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, MMM, FAAEM, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physician Executives

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD  Regional Director of Pharmacy, Sacred Heart & 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  Chair, Department of Emergency Medicine, Director of Medical Toxicology, Allegheny General Hospital; Associate Professor, Department of Emergency Medicine, Drexel University College of Medicine

Disclosure: Nothing to disclose.

John D Halamka, MD, MS  Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine

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.

References

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

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

  3. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Heard SE. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). Dec 2008;46(10):927-1057. [Medline]. [Full Text].

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

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

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

  7. 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. Jun 1991;25(6):646-9. [Medline].

  8. 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. Jul 2010;74(1):59-64. [Medline].

  9. 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. Jan; 2005;45(1):189-92. [Medline].

  10. Carducci B, Hedges JR, Beal JC, et al. Emergency phenytoin loading by constant intravenous infusion. Ann Emerg Med. Nov 1984;13(11):1027-31. [Medline].

  11. Dela Cruz FG, Kanter MZ, Fischer JH, Leikin JB. Efficacy of individualized phenytoin sodium loading doses administered by intravenous infusion. Clin Pharm. Mar 1988;7(3):219-24. [Medline].

  12. Donovan PJ, Cline D. Phenytoin administration by constant intravenous infusion: selective rates of administration. Ann Emerg Med. Feb 1991;20(2):139-42. [Medline].

  13. Earnest MP, Marx JA, Drury LR. Complications of intravenous phenytoin for acute treatment of seizures. Recommendations for usage. JAMA. Feb 11 1983;249(6):762-5. [Medline].

  14. Goldfrank L, Flomenbaum NE, Lewin NA. Anticonvulsants -- phenytoin. In: Goldfrank's Toxicologic Emergencies. 5th ed. New York: McGraw-Hill; 1994:591-4.

  15. Goldfrank L, Flomenbaum NE, Lewis NA, eds. Goldfrank's Toxicologic Emergencies. New York: McGraw-Hill; 1998.

  16. Jones GL, Wimbish GH. Hydantoins in antiepileptic drugs. In: Handbook of Experimental Pharmacology. New York: Springer-Verlag; 1985:725-65.

  17. Levine M, Chang T. Therapeutic drug monitoring of phenytoin. In: Clinical Pharmacokinetics. Vol 19. 1990:341-58.

  18. Murphy JM, Motiwala R, Devinsky O. Phenytoin intoxication. South Med J. Oct 1991;84(10):1199-204. [Medline].

  19. Plenge KL. The toxicity of the major anticonvulsants. Ariz Med. Mar 1978;35(3):177-9. [Medline].

  20. Prosser TR, Lander RD. Phenytoin-induced hypersensitivity reactions. Clin Pharm. Sep 1987;6(9):728-34. [Medline].

  21. Ramsay RE, Hammond EJ, Perchalski RJ, Wilder BJ. Brain uptake of phenytoin, phenobarbital, and diazepam. Arch Neurol. Sep 1979;36(9):535-9. [Medline].

  22. Salem RB, Wilder BJ, Yost RL, et al. Rapid infusion of phenytoin sodium loading doses. Am J Hosp Pharm. Mar 1981;38(3):354-7. [Medline].

  23. Tintinalli J, Ruiz E, Krome R. Phenytoin toxicity. In: Emergency Medicine: A Comprehensive Study Guide. New York: McGraw-Hill; 1996:807-11.

  24. Watson WA, Litovitz TL, Klein-Schwartz W, Rodgers GC Jr, Youniss J, Reid N. 2003 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2004;22(5):335-404. [Medline]. [Full Text].

  25. Yaari Y, Selzer ME, Pincus JH. Phenytoin: mechanisms of its anticonvulsant action. Ann Neurol. Aug 1986;20(2):171-84. [Medline].

 
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