Phenytoin and Fosphenytoin
Phenytoin and Fosphenytoin is a topic covered in the Washington Manual of Medical Therapeutics.
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General Principles
Pathophysiology
- Phenytoin exerts therapeutic activity by binding to neuronal sodium channels and inhibiting reactivation.
- Phenytoin exhibits saturable kinetics, and at plasma levels >20 μg/mL, toxic effects become rapidly apparent.
- Fosphenytoin is a prodrug that is converted to phenytoin after IV or IM injection.
Risk Factors
- Patients with mutations of the cytochrome P450 system that impair phenytoin metabolism are at risk for toxicity even with therapeutic use.
- Coadministration of xenobiotics that inhibit CYP 2C9, 2C19, or 3A4 impairs the metabolism of phenytoin and may lead to phenytoin toxicity.
- Phenytoin is highly albumin bound; patients with hypoalbuminemia (e.g., those with malnutrition or cirrhosis) may have higher levels of free (active) drug and experience toxicity despite seemingly normal total phenytoin concentrations.
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General Principles
Pathophysiology
- Phenytoin exerts therapeutic activity by binding to neuronal sodium channels and inhibiting reactivation.
- Phenytoin exhibits saturable kinetics, and at plasma levels >20 μg/mL, toxic effects become rapidly apparent.
- Fosphenytoin is a prodrug that is converted to phenytoin after IV or IM injection.
Risk Factors
- Patients with mutations of the cytochrome P450 system that impair phenytoin metabolism are at risk for toxicity even with therapeutic use.
- Coadministration of xenobiotics that inhibit CYP 2C9, 2C19, or 3A4 impairs the metabolism of phenytoin and may lead to phenytoin toxicity.
- Phenytoin is highly albumin bound; patients with hypoalbuminemia (e.g., those with malnutrition or cirrhosis) may have higher levels of free (active) drug and experience toxicity despite seemingly normal total phenytoin concentrations.
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Citation
Bhat, Pavat, et al., editors. "Phenytoin and Fosphenytoin." Washington Manual of Medical Therapeutics, 35th ed., Wolters Kluwer Health, 2016. The Washington Manual, www.unboundmedicine.com/washingtonmanual/view/Washington-Manual-of-Medical-Therapeutics/602705/all/Phenytoin_and_Fosphenytoin.
Phenytoin and Fosphenytoin. In: Bhat PP, Dretler AA, Gdowski MM, et al, eds. Washington Manual of Medical Therapeutics. Wolters Kluwer Health; 2016. https://www.unboundmedicine.com/washingtonmanual/view/Washington-Manual-of-Medical-Therapeutics/602705/all/Phenytoin_and_Fosphenytoin. Accessed February 2, 2023.
Phenytoin and Fosphenytoin. (2016). In Bhat, P., Dretler, A., Gdowski, M., Ramgopal, R., & Williams, D. (Eds.), Washington Manual of Medical Therapeutics (35th ed.). Wolters Kluwer Health. https://www.unboundmedicine.com/washingtonmanual/view/Washington-Manual-of-Medical-Therapeutics/602705/all/Phenytoin_and_Fosphenytoin
Phenytoin and Fosphenytoin [Internet]. In: Bhat PP, Dretler AA, Gdowski MM, Ramgopal RR, Williams DD, editors. Washington Manual of Medical Therapeutics. Wolters Kluwer Health; 2016. [cited 2023 February 02]. Available from: https://www.unboundmedicine.com/washingtonmanual/view/Washington-Manual-of-Medical-Therapeutics/602705/all/Phenytoin_and_Fosphenytoin.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC
T1 - Phenytoin and Fosphenytoin
ID - 602705
ED - Williams,Dominique,
ED - Bhat,Pavat,
ED - Dretler,Alexandra,
ED - Gdowski,Mark,
ED - Ramgopal,Rajeev,
BT - Washington Manual of Medical Therapeutics
UR - https://www.unboundmedicine.com/washingtonmanual/view/Washington-Manual-of-Medical-Therapeutics/602705/all/Phenytoin_and_Fosphenytoin
PB - Wolters Kluwer Health
ET - 35
DB - The Washington Manual
DP - Unbound Medicine
ER -