DILANTIN (Phenytoin)

A Hydantoin-Derivative Anticonvulsant.
BY
Ikome, Christiana
Johnson,Chalsetta
Kuyon, Korlu
Motari, Angeline

Classification, Pharmacodianamics,
indications and contraindications

Phenytoin (Dilantin)
Classification:
Phenytoin is a hydantoin-derivative anticonvulsant.
Mechanism of Action:
The precise mechanism of action of anticonvulsants is not
known, it is known that the drug use is accompanied by reduced
voltage frequency, and the spread of electrical charges in the
motor cortex, with antiarrythmic similar to those of lidocaine
and tocaninide.
The anticonvulsant action of hydration derivatives is due to the
selective block of high-frequency neuronal activity. The molecular
mechanism for this is their binding to the voltage-sensitive
sodium
channels responsible for the action potential.

Pharmacodynamics:
Antiepileptic drug useful in the treatment of epilepsy.
Primary site of action appears to be the motor cortex where
spread of seizure activity is inhibited.
Reduces the maximal activity of brain stem centers
responsible for the tonic phase of tonic-clonic (grand mal)
seizures.
Acts to dampen the unwanted, runaway brain activity seen in seizure by
reducing electrical conductance among brain cells.
Lacks the sedation effects associated with Phenobarbital.
Phenytoin has other effects, including anxiety control and mood
stabilization, although it has never been approved for those purposes by
the FDA. Phenytoin is primarily metabolized by CYP2C9 .

Indication
Tonic-Clonic Seizures
Partial Seizures.
Seizures Associated with Neurosurgery
Benzodiazepines (e.g., diazepam, lorazepam)
Concurrent administration with an IV benzodiazepine or shortActing barbiturate may be necessary for rapid control of
seizures.

Indications Cont.
Cardiac Glycoside Intoxication
Neuropathic Pain (e.g., trigeminal neuralgia)
Unlabeled Uses
Cardiac Arrhythmias
Contraindication:
Hyper sensitivity to hydantoin products; Rash;
seizures due to hypoglycemia, sinus bradycardia,
complete heart block; Adams Stokes Syndrome,
Pregnancy (category D), lactation.

Precautions:
Impaired liver or kidney function, alcoholism,
blood dyscrasias, hypotension, heart block,
bradycardia, severe myocardial insufficiency,
impending or frank heart failure, older adults,
debilitated , gravely ill patients, pancreatic
adenoma, Diabetes mellitus, hyperglycemia,
respiratory depression, and acute intermittent
porphyria.

Literature review
and
Evidence Based Guidelines

CLINICAL EVIDENCE AND PRACTICE

Dilantin can be used for arrhythmias

associated with cardiac glycoside toxicity
by improving AV conduction.
Dental health is a particular concern
especially those taking doses more than
500 mg/day due to risk for gingival
hyperplasia
Schlicher, M.L., Dilantin jeopardy: Avoiding the dangers of
phenytoin

Clinical evidence and Practice

Clinical standards for phenytoin
administration: the application of
evidence to practice.
C., & Hale, H. (2010). British Journal Of
Neuroscience Nursing, 6(3), 116-122.

Effects of fetal antiepileptic drug

exposure: outcomes at age 4.5 years.
Meador, K., Baker, G. et al, 2012

Clinical evidence and

Practice
Use of phenytoin in pregnancy for
epileptic seizure prevention: a case
report.
Fitzgerald, K. (2004).
Toxicology. Epilepsy and pregnancy:
maternal and fetal effects of
phenytoin.
Brewer, J., & Waltman, P. (2003).

Special Considerations
and Precautions

SPECIAL CONSIDERATIONS
Patients with Renal or Hepatic Disease- There is an increased fraction of
unbound phenytoin in this population, therefore the provider should
interpret total phenytoin plasma concentration with caution.
Patients with HIV/AIDS- Co-administration of phenytoin with delavirdine
is contraindicated due to potential for increased viral load and possible
resistance to delavirdine or to the class of non-nucleaoside reverse
transcriptase (NNRT) inhibitors.
Patients with mental illness: Antiepileptic drugs (AED), including
phenytoin, increase the risk of suicidal thoughts or behavior. Patients
should be monitored for emergence or worsening of depression, suicidal
behavior and ideation, unusual mood changes or behavior
Women Bone fracture phenytoin causes softening of the bones
(Osteoporosis, osteopenia and osteomalacia). Bone density study is
recommended especially in post menopausal women.

SPECIAL CONSIDERATIONS

Young People: Phenytoin induced gingival enlargement or overgrowth can

cause body image issues for this population. Dental appointments are a
must. Provider must re-enforce!!
Pediatric patients- initiate therapy with the pediatric dose factor of
5mg/kg/day in 2 or 3 equally divided doses. Subsequent dosage should be
individualized to a maximum of 300mg daily. Daily maintenance dose 4-8
mg/kg is recommended. Children 6 years and adolescents may require the
minimum adult dose (300mg/day).
Geriatrics-Phenytoin clearance is decreased slightly in elderly patients
therefore lower or less frequent dosing may be required
Pregnancy and Lactation: Category D- Use of effective contraception is
highly required for women of child bearing age. Phenytoin causes birth
defects and bleeding problem in the neonate exposed to the drug in utero.

SPECIAL CONSIDERATIONS
Hypersensitivity to hydantoins
Pregnancy
Category D - causes significant and
reasonable harm to the fetus (Fetal
hydantoin syndrome (FHS) (Singh et al.,
2012)

Lactation
Phenytoin is secreted in human milk
(Singh et al., 2012)

Precautions
Type 2 Diabetes because
it inhibits insulin release
it may raise serum glucose levels

Hypothyroidism
May decrease serum concentrations of
T4

Alcohol
Acute alcohol intake may increase
serum levels
Chronic alcohol use may decrease

Implementation plan including cultural

considerations, age, ethnicity

IMPLEMENTATION PLAN: CULTURAL,

AGE, ETHNICITY CONSIDERATIONS

Culture: Pay special attention to Africans, Chinese, Native Americans as they may
tend to take other herbal remedies that may have drug interaction with Phenytoin.

Ethinicity: Asians have a gene marker (HLA-B 1502) which predisposes them to
increase adverse reaction to Phenytoin. Consider another antiepileptic drug (AED)
for this ethnic group. FDA Alert!

Language barrier: Patient teaching is a very important issue with all patients, but
particularly these cultures. Provide drug information in language understandable to
patient, involve care-givers if possible.

Age: Phenytoin clearance tends to decrease with increasing age (as much as 20%
less in patients >70 years compared to patients 20-30 years of age). Special
consideration should be given to the elderly patient as regards dosing. Individualize
dosing!! As always start slow and titrate/adjust dosage based on serum level.

IMPLEMENTATION PLAN: ADHERENCE

Teach patients to take medication strictly as prescribed

Adjust dosing to minimum effective dosing recommendation to increase
compliance
Follow up with telephone calls to patients, care-givers, with reminders for
appointments, tend to increase adherence.
Teach side effects of Phenytoin to avoid patient abruptly withdrawing from
medication as this may cause status epilepticus.
TEACH, TEACH, TEACH, and TEACH!!!!!!!!!

references
Brewer, J., & Waltman, P. (2003). Toxicology. Epilepsy and pregnancy: maternal and
fetal effects of phenytoin. Critical Care Nurse, 23(2), 93-98.
Fitzgerald, K. (2004). Use of phenytoin in pregnancy for epileptic seizure prevention:
a case report. Journal Of Midwifery & Women's Health, 49(2), 145-147.
Meador, K., Baker, G., Browning, N., Cohen, M., Bromley, R., Clayton-Smith, J., & ...
Loring, D. (2012). Effects of fetal antiepileptic drug exposure: outcomes at age
4.5 years. Neurology, 78(16), 1207-1214.
Nemanja, T., Natasa, V., & Gordana, U. (2011, 05). Solvent effects on the structureproperty relationship of anticonvulsant hydantoin derivatives: A solvatochromic
analysis. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750111/

Phenytoin overview. (2014, 01). Retrieved from

http://web.b.ebscohost.com.ezproxy.welch.jhmi.edu/dynamed/detail .
Phenytoin. (2013, 09). Retrieved from http://www.drugbank.ca/drugs/DB00252
Roland,G., Mathias,N., & Thomas,S. (2012). Toxic epidermal necrolysis and
Stevens-Johnson syndrome: A review*.Critical Care Medicine,39(6), 1521-1532.
doi: 10.1097/CCM.0b013e31821201ed

references
Schachter, S. (2014, 03 19). Pharmacology of antiepileptic drugs . Retrieved from
http://www.uptodate.com/contents/pharmacology-of-antiepileptic-drugs?
source=search_result&search=dilantin&selectedTitle=2~150
doi:10.1155/2012/370412
Singh, R., Kumar, N., Arora, S., Bhandhari, R., & Jain, A. (2012). Fetal Hydantoin
Syndrome and its
Anaesthetic Implications: A Case Report. Case Reports in Anesthesiology, 2012.
Schlicher, M. L. (1998). Dilantin jeopardy: Avoiding the dangers of phenytoin. Medsurg
Nursing, 7(6), 343-7, 356. Retrieved from
http://search.proquest.com/docview/230519359?accountid=11752
Waknine, Y. (2008, November 25). FDA Investigates Genetic Link to Phenytoin Skin
Reactions. Medscape.
Retrieved March 27, 2014, from http://www.medscape.com/viewarticle/584162
Waterhouse, C., & Hale, H. (2010). Clinical standards for phenytoin administration: the
application of
evidence to practice. British Journal Of Neuroscience Nursing, 6(3), 116-122.
Wilder, B., Leppik, I., Hietpas, T., Cloyd, J., Randinitis, E., & Cook, J. (2001). Effect of food
on absorption of
Dilantin Kapseals and Mylan extended phenytoin sodium capsules. Neurology,

QUESTIONS