CENTRAL NERVOUS SYSTEM

AGENTS
BY
Ikome, Christiana
Johnson,Charlesetta
Kuyon, Korlu
Motari, Angeline

CENTRAL NERVOUS SYSTEM AGENTS

Medications for Attention-Deficit/Hyperactivity Disorder

Medications for Dementia
Analgesia and Pain Management
Migraine Medications
Antiepileptics
Antiparkinson Agents

ANTIEPILEPTICS

A class of drugs that are used to prevent

rapid, repetitive, stimulation of the brain
that causes seizure activity such as
in epilepsy.

Edmunds, M. W., Mayhew, M.S. Pharmacology for the Primary Care Provider. 4 th Ed. Elsevier Mosby 2013.

CENTRAL NERVOUS SYSTEM

AGENT SELECTED

Drug Name: PHENYTOIN: GENERIC

Dilantin: BRAND
Classification: Hydantoin

Classification, Pharmacodynamics,
indications and contraindications

PHAMACODYNAMICS:
Treatment of epilepsy
Primary site of action- Motor cortex where
spread of seizure activity is inhibited

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 .

MECHANISM of ACTION:
Precise mechanism of action- Unknown
Its 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 hydantoin derivatives is due to
the
selective block of high-frequency neuronal activity
The molecular mechanism for this is their binding to the
voltage-sensitive sodiumchannels responsible for the action
potential.

PHARMACOKINETICS

Lipid soluble, highly protein bound

Therapeutic range - 10-20mcg/mL

Half-life - 22 hours average

Peak- 1.5 to 3 hours after administration

Steady state- 7-10 days

Hepatic metabolism CYP2C9 & CYP2C19 enzymes

Renal excretion

INDICATIONS

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

Indications Contd.
Cardiac Glycoside Intoxication
Neuropathic Pain
(e.g., trigeminal neuralgia)
Unlabeled Uses:
Cardiac Arrhythmias
.

CONTRAINDICATIONS:

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
Bradycardia
Severe myocardial insufficiency,
Impending or frank heart failure
Pancreatic adenoma
Diabetes mellitus
Respiratory depression
Acute intermittent porphyria.

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.

Ethnicity: 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!!!!!!!!!

SPECIAL CONSIDERATIONS

SPECIAL CONSIDERATIONS
Patients with Renal or Hepatic Disease- There is an
increased fraction of unbound phenytoin in this population
Patients with HIV/AIDS- Co-administration of
phenytoin with delavirdine is contraindicated due to
potential for increased viral load
Patients with mental illness: Antiepileptic drugs (AED),
including phenytoin, increase the risk of suicidal thoughts
or behavior.
Women Bone fracture phenytoin causes softening of
the bones (Osteoporosis, osteopenia and osteomalacia).

SPECIAL CONSIDERATIONS

Young People: Phenytoin induced gingival enlargement or

overgrowth can cause body image issues for this population
Pediatric patients- initiate therapy with the pediatric dose factor of
5mg/kg/day in 2 or 3 equally divided doses
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
Phenytoin causes birth defects and bleeding problem in the neonate
exposed to the drug in utero.

Literature Review
&
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).

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 structure-property 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
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.
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
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
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, 57(4), 582589

QUESTIONS