3/27/2013

1

Cynthia Samantha Valle-Oseguera, PharmD

PGY1-Pharmacy Resident BVAMC

ISHP Spring Meeting 2013

• To understand the different types of seizure disorders

• To identify the basic pharmacological principles in management of seizure disorders

• To identify the common non-pharmacologic therapies for seizures disorders

http://schuylerpwr.blogspot.com/2011/03/imma-let-you-finish-but-this-video-may.html

• T/F Seizures are waves of abnormal electrical activity in the brain

http://www.zmescience.com/medicine/epilepsy-seizure-rats-10082012/

3/27/2013

2

• Seizure is a sudden change in behavior due to brain dysfunction

• Epilepsy is characterized by recurrent epileptic seizures due to an acquired brain disorder or genetically determined disorder• <1% of the population has epilepsy

• Some seizures are provoked• Drug or alcohol withdrawal

• Acute neurologic disorders

• Nonepileptic seizures (NES) are sudden changes in behavior that resemble epileptic seizures but are not associated with the typical neurophysiological changes of epileptic seizures

• Genetics

• Stroke

• Cerebral degeneration

• Head trauma

• Brain tumors

• Intracranial infection

• Congenital brain malformations

http://www.kurzweilai.net/health-tips-stroke-toxic-chemicals-in-receipts-and-new-alcohol-and-sugar-risks

• History

• Signs/symptoms

• Medication history

• Analgesics: Fentanyl, tramadol, meperidine

• Antidepresssants: Amitriptyline, bupropion, nortriptyline

• Antipsychotics: Haloperidol, prochlorperazine, thioridazine

• Local anesthetics: Bupivacaine, lidocaine, procaine

• Others: Amphetamines, alcohol, antihistamines, insulin, atenolol, folic acid

• Past medical history

• Head injury, alcohol/drug abuse, stroke

• Family history

• Intense exercise

• Lack of sleep

• Strong emotions

• Stress

• Loud music

• Fever

• Flashing lights

• Menstrual period

http://www.sikhnet.com/news/anger-really-can-kill-you-us-study-shows

3/27/2013

3

• 1997 Pokémon cartoon aired in Japan

• 685 children sought medical attention for neurologic symptoms

• 80% were felt to be seizures

• ¾ children had not experienced seizures previously

http://www.nypost.com/p/entertainment/tv/pokemon_seizure_gun_zZgqgECPXcy4zUn3HNC0IMhttp://elitedaily.com/elite/2012/revealed-military-developed-seizure-inducing-gun-inspired-cartoon-pokemon/

• Hypoglycemia

• Falls in serum sodium concentrations

• Associated with a high risk of mortality and must be treated urgently

• Hypocalcemia

• Magnesium levels below 0.8 mEq/L

• Renal failure

• Uremia

• Dialysis

• Hyperthyroidism

• Withdrawal states

• Drug toxicity/intoxication

• Psychological disorders

• Migraine

• Syncope

• Sleep disorders

• Other neurologic events

• Paroxysmal movement disorders

http://frannielovesmarie.wordpress.com/tag/psycho/

3/27/2013

4

• Partial Seizures• Simple Partial Seizures (consciousness not impaired)

• Motor symptoms• ie. Arrest of speech

• Somatosensory symptoms• ie. Visual, auditory, gustatory

• Autonomic• ie. Pallor, sweating

• Psychic• ie. hallucinations

• Complex Partial (with impaired consciousness)

• Partial Seizures (simple/complex) evolving to secondarily generalized seizures

• Generalized Seizures

• Nonconvulsive (absence)

• Convulsive

• Myoclonic

• Clonic

• Tonic

• Tonic-clonic

• Atonic

• Unclassified

http://nursingcrib.com/nursing-notes-reviewer/seizure-disorder/

• T/F An antiepileptic drug is generally started in individuals after a single provoked seizure

http://www.mnpets.com/blog/medications-we-use

• Goals

• Maintaining quality of life

• Controlling seizures

• Avoiding or minimizing treatment side effects

• AED treatment is started after ≥2 unprovoked seizures

• >50% chance for repeated seizures

3/27/2013

5

• No single AED is the most effective or best tolerated

Seizure type Antiepileptic drug

Broad Broad Broad Broad SpectrumSpectrumSpectrumSpectrum: : : : All All All All seizure seizure seizure seizure typestypestypestypes Lamotrigine, levetiracetam, topiramate, valproate,

zonisamide

Narrow Narrow Narrow Narrow SpectrumSpectrumSpectrumSpectrum: : : : Simple Simple Simple Simple partial, complex partial, partial, complex partial, partial, complex partial, partial, complex partial,

and secondarily generalized and secondarily generalized and secondarily generalized and secondarily generalized seizuresseizuresseizuresseizures

Carbamazepine, gabapentin, lacosamide,

oxcarbazepine, phenobarbital, phenytoin,

pregabalin, primidone, tiagabine

Absence Absence Absence Absence SeizureSeizureSeizureSeizure Ethosuximide

Table modified from UpToDate

• Patient-specific

• Dosing frequency

• Most prescribed are BID dosing

• More frequent dosing

• Pregabalin (t½ = 6 hrs)

• Once daily dosing

• Phenobarbital (t½ = 75-110 hrs)

• Side effects

• Drug Interactions

• T/F Oral contraceptives may decrease valproicacid clearance and their use is associated withincreased valproic acid blood levels

http://whatsthedose.com/spl/0591-4012.html

Drug Systemic side effects Neurotoxic side effects

Carbamazepine Nausea, n/v,

hyponatremia, rash,

Drowsiness, dizziness, blurred or double vision, lethargy,

headache

Ethosuximide Nausea, vomiting Sleep disturbance, drowsiness, hyperactivity

Gabapentin Infrequent Somnolence, dizziness, ataxia

Lamotrigine Rash, nausea Dizziness, tremor, diplopia

Levetiracetam Infection Fatigue, somnolence, dizziness, agitation, anxiety, irritability,

depression

Phenytoin Gingival hypertrophy,

rash

Confusion, slurred speech, double vision, ataxia

Pregabalin Weight gain Dizziness, somnolence, ataxia

Phenobarbital Nausea, rash Alteration of sleep cycles, sedation, lethargy, behavioral

changes, hyperactivity, ataxia, tolerance, dependence

Topiramate Weight loss,

paresthesias

Fatigue, nervousness, difficulty concentrating, confusion,

depression, anorexia, language problems, anxiety, mood

problems, tremor

Valproate Weight gain, n/v, hair

loss, easy bruising

Tremor, dizziness

Table modified from UpToDate

3/27/2013

6

Drug Side effects

Carbamazepine Agranulocytosis, Stevens-Johnson syndrome, aplastic anemia, hepatic failure,

dermatitis/rash, serum sickness, pancreatitis, lupus syndrome

Ethosuximide Agranulocytosis, Stevens-Johnson syndrome, aplastic anemia, hepatic failure,

dermatitis/rash, serum sickness

Lamotrigine Stevens-Johnson syndrome, hypersensitivity, aseptic meningitis

Phenytoin Agranulocytosis, Stevens-Johnson syndrome, hepatic failure, dermatitis/rash, neuropathy,

lupus-syndrome, hirsuitism

Phenobarbital Agranulocytosis, Stevens-Johnson syndrome, hepatic failure, dermatitis/rash, serum sickness

Rufinamide Stevens-Johnson syndrome, dermatitis/rash, shortened QT interval

Topiramate Acute myopia and glaucoma; kidney stones

Valproate Agranulocytosis, Stevens-Johnson syndrome, aplastic anemia, hepatic failure,

dermatitis/rash, serum sickness, pancreatitis, polycystic ovary syndrome

Table modified from UpToDate

• Seizure Calendar

• Generic Substitution

• Alcohol Intake

• Non-compliance

http://edmedkids.arizona.edu/content/educational-implications-1

• Melatonin and cannabis may have anticonvulsant effects

• Some herbal and dietary supplements may be proconvulsant

• Ephedra

• Gingko biloba

• Sage

• Star Fruit

• Medications supplements can affect the metabolism of AEDs and alter drug levels

• Ginkgo biloba reduces serum levels of phenytoin and valproate

• Chinese herb Bai Shao increases serum carbamazepine levels

• Insurance problems

• Decreased self-esteem

• Loss of independence

• Loss of employment

http://www.nbiweston.com/services/individual-psychological-treatment-psychotherapy/

3/27/2013

7

• T/F All states in the United States require drivers with epilepsy to report their condition

http://conicelli.blogspot.com/2010/11/mr-nice-guys-tips-for-teen-driving.html

• A person with uncontrolled epilepsy is at risk for a MVA

• For many adults, restrictions on driving significantly diminish independence and quality of life

http://blumenthals.com/blog/2013/01/31/the-pendulum-swings-on-googles-review-spam-filtering-as-google-relaxes-filter/

• Clinicians neither suspend nor grant driving privileges

• Physicians should counsel patients regarding the risks associated with driving and epilepsy

• Clinicians are required to report patients with seizures to driving authorities in six states (California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania)

• Physicians not reporting when required are open to legal actions

http://www.mrs-marine.com/2010/07/postcard-swap-idaho-8-of-50.html

3/27/2013

8

• “Any person who in the opinion of the department, based upon recommendation of the person's physician, is afflicted with or subject to any condition which brings about momentary or prolonged lapses of consciousness or control, which is or may become chronic,” shall have his or her license suspended, revoked, or denied [IDAHO CODE ANN. § 49-326(1)(c)(1) (2011)]

• Idaho Department of Transportation officials can request that a person submit to a medical examination for public safety reasons, based on observations or other evidence [IDAHO CODE ANN. § 49-202 (2011)]

State Idaho

Seizure-Free PeriodNo set seizure-free

period

Periodic Medical Updates Required After

LicensingAt discretion of DMV

Doctors Required to Report Epilepsy No

DMV Appeal of License Denial Within 20 days

Table obtained from epilepsyfoundation.org

• Keep calm and gently reassure other people who may be in close proximity

• Don’t physically hold the person down

• Time the duration of the seizure with your watch or cell phone

• Clear the area around the person of anything hard or sharp

• Loosen ties that may make breathing more difficult

• Put something flat and soft (such as a folded jacket) under their head

• Turn a seizing person onto their side

• Do not try to force the mouth open with any hard instrument or with fingers

• Don’t attempt artificial respiration

• Stay with the person until the seizure ends naturally

• Be friendly and reassuring as consciousness returns

• Offer to call a relative to help the person get home

Epilepsyidaho.org

• Watch the person carefully and explain to others what is happening

• Speak quietly in a friendly way

• Guide the person away from any danger

• Don’t grab them unless there is a danger of immediate threat to their safety

• Stay with the person until full consciousness returns

• Offer help in arranging their transport back to a residence

Epilepsyidaho.org

3/27/2013

9

• The person is pregnant, injured, or diabetic

• The seizure continues for more than five minutes

• The seizure takes place in water

• Another seizure begins shortly after the first has ended

• There’s no medical I.D., and no way of knowing the nature of the seizure

• Consciousness does not start to return after the shaking has ended

Epilepsyidaho.orghttp://www.huntingtonbeachca.gov/government/departments/fire/general_info/fireDepartmentRecruitmentInformation/ambulance_program.cfm http://www.esquire.com/the-side/feature/what-is/jay-z-kanye-video-seizures-6653872

• www.Epilepsyfoundation.org

• www.EpilepsyIdaho.org

• Schachter, SC. Evaluation of the first seizure in adults. In: UpToDate, Pedley, TA (Ed), UpToDate, Waltham, MA, 2013.

• Krumholz, A. Driving restrictions for patients with seizures and epilepsy. In: UpToDate, Pedley, TA (Ed), UpToDate, Waltham, MA, 2012.

• Karceski, S. Initial treatment of epilepsy in adults. In: UpToDate, Pedley, TA (Ed), UpToDate, Waltham, MA, 2012.

• Schachter, SC. Pharmacology of antiepileptic drugs. In: UpToDate, Pedley, TA (Ed), UpToDate, Waltham, MA, 2012.

• Schachter, SC. Overview of the management of epilepsy in adults. In: UpToDate, Pedley, TA (Ed), UpToDate, Waltham, MA, 2012.

• Samuels, N. Herbal medicine and epilepsy: Proconvulsive effects and interactions with antiepileptic drugs. Epilepsia, 2008, 49, 3, 373-380