Chapter 27 - Drugs for Seizure Disorders Flashcards
What is a seizure disorder?
a group of disorders characterized by excessive excitability of neurons in the CNS
Seizure symptoms:
-altered consciousness
-convulsions
-alterations in learning, memory, and mood
Is epilepsy more common in men or women?
both
What is a “focus”?
high-frequency discharge from hyper-excitable neurons that initiates a seizure
What can cause a “focus”?
-congenital defects
-hypoxia at birth
-head trauma
-brain infection
-stroke
-cancer
-genetic disorders
-fever
-disease states
Partial (focal) Seizures
seizure activity undergoes limited spread to areas beyond the focus
Generalized Seizures
focal seizure activity is conducted widely throughout both hemispheres
Simple Partial Seizures
-discrete symptoms that can be motor, sensory, autonomic, or psychoillusory
-NO loss of consciousness
-persist for 20-60s
Complex Partial Seizures
-impaired consciousness
-lack of responsiveness
-patient becomes motionless with a fixed gaze followed by automatism
-lasts 45-90s
Automatism
repetitive or purposeless movements (ie. lip smacking)
Secondary Generalized Seizures
-begin as simple or complex and become tonic-clonic
-consciousness is LOST
-last 1-2min
Tonic-Clonic (grand mal) Seizures
-immediate loss of consciousness
-major convulsions
-muscle rigidity (tonic)
-muscle jerks (clonic)
-often cause urination but not defecation
-postictal state
-lasts 90s or less
Postictal State
period of CNS depression after seizure
Absence Seizures (petit mal)
-brief loss of consciousness
-mild motor activity or no motor activity
-common in children
Atonic Seizures
-sudden loss of muscle tone
-neck may drop
-patient may collapse
-common in children
Myoclonic Seizures
-sudden muscle contraction lasting 1 second
-may involve one limb or entire body
Status Epilepticus Seizures
-persists for 15-30 mins or longer
-patient doesn’t regain consciousness
-several types
Febrile Seizures
-common in children age 6mo. to 5yr
-manifest as TC seizures
-not at high risk of later developing epilepsy
Mixed Seizures: Lennonx-Gastaut Syndrome
-severe epilepsy developing during preschool years
-various kinds of seizures
What do anti-seizure drugs do?
-suppress neuronal discharge in seizure focus
-suppress propagation of seizure activity away from focus
MOA of anti-seizure drugs:
-↓ sodium and calcium influx
-↑ potassium efflux
-antagonism of glutamate
-increased in strength of GABA
What is the goal of seizure treatment?
-↓ seizures to a manageable level
-balance seizure control with acceptable side effects
What are some other treatment options for epilepsy?
-surgery
-vagus nerve stimulation
-ketogenic diet
-cannabis
How is epilepsy diagnosed?
-physical, neuro, lab exam
-EEG
What is a major risk of anti-epileptic drugs?
suicide
Phenytoin, fosphenytoin, carbamazepine, valproic acid, ethosuximate, phenobarbital, and primidone are which category for AEDs?
traditional antieplieptic drugs
Gabapentin, lamotrigine, levitiracetam, oxacarbazepine, pregabalin, topiramate, and vigabatrin are which category of AEDs?
newer antiepileptic drugs
What does phenytoin inhibit? (MOA)
sodium channels
What makes phenytoin easily toxic?
liver has limited ability to metabolize phenytoin
What is phenytoin used for?
epilepsy and cardiac dysrhytmias
What is unique about the aborption of phenytoin?
-variable (can easily be toxic)
-small changes in dose largely affect absorption
-narrow therapeutic range
What are the adverse effects of phenytoin?
-gingival hyperplasia
-nystagmus, diplopia
-sedation
-ataxia
-hirsutism
-cognitive impairment
-skin rash
What is gingival hyperplasia?
swelling, tenderness, and bleeding of the gums
What can be used to prevent gum overgrowth?
folic acids (0.5mg/day)
What can reduce risk of gingival hyperplasia?
-oral hygiene
-flossing
-gum massage
Skin rash from phenytoin is more common in people of what descent?
Asian
What makes phenytoin high risk?
when it is administered IV
What are some drugs that interact with phenytoin?
-OC’s
-warfarin
-glucocorticoids
-diazepam
-isoniazid
-cimetidine
-alcohol (acute ↑ and chronic ↓)
-valproic acid
-carbamazepine
-phenobarbital
-barbiturates and other CNS depressants
Dosing of phenytoin is…
highly individualized
Should phenytoin be administered with or without food?
with food
Is phenytoin safe during pregnancy?
no - it is teratogenic
What are some rules about phenytoin admin via IV?
-never mix
-never piggyback onto dextrose
-administer directly into a large vein
-monitor for extravasation
What infusion rate should not be exceeded with phenytoin?
50 mg/min
What is the IV alternative to phenytoin?
fosphenytoin
How does dosing of phenytoin and fosphenytoin compare?
equivalent to phenytoin
What is a risk of IV fosphenytoin when administered faster than 150 mg/min?
-hypotension
-arrythmias
What is required during fosphenytoin administration?
cardiac monitoring
Fosphenytoin is a prodrug of phenytoin meaning…
it is converted to phenytoin when metabolized
What is carbamazepine used for?
-epilepsy
-bipolar disorder
-trigeminal and glossopharyngeal neuralglias
How does carbamazepine act?
suppresses high-frequency neuronal discharge around focus
Ataxia
poor muscle control causing clumsy movements
What are the adverse effects of carbamazepine?
-nystagmus
-ataxia
-leukopenia
-anemia
-thrombocytopenia
-teratogenic
-rash
-photosensitivity
Is carbamazepine safe during pregnancy?
no - it is teratogenic
Carbamazepine is not active against _________ seizures
absence
What does carbamazepine interact with?
-OC’s
-warfarin
-phenytoin
-phenobarbital
-grapefruit juice
How does valproic acid act?
-blocks sodium channels
-suppresses calcium (via T-type calcium channels)
-increases GABA
What is valproic acid used for?
-epilepsy
-bipolar disorder
-migraines
What are the adverse effects of valproic acid?
-GI effects
-liver failure
-pancreatitis
-teratogenic
-hair loss
-weight gain
Is valproic acid safe during pregnancy?
no - teratogenic
What is the drug of choice for absence seizures?
ethosuximide
How does ethosuximide act?
suppress neurons in THALAMUS that are responsible for generation of absence seizures
What are the adverse effects of ethosuximide?
-initially - drowsiness, dizziness, lethargy
-no significant AE
What is the action of phenobarbital?
-reduces seizures by increasing effects of GABA
What drug class is phenoBARBITal?
anticonvulsant barbiturate
What is phenobarbital used for?
-epilepsy
-sedation
-induction of sleep
What are the adverse effects of phenobarbital?
-neuropsychologic effects
-dependency
-nystagmus
-ataxia
Drug interactions of phenobarbital:
-OC’s
-warfarin
-alcohol
-benzodiazepines
-opiods
-valproic acid
Withdrawal of phenobarbital:
-should be done gradually to avoid side effects
Which seizure disorder is primidone not effective against?
absence seizures
What components of primidone are similar to phenobarbital?
AE and DI
What is oxcarbazepine used for?
seizures in adults and children
Oxcarbazepine is similar to __________
carbamazepine
What are the adverse effects of oxcarbazepine?
-dizziness
-drowsiness
-double vision
-nystagmus
-headache
-nausea
-vomiting
-ataxia
-skin reaction (stevens-johnson syndrome and toxic epidermal necrolysis)
What electrolyte imbalance is clinically significant with oxcarbazepine?
hyponatremia
Is oxcarbazepine safe during pregnancy?
no - teratogenic
What drugs interact with oxcarbazepine?
-phenytoin
-perampanel
-phenobarbital
-valproic acid
-eslicarbazepine
-OCs
-sodium depleting drugs
-alcohol
What is lamotrigine used for?
-broad spectrum of anti-seizure activity
-bipolar disorder
What are the adverse effects of lamotrigine?
-dizziness
-diplopia
-blurred vision
-nausea
-vomiting
-headache
-severe skin reactions
What is a major risk of lamotrigine?
suicide
Which AED does lamotrigine interact with?
valproic acid
Is lamotrigine safe during pregnancy?
no
What are some off label uses of Gabapentin?
-neuropathic pain
-migraines
-fibromyalgia
-postmenopausal hot flashes
What are the adverse reactions of gabapentin?
-somnolence (increased sleep)
-dizziness
-ataxia
-fatigue
-nystagmus
-peripheral edema
Pregabalin is an analogue of _____
GABA
What are the uses of pregabalin?
-diabetic neuropathy
-postherpetic neuralgia
-partial seizures
-fibromyalgia
What are the adverse effects of pregabalin?
-dizziness
-somnolence
-blurred vision
-weight gain
-brain fog
-headache
-peripheral edema
-dry mouth
-angioedema
-rhabdomyolysis
Pregabalin hypersensitivity causes ______________-
angioedema
Whic AED is different from the rest?
levetiracetam
What is the MOA of levetiracetam?
unknown
What drugs does levetiracetam interact with?
not other AEDs
What is topiramate used for?
-seizures
-bipolar disorder
-cluster headaches
-neuropathic pain
-diabetic neuropathy
-infantile spasms
-essential tremor
-binge-eating disorder
-bulimia
-alcohol and cocaine dependence
What are the adverse effects of topiramate?
-somnolence
-dizziness
-ataxia
-nervousness
-diplopia
-nausea
-anorexia
-weight loss
-confusion
-memory difficulty
-kidney stones
-brain fog
-paresthesia
-metabolic acidosis
-glaucoma
-SUICIDE
4 Goals of Treatment for Convulsive Status Epilepticus
- maintain ventilation
- correct HYPOglycemia
- terminate seizures (meds)
- long-term AEDs
What is the medication used for first-line seizure management of continuous tonic-clonic seizures?
lorazepam
What med is used if lorazepam is not available?
diazepam
