Epilepsy Flashcards
Seizure
episode causing movements or feelings patient cannot control. Electrical activity in the brain –> neurons fire at abnormally high rate
epilepsy
multiple seizures; group of disorders
What causes seizures
most are idiopathic; may also be caused by withdrawal from CNS depressant drugs (causes brain to rebound)
Two types of focal seizures
simple partial and complex partial
Two types of generalized seizures
primary and secondary
Where do focal seizures start
localized point in cortex –> agitates neighboring regions, but starts and stays in cortex
Where do secondary generalized seizures start
starts as focal –> activates thalamus –> causes all other regions to depolarize/fire abnormally
Thalamus
main relay station; connections to all other brain regions
Where do primary generalized seizures start
original seizure activity STARTS in the thalamus and leads to activation of both hemispheres
Describe simple partial seizures
WITHOUT altered mental state; patient stays awake; unexplained feelings of joy, anger, sadness, etc; ONLY time pt does not lose consciousness
Describe complex partial seizures
WITH altered mental status; loss of consciousness; repetitive behaviors; automatisms; lasts 30 seconds to 2-3 minutes
Absence seizure
Generalized. Very brief, often no symptoms, rapid blinking or nose rubbing, common in children –> often outgrow
Tonic seizure
Generalized. Bilateral increase in limb tone, arms curl inward
Clonic seizure
Generalized. Bilateral jerking of limbs –> rapid
Tonic-Clonic
Generalized. Bilateral increase in tone followed by bilateral jerking
Atonic
Generalized. Sudden loss of muscle tone and consciousness –> patient passes out
Myoclonic
Generalized. Brief, rhythmic jerks, lasts a few seconds
Tonic-Clonic (grand mal) description
Can be primary or secondary –> entire brain activated either way. Sensory aura often precedes seizure, followed by post-ictal state. Patient is unconscious and has no memory of event
Role of AMPA in Tonic stage
Sodium channel, open
Role of GABA in Tonic stage
Chlorine channel, open briefly at beginning
Role of NMDA in Tonic stage
Calcium channel, Opens after AMPA (AMPA must depolarize NMDA)
Role of G-coupled Calcium channels in Tonic stage
open
Role of AMPA in Clonic stage
Opens and closes
Role of GABA in Clonic stage
Opens and closes opposite of AMPA - when one is open the other closes
Role of NMDA in Clonic stage
closed - no role
Role of G-coupled Calcium channels in Clonic stage
open
Role of AMPA in Post-ictal stage
low level –> not much activity
Role of GABA in Post-ictal stage
open on full power –> pt unconscious
Role of NMDA in Post-ictal stage
no activity
Role of G-coupled Calcium channels in post-ictal stage
On full-power –> tons of Cl- leads to CNS depression
Status epilepticus
continuous seizure activity lasting more than 30 minutes OR two or more sequential seizures without full recovery of consciousness btwn seizures. Can lead to brain damage or death if not stopped.
Causes of status epilepticus
sudden withdrawal of meds (remove CNS depressant get seizure activity), stroke, acute head trauma
Sodium channel blockers
thought to be more effective in treatment of focal and secondary generalized, but can be used in primary generalized. Phenytoin (Dilantin) Carbamazepine (Tegretol) Lamotrigine (Lamictal) Valproic Acid (Depakene)
What do Sodium channel blockers do
Keep channels in refractory period for longer.
When refractory, no ions flow –> difficult to reopen
Blockers increase time in refractory period so no ions flow
AP dives below -70, making it harder to generate an AP (hyperpolarized).
No AP = harder to get abnormal neuron firing
Phenytoin kinetics
Zero order (rare)
drug eliminated at constant, set rate regardless of concentration
system can become saturated
take more drug than body can clear –> build-up –> can lead to CNS depression
Valproic Acid (Depakene)
not typical sodium blocker
also blocks calcium channels
increases GABA synthesis
Inhibits enzyme activity that degrades GABA
Side effects of Penytoin
Rash, gingival overgrowth, confusion
At high doses: CNS depression, hypotension, hyperglycemia
Side effects of Carbamazepine and Lamotrigine
Rash, constipation, N/V, dizzy. Can cause drowsiness or aplastic anemia
Side effects of Valproic acid
alopecia, weight gain, back pain. Tremor, pancreatitis, hepatic failure, depression
Calcium channel blockers
Ethosuximide (Zarontin)
Zonisamide (Zonegran)
Block Calcium - block NMDA - block tonic phase
Calcium channel modulators
Gabapentin (Neurontin) - modulator Pregabalin (Lyrica) - modulator unknown mechanism of action reduces clonic seizures may induce GABA release
Side effects of Ethosuximide (Zarontin)
sedation, headache, GI issues, rash
Side effects of Zonisamide (Zonegran)
Fatigue, dizziness, confusion, kidney stones, weight loss
Side effects of Gabapentin (Neurontin)
sedation, dizziness, ataxia, weight gain, blurred vision
How do Benzo’s work to reduce seizures
Target GABA system
typically given IV during status epilepticus
inducess GABA release
Vigabatrin (Sabril)
inhibits GABA transaminase –> leads to increase in GABA levels.
For seizures, NOT status epilepticus
Want LOTS of GABA in epilepsy
Tiagabine (Gabitril)
GABA transporter blocker. Blocks reuptake from synapse, so increases synaptic levels of GABA
Felbamate
Mixed mechanism
NMDA receptor antagonist –> antagonize, less calcium in so less depolarization –> less activity
Rufinamide
Sodium channel blocker and metabotrophic glutamate receptor blocker
Topiramate (Topamax)
Blocks sodium and calcium channels, enhances GABA and blocks AMPA/Kinate (prevents depolarization)
Levetriacetam (Kepra)
disrupts vesicles to prevent release of neurotransmitters; blocks calcium channels, may increase GABA activity
