Seizures Flashcards
Epilepsy definition
Disorder characterized by periodic occurrence of spontaneous, unprovoked seizures
Surround inhibition
Strongly firing neurons silence connected neurons via inhibitory interneurons
3 steps of seizure
Initiation
Propagation
Termination
Seizure initiation
High frequency bursts of APs and hyper synchronization of a group of neurons
Results in burst of action potentials driven by calcium influx through NMDA receptors
Seizure propagation
Increased extracellular potassium reduces hyperpolarization
Accumulation of calcium in presynaptic terminals increases neurotransmitter release
Activation of NMDA receptors causes more calcium influx and neuron activation
High enough activation can overcome surround inhibition and hyperpolarization
Seizure resolution and aftermath
Generally spontaneous, likely depletion of ionic gradients, neurotransmitters, and ATP plus activation of inhibitory circuits
Status epilepticus: long lasting seizure or burst of multiple seizures, potentially lethal
Postictal period: after resolution, characterized by drowsiness, confusion, depression/anxiety, sometimes psychosis
Seizure classes
Focal
Generalized
Non-convulsive (absence)
Focal seizures
Localized brain region
May become generalized
Simple: retains consciousness
Complex: loses consciousness
Jacksonian March
Muscle jerking that spreads from a specific point to nearby muscle groups, associated with focal seizures
Automatisms
Unusual, unconsciously created activities or movements associated with focal seizures
Generalized seizures
Typically no warning, always loss of consciousness
Tonic-clonic seizures
Generalized, involve sustained general muscle contractions followed by alternating contraction and relaxation
Myoclonic seizures
Generalized, involve brief shock-like contraction of muscles that may be general or localized
Absence seizures
Abrupt loss of consciousness without loss of muscle strength or large movements, may be followed by postictal disorientation
Atonic seizures
Sudden loss of muscle strength, usually retaining consciousness
Anti seizure drug mechanisms
Either enhancing GABA signaling or reducing glutamate signaling
Block ionic movement and/or neurotransmitter release
Inhibit or activate the postsynaptic membrane
Benzodiazepines
Positive allosteric modulator of GABAa receptors, no effect without GABA
Increase frequency of receptor opening, potency of GABA
Barbiturates
Positive allosteric modulator of GABAa receptor, agonist at high concentrations
Increase duration of receptor opening, efficacy of GABA
More overdose risk
Vigabatrin
Inhibits GABA-T enzyme (responsible for GABA degradation)
Tiagabine
Inhibits GAT-1 (GABA reuptake transporter)
Carbamazepine
Voltage gated sodium channel inhibitor
Rate dependent effect
Gabapentin
Minimal activity at GABA receptor
Voltage gated calcium channel inhibitor, binds alpha2delta subunit and disrupts it
Perampanel
Non competitive AMPA (glutamate) receptor antagonist
Serious psychiatric and behavioral side effects
Anti seizure drug pharmacokinetics
Good bioavailability, cross blood brain barrier, low extraction ratio
High potential for drug-drug interactions, serious side effects