Seizures Flashcards
what are seizures?
transient alteration in behaviour due to abnormally excessive and synchronous neuronal activity in brain
what is epilespsy?
disorder of brain function due to periodic and unpredictable seizures
what is the difference btwn symptomatic and asymptomatic brain seizures?
symp: occurs due to a known event (head trauma or cancer)
asymp: occurs due to genetics
what is the difference btwn provoked or unprovoked seizures?
provoked: by chemical or electrical stimulation
unprovoked: spontaneous (epilepsy)
t/f: everyone who experiences seizures has epilepsy
false
t/f: neurons normally fire asynchronously in the brain
true
what 2 factors inhibit the spread of elec. activity in neurons?
- refractory period (individual neurons)
2. surround inhibition (network of neurons)
what is surround inhibition?
physiological mechanism that focuses neuronal activity in CNS
t/f: primary afferent fibres will all produce APs w/ a stimulus
false, the afferents whose receptive field is closest to point of stimulation will produce more APs than those in periphery (surround inhibiton)
how is surround inhibition shown in second order neurons?
collateral inhibitory neurons project from central afferent neurons to inhibit peripheral second order neurons (focuses stimulus)
what are the 3 phases of a seizure?
initiation, propagation and termination
what 2 events occur in seizure initiation?
- high frequency bursts of APs (overcome ref. period)
2. hyper-synchronization of neuronal population (overcome surround inhibition)
how is neuronal depolarization sustained to produce a burst of APs?
AMPARs (Glu receptors) are activated and depol. cell (Na influx) which stimulates Mg release from NMDARs and additional influx of Na and Ca (importantly)
how is propagation of bursting activity normally prevented? (2)
refractory period (hyperpolarization) and surround inhibition
how does incr extracellular K cause propagation of neuronal activity?
K gradient is saturated (high extracellular [K] if incr previous APs) then neuron can’t hyperpolarize (overcomes refractory period)
what causes incr intracellular Ca in presynaptic terminal to allow propagation of neuronal activity?
opening of NMDA channels causes accumulation of intracellular [Ca] and incr NT release
how does depolarization-induced NMDAR activation cause propagation of neuronal activity?
allows further Ca influx and incr neuronal activation
what does incr extracellular K, incr intracellular Ca, and depolarization-induced NMDAR activation cause?
loss of surround inhibition and propagation of seizure activity
what 4 factors can terminate a seizure?
loss of ionic (Na) gradients, ATP depletion, NT (Glu) depletion, activation of inhibitory circuits (GABA)
t/f: seizures usually resolve spontaneously
true
what is status epilepticus?
seizure lasting longer than 5 min or >1 seizure in 5 min period
what is the postictal period?
5-30 min period after a seizure wherein individual is drowsy, confused, depressed/anxious, or psychotic (hallucinating/delusional)
what differentiates different types of seizures?
where in brain they initiate and how widely they propagate
what are the 3 types of seizures?
focal seizures, generalized seizures and non-convulsive (absence) seizures
what are focal seizures?
seizures in precise part of brain (don’t spread) that may include visual, psychic, autonomic, olfactory, or motor phenomena
what is the difference btwn simple vs complex focal seizures?
simple: retain consciousness
complex: loss of consciousness
what is a Jacksonian March?
propagation of a seizure in one body part to other/nearby body parts
what are automatisms?
unusual activities that are not consciously created (smacking lips)
t/f: focal seizures do not become generalized over time
false, focal seizures can become generalized over time
what are generalized seizures?
seizures that begin in a precise part of the brain and spread to entire brain, are spontaneous and cause unconsciousness
what is the difference btwn tonic-clonic and myoclonic generalized seizures?
tonic-clonic: sustained contraction (tonic) then convulsions of entire body (clonic) - grand mal seizures
myoclonic: brisk (~1s) contraction that can be localized or generalized (no convulsions)
what is the difference btwn absence and atonic non-convulsive seizures?
absence: abrupt impairment of consciousness (can be subtle and not cause falling) - petit mal seizures
atonic: sudden loss of muscle strength (conscious but falls down)
when are antiseizure drugs typically used?
chronically to prevent seizure in ppl w/ epilepsy (can be used to prevent seizures after neurosurgery/brain injury or during status epilepticus)
how do antiseizure drugs typically work?
incr inhibitory GABAergic neurotransmission or decr excitatory Glutamatergic neurotransmission
what are 3 mechanisms of antiseizure drugs?
- decr ion conductance (Na, Ca, K)
- block NT release (Glu)
- inh/act postsynaptic memb
t/f: one drug may have multiple targets to decr seizures but depends on conc.
true
what are benzodiazepines and barbiturates?
positive allosteric modulators of GABAa receptors
at what GABA conc do benzodiazepines and barbiturates work?
benzo: when GABA is present (DON’T work wo/ GABA)
barb: can work wo/ GABA (usually at higher conc)
what are GABAa receptors?
GABA-gated Cl-channels (hyperpolarize postsynaptic cell-inhibit)
do benzodiazepines vs barbiturates incr potency or efficacy of GABA? how
benzo: incr potency (incr f of GABAa receptor opening)
barb: incr efficacy (incr t GABAa receptor is open)
what is a risk of benzodiazepines vs barbiturates? which one is riskier?
both can overdose; barbs are riskier bcse direct gating at GABAaR and benzo require GABA to work
what are 4 symptoms of benzodiazepines or barbiturates overdose?
sluggishness, incoordination, faulty judgement, and death
t/f: risks of benzodiazepines and barbiturates are not affected by other CNS depressants such as alcohol or opioids
false
what is vigabatrin/what does it do?
inhibits GABA aminotransferase (GABA-T) in presynaptic cell; decr GABA breakdown which incr GABA activity (incr inhibitory action)
what is GABA aminotransferase (GABA-T)?
enzyme that breaks down GABA in presynaptic cell
what is tiagabine/what does it do?
inhibits GABA transporter (GAT-1) which prolongs activity of GABA (incr inhibitory action)
where is GABA transporter (GAT-1) located?
neurons and glia
what does carbamazepine do?
block V-gated Na channels
how does carbamazepine block Na conductance?
causes conf. change in inactivation gate (blocks channel)
t/f: drugs that block Na conductance (carbamazepine) are rate dependent
true, blockage incr w/ incr activity of neuron (avoids blocking entire brain activity)
t/f: drugs that block Na conductance (carbamazepine) result in a prolongation of inactivated state of Na channels and refractory period
true
what is the general structure of gabapentin?
GABA molecule w/ cyclohexane ring (lipophilic)
why was gabapentin developed?
GABA agonist that can cross BBB (lipophilic)
what does gabapentin actually do? (not initial intent)
inhibits V-gated Ca channels (has little activity at GABA receptor) to reduce NT release (Glu)
which subunit of Ca channel does gabapentin bind to?
a2∂ subunit (not direct block but alters regulatory function)
what is perampanel?
non-competitive antagonist at AMPAR
what are 2 Glu receptors that anti-seizure drugs can act as antagonists for? (decr Glu activity)
NMDARs and AMPARs
what are risks of perampanel? (AMPAR antagonist)
psychiatric/behavioural changes such mood disorders and suicidal/homicidal ideation (not selective for active neurons-blocks all brain activity)
why is it important to consider pharmacokinetics of antiseizure drugs?
to avoid toxicity and drug interactions
what are the general pharmacokinetic properties of anti-seizure drugs? (3)
well-absorbed, good bioavailability, can cross BBB, low extraction ratios (long acting)
t/f: since antiseizure drugs have a low extraction ratio/are long acting, they are less likely to have drugs interactions
false, are more likely to have drugs interactions
what are side effects of most antiseizure drugs?
depression of CNS (depression, suicidal thoughts, death)
