2- drugs for seizures Flashcards
what happens in the brain/neurons during a seizure
high frequency dischange of a group of neurons
starts in one area, then spreads
what determines the symptoms of seizures
the site of primary discharge and the extent of the spread
what happens with high frequency discharge (Seizure) in the motor cortex
convulsions
what happens with high frequency discharge (Seizure) in the brain stem
loss of consciousness
what is epilepsy
a disorder characterized by seizures
many different types with different origins, symptoms and causes
what are tonic/clonic seizures
- how long do they last
- how affect consciousness
- main features
obvious physical effects via muscle contraction followed by relaxation
severe
loss of consciousness
can last minutes
what are general absence seizures
- how long do they last
- how affect consciousness
affect consciousness, can be short (seconds)
what are partial seizures
- how long do they last
- how affect consciousness
- main features
confined to specific regions with minimal spread, consciousness retained (may be altered), can last minutes
what does tonic mean
loss of consciousness and muscle rigidity
what does clonic mean
muscles rapidly relax and contract
is glutamate excitatory or inhbitory to AMPA receptors
excitatory
is glutamate excitatory or inhbitory to NMDA receptors
excitatory
is GABA excitatory or inhbitory to GABA-A receptors
inhibitory
which ion flows through when GABA binds to GABA-A
what does this cause
Cl
hyperpolarization
which ions flow through when GLU binds to NDMA or AMPA
what does this cause
Na+, Ca++, K+
depolarization
what are the 4 targets for pharmacological intervention in seizures
- increase inhibitory influences (increase effects of GABA
- inhibit AP (voltage-gated Na influx)
- decrease spread of neuronal discharge (block low-voltage activated Ca channels)
- decrease excitatory influences (decrease glu LGIC receptor activity)
what are the common side effects of anti seixure drugs
sedation
what does GABA-T (GABA-transaminase) do
metabolizes free GABA in the nerve endings and astrocytes
what happens when you inhibit GABA-T
there will be more presynaptic GABA so that more can be released in depolarization events
what is Vigabatrin
what kind of seizures is it good for
partial seizures
how does Vigabatrin work
irreversible inhibitor of GABA-T
it may also inhibit GABA transporter
how does Tiagabine work
inhibits GAT
allows more GABA to accumulate in synapse
what does GAT do
transporter that removes GABA from the synaptic cleft
which drug helps with fibromyalgia and anxiety
tiagabine
what is use dependent block
when drugs preferentially bind to channels that have been open
more firing, more block produced
why does use-dependent block work best at high rates
there isnt enough time between firing events for the drug to leave the channel
why is use dependent block okay for normal function
because at normal firing rates, the drug leaves the site before the next potential is initiated
what kind of drug is carbamazepine
use dependent voltage-gated-sodium-channel blocker
side effects of carbamazepine
severe motor/mental disturbances, hyponatremia (dilution of Na in blood)
bone marrow depletion for Asians
speeds up its own metabolism
which drug is great for partial seizures
vigabtrin
also tiagabine and carbamazepine
which drug is good for most forms of epilepsy but not absence serizures
carbamazepine
which drug is “add-on” therapy for partial seizures
tiagabine
what do T-type low voltage activated calcium channels do in the brain
play a central role in depolarizing neurons and creating AP in the brain`
what does ethosuximide do
blocks T-type calcium channels and prevents abnormal pattern of firing
what kind of seizures is treatable with ethosuximide
absense serizures
what makes absence seizures so different
there is a specific pattern of abnormal thalamocortical discharge (3Hz)
this normally happens in non-REM sleep, but it happens in absence seizures
what is common about AMPA and NMDA receptors
they are both excited by glutamate
what is the role of AMPA and NMDA in seizures
they play a central role in foci of seizures and spreading excitation to surrounding neurons
what is peramphanel
allosteric AMPA receptor inhibitor
how selective is peramphanel towards AMPA
very
how selective is peramphanel towards NMDA
none
what types of seizures is perampanel good for
many types except for absense
half life of perampanel
long, like 110hours
side effects of perampanel
aggression, hostility and violence
what aggrevates perampanel side effects
more in adolescents and alcoholics, also dose-dependent
