L16 - epilepsy Flashcards
list the types of epilepsy
- generalised seizure (grand mal) -> tonic clonic seizures
- generalised seizures (petit mal) -> absent seizures
- partial seizures ( jacksonian epilepsy)
- status epilepticus
describe generalised seizure (grand mal)
tonic clonic seizure
sustained contraction of muscles (often along with respiration cessation) followed by waves of synchronous contractions
consciousness resumes after several minutes
describe generalised seizure (petit mal)
most common in children
absent seizures
not assoicated with motor fucntions but involves loss of attention for short period of time
describe partial seizures
muscle spasm in one digit / limb / side of body often spreading from one location to others
can be conscious
describe status epilepticus
when a grand mal seizure continus or repeats for a long period of time (30 mins)
can be life threatening due to repeated cessation of respiration
what is the EEG
a measure of summated changes in extracellular voltage caused by activity of many axons and synapses
recorded by attaching electrodes to scalp
measures brain activity in seizures
what can cause epilepsy
brain injury -> stoke / trauma can provide epileptic focus
infection -> can cause inflammation which provides epileptic focus
tumours
autoimmune disease -> can cause encephalitis which provides epileptic focus
idiopathic (most common)
explain the kindling experimental model foe epilepsy
- repetitive electtical / chemical stimulation of a small region of the brain (in an animal model)
initially the stimulation only excites the local area, but after repeating the stimulation several times the excitation spreads across the entire brain similarly to an epileptic fit
useful in studying anti-epileptics
what are the two main classes of drugs to treat epilepsy?
- drugs that enhance GAGA activity (BZDs, barbiturates, valproic acid, KBr)
- drugs that block VG Na/Ca channels in a use dependant manner - so that only repetitive nerve activity is blocked
where do barbiturates bind?
to inner foldings of the GABA(A) receptor pore (allosteric site)
function of barbiturates
bind to the allosteric site of GABA(A) opening the channel, and hold the channel open for longer allowing more Cl- to flow through
how is tolerance possible for Barbiturates?
upregulation of excitatory receptors
upregulation of CP450 enzymes in liver
where do BZDs bind
between the a and y subunit on GABA
explain mechanims of action of BZDs
positive modulators that increase agonist binding
- bind between the a and y subunits of GABA and increase the receptors affinity for GABA, increasing GABA binding and channel opening
when stage of epilepsy are BZDs given
during status epilepticus
usually too sedative for epilepsy prophylaxis
in epilepsy what is the route of administration of BZDs
anal suppositorys / IV
what are limitations of barbiturates in epilepsy
- low therapeutic index and can act in the absence of GABA - overdose could be fatal
suicide risk - tolerance through upregulation of excitatory receptors and P450 enzymes
limitations of BZDs in epilepsy
often too sedative for epilepsy prophylaxis
what effect does picrotoxin have?
blocks the GABA channel soo Cl- cant flow
promotes seizures
where does ethanol act
to enhance GABA(A) action
explains sedative effects of alcohol
explain use of KBr in epilepsy
bromide is more permeable through the GABA(A) channel than Cl-, and so enhances the inhibitory effect
KBr no longer used in humans due to its toxicity
first successful anti-epileptic
give examples of BZDs
diazepam
midalozam
give an example of a barbiturate
phenobarbital
describe the overall mechanism of use dependant Ca and Na channel blockers
in an inactivated state, part of the channel (inactivation gate) will bind to the open channel, blocking it
- use dependant channel blcokers can only bind to the channel when its open (as they bind within the channel)
- occasional APs and openings of the channel dont give the blocker much opportunity to enter and block the channel
- however repetitive APs and repetitive openings of the channel gives the drug many opportuities to enter the channel and block it
so the channel is only blocked with repetitive activity of the channel
give some examples of use dependant Na channel blockers
carbamazepine
phenytoin
how can tiagabin be used in epilepsy treatement
it is a GAT blocker, inhibiting GABA reuptake so increasing its concentration in the cleft and increasing receptor activation
how can vigabatrin be used as an anti-epileptic
it inhibits GABA aminotransferase, reducing GABA breakdown in the cleft
so increases [GABA] in cleft and increases GABA(A) activation
what two anti-epileptic drugs may trigger absent seizures in children
vigabatrin
tiagabin
what type of seizures do class 1 epileptics treat
tonic clonic
partial
temporal lobe seizures
what are the class 1 anti-epileptics
BZDs
barbiturates
Tiagabin
vigabatrin
what are the class 2 anti-epileptics and what type of seizures do they treat
use dependant VG Na / Ca blockers
tonic clonic
partial
temporal lobe seizures
what types of sezures are treated by the class 3 anti-epileptics
absent seizures only
give an example of a type 3 anti-epileptic and its mechanism
ethosuxamide
mechanism unknown, thought to be due to blockade of T-type VG Ca channels in thalamic neurones
(important in generation of rhythmic activity)
what types of seizures are class 4 anti-epileptics used to treat
tonic clonic and absent seizures
give 2 examples of class 4 anti-epileptics and their function
lamotrigine - use dependant Ca2+ blocker
sodium valproate -> mechanism not fully understood
combines weak use dependant Ca block and weak GABA transaminase block
what are the class 5 anti-epileptics
drugs that work by other mechanisms as anti-epileptics
give an example of a class 5 anti-epileptic
gabapentin -> interact with Ca2+ channel (in a different manner to blockers) inhibiting the channels activity and release of excitatory NTs
