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Summary Seizures and epilepsy

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summary of anticonvulsants in therapy for epilepsy and seizures

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  • May 4, 2024
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  • 2023/2024
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Seizures+Epilepsy
Causes of seizures
1. Imbalance between excitatory and inhibitory postsynaptic potential
 Excitatory: glutamate
 Inhibitory: GABA
 More excitatory postsynaptic potential causes seizures
2. Alterations in ion channel function
 Mutations in genes encoding ion channels
 Particularly Na+ and K+ channels
 Changes in ion function affects the spread of electrical signals
 Increased Na+ and Ca2+ causes seizures
3. Paroxysmal depolarization
 Sudden shift in the electrical charge across a neuron’s membrane
 Towards a more positive state
 Increasing the chance of depolarization
 Threshold is easier to reach
 Causing increased action potentials and electrical activity
How do we treat seizures?
Anticonvulsants: antiseizure medication

4 types of anticonvulsants
 Na+ channel inhibitors (category 1 e.g., valproate, phenytoin and carbamazepine)
 Ca2+ channel inhibitors (e.g., gabapentin and pregabalin)
 Enhanced GABA mediated inhibition (valproate, BZDs, levetiracetam)
 Glutamate receptor inhibitors (e.g., lamotrigine)

MOA Na+ channel inhibitors
 Blocks voltage gated sodium ion channels
 Prevents depolarization of the neuron
 Reducing the chance of an action potential forming
 Reducing the likelihood of abnormal electrical activity associated with seizures
 Stabilising them in the inactive state.
 During a seizure there can be an increased influx of sodium ions.
MOA of Ca2+ channel inhibitors
 During a seizure there can be an excessive influx of calcium ions into the neuron
 Causing an increased release of neurotransmitter across the synapse
 Causing increased firing of action potentials at the postsynaptic neuron
 Blocking calcium ion channels, you reduce the entry of calcium ions into the neuron
 Helps modulate the neurotransmitter release and stabilise neuronal membranes
MOA GABA enhanced mediated inhibitors work?
 GABA is the major inhibitory neurotransmitter in the brain.
 It binds to GABA-A receptors on neurons
 Leading to an influx of chloride ions and hyperpolarization of the neuron.
 Hyperpolarization inhibits neurons from firing.
 Modulating the imbalance of inhibitory and excitatory potentials

, MOA glutamate receptor inhibitors?
 act on the glutamatergic system in the brain
 glutamate is the primary excitatory neurotransmitter in the CNS
 It acts by blocking NMDA receptors
o these are inotropic glutamate receptors
o So by inhibiting these you reduce excessive excitatory neurotransmission.
o This channel is blocked by magnesium ions.
 They can also modulate AMPA receptors whicha re another glutamate receptor.
o Depending on the specific drug they can enhance or inhibit AMPA receptor
function.
ANKI TO UPLOAD:
What is sudep?
 sudden unexpected death in epilepsy
 unknown cause but likely complication from epilepsy
How do we diagnose epilepsy?
- establish paroxysmal event was actually a seizure and not something else
- epilepsy is spontaneous and recurrent
- good history and a witness is useful
- diagnosis should be made by a specialist
- no single diagnostic tool
- not one type of epilepsy
- blood test: infection cause
- ECG: cardiac cause
- Legal or illicit drug use
- Many common drugs lower threshold? Taking any
- Overdose on any drugs
- Description of the attack
Other causes of seizures that’s not epilepsy
- Head injury
- Infection
- Biochemical imbalance e.g. hyponatraemia
- Migraines
- Syncope (faining can cause limb shaking)
- Encephalitis (can get seizures but if you treat it then they will go)
- Non-epileptic attack disorder

Types of seizure
- Focal seizure: partial seizures, from an area in the brain
o Either retained: patient knows whats going on
o Or impaired: unconscious
- Tonic clonic
o Tonic: sudden stuffness of legs, diaphragm and arms
o Clonic: twitching or jerking
- Absence: brief lapses of consciousness, like staring into space, common in children
- Myoclonic: brief shock like jerks, limb jerming
- Atonic: sudden loss of strength, person may fall

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