32. Anticonvulsants Flashcards
What are seizures?
Sudden changes in behaviours caused by electrical hypersynchronisation of neuronal networks in the cerebral cortex
How is incidence of epilepsy changing?
Increasing
How can epilepsy be diagnosed?
- Electroencephalography (EEG)
* MRI
What are the different types of epilepsy seizures?
Generalised seizures • Tonic-clonic • Absence • Tonic/atonic • Myoclonic • Stutus epilepticus
Partial/focal seizures
• Simple
• Complex
What is a tonic-clonic seizure?
- Loss of consciousness
- Muscle stiffening
- Twitching
- Deep sleep
- Wakes up
Most common manifestation of epilepsy
What is an absence seizure?
Brief staring episodes with behavioural arrest (trance like)
What is a tonic/atonic seizure?
- Tonic - sudden muscle stiffening
* Atonic - sudden loss of muscle control
What is a myoclonic seizure?
Sudden, brief muscle contractions - lots of muscle movement
What is status epilepticus?
Over 5 minutes of continuous seizure activity
Most dangerous manifestation
What happens to awareness in a simple (partial) seizure?
Retained awareness
What happens to awareness in a complex (partial) seizure?
Impaired awareness
What happens in the brain during a generalised seizure?
Increased synchronisation simultaneously in both hemispheres of the brain
What happens in the brain during a partial/focal seizure?
- Begins within a particular area of the brain and may spread out
- Can progress into a generalised seizure
- Symptoms depend on where it occurs
Describe neurotransmission at a glutamatergic synapse
- AP arrives at pre-synaptic terminal
- Ca2+ influx through VGCCs
- Vesicle exocytosis
- Synaptic vesicle associated protein (SV2A) allows vesicle to attach to pre-synaptic membrane (docking protein)
- Glutamate is released into the synapse
- Glutamate activates excitatory post-synaptic receptors e.g. NMDA
What is carbamazepine and how does it work?
Voltage-gated sodium channel blocker • VGSCs open and enter an inactive state • Carbamazepine stabilises the inactive state of the Na+ channel - more likely to stay that way • Less neuronal depolarisation • Reduced neuronal activity
What is the onset activity and half-life of carbamazepine and lamotrigine?
Fast onset: 1 hour
Long half-life: 16-30 / 24-34 hours respectively
When is carbamazepine used?
- Tonic-clonic seizures
* Partial seizures
Why should you be careful when using carbamazepine?
- CYP450 inducer
- Reduces the activity of other drugs
- Potential severe skin side effects in individuals with a particular HLA-B allele (more common in oriental people)
What is Lamotrigine and how does it work?
Voltage-gated sodium channel blocker
• Directly inactivates Na+ channels
• Reduces glutamate neuronal activity (more selective for glutamatergic neurones)
What is Lamotrigine used for?
- Tonic-clonic seizures
* Absence seizures
How are the VGCCs found on the heart different to the ones found in the CNS?
- Heart: L-type - targeted by CCBs
* CNS: T-type
What is Ethosuximide, how does it work and what is its half-life?
- T-type VGCC antagonist
- Reduces activity in relay thalamic neurones
- Long half-life: 50 hours
What is ethosuximide used for?
Absence seizures
How does Levetiracetam and Topiramate affect glutamate exocytosis/receptors?
Levetiracetam
• Synaptic vesicle associated protein (SV2A) inhibitor
• Prevents and reduces glutamate exocytosis
Topiramate
• Glutamate receptor antagonist
• Inhibits NMDA and kainate receptors
(• also affects VGSCs and GABA receptors)
