33: Anti-Convulsants Flashcards
What is Epilepsy?
•A neurological condition causing frequent seizures
What is a seizure?
sudden changes in behaviour caused by electrical hypersynchronization of neuronal networks in the cerebral cortex
How can Epilepsy be diagnosed?
•Brain activity can be measured using:
- Electroencephalography (EEG)
- during seizures
- Magnetic resonance imaging (MRI)
- to see form underlying cuase of Epilepsy
What are the two main categories of seizures in regards to affected brain area?
- General Seizure
- Begins simultaneously in both hemispheres of brain
- Partial Seizure
- Begins within a particular area of brain and may spread out
What is a partial seizure?
Begins within a particular area of brain and may spread out
What is a general seizure?
Begins simultaneously in both hemispheres of brain
What are the different types of general seizures?
- Tonic Clonic
- Absence
- Tonic/atonic seizure
- Myolclonic
- Status epilepticus
What are the different types of partial or focal seizures?
- Simple: retained awareness/consciousness
- Complex: impaired awareness/consciousness
What are the characteristics of a tonic-clonic seizure?
Normally relatively clear pattern
- loss of consciousness
- muscle stiffening
- jerking/twitching
- deep sleep
- wakes upp
What are the characteristics of an absence seizure?
brief staring episodes with behavioural arrest
What are the characteristics of a tonic/atonic seizure?
- Tonic/atonic seizures
* sudden muscle stiffening/sudden loss of muscle control
What are the characteristics of a Myoclonic Seizure?
sudden, brief muscle contractions
What is a Status Epilepticus?
> 5 min of continuous seizure activity
Explain the release of Glutamate from a Glutaminergic Neuron
- AP–> Na+ influx
- K+ efflux
- Ca2+ influx
- vesicle exocitosis
- SV2A neeeded! (Synaptic Vesicle Associsated Protein)
Explain how Na+ channels can be a target in the treatment of Epilepsy and Name examples
If Na+ channels of glutamate signaling blocked–> Less exitory glutamate signals
E.g.
- Carbamazepine
- Lamotrigine
What is the MOA of Carbamazepine?
What is its indication?
Stabilises inactive state of Na+ channel –> reducing neuronal activity
- Used in
- Tonic-clonic seizures
- partial seizures
What are the Pharmacokinetic properties of Carbamazepine?
- Enzyme inducer
- Onset of activity within 1 hour
- 16-30 hour half-life
What are the pharmacokinetic propterties of anti-convulsants?
Overally: almost all have a relatively fast onset of action (about 1 h) and a lont duration of action
What is the MOA and indication of Lamotrigine?
It Inactivates Na+ channels –> reducing glutamate neuronal activity
Used in
- Tonic-clonic seizures; absence seizures
Which anti-convulsant drug targets the Voltage gated calcium channels of a glutaminergic neuron?
Ethosuximide
What is the MOA and indiction for the use of Ethosuximide?
It is a
T-type Ca2+ channel antagonist –> reduces activity in relay thalamic neurones
- used in absence seizures
What is the MOA and indication of Levetiracetam?
•Binds to synaptic vesicle associated protein (SV2A) –> preventing glutamate release
- Used in Myoclonic Seizures
What is the MOA and indication of use of Topiramate?
•Inhibits NMDA & kainate receptors
•Also affects VGSCs & GABA receptors
- Used in Myoclonic Seizures
When is GABA released?
1.GABA can be released tonically & also following neuronal stimulation
How is GABA removed from the Synapse?
GABA is taken up by
- GAT
- & metabolised by GABA transaminase (GABA-T) (to glutamate)
What is the MOA of Diazepam
GABA receptor PAM (=positive allosteric modulator) –> ® increases GABA-mediated inhibition (by increasing the affinitiy/efficycy of GABA on the GABA receptor
What ist the ROA and indication of the use of Diazepam in Epilepsy?
Used as rectal gel in status epilepticus
–> fast onset of action
What ist the MOA of Sodium Valproate?
Inhibits GABA transaminase –> increases GABA-mediated inhibition
What is the Indication of Sodium Valproate?
All forms of epilepsy
- fast onset, t1/2 12h
Which Drugs can be used in the treatment of a tonic-clonic seizure?
What are their MOA?
Sodium channels + Valporate
- Carbamazepine = stabelises inactive VGSC
- Lamotirgine = inactivates VGSC
Sodium Valproate = inhibition of GABAtransaminase
Which drugs can be used in treatement of an absence seizure?
What is their MOA?
Ethosuximide = T-type Ca2+ channel antagonist
Lamotrigine = inactivates VGSC
Valproate= GABA transaminase inhibitor
Which drug can be used in the treatment of Tonic/atonic seizures?
Valproate
Which drugs can be used in the treatment of Myoclonic Seizures?
Glutamate Binding + Release
- Levetiracetam = binds to SV2A and inhibits Glutamate release
- Topiramate= inhibits NMDA+ Kainate receptors
Valproate = GABA transaminase inhibior
Which drugs can be used in the treatment of Status epilepticus?
Diazepam
Which drugs can be used in the treatment of partial seizures?
Carbamazepine = stabelises inactive Na+ channels
Levetiracetam= Binds to SV2A –> inhibition of Glutamate release
Lamotrigine= inactivates VGSC
Valproate = GABA transaminase inhibitor
