Anti-convulsants Flashcards
What are the different types of seizures
General seizures = Affect the whole cortex; starts in both hemispheres at the same time
- Tonic-clonic seizure
- Absence seizure
- Tonic-atonic seizure
- Myoclonic seizure
- Status epilepticus
Partial seizures = Affect one part or paticular area of the brain and may spread out.
Describe the symptoms for tonic-clonic seizure
Loss of consciousness Muscle stiffness Jerking/twitching Deep sleep Wakes up
What are the symptoms of an absence seizure?
Brief staring episodes with behaviour arrest (loss of consciousness as well)
Losing muscle tone and falling over is also possible
What are the symptoms of a tonic-atonic seizure?
Sudden muscle stiffening and losing control
There is no muscle spasm/twitching so no clonus
What are the symptoms of a myoclonic seizure?
Sudden, brief muscle contractions
Jerking movements which are involuntary but are briefer than tonic/clonic seizures
What is status epilepticus?
More than 5 minutes of continuous seizure activity (it is basically multiple seizure after another without recovery in between)
This is the most dangerous type of seizure
What is a partial focal seizure what is the difference between a simple and a complex partial seizure
A partial seizure is a seizure which begins in a particular area of the brain and my spread out.
Simple = no impaired awareness and/or consciousness
Complex= impaired awareness and/or consciousness
Describe glutamatergic neurotransmission
- Voltage-gated Na+ channel (VGSC) opens = membrane depolarisation
- Voltage-gated K+ channel (VGKC) opens = membrane repolarisation
- Ca2+ influx through voltage-gated calcium channels (VGCCs)
- Synaptic vesicle associated (SV2A) protein allows vesicle attachment to presynaptic membrane for exocytosis
- Glutamate activates excitatory post-synaptic receptors
a. NMDA, AMPA & kainite receptors
What are the anti-epileptic drugs affecting glutamatergic neurotransmission?
Carbamazepine Lamotrigine Ethosuximide Levetiracetam Topiramate
What do the AEDs affecting glutamatergic neurotransmission have in common =
Fast onset of activity and long duration of action due to their long half-lives
How does carbamazepine work
Stabilises inactive state of Na+ channel
This is good as it causes use-dependency blockade meaning that it only blocks the nerve conduction when the neurones are firing excessively (i.e. during a seizure) and so the drugs inhibit seizures without affecting normal cognitive function
What are the indications of carbamazepine?
Tonic-clonic seizures and partial seizures
Note: In patients with the HLA-B+1502 polynorphism carbamazepine is dangerous;
Also carbamazepine is an enzyme inducer so need to be carefully monitored as drug-drug interactions can occur
How does lamotrigine work
Inactivity of Na+ channels –> less neuronal glutamate neuronal activity. Again use-dependant so good as it does not affect normal cognitive function as much while greatly inhibiting seizures.
What are the indications of lamotrigine
Tonic-clonic seizures and absence seizures
How does ethosuximide work?
T-type Ca2+ channels antagonist –> reduces activity in relay thalamic neurons (VGCC antagonist)
If ethosuximide affects voltage gated calcium channels how come it does not have as much effects in the vasculature?
Ethosuximide is selective for T-type Ca2+ channels. In the vasculature the voltage gated calcium channels are L-type channels which ethosuximide does not bind to.
What are the indications of ethosuximide
Absence seizures
How does levetiracetam work
Binds to synaptic vesicle associated protein (SV2A) preventing glutamate release
What are the indications of levetiracetam
Myoclonic seizures
How does topiramate work
It inhibits the action of glutamate by inhibiting NMDA and kainate receptors
Also affects VGSCs and GABA receptors
It isn’t really selective
What are the indications of topiramate
Myoclonic seizures
Although topiramate is mainly used for neuropathic pain more not epilepsy as much
Describe GABAergic neurotansmission
- GABA can be released tonically & also following neuronal stimulation
- GABA activates inhibitory post-synaptic GABA-A receptors
- GABA-A receptors are chloride (Cl-) channels => membrane hyperpolarisation
- GABA is taken up by GAT & metabolised by GABA transaminase (GABA-T)
What drugs affect the GABAergic neurotransmission to treat epilepsy
Diazepam and sodium valproate
How does Diazepam work?
Diazepam is an positive allosteric modulator (PAM) = it enhances GABA activity once GABA is bound to the GABA-A receptor
What are the pharmacokinetics of Diazepam?
Rectal gel
Fast-onset (within 15 minutes)
Half-life 32 h
What are the indications of diazepam?
Used for very serious epilepsy - status epilepticus as it has such a fast onset of 15 mins
How does sodium valproate work?
Sodium valproate inhibits GABA-T inhibiting GABA breakdown => increasing GABA mediated inhibition - also GABA-T produces GABA into Glutamate so has valproate has a dual effect by also reducing Glutamate produced => reducing Glutamate mediated excitation
OVERALL => Increased inhibition by inhibiting GABA breakdown and inhibiting Glutamate production from GABA breakdown
What are the pharmacokinetics of sodium valproate?
Fast onset
Half life = 12h (reasonably long)
What are the indications of sodium valproate
ALL forms of epilepsy
Only drug in this list which is indicated for tonic-atonic seizures.
