Anticonvulsants Flashcards
<p>What is epilepsy?</p>
<p>Epilepsy is a neurological condition causing frequent seizures.</p>
<p>What is a seizure?</p>
<p>Over-excitation due to too much glutamatergic activity</p>
<p>What is the prevalence and incidence of epilepsy?</p>
<p>Prevalence between 2-7% of the population – relatively common neurological condition. Incidence is increasing, and has been over the last 30-40 years.</p>
<p>How can epilepsy be diagnosed?</p>
<p>Brain activity can be measured using:
- Electroencephalography (EEG)
- Magnetic resonance imaging (MRI)
In an epileptic seizure, the waveforms seen on an EEG have a much higher frequency. The EEG is a useful tool for diagnosing different types of epilepsy, and can be used with sensitivity and specificity.</p>
<p>What are the different types of seizures?</p>
<p>Tonic-clonic Absence seizures Tonic/atonic Myoclonic seizure Status epilepticus</p>
<p>What are the features of tonic-clonic seizures?</p>
<p>Loss of consciousness which leads to muscle stiffening, jerking/twitching and deep sleep before they wake up – THIS IS THE MOST COMMON MANIFESTATION OF EPILEPSY.
</p>
<p>What are the features of absence seizures?</p>
<p>Brief staring episodes with behavioural arrest.
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<p>What are the features of tonic/atonic seizures?</p>
<p>Sudden muscle stiffening (tonic)/sudden loss of muscle control (atonic).
</p>
<p>What are the features of myoclonic seizures?</p>
<p>Sudden, brief muscle contractions – we see lots of muscle movement.
</p>
<p>What are the features of status epilepticus seizures?</p>
<p>Over 5 minutes of continuous seizure activity – THIS IS LESS COMMON BUT IS THE MOST DANGEROUS.</p>
<p>What are the two main categories of seizures?</p>
<p>Partial and generalised
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<p>What are the types of partial seizure?</p>
<p>Simple: Retained awareness/consciousness.
Complex: Impaired awareness/consciousness.
A partial seizure can progress into a generalised seizure. The symptoms are dependent on where it occurs.
</p>
<p>Describe transmission through a glutamatergic synapse</p>
<p>The action potential arrives at the presynaptic terminal.
Voltage-gated Na+ channel (VGSC) opens which leads to membrane depolarisation. Voltage-gated K+ channel (VGKC) opens leading to membrane repolarisation.
Ca2+ influx through VGCCs which results in vesicle exocytosis. Synaptic vesicle associated (SV2A) protein allows vesicle (containing glutamate) attachment to the presynaptic membrane (docking protein).
Glutamate is released into the synapse. Glutamate activates excitatory postsynaptic receptors (e.g. NMDA, AMPA and kainate receptors).
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<p>Name 2 VGSC blockers</p>
<p>Carbamazepine (tonic-clonic seizures and partial seizures)
Lamotrigine (tonic-clonic seizures and absence seizures)</p>
<p>How does carbamazepine work?</p>
<p>Carbamazepine stabilises the inactive state of the Na+ channel so it is more likely to remain in an inactive state which leads to reduced neuronal activity.</p>
<p>What are some things to bear in mind when using carbamazepine?</p>
<p>Because it is an enzyme inducer of the cytochrome P450 pathways, it reduces the activity of a number of other drugs.
Potential severe skin side effects (SJS and TEN) are seen in individuals with HLA-B*1502 allele.
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<p>How does lamotrigine work?</p>
<p>Lamotrigine directly inactivates Na+ channels which reduces glutamate neuronal activity. It has a fast onset of activity (within 1 hour), and a long half-life (24-34 hours). It is more selective for glutamatergic neurones.
</p>
<p>What is a VGCC?</p>
<p>The VGCCs are a large group of ion channels. L-type VGCCs are the ones that are found on the blood vessels and the heart – they are targeted by calcium channel blockers (used for treatment of hypertension). These channels are different to the channels found within the CNS (T-type VGCCs).
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<p>Name a VGCC blocker</p>
<p>Ethosuximide (absence seizures)</p>
<p>Describe how ethosuximide works</p>
<p>T-type Ca2+ channel antagonist which leads to reduces activity in relay thalamic neurones (prevents the propagation of the AP, leading to decreased neurotransmission).
It has a long half-life (50 hours).
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<p>Name two drugs that affect glutamate exocytosis and receptors</p>
<p>Levetiracetam (Myoclonic seizures)
| Topiramate (Myoclonic seizures)</p>
How does levetiracetam work?
Levetiracetam binds to synaptic vesicle associated protein (SV2A) which prevents and reduces glutamate exocytosis.
How does topiramate work?
Topiramate inhibits NMDA and kainate receptors and also affects VGSCs and GABA receptors. It affects a few receptors (so a bit of a ‘dirty drug’)
Describe neurotransmission of a GABAergic synapse.
You do not necessarily need excitation at the presynaptic terminal for GABA to be released – it is released often by itself. This is why GABA is the most active NT.
GABA can be released tonically. It can also be released following neuronal stimulation. GABA activates inhibitory postsynaptic GABA-A receptors.
GABA-A receptors are chloride (Cl-) channels. This leads to membrane hyperpolarisation.
GABA is taken up by the GAT transporter. GABA is then metabolised by GABA transaminase (GABA-T). GABA is broken down back into glutamate.
