Anticonvulsants Flashcards
what is meant by epilepsy ?
A neurological condition causing frequent seizures
What is meant by seizures ?
“sudden changes in behaviour caused by electrical hypersynchronization of neuronal networks in the cerebral cortex”
How would you diagnose epileptic patients?
Brain activity can be measured using:
- Electroencephalography (EEG)
- Magnetic resonance imaging (MRI)
compare between the 2 different seizure types in epilepsy?
a) General Seizures
b) Partial / Focal seizures
a) General Seizures
- begins simultaneously in BOTH hemispheres of brain
b) Partial / Focal seizures
- Begins within a particular area of brain and may spread out
What are the 5 types of seizure considered to be general seizures ?
a) Tonic-clonic seizures:
loss of consciousness –> muscle stiffening –> jerking/twitching –> deep sleep –> wakes up
b) Absence seizures:
brief staring episodes with behavioural arrest
(trans-like state)
c) Tonic/atonic seizures:
sudden muscle stiffening/sudden loss of muscle control
(no part before and after)
d) Myoclonic seizures:
sudden, brief muscle contractions
e) Status epilepticus: > 5 min of continuous seizure activity
(prolonged seizure activity)
What is the 2 types of seizure considered to be focal / partial seizures ?
What are the difference between the 2 types?
a) Simple: retained awareness/consciousness
b) Complex: impaired awareness/consciousness
Major drug target for epilepsy =
Glutmametergic synapses
major excitatory transmitter = glutamate
- -> causes increase in neuronal activity
- -> manifests as epileptic seizure
How does glutamate act as a major excitatory transmitter?
- Voltage-gated Na+ channel (VGSC) opens –> membrane depolarisation
- Voltage-gated K+ channel (VGKC) opens –> membrane repolarisation
- Ca2+ influx through voltage-gated calcium channels (VGCCs) –> vesicle exocytosis
a) Synaptic vesicle associated (SV2A) protein allows vesicle attachment to presynaptic membrane - Glutamate activates excitatory post-synaptic receptors (e.g. NMDA, AMPA & kainate receptors)
What are drugs that can be used for epilepsy?
via Glutamate inhibition method
- VGSC
a) Carbmazepine -IMP
Stabilises inactive state of Na+ channel –> reducing neuronal activity
- enzyme inducer
(used for Tonic-clonic Seizures + Partial Seizure)
b) Lamotrigine
Inactivates Na+ channels –> reducing glutamate neuronal activity
- VGCC Blockers
a) Ethosuximide
T-type Ca2+ channel antagonist –> reduces activity in relay thalamic neurones
(use for absence seizures) - Glutamate Exocytosis + receptor inhibitor (use for myoclonic seizures)
a) Levetiracetam
Binds to synaptic vesicle associated protein SV2A –> preventing glutamate release
b) Topiramate
- Inhibits NMDA & kainate receptors + also affects VGSCs & GABA receptors
Describe the characteristics of pharmacokinetics of the drugs used for epilepsy
- fast onset of activity
- long duration of action
LEARN ANTICONVULSANTS DRUG NAMES
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NOTE
L-type = latent
T-type = transiet
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Targeting Glutamatergic synapse
SUMMARY Of Pharmacology:
- VGSC antagonist: e.g Carbamazepine
- VGCC antagonist: Ethosuximide (T-type antagonist);
- SV2A inhibitor: Levetiracetam
- Glutamate receptor antagonist: Topiramate
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What are drugs that can be used for epilepsy?
via GABA enhancement method
- Diazepam
GABA receptor, PAM –> increases GABA-mediated inhibition
(*PAM = Positive Allosteric Modulator)
(used for status epilepticus) - given as rectal gel
- sodium Valporate
Inhibits GABA transaminase –> increases GABA-mediated inhibition
(used for all forms of epilepsy )
Describe the neurotransmission via the GABAergic synapse
- GABA can be released tonically & also following neuronal stimulation
- GABA activates inhibitory post-synaptic GABAA receptors
- GABAA receptors are chloride (Cl-) channels membrane hyperpolarisation
- GABA = taken up by GAT & metabolised by GABA transaminase (GABA-T)
