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
-
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)
What drugs would you use for : Tonic-clonic seizures
Carbamazepine
Lamotrigine
Valproate
What drugs would you use for : Absence seizures
Ethosuximide
Lamotrigine
Valproate
What drugs would you use for :
Tonic/atonic seizures
Valproate
What drugs would you use for :
Myoclonic seizures
Levetiracetam Topiramate
Valproate
What drugs would you use for :
Simple partial
Complex partial
Carbamazepine Levetiracetam
Lamotrigine
Valproate
What drugs would you use for :
Status epilepticus:
Diazepam
what type of seizure has the following symptoms: sudden muscle stiffening
a) absence seizure
b) atonic seizure
c) tonic seizure
d) tonic clonic seizure
e) myoclonic seizure
c) tonic seizure
what type of seizure has the following symptoms: brief staring episodes w behavioral arrest
a) absence seizure
b) atonic seizure
c) tonic seizure
d) tonic clonic seizure
e) myoclonic seizure
a) absence seizure
Name the anticonvulsant that will increase the synaptic GABA levels
a) Ethosuximide
b) Diazepam
c) Carbamazepine
d) Lamotrigine
e) Valproate
e) Valproate
Which anticonvulsant would you prescribe for a patient suffering from atonic seizures ?
a) Ethosuximide
b) diazepam
c) Carbamazepine
d) Lamotrigine
e) Valproate
e) Valproate
