Anticonvulsants Flashcards
(35 cards)
What is epilepsy?
- A neurological condition causing frequent seizures
- Seizures are “sudden changes in behaviour caused by electrical hypersynchronization of neuronal networks in the cerebral cortex”
Prevelance and Incidence of Epilepsy
- Prevalence between 2-7% of the population
- Incidence increased over the last 30-40 years
Diagnosis of Epilepsy
- Brain activity can be measured using:
- Electroencephalography (EEG)
- Magnetic resonance imaging (MRI)
Seizure types & Symptoms
General
- Tonic-clonic seizures: loss of consciousness -> muscle stiffening -> jerking/twitching -> deep sleep -> wakes up
- Absence seizures: brief staring episodes with behavioural arrest
- Tonic/atonic seizures: sudden muscle stiffening/sudden loss of muscle control
- Myoclonic seizures: sudden, brief muscle contractions
- Status epilepticus: > 5 min of continuous seizure activity
Focal/Partial
a) Simple: retained awareness/consciousness
b) Complex: impaired awareness/consciousness
General seizures
Begins simultaneously in both hemispheres of brain
-> 5 types
Epilepsy for more than 5 minutes
- Status epilepticus
- most dangerous type of seizure
- can be any type of seizure
Partial/focal seizures
Begins within a particular area of brain and may spread out
Glutaminergic synapse: 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) -> 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)
Name voltage gated Na+ channel blockers
Carbamazepine
Lamotrigine
Carbamazepine
Pharmacodynamics
- Stabilises inactive state of Na+ channel -> reducing neuronal activity
- doensn’t close the pore itself, just stabilises inactive state.
Pharmacokinetics
- Enzyme inducer
- lots of drug-drug interactions
- Onset of activity within 1 hour
- 16-30 hour half-life
Indications
- Tonic-clonic seizures; partial seizures
NB: potential severe side-effects (Steven Johnson Syndrome and TEN -> skin complications in individuals with HLA-B*1502 allele
Lamotrigine
Pharmacodynamics
- Inactivates Na+ channels -> reducing glutamate neuronal activity
Pharmacokinetics
- Onset of activity within 1 hour
- 24-34 hour half-life
Indications
- Tonic-clonic seizures; absence seizures
tends to be a better drug than carbamazepine, but also more expesive
Voltage-gated ion channels blockers
e.g. Ethosuximide
Pharmacodynamics
- T-type Ca2+ channel antagonist -> reduces activity in relay thalamic neurones
Pharmacokinetics
- Long half-life (50 hours)
Indications
- Absence seizures
Ethosuximide
Pharmacodynamics
- T-type Ca2+ channel antagonist -> reduces activity in relay thalamic neurones
Pharmacokinetics
- Long half-life (50 hours)
- reasonably fast onset of action
Indications
- Absence seizures
Name drugs targeting glutamate exocytosis and receptors
Levetiracetam
Topiramate
Name drugs targeting glutamate exocytosis and receptors
Levetiracetam
Topiramate
Levetiracetam
Pharmacodynamics
- Binds to synaptic vesicle associated protein (SV2A) -> preventing glutamate release
Pharmacokinetics
- Fast-onset (1 hour)
- half-life (10 hours)
Indications
- Myoclonic seizures
Topiramate
Pharmacodynamics
- Inhibits NMDA & kainate receptors
- Also affects VGSCs & GABA receptors
- > multiple targets
Pharmacokinetics
- Fast-onset (1 hour)
- long half-life (20 hours)
Indications
- Myoclonic seizures
- also used in treatment of some types of neuropathic pain
Glutaminergic synapse neurotransmission
- VGSC -> depolarisation
- VGKC -> repolarisation
- Ca2+ influx through VGCCs -> vesicle exocytosis
- SVA2 allows vesicle attachment to membrane
- Glutamate activates excitatory post synaptic receptor
Drugs acting on the glutaminergic synapse
- VGSC antagonist: e.g Carbamazepine, Phenytoin, Lamotrigine
- VGCC antagonist: Ethosuximide (T-type antagonist);
- SV2A inhibitor: Levetiracetam
- Glutamate receptor antagonist: Topiramate
=> correlates to transmission at. the glutaminergic synapse
=> prevent too much excitation
GABAergic Synapse neurotransmission
- 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 is taken up by GAT & metabolised by GABA transaminase (GABA-T)
NT secreted most is the brain?
GABA
Diazepam
Pharmacodynamics
- GABA receptor, PAM increases GABA-mediated inhibition
Pharmacokinetics
- Rectal gel - Fast-onset (within 15 min) -> this is very important
- half-life (2 hours)
Indications
- Status epilepticus
What is he only drug that is effective in status epilepticus?
Diazepam
Sodium Valproate
Pharmacodynamics
- Inhibits GABA transaminase -> increases GABA-mediated inhibition
Pharmacokinetics
- Fast onset (1h)
- half-life (12h)
Indications
- Indicated for ALL forms of epilepsy
