anticonvulsants Flashcards
anti-convulsants: recognise that anti-convulsant therapy is determined by the seizure type coupled with pharmacodynamics/pharmacokinetic properties of specific anti-convulsant drugs
describe neurotransmission at glutamatergic synapse (increases brain activity, so suppressed by epileptic treatments)
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 -> vesicle exocytosis -> glutamate activates excitatory post-synaptic receptors
3 types of ionotropic glutamate excitatory post-synaptic receptors
NMDA, AMPA, kainate
2 examples of voltage-gated Na+ channel blockers
carbamezepine, lamotrigine
pharmacodynamics of carbamezepine: how it works
stabilises inactive state of Na+ channel -> prevents Na+ channel activity -> reduces glutamatergic synapse activity -> membrane depolarisation-> reduces neuronal activity
pharmacokinetics of carbamezepine: onset time and half-life
enzyme inducer, onset within 1 hour (reasonably fast), 16-30 hour half-life (fairly long)
what seizures is carbamezepine used to treat
tonic-clonic seizures, partial seizures
when would carbamezepine exhibit severe side-effects
if patient has HLA-B1502 allele (causes severe skin conditions)
pharmacodynamics of lamotrigine: how it works
inactivates Na+ channels -> prevents Na+ channel activity -> reduces glutamatergic synapse activity -> membrane depolarisation -> reduces neuronal activity
pharmacokinetics of lamotrigine
onset within 1 hour, 24-34 hour half-life (very similar to carbamazepine, and safer during pregnancy)
what seizures is lamotrigine used to treat
tonic-clonic seizures, absence seizures
example of voltage-gated Ca2+ channel blocker
ethosuximide
pharmacodynamics of ethosuximide: how it works
T-type Ca2+ channel antagonist (present in pacemaker cells and CNS), reducing activity in glutamatergic relay thalamic neurones
pharmacokinetics of ethosuximide: onset and half-life
fairly fast onset, long half-life (50 hours)
what seizure is ethosuximide used to treat
absence seizures
2 examples of drugs which inhibit glutamate exocytosis and receptors
levetiracetam, topiramate
pharmacodynamics of levetiracetam: how it works
binds to synaptic vesicle associated (SV2A) protein, preventing glutamate release
pharmacokinetics of levetiracetam: onset and half-life
fast onset (1 hour), half-life of 10 hours (smaller duration)
what seizure is levetiracetam used to treat
myoclonic seizures
pharmacodynamics of topiramate: how it works
inhibits NMDA and kainate receptors, as well as affecting voltage-gated Na+ channels and GABA receptors (also treats neuropathic pain)
pharmacokinetics of topiramate: onset and half-life
fast onset (1 hour), long half-life (20 hours)
what seizure is topiramate used to treat
myoclonic seizures
describe neurotransmission at GABAergic synapse (decreases brain activity, so enhanced by epileptic treatments)
GABA released -> activates inhibitory post-synaptic GABA-A receptors (Cl- channels) -> membrane hyperpolarisation -> GABA taken up by GAT and metabolised by GABA transaminase (GABA-T) to glutamate
when is GABA released
tonically, as well as following neuronal stimulation
pharmacodynamics of diazepam (benzodiazepines): how it works
increases GABA-mediated inhibition
pharmacokinetics of diazepam: administration, onset and half-life
rectal gel: fast onset (<15 minutes) and half-life of 2 hours (very short); can be given orally
what seizure is diazepam used to treat
status epilepticus (very fast onset when given rectally)
pharmacodynamics of sodium valproate: how it works
inhibits GABA transaminase so increases GABA-mediated inhibition and prevents formation of glutamate
pharmacokinetics of sodium valproate
fast onset (1 hour) and half-life of 12 hours (relatively long)
what seizures is sodium valproate used for
all forms of epilepsy (can be used in status epilepticus)
pharmacological treatment for tonic-clonic seizures
carbamazepine, lamotrigine, valproate
pharmacological treatment for absence seizures
ethosuximide, lamotrigine, valproate
pharmacological treatment for tonic/atonic seizures
valproate
pharmacological treatment for myoclonic seizures
levetiracetam, valproate, topiramate
pharmacological treatment for status epilepticus
diazepam
pharmacological treatment for tonic simple and complex partial/focal seizures
carbamazepine, lamotrigine, levetiracetam, valproate
