Anticonvulsants and anti-epileptic drugs Flashcards
Define epilepsy
Tendency for recurrent, unprovoked seizures
Define seizure
sudden changes in behaviors characterised by electrical hyperchronisation of neuronal networks in the cerebral cortex
Types of seizures
Generalised
Partial/Focal
Define generlaised seizure
a seizure manifesting itself in both hemispheres
Define partial/focal seizure
a seizure originating from a discrete brain area in one hemisphere, has the potential to spread and develop into a global seizure
State the types of global seizures and what they’re charcterised by
Tonic-clonic = loss of consciousness -> muscle stiffening -> rapid jerky/twitching movements -> deep sleep -> awakes (with no recollection)
Absence = brief staring episodes and behavioural arrest
Tonic/atonic = sudden muscle rigidity/relaxation
Myoclonic = sudden brief muscle contractions
Status epilepticus = state of CONTINUOUS seizure activity for >5 mins
State the types of partial seizures and what they’re charcterised by
Simple = no impairment in awareness/consciousness Complex = impaired awareness/consciousness
2 most common types of central neurotransmission
Gluatminergic = excitatory GABA = inhibitory
Describe normal glutaminergic transmission
Depolarisation of presynaptic neurone
opening of VGSC, Na+ inlfux
opening of VGKC, K+ efflux
Opening of VGCC at synapse, Ca2+ influx
Stimulation of exocytosis of gluamate-containing vesicles
Docking at presynaptic membrane by SV2A docking protein
Glutamate binds to excitatiry NMDAR and Kainate-R on postsynaptic membrane
Depolarisation of postsynaptic neurone
Describe normal GABAergic transmission
GABA synthesised from GLU
Exocytosis and binding to inhibitory GABAAR
Cl- influx and hyperpolarisation
Reuptaken by GAT (GABA transporter) by presynaptic
Reuptaken by support cells and broken down to GLU by GABA-T (?GABA transaminase)
Examples of VGSC blockers
Carbamazepine, Lamotrigine
Carbamazepine MOA, PK
Stabilises inactive state of VGSC, reducing depol
ENZYME INDUCER
fast onset <1hr
long t1/2
Lamotrigine MOA, PK
Inactivates VGSC, reduced glutaminergic transmission
fast onset <1hr
long t1/2
Principles of anticonvulsant therapy
Inhibit excitatory central Glutaminergic transmission
Stimulate inhibitoy central GABAergic transmission
Types of anticonvulsant drug groups
Inhibit excitatory central Glutaminergic transmission: VGSC blockers VGCC blockers docking protein inhiitors Glutamate receptor inhibitors
Stimulate inhibitoy central GABAergic transmission
GABAAR agonists
GABA-T inhibitors
Example of VGCC blocker
Ethosuximide
Ethosuximide MOA, PK
T-type CC antagonist, reducing exocytosis of glu in relay thala mic neurones
long t1/2 50hrs
Example of docking protein inhibitor
Levetiracetam
Levetiracetam MOA, PK
binds to SV2A docking protein preventing exocytosis
fast onset <1hr, t1/2 shorter 10hrs
Example of glutamate receptor blockers
Topiramate
Topiramate MOA, PK
NMDA-R + Kainate-R antagonist (also affects VGSC + GABAAR)
fast onset <1hr, long t1/2
Example of GABAAR agonist
Diazepam
Diazepam MOA, PK
GABAAR PAM (positive allosteric mediator as binds to BDZ receptor), increases frequency of Cl- channel opening and reciprocal potentiation of GABA PR gel, fast onset 15mins, short t1/2 2hrs
Example of GABA-T inhibitor
(sodium) Valproate
Valproate MOA, PK
Inhibits GABA-T, increases synaptic [GABA]
fast onset <1hr, long t1/2
USED IN ALL TYPES OF EPILEPSY
Anticonvulsants used in tonic-clonic seizures
Carbamzepine
Lamotrigine
Valproate
Anticonvulsants used in absence seizures
Ethosuximide
Lamotrigine
Valproate
Anticonvulsants used in tonic/atonic seizures
Valproate
Anticonvulsants used in myoclonic seizures
Levetiracetam
Topiramate
Valproate
Anticonvulsants used in status epilepticus
Diazepam (due to fast onset)
Anticonvulsants used in simple/complex partial seizures
Carbamazepine
Levetiracetam
Lamotrigine
Valproate
Why are anticonvulsants very convenient for epilepsy patients?
Can be taken orally
Fast absorption in all (<1hr)
Long t1/2 therefore can be taken once a day
Factors affecting anticonvulsant prescription
Risk vs benefit
Specific anticonvulsant to match seizure type
usually keep on 1
Careful with drug interactions (eg carbamezapine is ENZYME INDUCER)
Previous effectiveness
Pharmacodynamic/pharmacokinetic factors
