anticonvulsants

Question 1

describe neurotransmission at glutamatergic synapse (increases brain activity, so suppressed by epileptic treatments)

Answer 1

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

Question 2

3 types of ionotropic glutamate excitatory post-synaptic receptors

Answer 2

NMDA, AMPA, kainate

Question 3

2 examples of voltage-gated Na+ channel blockers

Answer 3

carbamezepine, lamotrigine

Question 4

pharmacodynamics of carbamezepine: how it works

Answer 4

stabilises inactive state of Na+ channel -> prevents Na+ channel activity -> reduces glutamatergic synapse activity -> membrane depolarisation-> reduces neuronal activity

Question 5

pharmacokinetics of carbamezepine: onset time and half-life

Answer 5

enzyme inducer, onset within 1 hour (reasonably fast), 16-30 hour half-life (fairly long)

Question 6

what seizures is carbamezepine used to treat

Answer 6

tonic-clonic seizures, partial seizures

Question 7

when would carbamezepine exhibit severe side-effects

Answer 7

if patient has HLA-B1502 allele (causes severe skin conditions)

Question 8

pharmacodynamics of lamotrigine: how it works

Answer 8

inactivates Na+ channels -> prevents Na+ channel activity -> reduces glutamatergic synapse activity -> membrane depolarisation -> reduces neuronal activity

Question 9

pharmacokinetics of lamotrigine

Answer 9

onset within 1 hour, 24-34 hour half-life (very similar to carbamazepine, and safer during pregnancy)

Question 10

what seizures is lamotrigine used to treat

Answer 10

tonic-clonic seizures, absence seizures

Question 11

example of voltage-gated Ca2+ channel blocker

Answer 11

ethosuximide

Question 12

pharmacodynamics of ethosuximide: how it works

Answer 12

T-type Ca2+ channel antagonist (present in pacemaker cells and CNS), reducing activity in glutamatergic relay thalamic neurones

Question 13

pharmacokinetics of ethosuximide: onset and half-life

Answer 13

fairly fast onset, long half-life (50 hours)

Question 14

what seizure is ethosuximide used to treat

Answer 14

absence seizures

Question 15

2 examples of drugs which inhibit glutamate exocytosis and receptors

Answer 15

levetiracetam, topiramate

Question 16

pharmacodynamics of levetiracetam: how it works

Answer 16

binds to synaptic vesicle associated (SV2A) protein, preventing glutamate release

Question 17

pharmacokinetics of levetiracetam: onset and half-life

Answer 17

fast onset (1 hour), half-life of 10 hours (smaller duration)

Question 18

what seizure is levetiracetam used to treat

Answer 18

myoclonic seizures

Question 19

pharmacodynamics of topiramate: how it works

Answer 19

inhibits NMDA and kainate receptors, as well as affecting voltage-gated Na+ channels and GABA receptors (also treats neuropathic pain)

Question 20

pharmacokinetics of topiramate: onset and half-life

Answer 20

fast onset (1 hour), long half-life (20 hours)

Question 21

what seizure is topiramate used to treat

Answer 21

myoclonic seizures

Question 22

describe neurotransmission at GABAergic synapse (decreases brain activity, so enhanced by epileptic treatments)

Answer 22

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

Question 23

when is GABA released

Answer 23

tonically, as well as following neuronal stimulation

Question 24

pharmacodynamics of diazepam (benzodiazepines): how it works

Answer 24

increases GABA-mediated inhibition

Question 25

pharmacokinetics of diazepam: administration, onset and half-life

Answer 25

rectal gel: fast onset (<15 minutes) and half-life of 2 hours (very short); can be given orally

Question 26

what seizure is diazepam used to treat

Answer 26

status epilepticus (very fast onset when given rectally)

Question 27

pharmacodynamics of sodium valproate: how it works

Answer 27

inhibits GABA transaminase so increases GABA-mediated inhibition and prevents formation of glutamate

Question 28

pharmacokinetics of sodium valproate

Answer 28

fast onset (1 hour) and half-life of 12 hours (relatively long)

Question 29

what seizures is sodium valproate used for

Answer 29

all forms of epilepsy (can be used in status epilepticus)

Question 30

pharmacological treatment for tonic-clonic seizures

Answer 30

carbamazepine, lamotrigine, valproate

Question 31

pharmacological treatment for absence seizures

Answer 31

ethosuximide, lamotrigine, valproate

Question 32

pharmacological treatment for tonic/atonic seizures

Answer 32

valproate

Question 33

pharmacological treatment for myoclonic seizures

Answer 33

levetiracetam, valproate, topiramate

Question 34

pharmacological treatment for status epilepticus

Answer 34

diazepam

Question 35

pharmacological treatment for tonic simple and complex partial/focal seizures

Answer 35

carbamazepine, lamotrigine, levetiracetam, valproate