Anticonvulsants COPY

Question 1

Define epilepsy

Answer 1

A neurological condition causing frequent seizures

Question 2

Define seizure

Answer 2

Seizures are “sudden changes in behaviour caused by electrical hypersynchronization of neuronal networks in the cerebral cortex”

Question 3

Prevalence and incidence of epilspesy

Answer 3

Prevalence between 2-7% of the population Incidence increased over the last 30-40 years

Question 4

How is epilepsy diagnosed

Answer 4

Brain activity can be measured using: -Electroencephalography (EEG) -Magnetic resonance imaging (MRI)… more specific

Question 5

Two Main Seizure types

Answer 5

General Partial/focal

Question 6

Distinguish types of general seizures

Answer 6

Tonic-clonic Absence Tonic/atonic Myoclonic Status epilepticus

Question 7

Distingish partial/focal seizures

Answer 7

Simple Complex

Question 8

What are general seizures

Answer 8

Begins simultaneously in both hemispheres of brain

Question 9

Outline tonic-clonic seizure

Answer 9

loss of consciousness –> muscle stiffening (=tonic part) –> rhythmic jerking/twitching (=clonic part) –> deep sleep –> wakes up

Question 10

Outlin absence seizures

Answer 10

brief staring episodes with behavioural arrest

Question 11

Tonic/atonic seizure

Answer 11

sudden muscle stiffening/sudden loss of muscle control (similar but doesn’t have the phases in tonic-clonic)

Question 12

Outline myoclonic seizure

Answer 12

sudden, brief muscle contractions

Question 13

Outline status epilepticus

Answer 13

> 5 min of continuous seizure activity

Question 14

What are partial/focus seizues

Answer 14

Begins within a particular area of brain and may spread out

Question 15

Simple vs complex partial/focus seizure

Answer 15

Simple: retained awareness/consciousness Complex: impaired awareness/consciousness

Question 16

Activity at the glutamaterig synapse

Answer 16

1. VGSC open –> depolarization 2. VGKC opens –> repolarisation 3. Ca2+ influx through VGCC –> vesicle exocytosis 4. Glutatmate activates post synaptic receptors

Question 17

How are synpatic vesicles attached to presynaptic membrane for glutamate

Answer 17

Synaptic vesicle associated (SV2A) protein allows vesicle attachment to presynaptic membrane (a docking protein)

Question 18

Which receptors fores glutatmate bind to on the post-synaptic receptors

Answer 18

Glutamate activates excitatory post-synaptic receptors (e.g. NMDA, AMPA & kainate receptors)

Question 19

Outline the morphooy of the Na+ channel

Answer 19

Closed, open then inactive

Question 20

Outline mechanism of carbamezapine

Answer 20

Pharmacodynamics: Stabilises inactive state of Na+ channel –> reducing neuronal activity

Question 21

PK of carbamazapine

Answer 21

Enzyme inducer Onset of activity within 1 hour 16-30 hour half-life Basically all have fast onset, and long duration of action

Question 22

Indication of carbamazapine

Answer 22

Tonic-clonic seizures; partial seizures

Question 23

What are the very dangerous side effects of the carbamazepine

Answer 23

NB: potential severe side-effects (SJS (stephen-johnson syndrome) & TEN) in individuals with HLA-B*1502 allele Especially Han chinese

Question 24

What is the mechanism of lamotrigine action

Answer 24

Inactivates Na+ channels  reducing glutamate neuronal activity

Question 25

What is the PK of lamotrigine

Answer 25

Onset of activity within 1 hour 24-34 hour half-life (again, fast onset, long duration of action)

Question 26

Indication of lamotrigine

Answer 26

Tonic-clonic seizures; absence seizures

Question 27

Which drug blocks calcium channel

Answer 27

Ethosuximide

Question 28

Mechanism of Ethasuximide action

Answer 28

T-type Ca2+ channel antagonist --\> reduces activity in relay thalamic neurones (as opposed to dihydropyridines, which are used in treatment of HTN)

Question 29

Half life of ethasuximide

Answer 29

Long half life (50 hrs)

Question 30

What is the infication of ethosuximide

Answer 30

Absence seizures

Question 31

What drug inhibits SV2A

Answer 31

Levetiracetam

Question 32

What is the mechanism of levetiracetam

Answer 32

Binds to synaptic vesicle associated protein (SV2A)  preventing glutamate release

Question 33

PK of levetiracetam

Answer 33

Fast onset, half life 10hrs

Question 34

Infications of levetiracetam

Answer 34

Myoclonic

Question 35

What drugs block postsynaptic membane receptors

Answer 35

Topiramate

Question 36

What is the mechanism of topiramate action

Answer 36

Inhibits NMDA & kainate receptors Also affects VGSCs & GABA receptors

Question 37

What is the PK of topiramate

Answer 37

Fast-onset (1 hour); long half-life (20 hours)

Question 38

Indication of topiramate

Answer 38

Myoclonic seizures and neuropathic pain (more)

Question 39

Action at GABA receptor

Answer 39

DIFFERENCE TO OTHERS: there is always a small amount of GABA released as the brain is always in an inhibitory mode GABA can be released tonically & also following neuronal stimulation

Question 40

How does GABA get released and work on receptor

Answer 40

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)

Question 41

What is the acton of diazepam

Answer 41

GABA receptor, PAM --\> increases GABA-mediated inhibition POSITIVE ALLOSTERIC MODULATOR I.e. BDZs cannot activate the GABA-A receptor without the normal GABA ligand bindin

Question 42

What is the indication of diazepam in epilepsy + how it is administered in this case

Answer 42

Rectal gel - Fast-onset (within 15 min); half-life (2 hours) for Status epilepticus

Question 43

Function of sodium valproate

Answer 43

Inhibits GABA transaminase --\> increases GABA-mediated inhibition

Question 44

What does GABA transaminase do

Answer 44

Converts GABA-A to glutamate So with sodium valproate, a GAT inhibitor, you will have less Glu and more GABA :)

Question 45

What is the infication for sodium valproate

Answer 45

Indicated for ALL forms of epilepsy