Chapter 13: Antiseizure Drugs

Question 1

seizures are caused by ___ in the brain, so the treatment for them is to ___

Answer 1

irregular electrical activity, reduce electrical activity

Question 2

___ is the primary excitatory NT in the CNS

Answer 2

glutamate

Question 3

___ is the primary inhibitory NT in the CNS

Answer 3

GABA

Question 4

if we consider neuronal circuits to exist in a balance of excitation and inhibition, a disturbance in this balance can lead to excessive activity which can lead to ___

Answer 4

seizures

Question 5

the irregular AP of seizures disrupts CNS signalling and can lead to ___, ___, ___ or ___

Answer 5

unconsciousness, convulsions, confusion or altered awareness

Question 6

blocking Na and Ca ion channels on the PRESYNAPTIC neuron has what effect on activity?

Answer 6

prevents glutamate release and lowers activity

Question 7

blocking Na and Ca channels on the POSTSYNAPTIC neuron has what effect on activut?

Answer 7

reduces excitability of the postsynaptic neuron and lowers activity

Question 8

what is the effect of increasing K channel efflux on activity?

Answer 8

more K out gives hyper polarization which reduces excitability

Question 9

what is the effect of targeting synaptic fusion proteins (SV2A) on activity?

Answer 9

reduces fusion of NT vesicles with presynaptic membrane, inhibiting release and lowering activity

Question 10

besides lowering excitability signals, we can also enhance ____ signals to reduces seizures

Answer 10

inhibitory

Question 11

we can increase the inhibitory output of postsynaptic neuron by doing what 3 things concerning GABA?

Answer 11

1. activate GABA A receptor
2. preventing GABA reuptake
3. preventing GABA metabolism

Question 12

what needs to be inhibited to reduce GABA re-uptake at from the synapse?

Answer 12

GAT-1 transporter

Question 13

what needs to be inhibited to reduce GABA metabolsim>

Answer 13

GABA transaminase

Question 14

___ and ___ are examples of voltage gated Na channel blockers

Answer 14

carbamazepine, phenytoin

Question 15

Na channels blockers bind to the ___ configuration and prevent the channel from ___

Answer 15

inactive; retiring to its resting state

Question 16

what types of neurons are most susceptible to Na channel blockers?

Answer 16

those which are more active and spend more time at depolarized membrane potentials (those that cause seizures)

Question 17

blocking Na channels uses 2 types of blocks, what are they and how do they work?

Answer 17

1. use-dependent block: most active get blocked

2. voltage-dependent block: most depolarized get blocked

Question 18

what is important about Na channel blockers having more selectivity for overactive neurons?

Answer 18

preserves normal neuronal function of other neurons and maintains na channel functions in other parts of the body, such as the heart

Question 19

carbamazepine and phenytoin are ___ inducers

Answer 19

CYP

Question 20

phenytoin is highly ____

Answer 20

protein bound

Question 21

most drugs follow first order kinetics, where a ____ of drug is removed per unit time

Answer 21

constant fraction

Question 22

in zero order kinetics, a constant ___ of drug is removed per unit time

Answer 22

quantity

Question 23

when phenytoin levels in the blood rise too high, the ____ is reached and the kinetics switch from 1st to ___ order

Answer 23

max capacity of liver to metabolize the drug; 0

Question 24

what is a consequence of phenytoin stitching over to 0th order at high doses?

Answer 24

even small increases in dose may cause large changes in serum drug concentrations and can lead to ADR very quickly

Question 25

the most common ADR observed with Na channel blockers result from reduced ____

Answer 25

neuronal transmission

Question 26

with high doses or Na channel blockers, ___ can occur due to reduced neuronal transmission in the CNS

Answer 26

sedation

Question 27

what are some ADR of Na channel blockers?

Answer 27

1. visual disturbances (eye movement and double vision) 2. dizziness 3. ataxia 4. sedation 5. rare hypersensitivity reactions

Question 28

there is a relatively rare but important hypersensitivity reaction to phenytoin and other structurally similar drugs (carbemazepine), what is it called and what does it look like?

Answer 28

DRESS; drug rash with eosinophilla and systemic symptoms

Question 29

aside from DRESS; what are some other hypersensitivity reactions that can be seen w/ Na channel blockers?

Answer 29

rash, fever, agranulocytosis

Question 30

gabapentin was originally developed as a _____mimetic, however, it does not bind to the receptor or any other inhibitory receptor in the CNS at any relevant dose; however it is able to reduce ___

Answer 30

GABA; seizures

Question 31

gabapentin works by modulating the presence of ___ channels on membrane surface

Answer 31

Ca

Question 32

when gabapentin binds to the ___subunit of the Ca channel, what happens to the channel;?

Answer 32

alpha 2 delta; remains internalized, not trafficking back to the membrane like it normally would

Question 33

how does gabapentin preventing Ca channel trafficking to the membrane affect seizures?

Answer 33

less Ca channels means less Ca into neuron, leading to less NT release and reduced excitability

Question 34

gabapentin relies on a ___ for GI absorption

Answer 34

transporter

Question 35

how can the amount of gabapentin become saturated?

Answer 35

if the transporter becomes saturated

Question 36

gabapentin can be used to treat seizures, but is not the most effective; it is used mostly in the management of ___ where Ca channels appear upregulated

Answer 36

neuropathic pain

Question 37

ADR of gabapentin include :

Answer 37

drowsiness, dizziness, ataxia, tremor, headache

Question 38

retigabine is a ____ of K channels

Answer 38

positive allosteric modulator

Question 39

what is the effect of retigabine on seizures?

Answer 39

increase the efflux of K, causing hyper polarization, reducing excitability

Question 40

what are the ADR of retigabine?

Answer 40

drowsiness, dizziness, blurred vision, confusion

Question 41

what is the MOA of Levetiracetam for management of seizures?

Answer 41

bind to SVA 2 to prevent fusion of NT (glutamate) vesicles to presynaptic membrane, preventing their release and reducing activity

Question 42

does levetiracetam have hepatic metabolism? what is the effect of this?

Answer 42

no; results in few drug-drug interactions

Question 43

the majority of Levetiracetam is excreted in what form by what route?

Answer 43

unchanged; urine

Question 44

what are the ADR of Levetiracetam?

Answer 44

sedation, ataxia, dizziness

Question 45

barbiturates are more commonly used as ___ rather than sedatives

Answer 45

anti-seizure

Question 46

it is though that barbiturates may have additional mechanisms to managing seizures (besides Cl reducing activity), what are they?

Answer 46

may involve ca channels and/or AMPA receptors to further educe activity

Question 47

what is the MOA of Tiagabine?

Answer 47

inhibits the GAT-1 transporter, allowing GABA to remain in the synapse longer and prolongs the inhibitory effects of the GABA receptor

Question 48

Give 2 reasons drug-drug interactions may be high in Tiagabine

Answer 48

1. highly protein bound | 2. metabolized by CYP3A4, which metabolized most drug

Question 49

what are some ADR of Tiagabine?

Answer 49

dizziness, ataxia, drowsiness, tremor, confusion

Question 50

what is the MOA of Vigabatrin?

Answer 50

GABA transaminase inhibitor (blocks GABA metabolism)

Question 51

what allows Vigabatrin to have a long duration of action?

Answer 51

it binds reversibly to GABA-T

Question 52

Vigabatrin is structurally similar to ___

Answer 52

GABA

Question 53

what is a unique ADR of Viagabatrin? How serious is it?

Answer 53

may cause retinal dysfunction due to loss of GABA-T in retina. The vision loss is not substantial, but is irreversible

Question 54

t/f the effectiveness of anti-seizure drugs often outweighs the not knowing the MOA

Answer 54

t

Question 55

Valproate/ valproic acid is used in the treatment of ___ and __

Answer 55

seizures and mood disorders

Question 56

valproate has many drug interactions, including with __-and __

Answer 56

phenytoin and phenobarbital

Question 57

what are 2 common ADR of valproate?

Answer 57

significant weight gain and GI upset

Question 58

Topiramate likely acts on ___, ___ and ___ to reduce activity

Answer 58

Na channels, GABA receptors and glutamate receptors

Question 59

what are some ADRs of Topiramate?

Answer 59

impaired cognitive function, dizziness, weight loss