Anti-Seizure Drugs

Question 1

drugs that treat and prevent seizures ____ the likelihood of firing of neurons in various parts of the brain

Answer 1

• reduce

Question 2

a seizure is caused by the transient (ordered/disordered), (synchronous/asynchronous) rhythmic firing of whole populations of brain neurons

Answer 2

• disordered

- synchronous

Question 3

seizures are often referred to as an ____________ in the brain

Answer 3

• electrical storm

Question 4

___ seizures are localized to smaller regions in one hemisphere of the brain

Answer 4

• partial

Question 5

partial seizures are further defined as simple partial or complex partial depending on

Answer 5

• loss of consciousness

Question 6

generalized seizures affect which hemisphere

Answer 6

• both

Question 7

______ is a life-threatening medical emergency in which a seizure lasts for more than five minutes or in which two or more seizures occur within a five minute period without a return to normal status in between

Answer 7

• status epilepticus

Question 8

mutations in ion channels that do what can promote depolarization

importance of this

Answer 8

• promote Na+ or Ca2+ influx
• reduce K+ efflux
• reduce Cl+ influx
• what anti-seizure drugs act on

Question 9

_____ is the predominant excitatory neurotransmitter in the brain

_______ is the predominant inhibitory neurotransmitter in the brain

what do anti-seizure drugs do to alter these

Answer 9

• glutamate (inhibit)

- GABA (stimulate)

Question 10

MOA of Carbmazapine

Answer 10

• presynaptic VG Na+ channel inhibitor

- bind to inactivated Na+ channel and slows the rate it resets

Question 11

MOA of Lamotrigine

Answer 11

• presynaptic VG Na+ channel inhibitor

- bind to inactivated Na+ channel and slows the rate it resets

Question 12

MOA of Phenytoin

Answer 12

• presynaptic VG Na+ channel inhibitor

- bind to inactivated Na+ channel and slows the rate it resets

Question 13

MOA of Valproate

Answer 13

• presynaptic VG Na+/Ca2+ channel inhibitor
• bind to inactivated Na+ channel and slows the rate it resets
• ALSO inhibits GABA transaminase slowing breakdown of GABA. also inhibits a second enzyme in GABA breakdown

Question 14

action potentials travel down the length of the axon through the sequential opening of voltage gated ___ channels

Answer 14

• Na+

Question 15

do the VG Na+ channel inhibitors effect the neurons that are not involved in the seizure

Answer 15

• no

Question 16

toxicities of phenytoin

Answer 16

• gingival hyperplasia

Question 17

toxicities of carbamazepine

Answer 17

• water retention

- hyponatremia

Question 18

toxicities of valproate

Answer 18

• alopecia (hair loss)

- weight gain

Question 19

MOA of Gabapentin

Answer 19

• presynaptic VG Ca2+ channel inhibitor

- reduce release of glutamate into synapse

Question 20

MOA of Pregabalin

Answer 20

• presynaptic VG Ca2+ channel inhibitor

- reduce release of glutamate into synapse

Question 21

do Gabapentin and Pregabalin affect GABA signaling

Answer 21

• no

Question 22

MOA of Levetiracetam

Answer 22

• inhibits release of glutamate

- blocks vesicle fusion protein SV2A

Question 23

MOA of Felbamate

Answer 23

• MATES COMPETE WITH
• competitive antagonist of ligand-gated glutamate receptors (Na+ channel)
• NMDA

Question 24

MOA of Topiramate

Answer 24

MATES COMPETE WITH

• competitive antagonist of ligand-gated glutamate receptors (Na+ channel)
• AMPA
• GABA-A receptor positive modulator

Question 25

toxicities of Felbamate

Answer 25

- aplastic anemia | - acute liver failure

Question 26

toxicities of Topiramate

Answer 26

- weight loss | - kidney stones

Question 27

MOA of Ethosuximide used for what seizures

Answer 27

- post synaptic T-type Ca2+ channel inhibitor - slows depolarization and reduces circuit output - absence only

Question 28

MOA of Tiagabine

Answer 28

- increase synaptic levels of GABA by inhibiting GABA reuptake transporter on presynaptic neuron

Question 29

MAO of Vigabatrin

Answer 29

- increases synaptic levels of GABA - inhibit GABA transaminase slowing breakdown of GABA - Valproate has the same function BOTH START WITH A V

Question 30

toxcities of Vigabatrin indication for this drug

Answer 30

- permanent loss of vision | - only if other therapies fail

Question 31

MOA of Benzodiazepines examples of drug

Answer 31

- GABA-A receptor positive modulator - increase frequency of Cl- channel opening - Clonazepam

Question 32

MOA of Barbiturates examples of drug

Answer 32

- GABA-A receptor positive modulator - increase duration of Cl- channel opening - Phenobarbital

Question 33

toxicities associated with almost all anti-seizure drugs

Answer 33

- somnolence - dizziness - fatigue - ataxia - vision disruptions - nausea/vomiting

Question 34

which anti-seizure drugs are prone to drug-drug interactions how so how does this effect contraceptive meds

Answer 34

- Valproate - inhibit CYP2C9 - Carbamazepine - induce CYP2C9 (reduce effectiveness of contraceptive meds) - Phenytoin - induce CYP2C9 (reduce effectiveness of contraceptive meds)

Question 35

which anti-seizure drug can induce its own metabolism

Answer 35

- Carbamazepine

Question 36

importance of phenytoin metabolism

Answer 36

- at high doses it is metabolized by zero order kinetics - drug in excess compared to the enzymes that metabolize it - interferes with metabolism of other drugs

Question 37

which ant-seizure drugs are teratogenic how?

Answer 37

- phenytoin - reduce serum levels of folate - carbamazepine - reduce serum levels of folate - valproate - topiramate

Question 38

what do you give for status epilepticus

Answer 38

- benzo (lorazepam and diazepam) + phenytoin