Seizure pharm

Question 1

General strategies of seizure meds

Answer 1

1. decrease excessive rates of neuronal dishcarge w/in a focus
2. prevent propagation of siezure activity from focus to other brain regions

Question 2

Basic mechanism of action for antiseizure drugs

Answer 2

Affect abnormal membrane fnx; changes in voltage-regulated ion channels leading to excess depolarization,

correct decreased inhibition (increase GABA fnx),

reduce excitation (block glutamate)

Question 3

alters ion conductance, use dependent on Na chans, ≠generation of repetive AP by keeping inactivation gate closed = increased refractory period

Answer 3

Phenytoin

Question 4

MOA of Phenytoin and PharmK

Answer 4

alters ion conductance, use dependent on Na chans, ≠generation of repetive AP by keeping inactivation gate closed = increased refractory period

*depend on formulation, HIGH protein bound, use 10-20 mg

Question 5

what would you prescribe to someone with General Tonic-Clonic or Partial seizures that affecgts Na channels to keep them inactive

Answer 5

Phenytoin: for tonic-clonic or partial seizures

Question 6

Why do we measure blood levels of pt on Phenytoin

Answer 6

bc it’s dose dependent drug: there is NON-linear releationhip btwn daily dose of drug and steady-state plasma conc btwn individuals; daily dose varies person to person

Question 7

What side effects, specifically CNS are seen with PHenytoin use?

Answer 7

CNS is dose/depend= nausea, anorexia, apathy, sedation, nystagmus.

NOn-dose dependent= gingiva hyperplasia, hirsuitism, teratogenic, rash

Question 8

MOA of Carbamazepine

Answer 8

Sim MAO phenytoin; blocks Na chans at therapeutic conc, no GABA interaction. Unpredictable absorption w/ hepatic enZ induction

Question 9

best med for PARTIAL seizures, NOT absence (contraindicated)

Answer 9

Carbamazepine

Question 10

Causes dose releated toxicity; diplopia, ataxia, GI, drowsiness, rare blood dyscarsias (no dose related)

Answer 10

Carbamazapine

Question 11

What drug is teratogenic that can cause spina bifida?

Answer 11

Cabamazepine

Question 12

Impaired consciousness w/ staring spells, w/ or w/out eye blinks

Answer 12

Absence seizure

Question 13

seizure recurring so close together baseline consciousness is not regained btwn episodes

Answer 13

status epilepticus

Question 14

First line for absence seizures

Answer 14

Ethosuximide

Question 15

reduces low-threshold (T-type) Ca++ current in thalamic nucleus

Answer 15

Ethosuximide for absence seizures

Question 16

PharmK in Ethosuximide

Answer 16

well absorbed after oral, not protein bound, dist to entire body, met by liver w/ long ½ life

Question 17

Side effects and toxicity seen with Ehtosuximide use

Answer 17

Sides/toxicity: gastric distress and lethargy and fatigue

Question 18

MOA of Valproic Acid

Answer 18

Blocks repetitive firing, reduce T type Ca++ currents, increase GABA conc

Question 19

PharmK: plasma bound, distributes extracell, ≠metobolism phenobarbital/phenytoin, carbamazepine

Answer 19

Valproic Acid

Question 20

When can we use Valproic acid as seizure tx

Answer 20

absence seizure w/ or w/out tonic-clonic, general tonic-clonic, partial, myoclonic

Question 21

Side effects of valproic acid

Answer 21

GI, wt gain, hair loss, Hepatotoxic, teratogenic (spina bifida)

Question 22

MOA of Felbamate

Answer 22

At clycine modulatory site on NMDA receptor; potentiates GABA,

Question 23

for PARTIAL seizure not responseive to other tx, (-) is anaplastic and hepatic failure , very toxic, only use in refractory seizures

Answer 23

Felbamate

Question 24

Toxicity of Felbamate, when to use it

Answer 24

Parital seizures refractory to other tx.

Anaplastic and hepatic fail

Question 25

Use as adjunct therapy for Partial seizures w/or w/out tonic-clonic seizures also Used for neurpopathic pain and ALS

Answer 25

Gabapentin

Question 26

MOA of Gabapentin

Answer 26

Analogue of GABA, unclear what it does, not an agonist

Question 27

Sim to gabapentin, more potent. Interact w/ a2-delta subunit of volt-gated Ca+ channels à reduces NT release.

Answer 27

Pregabalin (Lyrica)

Question 28

used as adjuvant for PaRTIAL, neuropathic pain in diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia

Answer 28

Pregabalin

Question 29

What limits usefullness of Pregabalin

Answer 29

DEA class 5 drug

Question 30

MOA of Lamotrigine

Answer 30

Blocks repetitive AP, may block Na+ chan

Question 31

When can you prescribe Lamotrigine to pt?

Answer 31

Used: Partial, General T/C, Absence, bipolar disorder. No interference w/ other drug pharmK

Question 32

Use for Used: Partial, General T/C, Absence, bipolar disorder. No interference w/ other drug pharmK

Answer 32

Lamotrigine

Question 33

Serious side effect = rash or steven johnson syndrome

Answer 33

Lamotrigine

Question 34

From D-fructose, ≠excitatory transmission via antagonizing ability of excitatory AA to activate AMPA on glutamate receptor, can block Na channels (like phenytoin)

Answer 34

Topirimate

Question 35

What effect does Topirimate have on seizures

Answer 35

Blocks spread of seizure vs raising seizure threshold

Question 36

Use: as add-on in adult for Partial seizures and prevention migraines

Answer 36

Topirimate

Question 37

MOA of Tiagabine

Answer 37

≠GABA transporter, GAT-1 thus ≠reuptake of GABA to increase concentration in brain.

Question 38

≠GABA transporter, GAT-1 thus ≠reuptake of GABA to increase concentration in brain.

Answer 38

Tiagabine

Question 39

Uses of Tiagabine and side effects

Answer 39

add-on for Complex and Simple Partial seizures dizzy, tremor, somnolence

Question 40

Adj for Parital or adj for myoclonic seizures and Primary Generalized seizures Mech = ???; few interactions, often given w/ other seizure meds. Sides = somnolence, asthenia, dizzy

Answer 40

Levetiracetam

Question 41

Acts at Na+ and Ca+ channels, reduced voltage-gated (T-type) and stops spread of seizures while suppressing their focus

Answer 41

Zonisamide

Question 42

MOA of Zonisamide

Answer 42

Acts at Na+ and Ca+ channels, reduced voltage-gated (T-type) and stops spread of seizures while suppressing their focus

Question 43

Side effects of Zonisamide

Answer 43

CNS (-) reaction; ataxia, anorexia, nervous, fatigue, speech.

Question 44

What do we use Zonisamide for?

Answer 44

approve as adjunctive tx of adults w/ partial seizures

Question 45

MOA of Vigabatrin

Answer 45

Irreversibly ≠ GABA metabolism; GABA-transanimase inhibitor; has possible permanent effects on vision.

Question 46

used as adjuvant for refractory complex partial and infantile spasms

Answer 46

Vigabatrin

Question 47

Blocks voltage gated Na and Ca++ channels to ≠neuronal hypersynchronization and ≠caronic anhydrase

Answer 47

Clobazam

Question 48

Mech of Clobazam

Answer 48

Blocks voltage gated Na and Ca++ channels to ≠neuronal hypersynchronization and ≠caronic anhydrase

Question 49

Lacosamide MOA

Answer 49

Enchance slow inactivation volt Na channels, additive to AEDs via prolongation of inactivation

Question 50

Enchance slow inactivation volt Na channels, additive to AEDs via prolongation of inactivation

Answer 50

Lacosamide

Question 51

USe of Lacosamide

Answer 51

Adj for Partial seizures

Question 52

Postsynaptic AMPA antagonist; binds to allosteric site on glutamate-gated Na+/K+ AMPA channel thus is noncompetitive; prevents discharge of neurons

Answer 52

Perampanel

Question 53

Drug interactions seen iwth Perampanel

Answer 53

Interactions: CYP3A inducer antiseizure drug (caramasepine, oxcarbazepine, phenytoin)

Question 54

Adj for Partial seizures in adults MOA: K+ channel facilitator, unique to this drug; only when other drugs not tolerated; may have eye issues

Answer 54

Ezogabine

Question 55

Decreases sustained high-frequency fring of neurons; prolong inactive state of Na+ channel For adj in Lennox-Gastaut in pts over 4 years, works for all seizures in this sydnrome

Answer 55

Rufinamide