Anti Seizure Pharm

Question 1

What are the drugs of choice for myotonic/atonic/clonic seizures

Answer 1

Benzodiazepines (1), Clonazepam (2)

Question 2

What are the drugs of choice for tonic/clonic seizures

Answer 2

Carbamazepine, phenytoin, phenobarbital

Question 3

What are the drugs of choice for simple complex?

Answer 3

Lacosamide (1), Gabapentin, pregabalin, oxcarbazepine, Tiagabine, vigabatrin, ezogabin

Question 4

What are the broad spectrum anti epileptic drugs?

Answer 4

Valproate (old version), Lamotrigine (impt new one), topirimate, levetiracetam, zonisamide

Question 5

Which drugs limit excitation

Answer 5

Phenytoin, ethosuximide, carbamazepine, lamotrigine, fosphenytoin, levitiracetam, oxcarbazepine, zonisamide

Question 6

What drugs enhance inhibition?

Answer 6

phenobarbital, diazepam, tiagabine, vigabatrin

Question 7

What drugs limit excitation and enhance inhibition

Answer 7

valproate, topirimate

Question 8

What are the two channels where AEDs antagonize excitation

Answer 8

Voltage gated Na channels, low threshold Ca channels

Question 9

MOA for Phenytoin

Answer 9

Antagonize VGSC

Question 10

MOA for carbamazepine

Answer 10

antagonize VGSC

Question 11

MOA for lacosamide

Answer 11

Antagonize VGSC

Question 12

MOA for lamotrigine

Answer 12

antagonize VGSC

Question 13

MOA for oxcarbazepine

Answer 13

antagonize VGSC

Question 14

MOA for zonisamide

Answer 14

antagonize VGSC

Question 15

What are the two distinct mechanisms for VGSC modulation

Answer 15

Fast inactivation and slow inactivation (dimmers)

Question 16

What drugs use the fast inactivation of Na channels

Answer 16

Traditional: phenytoin, carbamazepine

New AEDs: lamotrigine, oxcarbazepine

Question 17

What drugs use the slow inactivation mechanism for inactivation of Na channels

Answer 17

New AEDs: lacosamide

Question 18

What Fast acting VGSC antagonist binds more effectively and has less side effects on cognitive function

Answer 18

phenytoin

Question 19

What fast acting VGSC antagonist binds less effectively, making it more effective in blocking high frequency firing

Answer 19

Carbamazepine

Question 20

How is lamotrigines MOA different from phenytoin and carbamazepine?

Answer 20

Besides targeting VGSC, it also targets N and P type voltage gated Ca channels in cortical neurons and neocortical potassium currents

Question 21

Lacosamide acts on which state of the sodium channel

Answer 21

Stabilizes the slow inactivated state

Question 22

What drug is the most effective at reducing the amplitudes and frequency of sustained repetitive firing spikes

Answer 22

lacosamide

Question 23

What is the hallmark of a abscence (petit mal) seizures

Answer 23

3Hz spike and wave activity in the thalamus - mediated by T type Ca channels

Question 24

Ethosuximide (condition tx, MOA, sedation?)

Answer 24

It is a narrow spectrum that is only used for abscence seizures. It only limits excitation (Ca channel). It is non-sedating

Question 25

What are the side effects of valproate

Answer 25

weight gain, tremor, hair loss, and lethargy. Assc with neural tube defects

Question 26

What is the MOA for zonisamide?

Answer 26

blocking voltage dependent sodium channels and blocking T type calcium channels

Question 27

MOA for tiagabine

Answer 27

inhibits GABA reuptake

Question 28

MOA for vigabatrin

Answer 28

inhibit GABA metabolism

Question 29

What drugs enhance post synaptic GABAergic neuronal transmission

Answer 29

phenobarbital, primidone (prodrug of phenobarbital), benzodiazapines

Question 30

What is the drug of choice for absence seizures

Answer 30

Ethosuximide

Question 31

MOA for benzodiazepines

Answer 31

Bind to distinct site --> allosteric change --> potentiate GABA binding --> chloride channels open. Does not work without GABA

Question 32

MOA for Phenobarbital

Answer 32

bind to distinct site-->allosteric change-->potentiate GABA binding--> open Cl channel. At high levels, it is GABA independent indicating that it is more lethal than BZD

Question 33

Adverse effects of phenobarbital

Answer 33

significant sedation, lethal respiratory depression, has abuse and addiction potential

Question 34

What are the causes of status epilepticus (continuous seizures)?

Answer 34

drug withdrawl (EtOH, BZD, opioids, AEDs), stimulant abuse (cocaine), poisons (strychnine), Brain tumor, high fever

Question 35

Tx for status epilepticus?

Answer 35

BZD- lorazepam (not distributed as quickly) or diazepam (absorbed, distributed, and redistributed quickly). If the seizure is not stopped -->Fosphenytoin

Question 36

drug of choice for myoclonic seizure

Answer 36

Clonazepam (a benzodiazepine)

Question 37

C/C the multiple MOA for Topirimate and valproic acid

Answer 37

``` VGSC - both LGSC - topirimate T type Ca Channel - valproic acid Increase GABA - both Potentiates GABA R - topirimate ```

Question 38

Gabapentin MOA

Answer 38

binds to voltage dependent Ca channels

Question 39

MOA for leviteracetam

Answer 39

binds to synaptic vesicle protein SV2A - blunts glutamate release

Question 40

Type of clearance of Pregabalin

Answer 40

100% renal

Question 41

MOA for Ezogabine

Answer 41

Opens voltage gated K channels

Question 42

What are the pharmacokinetics/dynamics of phenytoin

Answer 42

0 order pharmacokinetics - doubling drug doesnt double serum level inducer of CYP 450 enzymes

Question 43

What are the toxicities associated with phenytoin

Answer 43

Gingival hyperplasia, hirsutism, hypocalcemia, osteoporosis

Question 44

What are the complications assc with carbamazepine

Answer 44

inducer of CYP 450 enz ( it will induce its own metabolism) aplastic anemia - leukopenia, neutropenia, thrombocytopenia hypocalcemia & osteoporosis ( Vit D catabolizism --> inc PTH)

Question 45

What is the therapeutic window for AEDs

Answer 45

usually 2 fold

Question 46

What AEDs have mixed clearance

Answer 46

Topiramate, oxcarbazepine, levetiracetam, zonisamide

Question 47

How does oxcarbazepine differ from carbamazepine?

Answer 47

oxcarbazepine doesnt have an active metaolite | They both are assc with hyponatremia tho

Question 48

What drugs are 100% renally cleared

Answer 48

Gabapentin, pregabalin

Question 49

What is the serious side effect assc with lamotrigine?and mechanism?

Answer 49

stevens-johnson syndrome - assc with concurrent use with valproate. They inhibit conjugation of drugs by UGT enz

Question 50

What is the serious side effect of topiramate

Answer 50

nephrolithiasis

Question 51

What AEDs is assc with major congenital malformations

Answer 51

valproic acid