Anticonvulsants

Question 1

4 ways to treat seizures

Answer 1

1. Blockade of excitatory input
2. Strengthening of inhibitory input (GABA)
3. Block Na channels
4. Block thalamic Ca channels

Question 2

Block hyper-excitability by:

Answer 2

Elevate threshold for stimuli

Limit propagations discharged

Question 3

Blockage of Na channel activation does what

Answer 3

Reduces the ability of Na channels to recover from inactivation to inhibit constant firing and increases threshold potential

Question 4

Blocking of Ca channel does waht

Answer 4

ABSENCE SEIZURES

Reduces firing of thalamic neurons which are involved in cortical discharge and NT release (**)

Question 5

Activation of GABA(A) leads to

Answer 5

Increase inflow of Cl and inhibit post-synaptic cells

Question 6

GABA transmission can be enhanced by

Answer 6

block of GAT1 transporter and increase concentration in cleft

Question 7

Antagonists of NMDA and AMPA glutamate receptors do what

Answer 7

Anticonvulsant activity bc glutamate is an excitatory NT

Question 8

PD Properties of Classical AEDs

Answer 8

Narrow therapeutics
CNS depression (valproic is the least sedatative)
Hypersensitivity and hematotoxicity rxns
Teratogenicity and can cause unplanned pregnancy
Long half life
Multiple times a day dosing
Increased risk of osteoporosis bc interfere with Vit D metabolism

Question 9

Induction of P450

Answer 9

Phenobarbital
Phenytoin
Carbamazepine

Question 10

Inhibition of P450

Answer 10

Valproic acid

Question 11

Phenytoin

Answer 11

Dilantin

Question 12

Phenytoin MOA

Answer 12

Slows the rate of recovery of Na channels from inactivation

Question 13

Phenytoin treats

Answer 13

Partial and tonic-clonic seizures

Question 14

Water soluble form of phenytoin

Answer 14

Fosphenytoin

Question 15

Phenytoin Elimination

Answer 15

Halflife increases with dose increase but concentration disproportinately increases with dose increases

Question 16

Phenytoin down sides

Answer 16

Metabolized by CYP so many drug interactions

Question 17

Phenytoin AE

Answer 17

CNS depression
Gingival hyperplasia
Inhibits release of ADH and insulin so hyperglycemia and glycosuria

Question 18

Carbamazepine

Answer 18

Tegretol

Question 19

Carbamazepine MOA

Answer 19

Slows the rate of recovery of Na channels from inactivation

Question 20

Carbamazepine treates

Answer 20

Partial and tonic clonic

Question 21

Down sides to carbamazepine

Answer 21

Induces its own metbaolism
Decreased halflife after chronic therapy
Active metabolites
Induces 2C, 3A, UGT

Question 22

Carbamazepine AE

Answer 22

Acute toxication (stuper, coma)
Long term: drowsiness, vertigo, ataxia
SJS and necrolysis

Question 23

Ethosuximide

Answer 23

Zarontin

Question 24

Ethosuximide MOA

Answer 24

Blocks T type Ca channels in thalamus

Question 25

Ethosuximide treats

Answer 25

absence seizures

Question 26

Ethosuximide Metabolism

Answer 26

Liver | Few drug drug interactions

Question 27

Ethosuximide AE

Answer 27

GI and CNS

Question 28

Valproic acid

Answer 28

Depakene

Question 29

Valproic acid MOA

Answer 29

Na blocker Ca blocker Enhances GABA

Question 30

Valproic acid treats

Answer 30

Partial Generalized epilepsies Absence and myoclonic seizures

Question 31

Valproic inhibits and metabolized where?

Answer 31

2C9 and UGT | Liver

Question 32

Valproic acid SE

Answer 32

GI Weight gain Hair loss in children Minimal sedation

Question 33

Oxcarbazepine

Answer 33

Trileptal

Question 34

Oxcarbazepine MOA

Answer 34

Blocks Na channel | Similar to carbamazpine

Question 35

Oxcarbazepine PK

Answer 35

Pro-drug | Induces 3A4/5 and inhibits 2C19

Question 36

Oxcarbazepine Treats

Answer 36

Partial in >4 yo and can be mono or adjunct

Question 37

Oxcarbazepine AE

Answer 37

Dizziness Headache D/V/N Ataxia

Question 38

Gabapentin

Answer 38

Neurontin

Question 39

Gabapentin MOA

Answer 39

Promotes release of GABA

Question 40

Gabapentin treats

Answer 40

Partial seizures 2nd line as adjunct | - Neuropathic pain, migraines and spasticity

Question 41

Upsides to gabapentin

Answer 41

No known interactions with other AEDS | Well toelrated

Question 42

Lamotrigine

Answer 42

Lamictal

Question 43

Lamotrigine MOA

Answer 43

Delays recovery of Na channels from inactivation

Question 44

Lamotrigine Treats

Answer 44

Partial seizures Absences and GTCs Drop attacks

Question 45

AE and upside

Answer 45

U: no enzyme induction Dizziness, ataxia, N/V with other AEDs Anti-folate activity (risk of doubled oral clefts)

Question 46

Topiramate

Answer 46

Topamax

Question 47

Topiramate MOA

Answer 47

Antagonizes AMPHA/kainate glutamate receptors Block Na Activates hyperpolarizing K channels

Question 48

Topiramate treats

Answer 48

Partial or primary generalized seizures as mono >10 yo or adjunct >2

Question 49

Topiramate SE

Answer 49

((TERATOGENIC (only new one to be) Cognitive impairment (too fast titration) Kidney stones**

Question 50

Levetiracetam

Answer 50

Keppra

Question 51

Levetiracetam MOA

Answer 51

Unknown

Question 52

Levetiracetam treats

Answer 52

Myoclonic, partial onset and GTCs

Question 53

Levetiracetam SE

Answer 53

Well tolerated with some CNS | Possible anti-epileptogenic properties

Question 54

Zonisamide

Answer 54

Zonegran

Question 55

Zonisamide MOA

Answer 55

Blocks Na and Ca channels

Question 56

Zonisamide treats

Answer 56

Adjunctive for partial seizures

Question 57

Zonisamide side effects

Answer 57

SULFA!!! CNS Kidney stones Long-half life

Question 58

New Vs Old

Answer 58

``` Similar effectiveness Less sedative Well tolerated Improved PK (few p450 and interactions) Little to no teratogenicity (except topirimate) ```

Question 59

Outcomes with treatment

Answer 59

60% seizure free with AEDs 20% seizure reduction with AEDs 20% 2 drugs failed (pharmacoresistent and more common in kids)

Question 60

Ketogenic diet

Answer 60

high fat low protein low carbs - Very hard!!