Epilepsy

Question 1

What is a seizure?

Answer 1

• high frequency of bursts of APs (influx of Ca and activation of Na channels or a decrease in inhibitory interneurons) or hypersynchronization

Question 2

what are the 3 main MOAs for for anticonvulsants?

Answer 2

1. blockade of voltage-gated Na channels (AP generation) - used for partial and secondarily generalized tonic-clonic seizures
2. enhancement of principal inhibitory neurotransmitter in the CNS (GABA) - used for partial and secondarily generalized tonic-clonic seizures
3. inhibition of voltage-activated T-type Ca channels - used for absence seizures

Question 3

What are the Na channel blockers

Answer 3

Carbamazepine
Phenytoin
Topiramate
Lamotrigine
Valproate
Zonisamide

Question 4

Where do the anti-seizure drugs act in the GABA pathway?

Answer 4

1. benzos and barbiturates - act on post-synaptic side

2. Valproate works at pre-synaptic side by inhibiting GABA metabolism and increasing quantum yield release of GABA

Question 5

What is the net effect of the Ca channel blockers

Answer 5

to reduce activity of pacemaker currents that underlies the thalamic rhythm in spikes and waves

Question 6

What is a major ADE for anti-convulsants?

Answer 6

Suicidal ideation (1-24 weeks after starting drug) - educate patients, minimally effective drug levels should be used to manage epilepsy

Question 7

How should we treat epilepsy?

Answer 7

Monotherapy, switch if it doesn’t work, then consider polypharamcy
- adverse effects vary from minimal impairment to death from aplastic anemia or hepatic failure

Question 8

MOA of carbamazepine, Lacosamide, lamotrigine, phenytoin

Answer 8

block Na channels

Question 9

MOA of clonazepam

Answer 9

GABA allosteric agonist – shift dose reponse curve for GABA to left.

Question 10

MOA of ethosuximide

Answer 10

block T-type Ca channel

Question 11

MOA of felbamate

Answer 11

inhibit NMDA, activate GABA

Question 12

MOA of Gabapentin and Pregabalin

Answer 12

inhibit alpha 2 delta1 subunit of Ca channel

Question 13

MOA of oxcarbazepine

Answer 13

inhibit Na channel, possibly increase K channel and decrease Ca channel

Question 14

MOA of topiramate

Answer 14

inhibit Na channels, activate K current, activate GABA, decrease glutamate activity

Question 15

MOA of Valproate

Answer 15

activate GABA, inhibit Na chanel

Question 16

MOA of Zonisamide

Answer 16

inhibit N and T-type Ca channel

Question 17

ADMA summary of anti-convulsants

Answer 17

1. oral
2. limited protein binding -except phenytoin and valproate
3. hepatic metabolism w/ urinary elimination
4. CYP interactions
5. long half lives
6. slow release products facilitate adherence - fewer doses/day

Question 18

Which anti-convulsants don’t have hepatic metabolism

Answer 18

1. gabapentin
2. Pregabalin
3. minor topiramate

Question 19

Which anti-convulsants is eliminated in stool

Answer 19

phenytoin

Question 20

Which anti-convulsants have no CYP interaction?

Answer 20

Gabapentin, Levetiracetam, pregabalin, topiramate

Question 21

Which anti-convulsants have CYP activity that does it’s own hepatic metabolism?

Answer 21

• this leads to a drug decrease due to increased rate of hepatic metabolism
  Carbamazepine, phenytoin

Question 22

Which anti-convulsants need routine drug levels?

Answer 22

Carbamazepine, ethosuximide, gabapentin, phenytoin, valproate

Question 23

What is a concern w/ topiramate and zonisamide?

Answer 23

they are weak carbonic anhydrase inhibitors –> leads to renal bicarb loss –> metabolic acidosis and may promote stone formation by reducing urinary citrate excretion and increasing urinary pH

Question 24

What is abrupt discontinuation a problem w/ anti-convulsants?

Answer 24

can precipitate status epilepticus, increase the frequency of seizures and lead to various neurologic issues

Question 25

What anti-convulsant has 0 order elimination

Answer 25

phenytoin - elimination of time and concentration

Question 26

ADE effects of Phenytoin

Answer 26

1. CNS effects - nystagmus, ataxia, headache 2. Gingival hyperplasia 3. SJS, TEN, DRESS, hypertrichosis or hirsutism

Question 27

ADE of carbamazepine

Answer 27

1. CNS especially during initial treatment phase - Dizziness, drowsiness, ataxia, blurred vision 2. BBW for agranulocytosis. Aplastic anemia 3. rash to severe derm problems 4. Constipation or dry mouth, N/V

Question 28

When is the incidence of SJS higher when taking anti-convulsant drugs?

Answer 28

Asians who carry a SNP change in HLA-B 1502. Can determine w/ whole blood EDTA testing

Question 29

ADE of Valproic acid

Answer 29

1. CNS effects related to infusion rate - somnolence, dizziness, paresthesias, asthenia, headache 2. Thrombocytopenia, prolonged BT 3. Rare rashes 4. Nausea, diarrhea, hepatotoxicity more commonly in kids

Question 30

ADE of clonazepam, gabapentin

Answer 30

somnolence, ataxia/dizziness/fatigue

Question 31

ADE of ethosuximide

Answer 31

somnolence, ataxia/dizziness/fatigue, GI upset

Question 32

ADE of felbamate

Answer 32

BBW for aplastic anemia, bone marrow suppression, and hepatic dz. N/V, constipation

Question 33

ADE of Lacosamide

Answer 33

dizziness, headache, diplopia, N/V

Question 34

ADE of lamotrigine

Answer 34

BBW for serious rash | Dizziness, diplopia, ataxia, blurred vision, rhinitis

Question 35

ADE of levetiracetam

Answer 35

headache, URTI, somnolence

Question 36

ADE of oxcarbazepine

Answer 36

Dizziness, diplopia, headache, N/V, nystagmus, somnolence, ataxia

Question 37

ADE of pregabalin

Answer 37

Dizziness, somnolence, peripheral edema

Question 38

ADE of topiramate

Answer 38

dizziness, fatigue, ataxia, paresthesias, abnormal vision, psychomotor slowing

Question 39

ADE of zonisamide

Answer 39

somnolence, anorexia, dizziness

Question 40

What anti-convulsants are cat C?

Answer 40

lamotrigine

Question 41

What anti-convulsants are cat D?

Answer 41

carbamazepine, phenytoin, topiramate, phenobarbital

Question 42

What anti-convulsants are Cat X?

Answer 42

Valproate

Question 43

DOC for partial and secondary generalized seizures

Answer 43

Lamotrigine Carbamazepine Levetiracetam Oxcarbazepine

Question 44

DOC for primary generazlied tonic-clonic seizures and atypical absence/myoclonic/atonic seizures

Answer 44

Valproate Lamotrigine Levetiracetam

Question 45

DOC for absence seizures

Answer 45

Ethosuximide | Valproate

Question 46

Treatment for status epilepticus

Answer 46

initially give a benzodiazepines (lorazepam-IV) then add other anti-convulsants

Question 47

How do barbiutrate act on GABA receptors

Answer 47

they prolong opening time of Cl- channel