anticonvulsants

Question 1

Mechanisms of action of anticonvulsants (3)

Answer 1

1. enhancement of inhibitory activity (GABA)
2. inhibition of excitatory activity (glutamate or aspartate)
3. modulation of voltage dependent ion channels involved in propagating the action potential

Question 2

Sodium channel blockers for anticonvulsants

Answer 2

1. phenytoin

2. carbamazepine

Question 3

calcium channel blockers of anticonvulsants

Answer 3

1. ethosuximide

2. gabapentin

Question 4

GABA modulators for anticonvulsants

Answer 4

1. benzodiazepines

2. barbituates

Question 5

Main toxicities of anticonvulsants

Answer 5

1. CNS
2. GI
3. Germatologic’
4. Bone marrow supression

Question 6

Phenytoin

• MOA
• clearance
• Monitoring?
• SE

Answer 6

• MOA: blocks sodium channel (voltage-d)
• extensive CYP450 metabolism
• narrow therapeutic window

** zero order behavior

• Rashes, gingival hyperplasia and CV toxicity with rapid IV administration

Question 7

what is the deal with zero-order behavior?

Answer 7

it can quickly spiral out of control and there is no way to predict what is going to happen

Question 8

phenytoin induces or inhibits CYP450?

what happens to medications that also uses CYP450

Answer 8

• it induces cyp450

- leads to increase in clearence

Question 9

Carbamazepine

• MOA
• Clearance
• monitoring
• SE

Answer 9

• Blocks sodium voltage channels
• Cyp450 metabolism
• narrow window and its metabolite 10,11 epoxide leads to many of the SE
• rashes (HLA-B1502- Ascian deficit); bone marrow supression leading agranulocytosis + anaplastic anemia)

Question 10

Ethosuximide

• MAO
• well tolerated or nah?
• adverse effects

Answer 10

• interferes with L-type calcium channels
• well tolerated and used for absence seizures
• SE include sleep disturbances, nausea and vomiting

Question 11

GABA

• MOA

Answer 11

Mimics action of GABA or otherwise improve GABA effects

• MOA:
  1. reduce reuptake into neurons and glia
  2. increase production of GABA by promoting GAD (glutamic acid decarboxylase)
  3. reduce metabolism by GABA-T (transaminases)

Question 12

valproic acid

• MOA
• clearance
• monitoring
• SE

Answer 12

• MOA: interferes with sodium channels, blocks T-type calcium channels and increases GABA levels
• clearance by CYP450
• look at plasma levels; low therapeutic window

SE: neural tube defects, hepatoxicity, pancreatitis

Question 13

Gabapentin

• MOA
• Clearance?
• tolerated or nah?
• efficacy?

Answer 13

• interferes with P/Q-type calcium channels
• renal clearance
• well tolerated
• low efficacy not used for seizure tx

Question 14

Lamotrigine

• MOA
• SE

Answer 14

• interferes with sodium channels
• direct interference with glutamate and aspartate
• rashes that can be life threatening

Question 15

levetiracetam

• MOA
• clearance?
• efficacy?
• tolerated or nah?
• SE

Answer 15

• may involve binding with synaptic proteins (SV2A)
• renal clearance
• good efficacy
• tolerated
• irritability

Question 16

Dosing in anticonvulsants?

Answer 16

dose titration to therapeutic effect

Question 17

gabapentin, lamotrigine, levetiracetam

Answer 17

• wider therapeutic margins
• renal clearance
• fewer drug interactions
• improved tolerability
• narrow indications

Question 18

phenytoin, carbamazepine, valproic acid

Answer 18

• narrow therapeutic margin
• extensive hepatic metabolism
• drug interaction

Question 19

for almost every seizure except status epilepticus which drug can be used?

Answer 19

valproic acid

Question 20

meds used for status epilepticus

Answer 20

diazepam, lorazepam and midazlam (IV route)

Question 21

Indication ro use Diazepam in partial and generalized tonic-clonic

Answer 21

only used for acute indications

• chronic usage would require stronger doses