Exam 7: anti-seizure meds

Question 1

MOA of Carbamazepine

Answer 1

stabilized “inactivated” state of VG Na channels, decreasing repetitive firing

Question 2

MOA of Ethosuximide

Answer 2

Blocks VG T-type dependent calcium channel, disrupting pacemaker activity. Targets thalamic neurons

Question 3

MOA of Topiramate

Answer 3

Increased activation of VG Na channels; blocks presynaptic N and P/Q VG Calcium channels, enhances GABAa-receptor currents, limits activatino of AMPA subtypes by gultamate

Question 4

MOA of Phenytoin

Answer 4

Prolongs inactivation phase of VG Na channels which prevents rapid firing of action potentials

Question 5

MOA of Valproic acid

Answer 5

Decreases repetitive firing, potentially via multiple mechanisms: Block VG Na channel, blocks NMDA receptors, Decreases GABA reuptake, reduces flow of Calcium through T-type channels

Question 6

MOA of Phenobarbital

Answer 6

GABAa; increases duration of chloride channel opening events; depresses excitatory actions of glutamate via binding to AMPA receptor

Question 7

MOA of Diazepam/lorazepam

Answer 7

GABAa; increase in the frequency of chloride channel opening events

Question 8

MOA of Gabapentin

Answer 8

Designed as GABA analog, primarily inhibits high-VG Calcium channels

Question 9

What seizures are treated with carbamazepine?

Answer 9

Partial (focal) and secondarily-generalized tonic clonic seizures

Question 10

Where are carbamazepines metabolized?

Answer 10

Hepatic CYP3A4

Question 11

What are the adverse effects of carbamazepine?

Answer 11

Mild leukopenia and hyponatremia, Stevens-Johnson Syndrome in patients with human leukocyte antigen

Question 12

What seizures are treated with ethosuximide?

Answer 12

Absence

Question 13

Where is ethosuximide metabolized?

Answer 13

Hepatic microsomal enzymes CYP3A4; 25% of drug is excreted through urine unchanged

Question 14

What are adverse effects of ethosuximide?

Answer 14

Behavioral changes, psychotic behavior, SLE

Question 15

What seizures are treated with valproic acid?

Answer 15

Works for most; primarily generalized tonic-clonic seizures

Question 16

What are the pharmacokinetics of valproic acid? What liver enzyme can it inhibit?

Answer 16

Metabolized by liver, CYP2C9

Question 17

What are adverse effects of valproic acid?

Answer 17

alopecia, appetite stimulation, weight gain, elevation of hepatic transaminases

Question 18

What seizures are treated with phenytoin?

Answer 18

partial and secondarily generalized tonic-clonic seizures

Question 19

What are the pharamockinetics of phenytoin? Is it special in any way?

Answer 19

Rate of elimination varies as a function of it’s concentration; Metabolized by CYP2C9 and 2C10, which a smaller fraction by CYP2C19

Question 20

What seizure drug inhibits the metabolism of phenytoin?

Answer 20

Valproic acid

Question 21

What are adverse effects of phenytoin?

Answer 21

Nystagmus, cerebellar atrophy with long term use, gingival hyperplasia

Question 22

What seizures are treated with topirimate?

Answer 22

Focal and primarily generalized tonic-clonic seizures

Question 23

What are the pharmacokinetics of topirimate? What liver enzymes does it induce?

Answer 23

Mainly excreted unchanged in urine; very little binding to plasma proteins; Induces CYP3A and inhibits CYP2C19

Question 24

What are the drug-drug interactions of topirimate?

Answer 24

Carbamazepine and phenytoin decrease topiramate, reduces estradiol plasma concentrations with co-administration

Question 25

What are the adverse effects of topirimate?

Answer 25

Psychomotor slowing, word-finding difficulty, impaired concentration, interference with memory are common