Exam 7: anti-seizure meds Flashcards
MOA of Carbamazepine
stabilized “inactivated” state of VG Na channels, decreasing repetitive firing
MOA of Ethosuximide
Blocks VG T-type dependent calcium channel, disrupting pacemaker activity. Targets thalamic neurons
MOA of Topiramate
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
MOA of Phenytoin
Prolongs inactivation phase of VG Na channels which prevents rapid firing of action potentials
MOA of Valproic acid
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
MOA of Phenobarbital
GABAa; increases duration of chloride channel opening events; depresses excitatory actions of glutamate via binding to AMPA receptor
MOA of Diazepam/lorazepam
GABAa; increase in the frequency of chloride channel opening events
MOA of Gabapentin
Designed as GABA analog, primarily inhibits high-VG Calcium channels
What seizures are treated with carbamazepine?
Partial (focal) and secondarily-generalized tonic clonic seizures
Where are carbamazepines metabolized?
Hepatic CYP3A4
What are the adverse effects of carbamazepine?
Mild leukopenia and hyponatremia, Stevens-Johnson Syndrome in patients with human leukocyte antigen
What seizures are treated with ethosuximide?
Absence
Where is ethosuximide metabolized?
Hepatic microsomal enzymes CYP3A4; 25% of drug is excreted through urine unchanged
What are adverse effects of ethosuximide?
Behavioral changes, psychotic behavior, SLE
What seizures are treated with valproic acid?
Works for most; primarily generalized tonic-clonic seizures
What are the pharmacokinetics of valproic acid? What liver enzyme can it inhibit?
Metabolized by liver, CYP2C9
What are adverse effects of valproic acid?
alopecia, appetite stimulation, weight gain, elevation of hepatic transaminases
What seizures are treated with phenytoin?
partial and secondarily generalized tonic-clonic seizures
What are the pharamockinetics of phenytoin? Is it special in any way?
Rate of elimination varies as a function of it’s concentration; Metabolized by CYP2C9 and 2C10, which a smaller fraction by CYP2C19
What seizure drug inhibits the metabolism of phenytoin?
Valproic acid
What are adverse effects of phenytoin?
Nystagmus, cerebellar atrophy with long term use, gingival hyperplasia
What seizures are treated with topirimate?
Focal and primarily generalized tonic-clonic seizures
What are the pharmacokinetics of topirimate? What liver enzymes does it induce?
Mainly excreted unchanged in urine; very little binding to plasma proteins; Induces CYP3A and inhibits CYP2C19
What are the drug-drug interactions of topirimate?
Carbamazepine and phenytoin decrease topiramate, reduces estradiol plasma concentrations with co-administration
What are the adverse effects of topirimate?
Psychomotor slowing, word-finding difficulty, impaired concentration, interference with memory are common
