Anti Seizure Pharm Flashcards
What are the drugs of choice for myotonic/atonic/clonic seizures
Benzodiazepines (1), Clonazepam (2)
What are the drugs of choice for tonic/clonic seizures
Carbamazepine, phenytoin, phenobarbital
What are the drugs of choice for simple complex?
Lacosamide (1), Gabapentin, pregabalin, oxcarbazepine, Tiagabine, vigabatrin, ezogabin
What are the broad spectrum anti epileptic drugs?
Valproate (old version), Lamotrigine (impt new one), topirimate, levetiracetam, zonisamide
Which drugs limit excitation
Phenytoin, ethosuximide, carbamazepine, lamotrigine, fosphenytoin, levitiracetam, oxcarbazepine, zonisamide
What drugs enhance inhibition?
phenobarbital, diazepam, tiagabine, vigabatrin
What drugs limit excitation and enhance inhibition
valproate, topirimate
What are the two channels where AEDs antagonize excitation
Voltage gated Na channels, low threshold Ca channels
MOA for Phenytoin
Antagonize VGSC
MOA for carbamazepine
antagonize VGSC
MOA for lacosamide
Antagonize VGSC
MOA for lamotrigine
antagonize VGSC
MOA for oxcarbazepine
antagonize VGSC
MOA for zonisamide
antagonize VGSC
What are the two distinct mechanisms for VGSC modulation
Fast inactivation and slow inactivation (dimmers)
What drugs use the fast inactivation of Na channels
Traditional: phenytoin, carbamazepine
New AEDs: lamotrigine, oxcarbazepine
What drugs use the slow inactivation mechanism for inactivation of Na channels
New AEDs: lacosamide
What Fast acting VGSC antagonist binds more effectively and has less side effects on cognitive function
phenytoin
What fast acting VGSC antagonist binds less effectively, making it more effective in blocking high frequency firing
Carbamazepine
How is lamotrigines MOA different from phenytoin and carbamazepine?
Besides targeting VGSC, it also targets N and P type voltage gated Ca channels in cortical neurons and neocortical potassium currents
Lacosamide acts on which state of the sodium channel
Stabilizes the slow inactivated state
What drug is the most effective at reducing the amplitudes and frequency of sustained repetitive firing spikes
lacosamide
What is the hallmark of a abscence (petit mal) seizures
3Hz spike and wave activity in the thalamus - mediated by T type Ca channels
Ethosuximide (condition tx, MOA, sedation?)
It is a narrow spectrum that is only used for abscence seizures. It only limits excitation (Ca channel). It is non-sedating
What are the side effects of valproate
weight gain, tremor, hair loss, and lethargy. Assc with neural tube defects
What is the MOA for zonisamide?
blocking voltage dependent sodium channels and blocking T type calcium channels
MOA for tiagabine
inhibits GABA reuptake
MOA for vigabatrin
inhibit GABA metabolism
What drugs enhance post synaptic GABAergic neuronal transmission
phenobarbital, primidone (prodrug of phenobarbital), benzodiazapines
What is the drug of choice for absence seizures
Ethosuximide
MOA for benzodiazepines
Bind to distinct site –> allosteric change –> potentiate GABA binding –> chloride channels open. Does not work without GABA
MOA for Phenobarbital
bind to distinct site–>allosteric change–>potentiate GABA binding–> open Cl channel. At high levels, it is GABA independent indicating that it is more lethal than BZD
Adverse effects of phenobarbital
significant sedation, lethal respiratory depression, has abuse and addiction potential
What are the causes of status epilepticus (continuous seizures)?
drug withdrawl (EtOH, BZD, opioids, AEDs), stimulant abuse (cocaine), poisons (strychnine), Brain tumor, high fever
Tx for status epilepticus?
BZD- lorazepam (not distributed as quickly) or diazepam (absorbed, distributed, and redistributed quickly). If the seizure is not stopped –>Fosphenytoin
drug of choice for myoclonic seizure
Clonazepam (a benzodiazepine)
C/C the multiple MOA for Topirimate and valproic acid
VGSC - both LGSC - topirimate T type Ca Channel - valproic acid Increase GABA - both Potentiates GABA R - topirimate
Gabapentin MOA
binds to voltage dependent Ca channels
MOA for leviteracetam
binds to synaptic vesicle protein SV2A - blunts glutamate release
Type of clearance of Pregabalin
100% renal
MOA for Ezogabine
Opens voltage gated K channels
What are the pharmacokinetics/dynamics of phenytoin
0 order pharmacokinetics - doubling drug doesnt double serum level
inducer of CYP 450 enzymes
What are the toxicities associated with phenytoin
Gingival hyperplasia, hirsutism, hypocalcemia, osteoporosis
What are the complications assc with carbamazepine
inducer of CYP 450 enz ( it will induce its own metabolism)
aplastic anemia - leukopenia, neutropenia, thrombocytopenia
hypocalcemia & osteoporosis ( Vit D catabolizism –> inc PTH)
What is the therapeutic window for AEDs
usually 2 fold
What AEDs have mixed clearance
Topiramate, oxcarbazepine, levetiracetam, zonisamide
How does oxcarbazepine differ from carbamazepine?
oxcarbazepine doesnt have an active metaolite
They both are assc with hyponatremia tho
What drugs are 100% renally cleared
Gabapentin, pregabalin
What is the serious side effect assc with lamotrigine?and mechanism?
stevens-johnson syndrome - assc with concurrent use with valproate. They inhibit conjugation of drugs by UGT enz
What is the serious side effect of topiramate
nephrolithiasis
What AEDs is assc with major congenital malformations
valproic acid
