Seizure pharm Flashcards
General strategies of seizure meds
- decrease excessive rates of neuronal dishcarge w/in a focus
- prevent propagation of siezure activity from focus to other brain regions
Basic mechanism of action for antiseizure drugs
Affect abnormal membrane fnx; changes in voltage-regulated ion channels leading to excess depolarization,
correct decreased inhibition (increase GABA fnx),
reduce excitation (block glutamate)
alters ion conductance, use dependent on Na chans, ≠generation of repetive AP by keeping inactivation gate closed = increased refractory period
Phenytoin
MOA of Phenytoin and PharmK
alters ion conductance, use dependent on Na chans, ≠generation of repetive AP by keeping inactivation gate closed = increased refractory period
*depend on formulation, HIGH protein bound, use 10-20 mg
what would you prescribe to someone with General Tonic-Clonic or Partial seizures that affecgts Na channels to keep them inactive
Phenytoin: for tonic-clonic or partial seizures
Why do we measure blood levels of pt on Phenytoin
bc it’s dose dependent drug: there is NON-linear releationhip btwn daily dose of drug and steady-state plasma conc btwn individuals; daily dose varies person to person
What side effects, specifically CNS are seen with PHenytoin use?
CNS is dose/depend= nausea, anorexia, apathy, sedation, nystagmus.
NOn-dose dependent= gingiva hyperplasia, hirsuitism, teratogenic, rash
MOA of Carbamazepine
Sim MAO phenytoin; blocks Na chans at therapeutic conc, no GABA interaction. Unpredictable absorption w/ hepatic enZ induction
best med for PARTIAL seizures, NOT absence (contraindicated)
Carbamazepine
Causes dose releated toxicity; diplopia, ataxia, GI, drowsiness, rare blood dyscarsias (no dose related)
Carbamazapine
What drug is teratogenic that can cause spina bifida?
Cabamazepine
Impaired consciousness w/ staring spells, w/ or w/out eye blinks
Absence seizure
seizure recurring so close together baseline consciousness is not regained btwn episodes
status epilepticus
First line for absence seizures
Ethosuximide
reduces low-threshold (T-type) Ca++ current in thalamic nucleus
Ethosuximide for absence seizures
PharmK in Ethosuximide
well absorbed after oral, not protein bound, dist to entire body, met by liver w/ long ½ life
Side effects and toxicity seen with Ehtosuximide use
Sides/toxicity: gastric distress and lethargy and fatigue
MOA of Valproic Acid
Blocks repetitive firing, reduce T type Ca++ currents, increase GABA conc
PharmK: plasma bound, distributes extracell, ≠metobolism phenobarbital/phenytoin, carbamazepine
Valproic Acid
When can we use Valproic acid as seizure tx
absence seizure w/ or w/out tonic-clonic, general tonic-clonic, partial, myoclonic
Side effects of valproic acid
GI, wt gain, hair loss, Hepatotoxic, teratogenic (spina bifida)
MOA of Felbamate
At clycine modulatory site on NMDA receptor; potentiates GABA,
for PARTIAL seizure not responseive to other tx, (-) is anaplastic and hepatic failure , very toxic, only use in refractory seizures
Felbamate
Toxicity of Felbamate, when to use it
Parital seizures refractory to other tx.
Anaplastic and hepatic fail
Use as adjunct therapy for Partial seizures w/or w/out tonic-clonic seizures
also Used for neurpopathic pain and ALS
Gabapentin
MOA of Gabapentin
Analogue of GABA, unclear what it does, not an agonist
Sim to gabapentin, more potent. Interact w/ a2-delta subunit of volt-gated Ca+ channels à reduces NT release.
Pregabalin (Lyrica)
used as adjuvant for PaRTIAL, neuropathic pain in diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia
Pregabalin
What limits usefullness of Pregabalin
DEA class 5 drug
MOA of Lamotrigine
Blocks repetitive AP, may block Na+ chan
When can you prescribe Lamotrigine to pt?
Used: Partial, General T/C, Absence, bipolar disorder. No interference w/ other drug pharmK
Use for Used: Partial, General T/C, Absence, bipolar disorder. No interference w/ other drug pharmK
Lamotrigine
Serious side effect = rash or steven johnson syndrome
Lamotrigine
From D-fructose, ≠excitatory transmission via antagonizing ability of excitatory AA to activate AMPA on glutamate receptor, can block Na channels (like phenytoin)
Topirimate
What effect does Topirimate have on seizures
Blocks spread of seizure vs raising seizure threshold
Use: as add-on in adult for Partial seizures and prevention migraines
Topirimate
MOA of Tiagabine
≠GABA transporter, GAT-1 thus ≠reuptake of GABA to increase concentration in brain.
≠GABA transporter, GAT-1 thus ≠reuptake of GABA to increase concentration in brain.
Tiagabine
Uses of Tiagabine and side effects
add-on for Complex and Simple Partial seizures
dizzy, tremor, somnolence
Adj for Parital or adj for myoclonic seizures and Primary Generalized seizures
Mech = ???; few interactions, often given w/ other seizure meds.
Sides = somnolence, asthenia, dizzy
Levetiracetam
Acts at Na+ and Ca+ channels, reduced voltage-gated (T-type) and stops spread of seizures while suppressing their focus
Zonisamide
MOA of Zonisamide
Acts at Na+ and Ca+ channels, reduced voltage-gated (T-type) and stops spread of seizures while suppressing their focus
Side effects of Zonisamide
CNS (-) reaction; ataxia, anorexia, nervous, fatigue, speech.
What do we use Zonisamide for?
approve as adjunctive tx of adults w/ partial seizures
MOA of Vigabatrin
Irreversibly ≠ GABA metabolism; GABA-transanimase inhibitor; has possible permanent effects on vision.
used as adjuvant for refractory complex partial and infantile spasms
Vigabatrin
Blocks voltage gated Na and Ca++ channels to ≠neuronal hypersynchronization and ≠caronic anhydrase
Clobazam
Mech of Clobazam
Blocks voltage gated Na and Ca++ channels to ≠neuronal hypersynchronization and ≠caronic anhydrase
Lacosamide MOA
Enchance slow inactivation volt Na channels, additive to AEDs via prolongation of inactivation
Enchance slow inactivation volt Na channels, additive to AEDs via prolongation of inactivation
Lacosamide
USe of Lacosamide
Adj for Partial seizures
Postsynaptic AMPA antagonist; binds to allosteric site on glutamate-gated Na+/K+ AMPA channel thus is noncompetitive; prevents discharge of neurons
Perampanel
Drug interactions seen iwth Perampanel
Interactions: CYP3A inducer antiseizure drug (caramasepine, oxcarbazepine, phenytoin)
Adj for Partial seizures in adults
MOA: K+ channel facilitator, unique to this drug; only when other drugs not tolerated; may have eye issues
Ezogabine
Decreases sustained high-frequency fring of neurons; prolong inactive state of Na+ channel
For adj in Lennox-Gastaut in pts over 4 years, works for all seizures in this sydnrome
Rufinamide
