SM_93b: Anticonvulsants Flashcards
Many people with epilepsy are ____ to antiseizure medications
Many people with epilepsy are refractory to antiseizure medications
- Failure of previous AEDs diminishes seizure-free rates to future AEDs
Describe cellular mechanisms of seizure generation
Cellular mechanisms of seizure generation
- Too much excitation: ionic (inward Na+ or Ca2+ currents), neurotrasnmitter (glutamate, aspartate)
- Too little inhibition: ionic (inward Cl- or outward K+ currents), neurotransmitter (GABA)
Describe targets for anticonvulsants
Targets for anticonvulsants
- Increase inhibitory neurotransmission via GABA
- Decrease excitatory neurotransmission via glutamate
- Block voltage gated inward Na+ or Ca2+ currents
- Increase outward K+ current
1st generation enzyme-inducing anticonvulsants include ___, ___, and ___, while enzyme inhibitors include ___
1st generation enzyme-inducing anticonvulsants include phenobarbital, phenytoin, and carbamazepine, while enzyme inhibitors include valproate
Phenytoin acts by ____, can be dosed ____, and has ____
Phenytoin acts by inhibiting Na+ channel firing, can be dosed once per day, and has unpredictable kinetics
Phenytoin adverse effects include ____, ____, and ____
Phenytoin adverse effects include CNS sedation (drowsiness, ataxia, confusion, insomnia, nystagmus, etc), gum hyperplasia, and hirsutism
Carbamazepine acts by ____, is related to ____, and is dosed ____
Carbamazepine acts by inhibiting Na+ channels, is related to antidepressants (tricyclic structure), and is dosed twice per day
Carbamazepine side effects include ____ and ____ and has the interaction of ____
Carbamazepine side effects include agranulocytosis / aplastic anemia and hyponatremia and has the interaction of stimulating metabolism of other drugs by inducing enzymes (chemo, warfarin)
Phenobarbital acts by ____ and is dosed ____
Phenobarbital acts by allosterically modulating GABAA receptor to increase duration of opening and is dosed once daily
Can cause CNS sedation
Valproic acid is a first line drug for ____ but causes side effects of ____ and ____
Valproic acid is a first line drug for generalized epilepsy but causes side effects of hepatotoxicity and birth defects (NTDs)
Ethosuximide is used for ___ and acts by ____
Ethosuximide is used for abscence seizures and acts by blocking T-type Ca2+ currents in the thalamus
Oxcarbazepine acts by ____ but has side effect of ____
Oxcarbazepine acts by activity-dependent blockade of Na+ channels and augmentation of K+ channels but has side effect of prominent hyponatremia
____ worsens abscence
Carbamazepine worsens abscence
1st generation AEDs have ____ kinetics
1st generation AEDs have unfavorable kinetics (potent enzyme inducers and high protein binding)
Benzodiazepines are used for ____ and ____ and act by ____
Benzodiazepines are used for status epilepticus and myoclonic seizures and act by allosterically modulating GABAA receptors to increase the frequency of Cl- channel opening
_____ is an ineffective add-on therapy for partial seizures
Gabapentin is an ineffective add-on therapy for partial seizures
Lamotrigine acts by ____, ____, and ____ and is dosed ____
Lamotrigine acts by inhibiting Na+ channels, glutamate release, and Ca2+ channels and is dosed once daily
Lamotrigine has side effect of ____
Lamotrigine has side effect of Stevens-Johnson syndrome
____ is antiepileptic drug safe in pregnancy
Lamotrigine is antiepileptic drug safe in pregnancy
Felbamate has adverse effects of ____ and ____
Felbamate has adverse effects of aplastic anemia and severe hepatitis
Levetiracetam (Keppra) acts by ____
Levetiracetam (Keppra) acts by reducing high voltage-activated Ca2+ currents
Levetiracetam (Keppra) has side effect of ____
Levetiracetam (Keppra) has side effect of irritability
Zonisamide functions by ____, ____, and ____
Zonisamide functions by blocking Na+ channels, T-type Ca2+ channels, and carbonic anhydrase
Causes kidney stones
Topiramate functions by ____ and is dosed ____
Topiramate functions by blocking Na+ channels / increasing frequency of GABAA channel openings / interferes with glutamate binding to AMPA/KA receptor and is dosed twice daily
Topiramate side effects are ____, ____, and ____
Topiramate side effects are memory / cognitive, appetite suppression, and weight loss
____ is an anticonvulsant effective for migraine prophylaxis and treats neuropathic pain and tremor
Topiramate s an anticonvulsant effective for migraine prophylaxis and treats neuropathic pain and tremor
Lyrica (pregabalin) acts on ____ and is dosed ____
Lyrica (pregabalin) acts on voltage-gated Ca2+ channels and is dosed three times per day
Lyrica (pregabalin) causes side effects of ____
Lyrica (pregabalin) causes side effects of appetite increase / weight gain
Vigabatrin side effect is ____
Vigabatrin side effect is irreversible visual field constrrction
Vigabatrin acts by _____
Vigabatrin acts by blocking GABA metabolism by irreversibly inhibiting GABA transaminase
Lacosamide acts by ___
Lacosamide acts by prolonging the slow inactivation phase of Na channel opening (potent inhibitor of Na channel activity)
(dosed 2x/day)
Second generation AEDs are ____ and ____ but not ____
Second generation AEDs are safer and better tolerated but not more potent
Fewever drug interactions, lower protein binding, less likely to cause significant enzyme induction or inhibition
Absorption is ____
Absorption is entry of drug into blood
- Essentially complete for all AEDs (except gabapentin)
- Timing varies widely
- Generally slowed by food in stomach (except CBZ)
- Usually takes several hours
Enzyme inducers ____
Enzyme inducers increase clearance and decrease steady-state concentrations of other substrates
- CBZ autoinduces
- Results from hepatic synthesis of additional enzyme
- Slower in onset/offset than inhibition interactions
- Broad spectrum inducers: CBZ, phenytoin, phenobarbital
- Selective CYP3A inducers: felbamate, topiramate, oxcarbazepine
Enzyme inhibitors ____
Enzyme inhibitors decrease clearance and increase steady-state concentrations of other substrates
- Results from competition with other substrates at specific hepatic enzyme sites
- Onset typically rapid and concentration dependent
Valproate competitively inhibits ____, increasing plasma concentrations of ____ and ____, and inhibits ____, increasing plasma concentratiojns of ____ and ____
Valproate competitively inhibits UDP glucuronosyltransferase, increasing plasma concentrations of lamotrigine and lorazepam, and inhibits CYP2C19, increasing plasma concentrations of phenytoin and phenobarbital
Topiramate and oxcarbazepine inhibit ____, increasing plasma concentrations of ____
Topiramate and oxcarbazepine inhibit CYP2C19, increasing plasma concentrations of phenytoin
Felbamate inhibit ____, increasing plasma concentrations of ____ and ____
Felbamate inhibit CYP2C19, increasing plasma concentrations of phenytoin and phenobarbital
Describe common acute dose-related adverse effects of AEDs
Common acute dose-related adverse effects of AEDs
____ and ____ may exacerbate epileptic seizures
Tramadol and venflaxine may exacerbate epileptic seizures
