Antiepileptic Drugs Flashcards
How do drugs act on voltage gated sodium channels to tx epilepsy?
they stabilize the inactive state to inhibit recurrent depolarization
How do drugs act on voltage gated calcium channels to tx epilepsy?
they act on presynaptic membrane channels and block influx of calcium; thus leading to less excitatory neurotransmitter release.
Where are glutamate and Gaba receptors found?
Glutamate–>post synaptic membrane of excitatory synapses (Ca and Na ligand gated channels)
Gaba —>post synaptic membrane of inhibitory synapses (Cl ligand gated channels)
What are the 4 voltage gated Na channels used to tx epilepsy and how do they all act?
Phenytoin, Carbamazepine, Oxcarbamazepine, Lamotrigine; all stabilize the inactive conformation of the Na channel
What are Carbamazepine and Oxcarbamazepine useful in treating?
More effective for complex partial epilepsy than primary generalized; tx bipolar affective disorder, tx neuropathic pain
What are some of the pharmacologic considerations with Carbamazepine and Phenytoin?
highly protein bound, hepatic metabolism (both autoinducer and heteroinducer) thus effects on other hepatically metabolized meds, can cause contraceptive failure, short half life (Carbazepine)/ variable but longer half-life (Phenytoin)
What are some symptoms of Carbamazepine (and all sodium channel stabilizers) toxicity?
sedation, ataxia and diplopia “dizzy, drunk, double vision” possibly due to epoxide metabolite
What are some adverse reactions to taking Carbamazepine?
rash, Steven-Johnson (rare), mile hepatic enzyme elevation, mild myelosuppression
What is Phenytoin effective at treating?
Tonic-Clonic seizures of primary generalized epilepsy or partial onset and secondarily generalized seizures; effective for acute seizures (even those not related to epilepsy)
Explain the pros and cons of Phenytoin administration by IV
IV is useful to treat Status Epilepticus; IV infusion is limited by hypotension
What are some adverse reactions to taking Phenytoin?
mild hepatotoxicity, myelosuppression, gingival hyperplasia, rash, hirsutism (excess hair in women), Lupus-like rxn
long term: cerebellar degeneration, peripheral neuropathy, osteoporosis
What differentiates Oxcarbazepine from Carbamazepine?
it’s a prodrug designed to bypass carbamazepine epoxide (metabolite); thus is less protein bound, less autoinduction, fewer interactions, less toxic, and has a longer half life.
What is Lamotrigine effective in treating?
effective for primary generalized epilepsy, partial complex epilepsy and secondary generalization and absence seizures; indicated in children!! (i.e. very safe), tx bipolar affective disorder, neuropathic pain.
**note it’s less effective for and may exacerbate myoclonic seizures
What are some pharmacologic considerations when taking Lamotrigine?
hepatic metabolism, less protein bound, hepatic enzyme inducer, cause contraceptive failure, competes for excretion with Valproic Acid and as such has a synergistic action when both drugs taken together
What are the adverse reactions to taking Lamotrigine?
rash that’s dose dependent, rarely steven-johnson, slow initial titration is important!!
What does Valproate tx?
broad spectrum: absence, myoclonic, tonic-clonic seizures of primary generalized epilepsy and partial onset and secondarily generalized seizures; bipolar disorder and migraine prophylaxis
What are some pharmacologic considerations when taking Valproate?
highly protein bound, hepatic metabolism, rapidly absorbed and metabolized, short half-life, extended release preparations (IV route useful in Status Epilepticus)
What is the MOA for Valproate? What are signs of toxicity?
unsure of mechanism–>likely affects Na channels and GABA system.
toxicity signs include: sedation and tremor
What are some adverse reactions to taking Valproate?
nausea, weight gain, hair turnover, hyperammonemia, teratogenic
How do Benzodiazepines act to tx status epilepticus?
Binds to GABA-A receptors to help hyperpolarize the cell membrane; dose limited by sedation and long term usefulness limited by tolerance; short acting due to redistribution (w/in minutes)
What type of benzodiazepine is used for anesthesia or to tx refractory status epilepticus?
Midazolam (IV 1/2 life in minutes, orally ~1hr)
What is the MOA of Vigabatrine?
GABA transaminase binder that slows down intracellular breakdown of GABA (thus increasing GABA)
What is the MOA of Tiagabine?
GABA reuptake inhibtor (thus increasing GABA)
What are the MOA of Gabapentin and Pregabin and what are they used to treat?
GABA analogs that inhibit Ca currents; they are used as adjunctive treatment for partial complex epilepsy; more commonly used for neuropathic pain
What are the pharmacologic considerations when taking Gabapentin?
absorption limited at intestinal amino acid transporter, limited protein binding, no evidence of metabolism in humans (so few side effects), no interaction with other meds, eliminated unchanged in urine, no serious organ toxicity (toxicity related to sedation)
What type of drug is Ethosuximide and what’s it used to treat
it’s a voltage gated calcium channel blocker that blocks T-type calcium currents in thalamo-cortical circuits; used to treat Absence Seizures only
What are some pharmacological considerations and side effects of Ethosuximide?
readily absorbed with minimal first pass metabolism, not protein bound, half life 40-60hrs; side effects: transient nausea, sedation and irritability
What type of drug is Topiramate and what is it’s MOA?
Glutamate receptor blocker that blocks AMPA and Kainate calcium receptors with secondary effects at Na channels and GABA
What is Topiramate effectively treat?
partial onset and secondarily generalized seizures as well as primary generalized epilepsy; effective migraine prophylaxis too
What are some of the adverse reactions and toxicities related to Topiramate use?
carbonic anhydrase activity–>mild metabolic acidosis–>resp compensation–>mild alkalosis–> calcium ionization–>tingling; modest weight loss, kidney stones, rare acute glaucoma
toxicity includes sedation, and cognitive “word finding” problems
What is Levetiracetam used to treat and what is its MOA?
binds synaptic vesicle protein 2 causing decreased NT release; tx partial onset and secondarily generalized seizures with some evidence of activity against primary generalized epilepsy
What are the toxicities and side effects of Levetiracetam?
generally well tolerated, but reactions include irritability, aphasia, thrombocytopenia; toxicity signs include sedation
What type of drug is Felbamate and what is it used to treat?
it’s an NMDA receptor blocker with secondary effect at voltage-gated Na and Ca channels and GABA system; tx partial onset seizures with or w/out secondary generalization and for medically refractory epilepsy
What are some potential side effects of taking Felbamate?
aplastic anemia and acute hepatic failure (requires monitoring)
