Epilepsy Flashcards
molecular targets and actions of antiepileptic drugs
limit excitability or enhance inhibition
voltage gated sodium channels
membrane ion channel involved in action potential generation. stabilize inactive state inhibiting recurrent depolarization. phenytoin, carbamazepine, oxcarbamazepine, lamotrigine.
voltage gated calcium channels
presynaptic membrane channels. blocking influx of Ca leads to less excitatory neurotransmitter release. useful in treating in neuropathic pain. ethosuximide hits T type in thalamus. Gabapentin and pregabalin hit high voltage type
glutamate receptors
post synaptic membrane of excitatory synapses. ligand gated cation channels. Felbamate is NMDA receptor blocker. Topiramate is partially active as AMPA and Kainate receptor blocker. Selective and specific AMPA and Kainate receptor blockers are in development
GABA system
GABA-A receptors are found on post synaptic membranes of inhibitory synapses. ligand gated Cl channels. Phenobarbitol and benzodiazepines activate receptors.
voltage gated sodium channel drugs
stabilize inactive state inhibiting recurrent depolarization. similar efficacy, similar metabolism, similar toxicity. hepatic enzyme inducers. phenytoin, carbamazepine, oxcarbamazepine, lamotrigine
carbamazepine
sodium channel blocker. sedation, ataxia, and doplopia are toxicity. adverse reactions: rash, mild hepatic enzyme elevation, mild myelosuppression. more effective for complex partial epilepsy than primary generalized. also used for bipolar affective and neuropathic pain
carbamazepine pharmacologic considerations
highly protein bound. autoinduction. induces own metabolism. heteroinduction: induces metabolism of other drugs (like birth control). short half life, extended release preparations needed. toxicity due to epoxide metabolite
phenytoin
sodium channel blocker. dizziness, nystagmus, ataxia, incoordination toxicity. adverse reactions: mild hepatotoxicity and myelosuppression, gingival hyperplasia, rash, hirsutism, lupus like rxn. long term cerebellar degeneration, peripheral neurpathy, osteoporosis. IV infusion limited by hypotension. effective against tonic clonic seizures of primary generalized epilepsy or partial onset and secondarily generalized seizures. effective for acute seizures
phenytoin pharmacologic consideration
highly protein bound. hepatic metabolism. enzyme inducer. effects other hepatically metabolized meds. can be associated with contraceptive failure. variable but longer half life. IV route useful in status epilepticus
oxcarbazepine
same efficacy and indications as carbamazepine. designed to bypass carbamazepine epoxide. less protein bound, less autoinduction, less toxic, longer half life. useful for neuropathic pain
lamotrigine
sodium channel blocker. dizziness, sedation, ataxia, diplopia toxicity. rash is dose related, slow initial titration is important. effective for primary generalized epilepsy, partial complex epilep, and secondary generalization, and absence. good for kids. can make myoclonic seizures worse. used in bipolar and neuropathic pain
lamotrigine pharm considerations
hepatic metabolism. less protein bound. hepatic enzyme inducer. can cause contraceptive failure. competes for excretion with valproic acid. synergistic action with depakote.
benzodiazepines
used in status epilepticus. acts at GABA-A receptors. dose limited by sedation. long term usefullness limited by tolerance. short acting due to redistribution. midazolam used in anesthesia or refractory status epilepticus. lorazepam lasts 10-20 minutes. short half life but less distribution. diazepam is 5 minutes, longer halflife but more distribution
valproate
blocks Na channels and GABA system. sedation and tremor are toxicity. nausea, weight gain, hair loss, hyperammonemia, teratogenic effects are adverse reactions. broad spectrum of activity. useful in a lot of epilepsy types, migraine prophylaxis, and bipolar
