Antiepileptic Drugs Flashcards
Phenytoin: Class, Mech, Thera, SE’s, Other SE’s, Misc:
Class; Voltage-gated Na channel stabilizer
Mech: Stabilize inactive conformation of Na channel
Thera: Less effective for absence (particular pediatric), myoclonic, atonic seizures; effective against tonic-clonic seizures of primary generalized epilepsy or partial onset and secondarily generalized seizures; effective for acute seizures
Important SE’s: Rash, gingival hyperplasia, hirsutism, lupus-like reaction; can cause contraceptive failure
Other SE’s: Mild myelosuppression, increased LFT; long-term: cerebellar degeneration, peripheral neuropathy, osteoporosis
Misc: IV infusion limited by hypotension; hepatic enzyme inducer (both auto- and hetero-inducer), highly protein bound; IV route useful in STATUS EPILEPTICUS
Carbamazepine (Tegretol)
Class: Voltage-gated Na channel stabilizer
Mech: Stabilize inactive conformation of Na channel
Thera: More effective for complex partial seizure than primary generalized; bipolar disorder; neuropathic pain
Important SE’s: Rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs; can cause contraceptive failure
Misc: Hepatic enzyme inducer (both auto- and hetero-inducer); highly protein bound; must increase dose in 1-2 wks due to autoinduction; side effects likely due to epoxide metabolite
Oxcarbamazepine (Trileptal)
Class: Voltage-gated Na channel stabilizer
Mech: Stabilize inactive conformation of Na channel
Thera: More effective for complex partial seizure than primary generalized; bipolar disorder; neuropathic pain
Important SE’s: Rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs; can cause contraceptive failure
Misc: Designed to bypass carbamazepine epoxide; less protein-bound, less autoinduction, fewer interactions, less toxic, longer half-life than carbamazepine
Lamotrigine (Lamictal)
Class: Voltage-gated Na channel stabilizer
Mech: Stabilize inactive conformation of Na channel
Thera: Primary generalized epilepsies, absence seizures, partial complex epilepsy and secondary generalization; indicated in children; bipolar disorder; neuropathic pain
Important SE’s: Rash is dose related, (rarely, Stevens-Johnson): slow initial titration important; may lead to contraceptive failure
Misc: May exacerbate myoclonic seizures; competes with valproic acid for excretion (potential synergy); hepatic enzyme inducer; not very protein bound
Valproate (Depakote)
Mech: Unknown; likely affects Na-gated channels and GABA system
Thera: Broad spectrum: absence, myoclonic, tonic-clonic, primary generalized, partial onset, and secondary generalized seizures (but not absence seizures); IV for status epilepticus; bipolar treatment, migraine and long-term cluster headache prophylaxis
Important SE’s: Weight gain, hair turnover, hyperammonemia (which can be mitigated with oral carnitine), teratogenicity, blood dyscrasias
Other SE’s: Pancreatitis
Misc: highly protein bound, hepatic metabolism, rapidly absorbed and metabolized, short half-life, extended release preps!
Gabapentin (Neurontin)
Class: GABA analog
Mech: Block presynaptic influx of Ca
Thera: Adjunct for partial complex epilepsy; more commonly used for neuropathic pain
Important SE’s: Sedation
Misc: Absorption limited by intestinal AA transporter (there is a Tm); limited protein binding; no metabolism or drug interaction in humans (so few side effects)
Ethosuximide (Zarontin)
Class: Voltage-gated Ca channel blocker
Mech: Blocks T-type Ca-channels in thalamo-cortical circuits
Thera; Absence seizures only (and neuropathic pain)
Important SE’s: Nausea (transient), sedation, irritability
Misc: Readily absorbed, minimal first pass metabolism; not protein bound
Pregabalin
SAME as gabapentin (class, mech, thera)
Topiramate (Topamax)
Class: Glutamate Receptor Blockers
Mech: Partial AMPA, Kainate Ca receptor blocker; secondary effect at voltage-gated Na channel, GABA system
Thera: Partial onset seizures, secondary generalized seizures, primary generalized epilepsy; migraine prevention, long-term prevention of cluster headaches
Important SE’s: Mild metabolic acidosis, kidney stones (due to some carbonic anhydrase activity); modest weight loss; rare acute glaucoma; sedation
Other SE’s: Word-finding problems
Misc: Carbonic anhydrase activity leads to mild metabolic acidosis, which leads to respiratory compensation, which leads to mild alkalosis, which leads to calcium ionization, which leads to tingling; treat with vitamin C (acidify urine)
Levetiracetam (Keppra)
Class: Synaptic vesicle binder
Mech: Binds synaptic vesicle protein 2, leading to less NT release
Thera: Partial onset seizures, secondary generalized seizures; maybe primary generalized epilepsy
Important SE’s: Well tolerated; sedation, mostly; rarely, irritability, aphasia, thrombocytopenia
Lithium
Mech: Renal clearance related to serum [ ]; alters Na transport; inhibits Na reabsorption proximal tubule; contraindicated in those with arrhythmia or prone to dehydration; drug interactions with diuretics, ARB, NSAID
Thera: Anti-manic/mood-stabilizing (bipolar); long-term cluster headache prevention
Toxicity: lower level: sedation, dizzy, thirst, inc. urination, fine tremor;
higher level: “giddiness,” ataxia, blurred vision, large amt of dilute urine;
caution: Brugada syndrome, arrythmia, ask family history of sudden death <45
