Phenobarbitol (luminol) / Use as first line med. To unclassified neonatal seizures and status epilecticus (alternative for partial and tonic/clonic) / Inc. in GABA, dec. in Glutatmate / Not used much b/c of side effects / Drowsy, interfere w/ cognitive, behavioral changes (up to 44%), addiction?, additive sedative effects, potential for withdrawal siezure
Phenytoin (Dilantin) / -Weak organic acid, low sol. In plasma, penetrates brain rapidly, IM injection results in crystallization and possible muscle necrosis
-metabolized in liver / excreted as p-HPPH / A. inhibit seizure spread-
Stim. Of Na/K pump, block Ca influx,
B. suppression of focus-
Inc. affinity for inactivated Na channels at more depolarized membrane potential – red. Of SHFRH(sustained hi freq. Repetitive firing) / High for Generalized tonic-clonic, Partial, and Status epilepticus / -Cosmetic- thick facial features, darkened hair, gum hypertrophy (1/3), macrocytosis, n/v w/ high doses, sedation and cogn. Impairment at high doses, severe allergic rxns, DRUG interactions
Carbamazepine (Tegretol) / Related to tricylics, slow absorp. 75-80% protein bound, not displaced by other drugs, T ½ = 8-20 hrs. / -Na channel blockade red. Of SHFRH
-inc. firing rate of noradrenergic neurons (proposed to inhibit partial seizures / -Partial
-generalized tonic/clonic / -Lethargy, atazia, and diplopia
-Dose-dependent neutropenia
-Aplastic anemia (rare)
-Hyponatremia (up to 30%, elderly ; dose dependent)
Lamotrigine (Lamictal) / PKa = 5.7 sl. Sol. In water, 55% protein bound, does not sig. Displace other anticonvulsants, excreted in urineas inactive gluuronide-conj. Metabolite
T ½ = 20-30hrs. / -Inhibits voltage-sens. Na channels
-inhibits glutamate and aspartate rel.
-Ca channel blockade / -Adjunct in tx. Of partial +/- secondary generalization
-Absence seizures
-Lennox-Gastaut syn. (neonatal seizure type) / -Dizzi, headache, diplopia, ataxia, somnolence,
-metabolism induced by phenytoin, carbamazepine, inhibited by valproic acid,
-skin rash
Levetiracetam (Keppra) / Water sol. , renally cleared and unmetabolized, NO drug interactions, not protein bound, T1/2 = 6-8 hours / Unknown / Tx of partial seizures + 2 generalizations
Good for people w/liver probs or on warfarin / Somnolence, dizziness, HA
Topiramate (Topamax) / 15% protein bound, doesn’t displace other anticonvolsants, only 20% metabolized, excreted in urine, T ½ = 18-23 hrs. / -State dependent blockade of voltage-sensitive Na and Ca channels
-enhances GABA
-reduces Glu excitation by antagonizing kainite/AMPA-act. Glu rec. subtype / Adjunct Tx. Of partial and 2 generalizations / Dec. by 50% when receiving phenytoin or carbamazepine
-Somnolence and fatigue(25%)
-impaired concentration, mental slowing 20%
-Renal stone formation 1.5%
Weight loss
Valproate
(Depakote) / PKa = 4.95, highly water sol., rapid and near complete absorption, 90% protein bound, T ½ = 8-12 hrs., elim. Via urine mainly, similar to fatty acid / Inhibits SHFRF
Induces blockade of Na and Ca channels
High Conc. Increases GABA / -Absence seizures
-Myoclonic
-Reflex epilepsies
-Generalized Tonic-clonic
-Partial seizures / -N/V, (relieved by coated pill)
-Elevated liver enzymes (SGOT) dose dependent
-Idiopathic liver necrosis(<2yrs)
-increases phenobarb levels
ataxia and tremor at high doses
Anticonvulsant therapy
Ethosuximide (Zarontin) / Lipophilic but rel. water soluble, complete absorption from GI tract, absence of Protein binding, Met. In liver, T ½= 18-72 hrs after chronic tx / Blocks Ca channels of thalamic interneurons that appear to interrupt the neuronal hypersynchrony of thalmocortical pathways seen in absence seizures / DOC for Absences seizures / N/V, headacheLorazepam (Ativan) BZD / PKa = 1.3 and 11.5, insol. In water, 90% protein bound, rapidly absorbed, rapid penetration into CSF, T ½ = 8-25hrs., biotransformed to inactive glucuronide and excreted via urine / -Agonist action on BZD binding site of GABA rec. complex
-at sedating and antistatus doses, blocks Ca channels and SHFRF / Status epilepticus / -Sedation, anterograde amnesia, dysarthria,
-Withdraw seizures following abrupt cessation of chronic therapy