Anticonvulsant therapy
DRUG
Phenobarbitol
(luminol)
Pharmacokinetics
Use as first line med. To unclassified
neonatal seizures and status
epilecticus (alternative for partial and
tonic/clonic)
MOA
Inc. in GABA, dec. in Glutatmate
Effectiveness
Not used much b/c of
side effects
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 pHPPH
High for Generalized
tonic-clonic, Partial,
and Status epilepticus
Carbamazepine
(Tegretol)
Related to tricylics, slow absorp. 7580% protein bound, not displaced by
other drugs, T ½ = 8-20 hrs.
A. inhibit seizure spreadStim. Of Na/K pump, block Ca influx,
B. suppression of focusInc. affinity for inactivated Na
channels at more depolarized
membrane potential – red. Of
SHFRH(sustained hi freq. Repetitive
firing)
-Na channel blockade red. Of SHFRH
-inc. firing rate of noradrenergic
neurons (proposed to inhibit partial
seizures
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
Levetiracetam
(Keppra)
Water sol. , renally cleared and
unmetabolized, NO drug interactions,
not protein bound, T1/2 = 6-8 hours
Unknown
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 voltagesensitive Na and Ca channels
-enhances GABA
-reduces Glu excitation by
antagonizing kainite/AMPA-act. Glu
rec. subtype
-Adjunct in tx. Of
partial +/- secondary
generalization
-Absence seizures
-Lennox-Gastaut syn.
(neonatal seizure type)
Tx of partial seizures +
2 generalizations
Good for people w/liver
probs or on warfarin
Adjunct Tx. Of partial
and 2 generalizations
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
-Partial
-generalized
tonic/clonic
-Absence seizures
-Myoclonic
-Reflex epilepsies
-Generalized Tonicclonic
-Partial seizures
Potential Problems, etc
Drowsy, interfere w/
cognitive, behavioral changes
(up to 44%), addiction?,
additive sedative effects,
potential for withdrawal
siezure
-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
-Lethargy, atazia, and
diplopia
-Dose-dependent neutropenia
-Aplastic anemia (rare)
-Hyponatremia (up to 30%,
elderly ; dose dependent)
-Dizzi, headache, diplopia,
ataxia, somnolence,
-metabolism induced by
phenytoin, carbamazepine,
inhibited by valproic acid,
-skin rash
Somnolence, dizziness, HA
Dec. by 50% when receiving
phenytoin or carbamazepine
-Somnolence and
fatigue(25%)
-impaired concentration,
mental slowing 20%
-Renal stone formation 1.5%
Weight loss
-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
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
Lorazepam
(Ativan) BZD
PKa = 1.3 and 11.5, insol. In water,
90% protein bound, rapidly absorbed,
rapid penetration into CSF, T ½ = 825hrs., biotransformed to inactive
glucuronide and excreted via urine
Blocks Ca channels of thalamic
interneurons that appear to interrupt the
neuronal hypersynchrony of
thalmocortical pathways seen in
absence seizures
-Agonist action on BZD binding site
of GABA rec. complex
-at sedating and antistatus doses,
blocks Ca channels and SHFRF
DOC for Absences
seizures
N/V, headache
Status epilepticus
-Sedation, anterograde
amnesia, dysarthria,
-Withdraw seizures following
abrupt cessation of chronic
therapy