AED Flashcards
Phenobarbitol
Luminal (Barbituate) 2-6 hr half-life SE: Sedation Metab: Para-hydroxylation (2C9, 2C19) GABA-a Receptor Potent Inducer of P450 and some UGT
Primidone
Mysoline (Barbituate)
Prodrug for phenobarbital (oxidation), or PEMA (Multiple rx)
Overall effect from all three structures
Less sedating than phenobarbital
Phenytoin
Dilantin (Hydantoin) Blocks Na channels Less sedating than phenobarbital Inducer of P450 and UGT Metab: P-hydroxylation (2C9 major, 2C19) Arene Oxide intermediate leads to inactive hydroxylated metabolite, or reacts with GSH to create GHS + mercapturic acid. Potential cause for toxicity (SJS/TEN)
Fosphenytoin Sodium
(Hydantoin)
Water-soluble prodrug of phenytoin (IM or IV)
Converts to phenytoin + phosphate + formaldehyde in about 15 min in body
Ethosuximide
Zarontin (Succinimide)
Can be first choice for absence seizures uncomplicated by other seizure types
Blocks Ca Channels
Small alkyl group (vs aromatic group) correlates to effectiveness in absence seizures
Metab: Hydroxylation on the ethyl (3A4, 2E1)
Toxicities limit use: rare anemias, hepatotoxicity, reduced kidney fx
Blood and liver tests are required
Valproic Acid, Divalproex Sodium
Depakene, Depakote
Metab: Direct Glucuronidation (Inactive), Beta oxidation (double bond minor metabolite, know how to draw d/t toxicity)
9-16 hr half-life (reduced when taking other AED - E.g., phenobarbital or phenytoin)
Can inhibit 2C9, some UGT, and epoxide hydrolase
Hepatotoxicity - liver fx monitoring required, Also rare pancreantitis and can casue fatal malformations
Carbamazepine (CBZ)
Tegretol
Black Box Warning: Aplactic Anemia (agranulocytosis), Serious skin rx (SJS, Asian population), Clinical monitoring required, also rare liver toxicity
Blocks Na channels
Metab: 3A4
Strong P450 inducer (autoinducer), and UGT inducer
(Know how to draw metabolism d/t alkylated protein toxicity)
Oxcarbazepine
Trileptal
Metab: Reduced to licarbazepine (racemic) mono-hydroxy key active metabolite
9-11 hr half-life
Analog of CBZ that can’t form toxic epoxide
Induce 3A4 (less than CBZ), Inhibit 2C19
Lacks major blood (and minor liver) toxicity of CBZ, but can still cause some skin rx (much less common)
Eslicarbazepine acetate
Aptiom
Prodrug for Licarbazepine (Rapid Hydrolysis, S-enantiomer only)
Induce 3A4 (less than CBZ), Inhibit 2C19
Lacks major blood (and minor liver) toxicity of CBZ, but can still cause some skin rx (much less common)
GABA Metabolism
L-Glutamate
(GAD, CO2) - Valproate activates GAD
GABA
(GABA-AT, 2-oxoglutarate, L - Glu) - inhib by valproate & vigabatrin
Succinate Semialdehyde (SSA)
(NAD+, SSA-DH, NADH) - Inhib by valproate
Succinate –> TCA Cycle
Gabapentin
Neurontin
Acts at specific type of Ca channels (alpha2, delta)
Designed to be more lipophilic analog of gaba, but doesn’t work at GABA receptors
5-7 hr half-life
Keys for Gabapentin as Adjuctive Therapy
1) Not appreciably metabolized
2) Doesn’t induce/inhib hepatic enzymes
3) Doesn’t alter pharmecokinetics of other AED
4) It’s pharmacokinetics not altered much by other AED’s
5) Lacks blood/liver toxicity
Gabapentin enacarbil
Horizant
Lipophilic prodrug of gabapentin
Used to tx pain assoc. w/ shingles
Not for epilepsy
Pregabalin
Lyrica S-enantiomer Acts at same Ca channel as gabapentin Similar adj qualities < 2% Metab 6 hr half-life CV d/t some euphoria
Vigabatrin
Sabril Irreversible Inhib of GABA-AT Adj for refractive complex partial seizures not controlled by other drugs (BBW: Permanent Vision Loss) Racemic Mixture, but only S active 7.5 hr half-life Not sig metab Induces 2C9
