Antiepileptics Flashcards
initiation of seizures involves 2 things
1) high frequency bursts of APs
2) hypersynchronization
3 mechanisms for the recruitment of surrounding neurons
1) more extracellular K depolarizes neighbors
2) Ca2+ accumulates in presynaptic neurons–> more NT release
3) activation of NMDA glutamate receptors –> Ca2+ influx
4 AED mechanisms
1) inactivate Na and Ca channels
2) target glutamate receptors
3) target GABA receptors
4) multiple mechanisms
Simple partial seizure
- no impairment of consciousness
- usually confined to a limb or muscle group
Complex partial seizure
- consciousness impaired
- brain origin is localized
Partial seizures secondarily generalized
partial seizure–> generalized tonic clonic seizure
Generalized tonic clonic seizure
- tonic rigidity, followed by tremor
- massive jerking of the body
Absence seizure (petit mal)
- 10-45 seconds
- altered consciousness
- childhood, assoc with mental retardation
Myoclonic
-isolated rhythmic clonic jerks
Atonic
sudden loss of posture–> collapse
infantile spasms
- bilateral attacks of myoclonic jerks
- <1 yo, assoc with mental retardation
Glutamate receptors
- EXCITATORY
- found in all neurons
- blocked by Mg2+ (or glycine, rarely)
types: NMDA, AMPA, KA
GABA receptors
- INHIBITORY
- only in neurons with glutamate decarboxylase
types: GABA-a, GABA-b
Barbituates vs. Benzos at GABA-a receptors
Barbituates: increase duration of Cl- channel opening
Benzos: increase frequency of Cl- channel opening
Phenytoin (diphenylhydantoin) MOA
- blocks firing by inactivating Na+ channels
- reduces NT release
Phenytoin pharmacokinetics
- Time to peak varies from pt to pt*
- Gingival hyperplasia and hirsutism*
- shifts from 1st order to zero-order kinetics
- hard to predict serum conc–> need to monitor levels
Carbamazepine (a TCA) MOA
- blocks firing by inactivating Na+ channels
- reduces NT release
- potentiates GABA
Carbamazepine pharmacokinetics
- active metabolite
- Toxicities: aplastic anemia, rash common
- CNS effects: ataxia, diplopia, nystagmus, dizziness
- some tolerance to SEs
- many DDIs
Primidone MOA
- blocks firing by inactivating Na+ channels
- Phenobarbital is a metabolite–> enhances GABA
Primidone pharmacokinetics
- slow but complete absorption
- not highly prot bound
- induces hepatic enzymes
- toxicities: nystagmus, ataxia
Adjuvant therapies for partial seizures
Gabapentin
Lamotrigine
Vigabatrin
Gabapentin MOA
- does NOT interact with GABA-a (designed to though)
- binds voltage-gated Ca2+ channels–> decreases glutamate release
- inhibits GABA transaminase
Gabapentin pharmacokinetics
-not prot bound or metabolized–> very few drug interactions**
Lamotrigine MOA
-blocks firing by inactivating Na+ channels
- lots of DDIs
- rash common in children
