Antiepileptics for partial seizures and generalize TC's, the Narrow Spectrum agents Flashcards
What are the narrow spect agents?
Carbamazepine
Phenytoin
Fosphenytoin
Gabapentin
Pregabalin
Vigabatrin
Tiagabine
Mechanism of Carbamazepine
Indications
Inhibits Voltage gated Na+ channels. Binds and stabilizes the inactive form.
- Trigeminal neuralgia
- Partial, focal seizures
Mechanism of Phenytoin
Indications
Inhibits voltage gated Na channels, prolongs inactive state.
- for focal or tonic-clonic seizures
- Fosphenytoin for maintenance therapy in patients after status epilepticus (along with i.v. benzos to halt the acute episode)
Gabapentin and Pregabalin
Mechanism and indications
DONT AFFECT GABA CHANNELS, but
- Increase presynaptic GABA release.
- Block voltage gated CALCIUM channels
Indications:
Neuropathic pain
Fibromyalgia
Post-herpetic neuralgia
Vigabatrin mechanism and indications
Irreversibly inhibits GABA transaminase, decreased GABA metabolism,
increases CNS GABA levels
indication
Adjunct treatment for partial seizures only
Tiagabine mechanism and indications
Inhibits GAT-1
presynaptic GABA reuptake protein
Increases ynaptic GABA
indication
Adjunct treatment for partial seizures only
Vigabatrin SE.
30% of patients experience VIsual field loss with VIgabatrin
Carbamazepine SEs (a lot)
Diplopia - usually the first SE
Ataxia
SIADH
Potentially fatal Marrow suppression.
-Agranulocytosis
-Aplastic anemia
Routine blood counts are required
CYP inducer (shiny car bumper)
DRESS syndrome
Teratogenic - Neural tube defects
SJS and TEN, especially in Asians with a known HLA allele, screen for prior to admin.
Liver damage
Liver function tests required.
Withdrawal seizures if stopped abruptly.
Carbemazepine metabolism
Is both a CYP substrate AND a potent CYP inducer.
So, doses should be monitored.
Also is highly protein bound, competes with phenytoin, valporate, sulfonamides.
Phenytoin SEs ( a lot )
Diplopia AND Nystagmus
Ataxia
Folate Deficiency
-Megaloblastic anemia
Gingival hyperplasia in FIFTY PERCENT of patients after 3 months.
From increased PDGF and increased alveolar BONE growth.
Hirsuitism
Drug induced SLE
DRESS syndrome
SJS and TEN, also especially in Asians with known HLA
Teratogenic
CYP inducer
Decreases Bone density,
-Calcium and vitamin D supplemjent, as well as bone monitoring are indicated
Phenytoin injections i.m. WILL cause tissue necrosis
to give parenterally, you must use the Fosphenytoin formulation that is converted to phenytoin in blood.
Withdrawal seizures if stopped abruptly
Phenytoin kinetics
variable oral bioavailability from differences in first pass metabolism
RAPIDLY SATURABLE
Kinetics switch from first order to zero order at moderate/high doses.
Concentration increases rapidly once saturated.
Not easily predictable, and should be monitored.
Highly protein bound also, competes with phenytoin and carbamazepine.
Liver metabolized, CYP substrate AND inducer, like Carbamazepine.
Gabapentin and pregabalin SEs
Kinetics
SEs
Ataxia, Dizziness, falls
Kinetics
- Excreted by kidney, must be lowered in kidney disease
- Non-linear, zero order saturable ABSORPTION, making its dose unpredictable.