Seize the Night Narrow Spectrum Anti-Epileptics

4.3 – “Seize the night”: Narrow sspectrum pectrum anti anti-epile -epile -epileptics ptics (Car (Carbamazepine, bamazepine, phenytoin, gabapent gabapentin, in, tiagabine, vigabat vigabatrin) rin) • Generally used to treat focal seizures (waitress with shaking arm). Note that narrow spectrum prescriptions may be used to treat generalized tonic-clonic seizures, but should be avoided in other generalized disorders, including JME, as may cause exacerbation. • Carbamazepine (classic car) o Ineffective against absence seizures and should be avoided in other generalized disorders o Binds VG dependent Na channels, probably after closure of inactivation gate (closed bags of chips). preventing sustained high-frequency firing and sustaining inactivation phase of neurons. o First line for treatment of trigeminal neuralgia (three gems on seize the night sign). Reduces pain in 80% of patients o Adverse effects ▪ Dose related diplopia (cross car headlights). Often occurs first ▪ Dose related ataxia (toppling stack of burgers) ▪ Rare: SIADH (inappropriately wet head). Due in part to increased responsiveness of collecting tubules to ADH causing dose related hyponatremia that develops over the first few months of therapy. ▪ Idiosyncratic blood dyscrasias • Leukopenia (12% children, 7% adults). May be transient or persistent. Doesn’t usually require immediate discontinuation • Fatal aplastic anemia, Fatal agranulocytosis (hourglass; falling level of granulocytes in anemia). Usually within 3-4 months of initiating therapy. WBC < 3000 or neutrophil < 1000 are indications for lowering dose or cessation. ▪ CYP450 inducer; drug interactions (license plate) ▪ Rare, potentially life-threatening DRESS syndrome (=drug reaction with eosinophilia & systemic symptoms). Can occur 2-8 weeks after exposure; px with fever, generalized lymphadenopathy, diffuse morbilliform rash, facial edema (waitress wearing spotted dress) ▪ Teratogenic (greaser’s spider jacket) Neural tube defects, esp. spinal bifida. May be implicated in fetal malformation of nails, distal phalanges, hypertelorism, characteristic facial features. ▪ Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) (mask). Much more common with HLA-B15 allele, which occurs almost exclusively in people of Asian ancestry; screening for this allele prior to initiating treatment recommended. ▪ Drug induced lupus (lupus wolf) • Phenytoin (classic tow truck) o Ineffective against absence seizures and should be avoided in other generalized disorders o Binds VG dependent Na channels, probably after closure of inactivation gate (closed bags of chips). preventing sustained high-frequency firing and sustaining inactivation phase of neurons. o Treat status epilepticus with benzos or phenytoin (Order Status at Ben’s Diner). Maintenance therapy is usually with IV phenytoin or fosphenytoin (tow truck under Order Status sign) ▪ If patient doesn’t respond, start IV phenobarbital (barbershop) o Adverse effects ▪ Dose related ataxia (toppling stack of burgers) ▪ Diplopia, nystagmus ▪ Low folate & megaloblastic anemia have been reported; clinical significance unknown (spilled salad) ▪ Gingival hyperplasia (bubble gum) ▪ Hirsutism & coarsening of facial features (especially rugged man) ▪ Drug induced lupus (lupus wolf) ▪ Rare, potentially life-threatening DRESS syndrome (=drug reaction with eosinophilia & systemic symptoms). Can occur 2-8 weeks after exposure; px with fever, generalized lymphadenopathy, diffuse morbilliform rash, facial edema (waitress wearing spotted dress) ▪ Rash. Patients who have rash to phenytoin are more likely to have with carbamazepine too ▪ SJS/TEN (mask). Much more common with HLA-B15 allele, which occurs almost exclusively in people of Asian ancestry; screening for this allele prior to initiating treatment recommended. ▪ Teratogenic (greaser’s spider jacket) Orofacial clefts, genitourinary defects, cardiac malformations (cleft trucker hat). ▪ CYP450 inducer; drug interactions (license plate) ▪ Altered bone and mineral metabolism & decreased bone density (osteoporotic axel). Related to increased induction of CYP450 combined with decreased Vitamin D catabolism. Suggest supplementation • Gabapentin, pregabalin (grab a pint) o Sometimes used as addon therapy for refractory focal seizures o Binds avidly to VG calcium channels; may inhibit inward calcium currents and attenuate NT release (calci-yum ice cream door blocked). No binding to GABA o Used more often to treat neuropathic pain (Frayed wire), including post herpetic neuralgia (Zeus’s Ice Cream), fibromyalgia (fiber bars), & painful diabetic neuropathy (diasweeties candy). o Adverse effects ▪ Dose dependent dizziness, sedation, ataxia (tall falling ice cream cone) • Vigabatrin o Irreversible inhibitor of GABA transaminase (transmission), which is normally responsible to GABA degradation. Results in sustained elevation of GABA levels in the CNS (elevated Cab-A), resulting in tonic inhibition of the CNS o Used as adjunctive treatment for partial seizures • Tiagabine o Inhibits GABA uptake, prolonging inhibitory action of GABA in the synaptic cleft (cab driver stuck outside of cab) o Used as adjunctive treatment for partial seizures