93. Anticonvulsants Flashcards
What is the average response rate to Anti-Epileptic drugs?
What are the (4) mechanisms of seizure generation?
What are the targets for AEDs/Anticonvulsants?
60% respond, 40% refractory
Seizure generation:
1. Too much excitation: too much inward Na/Ca channels, too much Glutamate
2. Too little inhibition: to little inward Cl channel, too little outward K channel, too little GABA
Targets for AEDs
- more GABA, less Glutamate
- block V-gated inward positive currents (Na/Ca influx)
- increase positive outward current (K efflux)
Which first gen anticonvulsants are enzyme inducers? Which are enzyme inhibitors?
Inducers: Phenobarbital, Phenytoin, Carbamazepine
Inhibitors: Valproate
Phenytoin
- use
- mechanism
- difficulty, half-life
- SE
- interactions
Use: 1st line for focal epilepsy, tx of status epilepticus
Mech: inhibits rapid firing of Na Channels
Problem: 90% drug bound to proteins in plasma - only 10% active and variable
Half-life: 22-36hrs (1x/day)
SE: CNS Sedation (drowsy, ataxia, confusion, insomnia, nystagmus), gum hyperplasia, hirsutism
Interactions: (Enzyme inducer)
- increases levels of EtOH, diazepam, methylphenidate
- decrease levels of phenobarbital, carbamazepine
- valproate causes displacement from protein (higher levels)
Carbamazepine
- use
- mechanism
- half-life
- SE
- interactions
use: 1st line for partial seizures
Mech: inhibits Na Channels, (tricylic like TCAs)
Half: 6-12 hours (2x day)
SE: CNS sedation, Agranulocytosis/Aplastic Anemia (low WBC), leukopenia, hypoNa, WORSENS ABSENCE SEIZURES
Interactions: (Enzyme inducer)
Phenobarbital
- use
- mechanism
- half-life
- SE
- interactions
use: partial seizures in neonates (2nd line for adults due to SE)
Mech: allosteric modulator of GABA (increase duration of opening)
Half: 72hrs (1x/day)
SE: CNS sedation or paradoxical excitement; tolerance/dependence
Interactions: High CNS depression with EtOH/Benzos and Enzyme inducing
Valproate
- use
- mechanism
- problem, half-life
- SE
- interactions
Use: broad-spectrum, 1st line for generalized epilepsy, focal seizures, mood stabilizer, migraine prophylaxis
Mech: increase GABA, blocks Na/Ca channels, increases K Channels
Absorption: 90% protein bound
Half: 6-16 hrs (1x/day)
SE: GI upset, hair loss, weight gain, high liver enzymes (Hepatotoxicity rare), teratogenic (NTDs)
Interactions: (Enzyme-Inhibitor)
- potentiates CNS depressants, displaces phenytoin from protein
Ethosuximide
- type of drug
- use
- mechanism
- half-life
- SE
- interaction
First line AED
use: SPECIFIC FOR ABSENCE SEIZURES
mech: blocks T-type Ca channels in thalamus
Half: long (40hrs)
SE: GI Distress (pain, n/v), less CNS effects (fatigue, HA, dizzy)
Interaction: metabolism blocked by valproate
Oxcarbazepine
- use
- metabolism
- mechanism
- half life
- SE
- Interactions
Use: monotherapy for partial seizures (better carbamazepine)
Metabolism: reduction rxn (no CYPs = less SE)
Mech: blocks Na Channels, may augment K Channels
Half: 1-2 hrs, metabolite 8-12hrs (3x/day)
SE: less toxic CNS sedation than carbamazepine, more prominant hypoNa
Interactions: stim CYP3A4, inhibit CYP2C19
Benzodiazepines
- type
- use
- mech
- absorption
- SE
- interactions
Second Gen AEDs
use: rescue med in status epilepticus, myoclonic seizures
mech: increase freq of Cl channel opening thru modulation of GABAa receptor
Absorption: RAPID ONSET
SE: CNS sedative, tolerance/dependence, children paradoxical hyperexcitability
Interaction: increases action of other CNS depressants
Gabapentin
- type
- use
- mechanism
- absorption, half-life
- metabolism
- SE
- Interaction
2nd gen AED
use: add-on tx for partial seizures, 90% off-label use for neuropathic pain
mech: interferes with GABA uptake (unclear)
absorption: nonlinear, saturable (cannot OD)
half: short (5-9hrs); (2-3x/day)
metabolism: none, eliminated by kidneys
SE: less prominent CNS sedation, Weight gain, edema
Interaction: none known
Lamotrigine
- type
- use
- mech
- half-life
- SE
- Interactions
potent broad spectrum 2nd gen AED
use: monotx and adjunct tx for generalized/focal epilepsies, mood stabilizer for BPD
mech: inhibits Na/Ca channels, Glu release
half: 24 hrs (1x/day)
SE: well tolerated, less CNS sedation, SJS (life-threatening dermatitis), safe in pregnancy
Interactions: raise levels with valproate, decrease levels with carbamazepine, PB, phenytoin
Felbamate
- type
- use
- mech
- SE
- Interactions
2nd gen AED
use: 3rd line drug for refractory partial seizures (rarely used due to toxicity)
mech: freq-dependent inhibition of Na channels, decrease NMDA receptors via glycine receptor
SE: aplastic anemia, severe hepatitis, stimulant effects (insomnia, less appetite, weight loss)
Interactions: complex
- raises plasma phenytoin, valproate
- decreases plasma carbamazepine
- stim CYP3A4, inhibit CYP2C19
Levetiracetam
- type
- use
- mech
- half-life
- interactions
- SE
2nd gen AED
use: broad spectrum for partial/generalized epilepsies
mech: binds synaptic vesicle protein SV2A (inhibits NT release) and decreases V-gated Ca channels
half: 6-8hrs (short)
interactions: minimal
SE: CNS Depression, Irritability
Zonisamide
- type
- use
- mech
- SE
- interactions
2nd gen AED
use: broad spectrum add-on for partial/generalized; migraine prophylaxis, weight loss
mech: blocks Na Channels, T-type Ca channels, CA-i (cause kidney stone)
SE: CNS sedation, Memory/Cognitive effects, Kidney stones, appetite suppression/weight loss, anhydrosis
Interactions: minimal
Topiramate/Topamax
- type
- use
- mech
- half-life
- SE
- interactions
2nd gen AED
use: potent broad spectrum AED; migraine prophylaxis; neuropathic pain; tremor
mech: block Na Channels, increase freq of GABAa channel, interfere with Glu binding NMDA receptor
half: 20-30hrs (2x/day)
SE: CNS sedation, memory/cognitive effects, appetite suppression/weight loss
Interactions: stim cyp3A4, inhibit CYP2C19, lessens effectiveness of birth control
