Lecture 46: Antiepileptics Flashcards
Narrow-spectrum medications are useful for what kind of seizure? What two kinds are they not useful for?
Focal seizures; generalized tonic-clonic seizures and myoclonic seizures
Broad-spectrum medications are effective for…
Focal and generalized seizures
Name the narrow spectrum drugs (2)
Gabapentin, tiagabine
Name the broad spectrum drugs (6)
Phenytoin, carbamazepine, valproate, topiramate, levetiracetam, lamotrigine*
What drug treats absence epilepsy?
Ethosuximide**
What drug treats status epilepticus?
Lorazepam*
Three most common mechanisms of antiepileptics
Inhibit VG-Na+, inhibit VG-Ca2+, enhance GABA
Why is the hippocampus predisposed to seizures? (2)
Excitatory positive feedback to CA3 neurons; densely packed neurons
An epilepsy linked to a genetic defect might have a defect where?
Channels (i.e. increased excitatory/reduced inhibitory currents through VG-channels)
How do AEDs inhibit Na* channels? Name them (5)
Stabilize inactive state of channel; Carbamazepine, valproate, topiramate, phenytoin, lamotrigine
How do AEDs enhance GABA signaling? Name them (3)
Allosterically at GABAa; Benzos, phenobarbital (barbituate), topiramate
Which AED increases synaptic levels of GABA? How?
Tigabine; blocks GABA reuptake
What channel underlies absence epilepsy? Where? Usually associated with?
Ca2+ channels in thalamocrotical neurons; sleep spindles
Which two drugs inhibit T-type Ca2+ channels, making them good at treating…
Ethosuximide and Valproate; absence seizures
What other drug can be used to treat absence seizures?
Clonazepam
Two drugs inhibit another type of Ca2+ channel. What are these drugs?
Lamotrigine and levetiracetam
Topiramate inhibits Na+ channels. What is another mechanism of its action?
Modulates AMPA receptors
According to LC, the mechanism of this drug is unknown. According to lecture, it increases K+ conductance. Drug?
Levetiracetam
Key note about Phenytoin and relevant SEs (acute: 3, chronic: 1)
Non-linear pharacokinetics in therapeutic window make window narrow; nystagmus, ataxia, hypersensitivity (Stevens-Johnson); gingival hyperplasia
Is phenobarital commonly prescribed? SE?
No! Was once widely prescribed AED; sedation
Carbamazepine comes with what important 3 warnings. Which are rare?
Rare: blood dyscrasias, Stevens-Johnson; hyponatremia
Tigabine has what common side effect?
Dizziness
What is the most widely used AED, worldwide? Describe its clinical use
Valproate; Can be used for general, partial, absence AND myoclonic
Topiramate’s other uses and some SEs
Headache, alcoholism, tremor, obesity…paresthesias in 30%
While the mechanism fr this drug is unknown, it has some advantages…what are those?
Levetiracetam; does not induced liver enzymes and is well-tolerated
When you see Ethosuximide, think about this seizure type. How is it tolerated?
Absence; well
Four specific adverse events in AEDs
Serious hypersensitivity reactions, cognitive slowing, sedation, seizure induction
Which two drugs are associated with malformations in pregnancy?
Valproate and phenobarbital
What warning do all AEDs bear?
Increased suicide risk
Describe status epilepticus treatment (5 steps)
- Start ASAP to protect neurons; 2. Begin w/ benzos; 3. Give phenytoin to prevent recurrence; 4. If not controlled, give phenobarbital or valproate; 5. If still not, induce general ansethesia
Induction
Drug A increases enzyme for Drug B –> Drug B eliminated faster
Competition
Drug A and Drug B are substrates for same enzyme –> Drug B eliminated slower
Inhibition
Drug A inhibits enzyme for Drug B –> Drug B eliminate slower
Which pharmacokinetic interaction is important for AEDs? Which enzymes? Which drugs?
Induction; CYP450; phenytoin, carbamazepine, phenobarbital
