Term
| What are the 4 major therapeutic options for treating Epilepsy? |
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Definition
1) AEDs (first line- treat seizures not epileptogenesis)
2) Ketogenic diet
3) Vagus nerve stimulator (if not good surgical candidate)
4) Surgery ("last resort" unfortunately- only 3-5% of eligible people get it) |
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Term
| What are the principle mechanisms of AED action? |
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Definition
1) Inactivation of Na channels by keeping in inactive state
(Phenytoin and Carbamazepine)
2) Inactivation of Ca channels
(Ethosuximide)
3) Activation of K channels
4) Increased GABA
(Phenobarbital)
5) Decreased excitatory transmission
(Phenobarbital) |
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Term
| How do Phenytoin (PHT) and Cabamazepine (CBZ) prevent seizures? |
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Definition
| These AEDs bind to and stabilize inactive state of voltage-gated sodium channels |
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Term
| How does Phenobarbital prevent seizures? |
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Definition
1) Facilitates GABA binding to GABAa receptor
2) Interferes with post-synaptic Glutamate signaling |
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Term
| How was Topiramate (TPX) exert anti-seizure effects? |
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Definition
Multi-mechanisms
1) Blocks voltage-dependne Na channels
2) Enhances GABA at GABA-A receptor
3) Antagonism of glutamate effects at AMPA-R |
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Term
| How do Ethosuximide prevent seizures? |
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Definition
Inhibit calcium flux through T-type channels in thalamus
- Relevant for hypersynchronous discharge in absence seizures due to RTN volleys
**T-type channels require hyperpolarization through GABA-b receptors to become re-activated** |
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Term
| How do Vigabatrin and Tiagabine prevent seizures? |
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Definition
Increase inhibitory tone of cortex through GABA processing
1) Vigabatrin inhibits GABA transaminase (inhibits degradation)
2) Tiagabine inhibits ABA reuptake |
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Term
| Which drugs are useful in the acute seizure context and why is that the case? |
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Definition
They can be given IV (most are oral)
- Valproic acid
- Levetiracetam
- Diazepam (also rectally)
- Lorazepam (also sublingually in pill) |
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Term
| For which drugs are protein binding interactions a significant problem? |
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Definition
| Phenytoin and Valproate (bind to serum albumin and travel throughout body!) |
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Term
| What are the basic pharmacological properties of AEDs? |
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Definition
1) Most oral with rapid absorption
2) Most hepatically degraded (mixed-fuction oxidases) and excreted in urine
3) Older drugs are enzyme inducers (Phenytoin, primidone, phenobarbital, carbamazepine), newer drugs are enzyme inhibitors (Valproate and felbamate)
4) Most exhibit linear, first-order elimination kinetics (Phenytoin is dose-dependent) |
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Term
| Which AEDs are "enzyme inducers" and which are "enzyme inhibitors"? |
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Definition
Older are inducers (
- Phenytoin, Phenobarbitol, Carbamazepine, Phenytoin
Newer are inhibitors
- Felbamate |
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Term
| Which AED exhibits dose-dependent elimination kinetics? |
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Definition
Phenytoin
**others exhibit linear pharmacokinetics** |
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Term
| What are the key interactions to be aware of when prescribing Enzyme-inducing drugs such as Phenobarbital, Phenytoin, Carbamazepene or Primidone? |
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Definition
1) increase metabolism of Oral Contraceptives (Pregnancy)
2) decrease Warfarin (DVT/emboli)
3) Clear Statins (hypercholesterolism)
4) Decrease tricyclic concentration/increase AED (depression) |
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Term
| If your patient is on Statins and Birth control, which AED might you avoid prescribing? |
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Definition
1) Enzyme-inducers such as Phenytoin, Phenobarbital, Primidone and Carbamazepene.
- Increase statin clearance (increase cholesterol)
- Increase contraceptive metabolism (pregnancy)
2) Lamotrigine
- decrease LTG (breakthrough seizure) |
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Term
| If a patient is on Warfarin and is being treated for depression with TCAs, which AEDs might you avoid? |
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Definition
1) Enzyme-inducers (Phenobarbital, Phenytoin, Primidone and Carbamazepeme)
- Decrease warfarin (DVT, emboli)
- Decrease TCA concentration and increase AED concentration (more depression)
2) Felbamate
- increase warfarin concentration (bleading/stroke) |
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Term
| If your patient is on antacids, which AED might you avoid? |
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Definition
| Phenobarbital, PHT, CBZ, Gabapentin decrease AED absorption in gut (lower efficacy) |
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Term
| What are common side effects of AEDs? |
|
Definition
1) Neurological/psychiatric (dose-related)
- drowsiness, sedation, cognitive impairment, depression, mood changes, oculomotor and cerebellar issues
2) Systemic toxicity (idiosyncratic)
- GI, serum liver enzymes (benign), weight gain, leucopenia (benign), anorexia, osteopenia, renal stones |
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Term
| What are the major differences between older (CBZ, PB, PHT, valproate) and newer AEDs? |
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Definition
1) Newer not metabolized by liver- older is
2) Newer binds less protein- older binds serum protein
3) Newer have few interactions |
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Term
| What types of AEDs should be given to a patient with Focal seizures without impairment of consciousness or awareness? |
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Definition
First Choice
1) CBZ (not if on contraceptives or warfarin)
2) Gabapentin (not if on antacids)
3) Lamotigine (not if on contraceptives)
4) Levetiracetam |
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Term
| What types of AEDs should be given to a patient with Focal seizures WITH impairment of consciousness or awareness? |
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Definition
| Oxycarbazepine or Topiramate |
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Term
| What types of AEDs should be given to a patient with Focal seizures with evolving bilateral convulsions? |
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Definition
| Valproic acid or Zonisamide |
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Term
1) What types of AEDs should be given to a patient with generalized absence seizures?
2) What drugs are contraindicated? |
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Definition
1) Ethosuximide or Valproic acid
2) CBZ and PHT |
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Term
1) What types of AEDs should be given to a patient with generalized Myoclonic seizures?
2) What drugs are contraindicated? |
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Definition
1) Valproic acid or Lamotrigine
2) CBZ and PHT (Vigabatrin not approved) |
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Term
| What factors should be taken into account in AED selection? |
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Definition
1) Seizure type
2) Adverse effects
3) Dosing regimen (ease of use)
4) Interactions
5) coexisting nonepilepic conditions
6) Comorbid conditions
7) Cost |
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Term
| Why is monotherapy the preferred AED strategy? |
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Definition
1) fewer side effects
2) less chronic toxicity
3) fewer interactions
4) compliance
5) costs
6) teratogenicity
**Polytherapy only when 2 or 3 drugs prove innefective** |
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Term
| If a patient has a first, unprovoked seizure, what is the argument for them being given AED treatment? |
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Definition
2.8 x reduced risk of occurrence, but 50% will not have it anyways.
- If second unprovoked seizure, AED use is CLEAR |
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Term
| What is the probability that patients with Lennox-Gastaut syndrome will be responsive to AED? |
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Definition
LOW!
Kids with typical childhood absence epilepsy show complete control with Ethosuximide or Valproate though. |
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Term
| When should VNS or Epilepsy surgery be considered? |
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Definition
| In Medically-refractory epilepsy (fails 2-3 AEDs) |
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Term
| What are the risks of chronic AED use? |
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Definition
1) Bone turnover
2) Osteoporosis and bone quality alteration
3) Cognitive consequences (polytherapy) |
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