AEDs Flashcards by Danielle Himelfarb

What drugs are narrow spectrum and primarily used for partial seizures (and tonic-clonic seizures)?

Phenytoin
Carbamazepine
Oxcarbazepine
ESL
Lacosamide
Benzodiazepines
Phenobarbital (Barbiturates)
Gabapentin and Pregabalin

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What drugs are broad spectrum and used to treat both partial and all types of generalized seizures?

Valproate
Lamotrigine
Zonisamide
Topiramate
Felbamate
Levetiracetam

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What drug is used to treat only absence seizures?

Ethosuximide

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What are the drugs that induce their own metabolism by CYP450s?

Phenytoin
Carbamazepine
Oxcarbazepine
Phenobarbital
Topiramate

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What are the first line drugs to treat partial seizures?

Phenytoin - lots of side effects, drug-drug interactions
Carbamazepine - less side effects, also has dual action to suppress seizure foci AND prevent spread (often drug of choice)
Oxcarbazepine - less side effects and interactions, usually used as add-on

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What are first line drugs to treat generalized seizures?

Valproate

Also potentially Levetiracetam

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What is mechanism of action of Phenytoin?

Na+ channel blocker –> slows rate of channel recovery

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What is unique about the metabolism of Phenytoin?

Induces P450s, causing increase in own metabolism

Metabolism shows properties of saturation kinetics
- Enzymes become saturated at higher doses and small increase in dose can cause unpredictable increases in plasma drug concentration (causing toxicity)

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What are side effects of Phenytoin?

Gingival hyperplasia - common side effect
Ataxia
Nystagmus
Incoordination
Confusion
Hirsutism
Facial coarsening
Systemic skin rash

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What is the mechanism of action of Carbamazepine?

Na+ channel blocker –> slows rate of channel recovery

Unique in that has dual action in suppression of seizure foci and prevention of spread of activity

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What is unique about metabolism of Carbamazepine?

Induces P450s, causing increase in own metabolism
- Larger doses may be necessary to maintain constant serum concentrations in first 3-6 weeks

Active 10-11 epoxy metabolite may contribute to neurotoxicity

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What are side effects of Carbamazepine?

Sedation
Drowsiness
Headache
Dizziness
Blurred vision

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What is the mechanism of action of Oxcarbazepine?

Na+ channel blocker –> slows rate of channel recovery

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How dose oxcarbazepine compare to carbamazepine?

Some induction of P450s, but much less than Carbamazepine
Sedating, but less side effects
Fewer interactions with other AEDs - but does interact with oral contraception

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What is the mechanism of action of ESL?

Na+ channel blocker (higher affinity for inactive state)

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What is unique about the metabolism of ESL?

Is a pro-drug that gets metabolized into an active drug specific for the active site

NO autoinduction of P450s

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What are side effects of ESL?

Dizziness
Somnolence
Headache
Nausea
Vomiting

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What major drug interaction does ESL have?

Decreases oral contraceptive ability

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What is ESL used to treat?

Partial seizures

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What is Lacosamide used to treat?

Partial seizures - as add-on therapy

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What is mechanism of action of Lacosamide?

Na+ channel blocker by changing conformation of Na+ channel

What are Benzodiazepines used to treat?

Partial seizures, Tonic-clonic seizures
But NOT first line choice for any treatment
Typically only used to ablate seizures acutely

What is the mechanism of action of Benzodiazepines?

GABA-potentiation
Enhances affinity of GABA-A receptor for GABA –> increases frequency of Cl- channel opening when GABA is bound –> hyperpolarization –> reduced neuron firing

What are side effects of Benzodiazepines?

Sedation, dizziness, ataxia, drowsiness, tolerance

What drugs are given IV for status epilepticus?

Dizepam or Lorazepam (Benzos) | Phenytoin

What is Phenobarbital used to treat?

Partial seizures, Tonic-clonic seizures | but NOT first line

What is mechanism of action of Phenobarbital?

GABA-potentiation (increase affinity of GABA-A receptor for GABA) GABA-mimetic (can open GABA receptor itself)

What are side effects of Phenobarbital?

Heavily sedating, cognitive effects, tolerance, withdrawal

What are Gabapentin and Pregabalin used to treat?

Partial seizures, Tonic-clonic seizures | but as Add-on therapy

What is mechanism of action of Gabapentin and Pregabalin?

Bind Alpha2-Delta1 subunit of voltage-gated Ca2+ channels --> reduce Ca2+ current --> decreased neuron firing

What is Valproate used to treat?

Generalized seizures - first line | And Partial seizures, Absence seizures

What are mechanisms of action of Valproate?

Inhibits T-type Ca2+ channels Na+ channel blocker Increases availability of GABA at synapse by increasing its synthesis

What are side effects of Valproate?

``` Problematic sedation Tremor Hair loss Weight gain Elevated liver enzymes GI disturbances ```

What is a major deterrent to use of Valproate in women?

Teratogenicity - linked to ASD, sensory deprivation disorder, spina bifida

What drug interactions does Valproate have?

Valproate and Carbamazepine induce each other's metabolism (P450s) Valproate inhibits Phenobarbital metabolism Valproate displaces phenytoin from binding proteins - contributes to toxicity

What is Lamotrigine used to treat?

Partial seizures, Secondary generalized tonic-clonic | but only Add-on (rarely monotherapy)

What are mechanisms of action of Lamotrigine?

Na+ channel blocker Reduced glutamate release - glutamate receptor antagonist Inhibition of Ca2+ channels

How is Lamotrigine metabolized?

Glucuronidation in liver

What is Zonisamide used to treat?

Partial seizures (only thing FDA approved for) Sometimes used for myoclonic type generalized or for absence seizures

What are mechanisms of action of Zonisamide?

Na+ channel blocker Inhibits T-type Ca2+ channels Glutamate receptor antagonist (reduced glutamate release)

What is Topiramate used to treat?

generalized seizures EXCEPT absence

What are mechanisms of action of Topiramate?

Glutamate receptor antagonism GABA-potentiation Na+ and Ca2+ channel block Carbonic anhydrase inhibitor

What are side effects of Topiramate?

Kidney stones Cognitive/language difficulties Oral-contraceptive interaction

What is Felbamate used to treat?

Restricted to patients with refractory-to-treatment epilepsy due to serious side effects

What is mechanism of action of Felbamate?

Glutamate receptor antagonism

What are side effects of Felbamate?

Adverse behavioral effects | Cases of fatal aplastic anemia and liver failure

What is Levetiracetam used to treat?

Partial seizures | Generalized seizures

What is mechanism of action of Levetiracetam?

Modulates synaptic vesicles --> enhances release of GABA May prevent epileptogenesis

What is Ethosuxamide used to treat?

Absence seizure

What is mechanism of action of Ethosuxamide?

Inhibits T-type Ca2+ channels in thalamus