AEDs Flashcards
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
What drugs are broad spectrum and used to treat both partial and all types of generalized seizures?
Valproate Lamotrigine Zonisamide Topiramate Felbamate Levetiracetam
What drug is used to treat only absence seizures?
Ethosuximide
What are the drugs that induce their own metabolism by CYP450s?
Phenytoin Carbamazepine Oxcarbazepine Phenobarbital Topiramate
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
What are first line drugs to treat generalized seizures?
Valproate
Also potentially Levetiracetam
What is mechanism of action of Phenytoin?
Na+ channel blocker –> slows rate of channel recovery
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)
What are side effects of Phenytoin?
Gingival hyperplasia - common side effect Ataxia Nystagmus Incoordination Confusion Hirsutism Facial coarsening Systemic skin rash
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
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
What are side effects of Carbamazepine?
Sedation Drowsiness Headache Dizziness Blurred vision
What is the mechanism of action of Oxcarbazepine?
Na+ channel blocker –> slows rate of channel recovery
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
What is the mechanism of action of ESL?
Na+ channel blocker (higher affinity for inactive state)
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
What are side effects of ESL?
Dizziness Somnolence Headache Nausea Vomiting
What major drug interaction does ESL have?
Decreases oral contraceptive ability
What is ESL used to treat?
Partial seizures
What is Lacosamide used to treat?
Partial seizures - as add-on therapy
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
