Anti-Seizures Medications

• Seizure 


  excessive, hypersynchronous discharge of the cortical neuron activity
• Epilepsy 


  chronic seizure disorder, wherein the seizures occur and recur unpredictably
• Epilepsy: Symptomatic 


  if secondary to brain injury, tumor, or vascular malformation in the brain
• Epilepsy: Idiopathic 


  if secondary to genetic problem, with no structural or metabolic abnormality
• Convulsions 


  violent, involuntary contractions of the voluntary muscles
• A patient may have an epilepsy without convulsion (as in the case of petit mal)
• Classification of Seizure: Focal Onset Seizure

  • Are those that affects a local cortical site.
• Subtypes of FOS:

  • Focal Aware (simple partial seizure) - patient retains consciousness or awareness
  • Focal Impaired (complex partial seizure) - patient losses consciousness or awareness
  • Focal-to-Bilateral Tonic-Clonic (Secondary Generalized or grand mal) - seizure starts as a focal type and progress to a generalized tonic-clonic type.
• Classification of Seizure: Generalized Onset Seizures

  • Are those that affects both hemispheres of the brain.
• Subtype of GOS:

  • Generalized Tonic-Clonic (Primary Generalized or Grand mal) - commonly occurs as idiopathic or genetic generalized epilepsies
• Subtype of GOS:

  • Generalized Absence (Petit mal) - common among children, characterized as having a brief loss of consciousness with no warning or resumption of consciousness
• Subtype of GOS:

  • Myoclonic - occurs in juvenile seizure or in Dravet syndrome; exhibiting as a sudden brief involuntary single/ multiple muscle/ muscle group contractions
• Subtype of GOS:

  • Atonic (drop or astatic seizure) - occurs in Lennox-Gastaut syndrome; exhibiting as a sudden loss of muscle tone causing a forward fall
• Subtype of GOS:

  • Epileptic spasms (West syndrome) - infantile spasm exhibiting grimacing, head nodding, and subtle eye movement
• Treatment of Epilepsy

  • Oral antiseizure medication depending on the patient’s seizure type of syndromic classification.
  • Single medication is preferred, but for adults multiple medication is advised due to hard-to-control seizures. If medication is inadequate to control seizures, it can be referred to as “pharmacoresistant”.
• Treatment for Epilepsy:

  • Epilepsy surgery (common for focal) to resection the affected brain region
  • Electrical stimulation devices
  • Vagus Nerve Stimulation (VNS)
  • Responsive Neurostimulator (RNS)
  • Deep Brain Stimulation (DBS)
  • Dietary therapies especially ketogenic diet for more protein intake helps with children
• Mechanism of Action:

  • The MOA is primarily to interact with one or more molecular targets in the brain and ultimately inhibit local generation of discharges by decreasing high firing rate of action potential and by reducing neuronal synchronization
• Action of Antiseizure is broadly described:

  • Modulation voltage-gated Na, Ca, and K
  • Enhancement of fast GABA-mediated synaptic inhibition
  • Modification of synaptic release process
  • Diminution of fast glutamate mediated excitation
• Anti-seizure drug activity is generally acting on the balance between excitatory and inhibitory activity in the neurons since seizure occurs if there is imbalance leading to outcomes favorable to excitation.
• Voltage-Gate Ion Channels:

  • Na
  • Phenytoin/ Fosphenytoin (prodrug)
  • Carbamazepine / Oxcarbazepine
  • Eslicarbazepine
  • Lamotrigine
  • Lacosamide
  • Topiramate
  • Zonisamide
  • Rufinamide
  • Cenbamate
• Voltage-Gate Ion Channels:

  • Ethosuximide (Ca-channel T-type)
• Voltage-Gate Ion Channels:

  • Retigabine (K-channel)
• GABA Inhibition:

  • Phenobarbital
  • Primidone
  • Ganoxolone
  • BZDs
  • Topiramate
  • Felbamate
  • Cenobamate
  • Retigabine
  • Tiagabine (GAT-1 GABA Transporter)
  • Vigabatrin (GABA transaminase)
• Synaptic Release Machinery:

  • Levetiracetam (SV2A)
  • Brivaracetam (SV2A)
  • Gabapentin (𝛼2𝛿)
  • Pregabalin (𝛼2𝛿)
• Ionotropic Glutamate Receptors:

  • Perampanel (AMPA receptors)
• Disease Specific:

  • Everolimus (mTORC1 signalling)
• Mixed/ Unknown:

  • Valproate
  • Felbamate
  • Cenobamate
  • Topiramate
  • Zonisamide
  • Rufinamide
  • Adrenocorticotropin
  • Cannabidiol
• Focal Seizures:

  • 1st line drugs
  • Carbamazepine
  • Lamotrigine
  • 2nd line drugs
  • Levetiracetam
  • Oxacarbazepine
  • *sodium valproate
  • Others/ Adjunct
  • Clobazam
  • Gabapentin
  • Levetiracetam
  • Topiramate
• Generalized Onset:

  • 1st line drugs
  • Sodium valproate
  • 2nd line drugs
  • Lamotrigine
  • Others/ Adjunct
  • Clobazam
  • Levetiracetam
  • Topiramate
• Absence:

  • 1st line drugs
  • Ethosuximide
  • Sodium valproate
  • 2nd line drugs
  • Lamotrigine
  • Others/ Adjunct
  • Clobazam
  • Clonazepam
  • Levetiracetam
  • Topiramate
  • Zonisamide
• Myoclonic:

  • 1st line drugs
  • Sodium valproate
  • 2nd line drugs
  • Levetiracetam
  • Topiramate
  • Others/ Adjunct
  • Clobazam
  • Clonazepam
  • Piracetam
  • Zonisamide
• Tonic/ Atonic:

  • 1st line drug
  • Sodium valproate
  • 2nd line drug
  • Lamotrigine
• Other medications used in the management of seizures:

  • Diazepam — for acute repetitive seizure
  • Lorazepam — for status epilepticus
  • Midazolam — for acute repetitive seizures; out-of-hospital status epilepticus (IM)
  • Clonazepam — for absence, myoclonic, and atonic seizures
  • Nitrazepam — for infantile spasms and myoclonic seizures
  • Clorazepate — for focal seizures
  • Clobazam — for atonic seizures
  • Acetazolamide — for decreasing excitation due to bicarbonate influx