anticonvulsants

see also:

• seizures and Mx
• pharmacology main index
• RCH therapeutic drug level monitoring guidelines (pdf)
• anticonvulsant overdose/poisoning

• withdrawal of anticonvulsant Rx in seizure-free patients

• in general, if it is time for next dose within next 4hours, skip the missed dose & take next dose when it is due, otherwise take the missed tablet ASAP and then resume normal dosing.
• DO NOT take a double dose to make up for the missed dose as this may cause toxicity.

• potentiating GABA at GABA_A receptors
  • direct GABA_A receptor action
    • benzodiazepines
    • topiramate
  • GABA turnover
    • sodium valproate
    • vigabatrin
    • tiagabine
• voltage gated sodium channels
  • phenytoin
  • carbamazepine
  • sodium valproate
  • lamotrigine
  • felbamate
  • topiramate
  • oxcarbazepine
  • zonisamide
  • rufinamide
  • lacosamide
  • eslicarbazepine acetate
• HVA calcium channels
  • lamotrigine
  • gabapentin
  • pregabalin
  • felbamate
  • topiramate
• LVA calcium channels
  • ethosuximide
  • sodium valproate
  • zonisamide
• voltage gated potassium channels
  • retigabine
  • topiramate
• glutamate receptors
  • perampanel
  • felbamate
  • topiramate
• synaptic vesicle protein 2A
  • levetiracetam
• carbonic anhydrase
  • topiramate
  • zonisamide
  • lacosamide
• hydrocarboxylic acid receptor 2 (HCAR2)
  • niacin
  • β-hydroxybutyrate (β-HB) (ketogenic diets)

• ? via GABA-induced incr. Cl conductance;
• see benzodiazepines

• see diazepam

• see clonazepam

• see barbiturates

• see phenobarbitone
• limits spread of seizure activity & incr. seizure threshold - GABA effect;
• slow complete oral absorption ⇒ peak @ sev. hrs; Vd=0.5L/kg;
• 25% pH-depend. renal excretion unchanged, rest metab. by microsomes; T½=100hrs;
• tolerance develops to sedative effects; XS dose ⇒ nystagmus/ataxia;
• IV 12mg/kg load ⇒ peak brain [ ] 15min. but sedation +++ ⇒ not used much IV;

• see sodium valproate (Epilim)
• Approved in 1960's (Europe) & in 1978 (US) as anticonvulsant with minimal sedative & with particular use for absences but also for tonic-clonic GM.

• Anticonvulsant spectrum resembles trimethadione with the most prominent characteristic being protection against pnetylenetetrazol-induced seizures & also increases seizure threshold to ECT but only abolishing tonic response in anaesth. doses.
• Does not block Na-channels nor GABA effects;
• More effective in absences & lower risk of serious adverse effects than trimethadione
• see ethosuximide

• see carbamazepine

• Similar to carbamazepine in molecular structure, less potent on wt basis, probably less sedating in equi-effective anticonvulsant doses but greater tendency to cause hyponatraemia;

• see phenytoin
• Na channel blocker

• Released Aust. '94
• GABA analogue released Aust.'94 as adjunct with other anticonvulsants
• Not metabolised; Excreted mainly in urine; T1/2 = 5-7hrs
• Effective dose 900-1800mg/d, introduce gradually over a few days;
• 7% pts stopped Rx as adverse effects but on multiple anticonvulsants;
• Pancreatic tumours have occurred in rodents but ? relevance;
• Adverse effects:
  • somnolence, dizziness, ataxia, fatigue;
• see gabapentin (Neurontin)

• Released Aust '94;
• A phenyltriazine unrelated to other anticonvulsants;
• ? acts via inhib. release of excitatory neurotransmitters in brain;

• Released Aust'93;
• An irreversible GABA-transaminase inhibitor → raises brain GABA conc.
• Thus plasma levels do not correlate with anticonvulsant effects.
• May control partial seizures resistant to other anticonvulsants;
• No major P/K interactions with other anticonvulsants.
• As add-on Rx, start dose 0.5g bd adults, incr. in stages to 2.0g bd dependong on response;
• Main side effects: sedation (dose related);

• Under development still;
• GABA analogue as with Gabapentin;

• Marketed in USA not Aust.
• Uncertain mechanism of action;
• Useful in the difficult-to-treat Lennox-Gastaut synd. as well as other seizures;

• Marketed in Europe not Aust.
• Appears promising;

  *Under development;   *Interferes with excitatory amino acid receptors;

• introduced in Australia in 2005.
• analogue of GABA, although its actions may be on non-GABA pathways.
• reduces release of neurotransmitters by interfering with calcium channels in nerve terminals.
• used in Rx of epilepsy as well as neuropathic pain such as post-herpetic neuralgia & diabetic neuropathy.
• see pregabalin (Lyrica)

• ketogenic diets appear to have various neuroprotective effects including reducing some seizures
• a potential mechanism is via the antiseizure effect of β-hydroxybutyrate (β-HB)
  • this effect, along with niacin's antiseizure effect, appears to be mediated via the Hydrocarboxylic acid receptor 2 (HCAR2) ¹⁾