User Tools

Site Tools


anticonvulsants

anticonvulsants

General principles

missed tablets:

  • 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.

pregnancy and lactation

Brief overview of the anticonvulsants:

Benzodiazepines:

Diazepam:
Clonazepam: Rivotril

Barbiturates:

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;

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.

Ethosuximide: Zarontin;

  • 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

Carbamazepine: Tegretol

Oxcarbazepine:

  • 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;

Phenytoin:

Newer anticonvulsants:

Gabapentin:

  • 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;

Lamotrigine:

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

Vigabatrin:

  • 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);

Tiagabine:

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

Felbamate:

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

Flunarizine:

  • Marketed in Europe not Aust.
  • Appears promising;

Remacemide:

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

Pregabalin:

  • 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.
anticonvulsants.txt · Last modified: 2011/04/05 07:36 by gary