anticonvulsants
Table of Contents
anticonvulsants
see also:
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:
- ? via GABA-induced incr. Cl conductance;
- see benzodiazepines
Diazepam:
- see diazepam
Clonazepam: Rivotril
- see clonazepam
Barbiturates:
- see barbiturates
Phenobarbitone:
- 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;
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
- see ethosuximide
Carbamazepine: Tegretol
- see carbamazepine
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:
- see phenytoin
- Na channel blocker
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 127.0.0.1