Anticonvulsants
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Introduction
As the different types of seizure are diverse, so too are the different treatments that are used.
Treatment specificity is especially true with the absence type seizure.
Animal models have been useful for identiying drugs useful for treating epilepsy.
- pentylenetetrazol induces clonic seizures
- mutant mice show absence-like seizures
maximal elecroshock tests mimicks generalized tonic0clonic seizures and complex partial seizures
- led to the identifcation of drugs that inactivate voltage sensitive sodium channel
limbic seizures brought on by electrical kindling mimicks complex partial seizures
All anticonvulsant drugs have idiosyncratic or dose-dependent side effects. Treatment doses are increased until either seizure control occurs or dose-limiting side effects appear.
Benzodiazepines can be used to end seizures.
Indications
Common Medications
- GABA enhancement
- sodium channel inhibition
- calcium channel inhibition
- adjuncts
Enhancement of GABA action
works against a variety of seizures
- benzodiazepines
- pentobarbital
- vigabatrin: inhibits GABA transaminase; ramps GABA up 300%
- terrible behavioural side effects
- tiagabin: blocks GABA uptake
Inhibition of sodium channel function
good for partial seizures
phenytoin
Serum concentration increases by first order kinetics up to a certain point, when zero order kinetics take place.
It can be difficult to adjust serum concentrations when jumping past this point, which represents the exhaustion of the body's excretion capacity.
Increase dosage by 50 mg and reassess levels after 5-7 days, as the half-life is ~20h.
carbamazapine
- sodium channel active agent
- potent inducer of P450 enzymes; auto-inducer and lowering its own level
- will reduce many drugs, including OC
Inhibition of Calcium T-type channels
- ethosuximide - absence seizures
valproic acid - generalized seizures
- anti-seizure medication
- mood stabilizer
adverse effects
- can cause thrombocytopenia or inhibit platelet aggregation, potentially leading to increased bleeding
- hair loss, weight gain
- CNS problems: sedation, cognitive blunting
- increases liver enzymes
- polycystic ovary syndrome
~11% rate of congenital malformations; spina bifida and neural tube defects, heart defects, IUGR
ASA, used regularly for analgesia, can reduce valproic acid elimination
Used as adjuncts
- felbamate
- gabapentin
- lamotrigine
- topiramate
Guidance on Use
Most antiseizure drugs have oral activity, are well absorbed, and enter the CNS. Most are not highly bound to plasma proteins.
Antiseizure drugs are cleared chiefly by hepatic metabolism and clearance in stool.
Half-lives of antiseizure dtugs tend to be long - some over 12 hours.
Resources and References
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