Professional Documents
Culture Documents
The Pharmacokinetics of
Antiseizure Drugs
Antiseizure drugs are commonly used for
long periods of time
It is important to consider their
pharmacokinetics for avoiding toxicity and
drug interactions
Antiseizure drugs are well absorbed orally
and have good bioavailability
The Pharmacokinetics of
Antiseizure Drugs
Phenytoin :
The oral bioavailability is variable
Metabolism : nonlinear elimination (zero-order)
at moderate to high dose levels
The drug binds extensively to plasma protein
Interaction : the metabolism inhibited by
cimetidine, isoniazid and enhanced by inducer of
liver metabolism (sulfonamide, valproic acid
The Pharmacokinetics of
Antiseizure Drugs
Carbamazepine
Carbamazepine induces formation of liver drug-
metabolizing enzymes increase metabolism of the
drug itself, & may increase the clearance of many other
anticonvulsant
The metabolism can be inhibited by propoxyphene,
valproic acid
Valproic acid
Valproic acid inhibits the metabolism of phenytoin,
phenobarbital, and lamotrigine
Hepatotoxic
The Pharmacokinetics of
Antiseizure Drugs
Gabapentine & Vigabatrin
These drugs eliminated by the kidney, largely in
unchanged form
Other Mechanism
Enhancing K+ channel permeability
(valproic acid)
Antagonist at some glutamate receptors
(phenobarbital, felbamate, topiramate)
Clinical Uses
Generalized Tonic-Clonic & Partial Seizures
Valproic acid, carbamazepine, & fenitoin
are DOC for generalized tonic-clonic
seizure & partial seizure
Phenobarbital is a primary drug in infants
Absence Seizure
Ethosuximide and valproic acid are the
preferred drugs because they cause
minimal sedation
Clinical Uses
Myoclonic seizure syndromes
Valproic acid
Clonazepam, but the high doses cause
drowsiness
Status Epilepticus
Diazepam & lorazepam i.v (effective in
terminating attacks, providing short-term control)
Phenytoin i.v (for prolong therapy, because it is
less sedation)
Phenobarbital has been used in status
epilepticus, especially in children
Clinical Uses
Other Clinical Uses
Bipolar disorder (valproic acid,
carbamazepine, phenytoin, & gabapentin
Trigeminal neuralgia (carbamazepine)
Pain of neuropathic origin (gabapentin)
Migraine (phenytoin)
Toxicity
Teratogenicity (valproic acid, carbamazepin,
phenytoin)
Overdosage toxicity, include CNS depressants,
respiratory depression
(flumazenil may be used in benzodiazepine
overdose)
Fatal hepatotoxicity (valproic acid)
Skin rashes & Stevens-Johnson syndrome
(Lamotrigine)
Aplastic anemia & acute hepatic failure
(felbamate)
Withdrawal