Core pharmacology

Class Group

Anticonvulsant

Indications Uses

Anticonvulsant and antiarrhythmic (V-W class 1b)
Epilepsy
Trigeminal neuralgia
TCA toxicity
Digoxin-induced arrhythmias

Chemical Pharmaceutics

# Hydantoin derivative
# Precipitates at pH < 7
◦ → variable oral absorption
◦ → IM contraindicated

Presentation

Capsules, Syrups, Injections
# Doses 15-20 mg/kg IV loading  maintenance (plasma levels
required aim 10-20µg/mL)
# Rapidly achieves peak (<20mins after loading)
# Duration 30mins-1hr but highly variable

Mechanism of action

# Slows inward Na and Ca ion flux during depolarisation and delays outward K flux.
◦ Stabilises the inactive state of V-gated Na channels limiting repetitive generation of APs.
▪ Limits spread of seizure
◦ Reduce glutamate release and thus attenuating Ca entry
# Enhance action of GABA

Absorption

IV, PO – variable 30-75%

Protein binding

90% protein bound

Volume of distribution

Vd – 0.6-0.7 L/kg

Metabolism

# Hepatic to parahydroxyphenyl (inactive)
◦ hydroxylation by CYP450 2C9
▪ Metabolism effected by inducers or inhibitors of CYP450 2C9
◦ induces its own CYP450
# Mixed 1st and zero order kinetics as process is saturable
◦ 1st order at plasma [] 10 µg/mL ▪ t1/2 dose dependent

Excretion

< 3% unchanged in urine