This presentation describes the antiepileptic drug phenytoin, its mechanism of action, pharmacokinetics and therapeutic indications

1. DEVAANSH SYNGLE
2nd MBBS
SGRRIM&HS

2. } It is a major antiepileptic drug
} Not a CNS depressant
} Abolition of tonic phase of maximal electroshock
seizures
} With no effect on or prolongation of clonic phase
} Limits spread of seizure activity

3. • Membrane stabilising effect –prevents repetitive
detonation of normal brain cells during
depolarization shift.
• Achieved by prolonging the inactivated stage of
voltage sensitive neuronal sodium channel.
• As a result high frequency discharges are inhibited
Goodman and Gilman's Manual of Pharmacology and Therapeutics 2nd edition

4. • Reduction in calcium influx
• Inhibition of glutamate
• Facilitation of GABA responses

5. Absorption by oral route is slow
(poor aqueous solubility)
Widely distributed in body
80-90% bound to plasma proteins
Metabolised in liver by hydroxylation
involving CYP2C9 and 2C19 as well as
by glucuronide conjugation
Excreted in urine

6. The kinetics of
metabolism is
capacity limited
Small increments
in dose produce
disproportionately
high plasma
concentrations.
The plasma half life
progressively increases
when plasma
concentration rises above
10 µg/ml because
metabolising enzymes
get saturated.

7. Epilepsy
} First or second choice drug for partial and generalized tonic-
clonic seizures.
} Fosphenytoin is drug of choice for the emergency treatment
of status epilepticus.
} (Absence, myoclonic and akinetic seizures may worsen in
patientstreated with phenytoin).
} For seizure prophylaxis
Peripheral neuropathy
} One of the earliest drugs used
Trigeminal neuralgias
} Trigeminal neuralgia – 2nd to carbamazepine
Cardiac arrhythmias
} Mainly used when arrhythmias are due to digitoxicity