Neurology

Question 1

Phenytoin (Dilantin) MOA:

Answer 1

Inhibit generation of high-frequency repetitive action potentials by binding to voltage sensitive channels of neurons. Preferentially binds to Na+ channels in inactivated state and prolongs their refractory period in a manner analogous to class IB antiarrhythmics (see lidocaine). Thus, inhibits spread of epileptiform discharges without interfering with normal neuronal depolarization.

Question 2

Phenytoin (Dilantin) Clinical use:

Answer 2

Generalized tonic clonic and partial seizures (first line agent)
Treatment of status epilepticus after initial management with benzodiazepines.
Mixed seizures (tonic-clonic and myoclonic): second-line agent.
Digoxin-induced ventricular arrythmias (unline other epileptic drugs of this type, phenytoin exhibits cross-reactivity at cardiac Na+ channels.)

Question 3

Phenytoin (Dilantin) Side effects:

Answer 3

Toxicity: nystagmus, diplopia, ataxia, sedation, confusion, slurred speech.
Gingival hyperplasia, hirustism, and sensory neuropathy with long term use.
Teratogenic (fetal hydantoin syndrome).

Question 4

Phenytoin (Dilantin) Metabolism:

Answer 4

PO or IV (n.b.dissolved in potent vesicant). Must determine plasma levels and clearance rates in individual patients because undergoes saturable first-pass metabolism (i.e. zero-order kinetics).

Question 5

Phenytoin (Dilantin) Notes:

Answer 5

FOSPHENYTOIN (Ceberyx) is a water-soluble prodrug that is metabolized by plasma esterases to phenytoin. Solubility makes it safer to administer IV than phenytoin.
LAMOTRIGINE (Lamictal) also acts at Na+ channels and is used primarily to treat partial seizures.
ZONISAMIDE (Zonegran) is similar to lamotrigine; its ability to block T-type Ca+ channels may extend its use to absence and myoclonic seizures (see ethuximide)