Pharmacology for Dentistry

Antiepileptic Agents 107

neuronal Na+ channels & governs the refractory
period of a neurone.

After oral administration peak plasma con-
centration of phenytoin usually takes 2 to 4
hours with a second peak at 10 to 12 hours.
When administered intramuscularly, pheny-
toin is eventually absorbed completely, the
drug first crystallises out at the injection site
and then slowly redissolves in tissue fluids be-
fore entering into the circulation. As a result
absorption of phenytoin by IM route is too slow
to produce a reliable effect. In contrast a phos-
phate prodrug, fosphenytoin, is more soluble
and is well absorbed after IM administration.

In liver it is extensively biotransformed
by oxidation, with less than 5 percent of the
dose excreted unchanged in urine. Majority
of dose is excreted in urine with up to 15
percent of the dose is eliminated in the faeces.

Adverse effects include gum hypertro-
phy, hirsutism, hypersensitivity reaction,
megaloblastic anemia, osteomalacia and
hyperglycemia.

During pregnancy produces foetal
hydantoin syndrome. At higher
concentration produces ataxia, vertigo,
diplopia, nystagmus, behavioural alteration
and mental confusion.

It is used in prophylactic treatment of
all varieties of partial epilepsy whether or
not seizure becomes secondarily
generalised. It is also used in prophylactic
treatment of generalised convulsive
seizures and treatment of status
epilepticus; prophylactic management of
certain forms of supraventricular cardiac
arrhythmia as it has an ability to
selectively inhibit high frequency firing;
prophylactic management of certain

varieties of migraine (particularly

childhood, basilar artery and hemiplegic

migraine) and in treatment of myotonia.

IMINOSTILBENE DERIVATIVES

CARBAMAZEPINE

It is structurally and chemically related

to tricyclic antidepressant drug imipramine

and pharmacologically it is similar to

diphenyl hydantoin sodium. It is effective

in grandmal and psychomotor epilepsy and

also in the treatment of trigeminal neuralgia

(a condition characterized by paroxysms of

intense pain of stabbing nature within the

area of distribution of trigeminal nerve

without sensory loss).

It also exerts antidiuretic action by

enhancing ADH action on renal tubules.

Carbamazepine, because of its poor

water solubility has slow oral absorption. It

is metabolized in the liver to an active

metabolite, (10-11 epoxy carbamazepine) by

oxidation as well as by hydrolysis and

conjugation to inactive forms.

Adverse effects include sedation, ataxia,

dizziness and extrapyramidal side effects, dry

mouth, blurred vision and urinary retention;

hepatic damage, bone marrow depression,

hypertension, left ventricular failure and

cardiovascular collapse in toxic doses.

OXCARBAZEPINE

It is a keto analog of carbamazepine. It

produces blockade of voltage sensitive

sodium channels, leading to stabilisation of

hyperexcited neural membranes, inhibition

of repetitive neuronal firing and diminution

of propagation of synaptic impulses.