358
P A R T 4
Drugs acting on the central and peripheral nervous systems
Contraindications and cautions
Phenytoin is generally contraindicated in the presence of
allergy
to avoid hypersensitivity reactions.
These agents
are associated with specific birth defects and should not
be used in pregnancy or breastfeeding unless the risk of
seizures outweighs the potential risk to the fetus. In such
cases, the mother should be informed of the potential
risks. The risk of taking a woman with a seizure disorder
off an antiepileptic drug that has stabilised her condi
tion may be greater than the risk of the drug to the fetus.
Discontinuing the drug could result in status epilepticus,
which has a high risk of hypoxia for the mother and the
fetus. Research has not been able to show the effects
of even a minor seizure during pregnancy on the fetus,
making it important to prevent seizures during pregnancy
if at all possible. Women of childbearing age should be
urged to use barrier contraceptives while taking these
drugs. If a pregnancy does occur, the woman should
receive educational materials and counselling.
Caution should be used with elderly or debilitated
people,
who may respond adversely to the CNS depres-
sion
, and with people who have impaired renal or liver
function
which may interfere with drug metabolism
and excretion.
People with hepatic impairment are at
risk for increased toxicity from phenytoin. Other con
traindications include coma, depression or psychoses,
which could be exacerbated by the generalised CNS
depression.
Abrupt withdrawal of phenytoin in people
with epilepsy may precipitate status epilepticus, hence
any need for dosage reduction, discontinuation or sub
stitution of alternative antiepileptic medication should
be implemented gradually.
Adverse effects
The most common adverse effects relate to CNS depres
sion and its effects on body function: depression,
confusion, drowsiness, lethargy, fatigue, constipation,
dry mouth, anorexia, cardiac arrhythmias and changes
in blood pressure, urinary retention and loss of libido.
Specifically, phenytoin may cause severe liver
toxicity, bone marrow suppression, gingival hyper
plasia and potentially serious dermatological reactions
(e.g. hirsutism, Stevens–Johnson syndrome), all of which
are directly related to cellular toxicity.
Clinically important drug–drug interactions
Because the risk of CNS depression is increased with
phenytoin taken with alcohol, people should be advised
not to drink alcohol while they are taking these agents.
Always consult a drug reference before any drug is
added to or withdrawn from a therapeutic regimen that
involves any of these agents. Box 23.4 describes a haz
ardous drug–herbal therapy interaction associated with
antiepileptic medications.
B
arbiturates and barbiturate
-
like drugs
Barbiturates and barbiturate-like drugs include pheno
barbitone (generic) and primidone (
Mysoline
[not
available in New Zealand]). These drugs are associated
with significant CNS depression.
Therapeutic actions and indications
The barbiturates and barbiturate-type drugs inhibit
impulse conduction in the ascending reticular activating
system (RAS), depress the cerebral cortex, alter cere
bellar function and depress motor nerve output. They
stabilise nerve membranes throughout the CNS directly
by influencing ionic channels in the cell membrane,
thereby decreasing excitability and hyperexcitability to
stimulation. By decreasing conduction through nerve
pathways, they reduce the tonic–clonic, muscular and
emotional responses to stimulation. Phenobarbitone
depresses conduction in the lower brainstem and the
cerebral cortex, as well as depressing motor conduction.
People being treated for epilepsy should be advised not
to use the herb evening primrose because it increases
the risk of having seizures. People being treated with
barbiturates or phenytoin should be advised not to use
ginkgo, which could cause serious adverse effects.
Herbal and alternative therapies
BOX 23.4
Prototype summary: Phenytoin
Indications:
Control of tonic–clonic and
psychomotor seizures; prevention of seizures during
neurosurgery; control of status epilepticus.
Actions:
Stabilises neuronal membranes and prevents
hyperexcitability caused by excessive stimulation;
limits the spread of seizure activity from an active
focus; has cardiac antiarrhythmic effects similar to
those of lignocaine.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
Slow
2–12 hours
6–12 hours
IV 1–2 hours
Rapid
12–24 hours
T
1/2
:
6 to 24 hours; metabolised in the liver, excreted
in the urine.
Adverse effects:
Nystagmus, ataxia, dysarthria,
slurred speech, mental confusion, dizziness, fatigue,
tremor, headache, dermatitis, Stevens–Johnson
syndrome, nausea, gingival hyperplasia, liver
damage, haematopoietic complications, sometimes
fatal.
