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Phenytoin
Phenytoin is a drug of first choice in established status epilepticus. Its pharmacology and
clinical effects are well documented, and there is extensive experience in status epilepticus
in adults, children, and the new-born. It is a highly effective anticonvulsant, with the
particular advantage of a long duration of action. It can also be continued as chronic therapy.
Phenytoin causes relatively little respiratory or cerebral depression, although hypotension is
more common. The initial infusion of phenytoin takes 2030 minutes in an adult, and the
onset of action is slow. It is therefore often administered in conjunction with a short-acting
drug with a rapid onset of action, such as diazepam. The notorious saturable pharmacokinetics
of phenytoin cause fewer problems in the emergency setting than in chronic therapy, but
careful monitoring of serum levels is essential. The usual phenytoin solutions have a pH of
12 and, if added to bags containing large volumes of fluid at lower than physiological pH (for
example, 5% glucose), precipitation may occur in the bag or tubing; use in a solution of 0.9%
sodium chloride (normal saline) (520 mg/ml) is safer. There is also a serious risk of
precipitation if other drugs are added to the infusion solution. Administration via a side arm,
or directly using an infusion pump, is preferable. Due to the high pH, phenytoin can cause
thrombophlebitis (particularly with extravasation), and it is poorly and erratically absorbed
after intramuscular injection. Also, its vehicle, propylene glycol, can cause hypotension.

The rate of infusion of phenytoin solution should not exceed 50 mg/minute, and it is prudent
to reduce this to 2030 mg/minute in the elderly. The adult dose is 1520 mg/kg; this usually
amounts to about 1000 mg and therefore takes at least 20 minutes to administer. Regrettably,
a common and potentially serious mistake is to give a lower dose which results in suboptimal
cerebral levels. Phenytoin therapy can be continued after intravenous loading by oral or
further intravenous daily dosages of 56 mg/kg, guided by blood level measurements. For
older children, the dose of phenytoin is the same as for adults. For the newborn a dose of
1520 mg/kg, injected at a rate not exceeding 1 mg/kg per minute, should be given. Phenytoin
is usually available as 5 ml ampoules containing phenytoin sodium 250 mg.

Fosphenytoin
In order to overcome the problems associated with physiochemical properties of phenytoin,
fosphenytoin (3-phosphoryloxymethyl phenytoin disodium), a water-soluble phenytoin pro-
drug, was developed. Fosphenytoin is inactive, but is metabolised to phenytoin with a half-
life of 815 minutes. It is supplied in a ready-mixed solution. The equimolar equivalent of 1
mg of phenytoin is 1.5 mg of fosphenytoin, and the drug is supplied in a ready mixed solution
of 50 mg phenytoin equivalents (PE) per ml (i.e. 75 mg/ml). This is to standardise the solution
to that of parenteral phenytoin. Fosphenytoin should be given intravenously at 150 mg/minute
to achieve a similar serum concentration time profile to that obtained with intravenous
phenytoin in status epilepticus. Although fosphenytoin is more expensive than phenytoin,
these costs may be balanced by less phlebitis, less hypotension, ease of administration and
greater tolerability. Since it is water soluble, it can also be given as an intramuscular injection,
although experience of this route in status epilepticus is very limited and therefore not
advised. ECG monitoring is mandatory during intravenous administration of both phenytoin
and fosphenytoin.

Phenobarbitone
Phenobarbitone is a drug of choice for the treatment of established status epilepticus. It is
highly effective, has a rapid onset of action, and prolonged anticonvulsant effects. It has stable
and non-reactive physical properties, as well as convenient pharmacokinetics. Wide
experience has been gained of its use in adults and in children, and few drugs are as well tried
in the newborn. It has stronger anticonvulsant properties than most other barbiturates, and
may be preferentially concentrated in metabolically active epileptic foci. As well as excellent
anticonvulsant properties, it may also have cerebral-protective action. Acute tolerance to the
antiepileptic effect is unusual, in contrast to the benzodiazepines and, once controlled,
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