A Textbook of Clinical Pharmacology and Therapeutics

WITHDRAWAL OFANTI-EPILEPTICDRUGS 139

FURTHER ANTI-EPILEPTICS

Other drugs licensed for use in certain forms of epilepsy in the
UK include oxcarbamazepine, pregabalin,levetiracetam,zon-
isamide,acetazolamide(see also Chapter 36) and piracetam.

DRUG INTERACTIONS WITH

ANTI-EPILEPTICS

Clinically important drug interactions occur with several anti-
epileptics. The therapeutic ratio of anti-epileptics is often small
and changes in plasma concentrations can seriously affect both
efficacy and toxicity. In addition, anti-epileptics are prescribed
over long periods, so there is a considerable likelihood that
sooner or later they will be combined with another drug.
Several mechanisms are involved:

• enzyme induction, so the hepatic metabolism of the anti-
  epileptic is enhanced, plasma concentration lowered and
  efficacy reduced;


• enzyme inhibition, so the metabolism of the anti-epileptic
  is impaired with the development of higher blood
  concentrations and toxicity;


• displacement of the anti-epileptic from plasma binding sites.

In addition to this, several anti-epileptics (e.g. phenytoin,pheno-
barbital,carbamazepine) are powerful enzyme inducers and
alter the metabolism of other drugs. Table 22.2 lists the effects of
some drugs on the metabolism of widely used anti-epileptics, and
the effects of anti-epileptics on the metabolism of other drugs.

ANTI-EPILEPTICS AND THE ORAL

CONTRACEPTIVE

Phenytoin,phenobarbital,topiramateandcarbamazepine
induce the metabolism of oestrogen and can lead to unwanted
pregnancy: alternative forms of contraception or a relatively
high oestrogen pill may be appropriate.

ANTI-EPILEPTICS AND PREGNANCY

The risk of teratogenicity is greater if more than one drug is
used (see Chapter 9).

STATUS EPILEPTICUS

Status epilepticus is a medical emergency with a mortality of
about 10%, and neurological and psychiatric sequelae possible
in survivors. Management is summarized in Figure 22.3.
Rapid suppression of seizure activity is essential and can
usually be achieved with intravenous benzodiazepines
(e.g.lorazepam, administered i.v.). Rectal diazepamis useful
in children and if venous access is difficult (see Chapter 10).

Intravenousclonazepamis an alternative. False teeth should

be removed, an airway established and oxygen administered

as soon as possible. Transient respiratory depression and

hypotension may occur. Relapse may be prevented with intra-

venousphenytoinand/or early recommencement of regular

anticonvulsants. Identification of any precipitating factors,

such as hypoglycaemia, alcohol, drug overdose, low anticon-

vulsant plasma concentrations and non-compliance, may

influence the immediate and subsequent management. If

intravenous benzodiazepines and phenytoinfail to control

the fits, transfer to an intensive care unit (ICU) and assistance

from an anaesthetist are essential. Intravenous thiopentalis

sometimes used in this situation.

Key points

Status epilepticus

If fits are 5 minutes in duration or there is incomplete

recovery from fits of shorter duration, suppress seizure

activity as soon as possible.

• Remove false teeth, establish an airway and give
  oxygen at a high flow rate. Assess the patient, verify
  the diagnosis and place them in the lateral semi-prone
  position.


• Give i.v. lorazepam, 4 mg.


• Rectal diazepam and rectal paraldehyde are
  alternatives if immediate i.v. access is not possible).


• The lorazepam may be repeated once if fits continue.


• Take blood for anticonvulsant, alcohol and sugar
  analysis, as well as calcium, electrolytes and urea (if
  there is doubt about the diagnosis, test for prolactin).


• If glucose levels are low, give 50% dextrose. If alcohol is
  a problem, give i.v. vitamins B and C.


• If fits continue, give i.v. phenytoin by infusion, and
  monitor with electrocardiogram (ECG).


• If fits continue, transfer to intensive care unit, consult
  anaesthetist, paralyse if necessary, ventilate, give
  thiopental, monitor cerebral function, check
  pentobarbitone levels.

WITHDRAWAL OF ANTI-EPILEPTIC DRUGS

All anti-epileptics are associated with adverse effects. Up to

70% of epileptics eventually enter a prolonged remission and

do not require medication. However, it is difficult to know

whether a prolonged seizure-free interval is due to efficacy of

the anti-epileptic drug treatment or to true remission. Indivi-

duals with a history of adult-onset epilepsy of long duration

which has been difficult to control, partial seizures and/

or underlying cerebral disorder have a less favourable progno-

sis. Drug withdrawal itself may precipitate seizures, and the

possible medical and social consequences of recurrent seizures

(e.g. loss of driving licence; see Table 22.3) must be carefully

discussed with the patient. If drugs are to be withdrawn, the