Pharmacology/Antiepileptics

These notes are written by a pharmacy student for pharmacy students.

Status epilepticus

Benzodiazepines (sedatives & hypnotics) Indication: More commonly used for the treatment of status epilepticus rather than maintenance treatment. For the pre-hospital treatment of status epilepticus, buccal midazolam (or alternatively, the less socially desirable rectal diazepam) is used. IV Diazepam is given at hospitals in conjunction with IV Phenytoin to stop seizures.

MOA: The therapeutic effect of benzodiazepines in epilepsy is through acting on the benzodiazepine site of the GABA receptor which potentiate the binding of GABA to the GABA site on GABA A and B receptors (however the therapeutic effect is thought to be mostly due to the GABA A receptor) leading to the influx of Cl- ions to cause hyperpolarisation. The BZ site and GABA sites are on different subunits of the GABA receptor. By increasing GABA, neuronal firing is decreased, decreasing activation of nerves, causing the sedative, hypnotic and muscle relaxation effects.

Note: Benzodiazepines are recommended for short term use only (not more than a month) due to the potential of the individual of developing dependence, tolerance and withdrawal to the medication. The patient should be withdrawn slowly from the medication (dose titration) to avoid these effects. They should be used with caution in the elderly, due to altered pharmacokinetics in the elderly, are more susceptible to the sedative and hypnotic effects. This could lead to confusion and falls, however this practice point is more relevant in other uses of benzodiazepines, as it would be highly unlikely for a benzodiazepine to be used in long term use of controlling epilepsy.

While used for hospital treatment of status epilepticus, the patient should be monitored for signs of respiratory depression.

Maintenance treatment

More commonly used antiepileptics are Valproate, Carbamazepine and Lamotrigine in that order.

Things to note: Valproate has been found to be effective in most types of epilepsy and is often considered as first line treatment.

Carbamazepine is first line treatment in partial seizures, simple or complex. It is often used as an alternative to Valproate, eg. when the patient cannot tolerate the sedative effects of Valproate.

Lamotrigine is a newer drug which has been found to be an effective alternative, however can sometimes cause a rash which can lead to a more serious rash known as Steven-Johnson's syndrome (a life threatening condition where the skin falls off.) Therefore, early signs of skin rash should be taken seriously as it is a common adverse effect. Lamotrigine is considered for treatment during pregnancy due to less incidence of teratogenic effects compared to other anti-epileptics.

Epilepsy during pregnancy

A benefit risk assessment is important for the mother and child, and usually, the case is that there is more risk for both mother and child if the mother does not control her epilepsy during pregnancy. It is best that women with epilepsy who are wishing to get pregnant should have their epilepsy properly controlled before conceiving and have higher doses of folic acid supplements. However, should the woman learn that she is pregnant after the first trimester without preconception preparation, the teratogenic effects of more teratogenic anti-epileptics, eg. Valproate, would have already occurred and there is not benefit in switching anti-epileptics (if damage has occurred, 'the damage is already done' as the first trimester is when most of the development of the foetus occurs)