21st June 2023

Side Effects

Cytochrome P450 Enzyme

Cytochrome P (CYP) enzymes are haemoproteins that are key in drug metabolism. AEDs are known to either induce or inhibit Cytochrome P450. When a medication induces cytochrome P450, there is an increase in the metabolisation of the medication, which means the medication has less of an effect. When a medication inhibits cytochrome P450, there is reduced metabolisation of the medication and an increased risk of toxicity. Dose of these AEDs might have to be titrated accordingly.

Sodium valproate

Sodium valproate works by increasing GABA activity by decreasing its degradation and by blocking sodium, potassium, and calcium channels.

The severe side effects of sodium valproate, according to the British National Formulary (BNF), include teratogenicity, agranulocytosis, rhabdomyolysis, systemic lupus erythematosus (SLE), and severe cutaneous adverse reactions such as Stevens-Johnson Syndrome, DRESS syndrome, Toxic Epidermal Necrolysis.

Levetiracetam

The mechanism of action of levetiracetam has not been fully elucidated. So far, it has been found that it inhibits presynaptic calcium channels.

The severe side effects of levetiracetam include psychosis, suicidality agranulocytosis, and severe cutaneous adverse reactions.

Lamotrigine

Lamotrigine acts by inhibiting sodium channels and inhibits glutamate release.

The severe side effects of lamotrigine include suicidality, disseminated intravascular coagulation, haemolytic anaemia, and severe cutaneous adverse reactions.

Ethosuximide

Ethosuximide works by inhibiting T-type calcium channels that act in the hyperactive thalamocortical neuronal circuit.

The severe side effects of ethosuximide include suicidality, agranulocytosis, cytopaenia, SLE, and severe cutaneous skin reactions.

Topiramate

Topiramate acts on multiple targets. It acts on voltage-gated sodium channels, voltage-gated calcium channels, GABA receptors, and AMPA glutamate receptors.

The severe side effects of topiramate include facial oedema, glaucoma, neutropaenia severe cutaneous adverse reactions.

Phenytoin

Phenytoin is a voltage-gated sodium channel blocker.

The severe side effects of phenytoin include teratogenicity, agranulocytosis, pancytopaenia, SLE, and severe cutaneous adverse reactions.

Phenytoin toxicity can present with nystagmus, diplopia, slurred speech, ataxia, confusion, and hyperglycaemia.

The signs and symptoms of chronic phenytoin use are hirsutism, acne, coarsening of the facial features, gingival hyperplasia, and megaloblastic anaemia

Clobazam

Clobazam is a benzodiazepine that works by being a partial agonist of GABA-A receptors.

The severe side effects of clobazam include respiratory depression, drowsiness, ataxia, nystagmus, and coma.