ANTIEPILEPTICS USE:
Antiepileptics work either by
1: Blocking Na channels,
2: Blocking Clcium channels at presynaptic vesicles to stop release of neurotransmitters
3: Blocking glutamate activity (glutamate is excitatory neurotransmitter)
4: Promoting GABA activity (GABA inhibits neurons by opening Chloride Chanels).
Some of the drugs may have more than one mechanism of action with one as a main one and others as additional mechanisms.
As they suppress neuronal activity, so they have neuronal side effects such as cortical suppression (cognitive decline, affect on memory, drowsiness, psychomotor retardation, behavioural issues & psychiatric symptoms etc), cerebellar suppression (ataxia, nystagmus) etc. In addition they may have systemic side effects which are specific for each drug.
Usually started on low dose mono therapy and titrated up until epilepsy is controlled or maximum dose has been given or intolerable side effects or mono therapy isn’t adequate. Second drug is added on and titrated up on same principles.
For planned pregnancy, it’s better to first gradually switch over to drugs which are safer in pregnancy and then conceive. Contraception should be advised till this process is complete. Levetriacetam, lamotrigene, benzodiazepines such as clonazepam, gabapentin are safer than others.
However for unplanned pregnancy, whatever medication she was on, should be continued even if it’s teratogenic as risk of seizures to pregnancy is more than risk of these drugs. If need arise to increase the dose of the drug, then add on the one which is safer for pregnancy. Phenytoin, carbamazepine and valproate all have teratogenic affects & patient should be on folate at least for the first trimester. No drug is 100% safe for pregnancy, however, some are safer than others and this should be explained to patient.
Patient shouldn’t be allowed to drive personal vehicles until he / she has been seizure free for at least 6 months. Commercial vehicles and aeroplane restrictions should be more strict and longer. If any seizure recurs, counting of time will restart from zero again. Different countries or states have different restrictions so please follow the local guidelines.
Antiepileptics are usually started on second seizure especially if underlying cause was reversible. However if there is a known irreversible cause such as brain tumor or if patient has high risk job such as public vehicle driver /pilot etc then should be started even after first seizure. Some time prophylactic treatment is started at high risk patients such as brain tumor or SOL or organic brain damage.
Broad spectrum drugs are the one which cover almost all types of seizures including focal and generalised seizures. So can be used for a seizure which is not clearly classified. Generally choice of antiepileptics is based on side effect profile and patients comorbidities etc.
Some drugs such as penicillins and quinolone lowers seizures threshold and should be best avoided if possible.
Phenytoin is broad spectrum drug which is Na channel blocker. Causes cosmetic issues such as hair growth, gum hyperplasia etc. It also causes facial anomalies in children so not recommended during pregnancy or childhood. It’s also anti-arrhythmic drug as it blocks cardiac Na channels too and for the same reasons can be pro-arrhythmic too.
Carbamazepine: Broad spectrum drug which blocks Na channel. Cause cytopneia (like many other drugs starting with C), liver damage and teratogenic. It’s also used for neuropathic pain.
Valproate is broad spectrum drug which promotes GABA activity and hence suppress neurones. Side effects are cytopenia, hepatic dysfunction in adults. It also causes Vertebral column defects in fetus and hence contraindicated in pregnancy as it’s also antifolate.
Levetiracetam: broad spectrum drug, blocks presynaptic calcium channels and prevents release of neurotransmitters. Main issue is mood disorders and psychotic symptoms leading to suicide.
Topiramate: Broad spectrum drug which blocks carbonic anhydride and hence reduce HCO3 production leading to reduced pH which cause neuronal suppression. Specific side effects include renal stones due to acidic urine and glaucoma.
Lamotrigen, blocks glutamate release. It is an alternate to Valproate except for myoclonic seizures. Apart from its neurological side effects, there are no serious systemic side effects except dose related rash.
Lacosamide is like an amino acid serine and blocks Na channels. Arrhythmia, cytopenia etc are common side effects. Useful for focal and secondary generalised seizures.
GABApentin and PreGABAlin, ViGABAtrin , as name indicates, work by increasing GABA abs are mainly used for focal seizures. Gabapentin and pregabalin are also used for neuropathic pain.
Phenytoin, BDZ and Levertriacetam are also used during status as well and are available oral & intravenous route too.
Liver disease patients and epilepsy: Levetriacetam, topiramate, pregabalin, gabapentin are safer choices. Phenytoin, carbamazepine, valproate should be avoided due to extensive first pass hepatic metabolism and also due to hepatotoxic effects.