Newer Antiepileptic Drugs & GABA Modulators

Newer Antiepileptic Drugs & GABA Modulators

1. Definition, scope & nomenclature

• Epilepsy is a disorder of brain function characterised by the risk of periodic, unpredictable seizures — transient behavioural change due to disordered, synchronous, rhythmic firing of populations of cortical neurons (G&G 14e Ch.20, pp.385–6).
• Seizure (from Latin sacire, "to take possession of") vs epilepsy (the disorder) — a single seizure is not epilepsy; epilepsy implies enduring predisposition (G&G 14e Ch.20, p.386).
• Current pharmacotherapy is symptomatic — available ASMs inhibit seizures but provide neither prophylaxis nor cure; no antiepileptogenic agent has yet been identified (G&G 14e Ch.20, pp.386, 388).
• Terminology has shifted: the ILAE 2016/2017 revision renames partial → focal seizures; complex partial → focal with impaired awareness; secondarily generalised → focal-to-bilateral tonic-clonic (G&G 14e Ch.20, p.386).
• The preferred current term is antiseizure medication (ASM) / antiseizure drug (ASD), displacing "antiepileptic drug (AED)" because the drugs suppress seizures rather than the epilepsy (Katzung 16e Ch.24, pp.428–30; G&G 14e Ch.20, p.385).
• "Newer" / second- & third-generation ASMs = agents introduced from the 1990s onward: phenyltriazine (lamotrigine), GABA cyclic analogue (gabapentin), sulfamate monosaccharide (topiramate), nipecotic-acid derivative (tiagabine), pyrrolidine (levetiracetam), and the still-newer brivaracetam, lacosamide, perampanel, eslicarbazepine, rufinamide, stiripentol, cenobamate, cannabidiol, fenfluramine, ganaxolone, retigabine/ezogabine (G&G 14e Ch.20, p.391; KDT 8e Ch.30, pp.439, 445–8).
• Drivers for newer agents: the older drugs fail to control ~⅓ of patients, carry dose-limiting toxicity, and the enzyme-inducers (phenytoin, carbamazepine, phenobarbital) cause broad CYP/UGT drug–drug interactions; newer agents are generally less sedating, cleaner kinetically, and lower-interaction, though less extensively studied (G&G 14e Ch.20, p.391; KDT 8e Ch.30, pp.448; Katzung 16e Ch.24, p.430).