This chapter tries to address Section K2(iii) of the 2023 CICM Primary Syllabus, which expects the exam candidate to somehow "understand the pharmacology of anti-convulsant drugs". That's probably something of a tall order, as the scientific community still has no idea about how half of them work. The ones for which the mechanism of action is clear are usually brutally stupid general anaesthetics (like barbiturates and benzodiazepines) or sodium-channel-blocking local anaesthetics (like phenytoin), where the mechanism of antiepileptic action is clearly "put an end to all neuronal activity, including seizure activity". For the rest, the only thing we can be sure of is the pharmacokinetics and the clinical side effects, with minimal pharmacodynamic material available.
So, apart from the drug-specific comparison question, it is not inconceivable that one day the college could bring back a classification SAQ which 67% of the candidates would again probably fail. In fact they already have, in Question 4 from the second paper of 2023, but the classification section was only 30% of the marks. preparation for that dark day, a classification system is offered here, based on Hanada (2014).
Mechanism/class Drug target Examples
Ion channel modulators:
reduce neuronal excitability by altering the resting membrane potential, stabilising the channels involved in the conduction of action potentials, or inhibiting the intracellular calcium flux which triggers excitatory neurotransmitter release.
- Retigabine (ezogabine)
- Sodium valproate
GABA potentiators: Increased inhibitory neurotransmission by either directly affecting the GABA ligand-gated chloride channel, decreasing the reuptake of GABA from the synapse, or decreasing the breakdown of GABA. GABAA
GABA reuptake transporter
- Sodium valproate
Presynaptic neurotransmitter release modulators: decrease the release of neurotransmitters SV2A
Postsynaptic inhibitors of neurotransmission: decrease the effect of released neurotransmitter ligands on their receptors AMPA
- Sodium valproate
God only knows what effect
- Potassium bromide
Other potential classification systems abound. For example, on the Wikipedia page for anticonvulsants, the drugs are listed according to their chemistry, which is surely one way of doing it (you won't miss anything), but has the disadvantage of being difficult to remember and moreover tells you nothing about the drugs' clinical behaviour.
From the perspective of the CICM trainee, a laborious exploration of these classification systems would not be essential. There are only two other drugs in common use which have been explored in previous exam questions (valproate and carbamazepine) and they do have some interesting pharmacological features worth discussing.
Sodium valproate (or specifically valproic acid, as the sodium does nothing) was discovered accidentally in the course of testing potential antiepileptic agents, when Pierre Eymard used it as a solvent for his test drugs in 1962. Chemically, valproic acid (2-n-propylpentanoic acid) is a simple branched-chain fatty acid, and there are several other such acids (substituted butyric, pentanoic and hexanoic acids) which all seem to have some anticonvulsant activity. Cutting top the chase, its most usual pharmacological properties are:
Carbamazepine is basically a tricyclic antidepressant with antiepileptic properties (and no antidepressant effect). Its most memorable features include:
This thing (1-aminomethy1 cyclohexaneacetic acid) is basically a structural analogue of GABA, but it does nothing GABA-like, and its mechanism of action seems to have nothing to do with GABA.