K2iii: The physiological basis for the mechanism of action of commonly used anticonvulsant groups

AP Initiation & Propagation

  • Axon Hillock has high density voltage gated Na+ & K+ channels
  • Membrane depolarised
  • Voltage gated Na+ channel open = Na+ influx
  • +ve feedback = more Na+ channels open
  • Threshold reached (> – 55mV)
  • Activation gate of Na+ channel open & K+ channel closed → unopposed Na+ influx
  • AP generated
  • Na+ channel close & K+ channel open to repolarise nerve
  • Then both channels close & membrane potential returns to zero

Definition Seizures

The clinical manifestation of epileptic neuronal activity

Pathophysiology of Epileptic Neuronal Activity

  • Abnormal synchronisation
  • Excessive excitation
  • Inadequate inhibition

→ Affecting variable populations of neurons

Anticonvulsant Classification

  1. Modulation of voltage-gated ion channel
  2. GABA enhancing
  3. Attenuation of NT release

1) Modulation of Voltage Gated Ion Channel

Na+ channel

  • Na+ channel blockers have high affinity for protein in INACTIVE STATE
  • Increases refractory period
  • ↓repetitive neuron firing

E.g. Phenytoin, carbamazepine, lamotrigine

 Ca2+ channel

  • Ca2+ channel blockade will ↓depolarisation & NT release

E.g. Sodium valproate, Levetiracetam

 K+ channel

  • Activation of K+ channels will hyperpolarise cell
  • ↓neuronal excitability

E.g. Retigabine

2) GABA Enhancing

  • GABA = 1° inhibitory NT

GABA receptor activators

  • BZD → bind BZD receptor → ↑Freq Cl– channel opening → promote GABA activity
  • Barbiturates → Activate GABAA receptor

↓GABA Uptake

  • ∴↑[GABA]

E.g. Tiagabine

↓GABA Metabolism

  • ∴↑[GABA]

E.g. Vigabatrin

3) Attenuation of NT Release

E.g. Levetiracetam

  • Binds SV2A (synaptic vessel protein 2A)
  • Prevents exocytosis & NT release