K2iii / 23B04: Compare and contrast the pharmacology of phenytoin and levetiracetamClassify the mechanisms of action of anti-convulsant drugs (30% marks). Outline the pharmacology of gabapentin (70% marks)K2iii / 23B04: Compare and contrast the pharmacology of phenytoin and levetiracetam

23B04: Exam Report

Classify the mechanisms of action of anti-convulsant drugs (30% marks). Outline the pharmacology of gabapentin (70% marks)

21% of candidates passed this question.

The first part of this question required candidates to correlate the mechanism of action of anti epileptic drugs with atleast one example under each section.

These included GABA potentiation (Barbiturates/Tiaganbine), reduction in excitory transmission (including NMDA/AMPA antagonists) and modification of ionic conductances (sodium channel blockade-Phenytoin, Calcium channel blockade- Lamotrigine, Gabapentin, activation of potassium channels- Retigabine).
The second part of this question involved an overview of gabapentin pharmacology. amino acid analogue of GABA utilised in neuropathic pain and epilepsy. There a multiple proposed mechanisms of action including Ca+ antagonism, inhibited glutamate release and anatagonism and Gabapentin is an 2 increased GABA concentrations.

Important pharmacokinetic properties included dose dependent absorption, minimal protein binding, no metabolism with renal clearance and requirement for dose reduction in renal failure.

It has largely central neurological side effects with a rare but important association with steven johnson syndrome or toxic epidermal necrolysis.

K2iii /23B04: Classify the mechanisms of action of anti-convulsant drugs (30% marks). Outline the pharmacology of gabapentin (70% marks)

Site of action


Site of action

GABA-A receptor allosteric modulators


  • Benzodiazepines (midazolam, clonazepam)
  • Phenobarbital
  • Topiramate
  • Carbamazepine
  • Clobazam

Site of action

GABA uptake inhibitors/GABA-transaminase inhibitors


  • Tiagabine

Site of action

Na+ Channel Modulator: Enhance fast inactivation


  • Phenytoin
  • Carbamazepine
  • Lamotrigine
  • Topiramate
  • Sodium valproate

Site of action

Na+ Channel Modulator: Enhance slow inactivation


  • Lacosamide

Site of action

Ca2+ Channel Blockers


  • Sodium valproate
  • Lamotrigine

Site of action



  • Gabapentin
  • Pregabalin

Site of action

Activation of Potassium Channels


    • Retigabine

Site of action

NMDA antagonist


  • Felbamate

Site of action

AMPA/Kainate antagonism


  • Phenobarbital
  • Topiramate

Site of action

S2VA protein ligand


  • Levetiracetam
  • Brivaracetam

Site of action



    • Cannabidiol

** list from Goodman and Gilman’s




  • Acetic acid derivative, structural analogue to GABA
  • Tablets – 600/800 mg
  • Capsules 100/300/400 mg



  • Post-herpetic neuralgia
  • Post diabetic neuropathy
  • Partial seizures with or without secondary generalisation
  • Neuropathic pain

Mechanism of action

  • Structurally related to GABA but does not interact with GABA receptors.
  • Binds to alpha-2-delta subunit of voltage-gated calcium channels.
  • May also:
    • Partially reduce response to the glutamate agonist NMDA
    • Reduce the release of monoamine neurotransmitters in vitro
    • Stimulate glutamate decarboxylate (converts glutamate to GABA)
    • Increase the synaptic release of GABA


  • PO – titration scheme or alternatively an initial dose of 300 mg TDS
  • Long-term epilepsy – 900-3600 mg/day
  • Neuropathic pain – up to 3600 mg/day
  • Discontinuation should be gradually performed over a minimum of 1 week


  • Peak plasma 3hrs

DoA (duration)

  • t1/2b 5-7hrs



  • Analgesic
  • Anticonvulsant


  • Dizziness, ataxia, nystagmus, somnolence, tremor, diplopia, nausea and vomiting >5%
  • Leucopenia, erectile dysfunction and weight gain have all been reported
  • Steven-Johnson Syndrome
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)



  • Well absorbed orally
  • LAT1 transporter via intestine (saturable)
  • 60% oral bioavailability
  • Peak plasma levels of the drug occur within 2-3 hours of administration


  • Minimally bound to plasma proteins (<3%)
  • Vd 0.85L/kg
  • In patients with epilepsy, gabapentin concentrations approximately 20% of corresponding plasma concentrations (ie crosses BBB w 20% levels in CSF)


  • Gabapentin not metabolised in man and does not induce hepatic enzymes


  • Excreted unchanged by renal function (will require dose reduction in renal failure)
  • Elimination half-life is 5-7 hours

Special points

  • Gabapentin enhances analgesic effect of co-administered morphine
  • Removed by haemodialysis. Bioavailability of the drug decreases with increasing dose which may minimise toxicity resulting from overdose.
  • Co-administration of drug with antacids containing aluminium and magnesium may reduce bioavailability by up to 24%.  Suicidal idealtion

Author: Michael Wu