Seizures and anticonvulsants

Vivian Imbriotis | June 16, 2026

Classification of mechanisms

  • Na channel blockers: stabilize channel in inactive state \(\to\) increased refractory period \(\to \ \downarrow\)firing rate (phenytoin, carbemazepine, valproate); will also have cardiovascular effects
  • Voltage-gated Ca channel blockade; decreases neurotransmitter release \(\to\) impaired synaptic transmission (levetiracetam, gabapentin). Levetiracetam also binds to a synaptic vesicle glycoprotein to directly prevent NT exocytosis.
  • Enhanced GABA transmission, either from agonists (thiopentone), positive allosteric modulators (BZDs), or decreased reuptake (Tiagabine) / metabolism (vigabactrin)

Dose: Load 20mg/kg \(\to\) 100mg TDS IV

Mechanism: Na channel blocker \(\to\) stabilize channel in inactive state \(\to\) increased refractory period \(\to \ \downarrow\)firing rate

Adverse effects:

  • CNS: Ataxia, nystagmus, tremor, slurred speech, confusion all suggest toxicity!
  • CVS: (Vaughan Williams 1b) AV blocks, bradycardia, hypotension
  • HAEM: Aplastic anaemia
  • IMMUNE: DRESS, lupus, SJS

A: Oral BA 90%

D: 90% protein binding. Vd 0.6L/kg

M: Saturatable metabolism (i.e. Michaelis-Mentin kinetics) 1st order \(\to\) 0th order hepatic elimination. \(T_{\frac{1}{2}}\) = 22 hrs

E: Inactive metabolites in urine.

Narrow therapeutic index. Saturatable kinetics. Toxicity can occur with hypoalbuminaemia due to protein binding

Dose: 40mg/kg IV load in status -> 500mg BD

Mechanism: Voltage-gated Ca channel blockade; decreases neurotransmitter release \(\to\) impaired synaptic transmission; also binds to a synaptic vesicle glycoprotein to directly prevent NT exocytosis.

Adverse effects:

  • CNS: Fatigue, weakness, irritability

A: 100% OBA

D: Not protein bound. Vd 0.5L/kg

M: 30% metabolized extrahepatically \(\to\) inactive.

E: 70% unchanged in urine. T1/2=7 hours.


Dose: 100-800mg BD

Mechanism: Voltage-gated Ca channel blockade; decreases neurotransmitter release \(\to\) impaired synaptic transmission

Adverse effects:

A: 60% orally.

D: Not protein bound. Vd 0.8.

M: Nil

E: Renally eliminated. T1/2 6 hours

Dose: 40mg/kg IV in status.

Mechanism: Na channel blocker \(\to\) stabilize channel in inactive state \(\to\) increased refractory period \(\to \ \downarrow\)firing rate

Adverse Effects: Hepatotoxic., pancreatitis, oedema. Drowsiness.

A: 100% OBA

D: 90% protein bound. Vd=0.4L/kg

M: Hepatically metabolized \(\to\) active and inactive metabolites

E: Metabolites excreted in urine. T1/2 = 16hrs.

Dose: Cannot be given IV.

Mechanism: Na channel blocker \(\to\) stabilize channel in inactive state \(\to\) increased refractory period \(\to \ \downarrow\)firing rate. More potent CVS Na channel blocker than valproate.

Adverse Effects: SIADH, nephro- and hepatotoxic. SJS. Drowsiness.

A: 100% OBA

D: 75% protein bound. Vd=1L/kg.

M: Hepatically metabolized \(\to\) inactive, induces CYP2D6, it's own metabolizer \(\to\) needs dose increase with chronic use.

E: Metabolites excreted in urine. Half life initially 3 days \(\to\) decreased to 12 hours due to CYP2D6 effect.