Pharm 101: Bupivacaine

Class

Local anaesthetic

Pharmacodynamics

• Amide local anaesthetic that blocks voltage-gated Na channels in nerve:
  • Increases threshold for excitation
  • Impulse conduction slows
  • Rate of action potential (AP) rise declines
  • AP amplitude decreases
  • Finally, ability to generate an AP is abolished
• Blockade is voltage and time-dependent:
  • Greater affinity for activated (open state) and inactivated channels, which predominate at more positive membrane potentials, than channels in rested state (negative membrane potential)
• Other factors:
  • Nerve bundle core contains fibres innervating the most distal site. Therefore anaesthetic placed outside nerve bundle will anaesthetise proximal fibres located at outer portion of bundle first, and sensory block will occur from proximal to distal
  • Elevated extracellular Ca partially antagonises action of LA due to increase in surface potential on membrane, favouring low-affinity rested state
  • Elevated extracellular K depolarises membrane potential and favours inactivated state, enhancing effect of LA
• If Na current is blocked over a critical length of nerve, propagation is ceased

Pharmacokinetics

• Weak base
• Lipophilic
• Absorption depends on multiple factors:
  • Site of injection
  • Local tissue blood flow
  • Use of vasoconstrictor (e.g. adrenaline)
  • Tissue pH (adding bicarbonate raises effective concentration of nonionised form which better penetrates cell)
• 95% protein bound
• Large volume of distribution 72L
• Liver metabolism
• Distribution half-life 28 minutes
• Elimination half-life 3.5 hours
• Duration of action 4-8 hours (longer than lignocaine or ropivacaine)

Clinical uses

• Nerve blocks in low concentration 0.25%:
  • Local anaesthetic
  • Digital ring block, intra-articular
  • Femoral nerve block*
  • Intercostal, brachial plexus*
• Infusions in low concentration 0.25%:
  • Prolonged peripheral anaesthesia or epidural infusion for postoperative pain control
  • Epidural infusion for labour analgesia (often agent of choice)
• Max dose 2mg/kg
• *Intercostal blocks result in highest peak serum levels of LA, whilst sciatic and femoral are among the lowest

Adverse effects

• CNS toxicity:
  • Sedation
  • Visual and auditory hallucinations
  • Tongue/mouth numbness, metallic taste
  • Seizure
  • Respiratory depression
• Cardiac toxicity (high volume blocks):
  • Arrhythmias
  • Cardiovascular collapse
  • Hypotension and arrest
• Local toxicity: trauma, neurotoxicity

Precautions/contraindications

• *Due to cardiotoxicity, often avoided for techniques requiring high volumes of concentrations anaesthetic e.g. epidural or peripheral nerve blocks for surgical anaesthesia

Further reading

• Nickson C. Local Anaesthetic Toxicity

References

• The Royal Children’s Hospital Melbourne. Parkville, Victoria, Australia. July 2017. Femoral Nerve Block
• Katzung BG. Basic & Clinical Pharmacology. 14th ed. United States of America: McGraw-Hill Education; 2018. 459-472 p.