MSK Pharm – NMBD

Master answer

Pharmacodynamics

Prejunctional Factors:

• Electrolyte abnormalities
  • Hypo/Hypercalcaemia
    • ↓/↑ Prejunctional Ca entry on depoarisation → ↓/↑ ACh release
      • ↓ Ca → prolongation of blockade by NDMB due to ↓ Competitive antagonism
  • Hypo/Hyperkalaemia
    • Hyper/Hypopolarisation of pre-junctional membrane
      • ↓ [K] → Hyperpolarisation → prolonged effect of NDMB

Junctional Factors:

• Presence of co-administered anticholinesterase drugs (eg neostigmine
  • ↑ [Ach] in NMJ → ↑competitive antagonism of NDMB → ↓ duration of effect/delayed onset
• Effect of NDMB relates to receptor occupancy
  • 95% occupancy → TOF ¼
  • 90% occupancy → TOF ¾

Post-Junctional Factors:

• Thermal injury/UMN lesion/Burns
  • Upregulation of foetal type junctional and extra-junctional nAChRs
    • ↑ receptor numbers → greater dose required to get the same percentage of receptors occupied
    • Prolonged opening compared with adult receptors → predisposition to hyperkalameia → ↑’s RMP
  • ↓ Plasma cholinesterase → ↓ metabolism of mivacurium
• Co-administered local anaesthetic
  • Na-channel blockade →
    • pre-junctional membrane stabilisation → ↓ ACh release → ↑ NDMB effect duration
    • post-junctional membrane stabilisation → ↑’s receptor occupancy required to achieve excitatory post synaptic potential (EPSP) → prolonged effect of NDMB

CICMWrecks 2016