Neuromuscular Blockade — Pharmacodynamic Variability

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2008B Q01

Exam question

Outline three (3) factors that alter the pharmacodynamic response of non-depolarising neuro-muscular blocking drugs and describe the mechanism by which they may occur.

CICMWrecks answer

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

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Exam	Exact exam wording	Candidate success
2008B Q01	Outline three (3) factors that alter the pharmacodynamic response of non-depolarising neuro-muscular blocking drugs and describe the mechanism by which they may occur.	—