1999A12 Explain the phenomena known as fade and post-tetanic facilitation associated with
the use of neuromuscular blocking agents.

 

Fade:

Description

·  Progressive reduction in twitch height with high frequency stimulation (e.g. TOF)

·  Occurs in non-depolarising drugs only

Use

·  Degree of fade correlates with depth of blockade

·  (e.g. TOF ratio 0.25 at 85% receptor occupancy)

Mechanism

·  Blockade of pre-synaptic α3β2 nAChR

·  Loss of positive feedback

·  Inability to mobilise reserve pool of ACh

 

Post-tetanic potentiation:

Description

·  Temporary increase in single twitch height after tetanic stimulation (e.g. 50Hz 3 seconds)
(note may also account for TOF ratio >1)

·  Occurs with non-depolarising drugs only

·  Lasts for ~7 minutes

Use

·  Inverse correlation of post-tetanic count with degree of blockade

·  Useful during deep blockade e.g. brain surgery

·  PTC 9 -> TOF count 1

·  PTC 5 -> TOF count 1 in 10 minutes

·  PTC 2 -> TOC count 1 in 20 minutes

Mechanism

·  ↑ICF [Ca2+] via L-Ca2+ at pre-synaptic terminal

·  Repeated activation of the nerve

·  Repeated activation of the VDCC

·  Insufficient time for Ca2+ extrusion

·  Ca2+ gets farther up the cell

·  Reserve pool of ACh mobilized (larger, dispersed, tethered to cytoskeleton)

·  Stronger contraction