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




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

·   Occurs in non-depolarising drugs only


·   Degree of fade correlates with depth of blockade

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


·   Blockade of pre-synaptic α3β2 nAChR

·   Loss of positive feedback

·   Inability to mobilise reserve pool of ACh


Post-tetanic potentiation:


·   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


·   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


·   ↑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



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