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

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

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