Phase II Block
Phase II block is a complex phenomenon that occurs slowly at junctions
continuously exposed to depolarizing agents. The junction is depolarized by the
initial application of a depolarizing relaxant, but then the membrane potential gradually
recovers toward normal, even though the junction is still exposed to drug. Neuromuscular
transmission usually remains blocked throughout the exposure. Several factors are
involved. The repeated opening of channels allows a continuous efflux of potassium
and influx of sodium, and the resulting abnormal electrolyte balance distorts the
function of the junctional membrane. Calcium entering the muscle through the opened
channels can cause disruption of receptors and sub-end-plate elements themselves.
The activity of a sodium-potassium adenosine triphosphatase pump in the membrane
increases with increasing intracellular sodium and, by pumping sodium out of the
cell and
potassium into it, works to restore the ionic balance and membrane potential toward
normal. As long as the depolarizing drug is present, the receptor channels remain
open, and ion flux through them remains high.[59]
Factors influencing the development phase II block include the
duration of exposure to the drug, the particular drug used and its concentration,
and even the type of muscle (i.e., fast or slow). Interactions with anesthetics
and other agents also affect the process. All of these drugs may also have prejunctional
effects on the rate and amount of transmitter release and mobilization. With so
many variables involved in the interference with neuromuscular transmission, phase
II block is a complex and ever-changing phenomenon. The reversal response of a phase
II block produced by a depolarizing muscle relaxant to administration of cholinesterase
inhibitors is difficult to predict. It is therefore best that reversal by cholinesterase
inhibitors is not attempted, although the response to tetanus or train-of-four stimulation
resembles that produced by nondepolarizers.
