DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

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SECTION II
NEUROPHARMACOLOGY
myelin
sheath
axon
node of
Ranvier
Schwann
cell
subneural
space
terminal
membrane
postjunctional
membrane
mitochondria
sarcoplasma
myofibrils
A
ANATOMY of the Motor End Plate PHYSIOLOGY PHARMACOLOGY
B
B
A
B
nerve action
potential
(AP)
vesicular
acetylcholine
release
depolarization (EPP)
(increased
permeability
to Na + and K + )
hydrolysis
of acetylcholine
by cholinesterase
muscle action
potential
spread of excitation
in muscle
muscle contraction
tetrodotoxin
batrachotoxin
local anesthetics
hemicholinium
botulinus toxin
procaine, Mg 2+
4-aminopyridine
lack of Ca 2+
excess of Ca 2+
curare alkaloids
snake α-toxins
succinylcholine
decamethonium
cholinesterase
inhibitors
Ca 2+
veratridine
quinine
tetrodotoxin
metabolic poisons
lack of Ca 2+
procaine
dantrolene
enhancement
blockade
depolarization
and phase block
Figure 11–4. Sites of action of agents at the neuromuscular junction and adjacent structures. The anatomy of the motor end plate,
shown at the left, and the sequence of events from liberation of acetylcholine (ACh) by the nerve action potential (AP) to contraction
of the muscle fiber, indicated by the middle column, are described in Chapter 8. The modification of these processes by various agents
is shown on the right; an arrow marked with an X indicates inhibition or block; an unmarked arrow indicates enhancement or activation.
The insets are enlargements of the indicated structures. The highest magnification depicts the receptor in the bilayer of the postsynaptic
membrane. A more detailed view of the receptor is shown in Figure 11–2.
but the results were clear: Tubocurarine given intravenously,
even in large doses, has no significant central
stimulant, depressant, or analgesic effects.
Autonomic Ganglia and Muscarinic Sites. Neuromuscular
blocking agents show variable potencies in producing
ganglionic blockade. Just as at the motor end plate, ganglionic
blockade by tubocurarine and other stabilizing
drugs is reversed or antagonized by anti-ChE agents.
At the doses of tubocurarine once used clinically,
partial blockade probably is produced both at autonomic
ganglia and at the adrenal medulla, which results in a fall
in blood pressure and tachycardia. Pancuronium shows
less ganglionic blockade at common clinical doses.
Atracurium, vecuronium, doxacurium, pipecuronium,
mivacurium, and rocuronium are even more selective
(Naguib and Lien, 2005; Pollard, 1994)). The maintenance
of cardiovascular reflex responses usually is desired
during anesthesia. Pancuronium has a vagolytic action,
presumably from blockade of muscarinic receptors,
which leads to tachycardia.
Of the depolarizing agents, succinylcholine at
doses producing neuromuscular relaxation rarely causes
effects attributable to ganglionic blockade. However,
cardiovascular effects are sometimes observed, probably
owing to the successive stimulation of vagal ganglia
(manifested by bradycardia) and sympathetic ganglia
(resulting in hypertension and tachycardia).
Mast Cells and Histamine Release. Tubocurarine produces
typical histamine-like wheals when injected
intracutaneously or intra-arterially in humans, and some