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

Table 11–4
Comparison of Competitive (D-Tubocurarine) and Depolarizing (Decamethonium) Blocking Agents
D-TUBOCURARINE
DECAMETHONIUM
Effect of D-tubocurarine Additive Antagonistic
administered previously
Effect of decamethonium No effect, or antagonistic Some tachyphylaxis; but may
administered previously
be additive
Effect of anticholinesterase Reversal of block No reversal
agents on block
Effect on motor end plate Elevated threshold to acetylcholine; Partial, persisting depolarization
no depolarization
Initial excitatory effect None Transient fasciculations
on striated muscle
Character of muscle response Poorly sustained contraction Well-sustained contraction
to indirect tetanic stimulation
during partial block
anti-cholinesterase agents will not reverse depolarizing
neuromuscular blockade and, in fact, can enhance
it, the distinction between competitive and depolarizing
types of neuromuscular blocking agent must be
clearly communicated in healthcare settings to avoid
potential adverse clinical outcomes.
Many inhalational anesthetics exert a stabilizing effect on the
postjunctional membrane and therefore potentiate the activity of
competitive blocking agents. Consequently, when such blocking
drugs are used for muscle relaxation as adjuncts to these anesthetics,
their doses should be reduced. The rank of order of potentiation is
desflurane > sevoflurane > isoflurane > halothane > nitrous oxidebarbiturate-opioid
or propofol anesthesia (Naguib and Lien, 2005).
Aminoglycoside antibiotics produce neuromuscular blockade
by inhibiting ACh release from the preganglionic terminal
(through competition with Ca 2+ ) and to a lesser extent by noncompetitively
blocking the receptor. The blockade is antagonized by Ca 2+
salts but only inconsistently by anti-ChE agents (Chapter 54). The
tetracyclines also can produce neuromuscular blockade, possibly by
chelation of Ca 2+ . Additional antibiotics that have neuromuscular
blocking action, through both presynaptic and postsynaptic actions,
include polymyxin B, colistin, clindamycin, and lincomycin
(Pollard, 1994). Ca 2+ channel blockers enhance neuromuscular
blockade produced by both competitive and depolarizing antagonists.
It is not clear whether this is a result of a diminution of Ca 2+ -
dependent release of transmitter from the nerve ending or is a
postsynaptic action. When neuromuscular blocking agents are
administered to patients receiving these agents, dose adjustments
should be considered; if recovery of spontaneous respiration is
delayed, Ca 2+ salts may facilitate recovery.
Miscellaneous drugs that may have significant interactions with
either competitive or depolarizing neuromuscular blocking agents
include trimethaphan (no longer marketed in the U.S.), lithium, opioid
analgesics, procaine, lidocaine, quinidine, phenelzine, carbamazemine,
phenytoin, propranolol, dantrolene, azathioprine, tamoxifen, magnesium
salts, corticosteroids, digitalis glycosides, chloroquine, catecholamines,
and diuretics (Naguib and Lien, 2005; Pollard, 1994).
Toxicology
The important untoward responses of the neuromuscular
blocking agents include prolonged apnea, cardiovascular
collapse, those resulting from histamine
release, and rarely, anaphylaxis. Failure of respiration to
become adequate in the postoperative period may not
always be due directly to excessive muscle paralysis
from the drug. An obstruction of the airway, decreased
arterial PCO 2
secondary to hyperventilation during the
operative procedure, or the neuromuscular depressant
effect of excessive amounts of neostigmine used to
reverse the action of the competitive blocking drugs,
may also be implicated. Directly related factors may
include alterations in body temperature; electrolyte
imbalance, particularly of K + (see the next paragraph);
low plasma butyrylcholinesterase levels, resulting in a
reduction in the rate of destruction of succinylcholine;
the presence of latent myasthenia gravis or of malignant
disease such as small cell carcinoma of the lung
with Eaton-Lambert myasthenic syndrome; reduced
blood flow to skeletal muscles, causing delayed
removal of the blocking drugs; and decreased elimination
of the muscle relaxants secondary to hepatic dysfunction
(cisatricurium, rocuronium, vecuronium) or