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

Table 11–3
Dosing Ranges for Neuromuscular Blocking Agents
MAINTENANCE DOSE
CONTINUOUS
INITIATION INTERMITTENT INFUSION
AGENT DOSE (mg/kg) INJECTION (mg/kg) (μg/kg/min)
Succinylcholine 0.5-1 0.04-0.07 N/A
D-Tubocurarine a 0.6 0.25-0.5 2-3
Metocurine a 0.4 0.5-1 N/A
Atracurium 0.5 0.08-0.1 5-10
Cisatracurium 0.1-0.4 0.03 1-3
Mivacurium 0.15-0.25 0.1 9-10
Doxacurium a 0.03-0.06 0.005-0.01 N/A
Pancuronium 0.08-0.1 0.01-0.015 1
Rocuronium 0.6-1.2 0.1-0.2 10-12
Vecuronium 0.1 0.01-0.015 0.8-1
Gantacurium a 0.2-0.5 N/A N/A
a
Not commercially available in the U.S.
moiety by plasma esterases and by a spontaneous or Hofmann degradation
(cleavage of the N-alkyl portion in the benzylisoquinoline).
Hence two routes for degradation are available, both of which remain
functional in renal failure. Mivacurium is extremely sensitive to
catalysis by cholinesterase or other plasma hydrolases, accounting
for its short duration of action.
Side effects are not yet fully characterized for gantacurium,
but transient adverse cardiovascular effects suggestive of histamine
release have been observed at doses over three times the ED 95
.
Clinical Uses
Muscle Relaxation. The main clinical use of the neuromuscular
blocking agents is as an adjuvant in surgical
anesthesia to obtain relaxation of skeletal muscle, particularly
of the abdominal wall, to facilitate operative
manipulations. With muscle relaxation no longer
dependent on the depth of general anesthesia, a much
lighter level of anesthesia suffices. Thus, the risk of respiratory
and cardiovascular depression is minimized,
and post-anesthetic recovery is shortened. These considerations
notwithstanding, neuromuscular blocking
agents cannot be used to substitute for inadequate depth
of anesthesia. Otherwise, a risk of reflex responses to
painful stimuli and conscious recall may occur.
Muscle relaxation is also of value in various
orthopedic procedures, such as the correction of dislocations
and the alignment of fractures.
Neuromuscular blocking agents of short duration often
are used to facilitate endotracheal intubation and have
been used to facilitate laryngoscopy, bronchoscopy, and
esophagoscopy in combination with a general anesthetic
agent.
Neuromuscular blocking agents are administered
parenterally, nearly always intravenously. As potentially
hazardous drugs, they should be administered to
patients only by anesthesiologists and other clinicians
who have had extensive training in their use and in a
setting where facilities for respiratory and cardiovascular
resuscitation are immediately at hand. Detailed
information on dosage and monitoring the extent of
muscle relaxation can be found in anesthesiology textbooks
(Naguib and Lien, 2005; Pollard, 1994).
Measurement of Neuromuscular Blockade in Humans. Assessment of
neuromuscular block usually is performed by stimulation of the ulnar
nerve. Responses are monitored from compound action potentials or
muscle tension developed in the adductor pollicis (thumb) muscle.
Responses to repetitive or tetanic stimuli are most useful for evaluation
of blockade of transmission because individual measurements of twitch
tension must be related to control values obtained prior to the administration
of drugs. Thus, stimulus schedules such as the “train of four”
and the “double burst” or responses to tetanic stimulation are preferred
procedures (Drenck et al., 1989; Waud and Waud, 1972). Rates of
onset of blockade and recovery are more rapid in the airway musculature
(jaw, larynx, and diaphragm) than in the thumb. Hence, tracheal
intubation can be performed before onset of complete block at the
adductor pollicis, whereas partial recovery of function of this muscle
allows sufficient recovery of respiration for extubation (Naguib and
Lien, 2005). Differences in rates of onset of blockade, recovery from
blockade, and intrinsic sensitivity between the stimulated muscle and
those of the larynx, abdomen, and diaphragm should be considered.
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CHAPTER 11
AGENTS ACTING AT THE NEUROMUSCULAR JUNCTION AND AUTONOMIC GANGLIA