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

274 gastric emptying. Although the absorption of mecamylamine is less
erratic, a danger exists of reduced bowel activity leading to frank
paralytic ileus.
After absorption, the quaternary ammonium- and sulfoniumblocking
agents are confined primarily to the extracellular space and
are excreted mostly unchanged by the kidney. Mecamylamine concentrates
in the liver and kidney and is excreted slowly in an
unchanged form.
SECTION II
NEUROPHARMACOLOGY
Untoward Responses and Severe Reactions. Among the milder
untoward responses observed are visual disturbances, dry mouth,
conjunctival suffusion, urinary hesitancy, decreased potency, subjective
chilliness, moderate constipation, occasional diarrhea,
abdominal discomfort, anorexia, heartburn, nausea, eructation, and
bitter taste and the signs and symptoms of syncope caused by postural
hypotension. More severe reactions include marked hypotension,
constipation, syncope, paralytic ileus, urinary retention, and
cycloplegia.
Clinical Summary
Neuromuscular blocking agents paralyze skeletal muscle
by blocking neurotransmission through nicotinic
ACh receptors at the neuromuscular junction. They have
no sedative, amnestic, or analgesic properties, and are
mainly used in combination with narcotic or volatile
anesthetics to relax skeletal muscle and facilitate surgical
procedures. Depolarizing neuromuscular blocking
agents cause an initial depolarization of the motor end
plate that renders it refractory to further stimulation.
Competitive or non-depolarizing blocking agents compete
directly with ACh at its receptor in the motor end
plate. Neuromuscular blocking agents are preferably
administered as a single or as intermittent intravenous
injections. Depth of blockade is monitored by peripheral
nerve stimulation. Competitive agents can be
reversed by administration of anti-cholinesterase agents.
Succinylcholine, the most common depolarizing
neuromuscular blocking agent, is used to facilitate
endotracheal intubation during rapid-sequence induction
of anesthesia due to its rapid onset and short duration
of action. The numerous non-depolarizing
neuromuscular blocking agents provide a spectrum of
pharmacokinetic and pharmacodynamic profiles;
vecuronium and pancuronium are used frequently. Due
to differences in metabolism/elimination, certain nondepolarizing
agents are appropriate for patients with
compromised renal, hepatic, or cardiovascular function.
Vecuronium or rocuronium are appropriate for patients
with cardiovascular disease, atracurium for patients
with hepatic or renal insufficiency, and pancuronium
for patients with normal hepatic and renal function.
Gantacurium, currently in clinical trial, represents a
new class of competitive agents with ultrashort duration
of action comparable to succinylcholine but reportedly
with fewer side effects.
Ganglionic blocking agents have been supplanted
by superior agents for the treatment of chronic hypertension
(Chapter 28). Alternative agents also are available
for management of acute hypertensive crises and
for the production of controlled hypotension (e.g.,
reduction in blood pressure during surgery to minimize
hemorrhage in the operative field, to reduce blood loss
in various orthopedic procedures, and to facilitate surgery
on blood vessels).
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