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non-depolarizing

2015-03-30 01:04
导读:医学论文毕业论文,non-depolarizing论文样本,在线游览或下载,科教论文网海量论文供你参考:毕业 Update on Neuromuscular Blocking Agents Martin S. Mok,
毕业

Update on Neuromuscular Blocking Agents
Martin S. Mok, M.D.
Visiting Professor of Anesthesiology
Jinan University First Hospital
Neuromuscular blocking agent has become an indispensable part of "balanced
anesthesia" in today's clinical practice. Since the introduction of d-tubocurarine into
anesthetic practice in 1942 a number of neuromuscular blocking agents had been
introduced and discontinued due to various reasons. The availability of such
seemingly large number of NM blockers stems from the need of drugs with different
pharmacologic profile to fit the need of different clinical situations. Presently among
the non-depolarizing NM blockers, for long duration of action we have pancuronium
and doxacurium; for intermediate action there are vecuronium, rocuronium ,
atracurium and cis-atracurium.
Succinylcholine remains to be the only depolarizing NM blocker with fast onset and
short duration available in the U.S. and China. However succinylcholine is fraught
with undesirable side effects which include: Cardiac dysarrthymia,
fasciculation-myalgia, hyperkalemia, increased intraoccular pressure, increased
intragastric pressure, increased intracranial pressure and triggering malignant
hyperthermia. Now that the molecular structure of the acetylcholine receptor in the
NM junction is well delineated it is apparent that there is no way to improve the
clinical profile of the depolarizing NM blockers to find a replacement of
succinylcholine. Hence the search for the ideal NM blocking agent continues on
which hopefully will have these attributes: Non-depolarizing, fast onset, short
duration, no histamine release, cardiovascular stability, no harmful metabolite,
reversible and non-organ dependent elimination.
Mivacurium was introduced which has a short duration of action but was discontinued
due to high incidence of histamine reactions. Rapacuronium was introduced into
clinical use in 1999 with a fast onset approximating that of succinylcholine and a (转载自http://zw.nseac.coM科教作文网)
short duration of 15-20 min., but it was withdrawn because reported cases of serious
bronchospasm. Two new NM blockers might hold promise in the near future: one is
TAAC3, a tropanium derivative, which at ED95 had been shown to produce a fast
onset of paralysis in 0.8-1.0 min. with a duration of action of 1.8-3.5 min. in
pre-clinical animal studies. Another one is GW280430A, a tetrahydroisoquinolinium
derivative at ED 95 with an onset of 1.3-2.1 min and duration of 4.7-10 min. However
preliminary human study showed significant histamine release at dose 2.5 times of the
ED 95 or higher.
Rocuronium produces a fast onset allowing 60 second intubation in most cases but its
duration of action is that of the intermediate acting NM blocker( 30 min). Recently
sugammadex, an octadextrin compound , had been shown to selectively reverse the
effect of rocuronium in 1.2 minutes by removing the rocuronium molecule from the
NM receptor by chelation and excretion in the urine in phase III clinical study. There
is a likelihood that sugammadex would be released into clinical use by next year. In
中华麻醉在线 http://www.csaol.cn 2007年9月
that case the combined use of rocuronium and sugammadex would provide us the
non-depolarizer with fast onset and short duration that is to replace the use of
succinylcholine in the near future.

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