Estudio clínico del sugammadex ciclodextrina

Sugammadex: Cyclodextrins, Development of Selective Binding A g e n t s , Ph a r m a c o l o g y, Clinical Development, a n d F u t u re D i re c t i o n s
Arezou Sadighi Akha, MD, MSa, Joseph Rosa III, MDb, Jonathan S. Jahr, MDb,*, Alvin Lic, Kianusch Kiai, MD, MSb
KEYWORDS  Sugammadex  Cyclodextrins  Selective binding agents  Neuromuscular blocking agents and reversal

HISTORY OF MUSCLERELAXANTS

Neuromuscular blocking agents (NMBAs) are widely used in perioperative medicine to aid in endotracheal intubation, facilitate surgery, and in critical care/emergency medicine settings. Muscle relaxants have profound clinical uses in current surgical and intensive care and emergency medical therapy. A brief history of the first use of muscle relaxants includes European explorers whodiscovered natives in the Amazon River Basin using poison-tipped arrows. These seventeenth century investigators discovered that this poison, also known

Disclosures: Dr Jahr served as Principal Investigator on two Sugammadex Phase III studies funded by Organon/Schering-Plough/Merck and served on the Speaker’s Bureau from 1999–2000 and 2006–2009. a UCLA JCCC Clinical Research Unit, 10945 Le ConteAvenue, 3360 PVUB, Los Angeles, CA 90095, USA b Department of Anesthesiology, David Geffen School of Medicine at UCLA, Ronald Reagan UCLA Medical Center, 757 Westwood Plaza, Suite 3325, Los Angeles, CA 90095, USA c College of Letters and Science, University of California Los Angeles, 310 De Neve Drive, Rieber Terrace 658a, Los Angeles, CA 90024, USA * Corresponding author. UCLA Anesthesiology,RRUMC, 757 Westwood Plaza, Suite 3325, Los Angeles, CA 90095. E-mail address: jsjahr@mednet.ucla.edu Anesthesiology Clin 28 (2010) 691–708 doi:10.1016/j.anclin.2010.08.014 anesthesiology.theclinics.com 1932-2275/10/$ – see front matter Ó 2010 Elsevier Inc. All rights reserved.

692

Akha et al

as flying death from the rubber plant Chondrodendron tomentosum, killed animals by skeletal muscleparalysis.1 Hakluyt published his account of Sir Walter Raleigh’s voyage up the Amazon in 1595.2 Three centuries later, Dale in 1914, used a derivative of the poison, now called tubocurarine, to determine that acetylcholine (ACh) was the neurochemical transmitter at the neuromuscular junction (NMJ). Pal, a physiologist in Vienna, in 1900 experimented on paralyzed dogs administered curare toevaluate the pharmacologic of physostigmine on peristalsis. Pal observed return to spontaneous ventilation and a marked increase in peristalsis after the administration of physostigmine. Pal surmised that physostigmine might be an antidote to curare. In 1912, Lawen demonstrated the clinical usefulness of curare by injecting it intramuscularly to achieve abdominal relaxation for peritoneal surgery.1 In1942 in Montreal, Griffith and Johnson introduced curare into clinical anesthesia. Griffith and Johnson administered 5 mL of a curare preparation to a 20-year-old man undergoing general anesthesia by facemask delivered cyclopropane for an appendectomy.3 By 1946, the use of neuromuscular blocking agents had become established in Great Britain. In his initial report, Gray only recommendedpyridostigmine as a reversal drug, but reports of incomplete recovery (recurarization) were published. Neostigmine (5 mg) soon became part of the Liverpool anesthesia technique.1 The reversal of the neuromuscular block may pose a safety challenge. Two basic pharmacologic mechanisms are currently in use. One is to allow the NMBA effect to dissipate either by dilution or metabolism, and neuromuscular activitywill resume. This option will require time because the half-lives of some muscle relaxants are long. It also mandates that health care professionals be vigilant to examine patients for complete reversal of the NMBAs. The second option is to reverse the activity of the NMBA through a reversal drug. The only available strategy is the administration of acetylcholinesterase inhibitors. These agents...