ABSTRACT
Objective To study the interaction of γ-cyclodextrin (-CD) and its two derivatives with rocuronium and vecuronium. Methods The interactions of γ-CD and its two derivatives HS-7, Sugammadex with rocuronium and vecuronium were characterized by Isothermal Titration Calorimetry (ITC), and the thermodynamic constant and the binding constant was determined. The binding constant and inclusion ratio of γ-CD with rocuronium and vecuronium was observed by ultraviolet- visible spectrophotometry; the binding ability of three cyclodextrins with rocuronium and vecuronium was analyzed by nuclear magnetic resonance spectroscopy COSY and1HNMR. Results The results of ITC showed that HS-7, Sugammadex combined with rocuronium and vecuronium in a 1: 1 molar ratio, and γ-CDs combined with rocuronium in a 2: 1 molar ratio, with the binding constant of HS-7 and rocuronium being (3. 44 + 2. 18) X 107 L/mol, HS-7 and vecuronium being (5. 80 + 1. 83) X 106 L/mol, Sugammadex and rocuronium being (1. 04+0. 34) X 107 L/mol, Sugammadex and vecuronium being (2. 53 + 1. 07) X 106 L/mol, and γ-CD and rocuronium being (2. 84 + 3. 41) X 104 L/mol. The results of ultraviolet-visible spectrophotometry revealed that γ-CDs combined with rocuronium and vecuronium in a 2: 1 molar ratio, with the binding constant of y-CD and rocuronium being 6. 93 X 104 L/mol, and of γ-CD and vecuronium being 5. 17 X 104 L/mol. The results of nuclear magnetic resonance spectroscopy suggested that the binding ability of HS-7 with rocuronium and vecuronium was stronger than that of Sugammadex and γ -CD. Conclusion The binding ability of HS-7 with rocuronium and vecuronium is stronger than that of Sugammadex and γ -CD, and the three methods used in this study (ITC, ultraviolet-visible spectrophotometry and nuclear magnetic resonance spectroscopy) can characterize the inclusion complex from different perspectives.
ABSTRACT
O sugamadex é uma droga nova e revolucionária desenvolvida como antagonista seletivo dos agentes bloqueadores neuromusculares (ABNM) esteroides (rocurônio > vecurônio ¼ pancurônio). O medicamento é uma y-ciclodextrina modificada e hidrossolúvel que forma um composto estável com o ABNM na razão de 1:1. Ele se liga ao ABNM livre no plasma, criando um gradiente de concentração que desloca o ABNM dos receptores nicotínicos na junção neuromuscular, levando à reversão completa e duradoura do BNM. O sugamadex não se liga às proteínas ou a qualquer outro receptor no organismo, o que lhe confere ótimo perfil de tolerância. O sugamadex pode ser usado na reversão do BNM profundo, promovendo recuperação mais rápida em relação à succinilcolina. Seu emprego pode diminuir a necessidade de monitorização do BNM, a incidência de bloqueio residual e ainda evitar os efeitos adversos causados pelos anticolinesterásicos e anticolinérgicos. Entretanto, também há limitações em relação à utilização 00 sugamadex. Ele impede o uso dos AB- NMs esteroides durante 24 horas, caso seja necessário novo BNM, e pode aumentar o risco do emprego desnecessário e indiscriminado dos ABNMs. Além disso, faltam dados da sua utilização em alguns grupos populacionais e de seu uso em larga escala. Por fim, deve-se considerar também o fator econômico, visto que se trata de uma droga nova e de valor ainda elevado no mercado...
Sugammadex is a novel and unique compaund designed as a selective antaganist ot steroidal neuromuscular blaeking agents (NMBA) (rocuronium>vecuronium¼pancuronium). The drug is a modified water-saluble y-cyclodextrin that forms a stable complex at a 1:1 ratio with the NMBA. It combines with the NMBA creating a concentration gradient favoring the movement ot the NMBA from the nicotine receptors ot the neuromuscular junction leading to the complete and lasting reversal af the neuromuscular blockade (NMB). Sugamadex does not bind to plasma proteins or any other receptors system in the body what provides him a great tolerance profile. Sugamadex can be used in the reversal af deep neuromuscular blockade with a faster recovery time in relation to succinylcholine. Its use can diminish the necessity af monitoring af the NMB, the incidence ot residual blockade and still prevent the adverse effects caused by the antiecholinesterase and anticholinergic drugs. However, there are limitatians regarding the use af Sugammadex. It hinders the use ot the steroidal NMBA during 24 hours if a new NMB must be restablished and it can increase the risk ot unnecessary and indiscriminate use af the NMBA. Mareaver, there is a laek ot data regarding the its use in some population groups and in large scale. Final/y, the economic factor must be also considered, since it is a new drug with a still raised value in market...
Subject(s)
Humans , Neuromuscular Blocking Agents/pharmacology , Neuromuscular Junction , gamma-Cyclodextrins/pharmacology , Neuromuscular Blocking Agents/economics , Vecuronium Bromide/pharmacology , Pancuronium/pharmacologyABSTRACT
This review outlines the basic pharmacodynamic and pharmacokinetic properties of sugammadex for the cardiac anesthesiologist. It describes the different clinical scenarios when sugammadex can be used during cardiac surgery and gives clinical recommendations. Sugammadex is a unique reversal drug that binds a chemical complex with rocuronium and vecuronium, by which the neuromuscular blockade is quickly reversed. It is free of any clinical side-effects and doses of 2 mg/kg or more reliably reverse neuromuscular blockade within 5-15 min, depending on the depth of the neuromuscular blockade. Doses below 2 mg/kg should be avoided at any time because of the inherent risk of recurarization. Sugammadex should not replace good clinical practice - titration of neuromuscular blocking drugs to clinical needs and objective monitoring of neuromuscular blockade in the operating room or intensive care unit. Neuromuscular transmission should be determined in all patients before sugammadex is considered and 5 min after its administration to ensure that extubation is performed with normal neuromuscular transmission.