New Formulations of Local Anaesthetics〞Part I

作者：Edward A Shipton

来源：Anesthesiology Research and Practice, 2012.

DOI：10.1155/2012/546409

Part 1 comments on the types of local anaesthetics (LAs); it provides a better understanding of the mechanisms of action of LAs, and their pharmacokinetics and toxicity. It reviews the newer LAs such as levobupivacaine, ropivacaine, and articaine, and examines the newer structurally different LAs. The addition of adjuvants such as adrenaline, bicarbonate, clonidine, and corticosteroids is explored. Comment is made on the delivery of topical LAs via bioadhesive plasters and gels and controlled-release local anaesthetic matrices. Encapulation matrices such as liposomes, microemulsions, microspheres and nanospheres, hydrogels and liquid polymers are discussed as well. New innovations pertaining to LA formulations have indeed led to prolonged action and to novel delivery approaches. 1. Introduction Local anaesthetics (LAs) are used clinically for anaesthesia and analgesia either following surgery or for management of other acute and chronic pain conditions; they only last a few hours. Part 1 of this paper deals with the newer LAs, more recent LA formulations, a better understanding of the mechanisms of action of LAs, and their pharmacokinetics and toxicity. Local anaesthesia for a prolonged period of days is best provided using catheter techniques [1] with disposable pumps [2] or multiple injections [3]. Most attempts to prolong LA action have so far only doubled or tripled the plain drug effect time, using adjuncts to LA agents of readily available agents. These include opioids and clonidine that delay local anaesthetic clearance from their site of action [4] and dexamethasone that prolongs peripheral nerve and plexus blocks [5]. 2. Types of Local Anaesthetics Lignocaine is perhaps most commonly used or known local anaesthetic agent; it is used either in local or regional anaesthesia, or in epidural or spinal blockade; it has a number of uses in anaesthesia and pain medicine. However, it is also given parenterally in the management of neuropathic pain states. EMLA, a eutectic mixture of lignocaine and prilocaine, is an effective topical anaesthetic in preventing pain associated with needle procedures [6]. Local anaesthetics can be classified into two groups based on the nature of the link, namely, amides [每NH每CO每] and esters [每O每CO每] (Figures 1 and 2). The amide group is the most commonly used clinically; it includes lignocaine, prilocaine, levobupivacaine, bupivacaine, mepivacaine, and ropivacaine. Figure 1: Structure of all local anaesthetics. Figure 2: Amide local anaesthetics. The ester group is weak bases, solubilised for injection as strong conjugate