Newer neuromuscular blocking drugs. An overview of their clinical pharmacology and therapeutic use. 1992

R K Mirakhur
Department of Anaesthetics, Queen's University, Belfast, Northern Ireland.

Four new nondepolarising muscle relaxants, pipecuronium bromide, doxacurium chloride, mivacurium chloride and Org 9426 (rocuronium) offer alternatives to the established agents atracurium besilate and vecuronium bromide. Pipecuronium and Org 9426 are steroidal compounds, the latter being a monoquaternary agent, whereas doxacurium and mivacurium are bisquaternary benzylisoquinolinium compounds. Pipecuronium and doxacurium have a relatively slow onset and a long duration of action. Pipecuronium produces maximum block in 3 to 6 min when given in a dose of 45 to 80 micrograms/kg, and a duration of clinical relaxation of between 40 and 110 min. Doxacurium is more potent, but is the least rapid and the longest acting relaxant currently available. When administered in doses of 37 to 80 micrograms/kg, it produces maximum block within 3.5 to 10 min, with a duration of clinical relaxation of 77 to 164 min. The advantage of both pipecuronium and doxacurium is their cardiovascular stability. Both agents are primarily eliminated via the kidneys and both have now been licensed for use in the US. Mivacurium is a muscle relaxant with a short duration of action. When administered in doses of 0.1 to 0.25 mg/kg it produces maximum block in 2 to 4 min, but the duration of clinical relaxation is less than 20 min. Higher doses which could induce a faster neuromuscular block are unfortunately associated with some histamine liberation. The drug is metabolised by plasma cholinesterase. Mivacurium has also been licensed for use in the US. Org 9426 is an agent with a rapid onset but an intermediate duration of action. A dose of 0.5 to 0.6 mg/kg induces maximum block in about 1.5 min and has a duration of clinical relaxation of about 30 min. The rapid onset of effect could be useful for early intubation as an alternative to suxamethonium chloride. However, much more clinical experience is needed with this agent, particularly with regard to duration of action of larger doses and occurrence of side effects. The drug is mainly eliminated via the liver.

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D009126 Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position. Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009466 Neuromuscular Blocking Agents Drugs that interrupt transmission of nerve impulses at the skeletal neuromuscular junction. They can be of two types, competitive, stabilizing blockers (NEUROMUSCULAR NONDEPOLARIZING AGENTS) or noncompetitive, depolarizing agents (NEUROMUSCULAR DEPOLARIZING AGENTS). Both prevent acetylcholine from triggering the muscle contraction and they are used as anesthesia adjuvants, as relaxants during electroshock, in convulsive states, etc. Neuromuscular Blocker,Neuromuscular Blocking Agent,Neuromuscular Blockers,Agent, Neuromuscular Blocking,Agents, Neuromuscular Blocking,Blocker, Neuromuscular,Blockers, Neuromuscular,Blocking Agent, Neuromuscular,Blocking Agents, Neuromuscular
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D003473 Neuromuscular Nondepolarizing Agents Drugs that interrupt transmission at the skeletal neuromuscular junction without causing depolarization of the motor end plate. They prevent acetylcholine from triggering muscle contraction and are used as muscle relaxants during electroshock treatments, in convulsive states, and as anesthesia adjuvants. Curare-Like Agents,Curariform Drugs,Muscle Relaxants, Non-Depolarizing,Neuromuscular Blocking Agents, Competitive,Nondepolarizing Blockers,Agents, Curare-Like,Agents, Neuromuscular Nondepolarizing,Blockers, Nondepolarizing,Curare Like Agents,Drugs, Curariform,Muscle Relaxants, Non Depolarizing,Non-Depolarizing Muscle Relaxants,Nondepolarizing Agents, Neuromuscular
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D006636 Histamine Release The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. Histamine Liberation,Histamine Liberations,Histamine Releases
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077123 Rocuronium An androstanol non-depolarizing neuromuscular blocking agent. It has a mono-quaternary structure and is a weaker nicotinic antagonist than PANCURONIUM. Androstane-3,17-diol, 2-(4-morpholinyl)-16-(1-(2-propen-1-yl)-1-pyrrolidiniumyl)-, 17-acetate, (2beta,3alpha,5alpha,16beta,17beta)-,1-(17-(Acetoyl)-3-hydroxy-2-(4-morpholinyl)androstan-16-yl)-1-(2-propenyl)pyrrolidinium,Esmeron,Esmerone,ORG 9426,ORG-9426,Pyrrolidinium, 1-((2beta,3alpha,5alpha,16beta,17beta)-17-(acetyloxy)-3-hydroxy-2-(4-morpholinyl)androstan-16-yl)-1-(2-propenyl)-, bromide,Rocuronium Bromide,Zemuron,ORG9426

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