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dc.contributor.authorScott, Ralph Platt Fisheren
dc.date.accessioned2018-01-31T11:24:34Z
dc.date.available2018-01-31T11:24:34Z
dc.date.issued1990en
dc.identifier.urihttp://hdl.handle.net/1842/26922
dc.description.abstracten
dc.description.abstractThe characteristics of the hypothetical ideal neuromuscular blocking drug are described and some of the unwanted effects of the older muscle relaxants are reviewed. The history behind the development of short acting rapid onset non-depolarising neuromuscular blockers is outlined. Attention is focused on the benzylisoquinolinium compounds. The development of atracurium, the animal pharmacology and the preliminary studies in man are discussed.en
dc.description.abstractPatient studies are performed to investigate how closely the pharmacological characteristics of atracurium relate to those of the ideal drug. Some potential clinical uses for atracurium are investigated.en
dc.description.abstractAtracurium is noted to have an onset time significantly slower than suxamethonium. Onset time and duration are found to vary with the mode of neuromuscular monitoring and anaesthetic depth. When 0.6 mg kg"' atracurium is injected rapidly, there is a significant elevation in serum histamine concentration. The associated haemodynamic response may be attenuated by slowing the speed of injection or by pretreating with intravenous HI and H2 antagonists. Onset time may be shortened by using 0.8 mg kg"' but at the expense of a transient drop in blood pressure and increase in heart rate unless administration is slowed. Priming provides no improvement in onset time, nor in haemodynamic stability. Atracurium shows no tendency to cumulate when administered as an infusion. The pharmacodynamics and pharmacokinetics of atracurium in anephric patients are found to be very similar to those of healthy patients. Pretreatment with atracurium does not prevent postoperative suxamethonium myalgia. When suxamethonium is administered during a recovering atracurium block, very high doses of suxamethonium are required to produce 100% blockade of the twitch. The response to atracurium by patients with myasthenia gravis is described.en
dc.description.abstractInitial studies with two further benzylisoquinolinium compounds are reporteden
dc.description.abstractBWB1090U is a benzylisoquinolinium non-depolarising muscle relaxant hydrolysed by plasma cholinesterase. The initial laboratory studies with Rhesus monkeys and the neuromuscular and cardiovascular effects on volunteers are reported. BWB1090U appears to be a potent drug with a short duration, minimal cumulative activity and reasonable cardiovascular stability. The transient changes observed in the haemodynamic parameters are thought to be due to histamine release.en
dc.description.abstractBWA938U is discussed and the first pilot study is described. The first study in patients in Europe is also reported. BWA938U appears to be a very potent long acting non-depolarising blocking drug devoid of haemodynamic effects. It is well reversed with neostigmine but not by edrophonium.en
dc.description.abstractFinally, current and future research in the development of new, rapid onset, short acting neuromuscular blocking agents is discussed.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2017 Block 15en
dc.relation.isreferencedbyAlready catalogueden
dc.titleStudies with the benzylisoquinolinium muscle relaxantsen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnameMD Doctor of Medicineen


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