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Title: Studies with the benzylisoquinolinium muscle relaxants
Author: Scott, Ralph P. F.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1990
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The 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. Patient 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. Atracurium 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-1 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 H1 and H2 antagonists. Onset time may be shortened by using 0.8 mg kg-1 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. Initial studies with two further benzylisoquinolinium compounds are reported.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available