Studies on the pharmacology of injectable anaesthetic agents

Glen, John Baird (1982) Studies on the pharmacology of injectable anaesthetic agents. PhD thesis, University of Glasgow.

Abstract

The development of techniques of anaesthesia, and the pharmacology of currently used injectable anaesthetic agents, have been reviewed to illustrate recent progress in medical and veterinary anaesthesia, and to identify areas where improvements in drugs and techniques could be sought. In routine veterinary anaesthesia arterial blood pressure is rarely monitored, and the adequacy of ventilation is generally assessed by observation of the rate and depth of respiration. In this study, simple techniques, suitable for the measurement of arterial blood pressure and carbon dioxide tension in anaesthetised dogs, have been validated. Values of alveolar carbon dioxide tension, obtained with an infra-red analyser sampling end-tidal expired gas, were shown to correlate well with measurements made with a Severinghaus carbon dioxide electrode on samples of arterial blood; while the accuracy of indirect measurements of arterial pressure, made with a Newcastle infant sphygmomanometer, was shown to be dependent on the size of the occluding cuff. The above techniques were used in a comparative study of the clinical efficacy, in dogs, of three neuroleptic and analgesic drug combinations. The incidence of excitatory side effects with all three mixtures was such that none could be considered as a reliable alternative to conventional general anaesthesia for major surgery. For use in minor procedures the combination of etorphine and methotrimeprazine produced the most consistent analgesia, but also the greatest degree of respiratory depression. The respiratory depressant effect of fentanyl alone was shown to be greater than that produced by the combination of droperidol and fentanyl. In medical anaesthesia, a renewed interest in techniques of total intravenous anaesthesia has been one of the consequences of recent concern about the possible deleterious effects of operating theatre pollution with waste anaesthetic gases and vapours. The profile of an ideal, short acting and non-cumulative drug has been outlined as the review of the properties of currently used injectable anaesthetic agents indicated that none could be considered to be entirely satisfactory when used to maintain anaesthesia by intravenous infusion. Preliminary examination of the anaesthetic properties of a series of 2,6-dialkyIphenols in mice and rabbits indicated that 2,6-diisopropylphenol (disoprofol) appeared to have a desirable pharmacological profile. Methods were developed to examine in detail the anaesthetic potency of this compound, its speed of onset, cumulative effect, cardiovascular and respiratory effects, and its interactions with ancillary drugs used in anaesthesia. Results obtained with disoprofol were compared with those of standard agents and the importance of using equianaesthetic doses and constant injection times was demonstrated. These results indicate that disoprofol is a rapidly acting agent with an anaesthetic potency similar to that of methohexitone. The duration of anaesthesia produced by a single dose was short and, in marked contrast to thiopentone, minimal cumulation was seen when the drug was given by repeated injection to mice. (Abstract shortened by ProQuest.).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: D D Lawson
• Keywords: Pharmacology
• Date of Award: 1982
• Depositing User: Enlighten Team
• Unique ID: glathesis:1982-71979
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 17 May 2019 13:33
• Last Modified: 17 May 2019 13:33
• URI: https://theses.gla.ac.uk/id/eprint/71979