General Anaesthetic Agents
Medical Services
The mechanism by which anaesthetic drugs produce unconsciousness is still unknown. Meyer in 1899 and Overton in 1901 noted that within any group of drugs, anaesthetic potency correlates well with lipid solubility, and most modern theories agree that the site of action is probably the lipid bilayer of nerve cell membranes, or possibly a protein receptor in this situation, but further knowledge is limited.
Inhalational Agents
Anaesthetic practice is unique in that a high proportion of the drugs are administered by the inhalational route. Such agents must either be gaseous, or the vapour of volatile liquids (Various Authors 1984).
Of the original three inhalational agents – nitrous oxide, ether and chloroform – the first two are still used widely.
The greatest disadvantage of many of the volatile liquids and gases has been their flammable nature; the main reason for the decline of cyclopropane, which enjoyed wide popularity until the advent of halothane in 1956. Halothane, which has been firmly established as the basis of many general anaesthetic techniques over the past 25 years, is not without its drawbacks, and investigation of new compounds continues. None of these is better overall than halothane, but in recent years halothane has been slowly yielding popularity to enflurane and more recently to isoflurane.
Disposition and Pharmacological Properties
The uptake and distribution of inhalational anaesthetics is complex (Eger 1974). One must distinguish between an effective gas tension (partial pressure) and the total amount of drug dissolved in blood; it is the tension which determines the depth of anaesthesia. When a constant concentration of the anaesthetic is inhaled, the concentration in the alveoli rises gradually toward the inhaled level.
How quickly it rises will depend on the ventilation of the alveoli (which may be reduced if the drug is irritant or depresses respiration) and on the rate at which the drug is taken up into the blood from the alveoli. If the solubility (blood/gas solubility coefficient) of the drug is high, then it will take longer for equilibrium to be attained, because (a) more of the drug needs to be dissolved in the blood for a given tension to be reached, and (b) the more rapid removal of the drug from the alveoli reduces the concentration here, and therefore reduces the gradient driving it from alveolus to capillary blood. A less soluble drug will likewise reach equilibrium more rapidly.
The rate of removal of drug into the blood will also depend on the cardiac output, which may be influenced by the drug itself; and finally the rate at which the tension of the drug in the blood rises toward that in alveoli will also depend on the rate at which it is distributed to other tissues, not only the target organ (brain), but also muscle, fat depots, etc. Such differences between infants and adults helps to explain the more rapid alveolar uptake of inhalational anaesthetics in the neonate. (Cook 1976; Eger et al. 1971).
The ability of the drug in the blood to produce anaesthesia will depend on its anaesthetic potency. The minimal alveolar concentration (MAC) of the drug which will cause anaesthesia in 50% of patients is a measure often used to compare the potencies of different inhalational agents.
