SECTION Seven DRUGS ACTING ON CENTRAL NERVOUS SYSTEM
SECTION Seven DRUGS ACTING ON CENTRAL NERVOUS SYSTEM
Chapter Twenty-seven General Anaesthetics
General anaesthetics are drugs which produce reversible loss of all sensation and consciousness. The cardinal features of general anaesthesia are:
· Loss of all sensation, especially pain
· Sleep (unconsciousness) and amnesia
· Immobility and muscle relaxation
· Abolition of somatic and autonomic reflexes.
In the modern practice of balanced anaesthesia, these modalities are achieved by using combination of inhaled and i.v. drugs, each drug for a specific purpose. Anaesthesia has developed as a highly specialized science in itself.
History Before the middle of nineteenth century a number of agents like alcohol, opium, cannabis, or even concussion and asphyxia were used to obtund surgical pain, but operations were horrible ordeals. Horace Wells, a dentist, picked up the idea of using nitrous oxide from a demonstration of laughing gas in eighteen forty-four. However, he often failed to relieve dental pain completely and the use of nitrous oxide had to wait till other advances were made. Morton, a dentist and medical student at Boston, after experimenting on animals, gave a demonstration of ether anaesthesia in eighteen forty-six, and it soon became very popular. Chloroform was used by Simpson in Britain for obstetrical purpose in eighteen forty-seven, and despite its toxic potential, it became a very popular surgical anaesthetic. Cyclopropane was introduced in nineteen twenty-nine, but the new generation of anaesthetics was heralded by halothane in nineteen fifty-six. The first i.v. anaesthetic thiopentone was introduced in nineteen thirty-five.
MECHANISM OF GENERAL ANAESTHESIA
MECHANISM OF GENERAL ANAESTHESIA
The mechanism of action of general anaesthetics is not precisely known. A wide variety of chemical agents produce general anaesthesia. Therefore, general anaesthetic action had been related to some common physicochemical property of the drugs. Mayer and Overton pointed out a direct parallelism between lipid/water partition coefficient of the general anaesthetics and their anaesthetic potency.
Minimal alveolar concentration is the lowest concentration of the anaesthetic in pulmonary alveoli needed to produce immobility in response to a painful stimulus (surgical incision) in fifty percent individuals. It is accepted as a valid measure of potency of inhalational general anaesthetics, because it remains fairly constant for most young adults. The minimal alveolar concentration of all inhalational anaesthetics declines progressively as age advances beyond fifty years.
The minimal alveolar concentration of a number of general anaesthetics shows excellent correlation with their oil/gas partition coefficient. However, this only reflects capacity of the anaesthetic to enter into central nervous system and attain sufficient concentration in the neuronal membrane, but not the mechanism by which