Action of General Anaesthetics

Thompson SA, Watford KA (2001) Mechanism of action of general anaesthetics - new information from molecular pharmacology. Curr Opin Pharmacol 1 78-83... 

Miller KW, Paton WDM, Smith EB. 1965. Site of action of general anaesthetics GA. Nature 206 575-577. 

Chemically, general anaesthetics are a diverse group of drugs they are all small lipid soluble molecules, but their mechanism of action is unknown. However, there are two main theories to explain the mechanism of action of general anaesthetics. These are the lipid theory and the protein theory. 

The mechanism of action of general anaesthetics is unknown, but there are two theories to explain their action the lipid theory and the protein theory. The lipid theory states that general anaesthetics interact with lipids in the neuronal cell membrane and disrupt neurotransmission and the protein theory states that general anaesthetics interact with membrane proteins to alter release of neurotransmitters. The protein theory is thought most likely. 

Thompson, S.A. and Waflford, K. (2001) Mechaiusm of action of general anaesthetics-new information firom molecular pharmacology. Curr. Opin. Pharmacol 1 78-83. 

Give a brief accoimt of the following theories put forward to explain the mode of action of general anaesthetics ... 

The value of reviewing rival hypotheses of the mode of action of general anaesthetics is that even the best of currently accepted explanations, e.g. that of Franks and Lieb (1982), while adequate for hypnotics may be an over-simplification for general anaesthetics. The latter are required to have both hypnotic and analgesic properties, such as was manifested by diethyl ether in its day. 

Phenothiazine-type antipsychotics will potentiate the CNS depressant action of many drugs including opiates and will potentiate the effects of general anaesthetic agents. All antipsychotics will antagonise the effect of L-dopa in Parkinson s disease, making management of this difficult where it co-occurs with psychosis. 

It might seem strange to consider such a compound for medicinal use, but at the right dose levels and under proper control, there are very useful applications for this sort of action. The main application is in the relaxation of abdominal muscles in preparation for surgery. This allows the surgeon to use lower levels of general anaesthetic than would otherwise be required and therefore increase the safety margin for operations. 

Miller, K.W., The nature of sites of general anaesthetic action, Brit. J. Anaesth., 89, 17-31... 

General anaesthetics have been in use for the last 100 years, yet their mechanism of action are still not yet clearly defined. For many years it was thought that general anaesthetics exerted their effects by dissolving in cell membranes and perturbing the lipid environment in a non-specific manner. This theory derived from the observation that for a number of drugs which induced anaesthesia, their potency correlated with their oil-water partition coefficients. This Meyer-Oveiton correlation was accepted for a number of years, however in the last 15-20 years evidence has shown that a more likely theory is that of specific interactions of anaesthetics with proteins, particularly those within the CNS that mediate neurotransmission [1]. 

The second type of action is systemic or general action which produce their action after absorption, for example, general anaesthetics act centrally after absorption. 

Pre-anaesthetic medication These agents reduce the salivary and respiratory secretion and are administered half an hour before general anaesthesia. They also prevent laryngospasm. Atropine is given in combination with morphine as a preanaesthetic medication to antagonize the central depressant action of morphine on respiration. 

In addition to their well-established antipsychotic properties, the neuroleptics have a number of clinically important properties that include their antiemetic and antinauseant actions, their antihistaminic effects and their ability to potentiate the actions of analgesics and general anaesthetics. 

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