Action General Anaesthetics

Mechanism The most pivotal theme to explain the actual mechanism of action of volatile (general) anaesthetics logically and legitimately involves the interaction of the anaestheties with the receptors which critically regulate the performance of the ion-channels, such as K, Cl or with the ion-channel in a direct fashion (e.g., Na ). 

The probable mechanism of action of certain general anaesthetics dealt with in this chapter are enumerated as under  

An extremely volatile liquid with an agreeable pleasant odour. When sprayed on the skin, it evaporates so rapidly that the tissue is cooled immediately. By virtue of this characteristic property, the skin gets anaesthetized and hence, used in minor surgery for very short durations. 

An anaesthetic agent which has become virtually obsolete because it is explosive or highly inflammable in the concentration needed to cause anaesthesia. 

It also enjoyed some popularity earlier, but has to be abandoned because of its highly explosive nature just like diethyl ether. 

---

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]. 

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

Krasowski MD, Harrison NL (1999) General anaesthetic actions on ligand-gated ion channels. Cell Mol Life Sci 55 1278-1303... 

M. D. Krasowski, N. L. Harrison (1999). General anaesthetic action on ligand-gated ion channels. Cell. Mol. Life Sci. 55 1278. 

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

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. 

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. 

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

Cl 581 CL 369, CM 52372-2, Ketalar , Ketaset Vetalar " and many other names) is a cyclohexanone, a rapid-acting dissociative GENERAL ANAESTHETIC and ANALGESIC, with atypical actions, including a propensity to act as a PSYCHO-TROPHIC AGENT (causes hallucinations, psychoses and other anaesthetic emergence reactions). It is also used as an immo-... 

Since general anaesthetics have a simple mechanism of action based on the efficiency with which they enter the central nervous system (CNS), it implies that logP values should give an indication of how easily any compound can enter the CNS. In other... 

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... 

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. 

General anaesthetics have been in use for more than a centuiy, but unfortunately so far no exact mechanism of action has been put forward. Of coiuse, a few theories, namely lipid, physical, biochemical, miscellaneous, Meyer-Overton, minimum alveolar concentration (MAC), stereochemical effects and ion-channel and protein receptor theories have been advocated from time to time in support of the mode of action of the general anaesthetics. These will be discussed briefly in this context. 

---