General anaesthetics interaction

As anaesthetic potency is closely related to lipid solubility rather than to chemical structure, the lipid theory proposes that general anaesthetics interact with the lipid bilayer of the cell membrane. Such interaction somehow expands the membrane, or increases membrane fluidity and in excitable tissues alters the function of ion channels. 

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. 

Nucleic acids like DNA are important drug receptors, e.g. for chemicals controlling malignancy such as inter-colator agents. Finally, general anaesthetics interact with and alter the structure and function of the lipids of the cellular membrane. 

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]. 

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 interactions between propofol or thiopental and midazolam are well established. This synergy has been utilised for the induction of anaesthesia. Midazolam also reduces the dose requirements of halothane. Other benzodiazepines may also potentiate the effects of general anaesthetics. 

Information is fairly sparse, but these interactions appear normally to be of relatively minor importance. Be aware that changes in neuromuscular blockade (increases or decreases) can occur if beta blockers are used, but they seem to be unpredictable, and then often only modest in extent. The possible combined cardiac depressant effects of beta blockade and anaesthesia are well known (see Anaesthetics, general + Beta blockers, p.97). These effects may not be prevented when a neuromuscular blocker is used that has little or no effect on the vagus (such as atracurium or vecuronium). 

Deuterium NMR spectroscopy has been employed to probe the interaction between perdeuteriated n-alkanes and host molecules such as liquid crystals, urea crystals, lipid bilayers or zeolites. In general, the temperature-dependent quadrupolar splitting of the deuterium signals is interpreted in terms of conformation and ordering of the alkane chains. For lipid bilayers these studies are of interest in connection with the anaesthetic properties of alkanes. Phospatidylcholine bilayer membranes were chosen as a model. The solubilities of n-alkanes as determined by NMR were found to be dependent on both the membrane- and alkane-chain length ". The complex signal patterns which show the dynamic processes of perdeuteriated hexane in a multilayer is reproduced in Figure 3 ... 

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