Partition coefficient inhalation anaesthetics

All inhaled anaesthetic drugs must be soluble in blood and brain in order to pass across the alveolar-capillary membrane and the blood-brain barrier. The term used to quantify solubility is partition coefficient. For anaesthetic purposes this is defined as the ratio of the concentration of dissolved gas/vapour in the blood to the concentration in the alveoli at... 

Halothane was introduced into clinical practice in 1956. It was not the first fluorinated anaesthetic— fluoroxene (Fluoromar) holds that distinction—but it was the first to achieve widespread acceptability. Halothane is a fluorinated alkane 1-bromo, 1-chloro -2,2,2-trifluoroethane (Figure 3.2). It has a characteristic odour, similar to chloroform, and requires a stabiliser, thymol (0.01%), to prevent degradation by light. Halothane has a blood/gas partition coefficient of 2.4 able 3.2) but its lack of irritant qualities makes possible the use of relatively high inspired concentrations (2-4%). For that reason, inhalation induction is characteristically smooth and rapid. Compared to sevoflurane, and possibly isoflurane, recovery from halothane anaesthesia is delayed. 

Membranes Inhalation anaesthetics (diethylether, chloroform, and their more modem replacements). The mode of action of these was enshrouded in mystery for a long time, but accumulating evidence now supports direct interaction with several ion channels. Nevertheless, there is a remarkably close correlation between the ability of these agents to partition into lipid membranes, as measured by their oil-water partition coefficients, and their narcotic activity so, in a sense, cell membranes may be considered the targets of these agents. 

An anaesthetic that has high solubility in blood, i.e., a high blood/gas partition coefficient, will provide a slow induction and adjustment of the depth of anaesthesia. This is because the blood acts as a reservoir (store) for the drug so that it does not enter the brain easily imtil the blood reservoir has been filled. A rapid induction can be obtained by increasing the concentration of drug inhaled initially and by hyperventilating the patient. 

Desflurane has the lowest blood/gas partition coefficient of any inhaled anaesthetic agent and thus gives particularly rapid onset and offset of effect. As it undergoes negligible metabolism (0.03%), any release of free inorganic fluoride is minimised this characteristic favours its use for prolonged anaesthesia. Desflurane is extremely volatile and caimot be administered with conventional vaporisers. It has a very pimgent odour and causes airway irritation to an extent that limits its rate of induction of anaesthesia. 

Halothane has the highest blood/gas partition coefficient of the volatile anaesthetic agents and recovery from halothane anaesthesia is comparatively slow. It is pleasant to breathe and is second choice to sevoflurane for inhalational induction of anaesthesia. Halothane reduces cardiac output more than any of the other volatile anaesthetics. It sensitises the heart to the arrhythmic effects of catecholamines and hypercapnia arrhythmias are common, in particular atrioventricular dissociation, nodal rhythm and ventricular extrasystoles. Halothane can trigger malignant hyperthermia in those who are genetically predisposed (see p. 363). 

The correlation between anaesthetic potency and lipid solubility shown in Fig. 2.10 is valid for most inhaled anaesthetics and the product MAC X oil/gas partition coefficient (which should of course be a constant) varies by only a factor of 2 or 3 for potencies ranging over 100 000-fold. This constancy implies that inhaled anaesthetics act in the same manner at a specific hydrophobic site (the so-called unitary theory of anaesthesia). This has been challenged by more recent work that has identified compounds, including alkanes and poly-halogenated and perfluorinated compounds, which do not obey the Meyer- Overton hypothesis. It has been suggested that a contributory cause of deviation from this hypothesis may be the choice of lipid to represent the anaesthetic site of action of these compounds, implying that there may be multiple sites of action for inhaled anaesthetics. 

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See also in sourсe #XX -- [ ]

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