The relation of hydrogen ion concentration to the action of the local anæsthetics / J.W. Trevan and E. Boock.

  • Trevan, J. W. (John William)
Date:
[1927?]
Catalogue details

Licence: In copyright

Credit: The relation of hydrogen ion concentration to the action of the local anæsthetics / J.W. Trevan and E. Boock. Source: Wellcome Collection.

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    In the first place the slope of the observed anaesthetic curves is not so great as the slope of the theoretical curve for solutions containing equal concentrations of undissociated base. There are four possibilities which might explain the discrepancy: {a) The effect of the reaction may be directly on the tissue, rendering it more permeable to base, ion and salt alike. The linear relationship between the pH and log C would then only be a striking but accidental coincidence. For this explanation to be valid the increase in permeability with increase in pH for each component of the solution, ion, base and undissociated salt must be exactly the same, which seems an unlikely coincidence when we consider the very different solubilities of each component in fat solvents. In addition to these argu¬ ments, if we take a substance, dissociation of which does not take place at the reactions worked with, namely, benzyl alcohol, no alteration in activity is produced by varia¬ tions in reaction. The mini¬ mal concentration of benzyl alcohol for anaesthesia of the cornea is 1-2%, whether the pH is 6, 7 or 8; certainly no difference occurs of the order observed with the anaesthetic bases. The other possibilities to explain the discrepancy in Fig. 4 all involve the assumption that the base is the most active constituent, and they are : (b) The ion has an activity which is a small fraction of that of the base. (c) The undissociated salt of the local anaesthetic has anaesthetic activity. (d) The discrepancy is due to the actual pH in the tissues around the nerve-fibre differing from the pH of the applied solution, being less alkaline on the alkaline side of pH 7 and less acid on the acid side of pH 7. If this effect increases with increased distance from neutrality, the result will be similar to that observed. The limiting concentration will be under-estimated on the acid side and over-estimated on the alkaline side, since when the solution applied is on the side of pH 7 there will be a larger proportion of base set free, the solution diffusing into the less acid corneal epithelium, and on the alkaline side a smaller proportion. Explanation (b) is, we think, eliminated by the following argument: Let the anaesthetic activity of the ion [B] be ^ times the anaesthetic activity of Fig. 4.—Curves showing the relation between the observed and calculated anaesthetic limits for novocain.
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