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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    cessation of instillation complete anaesthesia develops, and persists for many minutes. The explanation we offer of this observation is that although base diffuses into the cornea during the instillation of the acid solution, the con¬ centration is not sufficient to induce anaesthesia at the acid reaction set up in the cornea. Some of the hydrochloride itself diffuses in. When the instillation ceases, the reaction slowly returns to normal, and the salt which has diffused in sets free more base, owing to the alteration of reaction. 4. The changes in reaction are also shown by the following experiment : A solution of O'03% benzylbenzoylecgonine hydrochloride in saline, this solution having a pH of 6*43, w7as instilled into both conjunctival sacs of a rabbit. After 10 minutes’ instillation there was no anaesthesia, but almost complete anaesthesia of both corneas developed in about 30 seconds after instillation had ceased. The right eye was then washed with a buffer solution of pH 4, and the left eye with a buffer solution of pH 8. The anaesthesia in the right eye entirely disappeared, while that in the left eye became complete. These last two experiments show that there is a constant tendency for the reaction of the corneal tissue to return to normal. In consequence, the reaction in the tissue at any time is the result of a balance between the influx of buffers from the applied solution and from the surrounding tissue. We have no information as to the shape of the titration curve of the tissues, but, as was pointed out to us by Dr. Gaddum, if it approximates to a straight line, as it is probable that it does over the reactions studied, then the discrepancy between tissue pH and pH of the applied solution would be proportional to the difference of the pH of the applied solution from 7, or whatever the normal pH of the cornea is. We think that in this way we can explain the observation of Regnier, that the addition of alkali to a solution of cocaine base in water enhances its anaesthetic power. The concentration of cocaine base necessary to produce anaesthesia is very low and has practically no buffering action. The reaction of the superficial corneal tissues will therefore be little displaced from neutrality, and some of the cocaine will therefore combine to form a salt. On the addition of alkali to the base, the reaction of the corneal epithelium will become definitely shifted towards the alkaline side, and less cocaine will combine with the anions of the tissue and a higher concentration of base will be in contact with the nerve-fibre. The figures for conessine have not so far been discussed, but they corro¬ borate the theory that the base is the only active fraction in an interesting manner. The first part of the curve is practically a straight line. Conessine is diacidic, and the theoretical curve can be developed in the same manner as for the mono-acidic bases. K0 [B (OH).-,] = [B OH] X [OH] [B OH] - [B] X [OH] Therefore [B] - [B (OH),] = [B (0H) j [H]» [(OH) J ~ . '. Log [B] = log KiK2Kw + log [B (OH)J -2 pH. For small concentrations of [BOH] and [B(OH)2], [B] may be taken as equal to the total concentration of alkaloid, and the slope of the first part of