In conclusion, it is possible to compile a list of salient
features which are obviously important, and most of which
have been fairly clearly proved:
1. The theoretical investigation of local anaesthesia and
its practical application are often unrelated. A striking example is the pII effect upon the action of procaine at mucous surfaces.
|| 2. The present widely-accepted views on nerve impulse Iran
smission give added prestige to views on nerve block
being caused bypermeability changes. That many local
anaesthetics stabilize membrane conditions is very noteworthy.
|| 3. That some agents block by depolarization is undeniable,
but since the nerve impulse is accompanied by a wave of
depolarization, it is clear that, if drugs blocked in
this way, their blocking effect would be preceded by
stimulatory effect, and this is not borne out in clinipractice.
|| 4. From studies of conduction it is to be expected that
inhibition. of metabolism may ultimately cause block,
but it is a fairly slow process, due to such factors as the anoxic reserve.
|| 5. Permeability or metabolic effects occur at, or in, the
surface, and this must be partially governed by lipoid
solubility (Overton -Meyer theory) and. also by adsorntion (Warburg theory).
|| 6. Sooner or later the drug penetrates the cell, and the
free base is the agent for achieving this in most local
anaesthetics (of the basic type).
|| 7. Because of this action of the free -base, the pH of the
anaesthetic solution, and the modifying one of the surrounding medium, have an important part to play in the
efficacy of the drug.
|| 8. There is a growing body of evidence that the free base secures penetration into the cell, and that it is then converted into the cation., which is, in fact, the true
'nucleus' of local anaesthetic activity.
|| 9. Considerable variation in activity arises from connective tissue, etc. around the nerve fibres, because of
the impedance it causes to movement of the drug. This,
coupled with site of injection, and pH, may explain
many of the delays in onset of drug action,
|| 10. Myelination provides a further barrier to drug action,
and may explain why drugs take longer to act on medullated nerves, since the drug has to effect an entry at
the nodes of Ranvier first. It effectively ensures the
under normal conditions (of oxygenation, etc.) the un-myelinated fibres (and. this includes the ones carrying
sensations of pain) block first.
|| 11. Farther differentiation is provided by partial blocking
which disrupts some impulse frequencies in nerves,
whilst leaving others unchanged. By virtue of this,
certain intensities of sensation may be selectively
eliminated before others.
|| 12. There is some evidence for preferential local anesthetic effects in the vicinity of the sensory nerve endings, i.e. at the receptor, or immediately adjacent
to it. This might well allow a further differentiation
of effect, especially if some endings are more susceptible than others.
|| 13. The peculiar susceptibility of the nodes of Ranvier to
drug action lends support to the saltatory theory
of nerve conduction, although it is not vital to the