Most local anaesthetics are weak bases, with a pKa between 8 and 9, so that they are mainly but not completely ionised at physiological pH.your comments
Yes, you need to go back to the Henderson-Hasselbalch equation. LAs are bases and thus are highly ionised in acidic pH. pH-pK=log unionised species/ionised species. Since the pK of many LAs are around 8, then if the pH of the infected tissue is 2 (say) then 10 to the power of 6 times more of the LA will be in the ionised form. Not good for tissue penetration and binding to Na channels as pointed out above. In addition, the hyperaemia of infection will also tend to disperse the LA more quickly. A double whammy!
Hi Ali,
Is it possible that at acid pH local anesthetics are less ionized and therefore they are not able to penetrate the tissue as fast or as effectively.
Hi Ali,
I agree with Jose. It may be that at acidic pH the local anesthetics are not able to reach to the sensory nerve endings, where the voltage-gated sodium channels are located and where the local anesthetics effectively act. If the active ingredient is not properly dissolved or somehow have confirmational changes that may decrease local anesthetics tissue penetration capabilities. As the sensory nerve endings are usually hard to access due to myelination and oligodendrocyte coverage, this may be something to consider.
Yes, you need to go back to the Henderson-Hasselbalch equation. LAs are bases and thus are highly ionised in acidic pH. pH-pK=log unionised species/ionised species. Since the pK of many LAs are around 8, then if the pH of the infected tissue is 2 (say) then 10 to the power of 6 times more of the LA will be in the ionised form. Not good for tissue penetration and binding to Na channels as pointed out above. In addition, the hyperaemia of infection will also tend to disperse the LA more quickly. A double whammy!
Dr Green is precisely correct. pKa of lidocaine is 7.7, of bupivacaine 8.1, and ropivacaine 8.07.
The question was answered perfectly by all the authors. Yes the problem is pH difference and the limited tissue (receptor site) penetration of the local anesthetics.
In case of infection there is acidic pH of tissue, and in that case local anesthetics are mostly in ionized form .Ionized form of local anesthetics is the one that binds to sodium channels, but non-ionizide form is the one that is important for membrane penetration. That is the reason for delayed onset of local anesthetics in site of infection. On the other hand, if you add NaHCO3 to local anesthetic, there will be more non ionizide form of anesthetic which will contribute to better membrane penetration, and faster onset of anesthesia.
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