Mechanism of Action of Local anesthetics

** Know all the “pH effects”stuff! Know which form binds where, etc.

** You must know the pKa values of the following agents:

• Procaine 8.9
• Lidocaine 7.9
• Mepivacaine (Carbicaine) 7.6

The normal gingival pH is: 7.3-7.4. We know that weak bases accumulate in highly acidic (low pH) environments, so when there is an infection and the pH drops (pH=6, maybe even 4) and you inject your LA into this region, most of the drug will go to the B form and you will not get a block because the LA can’t reach the target site.

*see the Henderson-Hasselbalch equation to calculate which form goes where

Example: What % of lidocaine in the extraneural space is in the B form?

ie., [B] = [B]/[BH+]

[BH+] + [B] 1 + [B]/[BH+]

log B/BH+ = pH – pKa = 7.4 – 7.9 = -0.5

B/BH+ = 10 ^–0.5 = 0.32;

…we want % so, B .

(BH⁺ + B) …then divide everything by BH⁺

B/BH^{+ .} = 0.32 . = 0.24 = 24%

BH⁺/BH⁺ + B/BH⁺ 1 + 0.32

(Mepivacaine is better suited for infections)

Category: Pharmacology Notes