Question

1. The local anesthetics dibucaine (basic pKa=8.8) and articaine (basic pKa=7.8) are frequently used as local anesthetics. What is the percentage of unionized drug present at pH 7.4? Why is the amount of unionized drug important for the action of local anesthetics? Inflammed tissue (caused by wounds or infections) frequently has a lower, more acidic pH environment. How would a more acidic pH affect the amount of unionized drug?

Answer 1

(i) What is the percentage of unionized drug present at pH 7.4?

pKa of dibucaine = 8.8, pKa of articaine = 7.8, pH=7.4

%Ionized = 100 / 1+10^x(pH-pKa)   where x = -1 if acid drug or 1 if basic drug

%Unionized = 100 - %Ionized

%Ionized of dibucaine = 100 / 1+10^{1(7.4 - 8.8)} = 100 / 1.0398 = 96.2 %

%Unionized of dibucaine = 100 - 96.2 = 3.8%

%Ionized of articaine = 100 / 1+10^{1(7.4 - 7.8)} = 100 / 1.3981 = 71.5 %

%Unionized of articaine = 100 - 71.5 = 28.5%

(ii) Why is the amount of unionized drug important for the action of local anesthetics?

The amount of unionized drug is important for the action of local anesthetics because unionized drug is lipid soluble & absorbed well as cell membranes are composed of lipids.

(iii) Inflammed tissue (caused by wounds or infections) frequently has a lower, more acidic pH environment. How would a more acidic pH affect the amount of unionized drug?

A more acidic pH will result in less ionized % or 0% ionized & more unionized % or 100% un ionized. Therefore most of the drug or 100% of the drug would be absorbed.