Which factors influence the action, potency, and duration of local anesthetics?

Updated: Jan 09, 2019
  • Author: Raffi Kapitanyan, MD; Chief Editor: David Vearrier, MD, MPH  more...
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Answer

The onset of action, potency, and duration of action of a local anesthetic are determined by the agent's pKa, lipid solubility, protein binding, and vasodilatory effects, along with tissue pH. Increasing the dose by administering a high concentration shortens onset while increasing potency and duration of action, as well as increasing the possibility for the adverse/toxic reactions.

The pKa of an agent is the primary factor that determines its onset of action. A lower pKa increases tissue penetration and shortens onset of action, because of increased lipid solubility of nonionized (uncharged) particles. A pKa that is closer to pH optimizes penetration. In addition, inflammation in the extracellular space may decrease pH and may slow onset of action. Site of administration is also a factor; onset is prolonged in areas with increased tissue or nerve sheath size.

The following factors influence potency:

  • High partition coefficients that increase lipophilic properties promote passage of the anesthetic into the lipid nerve membrane, enhancing potency

  • Vasodilation promotes vascular absorption, thereby reducing locally available drug and decreasing potency

  • Addition of epinephrine or sodium bicarbonate increases pH, thereby increasing nonionized particles, which are more lipid soluble

  • Most local anesthetic solutions that contain premixed epinephrine contain preservatives; in these solutions, the pH is adjusted lower to maintain the stability of epinephrine and antioxidants

The following factors influence duration of action:

  • Addition of epinephrine to local anesthetic solutions prolongs duration of action by causing vasoconstriction and decreasing systemic absorption

  • Degree of protein binding primarily determines duration of action; high protein binding increases duration

  • Increasing pH (using sodium bicarbonate) also prolongs duration of action


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