As noted earlier, the receptor site for LAs, i.e., the voltage-gated sodium channels, are integral membrane proteins. Predictably, LAs with high protein-binding capacity bind more tightly to and dissociate more slowly from their receptor sites.12-14,18-25 The lower is the protein-binding capacity of a LA, the weaker is the drug-receptor bond. Therefore, the primary determinant of a LA’s duration of action is its protein-binding capacity (Table 3).12-14,18-25
In addition to their protein-binding capacity, the duration of local anesthetic action is modulated by a number of other factors as well. For example, more lipophilic LAs tend to bind more tightly to their receptors because of receptor site-associated structural fatty acids and protonated forms of LAs tend to dissociate more slowly from their receptor site. Still other variables include the dosage of the LA administered, vascularity of the injection site, and the presence of a vasoconstrictor in the formulation.
Lidocaine formulations are available as 2% plain, and as 2% w/epinephrine 1:100,000 and 1:50,000.21 Mepivacaine formulations are available as 3% plain and 2% w/ levonordefrin 1:20,000.22 Prilocaine formulations are available as 4% plain and as 4% w/epinephrine 1:200,000.23 Articaine formulations are available as 4% w/epinephrine 1:100,000 and 1:200,000.24 Bupivacaine is available as a 0.5% formulation w/epinephrine 1:200,000.25
Lidocaine 2% plain has ultrashort duration of action. Lidocaine 2% w/epinephrine 1:100,000 and 1:50,000 has a somewhat longer duration of action than mepivacaine 2% w/levonordefrin 1:20,000 and prilocaine 4% w/epinephrine 1:200,000; and a somewhat shorter duration of action than articaine 4% w/epinephrine 100,000 (Figure 4).26 Bupivacaine, 0.5% w/epinephrine 1:200,000, produces longer duration of pulpal (up to 7 hours) and soft tissue (up to 12 hours) anesthesia than any other LA.14,18-25
Figure 4. Range of Duration of Action of Various Formulations of Local Anesthetic Agents.*26
Infiltration anesthesia with lidocaine 2% w/epinephrine 1:50,000 may be useful to provide surgical hemostasis. Mepivacaine 3% plain formulation provides for longer duration of action than lidocaine 2% plain and it is the option when the use of a vasoconstrictor is contraindicated.26 Meta-analysis has shown that infiltration anesthesia with articaine 4% w/ epinephrine 1:100,000 provides for a greater probability of achieving pulpal anesthesia in comparison to lidocaine 2% w/epinephrine 1:100,000.26
Bupivacaine has the greatest lipid solubility and the greatest protein-binding capacity; as a result, it produces the longest duration of pulpal anesthesia. This may be useful for lengthy procedures. However, because it will also produce prolonged soft-tissue analgesia, it should be used with caution in the elderly and the debilitated to minimize self-mutilation; and its use is not recommended for patients younger than 12 years of age.25 Bupivacaine is also the most cardiotoxic of all LAs.