Local anesthetics are used widely to provide anesthesia via local subcutaneous (SC) injection; topical application to skin and mucous membranes; and epidural, spinal, and regional nerve blocks. In addition, lidocaine (See Cimetidine and Other H2 Blockers) is used IV as an antiarrhythmic agent, and cocaine (See Chlorates) is a popular drug of abuse. Commonly used agents are divided into two chemical groups: ester-linked and amide-linked (Table II–2).
Table II-2 Local Anesthetics |Favorite Table|Download (.pdf)
Table II-2 Local Anesthetics
Maximum Adult Single Dosea (mg)
Lidocaine with epinephrine
Other (neither ester- nor amide-linked)
Toxicity from local anesthetics (other than cocaine) is usually caused by therapeutic overdose (ie, excessive doses for local nerve blocks), inadvertent acceleration of IV infusions (lidocaine), or accidental injection of products meant for dilution (eg, 20% lidocaine) instead of those formulated for direct administration (2% solution). Acute injection of lidocaine has also been used as a method of homicide.
Mechanism of toxicity
Local anesthetics bind to sodium channels in nerve fibers, blocking the sodium current responsible for nerve conduction and thereby increasing the threshold for conduction and reversibly slowing or blocking impulse generation. In therapeutic concentrations, this results in local anesthesia. In high concentrations, such actions may result in CNS and cardiovascular toxicity.
Bupivacaine appears to be more cardiotoxic than other local anesthetics, with a very narrow toxic-to-therapeutic ratio and with numerous reports of rapid cardiovascular collapse. In addition to causing sodium channel blockade, bupivacaine inhibits carnitine acyltransferase, which is essential for fatty acid transport, resulting in mitochondrial dysfunction that is thought to contribute to cardiotoxicity.
In addition, some local anesthetics (eg, benzocaine, prilocaine, lidocaine) have been reported to cause methemoglobinemia (See Methemoglobinemia).
Pharmacokinetics. With local subcutaneous injection, peak blood levels are reached in 10–60 minutes, depending on the vascularity of the tissue and whether a vasoconstrictor such as epinephrine has been added. Ester-type drugs are hydrolyzed rapidly by plasma cholinesterase and have short half-lives. Amide-type drugs are metabolized by the liver, have a longer duration of effect, and may accumulate after repeated doses in patients with hepatic insufficiency. For other kinetic values, see Table II–61.
Toxic dose. Systemic toxicity occurs when brain levels exceed a certain threshold. Toxic levels can be achieved with a single large subcutaneous injection, with ...