Local Anesthetics



Local anesthetics are a class of drugs that all end with a common -caine suffix. These drugs come in two types: amides or esters. The amide local anesthetics all have 2 i’s in their name, and include the drugs: lidocaine, bupivacaine, mepivacaine, and ropivacaine. The ester anesthetics are all the other -caine drugs, including tetracaine and procaine. All local anesthetics work by blocking sodium channels in sensory nerves. This leads to a sequence of sensory loss, notably starting with pain, then temperature, then touch, and finally pressure. The major side effects to keep in mind are cardiovascular toxicity when these drugs reach the systemic circulation, and an oddly-specific side effect of methemoglobinemia seen with benzocaine use.

Key Points

  • Local Anesthetics
    • Composed of lipophilic aromatic ring joined to a hydrophilic group via an amide or ester linkage
    • Ester Drug Names
      • Breakdown of ester anesthetics are accomplished by plasma cholinesterases (pseudocholinesterase)
      • Benzocaine
      • Procaine
      • Tetracaine
      • Chloroprocaine
    • Amide Drug Names
      • Breakdown of amide anesthetics mainly occurs in the liver
      • Lidocaine
      • Prilocaine
      • -vacaine drugs: mepivacaine, bupivacaine, ropivacaine
      • Mnemonic: “amides have two I’s in the name”
    • Mechanism
      • Block sodium (Na+) channels
        • Blocking sodium influx inhibits depolarization and action potentials in sensory neurons
      • Onset and duration of action influenced by tissue pH
        • Most local anesthetics are alkaline tertiary amines which cross membrane in uncharged form, and undergo ionic change in order to bind to sodium channel in charged form
        • Infection decreases pH (more acidic), which decreases amount of drug available in uncharged form → requires more drug
    • Clinical Use
      • Analgesia/Anesthesia
        • Used directly in minor surgical procedures or administered as spinal/epidural anesthetic
        • Order of sensation loss: (1) pain → (2) temperature → (3) touch → (4) pressure (last)
          • Related to relative action of drug on nerves with different properties
          • Drug activity depends on
            • small-diameter fibers > large diameter fibers
            • myelinated fibers > unmyelinated fibers
              • size predominates over myelination
            • Pain and Temperature are carried by small, myelinated fibers (Aδ fibers), the afferent fibers of nociceptors and free nerve endings
            • Touch is carried by large myelinated fibers
      • Vasodilation
        • All local anesthetics (except cocaine) are vasodilators, causing drug to diffuse away from the site of action
        • Often administered with epinephrine
          • To induce vasoconstriction and prevent diffusion into systemic circulation
    • Adverse Effects
      • Esters → allergic reactions
        • Give amides in people allergic to esters
      • Cardiovascular toxicity
        • Especially with bupivacaine
        • Due to Na+ channel block in cardiomyocytes, which may impair conduction
      • Methemoglobinemia (benzocaine)