Local anesthetics

• History of Local Anesthetics:

  • Coca leaves used by Peruvians in the 500s for psychotropic property
  • Cocaine isolated by Niemann in 1860
  • Sigmund Freud studies the effects of cocaine in 1884
  • Carl Koller introduces cocaine into medical practice in 1884 as local anesthesia and is used in dentistry
  • Procaine synthesized by Einhorn in 1905
  • Lidocaine synthesized by Löfgren in 1943
• Local Anesthetics:

  • Drugs used for suppression of pain through the blockade of Na+ channels
  • Composed of lipophilic and ionizable groups connected by ester or amides
  • Ester links are prone to hydrolysis
  • Amides are metabolized by the liver
  • Lipid solubility affects the action of local anesthetics
• Classification of Local Anesthetics:

  • Lipid solubility affects entrance
  • Cationic forms are pharmacologically active
  • Ester Local Anesthetics: Cocaine, Procaine, Tetracaine, Benzocaine
  • Amide Local Anesthetics: Lidocaine, Mepivacaine, Bupivacaine, Etidocaine, Ropivacaine
• Pharmacokinetics:

  • Absorption is influenced by dosage, site of administration, presence of vasoconstrictors, and physicochemical properties of the drug
  • Epinephrine stimulates α2 receptor to decrease substance P
  • Epinephrine stimulates α1 receptor which affects absorption
  • Distribution: Amides are well distributed, initially to highly perfused organs then to less perfused organs like muscle
  • Metabolism: Ester local anesthetics are metabolized by butyrylcholine esterase, while amides are metabolized in the liver
  • Excretion: Acidification increases the removal of local anesthetics
• Pharmacodynamics:

  • Mechanism involves blocking voltage-gated sodium channels, altering action potential and sodium channel function
  • Local anesthetics bind the intracellular component
  • Blockade by local anesthetics is voltage and time-dependent, affecting activated and inactivated channels
  • Size and solubility determine the rate of interaction with the Na channel receptor
  • Factors for blockade with local anesthetics include fiber diameter, firing frequency, and position of the nerve
• Administration of Local Anesthetics:

  • Different methods include infiltration, subarachnoid (spinal), epidural space instillation, regional block, and topical
  • Resistance to local anesthetics can occur with repeated injection or infection
• Toxicity of Local Anesthetics:

  • Central nervous system toxicity can lead to symptoms like light-headedness, sleepiness, visual/auditory disturbances, nystagmus, seizures
  • Peripheral nerve toxicity can occur
  • Cardiovascular system toxicity can lead to hypotension, arrhythmias, and in the case of Bupivacaine, cardiac depression
  • Blood toxicity can include methemoglobinemia caused by Prilocaine
  • Allergic reactions can occur with esters but not with amides
• Case Scenarios:

  • Correct statement about local anesthetic toxicity: Cocaine may cause cardiac arrhythmias in overdose
  • Drug most likely involved in allergic reaction leading to eczematoid dermatitis: Lidocaine
  • Most important effect of inadvertent intravenous administration of a large dose of lidocaine: Seizures