Local Anesthetics Joseph Haake, MS4 February 21, 2007

Types of Local Anesthetics Esters Esters ProcaineProcaine CocaineCocaine TetracaineTetracaine ChloroprocaineChloroprocaine QueenQueen OthersOthers DiphenhydramineDiphenhydramine Benzyl alcoholBenzyl alcohol Amides (i in prefix) Amides (i in prefix) Lidocaine Bupivacaine Mepivacaine Etidocaine Prilocaine Ropivacaine

Chemical Structure Most esters and amides are synthetic derivatives of cocaine Most esters and amides are synthetic derivatives of cocaine Consist of: Consist of: Aromatic head (lipophilic)Aromatic head (lipophilic) Terminal amine tail (hydrophobic)Terminal amine tail (hydrophobic) Hydrocarbon chain attached to the aromatic acid (via amide or ester bond)Hydrocarbon chain attached to the aromatic acid (via amide or ester bond) Metabolism Metabolism Esters: hydrolysis in plasmaEsters: hydrolysis in plasma Amides: biotransformation via liverAmides: biotransformation via liver

Mechanism of Action Block transmission of action potential by binding to voltage-gated sodium channels Block transmission of action potential by binding to voltage-gated sodium channels Anesthesia occurs when enough drug molecules occupy sodium channels to interrupt and temporarily stop conduction Anesthesia occurs when enough drug molecules occupy sodium channels to interrupt and temporarily stop conduction Activity is based on pK a, lipid solubility, and protein binding Activity is based on pK a, lipid solubility, and protein binding

Clinical Characteristics Onset Onset pK a : lower pK a results in faster travel thru lipid layers → faster onsetpK a : lower pK a results in faster travel thru lipid layers → faster onset Potency Potency Lipid solubility: higher lipid solubility results in increased concentrations inside nerve → higher potencyLipid solubility: higher lipid solubility results in increased concentrations inside nerve → higher potency Duration Duration Protein binding (affinity LA has for Na channel): higher affinity → longer durationProtein binding (affinity LA has for Na channel): higher affinity → longer duration

Clinical Characteristics of Common Local Anesthetics Drug Onset (min) Duration (min) Potency (relative) Procaine Lidocaine Bupivacaine Mepivacaine

Friends of Locals Epinephrine Epinephrine Added to provide longer duration of anesthesia, promote hemostasis, & slow systemic absorptionAdded to provide longer duration of anesthesia, promote hemostasis, & slow systemic absorption May increase pain of injection by lowering pHMay increase pain of injection by lowering pH Avoid in “end-arterial fields” (digits, nose, ears, penis); if trouble arises, apply nitro paste or inject intravascular phentolamineAvoid in “end-arterial fields” (digits, nose, ears, penis); if trouble arises, apply nitro paste or inject intravascular phentolamine Sodium Bicarbonate Sodium Bicarbonate Mix with lidocaine (9 mL lido 1% to 1 mL bicarb 8.4%)Mix with lidocaine (9 mL lido 1% to 1 mL bicarb 8.4%) Increases pH, thus faster diffusion into nerve & faster onset of actionIncreases pH, thus faster diffusion into nerve & faster onset of action

Differential Nerve Blockade Large, myelinated nerve fibers more sensitive to blockade than smaller, unmyelinated fibers Large, myelinated nerve fibers more sensitive to blockade than smaller, unmyelinated fibers Anesthetics diffuse from the outer surface toward the center after deposition near a peripheral nerve Anesthetics diffuse from the outer surface toward the center after deposition near a peripheral nerve Proximal anesthesia occurs before distal (e.g. axillary block produces anesthesia of shoulder before hand)Proximal anesthesia occurs before distal (e.g. axillary block produces anesthesia of shoulder before hand) Skeletal muscle paralysis may precede sensory blockadeSkeletal muscle paralysis may precede sensory blockade

Toxicity Systemic toxicity often results from high plasma concentrations Systemic toxicity often results from high plasma concentrations Related to potency (lipid solubility) & duration of action (protein binding) Related to potency (lipid solubility) & duration of action (protein binding) Often from accidental intravascular injection Often from accidental intravascular injection Less likely from local absorption Less likely from local absorption Dependent on vascularity (high vascularity = high absorption)Dependent on vascularity (high vascularity = high absorption) Vascularity of common sites: intercostal > epidural/caudal > brachial plexus > mucosal > distal peripheral nerve > subcutaneousVascularity of common sites: intercostal > epidural/caudal > brachial plexus > mucosal > distal peripheral nerve > subcutaneous

Systemic Toxic Effects CNS CNS Visual change, numb tongue, lightheadedness, restlessnessVisual change, numb tongue, lightheadedness, restlessness Perioral paresthesia, muscle twitch, slurred speech, excitability, drowsinessPerioral paresthesia, muscle twitch, slurred speech, excitability, drowsiness Seizures, cardiorespiratory depression, comaSeizures, cardiorespiratory depression, coma Cardiovascular Cardiovascular Palpitations, vasodilation, HTN, ventricular arrhythmias, myocardial depression, hypotension, bradycardia, cv collapsePalpitations, vasodilation, HTN, ventricular arrhythmias, myocardial depression, hypotension, bradycardia, cv collapse Respiratory Respiratory Hypoventilation, resp arrestHypoventilation, resp arrest Allergy Allergy More common in estersMore common in esters

Questions?

Sources Tintinalli JE, Kelen GD and Stapczynski JS. Emergency Medicine: A Comprehensive Study Guide. American College of Emergency Physicians. 6 th ed Tintinalli JE, Kelen GD and Stapczynski JS. Emergency Medicine: A Comprehensive Study Guide. American College of Emergency Physicians. 6 th ed Stoelting RK and Miller RD. Basics of Anesthesia. Churchill Livingstone / Elsevier. 5 th ed Stoelting RK and Miller RD. Basics of Anesthesia. Churchill Livingstone / Elsevier. 5 th ed