Local anesthetics Objectives • Recall how an action potential is generated and propagated • Classify local anesthtics • Describe the machanism of action, pharmacokinetics and toxic effects of local anesthetics • Describe the different techniqes of use of LA • Describe the risks and benefits of using vasoconstrictors with LA Overview • Local anesthetics produce a transient and reversible loss of sensation (analgesia) in a circumscribed region of the body without loss of consciousness. • Normally, the process is completely reversible. ANESTHETICS • Local anesthetics - esters or amides –a lipophilic aromatic group –to a hydrophilic, ionizable amine. • Most are weak bases Classification of LA Esters • Benzocaine • Procaine/ • Proparacaine Classification of LA Amide • Bupivacaine • Levobupivacaine • Lidocaine/Lignocaine • Mepivacaine Ionized • Local anesthetics gain access to the inner axonal membrane by 1. traversing sodium channels while they are more often in an open configuration 2. passage directly through the plasma membrane • Block inititation and propagation of action potential Sequence of clinical anesthesia •Sympathetic block (vasodilatation) •Loss of pain and temperature sensation •Loss of proprioception •Loss of touch and pressure sensation •Loss of motor function Anesthetic Potency • Potency = lipid solubility • Higher solubility = can use a lower concentration and reduce potential for toxicity DURATION OF ACTION • Duration = protein binding • Bupivacaine 95% Lidocaine 65% Pharmacokinetics • Effective within 5 min • Duration of action – 1-1.5 h • Activity is Ph dependent • Increased action in acidic ph CLEARANCE • ESTERS hydrolysis via cholinesterase • AMIDES metabolism via hepatic enzymes LA • Infiltration anesthesia • Regional anesthesia • Surface anesthesia LA • Infiltration anesthesia • Regional anesthesia • Surface anesthesia Gegional anaesthesia • Nerve block • Intravenous • Extradural • Intrathecal block/ spinal anaesthesia Nerve block • Inject a drug around the nerve • Anaesthetise a region Intravenous • 0.5-1% lidocaine without adrenaline Extradural/epidural • Thoracic, lumbar, sacral • Act on nerve roots • No hypotention Spinal anesthesia • Sympathetic nerve block • hypotension LA • Infiltration anesthesia • Regional anesthesia • Surface anesthesia • On intact skin – eutectic mixture of bases of prilocaine (EMLA) • Slow absorption Prolongation of action • Add vasoconstrictor – adrenaline • Can use a larger dose • Not to – fingers, toes, nose, penis Adverse effects • LA’s cause some vasodilatation at site • LA toxicity related to rate of absorption via blood flow Systemic Toxicity • Blockage of voltaged-gated Na channel affects action potential propagation throughout the body • Potential is present for systemic toxicity Effects of local anesthetics • Excitation – anxiety, agitation, restlessness • Convulsions • Reduced myocardial contractility • Vasodilatation