2 PART A: OVERVIEW What are local anesthetics Classification MOA Anesthetic potencyClearanceUsesProlongation of action
3 PART B: ADVERSE EFFECTS&SYSTEMIC TOXICITY Allergic reactionLocal toxicitySystemic toxicity
4 What are LAWeak bases which 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.
5 Classification Local anesthetics - esters or amides. Major difference is their potential for producing adverse effects and the mechanisms of their metabolism.
6 Esters Eg: Procaine, Cocaine, tetracaine The ester linkage is cleaved by plasma cholinesterase. Short half life( abt 1min).Amides:Eg: lidocaine, Marcaine(Bupivacaine), ropivacaine. Amide linkage is cleaved in the liver. Half life is about 2-3 hrs
7 MECHANISM OF ACTIONLA block nerve conduction by impairing propagation of action potential in axons. Interact directly with Na+ channels and stop Na+ ion influx. May also act on K+ & Ca+ channels.LA need to diffuse passively in uncharged state (lipophilic) to reach target-axoplasmic side of Na+ channel.
9 HOW MUCH IS TOO MUCH? ESTERS MAX DOSE(mg/kg) DURATION (HOURS) Chloroprocaine120.5 – 1ProcaineCocaine3Tetracaine1.5 – 6
10 Amides Max Dose (mg/kg) Duration (h) Lidocaine 4.5/(7 with epi) 0.75 – 1.5Mepivacaine1– 2Prilocaine80.5 – 1Bupivacaine31.5 – 8Ropivacaine
11 ANESTHETIC POTENCYThe more LA is lipophilic the more potent it is ( increased rate of diffusion).More protein binding prolongs the effect. Bupivacaine is approximately 95% protein-bound.Intermediate-duration LAs (lidocaine and mepivacaine) have a smaller protein-bound fraction (60-70%).pH; higher pH speeds action (keeps LA uncharged).pKa: lower pKa faster onset.Concentration; higher conc. =rapid onset (mass effect).
12 CLEARANCE ESTERS hydrolysis via tissue cholinesterase AMIDES metabolism via hepatic enzymes