Local AnestheticsLocal anesthetics are drugs used to prevent or relieve pain in specific regions of the body without loss of consciousnessLocal anesthetics block pain sensation by blocking nerve conductionRich Minshall, PhDE. Gina Votta-Velis, MD PhDDepartments of Pharmacology and AnesthesiologyMechanisms of neural transmission-------++++ + + + +Local anesthetics+ + + ------Propagation failureMechanism of actionLocal anesthetics reversibly bind to the voltage-gated Na+channel, block Na+influx, and thus block action potential and nerve conduction.Structure of local anestheticsProcaineLidocaineBupivacaineTetracaineH2NCOCH2CH2NC2H5C2H5OHN COCH2CH2NCH3CH3OC4H9CONCH3CH3NHC4H9COCH3CH3NH CH2NC2H5C2H5LipophilicgroupLinkHydrophilic groupEster-linkedAmide-linkedVoltage-gated Na+channel------- ++++ + + + +Local anesthetics+ + + ------++++ + ++ ++ ++ + + + + + + + + + + ++ + + Local anesthetics preferably block small nerve fibersPropagation failureNerves with higher firing frequency and more positive membrane potential are more sensitive to local anesthetic blockUse-dependent block by local anestheticsIn nerve bundles, fibers that are located circumferentially are affected first by local anestheticsEffectiveness of local anesthetics are affected by pH of the application site+++++low pHhigh pH Normal pH+++++++++++Metabolism of local anesthetics• Most ester-linked local anesthetics are quickly hydrolyzed by enzymes in blood. • Amide-linked local anesthetics can be widely distributed via the circulation and are hydrolyzed in the liver.• Water-soluble metabolites are excreted in the urine.Effect of vasoconstriction on local anestheticsLocal anesthetics are removed from depot site mainly by absorption into blood.Addition of vasoconstrictor drugs such as epinephrine reduces absorption of local anesthetics, thus prolonging anesthetic effect and reducing systemic toxicity.Epinephrine is included in many local anesthetic preparations. Know your patient’s health status!Examples of local anesthetic use:InfiltrationField blockNerve blockIntravenous regional blockSpinal nerve blockEpidural nerve blockTopical anesthesiaToxicity and side effects• Central nervous systemStimulatory effects: restlessness, tremor, convulsion.Suppression at high dosage may lead to respiratory failure.• Peripheral nervous systemInhibition of transmission at neuromuscular junctions and ganglionic synapse.• Smooth musclesDepress contractions of intestinal, vascular and bronchial smooth muscles.Toxicity and side effectsDecreases the electrical excitability, conduction rate and force of contraction in myocardium.Causes dilation of blood vessels.Cocaine may cause vasoconstriction, hypertension and cardiac arrhythmias.Bupivacaine may cause cardiovascular collapse and ventricular tachycardia.• Cardiovascular system:• Allergic reactionsEster Linked Local Anesthetics• 2 Chloroprocaine•Procaine• Tetracaine• CocaineEster Linked Local Anesthetics (cont.)• Hydrolysed by Plasma Pseudocholinesterase• Patients with Atypical Plasma Cholinesterase.• Allergic reactions• Formation of PABA.Cocaine• Used to provide topical anesthesia of the Upper Respiratory tract.• Vasoconstrictive propertiesProcaine• Low potency•Slow onset• Short duration of action• Infiltration Anesthesia and Diagnostic Nerve Blocks.2-Chloroprocaine• Breakdown in the Plasma less than a minute.• Low potential for Systemic Toxicity.2-Chloroprocaine (cont.)• Prolonged Sensory and Motor Blockade associated with the use of Sodium Meta-bisulfite• No reports of neurotoxicity with EDTA as the preservative.• Muscular pain2-Chloroprocaine (cont.)• Newer preparation• 3% 2-Chloroprocaine is the Local anesthetic of choice for PNB for surgical anesthesia of short duration with minimal postoperative pain• Duration (1.5-2 hours)Tetracaine• Longest acting amino ester• Rarely used.Amide-Linked Local Anesthetic• Lidocaine• Mepivicaine• Prilocaine• Etidocaine• Bupivicaine• Ropivicaine• LevobupivicaineAmide-Linked Local Anesthetic• Amide Linked Local Anesthetics are metabolised by the Liver.Lidocaine• Lidocaine can be used for:-Epidural blockade 2%-Bier blocks-Avoid for spinals-Intermediate durationMepivacaine• Intermediate duration local anesthetic• Anesthetic of choice for Peripheral Nerve blockade for intraoperativeAnesthesia for surgery that lasts 3-6 hours.Prilocaine• Intermediate Duration• Causes Methemoglobinemiaat an 8mg/kg dose.• Not frequently used.Etidocaine• Profound Motor Blockade that outlasts Sensory Blockade • Not usedBupivacaine• Long acting agent• Most commonly used local anesthetic -Spinal -Epidural-Peripheral Nerve BlockadeBupivacaine (cont.)• Cardiotoxicity-Most cardiotoxic (severe ventricular arrhythmias and myocardial depression )-Difficult to treat-Acidosis, Hypercarbia and HypoxemiaRopivacaine• Enantiomere of 1-propyl-2’,6’pipecolocylidine that has less toxicicity than Bupivacaine• Local anesthetic of choice for PNB for surgeries that last long.Levobupivacaine• Enantiomere of Bupivacaine• Excellent less toxic alternative to
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