Local Anesthetics Rich Minshall PhD E Gina Votta Velis MD PhD Departments of Pharmacology and Anesthesiology Local anesthetics are drugs used to prevent or relieve pain in specific regions of the body without loss of consciousness Local anesthetics block pain sensation by blocking nerve conduction Mechanisms of neural transmission Mechanism of action Local anesthetics reversibly bind to the voltage gated Na channel block Na influx and thus block action potential and nerve conduction Local anesthetics Propagation failure Structure of local anesthetics Ester linked Procaine Tetracaine H2N O C O CH2 CH2 N HN O C O CH2 CH2 N C4H9 CH3 Bupivacaine C2H5 CH3 O C N CH3 CH3 NH C4H9 O C CH2 CH3 Lipophilic group CH3 Amide linked NH Lidocaine C2H5 Link C2H5 N C2H5 Hydrophilic group Voltage gated Na channel Local anesthetics preferably block small nerve fibers Local anesthetics Propagation failure Nerves with higher firing frequency and more positive membrane potential are more sensitive to local anesthetic block Use dependent block by local anesthetics In nerve bundles fibers that are located circumferentially are affected first by local anesthetics Effectiveness of local anesthetics are affected by pH of the application site low pH high 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 anesthetics Local 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 Infiltration Topical anesthesia Field block Nerve block Intravenous regional block Spinal nerve block Epidural nerve block Toxicity and side effects Central nervous system Stimulatory effects restlessness tremor convulsion Suppression at high dosage may lead to respiratory failure Peripheral nervous system Inhibition of transmission at neuromuscular junctions and ganglionic synapse Smooth muscles Depress contractions of intestinal vascular and bronchial smooth muscles Toxicity and side effects Cardiovascular system Decreases 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 Allergic reactions Ester Linked Local Anesthetics 2 Chloroprocaine Procaine Tetracaine Cocaine Ester 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 properties Procaine 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 Metabisulfite No reports of neurotoxicity with EDTA as the preservative Muscular pain 2 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 Levobupivicaine Amide 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 duration Mepivacaine Intermediate duration local anesthetic Anesthetic of choice for Peripheral Nerve blockade for intraoperative Anesthesia for surgery that lasts 3 6 hours Prilocaine Intermediate Duration Causes Methemoglobinemia at an 8mg kg dose Not frequently used Etidocaine Profound Motor Blockade that outlasts Sensory Blockade Not used Bupivacaine Long acting agent Most commonly used local anesthetic Spinal Epidural Peripheral Nerve Blockade Bupivacaine cont Cardiotoxicity Most cardiotoxic severe ventricular arrhythmias and myocardial depression Difficult to treat Acidosis Hypercarbia and Hypoxemia Ropivacaine Enantiomere of 1 propyl2 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 bupivacaine
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