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Local Anesthetics

Local Anesthetics. By S. Bohlooli , PhD School of Medicine, Ardabil University of Medical Sciences. Introduction. History. Cocaine , the first local anesthetic introduced into medical practice, was isolated by Niemann in 1860 Procaine was synthesized by Einhorn in 1905

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Local Anesthetics

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  1. Local Anesthetics By S. Bohlooli, PhD School of Medicine, Ardabil University of Medical Sciences

  2. Introduction

  3. History • Cocaine, the first local anesthetic introduced into medical practice, was isolated by Niemannin 1860 • Procaine was synthesized by Einhornin 1905 • Lidocaine, which is still a widely used local anesthetic, was synthesized in 1943 by Löfgren.

  4. Basic Pharmacology of Local Anesthetics

  5. Chemistry: Structure Ester Cocaine Procaine (Novocain) Tetracaine (Pontocaine) Benzocaine

  6. Chemistry: Structure Amides Lidocaine (Xylocaine) Mepivacaine Bupivacaine; Levobupivacaine Ropivacaine (Naropin)

  7. Chemistry • Local anesthetics are weak bases • the pKa of most local anesthetics is in the range of 8.0–9.0 • Cationic form is the most active form • The uncharged form is important for rapid penetration of biologic membranes

  8. Pharmacokinetics • Local anesthetics are usually administered by injection into dermis and soft tissues around nerves • Absorption and distribution are not as important

  9. Absorption • Systemic absorption of injected local anesthetic depends on: • Dosage • Site of injection • Drug-tissue binding • Local tissue blood flow • Use of vasoconstrictors (eg, epinephrine) • Physicochemical properties of the drug

  10. Distribution, Metabolism and Excretion • The amide local anesthetics are widely distributed after intravenous bolus administration • The local anesthetics are converted in the liver (amide type) or in plasma (ester type) to more water-soluble metabolites • Decreased hepatic elimination of local anesthetics would be anticipated in patients with reduced hepatic blood flow or hepatic diseases

  11. Pharmacodynamics: Mechanism of Action

  12. Pharmacodynamics • The function of sodium channels can be disrupted in several ways: • batrachotoxin, aconitine, veratridine • bind to receptors within the channel and prevent inactivation • tetrodotoxin (TTX) and saxitoxin • block sodium channels by binding to channel receptors near the extracellular surface • Spinal neurons can be differentiated on the basis of tetrodotoxin effect into: • TTX-sensitive • TTX-resistant neurons

  13. Pharmacodynamics • With increasing concentrations of a local anesthetic • The threshold for excitation increases • Impulse conduction slows • The rate of rise of the action potential declines • The action potential amplitude decreases • The ability to generate an action potential is completely abolished • These effects result from binding of the local anesthetic to more and more sodium channels

  14. Effect of Extra cellurar Ions • Increase in extracellular calcium partially antagonizes the action of local anesthetics • Owing to the calcium-induced increase in the surface potential on the membrane. • Increases in extracellular potassium enhancing the effect of local anesthetics.: • Depolarize the membrane potential and favor the inactivated state.

  15. Relative Size and Susceptibility of Different Types of Nerve Fibers to Local Anesthetics

  16. Nerve fibers differ significantly in their susceptibility • Effect of Fiber Diameter • Effect of Firing Frequency • Effect of Fiber Position in the Nerve Bundle • Effects on Other Excitable Membranes

  17. Clinical Pharmacology of Local Anesthetics

  18. Clinical Pharmacology • Can provide highly effective analgesia in well-defined regions of the body • The usual routes of administration • Topical application • Injection in the vicinity of peripheral nerve endings (perineural infiltration) • Injection in the vicinity of major nerve trunks (blocks) • Injection into the epidural or subarachnoid spaces surrounding the spinal cord • Intravenous regional anesthesia (Bier block)

  19. Schematic diagram of the typical sites of injection of local anesthetics in and around the spinal canal

  20. The choice of local anesthetic • The choice of local anesthetic is usually based on the duration of action required • Short-acting: • Procaine and chloroprocaine • Intermediate duration : • lidocaine, mepivacaine, and prilocaine • long-acting : • tetracaine, bupivacaine, levobupivacaine, and ropivacaine

  21. Some tips • The onset of local anesthesia can be accelerated by the addition of sodium bicarbonate • Repeated injections of local anesthetics can result in loss of effectiveness • Pregnancy appears to increase susceptibility to local anesthetic toxicity

  22. Toxicity • Central Nervous System • Neurotoxicity • Lidociaine • Cardiovascular System • Bupivacaine • Hematologic Effects • Prilocaine: metabolite o-toluidine • Allergic Reactions • The ester-type local anesthetics: p-aminobenzoic acid derivatives

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