Chapter 17 LOCAL ANESTHETICS

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When applied locally to nerve tissue in appropriate concentrations, local anesthetics can act on any part of the nervous system and on every type of nerve fiber, reversibly blocking the action potentials responsible for nerve conduction.

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A local anesthetic in contact with a nerve trunk can cause both sensory and motor paralysis in the area innervated. These effects of clinically relevant concentrations of local anesthetics are reversible with recovery of nerve function and no evidence of damage to nerve fibers or cells in most clinical applications.

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Structures of two prototypical local anesthetics, the aminoester procaine and the aminoamide lidocaine.

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Local anesthetics bind reversibly to a specific receptor site within the pore of the Na+ channels in nerves and block ion movement through this pore.

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Background Knowledge

1. Nerve membrane (Na+,K+ pump)2. Conduction block

3. Myelin:Lipid insulating material covering some nervesImpulses travel fast along the myelin to nodes

4. pKa and pH effects: Weak bases Poorly soluble and unstable in water

5. Toxicity: Easy access to the CNS, CNS manifestations of toxicity

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Mechanism of Action

Local anesthetics block conduction by decreasing or preventing the large transient increase in the permeability of excitable membranes to Na+ that normally is produced by a slight depolarization of the membrane.

This action is due to direct interaction with voltage-gated Na+ channels.

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Two hypothesis

1. Specific receptor hypothesis: local anesthetics diffuse across the cell

membrane, bind to a spefic receptor at the opening of sodium channel

2. Membrane expansion hypothesis: local anesithetics absorbed in the cell

membrane, expanding the membrane and leading to the narrowing of sodium

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Classification of drugs

Ester local anestheticsProcaine; cocaine

Amide local anestheticsLidocaine; Prilocaine

13Inhibition of impulse conduction in different types of nerve fibers

Pharmacokinetics

Absorption The faster the absorption rate, the shorter

the duration of action, and the greater the potential for systemic toxicity

Vasoconstrictor drug: epinephrine

Pharmacokinetics

Distribution Depend primarily on the volume injected Hyaluronidase: enhance spread of local

anesthetics through tissues

Pharmacokinetics

Metabolism Ester anesthetics: plasma

pseudocholinerase and liver esterase

Amide anesthetics: hepatic microsomal enzyme P450

Types of local anesthesia and clinical application

Types of local anesthesia1. Surface/topical anesthesia2. Infiltration anesthesia3. Conduction anesthesia4. Spinal anesthesia5. Epidural anesthesia

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Clinical Uses of Local Anesthetics Topical Anesthesia Infiltration Anesthesia Field Block Anesthesia Nerve Block Anesthesia Intravenous Regional Anesthesia Spinal Anesthesia

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Adverse Reactions Hepersensitivity Central nervous system toxicities Cardiovascular toxicities