Local Anesthetics PDF

Local Anesthetics Presenter: Dr Karishma Jeeboo  Local Anesthetics Local anesthetics are generally applied locally and block nerve conduction of sensory impulses from the periphery to the CNS. additional uses—for example, the antiarrhythmic effect of lidocaine Loca...

Local Anesthetics Presenter: Dr Karishma Jeeboo  Local Anesthetics Local anesthetics are generally applied locally and block nerve conduction of sensory impulses from the periphery to the CNS. additional uses—for example, the antiarrhythmic effect of lidocaine Local anesthetics abolish sensation (and, in higher concentrations, motor activity) in a limited area of the body without producing unconsciousness (for example, during spinal anesthesia). At physiologic pH, these compounds are charged; it is this ionized form that interacts with the protein receptor of the Na+ channel to inhibit its function and, thereby, achieve local anesthesia. Lidocaine is the most frequently employed. – local anesthetic of intermediate duration.  Local Anesthetics Prevent/ relieve pain by never interrupting conduction. Prevent the generation and conduction of the nerve impulse. Primary site of action – cell membrane Bind to specific receptor sites within the pore of the Na+ channels and block the ion movement through the pore. Prevents depolarisation of the membrane and blocking conduction of the action potential Variety of routes – topical, infiltration, field/nerve block, intravenous regional, spinal, epidural.  Local Anesthetics Small, unmyelinated nerve fibres that conduct impulses for pain, temperature, and autonomic activity are most sensitive to actions of local anaesthetics. Most widely used: Bupivacaine lidocaine – the most widely used local anesthetic mepivacaine Procaine – first synthetic local anaesthetic Benzocaine – low solubility ropivacaine Tetracaine - ophthalmic use Cocaine Articane – fastest onset of action  Local Anesthetics The most widely used agents today are procaine, lidocaine, bupivacaine, and tetracaine. These agents were synthesized as substitutes for cocaine, preserving the local anaesthetic effect of cocaine but avoiding its toxicity and addictive properties. typical local anaesthetics contain hydrophilic and hydrophobic moieties Hydrophobicity increases both the potency and the duration of action the receptor site for these drugs on Na+ channels is thought to be hydrophobic so receptor affinity for anaesthetic agents is greater for more hydrophobic drugs. Hydrophobicity also increases toxicity, decreasing the therapeutic index for more hydrophobic drugs. Pharmacologic Effects Nerves – differential sensitivity of various types of nerve fibers depends on fiber diameter, myelination, physiologic firing and anatomic location. Smaller, myelinated fibers are blocked more easily. Pain sensation appears to be selectively blocked by local anesthetics. Fibers in the periphery if a thick nerve bundle are blocked sooner than those in the core – exposed earlier to higher concentrations. Weak blocking effects on skeletal muscle neuromuscular transmission  Local Anesthetics – prolonged action by vasoconstrictors The duration of action of a local anaesthetic is proportional to the time during which it is in contact with the nerve. Vasoconstrictors are added to keep the drug at the nerve and prolong the period of anaesthesia. When the vasoconstrictor epinephrine is added to the local anesthetic, the rate of anesthetic absorption decreases. This minimizes systemic toxicity and increases the duration of action. The vasoconstrictor is said to perform a dual service. By decreasing the rate of absorption of the anesthetic not only localizes the anaesthetic at the site but allows the rate at which is metabolized by the body to keep pace with the rate at which it is absorbed into the circulation (reducing toxicity)  Local Anesthetics – Action Onset of action may be accelerated by addition of sodium bicarbonate which enhances intracellular access of these weakly basic compounds. Used in spinal anesthesia and to produce autonomic blockade in ischemic conditions. Slow epidural infusion at low concentration has been used successfully for post-operative analgesia or IV forms can be used for reducing pain post-op Oral and parenteral forms – used adjunctly in neuropathic pain states.  Local Anesthetics – Undesired effects Adverse effects result from systemic absorption of toxic amounts of the locally applied anesthetic. Seizures and cardiovascular collapse are the most significant of these systemic effects. Restlessness and tremor proceeding to clonic convulsions. All are vasodilators – patients with existing CV disease may develop heart block and other disturbances of cardiac electrical function Bupivacaine - cardiotoxicity. - decreases in electrical excitability, conduction rate and force of contraction – ventricular tachycardia and fibrillation; hypotension.  Local Anesthetics – Undesired effects Mepivacaine should not be used in obstetric anesthesia due to its increased toxicity to the neonate. Allergic reactions may be encountered with procaine, which is metabolized to p-aminobenzoic acid. Spinal and epidural anesthesia and instillation of local anesthetics into the peritoneal cavity causes sympathetic nervous system paralysis, which can result in an increased tone of GI musculature  Local Anesthetics – Undesired effects Depress contractions in the intact bowel Relax vascular and bronchial smooth muscle Affects transmission at the neuromuscular junction Hypersensitivity reactions (rare).  Metabolism Metabolic fate is of great practical importance. The rate of degradation of local anaesthetics varies greatly, and this is a major factor in determining its safety. Because toxicity is related to the concentration of the free drug, binding of the anaesthetic to proteins in the serum and to tissues reduces the concentration of the free drug in the systemic circulation and consequently reduces toxicity.  Local Anesthetics - Uses Topical anaesthetic agents on the skin and/or mucus membrane Preparations are effective in the symptomatic relief of anal and genital pruritus, poison ivy rashes, acute and chronic dermatoses. Combined with glucocorticoids or antihistamines Used for minor surgical procedures