Local Anesthetics PDF

Local Anesthetics AWAD MOHAMMED ALQAHTANI BSc of Anesthesia Technology King Khalid University, Muhayil Asir  Introduction  Local and regional anesthesia and analgesia techniques depend on a group of drugs local anesthetics that transiently inhibit sensory, motor, or autonomic nerve funct...

Local Anesthetics AWAD MOHAMMED ALQAHTANI BSc of Anesthesia Technology King Khalid University, Muhayil Asir  Introduction  Local and regional anesthesia and analgesia techniques depend on a group of drugs local anesthetics that transiently inhibit sensory, motor, or autonomic nerve function, or a combination of these functions. What are local anesthetics? Local anesthetic: produce loss of sensation to pain in a specific area of the body without the loss of consciousness. Clinical aspects MECHANISMS OF LOCAL ANESTHETIC ACTION MECHANISMS OF LOCAL ANESTHETIC ACTION local anesthesia: block pain signal transmission by blocking sodium ion channels in the peripheral neurons to which they are applied. Which prevents neuronal depolarization and action potential formation. Local anesthetics are weak basis and because of their positive charge they cannot readily traverse the cellular membrane. They have to lose their hydrogen ions in order to diffuse. MECHANISMS OF LOCAL ANESTHETIC ACTION Once inside the neuron they regain they're ionized active form again, and they are trapped inside. In the protonated form the molecules went to the local anesthesia binding site on the inside of the ion Channel neard the cytoplasmic end and blocked sodium ion entrance. local anesthesia effect process as long as the molecules remain in an enough concentration and wears off gradually as they diffuse throughout the body.  Sensitivity of nerve fibers to inhibition by local anesthetics is determined by axonal diameter, myelination, and other anatomic and physiological factors.  In comparing nerve fibers of the same type, small diameter increases sensitivity to local anesthetics. Nerve fiber classification Nerve fiber classification  Thus, larger, faster Aα fibers are less sensitive to local anesthetics than smaller, slower-conducting Aδ fibers,  Larger unmyelinated fibers are less sensitive than smaller unmyelinated fibers.  small unmyelinated C fibers are relatively resistant to inhibition by local anesthetics as compared with larger myelinated fibers Nerve fiber classification  In spinal nerves local anesthetic inhibition (and conduction failure) generally follows the sequence autonomic > sensory > motor.  Local anesthetics - Classes 1-Esters : Ester local anesthetics: are mostly metabolized by pseudocholinesterase (plasma cholinesterase or butyrylcholinesterase).  Ester hydrolysis is very rapid, and the water-soluble metabolites are excreted in the urine. Pseudocholinesterase: an enzyme present in the blood and certain organs that hydrolyzes acetylcholine more slowly than acetylcholinesterase. Acetylcholinea: compound which occurs throughout the nervous system, in which it functions as a neurotransmitter. 2-Amides : Amide local anesthetics: are metabolized (N-dealkylation and hydroxylation) by microsomal P-450 enzymes in the liver.  Decreases in hepatic function (eg, cirrhosis of the liver) or liver blood flow (eg, congestive heart failure, β blockers, or H 2 - receptor blockers) will reduce the metabolic rate and potentially predispose patients to having greater blood concentrations and a greater risk of systemic toxicity. Amide local pKa Ester local pKa anesthetics anesthetics Bupivacaine 8.2 Chlorprocaine 9.1 Lidocaine 8.2 Procaine 9.1 Mepivacaine 7.9 Cocaine 8.7 Ropivacaine 8.2 Tetracaine 8.6 Prilocaine 8.0  Potency correlates with octanol solubility, which in turn reflects the ability of the local anesthetic molecule to permeate lipid membranes.  The minimum concentration of local anesthetic that will block nerve impulse conduction is affected by several factors, including fiber size, type, and myelination; pH (acidic pH antagonizes block); frequency of nerve stimulation; and electrolyte concentrations (hypokalemia and hypercalcemia antagonize blockade(.  Onset of local anesthetic action depends on many factors, including lipid solubility and the relative concentration of the nonionized lipid soluble form (B) and the ionized water-soluble form (BH + ), expressed by the pKa.  The pKa is the pH at which the fraction of ionized and nonionized drug is equal.  Less potent, less lipid-soluble agents generally have a faster onset than more potent, more lipid soluble agents.  Duration of action correlates with potency and lipid solubility. Highly lipid-soluble local anesthetics have a longer duration of action because they more slowly diffuse from a lipid-rich environment to the aqueous bloodstream.  Toxicity Toxicity:is the peak circulation levels of local anesthetics. Levels of local anesthetic concentration administered to patients are varied according to age, weight, and health. Maximum dose for an individual is usually between 70mg to 500mg. Some common toxic effects: 1-light headedness. 2-shivering or twitching. 3-seizures. 4-hypotension (low blood pressure). 5-numbness. Local Anesthetics-Toxicity Tissue toxicity (Rare): Systemic toxicity (Rare): Can occur if administered Related to blood level of in high enough drug secondary to concentrations (greater than absorption from site of those used clinically(. injection. Usually related to Range from lightheadedness, preservatives added to tinnitus to seizures and solution. CNS/cardiovascular collapse.  Local Anesthetics - Allergy True allergy is very rare. Most reactions are from ester class - ester hydrolysis. Patient reports of “allergy” are frequently due to previous intravascular injections. Regional anesthesia - Definition Regional anesthesia: Rendering a specific area of the body example:foot, arm, lower extremities, insensate to stimulus of surgery or other instrumentation.  Regional anesthesia - Uses Provide anesthesia for a surgical procedure. Provide analgesia post-operatively or during labor and delivery. Diagnosis or therapy for patients with chronic pain syndromes.  Regional anesthesia - types Topical. Local/Field. Intravenous block (“Bier” block(. Peripheral nerve block. Plexus - brachial, lumbar. Central neuraxial - epidural, spinal. Questions are welcome Thank You  Reference Clinical Anesthesiology 6th edition 2018 the Author ; G.Morgan. Maged Mikhail and Michael Murray, chapter 16, page : 263 – 276.