Transcript File
Dr. Naila Abrar After this session you should be able to: define local anesthesia; classify local anesthetics; describe pharmacokinetic properties of commonly used local anesthetics; describe the mechanism of action; comprehend the structure-activity characteristics of local anesthetics; and describe the toxicity of local anesthetics. DEFINITION Loss of sensory blockade of neuronal cell perception sodium due channels membrane in restricted/localized area of the body. in a CHARACTERISTICS Topical application or local injection Peripheral nerves Consciousness not altered No amnesia Vital functions not affected No change in physiological functions Recovery is spontaneous, predictable & without residual changes ACCORDING TO CHEMISTRY ESTERS Cocaine Procaine Tetracaine Benzocaine AMIDES Lignocaine Prilocaine Mepivacaine Bupivacaine Ropivacaine ACCORDING TO DURATION OF ACTION SHORT Procaine, Chlorprocaine MEDIUM Cocaine, Lidocaine, Mepivacaine, Prilocaine LONG Tetracaine, Bupivacaine, Levobupivacaine, Ropivacaine ACCORDING TO THERAPEUTIC USES SURFACE ANESTHESIA Cocaine, lignocaine, tetracaine, benzocaine FEILD BLOCK & INFILTRATION ANESTHESIA Procaine, lignocaine, bupivacaine NERVE BLOCK Procaine, lignocaine, bupivacaine, tetracaine, ropivacaine SPINAL ANESTHESIA Lignocaine, bupivacaine, tetracaine EPIDURAL ANESTHESIA Lignocaine, bupivacaine OPHTHALMOLOGICAL ANESTHESIA Proparacaine ESTERS Cocaine Procaine Tetracaine Benzocaine AMIDES Lidocaine Mepivacaine Bupivacaine Ropivacaine Articaine ABSORPTION Dosage Site of injection Termination of action Systemic effects intercostal>caudal>epidural>brachial>sciatic Drug-tissue binding Local tissue blood flow Use of vasoconstrictors- epinephrine Physiochemical properties of the drug USE OF VASOCONSTRICTORS EPINEPHRINE used Blood supply limited Absorption restricted More time of contact-more pronounced effect Delayed healing & tissue necrosis a2 receptors- decrease release of substance P- clonidine DISTRIBUTION Amides widely distributed Initial rapid distribution phase Slower distribution phase METABOLISM & EXCRETION Converted to more water soluble forms • liver- amides Prilocaine>lidocaine>mepivacaine>ropivacaine plasma- esters (butyrylcholinesterase) Toxicity of amide type increased in liver disease • MECHANISM OF ACTION Reversible Diffusion into nerve fibre (only in nonionizable form) Block voltagegated sodium channels Threshold for excitation increases Impulse conduction slows Rate of rise AP decreases Ability to generate AP is abolished Propagation blocked if Na current blocked over a critical length Higher affinity for inactivated phase Voltage & time dependent Less affinity for resting state More effect on high frequency firing Use dependent block Resting potential not significantly altered Biological toxins-batrachotoxin, aconitine, scorpion venoms Bind to receptors within Na channel and prevent inactivation Prolonged influx of Na & depolarization Marine toxins tetrodotoxins & saxitoxin have effects similar to LA LIPID SOLUBILITY pKa CARBON DIOXIDE HYDROPHOBIC NATURE TACHYPHYLAXIS SUSCEPIBILITY OF NERVE FIBRES TO LOCAL ANESTHETICS Firing frequency Size State of myelination Fibre diameter Fibre position Pain sensation>temperature>touch>deep pressure> motor TOXICITY 1. SYSTEMIC EFFECTS Absorption from site of administration 2. DIRECT NEUROTOXICITY Local effects when high concentrations are administered in close proximity to the spinal cord and other major nerve trunks TOXICITY A. CNS Circumoral & tongue numbness, metallic taste Nystagmus, muscle twitching, tonicclonic convulsions Depression of cortical inhibitory pathways-unopposed activity of excitatory neuronal pathways Generalized CNS depression Death due to respiratory failure TOXICITY B. NEUROTOXICITY More with chloroprocaine and lidocaine Transient radicular irritation or neuropathic pain Interference with axonal transport and disruption of calcium homeostasis TOXICITY C. CARDIOVASCULAR SYSTEM Direct effects on cardiac & smooth muscle membranes • • Myocardial depression Arteriolar dilation-hypotension Indirect effects on ANS Bupivacaine is more cardiotoxic than othersslow idioventricular rhythm & broad QRS complexes Cocaine blocks norepinephrine reuptakevasoconstriction & hypertension, cardiac arrythmias TOXICITY D. HEMATOLOGIC EFFECTS Prilocaine – metabolite O-toluidine An oxidizing agent converts Hb to met Hb TOXICITY E. ALLERGIC REACTONS Esters converted to p -aminobenzoic acid (PABA) derivatives Sympathomimetic action Potent vasoconstrictor Cardiac stimulation Marked pyrexia with overdose Low aqueous solubility Topical local anesthetic – not absorbed Relief of pain & irritation Anesthesia of mucous membranes PABA derivatives – antagonize effect of sulfonamides locally Most widely used Effective by all routes but oral BA low High 1st pass metabolism Fast onset, more intense & lasting effect Alternative for ester allergic pts Toxicity equal to procaine but more sedative than others Not effective topically Slower onset, longer acting Unique property of sensory & motor dissociation Popular for anesthesia during labor More cardiotoxic SURFACE ANESTHESIA Ear, eye, nose, throat, abraded skin Only superficial layer Soluble LA – rapid systemic absorption Eutectic lidocaine/prilocaine – intact skin INFILTRATION ANESTHESIA Dilute solution infiltrated under skin Immediate onset & DoA is short Minor operations: incisions, excisions FIELD BLOCK or NERVE BLOCK Injected around nerve trunk Area distal to injection is anesthetized and paralyzed Lidocaine Bupivacaine for longer BIER BLOCK INTRAVENOUS REGIONAL BLOCK Short surgical procedures Upper or lower extremities SPINAL ANESTHESIA Subarachnoid space L2-3 or L3-4 – cauda equina Abdominal or pelvic surgery Effective analgesia & muscle relaxation Complications: respiratory paralysis, hypotension (sympathetic reflexes inhibited), headache, cauda equina syndrome, infection, neurotoxicity EPIDURAL Injection into epidural space at L2-3 Used in obstetrics, lower abdomen & pelvic surgery Unwanted effects similar to spinal but less because longitudinal spread is reduced Lidocaine, bupivacaine, ropivacaine