Local Anesthetics - Modified PDF

Local Anesthetics Prepared by: Dr. Samah M. Elaidy, MD, PhD Professor of Clinical Pharmacology Faculty of Medicine, Suez Canal University Presented by: Dr. Fatema Saad, MD...

Local Anesthetics Prepared by: Dr. Samah M. Elaidy, MD, PhD Professor of Clinical Pharmacology Faculty of Medicine, Suez Canal University Presented by: Dr. Fatema Saad, MD, PhD Lecturer of Clinical Pharmacology Faculty of Medicine, Suez Canal University  Outlines Definition of local anesthetics. Properties of Local Anesthetics Chemistry. Classification. Pharmacodynamics and Pharmacokinetics  Definition: Drugs that block the nerve conduction producing a transient and reversible loss of sensation in a (localized) limited region of the body without loss of consciousness. accomplished by disruption of afferent neural traffic via inhibition of impulse generation or propagation.  with local anesthesia the drug is delivered directly to the target organ, and the systemic circulation serves only to diminish or terminate its effect. Available in the form of injections, sprays, solutions.  Properties of Local Anesthetics 1) Not irritating to the tissue 2) No permanent alteration of nerve structure 3) Systemic toxicity should be low 4) Effective whether injected or applied topically 5) Time of onset of anesthesia should be as short as possible 6) Duration of action must be long enough to complete the procedure but not so long as to require an extended recovery 7) Should be stable in solution and easily biotransformed 8) Should not cause allergic reactions 9) Should be sterile or capable of being sterilized by use of heat  Chemistry All local anaesthetics have almost the same basic chemical structure. They are weak bases & are usually in solution as the hydrochloride salt. Classifications According to chemistry: A) Natural esters......metabolized by pseudo choline-esterase e.g. cocaine B) Synthetic esters......metabolized by pseudo choline-esterase, e.g. procaine, benzocaine C) Synthetic amides…..metabolized by hepatic microsomal enzymes e.g. lidocaine, mepivacaine, bupivacaine Classifications According to solubility and use: A) Soluble L.A. 1. L.A. suitable for injection and surface anesthesia e.g. lidocaine,dibucaine and procaine"procaine" used by infiltration not surface anethesia 2. L.A. for topical use only e.g. eye ….cocaine B) Insoluble L.A. for surface anethesia e.g. powder and ointments for wounds and ulcers …..benzocaine  amide esters.Metabolized by liver Rapidly hydrolyzed by Long duration of action pseudocholinesterase Affected by liver diseases Short duration. Liable to allergy. Lidocaine: Procaine: Intermediate (1-2 h). Slow penetration : not for surface anesthesia. Rapid penetration. Benzocaine: Bupivacaine: Low solubility: used for surface anesthesia Long duration 3h. only Moderate penetration The duration of local anaesthesia varies.....less than one hour (procaine).......... 1 to 2 hours (lignocaine)............greater than 2 hours (bupivacaine).  Pharmacodynamics Mechanism of Action L.A. block voltage dependant sodium channels from inside the nerve fiber. The free non-ionized base passes the neuronal membrane inside the nerve ionized active form block sodium channels membrane stabilization and decrease impulse generation and propagation  Open inactivated Closed resting active  Channels in the rested state, which predominate at more negative membrane potentials, have a much lower affinity for local anesthetics than activated (open state) and inactivated channels  The receptor site is at the inner side of the Na channel. The uncharged form is important for cell penetration. After penetration into the cytoplasm, equilibration leads to formation and binding of the charged cation at the sodium channel. When injected around a nerve, the local anaesthetic penetrates the nerve fiber & blocks nerve impulse by blocking the voltage dependent sodium channels. The blockade is conc. dependent. pH and local anesthesia  Local anesthetics are weak bases and are usually made available clinically as salts to increase solubility and stability. In the body, they exist as the uncharged base. The relative proportions of these two forms are governed by the pH of the body fluids. local anesthetics are less effective when they are injected into infected tissues because the low extracellular pH favors the charged form, with less of the neutral base available for diffusion across the membrane.  Adding bicarbonate to a local anesthetic: will raise the effective concentration of the non-ionized form and thus shorten the onset time of a regional block. Systemic absorption of injected local anesthetic from the site of administration is determined by several factors: Dosage, Site of injection, Drug-tissue binding, Local tissue blood flow, Use of a vasoconstrictor (eg, epinephrine), and the physicochemical properties of the drug itself.  Anesthetics that are more lipid soluble are generally more potent, have a longer duration of action. Extensive protein binding also serves to increase the duration of action. Application of a local anesthetic to a highly vascular area results in more rapid absorption and thus higher blood levels than if the local anesthetic is injected into a poorly perfused tissue such as subcutaneous fat.  When vasoconstrictors are used with local anesthetics, the resultant reduction in blood flow serves to reduce the rate of systemic absorption and thus diminishes peak serum levels. And lower total anesthetic requirement ??Co-administration of α1 agonists º↓ local anaesthetic absorption into the systemic circulation º Prolong effects and ↓ toxicity  :Factors affecting L.A 1. Elevated extracellular calcium partially antagonizes the action of local anesthetics owing to the calcium- favors the low- affinity rested state). 2. Conversely, increases in extracellular potassium favor the inactivated state, enhancing the effect of local anesthetics. 3. Rate of firing : the effect of a given drug concentration is more marked in rapidly firing axons than in resting fibers. 4. Nerve size: small fibers are more affected than large one. But myelinated nerves tend to be blocked before unmyelinated nerves of the same diameter 5. pH. And drug pKa. 6. Adding vasoconistrictors. 7.Lipid solubility.  Adverse Effects Adverse Effects: allergic reactions.......rashes, asthma & anaphylactic shock may occur. All local anesthetics have the ability to produce sedation, light- headedness, visual and auditory disturbances, and restlessness when high plasma concentrations result from; rapid absorption or accidental intravascular administration.  An early symptom of local anesthetic toxicity is : Circumoral and tongue numbness and a metallic taste. At higher concentrations: 1. CNS stimulation leading to muscular twitching occur, followed by tonic-clonic convulsions. 2. Respiratory depression. 3. Cardiac depression. 4. Hypotension due to cardiac depression and reduction of the compensatory sympathetic tone.  Drug interactions CNS depressants + L.A -1 ) opioids , antianxiety drugs, phenothiazines , barbiturates ( lead to potentiation of CNS depressant action of L.A Drugs that share a common metabolic pathway + L.A -2 Lead to adverse reaction Barbiturates Hepatic Microsomal enzymes So metabolism rate of amides  1. Surface anesthesia: Direct application of the drug Infiltration anesthesia: They are injected directly by.2 S.C injection Nerve block anesthesia: The anesthetic in injected close to nerve.3.trunks Caudal anesthesia injected in sacral canal.4 Spinal and epidural anesthesia.5 FDA drug risk classification in pregnancy  Outlines Definition of local anesthetics. Chemistry. Classification. Pharmacodynamics and Pharmacokinetics Home Message THANKS