Pharmacology of Local Anesthetics - Part 1 PDF

Pharmacology of local anesthetics, vasoconstrictors and clinical action of specific agents (Part 1) Dr. Dina Abdel Hamid Oral Surgery Division Learning outcomes: Explain the classification, pharmacokinetics of local anesthetic drugs and vasoconstrictors.  Outline ▪ Classification of local ane...

Pharmacology of local anesthetics, vasoconstrictors and clinical action of specific agents (Part 1) Dr. Dina Abdel Hamid Oral Surgery Division Learning outcomes: Explain the classification, pharmacokinetics of local anesthetic drugs and vasoconstrictors.  Outline ▪ Classification of local anesthetics ▪ Pharmacokinetics of Local Anesthetics ▪ Systemic Actions of Local Anesthetics ▪ Composition of Local Anesthetics Solution ▪ Clinical action of specific agents: Procaine Propoxycaine Lidocaine Mepivacaine Prilocaine Articaine Bupivacaine ▪ Topical anesthetics ▪ Vasoconstrictors: Epinephrine Levonordefrin Introduction Ancient time : dental treatment was associated with pain 1884 : birth of local anesthesia 1886: Cocaine 1905: Procaine 1946: other local anesthetic agents Classification of local anesthetics: ▪ Based on chemical structure ▪ Based on duration of action ▪ Based on biological site and mode Of action ▪ Based on mode of application Classification – Based on chemical structure ESTERS: AMIDES: Benzoic acid esters: Articaine Benzocaine Bupivacaine Cocaine Etidocaine Tetracaine Lidocaine Para-amino benzoic esters: Mepivacaine Chlorprocaine Prilocaine Procaine Propoxycaine Classification – Based on duration of action Short duration: – eg: Mepivacaine HCl 3% Intermediate duration: – eg: Lidocaine HCl 2% + epinephrine 1:1,00,000 Long duration: – eg: Bupivacaine HCl 0.5% + epinephrine 1:2,00,000, Etidocaine Classification – Based on biological site and mode Of action BIOTOXINS Benzocaine NERVE Quaternary ammonium analogs of Lidocaine Articaine Lidocaine All local anesthetics have the same mechanism of action regardless their classification which is blocking Na channels on the nerve cell membrane to prevent nerve impulse conduction. Classification – Based on biological site and mode Of action Classification – Based on mode of application Injectable: Procaine, lidocaine Surface anesthetic (topical): Soluble : o Cocaine o Lidocaine Insoluble : o Benzocaine Pharmacokinetics of Local Anesthetics Uptake When injected into soft tissues, local anesthetics exert a pharmacological action on the blood vessels in the area. All local anesthetics possess a degree of vasoactivity, most producing dilation of the vascular bed into which they are deposited, although the degree of vasodilation may vary, and some may produce vasoconstriction. Time to Achieve Peak Blood Level Route Time (min) Intravenous 1 Topical 5 (approximately) Intramuscular 5–10 Subcutaneous 30–90 Peak blood level refers to the highest concentration of the drug in blood stream after administration Pharmacokinetics of Local Anesthetics Distribution Once absorbed into the blood, local anesthetics are distributed throughout the body to all tissues. Highly perfused organs (and areas), such as the brain, head, liver, kidneys, lungs, and spleen, initially have higher blood levels of the anesthetic than do less highly perfused organs. Skeletal muscle, although not as highly perfused as these areas, contains the greatest percentage of local anesthetic of any tissue or organ in the body because it constitutes the largest mass of tissue in the body. Pharmacokinetics of Local Anesthetics Metabolism Ester Local Anesthetics: Ester local anesthetics are hydrolyzed in the blood plasma by the enzyme pseudocholinesterase. Amide Local Anesthetics: The biotransformation of amide local anesthetics is more complex than that of the esters. The primary site of biotransformation of amide drugs is the liver. Virtually the entire metabolic process occurs in the liver for lidocaine, mepivacaine, articaine, etidocaine, and bupivacaine. Prilocaine undergoes primary metabolism in the liver, with some also possibly occurring in the lung. Excretion The kidneys are the primary excretory organ for both the local anesthetic and its metabolites. Systemic Actions of Local Anesthetics System Effect Central Nervous System o Cross blood brain barrier o Low blood levels : no CNS effects o High blood levels: Generalized tonic – clonic convulsion Cardiovascular System o Produce myocardial depression o Decrease the electrical excitability of Myocardium (as they affect the heart’s ability to beat strongly and quickly, so slow heart rate) o Decrease the force of contraction (the heart does not pump blood as it normally does) o Hypotension (as it causes vasodilation) Respiratory System o Non overdose levels : Direct relaxant action on bronchial smooth muscles o Overdose levels : Respiratory arrest Composition of Local Anesthetics Solution Component Function Local anesthetic drug (e.g., -Blockade of nerve conduction Lidocaine HCL) Sodium Chloride -Isotonicity of the solution (to prevent cell damage) Sterile water -Volume Vasoconstrictor -Increase depth and duration of (e.g., epinephrine) anesthesia, Reduced absorption of Local anesthetic so reduced toxicity. Sodium meta bisulfite -Antioxidant to vasoconstrictor Methyl paraben -Bacteriostatic agent Clinical action of specific agents Procaine Propoxycaine Lidocaine Mepivacaine Prilocaine Articaine Bupivacaine Procaine Classification: Ester Potency: 1 (procaine = 1) Toxicity: 1 (procaine = 1) Metabolism: Hydrolyzed rapidly in plasma by plasma pseudocholinesterase. Excretion: More than 2% unchanged in the urine (90% as para-aminobenzoic acid [PABA], 8% as diethylaminoethanol). Vasodilating Properties: Produces the greatest vasodilation of all currently used local anesthetics. Onset of Action: 6 to 10 minutes. Effective Dental Concentration: 2% to 4%. Anesthetic Half-Life: 0.1 hour (6 minutes). Short acting. Topical Anesthetic Action: Not in clinically acceptable concentrations. Procaine Anesthetic Half-Life: refers to the time it takes for the concentration of L.A in the blood stream to decreased by half (shorter half life means it is eliminated quickly). Ester half life is shorter than amide as it is metabolized by plasma. Use of Procaine: 1. Immediate management of accidental intraarterial (IA) injection of a drug. 2. Aid in breaking arteriospasm. Propoxycaine PROPOXYCAINE: o Usually combined with procaine to provide more rapid onset & a more prolonged & long lasting anesthesia. o Not available alone because of high toxicity. PROCAINE + PROPOPXYCAINE: o When amide agents are absolutely contraindicated. o maximum recommended dose was 6.6 mg/kg of body weight for the adult patient Lidocaine Classification: Amide Potency: 2 (compared with procaine) (procaine = 1) Toxicity: 2 (compared with procaine). Metabolism: In the liver, by the microsomal fixed-function oxidases, to monoethylglyceine and xylidide; xylidide is a local anesthetic that is potentially toxic. Excretion: Via the kidneys; less than 10% unchanged, more than 80% various metabolites. Vasodilating Properties: Considerably less than those of procaine; however, greater than those of prilocaine or mepivacaine. Lidocaine Effective dental concentration 2% with Epinephrine Onset of action Rapid 3 to 5 minutes Pulpal anesthesia ( with 60 minutes (intermediate acting 1:100,000 epinephrine) duration) Soft tissue anesthesia ( with 180 -300 minutes (3-5 hours) 1:100,000 epinephrine) Maximum recommended dose Adult: 7.0 mg/kg body weight (with epinephrine) Pregnancy classification B (safe during pregnancy)  Lidocaine Use : ❖ 2% lidocaine (plain) – no dental indication ❖ 2% lidocaine with 1: 50,000 epinephrine – hemostasis (green) ❖ 2% lidocaine with 1: 100,000 or 1: 200,000 – local anesthesia (red) ❖ Comparison of lidocaine with procaine: o More rapid onset of action o More profound anesthesia o Longer duration of action o Greater potency  Mepivacaine Classification : Amide Potency: 2 (procaine = 1; lidocaine = 2). Toxicity: 1.5 to 2 (procaine = 1; lidocaine = 2). Metabolism: In the liver, by microsomal fixed-function oxidases. Excretion: Via the kidneys; approximately 1% to 16% of anesthetic dose is excreted unchanged. Vasodilating Properties: Mepivacaine produces only slight vasodilation. Mepivacaine Effective dental concentration 3% (plain)without vasoconstrictor (short duration); 2% with a vasoconstrictor (intermediate duration) Onset of action Rapid 3 to 5 minutes Pulpal anesthesia 20-40 minutes for 3% and 60 min for 2% Soft tissue anesthesia 2-3 hours for 3% and 3-5 hours for 2% Maximum recommended dose Adult: 6.6 mg/kg body weight Pregnancy classification C (not safe)  Mepivacaine a) 3% mepivacaine plain (short acting) : pediatric & geriatric patients, recommended for patients whom vasoconstrictor not indicated & shorter dental procedure. b) 2% Mepivacaine with vasoconstrictor may be levonordeferin (1:20,000) & epinephrine (1:100,000) (intermediate acting) Levonordefrin does not provide the intensity of hemostasis noted with epinephrine. Prilocaine Classification: Amide. Use : Prilocaine 4% plain (no vasoconstrictor) or 4% with 1:200,000 epinephrine used in epinephrine sensitive individuals. Considered to be safe amide local anesthetic because it is rapidly biotransformed. Maximum recommended dose :8mg/kg. Contraindication: o Idiopathic or congenital methemoglobinemia. (methemoglobin is an oxidized form of Hemoglobin which is not effectively release oxygen to body tissues (Cyanosis, dizziness, short breathing, confusion, seizure). o Hemoglobinopathies (sickle cell anemia) o Cardiac or respiratory failure.  Reference Clinical Action of specific agents, Melamed S, Stanley. Handbook of Local Anesthesia. Elsevier. 7th Edition; Chapter 4. Thank you