Pharmacology of Local Anesthetics (Part 2) PDF

Pharmacology of local anesthetics, vasoconstrictors and clinical action of specific agents (Part 2) Dr. Dina Abdel Hamid Oral Surgery Division Learning outcomes: Explain the classification, pharmacokinetics of local anesthetic drugs and vasoconstrictors.  Outline ▪ Classification of local an...

Pharmacology of local anesthetics, vasoconstrictors and clinical action of specific agents (Part 2) 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 Articaine Classification: Hybrid molecule. Classified as an amide; however, it possesses both amide and ester characteristics. Potency: 1.5 times that of lidocaine. Toxicity: Similar to lidocaine and procaine. Metabolism: Articaine is the only amide-type local anesthetic that contains a thiophene group (Thiophene ring enhances articaine lipid solubility allowing better penetration into tissues). Because articaine HCl is the only widely used amide-type local anesthetic that contains an ester group, biotransformation of articaine HCl occurs in both plasma (hydrolysis by plasma esterase) and liver (hepatic microsomal enzymes). Excretion: Via the kidneys; approximately 5% to 10% unchanged, approximately 90% metabolites. Vasodilating Properties: Articaine has a vasodilating effect equal to that of lidocaine. Procaine is slightly more vasoactive. Articaine Effective dental concentration 4% Onset of action Infiltration 1 to 2 minutes Block 2 to 3 minutes Pulpal anesthesia ( with 1:100,000 epinephrine) 60 – 75 minutes ( with 1:200,000 epinephrine) 45– 60 minutes Soft tissue anesthesia ( with 1:100,000 epinephrine) 180 -360 minutes (3-6 hours) ( with 1:200,000 epinephrine) 120-300 minutes (2-5 hours) Maximum recommended dose Adult: 7.0 mg/kg body weight Pregnancy classification C (not safe) Articaine Side effect: Methemoglobinemia Contraindication : o Idiopathic or congenital methemoglobinemia. o Cardiac & respiratory failure. o Allergy to sulfite - containing drugs. (Sodium meta bisulfite acts as antioxidant to vasoconstrictor in the local anesthetic solution, for patients who are allergic to sulfites, it is important to choose local anesthetic without vasoconstrictor as Mepivacaine 3% as it is plain (without vasoconstrictor). Bupivacaine Classification: Amide It is a long acting local anesthetic drug. Bupivacaine HCl 0.5% + epinephrine 1:100,000 or 1:200,000. Potency : 4 times than Lidocaine. Pregnancy classification: C (not safe) Indications: 1. Lengthy dental procedures (Oral Surgery, implant surgery, periodontal procedures). 2. Management of postoperative pain. Contraindication: 1. Physically & mentally disabled children. 2. Patients with cardiovascular issues. Duration of action of local anesthetics: Topical anesthetics ⦿Intact skin forms a barrier to the diffusion of local anesthetics. ⦿ Mucous membranes and injured skin (e.g., burns and abrasions) lack the protection afforded by intact skin, permitting topically applied local anesthetics to diffuse through to reach free nerve endings lying below intact skin. ⦿ As a rule, topical anesthesia is effective only on surface tissues (2 to 3 mm). Tissues deep to the area of application are poorly anesthetized. However, surface anesthesia does allow for atraumatic needle penetration of the mucous membrane. Topical anesthetics ⦿ To increase the clinical efficacy of topical anesthetics, a more concentrated form of the drug commonly is used (5% or 10% lidocaine) than for injection (2% lidocaine). Commonly used topical local anesthetics: Benzocaine, Dyclonine hydrochloride, EMLA, Lidocaine. Benzocaine 20%: -It is an ester local anesthetic. -Poorly soluble in water, remains at the site of application longer, providing a prolonged duration of action, not suitable for injection. Dyclonine Hydrochloride: It is classified chemically as a ketone derivative without an ester or amide linkage that may be used in patients that are allergic to the common anesthetics. EMLA (Eutectic Mixture of Local Anesthetics) ⦿ EMLA cream = 2.5% Lidocaine + 2.5% Prilocaine ⦿An emulsion in which oil phase is eutectic mixture of lidocaine and prilocaine in ratio 1:1 by weight. ⦿ Works on intact skin. ⦿ To be applied 1 hr prior to procedure. ⦿ Contraindications: o Congenital or idiopathic methemoglobinemia.(Prilocaine) o Infants younger than 12 months receiving treatment with methemoglobin inducing agents. o Known sensitivity to amide type local anesthetics. Selection of Local anesthetic for a patient Factors: ⦿ Length of time pain control is necessary. ⦿ Potential need for post treatment pain control. ⦿ Possibility of self-mutilation (self harm) in the post operative period. ⦿ Requirement for hemostasis. ⦿ Presence of any contraindications.(Medical History- Allergies -Pregnancy) VASOCONSTRICTORS Classification – Based on chemical structure Catecholamines Noncatecholamines Epinephrine Amphetamine Norepinephrine Methamphetamine Levonordefrin Ephedrine Isoproterenol Hydroxyamphetamine Dopamine Metaraminol Methoxamine Phenylephrine Catecholamines and Non- catecholamines are both categories of adrenergic agents that can interact with adrenergic receptors in the body. Classification – Based on mode of action Directly Acting Indirectly Acting Mixed Acting Epinephrine Amphetamine Metaraminol Norepinephrine Methamphetamine Ephedrine Levonordefrin Hydroxyamphetamine Isoproterenol Tyramine Dopamine Methoxamine Phenylephrine Action of vasoconstrictors 1. Decrease blood flow 2. Decreased rate of absorption of L.A into CVS, lower anesthetic blood levels. 3. Decrease the risk of toxicity. 4. Increases duration of action. 5. Decrease bleeding (hemostasis). Adrenergic receptors Adrenergic receptors : are special proteins found on the surface of the cell in your body, they are like stations for catecholamines (Epinephrine). Two types of receptors Alpha () – vasoconstriction Beta () - vasodilation and bronchodilation + cardiac stimulation Epinephrine Mode of action: Acts directly on alpha () and beta () adrenergic receptors. Systemic Effects of Epinephrine ▪ Myocardium - ↑ heart rate & cardiac output ▪ B P- ↑ systolic pressure ▪ Vasculature – vasoconstriction smaller arterioles ▪ Respiratory - Bronchodilator ▪ CNS - Not a potent CNS stimulant ▪ Metabolism: ▪ Increase oxygen consumption ▪ Glycogenolysis - ↑ blood sugar Epinephrine Clinical applications: ▪ Management of acute allergic reactions (anaphylaxis). ▪ Management of refractory bronchospasm (status asthmaticus). ▪ Management of cardiac arrest. ▪ As a vasoconstrictor in local anesthetics. ▪ To produce mydriasis (dilatation of the pupil). ASA Classification:: ASA system is developed by American Society of Anesthesiologist for assessing the preoperative physical status of patients. Epinephrine Recommended maximum dosages for Epinephrine Epinephrine Normal healthy patient Patient with clinically concentration (µg / (ASA I) significant CVS disease cartridge) Cartridges* (ASA III or IV) Cartridges^ 1: 50000 (36) 5.5 1 1: 100000 (18) 11 2 1: 200000 (9) 22 4 * Maximum epinephrine dose of 0.2 mg or 200 µg per appointment for normal healthy patients.(11 carpules) ^ Maximum epinephrine dose of 0.04 mg (2 carpules) or 40 µg per appointment for ASA III or ASA IV. o Each dental cartridge = 1.8 ml. Levonordefrin Mode of Action It appears to act through direct α-receptor stimulation (75%), with some β activity (25%).Levonordefrin is 15% as potent a vasopressor as epinephrine. Systemic Actions Levonordefrin produces less cardiac and CNS stimulation than is produced by epinephrine. Side Effects and Overdose These are the same as with epinephrine but to a lesser extent. With higher doses, additional side effects include: Hypertension, ventricular tachycardia, and anginal episodes in patients with coronary artery insufficiency. Levonordefrin Clinical Applications Levonordefrin is used as a vasoconstrictor in local anesthetics. Levonordefrin is combined with Mepivacaine in a 1:20,000 dilution. Maximum Doses o For all patients, the maximum dose should be 1 mg per appointment; of a 1:20,000 dilution (11 cartridges); the maximum volume for administration may be limited by the dose of the local anesthetic. Selection of Vasoconstrictors 1. Length of the dental procedure. 2. Need for hemostasis during and following the procedure. 3. Requirement for postoperative pain control. 4. Medical status of the patient. Contraindications of Vasoconstrictors Few contraindications are known to administration of vasoconstrictors in the concentrations in which they are found in dental local anesthetics. For all patients, and for some in particular, the benefits and risks of including the vasopressor in the local anesthetic solution must be weighed against the benefits and risks of using a plain anesthetic solution. In general, these groups consist of: o Patients with more significant cardiovascular disease (ASA class 3 and 4) o Patients with certain non-cardiovascular diseases (e.g., thyroid dysfunction, diabetes, sulfite sensitivity) o Patients receiving MAO inhibitors (monoamine oxidase inhibitors) as they prevent breakdown of Epinephrine and tricyclic antidepressant.  How to calculate the maximum number of carpules (cartridges) per appointment? -2% Mepivacaine with Epi 1:100,000 (red color): Body weight X 6.6mg/kg = …..No of carpules/visit Maximum number of carpules= 36 mg/cartridge 36mg came from 2% means 20 mg of mepivacaine/ml, so 20mg x 1.8 ml = 36 mg/cartridge. -3% Mepivacaine without Epi (green color): Body weight X 6.6mg/kg = ……No of carpules/visit Maximum number of carpules= 54 mg/cartridge 54mg came from 3% means 30 mg of mepivacaine/ml, so 30mg x 1.8 ml = 54mg/cartridge. -4% Articaine with Epi (blue color): Body weight X 7 mg/kg = …..No of carpules/visit Maximum number of carpules= 72 mg/cartridge Reference: Reference Pharmacology of vasoconstrictors, Melamed S, Stanley. Handbook of Local Anesthesia. Elsevier. 7th Edition; Chapter 3. Thank You