Pharmacology of Local Anesthetics


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Anaesthesia & Exodontia
Third Year

Pharmacology of Local Anesthetics

  1. 1. Pharmacology of Local Anesthetics By Hesham Marei BDs, MSc, PhD, MFDS (RCS-Eng)
  2. 2.  LA differs from most other drugs in one important manner.  The presence of a LA in the circulatory system means that the drug will be transported to every part of the body.
  3. 3. Pharmacokinetics of LA     Uptake Distribution Biotransformation Excretion
  4. 4. Uptake  When injected into soft tissue, LA exerts a pharmacological action on blood vessels in the area. All LA have a degree of vasoactivity, most producing dilatation of the vascular bed into which they are deposited.  Procaine (Ester LA) is the most potent vasodilator drug  Cocaine is the only LA producing vasoconstriction.
  5. 5. A significant clinical effect of vasodilatation is an increase in the rate of absorption of LA into the blood. Decreasing in the duration, quality, and depth of pain control while increasing the possibility of toxic overdose.
  6. 6. Uptake  Oral Route. With the exception of cocaine, LA are absorbed poorly from GIT.  Topical Route (Tracheal mucosa, Pharyngeal mucosa, esophageal or bladder mucosa) (Skin)  Injection. The rate of uptake is related to the vascularity of the injection site and the vasoactivity of the drug. (IV, IM,SC).
  7. 7. Distribution  Once absorbed into the blood, LA are distributed throughout out the body to all the tissues.  Highly perfused organs such as brain, head, liver, kidneys, lungs, and spleen initially have higher blood levels of the anesthetic than do less highly perfused organs.
  8. 8. The blood level of LA is influenced by: 1. Rate of absorption 2. Rate of distribution of the drug from the vascular compartment to the tissues 3. Elimination of the drug through metabolic or excretory pathways.  Elimination half life: is the time necessary for 50% reduction in the blood level.
  9. 9. Metabolism (Biotransformation)  Ester LA Hydrolyzed in the plasma by the enzyme pseudocholinesterase.  Amide LA The primary site of biotransformation of amide LA is the liver therefore liver function and hepatic perfusion influence the rate of biotransformation.
  10. 10. Excretion  The kidneys are the primary excretory organ for both the local anesthetic and its metabolites.  Esters appear in only very small concentrations as the parent compound in the urine.
  11. 11. Systemic action of LA     CNS CVS Respiratory System Local tissue toxicity
  12. 12. CNS I-Anticonvulsant Properties:  Procaine, mepivacaine, and lidocaine have been used IV to terminate or decrease the duration of both grand mal, and petite mal seizures.  The anticonvulsive blood level of lidocaine is 0.5 to 4µg/ml.  Epileptic patients possess hyperexcitable cortical neurons at a site with in the brain. LA has a depressant action on CNS, raise the seizure threshold by decreasing the excitability of these neurons.
  13. 13. II- Pre-convulsive SS: The initial SS of overdose are CNS in origin. With lidocaine, this second phase is observed at a level between 4.5 and 7µg/ml in the average normal healthy patient. The initial clinical SS of CNS toxicity are usually excitatory in nature. Slurred speech, Shivering, Muscular twitching, Tremors of muscles of the face, Visual disturbance, Dizziness, Numbness of the tongue and circum oral region, warm flushed feeling of skin.
  14. 14. III- Convulsive Phase: Further elevation of the local anesthetic blood level produces clinical SS consistent with a generalized tonic – clonic convulsive episode. The duration of seizure activity is related to the LA blood level and inversely related to Pco2 level
  15. 15. CVS  LA has a direct depressant action on the myocardium. LA decrease electrical excitability of the myocardium, decrease conduction rate, and the force of contraction.  The therapeutic blood level of lidocaine for antidysrhythmic action range from 1.8 to 6µg/ml.  SS of LA overdose will be noted if the blood level rises beyond 6µg/ml of blood.  All LA except cocaine produce a peripheral vasodilatation, through relaxation of the smooth muscle in the wall of the blood vessels.
  16. 16. Respiratory System  At non-overdose level, they have a direct relaxant action on bronchial smooth muscle, where as at overdose levels they may produce respiratory arrest as a result of generalized CNS depression.
  17. 17. Local tissue Toxicity  Skeletal muscle appears to be more sensitive to the local irritant properties of LA than other tissues. Longer acting LA produce more localized skeletal muscle damage than shorter acting drugs.
  18. 18. Amides Lidocaine Mepivacaine Prilocaine Bupivacine
  19. 19. Esters Procaine Cocaine Benzocaine Tetracaine
  20. 20. Lidocaine Concentration - 2% Potency - 2X Procaine Toxicity - 2X Procaine Metabolized - Liver Excreted - Kidney
  21. 21. Lidocaine Time to onset Half life Max rec dose (Malamed) (manufac.) w/o epi with epi 2-3 mins 90 mins 4.4 mg/kg (2 mg/lb) 4.4 mg/kg (2 mg/lb) 6.6 mg/kg (3 mg/lb)
  22. 22. Lidocaine Maximum safe dose - 2% with 1:100,000epi Malamed - 300 mg or 8 carpules manufac. - 500 mg or 13.5 carpules
  23. 23. Mepivacaine Concentration - 2% or 3% Potency - 2X Procaine Toxicity - 1.5-2X Procaine Metabolized - Liver Excreted - Kidney
  24. 24. Mepivacaine % Vasoconstrictor 3 without mins Duration * pulp - 20-40 tissue - 2-3 hrs 2 1:20,000 mins Levonordefrin pulp - 60-90 tissue - 3-5 hrs
  25. 25. Mepivacine Time to onset Half life Max rec dose (Malamed) (manufac.) 1.5-2 mins 1.9 hrs 4.4 mg/kg (2 mg/lb) 6.6 mg/kg (3 mg/lb)
  26. 26. Mepivacaine Maximum safe dose - 3% w/o vasoconstrictor Malamed - 300 mg or 5.5 carpules manufac. - 400 mg or 8 carpules
  27. 27. Mepivacaine Maximum safe dose - 2% with constrictor Malamed - 300 mg or 8 carpules manufac. - 400 mg or 11 carpules
  28. 28. Bupivacaine Concentration - 0.5% Potency - 8X Procaine (4X Lidocaine) Toxicity - 8X Procaine (4X Lidocaine) Metabolized - Liver Excreted - Kidney
  29. 29. Bupivacaine % Vasoconstrictor 0.5 1:200,000 epi mins Duration pulp - 90-180 tissue - 4-9 hrs, up to 12 hrs reported
  30. 30. Bupivacaine Time to onset Half life Max rec dose Max safe dose 6-10 mins 2.7 hrs 1.3 mg/kg (0.6 mg/lb) 90 mg or 10 carpules
  31. 31. Procaine Concentration - 2-4% Potency - 1 Toxicity - 1 Metabolized - hydrolyzed in plasma by pseudocholinesterase to PABA Excreted - Kidney No longer available in dental carpules
  32. 32. Procaine Time to onset Half life Duration (with v/c) Max rec dose Max safe dose 6-10 mins 0.1 hr pulp - 30-60 mins tissue - 2-3 hrs 6.6 mg/kg (3 mg/lb) 400 mg
  33. 33. Procaine Strong vasodilatation - very short duration of pulpal anesthesia High incidence of allergic reactions Drug of choice for Tx of inadvertent intraarterial injection (relieves pain and spasm) Consider for Amide allergic patient
  34. 34. Dosage of LA in children  Young’s rule (age) & Clark’s rule (weight) Which is accurate?  Max. child dose = child weight (kg)/70kg X max. adult dose. E.g.: Child dose of lidocaine with adrenalin = 20/70 X 500 mg = 143 mg Child dose of lidocaine without adrenalin = 20/70 X 300 mg = 86 mg
  35. 35. LA agents and vasoconstrictors
  36. 36. Importance of adding VC  What is the value of adding VC to the LA solution? 1.……. 2.…….. 3.…….. 4.………. 5……….
  37. 37. Vasoconstrictors Constrict blood vessels Decrease blood flow Decrease the blood level of the drug Increase the concentration of drug at the site Decrease bleeding at site
  38. 38. Factors in Selection of Vasoconstrictor Length of the dental procedure The need for hemostasis during and following procedure The medical status of the patient
  39. 39. Dosage of vasoconstrictor  1:100,000 means 1 gm (1000 mg)/100,000 mL. = 0.01 mg/ml  E.g.: concentration of adrenalin in a solution = 1:50,000 Therefore each mL contains = 1000/50,000 =1/50 = 0.02 mg/mL. The cartridge contents = 0.02 X 2 or (1.8) = 0.04 mg. = 40 microgram
  40. 40. References  Meechan, et al., Hand book of local anaesthesia, 1998. SF  Malamed: Pain and anxiety control for the conscious dental patient, 1997.