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Pharmcaology ppt

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Pharmcaology

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Pharmcaology ppt

  1. 1. PHARMACOLOGY OF LOCAL ANESTHESIA PRESENTED BY DR/ NERMINE RAMADAN MAHMOUD Lecturer Oral & Maxillofacial surgery in OMFS department Faculty of Dentistry O6U B.D FACULTY OF DENTISTRY, O6U , 2006 MSC ORAL & MAXILLOFACIAL SURGERY, FACULTY OF DENTISTRY, CAIRO UNIVERSITY , 2012 PHD ORAL & MAXILLOFACIAL SURGERY, FACULTY OF DENTISTRY, CAIRO UNIVERSITY, 2015
  2. 2. • Anaesthesia is the loss of consciousness and all form of sensation. • Local Anaesthesia is the local loss of pain, temperature, touch, pressure and all other sensation. • In dentistry, Only loss of pain sensation is desirable. Local Analgesia. Local anaesthesia / analgesia
  3. 3. • Local anesthetics produce a transient and reversible loss of sensation (analgesia) in a circumscribed region of the body without loss of consciousness. • Normally, the process is completely reversible.
  4. 4. CONTENTS OF THE LOCALANESTHETIC CARPULE (CARTRIDGE ) 1- the anesthetic drug 2- vasoconstrictor 3- preservative 4- vehicle 5- distilled water Pharmacology of local anesthesia
  5. 5. Pharmacology of local anesthesia 1- The anesthetic drug
  6. 6. Pharmacology of local anesthesia Anesthesia with V.C Plain Anesthesia without V.C 1- Local anesthetic agent (L.A) 2- Vaso - Constrictor (V.C) 3- Preservative for V.C agent (anti-oxidant) 4- Vehicle (0.9 % NaCl ) to make solution isotonic 1- Local anesthetic agent (L.A) 2- Vehicle (0.9 % NaCl ) to make solution isotonic Constituents of the anesthetic carpule
  7. 7. Pharmacology of local anesthesia Local anesthetic agents
  8. 8. Pharmacology of local anesthesia Local anesthetic agents Ester Amide
  9. 9. Local anesthetics generally have a lipid- soluble hydrophobic aromatic group and a charged, hydrophilic amide group.
  10. 10. The bond between these two groups determines the class of the drug, and may be amide or ester.
  11. 11. Pharmacology of local anesthesia
  12. 12. Pharmacology of local anesthesia
  13. 13. The clinically significant differences between esters and amides ??
  14. 14. Ester Amide Linkage Easily broken Difficult Stability in the solution Less More Storing time Less More Heat stable Less More Autoclavable Not Yes Allergy Produce PABA w produce allergic reaction Very rarely
  15. 15. Pharmacology of local anesthesia Requirements of an ideal local anesthetic drug 1) should not be irritating to the tissue to which it is applied 2) should not cause any permanent alteration of nerve structure 3) its systemic toxicity should be low 4) must be effective regardless it is injected into the tissue or applied topically to mucous membrane 5) time of onset of anesthesia should be as short as possible 6) duration of action must be long enough to permit completion of the procedure 7) should have potency sufficient to give complete anesthesia without the use of harmful concentrated solutions 8) should be relatively free from producing allergic reactions
  16. 16. Pharmacology of local anesthesia Pharmacokinetics of local anesthetics Uptake Potency Duration Biotransformation Excretion
  17. 17. Pharmacology of local anesthesia Pharmacokinetics of local anesthetics 1- Uptake  Most L.A agents producing vasodilatation  Vasodilatation results in: - Increase rate of absorption - Decrease duration of action - Increase blood level & risk for toxicity
  18. 18. Pharmacology of local anesthesia Pharmacokinetics of local anesthetics 1- Uptake  Procaine is the most potent vasodilator  Cocaine is the only L.A agents that produces vasoconstriction
  19. 19. Pharmacology of local anesthesia Pharmacokinetics of local anesthetics Uptake Potency Duration Biotransformation Excretion
  20. 20. Pharmacology of local anesthesia Pharmacokinetics of local anesthetics 2- Potency  The majority of local anesthetics are tertiary amines  Few local anesthetic are secondary amines as procaine  NH3  NR3  Local anesthetic agent is prepared in the carpule in the form of hydrochloride salt of tertiary amine (NR3-HCL)
  21. 21. The importance of the pKa of a local anaesthetic drug. All local anaesthetic agents are weak bases, meaning that they exist in two forms: - unionised (B) and - ionised (BH+).
  22. 22. The importance of the pKa of a local anaesthetic drug. The pKa of a weak base defines the pH at which both forms exist in equal amounts. As the pH of the tissues differs from the pKa of the specific drug, more of the drug exists either in its charged or uncharged form.
  23. 23. The importance of the pKa of a local anaesthetic drug. Pka drug PH tissue
  24. 24. The pKa of a local anaesthetic determines the amount which exists in an ionised form at any given pH. At physiological pH (7.4) all local anaesthetics are more ionised than unionised (as all the pKa values are greater than 7.4).
  25. 25. As the drug must enter the cell in order to have its effect it must pass through the lipid cell membrane Unionised drug will do this more readily than ionised drug.
  26. 26. However the proportions vary between the drugs: lignocaine has a pKa of 7.9 and is approximately 25% unionised at pH 7.4 . Bupivacaine has a pKa of 8.1 and hence less of the drug is unionised at pH 7.4 (about 15%). why lignocaine has a faster onset of action than bupivacaine.
  27. 27. Therefore the drug which is more unionised at physiological pH will reach its target site more quickly than the drug which is less so. This explains why lignocaine has a faster onset of action than bupivacaine.
  28. 28. Pharmacology of local anesthesia (NR3 – HCL ) The free base (NR3) of the hydrochloride salt of tertiary amine is liberated from its salt (HCL ) by interaction with alkaline medium , alkaline PH , (body fluids , NaHCO3) (NR3-HCL) + NaHCO3  NR3 + NaCL +H2CO3 ?
  29. 29. In presence of tissue infection or inflammation (acidic PH)
  30. 30. Pharmacology of local anesthesia In presence of tissue infection or inflammation (acidic PH) The free base (NR3) of the hydrochloride salt of tertiary amine (NR3 – HCL ) fall to liberated from its salt (HCL) & failure of anesthesia occurs (NR3-HCL) + ACIDIC PH -- (NR3-HCL)
  31. 31. Local anesthetics with lower pK have a more rapid onset of action (more uncharged form more rapid diffusion to cytoplasmic side of Na+ channel) pK % free base at pH 7.7 Onset of anesthesia (min) lidocaine 7.9 25 2-4 bupivacaine 8.1 18 5-8 procaine 9.1 2 14-18 Duration (minutes) 180-600 90-200 60-90
  32. 32. Pharmacology of local anesthesia Pharmacokinetics of local anesthetics Uptake Potency Duration Biotransformation Excretion
  33. 33. Pharmacology of local anesthesia Pharmacokinetics of local anesthetics 3- Duration Factors affecting duration & depth of anesthetic action : 1- factors related to individual : Individual response variation
  34. 34. Pharmacology of local anesthesia Pharmacokinetics of local anesthetics 3- Duration Factors affecting duration & depth of anesthetic action : 2- factors related to anesthetic agent : 1- lipid solubility 2-concentration & type of drug 3- +/- V.C 4- duration of exposure
  35. 35. Pharmacology of local anesthesia Pharmacokinetics of local anesthetics 3- Duration Factors affecting duration & depth of anesthetic action : 3- factors related to injection technique : 1- infiltration / nerve block 2- volume of solution 3- accuracy of technique 4- anesthetic variations
  36. 36. Pharmacology of local anesthesia Pharmacokinetics of local anesthetics 3- Duration Factors affecting duration & depth of anesthetic action : 4- factors related to site of injection : 1- alkalinity : affect ionization of drug & rate of liberation of free base 2- vascularity of tissue
  37. 37. Pharmacology of local anesthesia Pharmacokinetics of local anesthetics Uptake Potency Duration Biotransformation Excretion
  38. 38. Pharmacology of local anesthesia 4- Biotransformation ( metabolism ) Ester Amide Metabolized in Plasma Liver By Plasma pseudo- cholinesterase enzyme Microsomal enzyme And in Liver By Esterase enzyme Toxicity occurs in patients with Plasma pseudo cholinesterase enzyme deficiency Impaired liver function Liver dysfunction
  39. 39. Pharmacology of local anesthesia Biotransformation of L.A drugs Ester group undergo biotransformation in : - Liver by the esterase enzyme - Plasma by cholinesterase enzyme Amide group undergo biotransformation in: - Liver
  40. 40. Pharmacology of local anesthesia Pharmacokinetics of local anesthetics Uptake Potency Duration Biotransformation Excretion
  41. 41. Pharmacology of local anesthesia Pharmacokinetics of local anesthetics 5- Excretion Both groups of local anesthetics & their metabolites are excreted by kidneys Patients with renal dysfunction may be unable to eliminate local anesthetic & their metabolites from the blood with increase risk of toxicity
  42. 42. Pharmacology of local anesthesia
  43. 43. Pharmacology of local anesthesia
  44. 44. Pharmacology of local anesthesia Systemic actions of Local anesthetics • Drugs temporary interrupt nerve conduction when absorbed into it and have little or no irritating effect when injected • They are all synthetic compounds except the cocaine CVS & CNS are susceptible to L.A action
  45. 45. Local anaesthetic agents: • Are drugs that block nerve conduction when applied locally to nerve tissues in appropriate concentrations, acts on any part of the nervous system, peripheral or central and any type of nerve fibres, sensory or motor.
  46. 46. Pharmacology of local anesthesia Systemic actions of Local anesthetics - CNS - CVS - RESPIRATORY SYSTEM - DRUG INTERACTION - MALIGNANT HYPERTHERMIA (MH)
  47. 47. Pharmacology of local anesthesia Systemic actions of Local anesthetics Effects of local anesthetics on CNS • As is the case with CNS depressants generally (e.g., alcohol) local anesthetics (at toxic doses) produce a biphasic pattern of excitation followed by depression • The excitatory phase likely reflects the preferential blockade of inhibitory neurons and effects can range from mild hyperactivity to convulsions) • The subsequent depressive phase can progress to cardiovascular collapse and even death if unmanaged.
  48. 48. Pharmacology of local anesthesia Systemic actions of Local anesthetics Effects of local anesthetics on heart • Local anesthetics can reduce myocardial excitability pacemaker activity prolong the refractory period of myocardial tissue – this is the basis of the antiarrhythmic effects of local anesthetics • Local anesthetic-induced myocardial depression hypotension) can also be a manifestation of toxicity and can lead to cardiovascular collapse and even death!
  49. 49. Pharmacology of local anesthesia Systemic actions of Local anesthetics Effects of local anesthetics on respiratory system Unaffected by L.A until overdose levels . Overdose  respiratory arrest Due to generalized CNS depression
  50. 50. Pharmacology of local anesthesia Systemic actions of Local anesthetics Effects of local anesthetics on malignant hyperthermia (MH) Disorder in which a genetic variant in an individual alters his response to certain drug Tachycardia / unstable blood pressure / cyanosis / fever (up to 42 C) / muscle rigidity / death
  51. 51. Functional consequences of Na+ channel blockade by local anesthetics • nerves: decrease or abolition of conduction • vascular smooth muscle: vasodilatation • heart: decreased excitability (reduced pacemaker activity, prolongation of effective refractory period) • central nervous system: increased excitability, followed by generalized depression
  52. 52. Clinical aspects local anesthetic toxicity (cont’d) • allergic reactions: restricted to esters – metabolized to allergenic p-amino benzoic acid (PABA) (∴ amides usually preferred for nerve block) • cardiovascular: may be due to anesthetic (cardiodepression, hypotension) or vasoconstrictor (hypertension, tachycardia) ∴ monitor pulse/blood pressure • CNS: excitability (agitation, increased talkativeness – may → convulsions) followed by CNS depression (∴ care in use of CNS depressants to treat convulsions - may worsen depressive phase – convulsions usually well tolerated if brain oxygenation maintained between seizures)
  53. 53. Pharmacology of local anesthesia 2- The vasoconstrictor
  54. 54. Pharmacology of vasoconstrictors V.C commonly used in conjunction with injected L.A are chemically similar to the sympathetic nervous system mediators i.e : - epinephrine & - norepinephrine
  55. 55. Advantage of V.C 1- delayed absorption of anesthetic drug 2- it decrease the amount of solution needed 3-controls the rate at which the anesthetic drug enters the circulation (decrease risk of toxicity) 4- haemostasis 5- it causes local anaemia
  56. 56. What happens if you don’t use a vasoconstrictor? *Plain local anesthetics are vasodilators by nature 1) Blood vessels in the area dilate 2) Increase absorption of the local anesthetic into the cardiovascular system (redistribution) 3) Higher plasma levels  increased risk of toxicity 4) Decreased depth and duration of anesthesia  diffusion from site 5) Increased bleeding due to increased blood perfusion to the area
  57. 57. Contra-Indication of V.C Relative Absolute 1- diabetes 1- toxic goiter 2- hypertension (hyperthyroidism) 3- cardiac 4- pregnancy
  58. 58. Pharmacology of local anesthesia 1- diabetes : as V.C counteract the action of insulin i.e (increase blood glucose level ) 2- hypertension : as V.C raises patient’s blood pressure 3- cardiac : as V.C stimulate the heart, produce tacchycardia & increase H.R This is doubtful because of small amount used about 0.04 mg if 2ml of 1: 50 000 Is used & this is about 1/5 permissible dose that can be given to cardiac patient without ill effect Contra-Indication of V.C
  59. 59. Pharmacology of local anesthesia Contra-Indication of V.C 4- pregnancy : because V.C causes uterine contraction & may cause abortion 5- hyperthyroidism (toxic goiter) : because V.C esp. adrenaline may cause thyroid crisis & sudden death (Prilocaine with felypressine)
  60. 60. Pharmacology of local anesthesia
  61. 61. Pharmacology of local anesthesia
  62. 62. Pharmacology of local anesthesia
  63. 63. Pharmacology of local anesthesia
  64. 64. Pharmacology of local anesthesia
  65. 65. Pharmacology of local anesthesia 3- VEHICLE
  66. 66. Pharmacology of local anesthesia 3- VEHICLE 1- add to L.A carpule to make solution ‘isotonic’ 2- 0.9 % sodium chloride - Ringer solution (0.5% sodium chloride + 0.4 % potassium chloride)
  67. 67. Pharmacology of local anesthesia
  68. 68. Pharmacology of local anesthesia
  69. 69. Pharmacology of local anesthesia 4- PRESERVATIVE
  70. 70. 4- PRESERVATIVE 1- Is added to L.A carpule to prevent the oxygenation of the V.C 2- Na Metabisulphite is the most commonly used preservative 3- Na Metabisulphite when oxygenated is transferred to Na metabisulphate with a characteristic yellowish discoloration of carpule
  71. 71. Pharmacology of local anesthesia Maximum doses of L.A agents
  72. 72. Pharmacology of local anesthesia
  73. 73. Pharmacology of local anesthesia Dilution of L.A agents
  74. 74. Concentration of V.C in L.A 1/ 50.000  0.02 mg/ml 1/100.000  0.01 mg/ ml 1/200,000  0.005 mg/ml
  75. 75. 2 % lidocaine of 1/100.000 epinephrine in patient weighted 90 kg .. What is the max permissible dose ? Lidocaine max.dose 300 mg / normal 4.4 mg/kg 90 kg X 4.4 = 396 mg  over absolute maximum 2% lidocaine means = 20 mg/ml (2g/100 ml = 2000 mg / 100 ml Carpule 1.8 ml of solution So  20 X 1.8 = 36 of lidocaine / carpule
  76. 76. How much lidocaine in cartridge of 2% lidocaine with 1/100.000 epinephrine 2% lidocaine = 20 mg/ml 20mg/ml X 1.8 ml / cartridge = 36 mg lidocaine/ cartridge Epinephrine 1/100.000 = 0.01 mg/ml 0.01 mg/ml X 1.8 ml/ cartridge = 0.018 mg epinephrine / cart Maximum epinephrine dose 0.2 mg 1 carpule of 1:100,000 = 0.018 mg
  77. 77. So maximum permissible dose of 2% lidocaine with 1/100.000 Maximum epinephrine dose 0.2 mg 1 carpule of 1:100,000 = 0.018 mg 0.2 / 0.018 = 11 carpules
  78. 78. So maximum permissible dose of 2% lidocaine with 1/100.000 in cardiac patient Maximum epinephrine dose 0.05mg 1 carpule of 1:100,000 = 0.018 mg 0.05 / 0.018 = 2.7 carpules
  79. 79. 1.8 ml Cartridge of 2% Lidocaine 1:100,000 epi Maximum Epinephrine: 11 Cartridges Maximum Anesthetic: 300 mg 1.8 ml Cartridge of 2% Lidocaine 1:200,000 epi Maximum Epinephrine: 22 Cartridges Maximum Anesthetic: 300 mg
  80. 80. Max allowed dose (mg / kg) X (weight in kg / 10) X (1/concentration of L.A) = ml lidocaine 7 mg / kg for lidocaine with epinephrine , using 1 % lidocaine with epinephrine for 60 kg patient 7 X 6 X 1 = 42 ml lidocaine With epinephrine 7 mg/ kg Without epinephrine 3 mg/ kg
  81. 81. How much Epinephrine in CV patients? Maximum Epinephrine 0.04 mg Two cartridges of 1:100,000 epinephrine
  82. 82. Pharmacology of local anesthesia Keep in mind 1- The main agent in the carpule is the L.A agent 2- the other ingredients of the local anethetic carpule are added : a- to potentiate the action of the L.A agent b- to prevent deterioration of the contents
  83. 83. Pharmacology of local anesthesia TOPICALANESTHETICS
  84. 84. TOPICALANESTHETICS The use of topically applied L.A is an important component of atraumatic administration of intraoral L.A The concentration of a local anesthetic applied topically is typically greater than that of the same local anesthetic administered by the injection The higher the conc facilitates diffusion of the drug thru mucous membrane Lidocaine (xylocaine) is the most commonly used
  85. 85. Clinical aspects Applications of local anesthesia:  nerve block: injected locally to produce regional anesthesia (e.g., dental and other minor surgical procedures)  topical application: to skin for analgesia (e.g., benzocaine) or mucous membranes (for diagnostic procedures)  spinal anesthesia: injection into CSF to produce anesthesia for major surgery (e.g., abdomen) or childbirth  local injection: at end of surgery to produce long-lasting post- surgical analgesia (reduces need for narcotics)  i.v. infusion: for control of cardiac arrhythmias (e.g., lidocaine for ventricular arrhythmias)

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