1. Local anesthesia Lecture 3

2. Composition of local anesthetic solution Local anesthetic agent Vasoconstrictor Preservative Reducing agent Fungicidal agent Sodium chloride and distilled water

3. Local anesthetic agent Amide  Lidocaine Lidocaine  Mepivicaine Mepivicaine  Prilocaine Prilocaine  Articaine Articaine  Bupivicaine Bupivicaine  Etidocaine Etidocaine Ester  Cocaine Cocaine  Procaine Procaine  Propoxycaine Propoxycaine ba ck

4. Lidocaine  Most common agent  Discovered in 1948 ( first of amide group)  Regarded as the standard  Minimal allergisity  Have topical anesthetic activity  Vasodilating activity  PKa =7.9  Onset of action = 2-3 min  Duration = 60 min (pulpal) and 60-120 min (soft tissue)  Maximum recommended dose (MRD)= 4.4mg/kg =300 mg

5. Metabolism and safety  Lidocaine metabolized in liver and excreted in urine (10% unchanged completely)  On CNS large dose cause initial stimulation followed by depression ( anticonvulsant effect)  On CVS large dose cause myocardial depression ( used in ventricular tachycardia)

6. Maximum dose calculation  Available concentration =2% =2gm in each 100 ml /100  →→→→ 0.02gm/ml = 20 mg/ml  * 1.8ml/dental cartridge =36 mg /dental cartridge  300 /36 = 8.3 dental cartridge (MRD) back

7. Mepivicaine  Same potency to lidocaine  Similar to lidocaine in metabolism and excretion  Same onset  slight extended duration (weak vasodilatation)  PKa =7.6  Less toxic than lidocaine  Used for child and geriatric patient when vasoconstrictor contraindicated  MRD =4.4 mg/Kg= 300mg  2% → 8.3 cartridge  3% → 5.5 cartridge back

8. Prilocaine (citanest)  Same potency to lidocaine  Less toxicity  Less vasoldilating activity  PKa =7.9  MRD =6mg/kg  3% → 7.5 cartridge  4% → 5 cartridge

9. Prilocaine (citanest)  Metabolism occur mostly in liver into orthotolidine which can cause methemoglobulinemia in susceptible individual (patient with hemolytic anemia) if used in large dose → poor oxygen carrying capacity resulting in cyanosis  Clinically patient may have cyanosis in the lip, mucous membrane and skin. Patient may also have respiratory distress in severe cases  Treatment by methyline blue 1% injection 1-2 mg/kg IV/5min back

10. Articaine  Slightly more potent than lidocaine  Similar toxicity, and vasodilating activity  Some literature present a cross allergisity with sulfate so it is best to be avoided in patient allergic to sulfonamide  MRD =7mg/kg  4% → 7 cartridge  Similar to prilocaine in producing methemoglbulinemia back

11. Bupivicaine Four times more potent than lidocaine and 4 times less toxic Slower onset (5-10 min) and extended duration lasting for 90-180 min MRD =1.3mg/kg 0.5% → 10 cartridge Dental Indication 1.Prolonged dental procedure 2.Expected post operative pain Contraindication Child and mentally retarded patient back

12. Etidocaine Similar to bupivicaine except:  More toxic than lidocaine  MRD= 8mg /kg available in1.5% → 13 cartridge In general surgery both indicated in prolonged procedure when uses of vasoconstrictor is contraindicated systemically or locally back

13. Local anesthetic agent Amide  Lidocaine Lidocaine  Mepivicaine Mepivicaine  Prilocaine Prilocaine  Articaine Articaine  Bupivicaine Bupivicaine  Etidocaine Etidocaine Ester  Cocaine Cocaine  Procaine Procaine  Propoxycaine Propoxycaine ba ck

14. Cocaine  Oldest anesthetic agent used since 18 th century  It is the only agent having a vasoconstrictor activity( sympathomimatic activity) and can be used topically because it is rapidly absorbed through mucous membrane  It has liability for dependence which makes its uses very limited back

15. Procaine Has 50% potency and toxicity than lidocaine It has prominent vasodilating activity which reduce its duration PKa =9.1 (slow onset) MRD =1000mg Its hydrolyses occurs in plasma by enzyme pseudocholine esterase High incidence of allergisity back

16. Propoxycaine  More potent and more toxic than lidocaine  Has rapid onset and adequate duration  It is available in combination form with procaine to reduce toxicity  0.4% propoxycaine + 2% procaine =24mg/ml  MRD =400 mg  It is indicated only in patient allergic to amide form of local anesthesia back

17. Composition of local anesthetic solution Local anesthetic agent Vasoconstrictor Preservative Reducing agent Fungicidal agent Sodium chloride and distilled water

18. Vasoconstrictor Advantages of vasoconstrictor in combination with local anesthesia: 1.Reduce blood flow thus reduce bleeding 2.Reduce local anesthetic absorption and toxicity (reduce systemic effect) 3.Increase duration and depth of anesthesia

19. Types of vasoconstrictor 1.Adrenergic agonist agent 2.Vasopressin

20. Adrenergic agonist agent (sympathomimetic agent) - catecholamine Mode of action: 1.Direct (binding) 2.Indirect (displacing) 3.Mixed action

21. Sympathetic receptors: 1.  1 vasoconstriction 2.  2 Reuptake 3.  1 Cardiac stimulation 4.  2 Vasodilatation

22. Affinity of adrenergic agents on receptors 22 11 22 11 ++ Adrenaline --++ Nor - adrenaline +++ + Levonordephrine --++ Phenylphrine

23. OH CH 1 NH Epinephrine Levonordefrin Norepinephrine CH H H 3 H H 3 1 2 HO 2

25. Adrenaline  Synthetic or natural abstract from adrenal medulla. It is the most common and potent vasoconstrictor.  Concentration: Expressed in ratio gm: ml / 1: 100000 Meaning 1 gm in 100000 ml

26. Concentration 1:100000 means: =1 gm in 100000 ml =1000 mg in 100000 ml = 0.01 mg /ml In single dental cartridge (1.8 ml) = 0.018 mg =18  g (microgram)

27. Adrenaline availability (concentration)  1:1000 (alone) is used for control of bleeding?  contraindicated in arterial bleeding- Rebound bleeding  1:50000 for surgery where hemostasis is necessary  1:80000 and 1:100000 commonly used concentration  1:200000 low concentration used for medically compromised patient (vasoconstrictor contraindicated) and where hemostasis is of little importance

28. Maximum recommended dose (MRD) PotencyAvailable concentration MRD (mg) 1000.2Adrenaline 251:300000.34Nor - adrenaline 51:25004Phenylphrine 151:200001levonordephrine

29. Other adrenergic agonist vasoconstrictor  Nor-adrenaline and phenylphrine have prominent alpha activity comparing to beta activity which may result in severe vasoconstriction (increase blood pressure) and ischemia.  It is contraindicated in patients with cardiac problem.  It is contraindicated in terminal extremities

30. Metabolism of catecholamines MAO Receptor  Extraneuronal tissues Renal excretion [ COMT ] Adrenergic nerve terminal Injected drug COMT: Catechol-O-methyltransferase MAO: monoamine oxidase

31. Side effects and overdose CNS: Fear apprehension palpitation CVS: Cardiac stimulant effects, increase blood pressure and rebound bleeding at prolonged dental procedure. Causes of rebound bleeding: Adrenaline selectivity on receptor:  Low concentration  effect  High concentration  effect

32. Limitation of adrenergic vasoconstrictor Precautions/contraindications –Uncontrolled Cardiovascular disease –Uncontrolled thyrotoxic goiter Drug interactions –Tricyclic antidepressants –General anesthetics –Adrenergic antagonists –COMT inhibitors –Not MAO inhibitors

33. Vasoconstrictors (epinephrine, Levonordefrin) with Tricyclic antidepressants (imipramine, desipramine) –Hypertensive and/or cardiac reactions are more likely. Use epinephrine cautiously; avoid Levonordefrin.

34. Vasoconstrictors (epinephrine, Levonordefrin) with Volatile anesthetics (halothane) –Increased possibility of cardiac arrhythmias exists for some agents.

35. Vasoconstrictors (epinephrine, Levonordefrin) with Nonselective beta blockers (Propranolol, Nadolol) –Hypertensive and/or cardiac reactions are more likely. Use cautiously.

36. COMT inhibitors (Tolcapone, Entacapone) –Hypertensive and/or cardiac reactions are more likely. Use cautiously. Vasoconstrictors (Epinephrine, Levonordefrin) with

37. Consideration  MRD for cardiovascular disease patient = 0.04 mg of adrenaline = 2 dental cartridge of 2ml 1:100000 concentration adrenaline  Controversy still exists on using adrenaline in controlled cardiovascular diseased patient. Explain why?

38. Uses of small amount available in dental cartridge is better than exposing the patient to failure anesthesia which produce pain and bleeding that can stimulate fear and increase intrinsic adrenaline that may have more dangerous effect than extrinsic adrenaline

39. Vasopressin (Felypressin)  Synthetic analogue of posterior pituitary hormone (Octopressin)  Act on V1 receptor that is found on venous site of microcirculation  It posses mild hemostatic effect and used only when other vasoconstrictor contraindicated  Available concentration = 0.03 IU/ml in combination with prilocaine 2% or 3%  MRD= 0.27 IU back

40. Preservative  Maintains sterility of the solution  Caprylhydrocuprienotoxin used for this purpose  Methylparaben used in the past but nowadays not used ? back

41. Reducing agent (in vasoconstrictor containing solution)  Antioxidant (reducing agent) used to prevent oxidation of vasoconstrictor that may deteriorate on exposure to sunlight (brown discoloration)  Sodium metabisulfite used for this purpose  On exposure to oxygen it will diffuse through the rubber of the cartridge where sodium metabisulfite will be converted to sodium metabisulfate (oxidized)  Oxidized instead of vasoconstrictor  Why is an old solution more acidic? Painful ? Irritant? back

42. Fungicide Thymol Sodium chloride and distilled water (ringers solution) For isotonicity of injected solution to reduce edema and discomfort on injection