INTRODUCTION to LOCAL ANESTHESIA and NEUROPHYSIOLOGY.pptx

Local Anesthesia

1. INTRODUCTION to LOCAL ANESTHESIA and NEUROPHYSIOLOGY

2. Definition of Local Anesthesia a loss of sensation in a circumscribed area of the body caused by a depression of excitation in nerve endings Or an inhibition of the conduction process in peripheral nerves; no loss of consciousness occurs

3. Properties of Local Anesthetics : 1) Not irritating to the tissue 2) No permanent alteration of nerve structure 3) Systemic toxicity should be low 4) Effective whether injected or applied topically 5) Time of onset of anesthesia should be as short as possible 6) Duration of action must be long enough to complete the procedure but not so long as to require an extended recovery 7) Should be stable in solution and easily biotransformed 8) Should not cause allergic reactions 9) Should be sterile or capable of being sterilized by use of heat

4. Neurophysiology The Neuron The neuron is the structural unit of the nerve Two types of neurons 1) Sensory afferent (toward the CNS) 2) Motor efferent (away from the CNS)

5. Sensory Neurons: transmit pain 1) Dendritic Zone - free nerve endings; most distal portion of the neuron 2) Axon - synapses with the CNS to transmit input to the brain 3) Cell Body - provides metabolic support for the entire neuron

6. Sensory Neurons (afferent)

7. Motor Neuron (efferent)

8. Electrophysiology of Nerve Conduction Nerve resting potential is -70 mV; this is produced by differing concentrations of ions on either side of the nerve membrane Interior of the nerve is negative compared to the exterior before a stimulus excites the nerve

9. STEP 1 - S timulus excites nerve which leads to: 1) Slow Depolarization- inside of nerve becomes less negative 2) Threshold Potential- extremely rapid depolarization occurs from the falling electrical potential 3) Rapid Depolarization- interior is electrically positive +40 mV and the outside is negative (-70 mv)

10. Resting to Threshold Potential

11. Threshold Potential to Rapid Depolarization

12. STEP 2 - after depolarization, repolarization occurs Repolarization - electric potential inside the cell gradually becomes more negative until the interior is again restored to –70 mV

13. Depolarization Repolarization

14. Depolarization - excitation leads to increase in permeability of the cell membrane to sodium ions -transient widening of transmembrane ion channels allow passage of the sodium ions -rapid influx of sodium ions into the interior of the nerve cell causes depolarization of the cell membrane from resting to firing threshold which is -50 to -60 mV

15. Firing Threshold  magnitude of the decrease in negative trans-membrane potential that is necessary to initiate an action potential (impulse); getting more positive with more influx of Na+

16. Firing Threshold

17. - decrease in negative transmembrane potential of +15 mV; from –70 mV to –55 mV is necessary to reach the firing threshold; voltage differences of less than +15 mV will not induce firing -exposure to a nerve with local anesthetic raises its firing threshold -elevating the firing threshold means that more sodium must pass through the membrane to decrease the negative transmembrane potential to a level where depolarization occurs

18. -when the firing threshold is reached, sodium rapidly enters the axoplasm due to increased membrane permeability -depolarization lasts ~ .3 msec

19. Repolarization The action potential is terminated when the membrane repolarizes ; this is caused by the inactivation of increased permeability to sodium The movement of Na+ and K+ during depolarization is passive

20. Repolarization

21. After the membrane potential returns to –70 mV there is still a slight amount of excess sodium within the nerve cell and a slight excess of potassium extracellularly Sodium is moved out of the cell using ATP and the sodium pump Repolarization requires ~ .7 msec

22. Absolute Refractory Period  the nerve is unable to respond to another stimulus regardless of its strength Relative Refractory Period  a new impulse can be initiated at this time but only by a stronger than normal stimulus; follows the absolute refractory period

23. Impulse Propagation Activation of an action potential by a stimulus Disruption of the resting nerve membrane potential Interior of the cell goes from negative (–70 mV) to positive (+40 mV) Exterior of the cell changes from positive to negative Local currents begin flowing between the depolarized segment and the adjacent resting area Local currents flow from positive to negative extending for several mm along the nerve membrane As a result, the interior of adjacent areas become less negative and the exterior becomes less positive

24. Impulse Propagation Transmembrane potential decreases approaching firing threshold for depolarization When transmembrane potential decreases by 15mV from resting potential, firing threshold is reached and rapid depolarization occurs The newly depolarized segment sets up local currents and it all starts over again Newly depolarized segments return to resting state after absolute and relative refractory periods Waves of depolarization can move in only one direction due to the absolute and relative refractory periods, thus retrograde (backward) movement is prevented

25. Impulse Spread 1) Unmyelinated Nerves -high electrical resistance cell membrane -slow forward “creeping” spread of impulses -conduction of unmyelinated C fibers is1.2 m/sec

26. 2) Myelinated Nerves -insulating myelin separates the extra/intracellular charges -the farther apart the charges the smaller the current necessary to charge the membrane -current leaps from node to node  saltatory conduction

27. Myelinated Nerves if conduction of an impulse is blocked at one node, the local current skips that node and continues to the next node

28. A minimum of 8 to 10 mm of nerve must be covered by anesthetic solution to ensure adequate block of impulse spread

29. Mode and Site of Action of Local Anesthetics Local anesthetics interfere with the excitation process in the nerve membrane in one or more of the following ways: 1) Altering the basic resting potential of the nerve membrane 2) Altering the threshold potential (firing level) 3) Decreasing the rate of depolarization* 4) Prolonging the rate of repolarization

30. Because of local anesthetics, cellular depolarization is not sufficient to reduce the membrane potential of a nerve fiber to its firing threshold and a propagated action potential does not develop

31. Where Do Local Anesthetics Work ? Specific Receptor Theory  local anesthetics act by binding to specific receptors on the sodium channel the action of the drug is direct and is not mediated by some change in the general properties of the cell membrane a specific receptor site for local anesthetics exists in the sodium channel which eliminates permeability to sodium ions Therefore: no impulse conduction

32. Mechanism of Action of Local Anesthetics 1) Displacement of calcium ions from the sodium channel receptor site 2) Binding of the local anesthetic molecule to this receptor site 3) Blockade of the sodium channel 4) Decrease in sodium conductance 5) Depression of the rate of electrical depolarization 6) Failure to achieve the threshold potential level (firing level) 7) Lack of development of propagated action potentials 8) Conduction blockade

33. 1) The nerve remains in a polarized state, therefore there is no depolarization because the ionic movements responsible for the action potential fail to develop 2) The membrane’s electrical potential remains unchanged, therefore local currents do not develop and the self-perpetuating mechanism of impulse propagation is stalled 3) Nerve block produced by local anesthetic is called a nondepolarizing nerve block

34. Four Factors Are Involved In The Action of a Local Anesthetic : 1) Diffusion of the drug through the nerve sheath 2) Binding of the drug at the receptor site in the membrane channel 3) Free bases (RN) cross the nerve membrane 4) Cation (RNH+) blocks the receptor The uncharged, lipid-soluble free base (RN) form of the local anesthetic is responsible for diffusion through the nerve membrane

35. Local Anesthetics with lower pKa have large number of free base molecules (RN) that are able to diffuse through the nerve sheath But the anesthetic action of this drug is inadequate because at intracellular pH of 7.4 a very small number of base molecules dissociate back to the cationic form (RNH+) necessary for binding at the receptor site (e.g., Benzocaine = pKa 3.5)

36. The rate of onset is related to the pKa of the local anesthetic Bupivacaine at pKa 8.1 has a slower onset than Lidocaine pKa 7.7

37. Antioxidants and pH Antioxidants are added to local anesthetics to delay the oxidation of the vasopressor; oxidation will turn the solution a reddish-brown Sodium bisulfite is a common antioxidant placed in local anesthetic solution Lidocaine 2% with a pH of 6.8 is acidified to a pH of 4.2 with the addition of the antioxidant sodium bisulfite The shelf life of local anesthetics decrease as the pH of the solutions decreases

38. The large buffering capacity of the tissue (pH 7.4) is able to maintain a normal tissue pH, however, it takes a longer time to do so after an injection of a pH 4.2 solution than with a pH 6.8 solution the end result is a slower clinical onset of action while the tissue pH equilibrates the pH of the solution with the pH of the tissues

39. Induction Time Factors Under Clinician’s Control : 1) Concentration of the drug 2) pH of the local anesthetic solution Factors not Under Clinician’s Control : 1) Diffusion constant of the anesthetic drug 2) Anatomical diffusion barriers of the nerve

40. What is the order of recovery from Local Anesthetic ? Follows same diffusion patterns as induction only in the reverse order Mantle fibers lose anesthesia before the core fibers Third molars would regain sensation before incisors if an inferior alveolar nerve block were administered Recovery is a slower process than induction because the local anesthetic molecule is bound to the drug receptor site in the sodium channel and is released more slowly than it is absorbed

41. -The combination of residual local anesthetic and the newly deposited supply results in rapid onset of profound anesthesia with a smaller volume of the drug being administered - Tachyphylaxis is an increased tolerance to a drug that is administered repeatedly; this could result in less anesthesia after re-injection