LOCAL ANESTHETICS

1. LOCAL ANESTHETICS Jeffrey Groom, PhD, CRNAAnesthesiology Nursing ProgramNGR 6174 Pharmacology of Anesthesiology Nursing II

2. LOCAL ANESTHETICS • What role do LA’s play in anesthesia? • How are LA’s classified? • How can the LA name identify the class? • How are LA’s metabolized? • How are nerve impulses conducted? • What is the mechanism of action of LA’s? • Discuss allergy to LA’s

3. LOCAL ANESTHETICS • What determines LA potency? • What determines LA duration of action? • What determines LA onset time? • How does onset proceed? • Why didn’t LA work in a septic wound? • What is ion trapping? • How is toxic limit of LA established? • Why add a vasoconstrictor agent to LA’s? • How does a patient become toxic? S&S? • How is anatomic site related to absorption?

4. LOCAL ANESTHETICS USE - topical (skin, mucosa) SQ & Infiltration Intravascular Peripheral nerve Epidural space Spinal ACTION - central or site specific TOXICITY - therapeutic index

6. Local Anesthetics Target Site of Action Local vs Systemic

8. Classification, Structure and Function

9. ANESTHETICS

12. CONDUCTION of a NERVE IMPULSE

13. Conduction Blockade LAH+ LAIonized Nonionized

14. SEQUENCE OF EVENTS WHICH RESULT IN CONDUCTION BLOCKADE 1. Diffusion of the base (nonionized) form across the nerve sheath and nerve membrane 2. Re-equilibration between the base and cationic forms in the axoplasm 3. Penetration of the cation into and attachment to a receptor site within the sodium channel. 4. Blockade of the sodium channel

15. SEQUENCE OF EVENTS WHICH RESULT IN CONDUCTION BLOCKADE 5. Inhibition of sodium conduction 6. Decrease in the rate and degree of the depolarization phase of the action potential 7. Failure to achieve the threshold potential 8. Lack of development of a propagated action potential 9. Blockade of impulse conduction

16. Ionized

17. Common features of Local Anesthetics • Weak bases (pKa > 7.4) [poorly water soluble] • Packaged as an acidic hydrochloride [pH 4-7 now soluble] • In solution- non-ionized lipid soluble (free base) AND ionized water soluble (cation) • Body buffers raise the Ph, increase free base • lipid soluble form crosses axonal membrane • water soluble form blocks sodium channel

18. Important Clinical Properties of Local Anesthetics • ONSET • POTENCY • DURATION OF ACTION

19. Important Clinical Properties of Local Anesthetics • ONSET = pKa • pKa = pH at which 50% of drug is ionized • LA’s <50% exists in the lipid soluble nonionized form • Only the nonionized form crosses into the nerve cell

20. ROLE of pH and pKa in LOCAL ANESTHETICS

21. Important Clinical Properties of Local Anesthetics • Speed of Onset • low pKa = fast onset • Bupivacaine 8.1Lidocaine 7.7 • ? LA action in septic tissue • acid tissue -> éionized % of LA-> slow entry into membrane -> low concentration of LA for block

22. Important Clinical Properties of Local Anesthetics • Anesthetic Potency • Potency <=> lipid solubility • Higher solubility <=> can use a lower concentration and reduce potential for toxicity [LA]

23. Important Clinical Properties of Local Anesthetics • DURATION OF ACTION • Duration <=> protein binding • Bupivacaine 95%Lidocaine 65%Procaine 6%

24. Important Clinical Properties of Local Anesthetics • CLEARANCE • ESTERShydrolysis via pseudocholinesterase • AMIDESmetabolism via hepatic enzymes

25. Properties of Local Anesthetic Agents

26. Important Clinical Properties of Local Anesthetics • INCREASED DOASGE • Intensity & Duration <=> INCREASED • Increase dose via increased volume or concentration of LA

27. Important Clinical Properties of Local Anesthetics • Absorption of local at site • LA’s cause some vasodilitation @ site • LA washout related to blood flow • LA toxicity related to rate of absorption via blood flow

28. Important Clinical Properties of LA’s • ADDITION of VASOCONSTRICTORS • Vasoconstriction <=> slows systemic absorption & é duration • Epi 1:200,000 or 5 mcg/ml • Least effective with high lipid soluble LA’s (bupivacaine/etidocaine) • Epi may produce distal and systemic effects

29. Important Clinical Properties of LA’s • ADDITION of Sodium Bicarbonate • NaHCO3 - é pH & nonionized base • Speeds onset of block • 1 mEq NaHCO3 per 10 ml Lido/Mepiv • .1 mEq NaHCO3 per 10 ml Bupiv

30. Nerve Fiber and Local Anesthetic Effects • Fiber diameter - larger the fiber the higher the concentration of LA required • Myelination - LA • Position in nerve bundle - mantle -> core • Mantle fibers innervate PROXIMAL nerves • Core fibers innervate DISTAL nerves

31. Nerve Fiber and Local Anesthetic Effects

32. Nerve Fiber and Local Anesthetic Setup • Sequence of clinical anesthesia Sympathetic block (vasodilate & éskin T0) Loss of pain and temperature sensation Loss of proprioception Loss of touch and pressure sensation Loss of motor function

33. Local Anesthetic Toxicity • Local vs Systemic • Neuro vs Cardiovascular • Concentration and Rate of Absorption vs rate of metabolism • Toxicity limits (and epi concentrations) • Clinical scenarios - toxicity risk increased • Symptoms • Management

34. Local Anesthetic Toxicity

35. LOCAL ANESTHETICS • What role do LA’s play in anesthesia? • How are LA’s classified? • How can the LA name identify the class? • How are LA’s metabolized? • How are nerve impulses conducted? • What is the mechanism of action of LA’s? • Discuss allergy to LA’s

36. LOCAL ANESTHETICS • What determines LA potency? • What determines LA duration of action? • What determines LA onset time? • How does onset proceed? • Why didn’t LA work in a septic wound? • What is ion trapping? • How is toxic limit of LA established? • Why add a vasoconstrictor agent to LA’s? • How does a patient become toxic? S&S? • How is anatomic site related to absorption?