Chapter 8 Local Anesthetics
Structure activity relationships
2. What is the basic structure of local anesthetics?
3. Why are local anesthetics marketed as hydrochloride salts?
4. What are two differences between ester and amide local anesthetics that make classifying local anesthetics important?
5. Name four ester local anesthetics.
6. Name seven amide local anesthetics.
7. What is an easy way to remember whether a local anesthetic is an ester or an amine?
Mechanism of action
8. What is the mechanism of action of local anesthetics?
9. Where is the major site of local anesthetic effect?
10. How is the effect of a local anesthetic on the nerve terminated?
11. How is the resting membrane potential and the threshold potential altered in nerves that have been infiltrated by local anesthetic?
12. What is the temporal progression of the interruption of the transmission of neural impulses between the autonomic nervous system, motor system, and sensory system after the infiltration of a mixed nerve with local anesthetic?
13. What is frequency-dependent blockade? How does frequency-dependent blockade relate to the activity of local anesthetics?
Classification of nerves and sensitivity to local anesthetics
14. What three characteristics are nerve fibers classified by? What are the three main nerve fiber types?
15. Which types of nerve fibers are myelinated? What is the function of myelin and how does it affect the action of local anesthetics?
16. How many consecutive nodes of Ranvier must be blocked for the effective blockade of the nerve impulse by local anesthetic?
17. Which two nerve fiber types primarily function to conduct sharp and dull pain impulses? Which of these two nerve fibers is more readily blocked by local anesthetic?
18. Which two nerve fiber types primarily function to conduct impulses that result in large motor and small motor activity?
19. What is meant by differential block? Name an anesthetic that has had limited use because of its poor sensory selectivity.
20. How do local anesthetics diffuse through nerve fibers when deposited around a nerve? Which nerve fibers are blocked first as a result?
Spread of anesthesia and peripheral nerve blockade
21. How are the nerve fibers arranged from the mantle to the core in a peripheral nerve with respect to the innervation of proximal and distal structures? How does this correlate with the temporal progression of local anesthetic-induced blockade of proximal and distal structures?
22. What very fundamental difference exists between the local anesthetics and most systemically administered drugs?
Pharmacokinetics
23. Is the pKa of local anesthetics more than or less than 7.4?
24. At physiologic pH, does most local anesthetic exist in the ionized or nonionized form? What form must the local anesthetic be in to cross nerve cell membranes?
25. Does local tissue acidosis create an environment for higher or lower quality local anesthesia? Why?
26. What is the primary determinant of local anesthetic potency?
27. After a local anesthetic has been absorbed from the tissues, what are the primary determinants of local anesthetic peak plasma concentrations?
28. How are ester local anesthetics cleared?
29. How are the amide local anesthetics metabolized?
30. What percent of local anesthetic undergoes renal excretion unchanged?
31. What are two organs that influence the potential for local anesthetic systemic toxicity?
32. What accounts for chloroprocaine’s relatively low systemic toxicity?
33. Patients with atypical plasma cholinesterase are at an increased risk for what complication with regard to local anesthetics?
34. What disease states may influence the rate of clearance of lidocaine from the plasma?
35. How extensive is renal excretion of the parent local anesthetic compound?
36. How does the addition of epinephrine or phenylephrine to a local anesthetic solution prepared for injection affect its systemic absorption?
37. How does the addition of epinephrine or phenylephrine to a local anesthetic solution prepared for injection affect its duration of action?
38. How does the addition of epinephrine or phenylephrine to a local anesthetic solution prepared for injection affect its potential for systemic toxicity?
39. How does the addition of epinephrine or phenylephrine to a local anesthetic solution prepared for injection affect the rate of onset of anesthesia?
40. How does the addition of epinephrine or phenylephrine to a local anesthetic solution prepared for injection affect local bleeding?
41. What are some potential negative effects of the addition of epinephrine to a local anesthetic solution prepared for injection?
42. Name some situations in which the addition of epinephrine to a local anesthetic solution prepared for injection may not be recommended.
Side effects
43. What are some potential negative side effects associated with the administration of local anesthetics?
44. What is the most common cause of local anesthetic systemic toxicity?
45. What are the factors that influence the magnitude of the systemic absorption of local anesthetic from the tissue injection site?
46. From highest to lowest, what is the relative order of peak plasma concentrations of local anesthetic associated with the following regional anesthetic procedures: brachial plexus, caudal, intercostal, epidural, sciatic/femoral?
47. Which two organ systems are most likely to be affected by excessive plasma concentrations of local anesthetic?
48. What are the initial and subsequent manifestations of central nervous system toxicity due to increasingly excessive plasma concentrations of local anesthetic?
49. What is a possible pathophysiologic mechanism for seizures that result from excessive plasma concentrations of local anesthetic?
50. What are some potential adverse effects of local anesthetic-induced seizures?
51. How should local anesthetic-induced seizures be treated?
52. What is the indication for and disadvantage of the administration of neuromuscular blocking drugs for the treatment of seizures?
53. Is the cardiovascular system more or less susceptible to local anesthetic toxicity than the central nervous system?
54. What are two mechanisms by which local anesthetics produce hypotension?
55. What is the mechanism by which local anesthetics exert their cardiotoxic effects? How is this manifested on the electrocardiogram?
56. How is the relative cardiotoxicity between local anesthetic agents compared? What is the relative cardiotoxicity between lidocaine, bupivacaine, and ropivacaine?
57. How does bupivacaine differ from lidocaine with respect to their cardiotoxic effects, and what underlying electrophysiologic differences exist between lidocaine and bupivacaine that might contribute to their differing clinical toxicities?
58. What is the maximum recommended concentration of bupivacaine to be administered for obstetric epidural anesthesia? Why?
59. What relatively simple and apparently effective therapy for treatment of systemic local anesthetic toxicity has been recently introduced into clinical practice? What appears to be its predominant mechanism of action?
60. The administration of which local anesthetics have been associated with methemoglobinemia? What is the mechanism by which this occurs? How can it be treated?
61. What is the nature of the neurotoxicity that has been reported in association with the use of chloroprocaine? What is the mechanism by which this occurs?
63. What is the mechanism by which local anesthetics have resulted in cauda equina syndrome?
64. What changes have been recommended with respect to the dose of lidocaine used for spinal anesthesia?
65. What changes in practice have occurred with respect to the relative use of lidocaine for spinal anesthesia?
66. What is the allergenic potential of local anesthetics? What are the potential causes of an allergic reaction associated with administration of local anesthetics?
67. Does cross-sensitivity exist between the classes of local anesthetics?
Clinical uses
Answers*
Structure activity relationships
2. Local anesthetics consist of a lipophilic end and a hydrophilic end connected by a hydrocarbon chain. The lipophilic end is an aromatic ring, and the hydrophilic end is a tertiary amine and proton acceptor. The bond that links the hydrocarbon chain to the lipophilic end of the structure is either an ester (—CO—) or an amide (—HNC—). The local anesthetic is thus classified as either an ester or an amide local anesthetic. (131, Figure 11-2)
3. Local anesthetics are bases that are poorly water-soluble. For this reason they are marketed as hydrochloride salts. The resulting solution is generally slightly acidic with a pH of about 6. (133)
4. The metabolism and possibly the potential to produce allergic reactions differ between ester and amide local anesthetics, making this classification of local anesthetics important. (131)
5. The ester local anesthetics include procaine, chloroprocaine, cocaine, and tetracaine. (132, Figure 11-3)
6. The amide local anesthetics include lidocaine, mepivacaine, bupivacaine, levobupivacaine, etidocaine, prilocaine, and ropivacaine. (132, Figure 11-3)
7. As a general rule, ester local anesthetics will have only one “i” in their generic name, while the amides will have two. (132, Figure 11-3)
