AL Flashcards
1
Q
- What was the first local anesthetic introduced into clinical practice? What is its structural class?
A
- The first local anesthetic introduced into clinical practice was cocaine in the 1880s. Cocaine’s amino-ester structure was adapted to make benzocaine (topical), procaine, tetracaine, and chloroprocaine (injectable). (139)
2
Q
- What was the first amino-amide local anesthetic introduced into clinical practice?
A
- The first amino-amide local anesthetic introduced into clinical practice was lidocaine in 1948. It was considered to be more stable and to have less allergic potential than the amino-ester local anesthetics. (139)
3
Q
- What are two differences between amino-ester and amino-amide local anesthetics that make classifying local anesthetics important?
A
- The metabolism and the potential to produce allergic reactions differ between amino-ester and amino-amide local anesthetics. (139)
4
Q
- Name seven amino-amide local anesthetics.
A
- The amino-amide local anesthetics include lidocaine, mepivacaine, bupivacaine, levobupivacaine, etidocaine, prilocaine, and ropivacaine. (139)
5
Q
- What distinguishes ropivacaine and levobupivacaine from the other local anesthetics?
A
- Ropivacaine and levobupivacaine are single enantiomers (S(–) forms) rather than racemic mixtures, developed in response to the cardiotoxic effects of bupivacaine. (139)
6
Q
- What mediates nerve conduction when a nerve gets stimulated under normal circumstances?
A
- When a nerve is stimulated, there is an increase in membrane permeability of sodium channels to sodium ions, leading to depolarization and propagation of an action potential. (140)
7
Q
- What three characteristics are nerve fibers classified by? What are the three main nerve fiber types?
A
- Nerve fibers are classified by fiber diameter, the presence or absence of myelin, and function. The three main types are A, B, and C fibers. (140)
8
Q
- How does the diameter of a nerve influence nerve conduction velocity?
A
- A larger nerve diameter correlates with a faster conduction velocity. (140)
9
Q
- Which types of nerve fibers are myelinated? What is the function of myelin?
A
- A and B nerve fiber types are myelinated, while C fibers are unmyelinated. Myelin insulates the nerve, increasing conduction velocity by allowing saltatory conduction at the nodes of Ranvier. (140)
10
Q
- What is the mechanism of action of local anesthetics?
A
- Local anesthetics produce conduction blockade by preventing sodium ions from passing through voltage-gated sodium channels in nerve membranes, thus slowing depolarization and preventing action potential propagation. (140)
11
Q
- Where is the major site of local anesthetic effect?
A
- Local anesthetics exert their predominant effect by binding to a receptor within the inner vestibule of the sodium channel on the nerve membrane. (140)
12
Q
- What is frequency-dependent blockade? How does frequency-dependent blockade relate to the activity of local anesthetics?
A
- Frequency-dependent (or use-dependent) blockade refers to the phenomenon in which local anesthetics bind more avidly to sodium channels that are frequently activated, thereby progressively enhancing nerve conduction blockade with repetitive stimulation. (142)
13
Q
- How does myelin affect the action of local anesthetics?
A
- Myelin increases the susceptibility of nerve fibers to blockade by local anesthetics. (142)
14
Q
- How many consecutive nodes of Ranvier must be blocked for the effective blockade of the nerve impulse by local anesthetic?
A
- Generally, three consecutive nodes of Ranvier must be exposed to local anesthetic to effectively block nerve conduction. (142)
15
Q
- How is the resting membrane potential and the threshold potential altered in nerves that have been infiltrated by local anesthetic?
A
- Neither the resting membrane potential nor the threshold potential is appreciably altered by local anesthetics. (142)
16
Q
- How is the effect of a local anesthetic on the nerve terminated?
A
- The conduction blockade produced by a local anesthetic is completely reversible as the drug dissociates from the sodium channels, allowing normal nerve function to return. (142)
17
Q
- What is the basic structure of local anesthetics?
A
- Local anesthetics consist of a lipophilic aromatic ring and a hydrophilic tertiary amine linked by a hydrocarbon chain. The linkage is either an amino ester (—CO—) or an amino amide (—HNC—), determining their classification. (142)
18
Q
- Why are local anesthetics marketed as hydrochloride salts?
A
- Local anesthetics are marketed as hydrochloride salts because they are bases that are poorly water-soluble; forming the hydrochloride salt improves solubility for injection. (142)
19
Q
- Is the pKa of local anesthetics more than or less than 7.4?
A
- The pKa of most local anesthetics is greater than 7.4 (with benzocaine being a notable exception). (142)
20
Q
- 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?
A
- At physiologic pH, most local anesthetics exist in the ionized form; however, the nonionized, lipid-soluble form is necessary to cross the nerve cell membrane. (142)
21
Q
- Does local tissue acidosis create an environment for higher or lower quality local analgesia? Why?
A
- Local tissue acidosis creates an environment for lower quality analgesia because it increases the ionized fraction of the anesthetic, reducing the amount of nonionized drug available to penetrate nerve membranes. (142)
22
Q
- What is the primary determinant of local anesthetic potency?
A
- The primary determinant of potency is lipid solubility. (142)
23
Q
- Is nerve conduction blockade facilitated by increasing the concentration of local anesthetic or by increasing the length of nerve exposed to more dilute concentrations of local anesthetic?
A
- Both increasing the concentration and increasing the length of nerve exposed to the anesthetic enhance nerve conduction blockade. (143)
24
Q
- What is meant by differential block?
A
- Differential block refers to the phenomenon where, at dilute concentrations, local anesthetics preferentially block autonomic and sensory fibers while sparing motor fibers. (144)
25
Q
- How do local anesthetics diffuse through nerve fibers when deposited around a nerve? Which nerve fibers are blocked first?
A
- Local anesthetics diffuse along a concentration gradient from the outer (mantle) to the inner (core) regions of the nerve, so fibers in the mantle are blocked before those in the core. (144)
26
Q
- 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? What is the clinical implication of this?
A
- In peripheral nerves, fibers in the mantle typically innervate proximal structures, while fibers in the core innervate distal structures; this explains why proximal analgesia occurs initially, followed by progressive distal spread as the anesthetic diffuses. (144)
27
Q
- 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 peripheral nerve with local anesthetic?
A
- The blockade typically progresses in the following order: autonomic, then sensory, and finally motor fibers. (144)
28
Q
- 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?
A
- A-δ fibers conduct sharp, fast pain and C fibers conduct dull, burning pain; the larger, myelinated A-δ fibers are generally more readily blocked than the smaller, unmyelinated C fibers, although high concentrations can overcome this difference. (144)
29
Q
- Which two nerve fiber types primarily function to conduct impulses that result in large motor and small motor activity?
A
- A-α fibers conduct large motor impulses and A-β fibers conduct small motor impulses. (144)
30
Q
- What very fundamental difference exists between the local anesthetics and most systemically administered drugs with regard to drug efficacy and absorption?
A
- Local anesthetics are deposited directly at the target site, and systemic absorption competes with local nerve penetration, potentially diminishing efficacy if uptake is rapid. (144)
31
Q
- After a local anesthetic has been absorbed from the tissues, what are the primary determinants of local anesthetic peak plasma concentrations?
A
- The peak plasma concentration is determined by the rate of systemic uptake and the clearance of the drug from the injection site. (144)
32
Q
- What are some physicochemical properties of local anesthetics and of the target site of injection that influence the systemic uptake of an injected local anesthetic?
A
- Properties include the lipophilicity, protein binding of the anesthetic, and the vascularity at the injection site. (144)
33
Q
- What is the clinical implication of the variability in local anesthetics to cause vasoconstriction?
A
- Variability in vasoconstrictive properties influences systemic absorption rates and duration of action; agents that cause inherent vasoconstriction may have lower systemic toxicity and longer clinical duration. (144)
34
Q
- How are amino-ester local anesthetics cleared?
A
- Amino-ester local anesthetics are cleared by hydrolysis via pseudocholinesterase enzymes in the plasma. (147)
35
Q
- How are the amino-amide local anesthetics metabolized?
A
- Amino-amide local anesthetics are metabolized in the liver by hepatic microsomal enzymes. (147)
36
Q
- What are two organs that influence the potential for local anesthetic systemic toxicity (LAST)?
A
- The lungs (first-pass pulmonary extraction) and the liver (metabolism) both influence the risk of LAST. (147)
37
Q
- What accounts for chloroprocaine’s relatively low systemic toxicity?
A
- Chloroprocaine is rapidly hydrolyzed by plasma cholinesterase, resulting in low systemic toxicity. (147)
38
Q
- Patients with atypical plasma cholinesterase are at an increased risk for what complication with regard to local anesthetics?
A
- Such patients are at increased risk for prolonged or excessive plasma concentrations of amino-ester local anesthetics, leading to toxicity. (147)
39
Q
- What is the correlation between the clearance of lidocaine from plasma and hepatic blood flow?
A
- The clearance of lidocaine is directly proportional to hepatic blood flow. (147)
40
Q
- What percent of local anesthetic undergoes renal excretion unchanged?
A
- Less than 5% of an injected local anesthetic is excreted unchanged by the kidneys. (147)
41
Q
- How does the addition of epinephrine to a local anesthetic solution prepared for injection affect its systemic absorption?
A
- The addition of epinephrine causes local vasoconstriction, which slows systemic absorption of the local anesthetic. (147)
42
Q
- How does the addition of epinephrine to a local anesthetic solution prepared for injection affect its duration of action?
A
- Epinephrine prolongs the duration of local anesthesia by reducing systemic absorption, thereby keeping the anesthetic in contact with nerve fibers for a longer period. (147)
43
Q
- How does the addition of epinephrine to a local anesthetic solution prepared for injection affect its potential for systemic toxicity?
A
- By slowing systemic absorption, epinephrine decreases the potential for systemic toxicity. (147)
44
Q
- How does the addition of epinephrine to a local anesthetic solution prepared for injection affect the rate of onset of anesthesia?
A
- The addition of epinephrine has little effect on the onset rate of local anesthesia. (147)
45
Q
- How does the addition of epinephrine to a local anesthetic solution prepared for injection affect local bleeding?
A
- Epinephrine decreases local bleeding by inducing vasoconstriction at the injection site. (147)
46
Q
- What are some potential negative effects of the addition of epinephrine to a local anesthetic solution prepared for injection?
A
- Potential negative effects include systemic absorption of epinephrine leading to cardiac dysrhythmias or hypertension. (147)
47
Q
- Name some clinical situations in which the addition of epinephrine to a local anesthetic solution prepared for injection may not be recommended.
A
- Epinephrine is contraindicated in patients with unstable angina, cardiac dysrhythmias, uncontrolled hypertension, uteroplacental insufficiency, and for blocks in areas with limited collateral blood flow (e.g., digits). (147)
48
Q
- Other than epinephrine, what are some additives to local anesthetic solution that have been shown to prolong the duration of anesthesia?
A
- Additives such as clonidine and dexamethasone have been shown to prolong the duration of anesthesia. (147)
49
Q
- What are some potential negative side effects associated with the administration of local anesthetics?
A
- Negative side effects include systemic toxicity (LAST), neurotoxicity, and allergic reactions. (147)
50
Q
- What is the most common cause of LAST?
A
- LAST most commonly occurs due to accidental intravascular injection of local anesthetic solution during peripheral nerve block procedures. (147)
51
Q
- What are the factors that influence the magnitude of the systemic absorption of local anesthetic from the tissue injection site?
A
- Factors include the pharmacologic properties of the anesthetic, the total dose injected, the vascularity of the injection site, and whether a vasoconstrictor is added. (147)
52
Q
- 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?
A
- The order is: intercostal > caudal > epidural > brachial plexus > sciatic/femoral. (147)
53
Q
- Which two organ systems are most likely to be affected by excessive plasma concentrations of local anesthetic?
A
- The central nervous system and the cardiovascular system are most likely to be affected. (147)
54
Q
- What are the initial and subsequent manifestations of central nervous system toxicity due to increasingly excessive plasma concentrations of local anesthetic?
A
- Initially, CNS toxicity manifests as circumoral numbness, facial tingling, restlessness, vertigo, tinnitus, and slurred speech. As concentrations increase, CNS excitation (e.g., muscular twitching, tremors, seizures) occurs, eventually leading to depression, apnea, and death. (147)
55
Q
- What is a possible pathophysiologic mechanism for seizures that result from excessive plasma concentrations of local anesthetic?
A
- Excessive local anesthetic concentrations initially depress inhibitory pathways in the cerebral cortex, allowing unopposed excitatory activity to cause seizures. (148)
56
Q
- What are some potential adverse effects of local anesthetic-induced seizures?
A
- Adverse effects include arterial hypoxemia, metabolic acidosis, and pulmonary aspiration. (148)
57
Q
- How should local anesthetic-induced seizures be treated?
A
- Treatment includes ensuring airway protection, supplemental oxygen, and administration of anticonvulsants (e.g., benzodiazepines such as diazepam). (148)
58
Q
- What is the indication for, and disadvantage of, the administration of neuromuscular blocking drugs for the treatment of seizures?
A
- Neuromuscular blocking drugs may be used to control peripheral manifestations of seizures (e.g., to facilitate intubation), but they do not affect the underlying cerebral electrical activity, so anticonvulsants are still needed. (148)
59
Q
- Is the cardiovascular system more or less susceptible to local anesthetic toxicity than the central nervous system?
A
- The CNS is more susceptible to local anesthetic toxicity than the cardiovascular system. (148)
60
Q
- What are two mechanisms by which local anesthetics can produce hypotension?
A
- Hypotension may result from relaxation of peripheral vascular smooth muscle and direct myocardial depression. (148)
61
Q
- What is the mechanism by which local anesthetics exert their cardiotoxic effects? How is this manifested on the electrocardiogram?
A
- Local anesthetics block sodium channels in the myocardium, increasing conduction time (prolongation of the PR interval, widening of the QRS complex) and producing a dose-dependent negative inotropic effect. (148)
62
Q
- How is the relative cardiotoxicity between local anesthetic agents compared? What is the relative cardiotoxicity between lidocaine, bupivacaine, and ropivacaine?
A
- Relative cardiotoxicity is compared by the dose or plasma concentration required to cause cardiovascular collapse relative to CNS toxicity. Bupivacaine is roughly twice as cardiotoxic as lidocaine, while levobupivacaine and ropivacaine have intermediate cardiotoxicity. (148)
63
Q
- What is the standard treatment of LAST?
A
- The standard treatment for LAST is the intravenous infusion of lipid emulsion (“lipid rescue”). (148)
64
Q
- What is the dose of lipid emulsion that should be used for LAST, according to the American Society of Regional Anesthesia and Pain Medicine (ASRA) guidelines?
A
- The ASRA guidelines recommend an initial bolus of lipid emulsion of 1.5 mL/kg (100 mg in adults) followed by a continuous infusion at 0.25 mL/kg/min. (148)
65
Q
- What are some modifications to standard advanced cardiac life support (ACLS) protocols in the event of LAST leading to cardiovascular collapse, according to ASRA guidelines?
A
- Modifications include avoiding vasopressin, calcium channel blockers, β-blockers, and additional local anesthetics, and using incremental dosing of epinephrine (<1 µg/kg). (148)
66
Q
- What are some factors that may contribute to local tissue toxicity from local anesthetic injection?
A
- Factors include high local anesthetic concentration, prolonged exposure, preexisting nerve dysfunction, metabolic/inflammatory conditions, increased tissue pressure, and systemic hypotension. (148-149)
67
Q
- What is the allergic potential of local anesthetics?
A
- True allergic reactions to local anesthetics are rare (<1% of adverse reactions). (149)
68
Q
- What are the potential causes of a hypersensitivity reaction associated with the administration of local anesthetics?
A
- Hypersensitivity may result from the local anesthetic itself, its metabolites (e.g., para-aminobenzoic acid from amino-esters), or other components such as preservatives (e.g., methylparaben). (149)
69
Q
- Does cross-sensitivity exist between the classes of local anesthetics?
A
- Cross-sensitivity between amino-ester and amino-amide local anesthetics is not typically observed, assuming the reaction is due to the anesthetic molecule and not a preservative. (149)
70
Q
- What was the primary use of procaine during the early 1900s?
A
- Procaine was primarily used as a spinal anesthetic in the early 1900s. (149)
71
Q
- How does procaine compare to lidocaine with respect to stability and risks of hypersensitivity, transient neurologic symptoms (TNS), and nausea?
A
- Procaine is less stable, has a higher risk of hypersensitivity and nausea, and only a small advantage regarding TNS compared to lidocaine. (149)
72
Q
- What is the principal use of tetracaine in current clinical practice? What is a potential adverse effect of tetracaine?
A
- Tetracaine is primarily used as a spinal anesthetic; however, when used with a vasoconstrictor it carries a high risk of TNS. (149)
73
Q
- What properties of tetracaine limit its usefulness for use in epidural anesthesia or peripheral nerve blockade?
A
- Tetracaine’s slow onset, profound motor blockade, and potential toxicity at high doses limit its use for epidural anesthesia or peripheral nerve blocks. (149)
74
Q
- How does the rate of metabolism of tetracaine compare to the other amide-ester local anesthetics?
A
- Tetracaine is metabolized much more slowly than other amino-ester local anesthetics – about one fourth as fast as procaine and one tenth as fast as chloroprocaine. (149)
75
Q
- What is the nature of the neurotoxicity that has been reported in association with the use of epidural chloroprocaine? What is the mechanism by which this occurs?
A
- Epidural chloroprocaine has been associated with neurotoxic injury, possibly due to inadvertent intrathecal administration at high doses, with early theories implicating low pH and preservatives (sodium bisulfite) leading to sulfur dioxide release; however, more recent studies suggest that high doses are the main factor. (149)
76
Q
- What are some advantageous properties of chloroprocaine?
A
- Chloroprocaine has a rapid onset and rapid hydrolysis, which limits its systemic toxicity. (149)
77
Q
- What are some uses of chloroprocaine in current clinical pediatric practice?
A
- Chloroprocaine is used as a continuous epidural infusion in neonates and young infants, and for repeated loading doses in postoperative peripheral nerve blocks to avoid toxic plasma concentrations. (150)
78
Q
- What are some uses of lidocaine in current clinical practice?
A
- Lidocaine is used for local, topical, regional, intravenous, peripheral nerve, spinal, and epidural anesthesia. (150)
79
Q
- What are two adverse neurologic outcomes associated with lidocaine spinal anesthesia?
A
- Lidocaine spinal anesthesia is associated with major sequelae like cauda equina syndrome and minor sequelae such as transient neurologic symptoms (TNS). (150)
80
Q
- What is the mechanism by which spinal lidocaine has resulted in cauda equina syndrome?
A
- Cauda equina syndrome is thought to result from pooling of lidocaine in the dependent portions of the intrathecal space when administered via microbore catheters, leading to high local concentrations and neurotoxicity. (150)
81
Q
- What is TNS?
A
- TNS (Transient Neurologic Symptoms) is a syndrome of pain or dysesthesia in the lower back, posterior thighs, or buttocks that occurs within 12 to 24 hours after spinal anesthesia and usually resolves within 3 days without motor weakness or sensory loss. (150)
82
Q
- What are some risk factors for TNS?
A
- Risk factors include the use of lidocaine for spinal anesthesia, the lithotomy position, and outpatient status. (150)
83
Q
- What is the treatment for TNS?
A
- First-line treatment for TNS is the use of nonsteroidal anti-inflammatory drugs (NSAIDs). (150)
84
Q
- How does mepivacaine compare with lidocaine with respect to its clinical use, duration of action, and incidence of TNS?
A
- Mepivacaine has similar clinical uses as lidocaine but is not effective topically, has a slightly longer duration of action, and a lower incidence of TNS. (150)
85
Q
- What is a potentially adverse effect of prilocaine that limits its use in clinical practice? What is the mechanism for this?
A
- Prilocaine can cause methemoglobinemia due to the accumulation of ortho-toluidine, an oxidizing metabolite, which converts hemoglobin to methemoglobin. (150)
86
Q
- What are some uses of bupivacaine in current clinical practice?
A
- Bupivacaine is used for peripheral nerve blocks, spinal anesthesia, and epidural anesthesia. (150)
87
Q
- How does bupivacaine compare to lidocaine when used for epidural anesthesia?
A
- Bupivacaine provides a longer duration of sensory anesthesia with relatively less motor blockade, which is advantageous for labor epidurals and postoperative pain management. (150)
88
Q
- How does bupivacaine compare to lidocaine with respect to its cardiotoxic effects? What is the mechanism for this?
A
- Bupivacaine is more cardiotoxic than lidocaine; it exhibits a ‘fast-in, slow-out’ effect on sodium channels in ventricular myocytes, leading to prolonged blockade during diastole, which can cause conduction abnormalities and decreased contractility. (151)
89
Q
- What is an enantiomer?
A
- Enantiomers are stereoisomers that are non-superimposable mirror images of each other; they have identical physical properties except for the direction in which they rotate plane-polarized light. (151)
90
Q
- What is an advantage of ropivacaine and levobupivacaine over bupivacaine for epidural anesthesia?
A
- Ropivacaine and levobupivacaine, being single enantiomers, are associated with less cardiotoxicity and less motor blockade compared to racemic bupivacaine. (151)
91
Q
- What are some clinical uses and a potential risk of topical local anesthesia?
A
- Topical local anesthesia is used for skin procedures and needle-related procedures in children, but there is a risk of systemic toxicity due to rapid mucosal absorption if overdosed. (151)
92
Q
- Which local anesthetics are in eutectic mixture of local anesthetics (EMLA) cream?
A
- EMLA cream contains a eutectic mixture of lidocaine 2.5% and prilocaine 2.5%. (152)
93
Q
- What are some clinical uses and a potential risk of tumescent local anesthesia?
A
- Tumescent local anesthesia is used in plastic and cosmetic procedures; a potential risk is systemic toxicity due to the large total dose administered. (152)
94
Q
- After the administration of lidocaine tumescent anesthesia, when does the plasma concentration of lidocaine peak?
A
- Plasma concentrations of lidocaine after tumescent anesthesia typically peak around 12 hours post-injection. (152)
95
Q
- What are some clinical uses of systemic local anesthesia?
A
- Systemic local anesthesia (e.g., IV lidocaine infusions) is used as an analgesic adjuvant for postoperative pain management and in some patients with neuropathic pain for extended pain relief. (152)
96
Q
- What are some potential causes of local anesthesia failure?
A
- Causes include technical errors (e.g., improper needle placement), incorrect understanding of neuroanatomy, diminished efficacy in infected or inflamed tissue (due to acidosis, edema, hyperemia), and rapidly developing tolerance (tachyphylaxis). (152)
97
Q
- What are some techniques that can be used to confirm proper needle placement when administering local anesthetic for epidural anesthesia and peripheral nerve blocks?
A
- Techniques include ultrasound guidance, nerve stimulation (e.g., Tusi’s technique), transduction of epidural space pressure waves, and fluoroscopy. (152)
98
Q
- What are some risk factors for developing tachyphylaxis to local anesthetics?
A
- Repeated dosing and prolonged infusions are risk factors for developing tachyphylaxis. (152)
99
Q
- What is a potential adverse effect of developing tachyphylaxis to local anesthetics, and how can this be minimized?
A
- A potential adverse effect is hyperalgesia, which can be minimized by coadministering antihyperalgesic drugs or other centrally acting analgesics. (152)
100
Q
- What is the mechanism by which chronic pain alters the patient’s response to local anesthetics?
A
- Chronic pain may alter sodium channel expression and electrophysiology in peripheral nerves, often requiring higher doses or coadministration of additional analgesics to achieve effective blockade. (153)
