LOCAL ANESTHETICS A 47-year-old woman presented to the undergraduate teaching clinic in need of simple restorative work and an upper partial denture. The patient has no medical history of self-reported allergy to drugs or other compounds. Simple restorative procedures were commenced in the left maxillary region under latex dam following placement of local anesthesia. 1) Which of the following drugs are suitable for local infiltration anesthesia for dental procedure? (A) Cocaine (B) Lidocaine (C) Procaine (D) Nitrous oxide (E) Morphine Answer 1. True answer is (B). Local anesthesia in our patient was achieved by administration of 1 ml of XYLESTESIN-A (lidocaine + adrenaline), a recommended anesthetic for routine dental procedures. A 45 min anesthesia produced by this combination was sufficient and well tolerated by the patient.
2. Properties of local anesthetics include all of the following EXCEPT (A) Blockade of voltage-dependent sodium channels (B) Preferential binding to resting channels (C) Slowing of axonal impulse conduction (D) An increase in membrane refractory period (E) Effects on vascular tone Answer 2. Local anesthetics bind preferentially to sodium channels in the open and inactivated states. Recovery from drug-induced block is 10-1000 times slower than recovery of channels from normal inactivation. Resting channels have a lower affinity for local anesthetics. The answer is (B). 3. The pKa of lidocaine is 7.9. In infected tissue at pH 6.9, the fraction in the ionized form will be (A) 1% (B) 10% (C) 50% (D) 90% (E) 99% Answer 3. Since the drug is a weak base, it will be more ionized (protonated) at pH values lower than its pKa. Since the pH given is 1 log unit lower (more acid) than the pKa, the ratio of ionized to nonionized drug will be approximately 90:10. The answer is (D). 4. Which of the following statements about nerve blockade with local anesthetics is most correct? (A) Block is faster in onset in infected tissues (B) Block is faster in onset in unmyelinated fibers (C) Block is slower in onset in hypocalcemia
(D) Block is faster in onset in hyperkalemia (E) Block is slower in onset in the periphery of a nerve bundle than in the center of a bundle Answer 4. Smaller-diameter nerve fibers are more sensitive to local anesthetics and are blocked more rapidly than those of larger size. As the local concentration of drug declines during recovery from local anesthesia, smaller fibers continue to be blocked and are the last to recover. The answer is (B). 5. The most important effect of inadvertent IV administration of a large dose of an amide local anesthetic is (A) Bronchoconstriction (B) Hepatic damage (C) Nerve damage (D) Renal failure (E) Seizures Answer 5. Of the effects listed, the most important in local anesthetic overdose (of both amide and ester types) concern the CNS. Such effects can include sedation or restlessness, nystagmus, convulsions, coma, and respiratory depression. Diazepam is used for seizures caused by local anesthetics, usually without significant effects on ventilation or circulation. The answer is (E). 6. Factors that influence the action of local anesthetics include all of the following EXCEPT (A) Blood flow through the tissue in which the injection is made (B) Use of vasoconstrictors (C) Activity of acetylcholinesterase in the area (D) Amount of local anesthetic injected (E) Tissue pH Answer 6. The ester group of ester-type local anesthetics is hydrolyzed by plasma (and tissue) pseudocholinesterases. These drugs are poor substrates for acetylcholinesterase; the activity of this enzyme does not play a part in terminating the actions of local anesthetics. Individuals with genetically based defects in pseudocholinesterase activity are unusually sensitive to procaine and other esters. The answer is (C). 7. You have a vial containing 4 mL of a 2% solution of lidocaine. How much lidocaine is present in 1 mL? (A) 2 mg (B) 8 mg (C) 20 mg (D) 80 mg (E) 200 mg Answer 7. The fact that you have 4 mL of the solution of lidocaine is irrelevant. A 2% solution of any drug contains 2 g per 100 mL. The amount of lidocaine in 1 mL of a 2% solution is thus 0.02 g, or 20 mg. The answer is (C). 8. Which one of the following statements about the toxicity of local anesthetics is most correct?
(A) Serious cardiovascular reactions are more likely to occur with procaine than with bupivacaine (B) Cyanosis may occur following injection of large doses of lidocaine, especially in patients with pulmonary disease (C) Intravenous injection of local anesthetics may stimulate ectopic cardiac pacemaker activity (D) In overdosage, hyperventilation (with oxygen) is helpful to correct acidosis and lower extracellular potassium (E) Most local anesthetics cause vasoconstriction Answer 8. Acidosis due to tissue hypoxia favors local anesthetic toxicity because these drugs bind more avidly (or release less rapidly) from the sodium channel binding site when they are in the charged state. (Note that onset of therapeutic effect may be slower because charged local anesthetics penetrate the membrane less rapidly; see text.) Hyperkalemia depolarizes the membrane, which also favors local anesthetic binding. Oxygenation reduces both acidosis and hyperkalemia. The answer is (D). 9. Epinephrine added to a solution of lidocaine for a peripheral nerve block will (A) Increase the risk of convulsions (B) Increase the duration of anesthetic action of the local anesthetic (C) Both (A) and (B) (D) Neither (A) nor (B) Answer 9. Epinephrine will increase the duration of a nerve block when it is administered with short- and medium-duration local anesthetics. As a result of the vasoconstriction that prolongs the duration of this block, less local anesthetic is required, so the risk of toxicity, eg, a convulsion, is reduced. The answer is (B). 10. A child requires multiple minor surgical procedures in the nasopharynx. Which of the following drugs has high surface activity and vasoconstrictor actions that reduce bleeding in mucous membranes? (A) Benzocaine (B) Bupivacaine (C) Cocaine (D) Lidocaine (E) Procaine (F) Ropivacaine (G) Tetracaine Answer 10. Cocaine is the only local anesthetic with intrinsic vasoconstrictor activity. It also has significant surface activity and is favored for head, neck, and pharyngeal surgery. Cocaine is an ester. The answer is (C). 11. A 24-year-old woman was given an epidural anesthetic for pain relief during labor. The drug selected had a slower onset and a longer duration of action than any of the other local anesthetics. Unfortunately, some of the drug was inadvertently injected intravenously and caused a marked drop in blood pressure and an arrhythmia. The drug was most likely (A) Benzocaine (B) Bupivacaine
(C) Cocaine (D) Lidocaine (E) Procaine (F) Ropivacaine (G) Tetracaine Answer 11. You should be able to identify this drug as bupivacaine from its long duration of action. Unlike lidocaine, the actions of bupivacaine on cardiac cells occur in the normal heart. Accidental intravenous administration of bupivacaine may lead to arrhythmias and cardiovascular collapse. The answer is (B). 12. This drug has very poor surface activity, a short duration of action, and an ester structure. (A) Benzocaine (B) Bupivacaine (C) Cocaine (D) Lidocaine (E) Procaine (F) Ropivacaine Answer 12. Procaine is an ester with short duration of action and negligible surface activity. The answer is (E).
Local anesthetics in dentistry Duration of action (min) Maxillary infiltration Inferior alveolar block Pulp Soft tissue Pulp Soft tissue 60 190 90 230 40 60 50 25 40 20 340 170 130 90 140 105 240 85 75 40 60 55 440 190 185 165 220 190
Formulation Articaine 4% with epinephrine 1:100,000 or 1:200,000 Bupivacaine 0.5% with epinephrine 1:200,000 Lidocaine 2% with epinephrine 1:50,000 or 1:100,000 Mepivacaine 2% with levonordefrin 1:20,000 Mepivacaine 3% plain Prilocaine 4% with epinephrine 1:200,000 Prilocaine 4% plain
Skill Keeper: Cardiac Toxicity of Local Anesthetics Sodium channel blockers, eg, local anesthetics, bind more readily to open inactivated sodium channels. Hyperkalemia depolarizes the resting membrane so more sodium channels are in the inactivated state. (Conversely, hypercalcemia to hyperpolarize the resting potential and reduces the block of sodium channels.).