Nociception or pain perception is __________. A. the sensory detection of noxious events in the CNS B. transduction of noxious events to the CNS C. neuronal transmission of noxious events to the CNS D. All of the above. Which of the following are noxious stimuli that affect “high-threshold” primary afferent sensory neurons or nociceptors? A. Intense mechanical stimuli B. Intense thermal stimuli C. Chemical activators D. All of the above. Which of the following are chemical activators of nociceptors? A. Ischemia- and inflammation-associated protons. B. Cellular injury-associated extracellular ATP. C. Tissue damage- and inflammation-associated kinins. D. All of the above. Which of the following statements associated with the kinins (bradykinin) is correct? A. Kinins directly excite primary afferent fibers. B. Activation of Gs-protein-coupled bradykinin B2 receptors promote prostaglandin PGE2 synthesis. C. PGE 2 increases the sensitivity of primary afferent sensory neurons to chemical activators. D. All of the above. Which of the following statements is correct with reference to the activation of peripheral sensory neurons? A. Activation of peripheral sensory terminals by noxious stimuli leads to intracellular sodium and calcium ion influx and neuronal depolarization. B. Membrane depolarization leads to action potential generation if the activation threshold of voltage-sensitive sodium channels is reached. C. Four types of voltage-sensitive sodium channels are expressed in primary afferent sensory fibers and two of these only respond to high-threshold peripheral stimuli. D. All of the above. Which of the following statements is correct with reference to neuronal transmission in the trigeminal nucleus? A. Incoming action potentials activate pre-synaptic voltage-sensitive calcium channels. B. Calcium ion influx into the primary sensory neuron terminal leads to synaptic release of glutamate. C. Glutamate receptor activation leads to action potential generation in secondary relay neurons. D. All of the above. Which of the following statement is correct with respect to secondary or tertiary afferent neurons? A. Secondary afferent neurons project to the thalamus where they synapse with tertiary afferent neurons. B. Tertiary afferent neurons project to the somatosensory cortex, which is responsible for the localization of pain. C. Tertiary afferent neurons project to the limbic system, which is responsible for the emotional aspects of pain. D. All of the above. Pain arising slowly after injury, which is perceived as burning, aching, dull, poorly localized, and persistent, i.e., second pain, is most likely due to the activation of __________. A. A-delta fibers B. C fibers C. B fibers D. A-gamma fibers Pain arising rapidly after tissue injury, which is perceived as sharp, bright, well-localized, but not particularly persistent, i.e., first pain, is most likely due to the activation of __________. A. A-delta fibers B. C fibers C. B fibers D. A-gamma fibers Which of the following statements is correct with respect to homeostatic mechanisms in excitable neuronal cells? A. Excitable neuronal cells maintain a chemical gradient with high extracellular sodium concentrations. B. Excitable neuronal cells maintain a chemical gradient with high intracellular potassium concentrations. C. The inside of neuronal cells is electronegative (-50 to -90 mV) and the outside is electropositive. D. All of the above. Which of the following statements is correct with respect to the ionic disequilibrium associated with action potential generation? A. Nociceptive signals alter the distribution of sodium and potassium ions and briefly reverse electrical polarity, which leads to neuronal membrane depolarization. B. If the threshold for activation of voltage-gated sodium channels is reached, sodium ions flow into the cell and an action potential is generated. C. Following inactivation of voltage-gated sodium channels, Na/K ATPase pumps sodium out of the cells and the leak of potassium ions through passive ion channels restore the resting membrane potential. D. All of the above. Which of the following statements is correct with respect to the mechanism of action of local anesthetic agents (LAs)? A. LAs reduce the amplitude and conduction velocity of action potentials in a reversible, concentration-dependent manner. B. The site of action of LAs is the voltage gated-sodium channels, which are integral membrane proteins. C. To gain access to their receptors, LAs must diffuse across lipophilic neuronal membranes at the site of administration. D. All of the above. All of the following statements related to the ability of LAs to cross biological membranes are correct EXCEPT which one? A. LAs cross biological membranes by passive diffusion. B. Since LAs are weak bases, in an aqueous environment they exist as a mixture of protonated or positively charged (ionized) and deprotonated or neutral (unionized) molecules. C. The ratio of ionized to unionized forms of a LA is predicated on its dissociation constant or pKa and the pH of the drug’s milieu, i.e., the environment at the site of drug administration. D. When lidocaine with a pKa of 7.9 is deposited into an infected/inflamed site with a pH less than 7.9, more than 50% of its molecules become unionized. Which of the following statements is correct with respect to the mechanism of action of local anesthetic agents (LAs)? A. LAs consist of an aromatic group connected by either an ester- or amide-linkage to an aliphatic chain, which contains a secondary or tertiary amine group. B. Agents that have an ester-linkage connecting the aromatic group to the amine group are referred to as ester or aminoester LAs. C. The structural components of LAs affect their potency, onset of action, and duration of action. D. All of the above. The rate of absorption of LAs into the systemic circulation is determined by __________. A. the vascularity of the injection site, i.e., the density of capillaries B. physiochemical properties of LAs, i.e., lipid solubility, pKa, inherent vasoactivity C. the presence of a vasoconstrictor D. All of the above. Which of the following statements is correct relative to the volume of distribution (Vd) of LAs? A. The degree of tissue uptake of a LA is expressed as its Vd. B. LAs with lower plasma protein-binding and greater lipid solubility have a greater Vd. C. The Vd of a LA is the primary determinant of its elimination half-life or T 1/2β D. All of the above. All of the following statements are correct with respect to the metabolism of LAs EXCEPT which one. A. The metabolism of aminoamide-type LAs takes place primarily in the liver by cytochrome P450 isoenzymes CYP3A4 and CYP1A2. B. With some exceptions, the excretion of metabolites and any unchanged LA takes place in the kidneys. C. Prilocaine is unique in that it contains a thiophene-based nucleus and is rapidly inactivated via hydrolysis by plasma carboxyesterase. D. As a general rule, aminoamide-type LAs require 5 half-lives, i.e., T 1/2β x 5, for systemic clearance. While the vehicle of LAs is sterile water, formulations may contain __________. A. citric acid, an antioxidant; and edetate calcium, a stabilizer B. sodium chloride to produce isotonicity C. sodium hydroxide and/or hydrochloric acid to adjust the pH D. All of the above. Which of the followings statements related to vasoconstrictors in LAs is correct? A. Vasoconstrictors cause vascular smooth muscle contraction at the site of LA administration, slow the rate of LA absorption into the systemic circulation, and enhance the duration of local anesthetic action. B. To minimize oxidation of the vasoconstrictor, sodium or potassium metabisulfite is included in LA formulations containing a vasoconstrictor. C. Epinephrine 1:100,000 is physiologically equivalent to levonordefrin 1:20,000. D. All of the above. All of the following statements relative to a LA’s potency are correct EXCEPT which one? A. Lipid solubility, which is a function of the aromatic group, affects the ability of LAs to pass through biological membranes. B. As lipid solubility increases, the partition of drugs through the neuronal membrane decreases. C. The primary determinant of a LA’s potency is its partition coefficient. D. The relative potencies of LAs are reflected by their concentrations in aqueous formulations. All of the following statements relative to a LAs onset of action are correct EXCEPT which one? A. The amine group confers hydrophilicity and in aqueous solutions LAs exist as a mixture of protonated and deprotonated forms. B. The ration of protonated to deprotonated forms is predicated on the drug’s dissociation constant (pKa) and the pH of the environment. C. The closer is a LA's pKa to the pH at the site of its administration (physiologic pH of 7.4), greater is its fraction of protonated that can translocate across neuronal membranes. D. Since only the deprotonated form can translocate across neuronal membranes, the pKa is the primary determinant of a LAs onset of action. All of the following statements relative to a LA’s duration of action are correct EXCEPT which one? A. The receptor site for LAs, i.e., the voltage gated sodium channel, is an integral membrane protein. B. LAs with low protein-binding capacity bind more tightly and dissociate slowly from their receptor sites. C. A LA’s protein-binding capacity is the primary determinant of its duration of action. D. The duration of a LA’s action is also modulated by its lipid solubility, the dosage of the LA administered, vascularity of the injection site, and the presence of a vasoconstrictor in the formulation. In general, which of the following is the LA of choice, because of its longer duration of action, when the use of a vasoconstrictor is contraindicated? A. Lidocaine 2% plain B. Mepivacaine 3% plain C. Prilocaine 4% plain D. Mepivacaine 2% with levonordefrin 1:20,000 All of the following statements relative to LAs are correct EXCEPT which one? A. Infiltration anesthesia with lidocaine 2% w/epinephrine 1:50,000 may be useful to provide surgical hemostasis. B. Meta-analysis has shown that when administered by infiltration, articaine provides for a greater probability of achieving anesthesia in comparison to lidocaine. C. Articaine is the most cardiotoxic of all LAs. D. Bupivacaine has the greatest lipid solubility and the greatest protein-binding capacity; as a result, it produces the longest duration of pulpal anesthesia. Which of the following statements are correct with respect to bupivacaine when compared to other LAs? A. Bupivacaine should be used with caution in the elderly and the debilitated to minimize self-mutilation. B. The use of bupivacaine is not recommended for pediatric patients younger than 12 years of age. C. Bupivacaine is the most cardiotoxic of all LAs. D. All of the above. A practical approach to determine the dosage of LAs in healthy adults is based on weight, e.g., milligram of drug per pound of body weight; however, if a patient weighs ≥150 lbs. no more than the maximum recommended dose (MRD) should be administered. A. True B. False Although there are many rules and formulae, manufacturer’s recommendations provide a reasonable approach to calculating pediatric dosages. A. True B. False All of the following statement related to technical issues, storage, and sterilization/disinfection of LA cartridges are correct EXCEPT which one? A. Both the plunger and the diaphragms of LA cartridges contain rubber (latex). B. Cartridges of LAs should be stored at room temperature, i.e., about 25°C (77°F). C. Cartridges of LAs should be sterilizer or immersed in chemical disinfectants before use. D. Leakage from a LA cartridge may also result when using a badly worn syringe, an aspirating syringe with a bent harpoon, a syringe not intended to take 1.8 mL cartridges. Technical issues related to the administration of LAs that modulate the efficacy of intraoral topical anesthetic agents to reduce needle-insertion pain include __________. A. needle gauge B. depth of needle placement C. needle contact with periosteum D. All of the above. Which of the following statements is correct with respect to phentolamine mesylate for the reversal of soft-tissue anesthesia? A. Phentolamine mesylate is a non-selective α 1-adrenergic-receptor antagonist. B. Studies concluded that phentolamine mesylate administered at the same volume and at the same site as a LA with a vasoconstrictor significantly and safely reduces the duration of soft-tissue anesthesia and associated functional deficits. C. The use of phentolamine mesylate is not approved by the FDA in children under the age of 6 years or in children who weigh less than 33 lbs. (15 kg). D. All of the above. Which of the following statements is correct with respect to local toxicity of LAs? A. LA-induced epithelial and vascular reactions may include edema, desquamation, and ischemic necrosis; myotoxicity may manifest as acute pain and trismus. B. Most cases of LA-induced neurotoxicity manifest as anesthesia or paresthesia of the lip, tongue, and other oral tissues and may take 2 to 6 months to resolve. C. The reported incidence of permanent paresthesia following mandibular nerve block is significantly higher with 4% LA formulations. D. All of the above. Which of the following statements is correct with respect to LA-associated CNS toxicity? A. CNS effects of LAs may be excitatory and/or depressant in nature. B. The excitatory manifestations may be brief or absent. C. The depressant effect may progress from drowsiness to unconsciousness, to respiratory depression, and finally, to respiratory arrest. D. All of the above. Which of the following settlements is correct with respect to LAs’ cardiovascular toxicity? A. Signs and symptoms of depressed cardiovascular function may be the direct effect of LAs, which depress cardiac conduction, excitability, and contractility. B. Signs of reduced cardiac output include sweating, faintness, altered mentation, bradycardia, hypotension, progressive cerebral hypoxia, and seizures. C. With high plasma concentration of LAs, cardiovascular toxicity may progress to ventricular arrhythmias, atrioventricular block, and cardiac arrest. D. All of the above. All of the following statements are correct with respect to LA-induced allergic reactions EXCEPT which one? A. A breakdown product of ester-type LAs, para-aminobenzoic acid (PABA), is capable of sensitizing lymphocytes or eliciting the formation of IgE antibodies. B. True allergy to amide-type LAs is rare, but cross sensitivity among members of amide-type LAs is common. C. LAs formulated with a vasoconstrictor contain metabisulfite may precipitate an allergic reaction in susceptible patients. D. The prevalence of sulfite sensitivity in the general population is unknown, but sulfite sensitivity is seen more frequently in patients with asthma. Which of the following statements related to methemoglobinemia is correct? A. Methemoglobinemia is an uncommon idiosyncratic reaction most notably to prilocaine and topical benzocaine. B. Signs and symptoms of methemoglobinemia usually appear 3 to 4 hours after exposure to large doses and may include cyanosis, fatigue, weakness, nausea, sedation, seizures, and coma. C. Very young patients and those with congenital methemoglobinemia or glucose-6-phosphate deficiency are the most susceptible. D. All of the above. Which of the following statements is correct with respect to the use of vasoconstrictors in conjunction with LAs? A. It is generally accepted that a healthy adult can safely receive up to 0.2 mg of epinephrine. B. Vasoconstrictors must be avoided in patients under the influence of cocaine; in other clinical situations, the patient’s functional capacity should be the guide. C. Cardiac risk is association with noncardiac procedures is increased in patients unable to meet a 4-MET demand for oxygen. D. All of the above. Which of the following statements is correct with respect to the use of LAs during pregnancy? A. In 2014, the FDA amended its regulations governing the content and format of labeling for human prescription drugs and biological products. B. The amendment, which became effective on 30 June 2015, required the removal of the old pregnancy categories A, B, C, D, and X from all drug product labeling. C. Information about LA-related risks to the fetus and recommendations about the use of LAs during pregnancy can now be found in the new “Pregnancy” subsection of specific package inserts. D. All of the above. Which of the following statements is correct with respect to the use of LAs containing a vasoconstrictor during pregnancy? A. There is general concern that epinephrine may decrease uterine contraction and prolong labor; and that it may decrease uterine blood flow and fetal circulation. B. Bolus doses of epinephrine up to 0.1 mg do not prolong labor and in healthy pregnant women does not affect placental blood flow and fetal circulation. C. Investigators considered the addition of epinephrine to LAs beneficial for it reduced the dosage of LA required for pain relief. D. All of the above. Which of the following statements is correct with respect to the use of LAs and the nursing woman? A. In 2014, the FDA amended its regulations governing the content and format of labeling for human prescription drugs and biological products. B. The FDA requires the inclusion of a “Lactation” subsection in the package insert with information about LA-related risks to a breastfeeding child. C. The “Lactation” subsection of package insert makes recommendations on how to minimize drug exposure when a drug is administered to the mother. D. All of the above. All of the following statements related to LA-related drug-drug interactions are correct EXCEPT which one? A. The dosage of LA’s should be reduced in patients taking other CNS depressants as they are additive. B. Vasoconstrictors in LAs interact with tricyclic antidepressants, some β<sub>1</sub>-adrenergic receptor antagonists, and some general anesthetics. C. Vasoconstrictor-related drug-drug interactions may cause severe hypertension, cardiac arrhythmias, and cerebrovascular accidents. D. Evidence of drug-drug interactions between vasoconstrictors in LAs with antipsychotic agents and thyroid hormone is compelling.