Lippincott's Anesthesia Review: 1001 Questions and Answers
Chapter 6. Anesthetic Pharmacology
Mian Ahmad and Ashish Sinha
1. Correct statement about metabolism of drugs by the liver is
A. For drugs with low extraction ratio, liver blood flow is the rate-limiting step in their metabolism
B. For drugs with high extraction ratio, the capacity of the liver to metabolize the drug is the rate-limiting step
C. Cytochrome P450 system is highly drug-specific
D. Removal of the drug from the blood by hepatic clearance is directly proportional to hepatic blood flow and intrinsic clearance
2. When asked to describe the symptoms of her allergy to a local anesthetic that a 26-year-old female had at the dentist’s office, the patient describes a feeling of light-headedness, palpitations, and flushing. This reaction is most likely caused by
A. Methylparaben reaction
B. Vasovagal reaction
C. Para-aminobenzoic acid allergy
D. Epinephrine in the local anesthetic
3. All of the following drugs increase the mean arterial blood pressure, except
4. All of the following drugs increase cardiac output, except
5. In general, norepinephrine causes increase in all of the following, except
A. Mean arterial blood pressure
B. Heart rate
C. Cardiac dysrhythmias
D. Systemic vascular resistance
6. Stimulation of α2 receptors causes
7. Labetalol is relatively contraindicated for
A. Treatment of hypertension in aortic dissection
B. Treatment of hypertension in preeclampsia
C. Hypertensive emergencies after cardiac surgery involving second-degree heat block
D. Hypertension secondary to clonidine withdrawal
8. The best initial treatment for anaphylaxis during general anesthesia is
9. Compared with thiopental, etomidate causes
A. Less nausea
B. Increased seizure threshold
C. Greater myoclonic activity
D. Greater histamine release
10. Compared with propofol, ketamine causes
A. More depression of respiratory drive
B. More depression of airway reflexes
C. More bronchodilation
D. Less analgesia
11. A 65-year-old African American patient is undergoing laparoscopic repair of inguinal hernia under general anesthesia. He has a history of hypertension, diabetes, and depression. His medication list includes lisinopril, hydrochlorothiazide, metformin, and phenelzine. Intraoperative hypotension develops secondary to injury to inferior epigastric artery. Which of the following medications is relatively contraindicated to treat this hypotension?
12. True statement regarding flumazenil is
A. It binds irreversibly with benzodiazepine receptor
B. It causes hypertension and tachycardia
C. It has a shorter duration of action than midazolam
D. It reverses opioid-induced respiratory depression
13. Midazolam can be administered through all of the following routes, except
14. When sodium bicarbonate is added to lidocaine, more rapid onset of action of lidocaine occurs because of
A. Increased nonionized lidocaine concentration
B. Increased ionized lidocaine concentration
C. Decreased extracellular pH
D. Increased intracellular pH
15. Which of the following findings suggests current use of cocaine in a patient undergoing preoperative evaluation?
C. Pinpoint pupils
16. Which of the following local anesthetics is an ester?
17. Which of the statements among the following is true?
A. Ropivacaine is more potent than bupivacaine
B. Ropivacaine causes more motor than sensory block
C. Bupivacaine causes more vasoconstriction than ropivacaine
D. Ropivacaine is an S-enantiomer of bupivacaine
18. A 75-year-old patient is shivering and has chest pain in the recovery room following exploratory laparotomy for a rupture-obstructed hernia. His heart rate is 123/min, blood pressure is 200/100 mm Hg, and SpO2 is 97% on 2 L of oxygen via nasal cannula. An EKG shows ST-T wave changes, which are treated with nitroglycerine with no effect. Which of the following is the most appropriate next step?
A. Administration of hydralazine
B. Administration of nitroprusside
C. Administration of esmolol
D. Application of a warming blanket
19. Which of the following statements about the local anesthetics is false?
A. They are weak bases
B. They contain either ester or amide linkage
C. It is their charged form that interacts with the receptor
D. They bind the receptor inside the cell
20. Local anesthetics cause their effects by
A. Increasing the threshold potential
B. Altering the resting membrane potential
C. Increasing the rate of depolarization
D. Decreasing the rate of depolarization
21. Lipid solubility of local anesthetics
A. Generally correlates directly with the time to onset of action
B. Increases as the fraction of ionized form of the local anesthetic increases
C. Increases as the fraction of unionized form of the local anesthetic increases
D. May be different in in vivo or in vitro systems
22. Which is the correct expected duration of anesthesia after infiltration with the following local anesthetics?
60 to 120 minutes
120 to 240 minutes
120 to 180 minutes
120 to 180 minutes
23. Use of which of the following local anesthetics for spinal anesthesia is controversial?
The following three questions belong to this clinical situation:
During placement of an interscalene block utilizing 0.5% bupivacaine, a 62-year-old patient suddenly starts experiencing seizures and loses consciousness.
24. Which of the following statements regarding local anesthetic toxicity is correct?
A. Seizure is a sign of neurotoxicity from high dose of local anesthetic
B. Loss of consciousness is a sign of low-dose local anesthetic neurotoxicity
C. The seizure threshold is increased by the administration of thiopental
D. Seizure may have been caused by injection of the local anesthetic into cervical nerve root
25. Which of the following statements is false?
A. Seizure may have happened secondary to the injection of local anesthetic into vertebral artery
B. Loss of consciousness may be secondary to high epidural anesthesia
C. Loss of consciousness may be secondary to high spinal anesthesia
D. In general, decreased local anesthetic protein-binding decreases potential CNS toxicity
26. Which of the following statements is false?
A. Repeated attempts at aspiration would have prevented this complication
B. Addition of epinephrine to the local anesthetic may have helped to prevent this complication
C. Loss of consciousness means that patient has developed cardiac arrest
D. Amiodarone is the first line of treatment for cardiovascular toxicity caused by bupivacaine
27. During induction of anesthesia for cesarean delivery in a 22-year-old female, rocuronium is inadvertently substituted for succinylcholine. The neonate does not show any sign of muscle relaxation because rocuronium is
A. Highly protein bound
B. “Unaffected by ion trapping”
C. Lipid soluble
D. Highly ionized
28. All of the following can lead to hyperkalemic response to the administration of succinylcholine, except
A. Burn injury
B. Spinal cord injury
C. Prolonged ICU stay
D. Cerebral palsy
29. The dibucaine number in a patient having heterozygous type of plasma cholinesterase will be
A. 20% to 30%
B. 30% to 40%
C. 60% to 80%
D. 50% to 60%
30. Which of the following muscle relaxants is eliminated mostly by the kidneys?
31. The correct recommended intubating dose among the following muscle relaxants is
0.08 to 0.1 mg/kg
0.05 to 0.07 mg/kg
0.5 to 0.07 mg/kg
0.5 to 0.8 mg/kg
32. Which of the following drugs is able to cross the blood–brain barrier?
33. All of the following are side effects of anticholinesterase drugs, except
A. Excessive salivation
B. Increased bowel motility
34. Which of the following characteristics of electrical stimulation is the correct representation of the stimulus generated by the nerve stimulator used for monitoring the neuromuscular blockade?
A. Tetany: A sustained stimulus of 50 to100 Hz, usually lasting 2 seconds
B. Twitch: A single pulse 0.5 second in duration
C. Train of four: A series of four twitches in 2 seconds (2-Hz frequency), each 0.2 ms long
D. Double-burst stimulation: Three short (0.2 ms) high-frequency stimulations separated by a 30-ms interval and followed 1 second later by two or three additional impulses
35. Which of the following antibiotics augments the action of nondepolarizing muscle relaxants?
36. Immediately after induction of general anesthesia for hip replacement surgery, a 56-year-old patient with severe mitral stenosis and a normal ejection fraction develops a blood pressure of 70/35 mm Hg with a heart rate of 90 bpm. Which of the following is the most appropriate initial treatment?
37. Mechanism of action of droperidol involves antagonism at all of the following receptors, except
38. Which of the following is not seen in acute cyanide poisoning?
A. Metabolic acidosis
B. Cardiac arrhythmias
C. Tolerance to the antihypertensive effect of nitroprusside
D. Decreased mixed venous oxygen saturation
39. Which of the following medications is associated with extrapyramidal effects?
40. Which of the following medications should be discontinued before the elective surgery?
B. Monoamine oxidase inhibitors
41. Administration of magnesium sulfate for preeclampsia results in a decreased dose requirement for each of the following, except
42. Benefits of epinephrine 1:200,000 added to lidocaine for an epidural injection include all of the following, except
A. Prolongation of duration of action of lidocaine
B. Better quality of block
C. Prophylactic treatment of hypotension associated with the bolus administration of lidocaine
D. Delayed absorption into systemic circulation, thereby decreasing probability of local anesthetic toxicity
43. Which of the following choices is correct regarding the blood gas partition coefficient?
A. Nitrous oxide 0.47
B. Desflurane 0.62
C. Isoflurane 2.4
D. Sevoflurane 0.85
44. The use of neostigmine to reverse residual neuromuscular block may slow the metabolism of which of the following drugs administered subsequently?
45. A 45-year-old patient with history of hypertrophic subaortic cardiomyopathy becomes hypotensive. Which of the following drugs is most appropriate for treatment of hypotension?
46. Factors that contraindicate ketorolac administration include all of the following except
A. Renal insufficiency
B. Factor VIII deficiency
C. Active peptic ulcer disease
D. Daily ingestion of aspirin
47. After receiving massive blood transfusion, a patient anesthetized with isoflurane, fentanyl, and nitrous oxide develops acute pulmonary edema. The drug most likely to help him acutely is
48. A 22-year-old college athlete with a history of prolonged QT syndrome presents for an inguinal hernia repair. Which of the following agents would be least likely to further lengthen the QT interval?
49. Which of the following statements concerning naloxone is true?
A. Elimination half-life is longer than most of the μ-receptor opioids
B. It has mixed agonist–antagonist activity
C. It relieves opioid-induced spasm of the sphincter of Oddi
D. It does not cross the placenta
50. Which of the following drugs is most likely to cause tachycardia?
51. Addition of fentanyl to epidural bupivacaine will cause
A. No change in duration of analgesia
B. More rapid onset of analgesia
C. Increased vagal activity
D. Increased sensory block
52. Compared with sufentanil, alfentanil is characterized by
A. Higher pKa
B. Larger unionized fraction at physiologic pH
C. Less protein-binding
D. Greater lipid solubility
53. An inhaled anesthetic has blood/gas partition coefficient of 14.8. Recovery time primarily depends on
A. Oil/gas solubility of the agent
B. Cardiac output
C. Duration of administration
D. MAC of the drug
54. Nitroprusside therapy for hypertension should be discontinued in the presence of
A. Acute myocardial infarction
B. Increasing metabolic acidosis
C. Mitral regurgitation
D. Renal failure
55. A 24-year-old man is apprehensive of general anesthesia and prefers a regional anesthetic. Decision is made to conduct spinal anesthesia for the repair of inguinal hernia along with midazolam and fentanyl to allay anxiety. During the procedure, he suddenly loses consciousness. There is profound hypotension with systolic blood pressure of 44 mm Hg and a heart rate of 28 bpm. Cardiopulmonary resuscitation is started. The next most appropriate intervention is administration of
56. The effect of gentamycin at the neuromuscular junction is
A. Prevented by pretreatment with magnesium
B. Potentiated by anticholinesterases
C. Decreased by depolarizing relaxants
D. Partially reversed by calcium
57. Compared with lorazepam (Ativan), midazolam (Versed)
A. Has a shorter elimination half-life
B. Has more rapid clearance
C. Has a larger volume of distribution
D. Undergoes slower hepatic metabolism
58. The drug that causes dose-dependent EEG evidence of both central nervous system excitation and depression is
59. Normal pseudocholinesterase
A. Is produced primarily at nerve terminals
B. Is antagonized by acetyl cholinesterase
C. Resists dibucaine inhibition more than atypical pseudocholinesterase
D. Metabolizes succinylcholine by Hofmann elimination
60. Succinylcholine has prolonged action in patients carrying homozygous pseudocholinesterase. Which of the following best explains this phenomenon?
A. Diffusion away from the neuromuscular junction is slow
B. Hepatic clearance of succinylcholine is reduced
C. Succinylmonocholine induces neuromuscular block
D. An increased proportion of succinylcholine reaches the neuromuscular junction
61. Opioid analgesics cause all of the following effects except
A. Contraction of smooth muscle of the gallbladder
B. Contraction of detrusor muscle of the urinary bladder
C. Depress cellular immunity
D. Delayed gastric emptying
62. Opioids may have more pronounced action in all of the following except
A. In men compared to women
B. In older than in younger patients
C. During liver transplant surgery
D. In kidney failure
63. Which of the following drugs decreases lower esophageal sphincter tone?
64. A 28-year-old burn patient needs daily wound debridement. Which of the following agents is not appropriate to provide a short duration of anesthesia?
A. Nitrous oxide
65. Eutectic mixture of local anesthetics (EMLA cream) is sometimes used to numb the skin before attempting an intravenous access in pediatric patients. Which of the following local anesthetics is combined with prilocaine to produce this cream?
66. A 76-year-old man with history of hypertension and cancer of the colon had colectomy under general anesthesia 24 hours ago. He is receiving an epidural infusion of fentanyl at the rate of 100 micro symbol g/h. Which of the following is least likely?
C. Respiratory depression
67. Which of the following may help in mapping of a seizure focus under general anesthesia by enhancing the EEG activity or inducing the seizure?
68. Which of the following anesthetic agents is contraindicated for use in patients with intermittent porphyria?
69. Replacing 10 mg of morphine with 30 mg of ketorolac can increase the risk of
A. Respiratory depression
70. The minimum anesthesia concentration (MAC) of desflurane is decreased by
A. Chronic alcohol use
B. Respiratory alkalosis
C. Chronic anemia with hemoglobin of 7.5 gm/dL
D. Hypothermia to 34°C
71. A 45-year-old woman has been using heroin for last 20 years. Use of which of the following drugs will cause acute withdrawal symptoms?
72. Ketamine administered in anesthetic doses
A. Decreases intracranial pressure
B. Causes respiratory depression
C. Is metabolized by the liver
D. Increases bronchomotor tone
73. Which of the following drugs is the most appropriate agent for acute treatment of hypertension in a preeclamptic patient?
74. Which of the following provides the best estimate of complete reversal of neuromuscular blockade?
A. Double-burst ratio of 1
B. Train-of-four-ratio of 1
C. Absence of fade on tetanic stimulation at 50 Hz
D. Absence of fade of single twitch
75. Which of the following is contraindicated in a patient with Guillain–Barré syndrome?
A. Intrathecal opioids
B. Nondepolarizing muscle relaxant
C. Epidural local anesthetics
76. Which of the following drugs is the most appropriate for management of anesthesia in a patient who needs emergency surgery and admits to using cocaine in last 3 hours?
A. Labetalol before induction
B. Ketamine for induction
C. Propofol for induction
D. Ephedrine for treatment of hypotension
77. During general anesthesia, which of the following agents is most appropriate to treat an acute episode of cyanosis in a child with tetralogy of Fallot?
D. 100% oxygen
78. Rebound hypertension is most likely after sudden discontinuation of which of the following classes of antihypertensive drugs?
A. Thiazide diuretics
B. Calcium channel blockers
D. Angiotensin-converting enzyme inhibitors
79. A 65-year-old man has nausea and vomiting in the post–anesthesia care unit, needing antiemetic therapy. He develops involuntary facial movements, difficulty swallowing, and torticollis. Which of the following drugs is most likely to be the cause of these symptoms?
A. Promethazine (Phenergan)
B. Diphenhydramine (Benadryl)
C. Metoclopramide (Reglan)
D. Granisetron (Kytril)
80. Which of the following statements about ketamine is true?
A. Tolerance may develop after repeated administration
B. It is extensively bound to plasma protein
C. Primary site of action is GABA receptor
D. Kidney is the primary route of elimination
81. Which of the following statements about etomidate is most likely true?
A. It causes significant dose-dependent respiratory depression
B. It causes cerebral vasodilatation
C. It increases frequency of excitatory spikes on the EEG more than thiopental
D. Most of the administered dose is excreted unchanged by the kidney
82. The MOST likely analgesic mechanism of action of gabapentin for neuropathic pain is
A. Antagonism at the GABA receptor
B. NMDA receptor inhibition
C. Sodium channel blockade
D. Calcium channel modulation
83. Which of the following properties of local anesthetics is most likely a primary determinant of potency?
D. Lipid solubility
84. Which of the following statements about etomidate is most likely true?
A. It is water soluble at an acidic pH and lipid soluble at physiologic pH
B. It may be used as an infusion for sedation in the ICU
C. It is related to propofol in its chemical structure
D. Awakening from induction dose is secondary to very rapid liver metabolism
85. A 64-year-old man is scheduled for an open abdominal aortic aneurysm surgery. Anesthetic plan includes placement of an epidural catheter for postoperative pain relief. On review of his medication list, it is noted that he has been taking clopidogrel for a coronary artery stent that was inserted 2 years ago. Which of the following statements about clopidogrel is most likely true?
A. The American Society for Regional Anesthesia recommends that clopidogrel be stopped 3 days before neuraxial anesthesia
B. A single dose of clopidogrel may have a clinically significant effect on platelet function
C. Clopidogrel is associated with pancytopenia
D. Inhibition of platelet function by clopidogrel is reversible
86. Which of the following statements about ketamine is most likely true?
A. Analgesic efficacy of epidural ketamine is equivalent to epidural morphine
B. Ketamine decreases the duration of action of nondepolarizing neuromuscular-blocking drugs
C. Ketamine is a direct myocardial depressant
D. Ketamine decreases the cortical amplitude of somatosensory-evoked potentials
87. A patient has a history of an allergic reaction to a local anesthetic but does not recall the name. Which of the following local anesthetics will most likely be the cause of a true allergic reaction?
88. Which of the following is most likely the (analgesic) mechanism of action of lidocaine when used for neuropathic pain?
A. Inhibition of G-protein–coupled receptors
B. Antagonism of NMDA receptors
C. Calcium channel blockade
D. Sodium channel blockade
89. A 45-year-old farmer is brought into the emergency room. He is agitated and confused. On examination, he has dry skin with fever and rapid heart rate. Anticholinergic poisoning is suspected. Which of the following medications is most appropriate to treat his condition?
90. Which of the following medications will prolong the neuromuscular blockade produced by vecuronium?
91. The shorter duration of action of remifentanil compared with fentanyl is primarily due to its
A. Rapid redistribution
B. Renal elimination
C. Metabolism by esterases
D. Hepatic extraction ratio
92. Which of the following statements about dexmedetomidine is most likely true?
A. It has more α2 selectivity than clonidine
B. It can increase opioid-induced rigidity
C. Context-sensitive half time increases markedly after prolonged infusion of dexmedetomidine
D. It has no effect on systemic vascular resistance
93. Which of the following can precipitate an episode of myotonia in a patient with myotonic dystrophy?
A. Lidocaine administration
B. Neostigmine administration
C. Nondepolarizing neuromuscular-blocker administration
94. A 50-year-old woman had cholecystectomy done under general anesthesia. Rocuronium was used as muscle relaxant, and a combination of anticholinergic and anticholinesterase was used for reversal of muscle-relaxant action. The patient is now bradycardic. The combination of reversal agents most likely to cause the bradycardia is
A. Atropine and edrophonium
B. Glycopyrrolate and edrophonium
C. Atropine and neostigmine
D. Glycopyrrolate and neostigmine
95. A 68-year-old man is undergoing exploratory laparotomy for intestinal obstruction. Cause of obstruction is found to be an ileal carcinoid tumor. Suddenly, the patient develops bronchospasm, and the peak airway pressure increases from 24 to 45 cm of H2O. Which of the following is the best treatment for the bronchospasm in this situation?
96. A 15-year-old boy has severe gastroenteritis with nausea, vomiting, and diarrhea for last 3 days. A CT scan of the abdomen shows intussusceptions, which needs exploratory laparotomy for relief of intestinal obstruction. The patient’s systolic blood pressure is 78 mm Hg and heart rate is 112 bpm. Thiopental is selected as the induction agent for general anesthesia. A decreased dose of this agent is recommended in patients with hypovolemic shock primarily because
A. Delivery of the drug to the brain is increased
B. Hepatic clearance is decreased
C. Thiopental is a myocardial depressant
D. Thiopental is a vasodilator
97. A 75-year-old woman is scheduled for mitral valve repair. High-dose fentanyl is used to induce anesthesia. In order to counteract the bradycardia caused by fentanyl, pancuronium is administered. Pancuronium blocks the bradycardia caused by fentanyl by acting on which of the following?
A. β-Adrenergic receptors
B. Cardiac muscarinic receptors
C. Carotid baroreceptors
D. Central vagal nuclei
98. Which of the following medications would be most appropriate to treat symptomatic bradycardia 1 month after cardiac transplant?
99. Which of the following statements about propofol infusion syndrome is most likely false?
A. Mortality rate in an established case is very high
B. Rhabdomyolysis is one of the diagnostic criteria
C. Tachycardia is an early sign of this syndrome
D. Cardiac dysfunction is very common in this condition
100. A patient is undergoing resection of a supratentorial brain tumor. He is normocarbic, and his mean blood pressure is 70 mm Hg. Administration of which of the following is most likely to decrease cerebral blood volume?
A. Nitrous oxide at 0.5 minimum alveolar concentration (MAC)
B. Desflurane at 1 MAC
C. Thiopental 2 mg/kg
D. Phenytoin 15 mg/kg
101. Which of the following classes of drugs is most likely to be responsible for an anaphylactic reaction during general anesthesia?
A. Neuromuscular-blocking drugs
D. Radio contrast dyes
CHAPTER 6 ANSWERS
1. D. Clearance of drugs that are mainly metabolized in the liver is a function of the amount of drug brought into the liver by its blood flow multiplied by ability of the hepatocytes to clear the blood of that drug. For drugs that have a high extraction ratio, the liver removes the entire drug entering the liver in one pass. Lidocaine and propranolol are examples of this kind of clearance. Alfentanil, on the other hand, has a low extraction ratio, and liver blood flow does not really affect its clearance. Instead, it is the intrinsic ability of the liver to clear the blood of this drug that determines alfentanil’s clearance. Cytochrome P450 system can metabolize a wide variety of drugs by a single group of enzymes.
2. D. Many patients believe that they are allergic to local anesthetic. Questioning them about it is important; otherwise, options for safe delivery of anesthesia can get challenging. Dentists usually add epinephrine to the local anesthetic to decrease the bleeding associated with the dental procedure. If any epinephrine gets access to the vascular system, it can cause transient tachycardia and hypertension that patient may describe as palpitations, flushing, and dizziness. If labeled as an allergic reaction, it may limit anesthetic options for the patient in the future. In an emergent situation where a spinal anesthetic could have been possible, one may have to utilize general anesthesia and risk airway complications. It is important to elucidate the real allergic reaction for an elective case by subjecting the patient to allergy testing. Serum testing is available. Skin testing is not indicated because of the risks involved. Most of the allergic reactions observed with local anesthetics are not due to the local anesthetic molecule but either to para-aminobenzoic acid, a metabolite of ester local anesthetics, or to methylparaben and metabisulphite, which are both preservatives. True type 1 allergic reaction with local anesthetic is extremely rare but will present as anaphylaxis with hypotension and respiratory symptoms. Vasovagal response usually manifests as pale skin with very low heart rate and blood pressure. Although this patient did have light-headedness, she also had flushing and palpitation which is not consistent with vasovagal reaction.
3. D. Effect of sympathomimetic drugs on the mean arterial blood pressure is mediated through their effect on the adrenergic receptors they stimulate. Ultimate effect is generated through complex interaction of different factors based on baseline sympathetic tone, patient’s volume status, and condition of the heart. Although isoproterenol increases contractility through its action on β2 receptors, it also stimulates β1 receptors in big vascular beds like muscle, causing vasodilatation and decreasing the systemic vascular resistance. So despite increasing contractility of the heart and increasing the cardiac output, the mean arterial blood pressure can decrease with administration of this drug. Other medications increase the mean arterial blood pressure by their effect on α1 and β1 receptors.
4. D. All of these catecholamines cause stimulation of β1 receptors, thus increasing cardiac contractility, but norepinephrine also has a very strong effect on α1 receptors, thus increasing afterload to such a degree that cardiac output may actually decrease after administration of this drug.
Cardiac output = Systemic blood pressure/Systemic vascular resistance
According to this formula, systemic vascular resistance (SVR) is inversely related to cardiac output; thus, an increase in the SVR may decrease the cardiac output. Other drugs have more effect on cardiac contractility than on SVR, and thus, cardiac output increases with their administration.
5. B. Effect of norepinephrine is on α1 receptors and systemic vascular resistance, and thus on systemic mean arterial blood pressure may be so pronounced that there may be a decrease in heart rate secondary to baroreceptor response. It does increase the likelihood of cardiac dysrhythmias in the presence of some older anesthetics like halothane as well as in hypoxia and hypercarbia.
6. B. Stimulation of α2 receptors causes inhibition of release of norepinephrine, thus decreasing the activity of the sympathetic nervous system. Hypotension and bradycardia are side effects that sometimes limit the use of medications like clonidine and dexmedetomidine. In the past, these drugs were used mainly as antihypertensives, but applications based on their sedative, anxiolytic, and analgesic properties are becoming increasingly common. Dry mouth may also result from the use of dexmedetomidine.
7. C. Labetalol is a competitive antagonist at the α1 and β adrenergic receptors. It is a useful agent in the perioperative period because vasodilatation caused by α1 blockade is not accompanied with tachycardia with its attendant risks. It is a particularly useful drug in hypertensive patient with diagnosis of aortic dissection as it decreases the sheer force across the dissection. It does not cross the placenta and does not decrease the uterine blood flow even when patient is hypotensive, so it is used in obstetric patients with preeclampsia to control their blood pressure. Clonidine is a stimulant of α2 receptors, thus decreasing sympathetic activity, and its long-term administration leads to up regulation of adrenergic receptors. Sudden withdrawal of this medication leads to overactivity of the sympathetic system and a β-blocker antagonist is very helpful in controlling the manifestations of this overactivity. Abnormalities of cardiac conduction system are a relative contraindication to the administration of labetalol as it may worsen the degree of conduction blockade.
8. D. Although all of these medications may be useful in the event of anaphylaxis during a general anesthetic, epinephrine is considered to be the drug of choice and is indicated as the first line of treatment. Dose depends on the severity of the reaction and may be anywhere from 10 μg to 1 mg if cardiac arrest develops. Its α1 action counteracts the severe vasodilatation, which is the hallmark of this condition. Its β2 action helps treat bronchoconstriction while β1 action helps support the cardiac output. H1- and H2-blockers are also indicated in the treatment of anaphylaxis and help mitigate the effects of type 1 antigen antibody reaction on mast cells and other mediators, causing vascular dilatation and increased capillary permeability, but their actions are neither as rapid nor as profound as epinephrine. Steroids stabilize the cell membranes of mast cells and eosinophils, thus decreasing the intensity of the immunologic response, but their action takes 4 to 6 hours to develop, and there is little evidence to support the use of steroids for the acute treatment of anaphylaxis.
9. C. Etomidate actually causes a decrease in the seizure threshold, and is thus useful in cases of electroconvulsive therapy for severe depression. Spontaneous movements characterized as myoclonus occur in more than 50% of patients receiving etomidate and may be associated with seizure-like activity on the EEG. Another side effect is an increased incidence of nausea and vomiting in the postoperative period. It does not cause histamine release in contrast to thiopental, which has been shown to release histamine in vitro.
10. C. Ketamine differs from other induction agents used in contemporary practice of anesthesia in many important ways. Instead of acting directly on the reticular-activating system (RES), it causes dissociation of thalamus (which relays sensory information from the RES to cerebral cortex) from the limbic cortex (which is involved with the awareness of sensation). In sharp contrast to other anesthetic agents, it increases blood pressure, heart rate, and cardiac output by central stimulation of sympathetic system and inhibition of uptake of norepinephrine. In the same vein, its effect on the ventilator drive and airway reflexes is minimal, if any. It is an excellent bronchodilator and analgesic. Thiopental, propofol, and etomidate, on the other hand, may be anti-analgesic.
11. B. Phenelzine inhibits monoamine oxidase, an enzyme that metabolizes catecholamines, allowing their levels to build up in the adrenergic neurons. Ephedrine has both direct and indirect actions on adrenergic system. Indirect action involves release of exaggerated amounts of norepinephrine from the adrenergic neurons leading to catastrophic increase in blood pressure. More direct-acting medication like phenylephrine is a better choice in a patient using monoamine oxidase inhibitors.
12. A. Flumazenil is useful as a specific reversal agent for benzodiazepine overdose. It has minimal intrinsic activity on this receptor, but because of similarity in the chemical structure, it acts as a competitive antagonist in the presence of agonist at the receptor site. Duration of action is short (60–90 minutes), so repeated doses or infusion is required if recurrence of sedation is desired. Reversal of benzodiazepine action does not lead to cardiovascular side effects or evidence of acute stress response. It does not have any effect on opioid receptor, so is not useful to reverse respiratory depression caused by narcotic overdose.
13. C. Although most common route of administration of midazolam in anesthesia is intravenous, this drug can be given via many routes. Midazolam oral suspension is used routinely in pediatric anesthesia. Intramuscular injection can be painful, but intranasal route utilizing mucosal atomization device may be useful to treat seizure activity. Bioavailability of sublingual midazolam is much better than orally administered drug. Exposure of the acidic midazolam preparation to the physiologic pH of blood causes a change in the ring structure that renders the drug more lipid soluble, thus speeding its passage across the blood–brain barrier. There is no preparation available for transcutaneous delivery of this drug in comparison to fentanyl.
14. A. Since local anesthetics are weak bases, they exist largely in the ionic form, making it difficult for them to cross the cell membrane, thus delaying their local anesthetic action. Addition of sodium bicarbonate promotes nonionized fraction of local anesthetic, promoting more rapid onset of its action. Depending on the amount injected, the local pH may increase, but effect on the intracellular pH is minimal, if any.
15. B. Cocaine inhibits reuptake of catecholamines into preganglionic nerve terminal; it has a sympathomimetic effect, causing tachycardia, hypertension, pupillary dilatation, and increased skin temperature. Chronic use may lead to cardiomyopathy and depletion of catecholamine stores with unpredictable manifestations during anesthesia.
16. D. There are important differences between the two classes of local anesthetics. Ester local anesthetics are metabolized by plasma cholinesterase, and so patients with atypical variety of enzyme is liable to develop local anesthetic toxicity because of slow metabolism. They are metabolized to para-aminobenzoic acid (PABA), and individuals known to have allergy to this substance should not be given ester kind of local anesthetic. Commercial multidose preparations of amides often contain methylparaben, which has a chemical structure similar to that of PABA. This preservative may be responsible for most of the rare allergic responses to amide agents. Amide local anesthetics are metabolized by liver, and decreased liver blood flow or history of liver failure may lead to toxicity even when less-than-maximum-recommended dose is used. All of the local anesthetics included in this question have amide structure in their molecule, except cocaine.
17. D. Ropivacaine is less lipid soluble, and thus less potent than bupivacaine. For a given dose, the sensory block is more than the motor block. Part of the reason ropivacaine may be less cardio toxic than bupivacaine is that it causes vasoconstriction in the tissues, thus decreasing the rate of absorption into systemic circulation.
Enantiomers are stereoisomers that exist as mirror images. Enantiomers have identical physical properties except for the direction of the rotation of the plane of the polarized light. Ropivacaine is an S-enantiomer of mepivacaine and bupivacaine.
18. C. Oxygen demand of the myocardium increases with increase in heart rate and blood pressure. Esmolol will decrease both the heart rate and blood pressure rapidly, thus decreasing the oxygen demand. Hydralazine will decrease the blood pressure but may make the tachycardia worse. Same is true for nitroprusside. Shivering increases oxygen demand and needs to be treated promptly. Application of warming blanket may be effective if patient is hypothermic, but it may take a while for the body temperature to improve. It may not be effective in this patient if his temperature is normal and if the mechanism of shivering involves inhibition of thermoregulatory mechanisms of the body by the residual anesthetic.
Esmolol is a short-acting β-blocker that will decrease the heart rate and myocardial contractility through its inhibition of β1 receptors, thus decreasing the myocardial oxygen demand. Improved heart rate will also help with improved supply of oxygen to the myocardium by increasing the diastolic time during which most of the left-ventricular myocardium gets its oxygen.
19. C. Local anesthetics exert their electrophysiologic effects by blocking sodium ion conductance. This effect is primarily mediated by interaction with specific receptors that are within the inner vestibule of the sodium ion channel.
20. D. Local anesthetics decrease the rate of depolarization of the cell membrane when a nerve impulse arrives and changes the resting membrane potential of the neuron. Normally, this potential is −90 mV inside the cell. When an impulse reaches the cell, it increases the inflow of sodium into the cell, causing this potential to move toward a positive value. If this change is enough to reach a critical level called the threshold potential, an action potential is generated; otherwise, the impulse dies down. Local anesthetics decrease the rate of change of this potential so that it does not reach the threshold level. They do not change the threshold potential or resting membrane potential per se.
21. D. Lipid solubility of a local anesthetic is directly proportional to its potency. It is ordinarily expressed as a partition coefficient, which is determined by comparing the solubility in aqueous phase, generally water or buffered solution. Since the site of action of the anesthetic molecule is inside the nerve cell, higher the proportion of neutral base or the unionized form, higher the lipid solubility and higher the potency. Ionization makes it more resistant to enter the cell and decreases its potency.
It is important to appreciate that measures of anesthetic activity may be affected by the in vitro and in vivo system in which these effects are determined. For example, tetracaine is 20 times more potent than bupivacaine when studied in isolated nerve tissue but has equivalent potency compared with bupivacaine when tested in intact in vivo systems. The effect actually may vary even in different areas of the body like epidural space vs. peripheral nerve block because of secondary effects such as the inherent vasoactive properties of the anesthetic.
22. A. Infiltration of local anesthetic in peripheral tissues is different from injection into a nerve sheath for a peripheral nerve block. Duration of anesthesia after infiltration is much less than after a nerve block. Anesthesia after ropivacaine and bupivacaine lasts 4 to 8 hours, while lidocaine is effective only from 1 to 2 hours. Mepivacaine is in between with duration of action from 90 to 180 minutes.
23. D. Use of many local anesthetics for spinal anesthesia is still evolving. Lidocaine was introduced into clinical practice in 1946. It was commonly used for spinal anesthesia until reports of transient neurologic symptoms (TNS) started appearing in the literature. Incidence of TNS is relatively high with up to one-third of patients complaining of pain and dysesthesia 12 to 24 hours after the surgery. Although symptoms are transient, pain sometimes is so severe that it may exceed the pain of surgery and may necessitate readmission into the hospital. This issue has raised questions regarding the advisability of continued use of lidocaine for spinal anesthesia.
24. A. If central nervous system toxicity was to happen from slow absorption of local anesthetic or injection into a vein, symptoms are usually milder to begin and escalate finally to the seizure level. Early symptoms of local anesthetic toxicity may manifest as circumoral numbness, metallic taste in the mouth, and tremors. As the serum levels of the local anesthetic increase further, seizure may result due to excitation of some focus in the central nervous system. Further increase in these levels leads to depression of the nervous system manifesting as lethargy and coma.
Direct injection into a nerve usually causes a shooting pain along the length of the nerve with involuntary withdrawal of the limb in an awake patient, not a seizure. It is recommended to avoid performance of a nerve block under general anesthesia so that patient could point to this, and thereby avoidance of nerve injury. Treatment is supportive. Specific treatment for the seizure is either benzodiazepine or barbiturates that increase the seizure threshold. It is important to control the seizure because intense muscular activity increases oxygen utilization and carbon dioxide production, causing both metabolic as well as respiratory acidosis. If the dose of bupivacaine that gained access to vascular system is high, the major danger is cardio toxicity that is made much worse and is extremely difficult to treat in the presence of acidosis.
25. D. It is recommended that the needle used for interscalene block should be of appropriate length for the given patient. Nerve roots in this region are very superficial and if a longer needle is used, a medially directed needle may end up in either epidural or intrathecal space leading to high epidural or intrathecal block respectively. This usually presents as catastrophic hypotension, respiratory distress followed by cardiovascular collapse depending on the dose injected. Seizure is not a presentation of high epidural or intrathecal injection. Higher protein-binding decreases the chance of neurotoxicity by decreasing the free fraction of the drug available for absorption into the circulation.
26. D. Frequent attempts at aspiration are recommended whenever large dose and volume of local anesthetic is injected for epidural or peripheral nerve block to avoid injecting the local anesthetic in the vascular or intrathecal space. Cases of local anesthetic toxicity have been reported even when aspiration was negative for blood or CSF.
Addition of a dilute concentration of epinephrine to local anesthetic is helpful as it may alert the practitioner to inadvertent vascular injection of the local anesthetic by increase in the heart rate. It also helps delay the systemic absorption of local anesthetic, thus keeping the maximum serum concentration lower.
It is possible that loss of consciousness is secondary to cardiac arrest, but it may also be secondary to high-dose CNS toxicity, respiratory arrest, or high neuraxial anesthesia.
Amiodarone was the drug of choice to treat cardiovascular toxicity of bupivacaine in the past, but now 20% intralipid has replaced this drug. Recommended dosage for cardiovascular collapse secondary to bupivacaine toxicity is 1.5 mL/kg bolus, followed by 0.25mL/kg/min for the next 10 minutes. Oxygenation, ventilation, and good basic and advanced life support are extremely essential as bupivacaine toxicity is adversely affected by hypercarbia, acidosis, and hypoxia.
27. D. Neuromuscular-blocking drugs (NMBDs) are highly charged molecules because of the presence of a quaternary ammonium group in their structure. This makes them poorly lipid soluble so that they do not cross biologic membranes like blood–brain barrier, renal tubular epithelium, and placenta. Administration of these drugs thus does not produce central nervous system effects; renal tubular reabsorption is minimal, and maternal administration does not adversely affect the fetus. Issue of ion trapping can only develop if a drug gets trapped in the acidic environment of fetal blood after it has crossed the placenta.
28. D. Any time prolonged skeletal muscle inactivity or extensive muscle damage exists, patient may be susceptible to hyperkalemia after the administration of succinylcholine and is dependent on development of extrajunctional atypical receptors. In some patients, potassium levels may exceed 10 mEq/L. This can lead to serious cardiac arrhythmias and even cardiac arrest. The duration of susceptibility to the hyperkalemic response to succinylcholine is unknown but probably decreases after 3 to 6 months of denervation injury.
Although cerebral palsy seems to be a muscular problem, consensus is that it is safe to use succinylcholine for these patients if airway management will be facilitated by its use.
29. B. Atypical plasma cholinesterase lacks the ability to hydrolyze ester bonds in drugs such as succinylcholine and remifentanil. Diagnosis of presence of atypical enzyme can be made by measuring the ability of dibucaine, a local anesthetic, to inhibit the activity of this enzyme. A normal enzyme gets inhibited the most (80%), while atypical homozygous type is minimally inhibited (20%). Heterozygous variety has lesser inhibition.
In clinical terms, this leads to prolonged paralysis following administration of succinylcholine, with duration ranging from 5 to 10 minutes with normal enzyme to 60 to180 minutes for patients having homozygous atypical variety of enzyme.
30. D. Choice of the muscle relaxant for any given anesthetic depends on many factors like duration of surgical procedure, comorbidities of the patient, required speed of onset, route of elimination, duration of action, and associated side effects like tachycardia or hyperkalemia. Out of these factors, the duration of action depends on the dose, presence of associated conditions like hypothermia, concomitant use of drugs that influence the muscle relaxation like magnesium or calcium channels blockers, and the presence of hepatic or renal disease. Intermediate acting neuromuscular blockers like rocuronium and vecuronium undergo primarily hepatic metabolism and biliary excretion with minimal renal excretion (10%–25%).
Many of the long-acting neuromuscular blockers are excreted by the kidney, and their use in patients with renal failure may lead to prolonged neuromuscular blockade. Pancuronium is one of these long-acting agents, and 80% of its administered dose is excreted by the kidney. As discussed in the previous question, succinylcholine is metabolized by the plasma cholinesterase and only a fraction of the administered dose reaches the neuromuscular junction.
31. A. Onset and duration of action are largely dependent on the dose administered. Although smaller doses can be effective, the recommended intubating dose is usually two to four times higher than ED95. This provides a higher incidence of better and earlier intubating conditions than would be possible with ED95. Higher doses do lead to longer duration of action so that the return of the first twitch on train of four, a prerequisite before a reversal agent can be administered, is delayed.
32. A. Anticholinesterases are used to reverse the effects of nondepolarizing neuromuscular-blocking agents (NMBDs). Selection of these drugs depends on many factors. One of the considerations is the ability of the selected drug to cross the blood–brain barrier. As NMBDs do not cross the blood–brain barrier, there is no effect on the central nervous system. Using an anticholinesterase with only peripheral action thus makes sense because central nervous system side effects of a drug like physostigmine can be avoided. These effects can be very pronounced in elderly patients, leading to confusion and agitation in the recovery room. Neostigmine and pyridostigmine, with their quaternary ammonium structure and consequent inability to cross the blood–brain barrier, are thus preferred agents to reverse the actions of NMBDs than physostigmine which crosses that barrier readily. Same principle applies to anticholinergic agents that are administered along with anticholinesterase drug to counteract the surge of acetylcholine causing bradycardia. Atropine and scopolamine, with their tertiary character, may cross the blood–brain barrier and may cause central nervous system effects. Glycopyrrolate, on the other hand, has quaternary structure and lacks central nervous system effects and has largely replaced atropine for blocking the adverse muscarinic effects.
33. D. Administration of anticholinesterase agent leads to accumulation of acetylcholine, manifesting increased cholinergic actions in the body. Vagal stimulation causes bradycardia and, if not antagonized by concomitant administration of a cholinergic agent, may lead to cardiac standstill. Antisialagogue actions of these agents are also helpful in reducing the excessive salivation induced by parasympathetic overactivity of acetylcholine generated by inhibition of cholinesterase. Disruption of gastrointestinal anastomosis is another consideration, secondary to increased peristalsis of the bowel. Cholinergic activity may also lead to bronchospasm and not bronchodilation.
34. C. Impulses generated by the nerve stimulator are standardized to ensure uniformity of monitoring. Out of the different patterns described in the question, only the characteristic of train of four is correct. Although this mode is used more often in modern clinical practice of anesthesia, in fact the absence of fade—a hallmark of nondepolarizing block—is a more reliable indicator of reversal of neuromuscular blockade with tetanic or double-burst stimulation. A depolarizing block is characterized by absence of fade but takes on characteristics of a nondepolarizing block if enough depolarizing agent is administered.
35. D. Many physiologic factors and anesthetic and nonanesthetic drugs interact with nondepolarizing muscle relaxants (NDMRs). Volatile and local anesthetics potentiate, while depolarizing muscle relaxants antagonize the effects of these drugs. Intravenous anesthetic agents do not have any appreciable muscle-relaxant effect in normal doses. Aminoglycoside antibiotics potentiate the effects of NDMRs, while penicillin, cephalosporins, erythromycin, and tetracycline are devoid of neuromuscular effects. Streptomycin belongs to aminoglycoside family, and thus augments the effects of NDMRs.
36. C. Induction of anesthesia in a patient with severe valvular stenosis can lead to decreased ventricular filling secondary to vasodilatation and decreased venous return. Increase in the heart rate is very poorly tolerated as the ventricular filling is impaired because of decreased diastolic time. In the presence of normal ejection fraction, augmentation of cardiac contractility with administration of milrinone, epinephrine, or dobutamine may not be needed. Administration of phenylephrine will cause venoconstriction through stimulation of α1 receptors and increase the left-ventricular filling pressure, thus increasing the cardiac output and blood pressure. Increase in blood pressure will cause baroreceptor-induced decrease in heart rate, allowing more time in diastole, improving the left-ventricular filling. Increasing afterload with phenylephrine will decrease abnormal transmitral valvular pressure gradient that will help with restoration of perfusion pressure.
37. D. Droperidol is a butyrophenone and is structurally related to haloperidol. It affects many receptors in the central nervous system, including dopamine receptors in the caudate nucleus and the medullary chemoreceptor trigger zone. The latter effect explains its ability to counteract nausea and vomiting. Apart from that it also interferes with transmission mediated by serotonin, norepinephrine, and GABA. The net effect is appearance of tranquility and sedation in patients premedicated with this drug, but they are often extremely apprehensive and fearful. For this reason, droperidol has fallen into disfavor as a sole premedication. Peripherally, droperidol causes α blockade. Administration of droperidol may lead to hypotension in a hypovolemic patient. It may also cause prolongation of QT interval and torsades de pointes, and because of this, the US Food and Drug Administration has associated a black box warning with droperidol. Prior to use of droperidol, a 12 lead should be recorded, and in the presence of QT interval being more than 440 ms in men and more than 450 ms in women, droperidol should not be given.
38. D. A healthy adult can eliminate cyanide via the liver at a rate equivalent to cyanide production during sodium nitroprusside (SNP) infusion at the rate of 2 μg/kg/min. When the rate of SNP infusion exceeds that or when sulfur donors and methemoglobin are exhausted, cyanide toxicity may develop. Free cyanide radical binds with inactive tissue cytochrome oxidase and prevent oxidative phosphorylation. This may cause tissue anoxia, metabolic acidosis, and increased oxygen saturation of venous blood because of inability of the cells to extract oxygen from arterial blood. Ultimately, cardiac arrhythmias may develop. Cyanide toxicity must be suspected earlier than that stage in any patient who develops resistance to the hypotensive action of a maximum dose of SNP.
39. C. Dopamine is a major neurotransmitter in extrapyramidal system. Drugs that antagonize dopamine and are able to cross the blood–brain barrier may lead to extrapyramidal symptoms, which may manifest as torticollis, oculogyric crisis, and agitation. List of drugs that can precipitate these symptoms is long, but important ones in the perioperative period are droperidol, metoclopramide, haloperidol, and promethazine. Fortunately, it is readily treated by administration of diphenhydramine. Midazolam is also helpful in treating this condition. Famotidine and glycopyrrolate are not associated with any extrapyramidal effects.
40. B. All of the medications mentioned in the question should be continued in the perioperative period, except monoamine oxidase inhibitors. By decreasing the metabolism of catecholamines, these medications cause an increase in the amount of norepinephrine available at the presynaptic adrenergic nerve ending. Use of indirect-acting sympathomimetic drug like ephedrine to treat hypotension will lead to exaggerated response with severe degree of hypertension and cardiac arrhythmias. Recommendation is to stop these agents at least 2 weeks before the planned surgery. Since this can cause problem in a patient who is dependent on this medication, this group of medication is falling out of favor.
There is strong evidence to continue the use of β-blockers, cholesterol-lowering agents, and H2-blockers. Most hospitals have policies to ensure that patients using long-term β-blockers receive them in the perioperative period. Similarly, there is evidence that perioperative continued use of statins leads to better outcomes.
41. D. Dose of magnesium sulfate used to treat preeclampsia is high and can interfere with the effects of many medications used in anesthesia. It decreases the MAC of volatile anesthetics and potentiates the muscle relaxation caused by both depolarizing as well as the nondepolarizing muscle relaxants. The doses of these agents need to be reduced, and the ability of the patient to breathe spontaneously the end of general anesthetic where muscle relaxant was used needs to be assessed very carefully. Magnesium does not affect the dose of local anesthetic.
42. C. The absorption of the epinephrine from the epidural space into systemic circulation is too slow for it to counteract the hypotension which is caused by a bolus of lidocaine. Local vasoconstriction by epinephrine slows down the systemic absorption of lidocaine, leading to lower serum levels, decreasing the chance of local anesthetic toxicity as well as prolongation of the block by allowing the lidocaine to work longer on the neuronal tissue. Epinephrine improves the quality of block by acting on the analgesic adrenergic receptors in the spinal cord.
43. A. The relative solubility of an anesthetic in air, blood, and tissues is expressed as partition coefficients. Each efficient is the ratio of the concentration of the anesthetic gas in each of the two phases at equilibrium. Lower the partition coefficient, higher the rate of equilibration. In other words, for an anesthetic with a lower alveolar to blood partition coefficient, the rate of rise of alveolar concentration, and thus alveolar partial pressure, will be higher than an anesthetic with higher partition coefficient. Since it is the alveolar partial pressure that determines the partial pressure in the brain, more rapid rise of alveolar pressure is translated into faster anesthetic induction. Another factor that plays a role in this regard is the concentration effect. Nitrous oxide, being a less potent anesthetic with a MAC of 104, is administered in much larger quantities to induce anesthesia than a potent agent like sevoflurane. The massive inflow (higher concentration) of nitrous oxide leads to higher rate of rise of alveolar concentration (FA) of with a blood gas partition coefficient of 0.46 compared with desflurane with partition coefficient of 0.42.
44. D. Neostigmine causes inhibition of plasma cholinesterase. As succinylcholine is metabolized by this enzyme, administration of succinylcholine after the use of neostigmine for reversal of neuromuscular blockade may lead to longer-than-expected duration of action of succinylcholine. In this situation, continue to mechanically ventilate the patient until the patient meets extubation criteria. Rocuronium is mainly metabolized by liver and excreted into bile, cisatracurium via Hofmann elimination and pancuronium via kidney. Neostigmine does not interfere with any of these processes.
45. C. Patients with hypertrophic cardiomyopathy behave as if they have aortic stenosis except that the left-ventricular outflow obstruction is dynamic instead of being fixed. Decreased afterload under general anesthesia causes the gradient between the left-ventricular pressure and the aortic pressure to increase, leading to collapse of the left-ventricular outflow tract, increasing the obstruction, and decreasing the cardiac output. Restoration of the afterload with administration of phenylephrine reverses this effect. It also decreases the heart rate, allowing more time for left-ventricular perfusion to take place during the diastole. Decreasing the cardiac contractility may also be helpful as that will prevent the opposing walls of the outflow tract to come together relieving the obstruction. Amrinone will actually increase the contractility while reducing the afterload: both effects being undesirable in this clinical situation. Ephedrine will increase the heart rate as well as cardiac contractility, thus making the situation worse as described above. Nitroglycerine may worsen the hypotension and may not be a good choice for a hypotensive patient.
46. D. Ketorolac is a valuable nonsteroidal analgesic with modest anti-inflammatory action. It was the sole nonsteroidal anti-inflammatory drug available in intravenous form prior to the availability of IV ibuprofen. Thirty milligrams of ketorolac is equivalent in potency to 100 mg of meperidine or 10 mg of morphine. Unfortunately, it has many side effects that limit its use in the perioperative period. Inhibition of prostaglandin which is part of its analgesic mechanism of action leads to afferent arteriolar constriction.
47. B. As the clinical situation seems to indicate the need for an agent that is potent and extremely fast in its onset of action, nitroglycerine will be more helpful in this situation. Nitroglycerine is converted into nitric oxide, which is a very potent vasodilator increasing the venous capacitance. This action of nitroglycerine helps relocate the intravascular volume into peripheral compartment, thus unloading the central compartment and allowing the pulmonary edema fluid to be reabsorbed into the circulation.
48. D. Ondansetron has been shown to increase the QT interval. This response is comparable to that occurring with droperidol. Although there is no clear association between torsades de pointes and this drug, it is recommended that this drug be avoided in patients with congenital prolonged QT syndrome. Metoclopramide has a similar effect. Succinylcholine administration can prolong QT interval possibly from potassium efflux and by its effect on the autonomic nervous system. Propofol, on the other hand, has been shown to be safe in patients with this condition and may actually decrease the QT interval increase induced by sevoflurane.
49. C. Naloxone is a nonselective opioid antagonist at all three μ-receptors. It does not seem to have any agonist activity at the opioid receptors. Unfortunately, half-life is shorter (30–45 minutes) than most commonly used opioids. So renarcotization is a possibility. It is useful in the treatment of opioid-induced spasm of the sphincter of Oddi. Naloxone easily crosses the placenta. For this reason, administration of naloxone to an opioid-dependent parturient may produce acute withdrawal in the neonate.
50. B. Opioids usually cause bradycardia. This effect is mediated through central nervous system. They also have direct effect on the cardiac pacemaker cells. Morphine causes vasodilatation, and in the presence of preexisting hypovolemia, it may lead to decreased blood pressure and baroreceptor-induced tachycardia. Meperidine is an exception; it has intrinsic atropinelike activity that may cause tachycardia after its administration.
51. B. Opioid receptors are found inside substantia gelatinosa in the spinal cord. Addition of fentanyl to local anesthetic injected in the epidural space decreases the onset of analgesia time. Since epidural bupivacaine has a longer duration of action than epidural fentanyl, the duration of block may not be prolonged. Epidural fentanyl has no effect on the vagus nerve. Degree of analgesia is enhanced by addition of fentanyl to epidural local anesthetic, but the effect on the sensory and motor block is not augmented.
52. B. Alfentanil has a fast onset of action compared with sufentanil because of a very high proportion of it being unionized at physiologic pH: 90% vs. 20%. This is explained by the lower pKa of alfentanil (6.5) vs. sufentanil (8.0). So its penetration into brain is much faster than sufentanil. Its protein-binding is comparable to sufentanil, while lipid solubility is much less, leading to lower total volume of distribution.
53. C. Higher oil/gas partition coefficient means higher proportion of inhaled agent is in soluble form in blood before enough partial pressure is achieved at the alveolar, and finally in the brain, to anesthetize the patient. Same process is reversed at the time of awakening. With increased time of administration, so much anesthetic is found in the tissues in a soluble form that all other factors become much less important as determinants of recovery time. Higher cardiac output may slow down the recovery time, but its effect will be smaller than the effect of duration of administration. MAC of the drug in itself does not determine the time of induction or recovery.
54. D. Hallmark of nitroprusside poisoning is increasing metabolic acidosis secondary to impaired oxidative phosphorylation in the cell because of accumulation of cyanide ions. Acute myocardial infarction is not a contraindication in itself of nitroprusside therapy as long as it is needed to treat high blood pressure. Same is true for mitral regurgitation, and in fact, nitroprusside may be helpful as it may increase the cardiac output in this condition by decreasing the afterload.
Renal failure may increase the availability of sulfate ion, which allows production of more thiosulfate to act as a donor and thus convert cyanide to thiocyanate. Prolonged administration of high doses of nitroprusside may lead to thiocyanate accumulation and toxicity.
55. C. Spinal anesthesia is rarely associated with dramatic drop of heart rate and blood pressure in young individuals. The mechanism is poorly understood. Proposed mechanism includes preexisting hypovolemia, unrecognized hypoxemia secondary to sedation, or a high spinal with inhibition of cardioacceleratory sympathetic nerves arising from T1 to T4 segments of the spinal cord.
In the clinical scenario described, atropine in itself may not be able to correct the hemodynamics, and the situations call for initiation of measures required in advanced cardiac life support. If there is no pulse, chest compressions along with administration of epinephrine may be the best course of action.
56. D. Gentamycin is an aminoglycoside antibiotic that enhances neuromuscular blockade action of muscle relaxants used in anesthesia. Magnesium in itself potentiates neuromuscular-blocking agents’ action and so acts synergistically to prolong the neuromuscular blockade. Anticholinesterases increase the amount of acetylcholine available at the neuromuscular junction by inhibiting the enzyme that metabolizes it. Succinylcholine-induced neuromuscular blockade enhances the weakness produced by aminoglycoside antibiotics.
Proposed mechanism of action of these antibiotics in causing the potentiation of action of neuromuscular-blocking agents is the inhibition of release of acetylcholine at the prejunctional site. Calcium antagonizes this action of antibiotics, and at least temporarily reverses their effect on enhancement of neuromuscular-blocking action of these antibiotics. But since calcium also stabilizes the postjunctional membrane to the effect of acetylcholine, sometimes the effect of calcium on antagonism of antibiotic-induced enhancement of neuromuscular blockade produced by nondepolarizing neuromuscular-blocking agents is unpredictable.
57. A. Lorazepam is conjugated in the liver with glucuronic acid to produce inactive metabolites, but this process is much slower than the metabolism of midazolam. As a result, the elimination half-life of lorazepam is much longer (10–20 hours) compared with midazolam (1–4 hours). Similarly, the clearance of midazolam is six to eight times that of lorazepam. Volume of distribution of lorazepam is comparable to midazolam.
58. B. Volatile anesthetics cause characteristic dose-dependent changes in the EEG. Increasing depth of anesthesia with isoflurane from the awake state is characterized by increased amplitude and synchrony. Periods of electrical silence begin to occupy a greater portion of the time as depth increases (burst suppression). Midazolam and thiopental both increase the inhibitory action of GABA receptor and slow down the EEG. Lidocaine, on the other hand, has a biphasic action. At a lower serum level, it causes restlessness, tremor, tinnitus, and vertigo culminating in tonic–clonic seizure, which reflects inhibition of cortical inhibitory neurons. Larger doses inhibit both inhibitory and excitatory neurons, leading to central nervous system depression and coma.
59. B. Plasma pseudocholinesterase or nonspecific cholinesterase is an enzyme with molecular weight of 320,000. It is found in plasma and most tissues but not in red blood cells. It degrades acetylcholine released at the neuromuscular junction. It is primarily produced in the liver, so end-stage liver disease may decrease plasma cholinesterase activity. Normal plasma pseudocholinesterase does not resist dibucaine inhibition, while the abnormal one does. So the dibucaine number is a good estimation of the degree of qualitative abnormality of the enzyme. Acetylcholinesterases antagonize this enzyme. Metabolism of succinylcholine by pseudocholinesterase is a two-step process of hydrolysis. First step converts succinylcholine to succinylmonocholine, and the second step to succinic acid.
60. D. As mentioned in the previous discussion pseudocholinesterase metabolizes the injected succinylcholine before it reaches neuromuscular junction. This process is so fast that only 5% of injected succinylcholine reaches the neuromuscular junction. In the presence if atypical pseudocholinesterase, this metabolism is slow, and greater quantity of succinylcholine reaches neuromuscular junction, leading to prolonged apnea, following the standard dose of succinylcholine. Diffusion away from the neuromuscular junction stays the same whether the patient has normal or atypical enzyme and does not contribute much to the cessation of action of succinylcholine. Succinylcholine is not metabolized in the liver, although pseudocholinesterase is produced in the liver. Liver disease has to be severe before decreases in plasma pseudocholinesterase production sufficient to prolong succinylcholine-induced neuromuscular block will occur because an increased proportion of succinylcholine reaches the neuromuscular junction.
61. B. Effects of narcotics on smooth muscles are variable in different areas of the body. It causes contraction of the smooth muscle of the gastrointestinal tract, causing variety of side effects like constipation, biliary colic, and delayed gastric emptying. Increased biliary pressure occurs when the gallbladder contracts against a closed or narrowed sphincter of Oddi. Urinary urgency is produced by opioid-induced augmentation of detrusor tone, but, at the same time, the tone of the bladder sphincter is enhanced, causing urinary retention. Opioids alter the development, differentiation, and function of immune cells. Chronic rather than acute use of opioids is associated with immunosuppression, and withdrawal from opioids can also increase the degree of immunosuppression.
62. A. Morphine exhibits greater analgesic potency and slower onset of action in women than men. Older individuals are also more prone to the sedative effect of opioid drugs compared with younger individuals. Liver disease does not seem to affect the sensitivity of the individual to opioid administration except during liver transplant surgery; when in anhepatic phase, the effect of opioids may be enhanced. Morphine-6-sulfate may accumulate in cases of renal failure, causing unexpected ventilatory depressant effects from even a small dose of morphine.
63. B. Lower esophageal sphincter mechanism consists of the intrinsic tone of the intrinsic smooth muscle of the distal esophagus and the skeletal muscle of the diaphragm. Under normal circumstances, the lower esophageal sphincter is approximately 4 cm long. Muscle tone in the lower esophageal sphincter is the result of neurogenic and myogenic mechanisms. A substantial portion of the neurogenic tone in the humans is due to cholinergic innervation via the vagus nerve. The presynaptic neurotransmitter is acetylcholine, and postsynaptic neurotransmitter is nitric oxide. The normal lower esophageal sphincter pressure is 10 to 30 mm Hg at end exhalation. Succinylcholine increases intragastric and lowers esophageal pressures. Neostigmine also increases this sphincter’s tone by increasing the concentration of acetylcholine. Metoclopramide also increases lower esophageal sphincter tone and is helpful in treating the symptoms of gastroesophageal reflux and associated esophagitis. Glycopyrrolate, on the other hand, relaxes the smooth muscle of this sphincter.
64. C. All of the agents mentioned in this question can be used to anesthetize a patient for a short duration of time on frequent basis except for etomidate as its adrenal suppressive action will impair the ability of the patient to mount a stress response, which this patient will need on an ongoing basis.
65. B. Eutectic mixture is a combination of two substances whose melting point is lower than that of either of the constituents. EMLA cream is a eutectic mixture of lidocaine (2.5%) and prilocaine (2.5%) with a melting point of 180°C so that the mixture is an oily liquid at body temperature.
Five percent EMLA cream is applied to dry intact skin and covered with an occlusive dressing for at least an hour. It provides topical anesthesia for 1 to 2 hours. The amount of drug absorbed depends on application time, dermal blood flow, skin thickness, and total dose administered. Some patients may dislike the tingling feeling that is produced by this drug. It should not be applied to broken skin or mucous membranes. Side effects include skin blanching, erythema, edema, and methemoglobinemia. The last side effect is secondary to metabolism of prilocaine O-toluidine and may be more common if the patient is concurrently taking sulfonamides and other methemoglobin-inducing drugs.
66. D. Epidural opioids can cause nausea, pruritus, and respiratory depression. Biggest advantage of these agents over epidural administration of local anesthetics is the hemodynamic stability, as there is no inhibition of sympathetic system. Hypotension is highly unlikely with epidural fentanyl administration.
67. B. Intractable seizures are sometimes treated with excision of the seizure focus in the brain. Anesthesiologist is sometimes asked in these cases to help locate the focus through enhancing the EEG activity or actually inducing the seizure during the anesthetic. Some anesthetic agents are known to increase the seizure activity and can be utilized for that purpose. Etomidate, methohexital, older inhaled anesthetic enflurane, and, to some degree, ketamine can be helpful in this regard. Other anesthetics actually increase the seizure threshold and make it difficult for the surgeon to find the area of interest.
68. D. All the porphyrias result from a defect in heme synthesis. Heme is an essential component of hemoglobin, myoglobin, and cytochromes, that is, compounds involved in the transport and activation of oxygen and the electron transport chain. For anesthesiologists, porphyria can be divided into inducible and noninducible. Inducible ones are those that are triggered by an exogenous factor like administration of a drug. Drugs that induce cytochrome enzymes like barbiturates and phenytoin can precipitate an episode of porphyria. Signs and symptoms depend on the type of porphyria, but anesthesiologist is usually involved in a case where patient is brought to the operating room for exploratory laparotomy secondary to nausea, vomiting, and pain in the abdomen. No organic cause of these symptoms is found, and patient may then develop other signs of porphyria postoperatively like neurologic signs of hemiplegia, quadriplegia, psychiatric disturbances, and alteration of consciousness or pain.
Inhaled anesthetics, nitrous oxide, induction agents other than barbiturates, and opioids are all safe to use in these patients. Elicitation of family history and past history of similar episodes can help with the diagnosis. Perioperatively, disturbances of autonomic system and electrolyte imbalance are common and need to be addressed.
69. D. Ketorolac is a nonsteroidal anti-inflammatory analgesic that is available in parenteral form. Administration of this medication will help avoid side effects that are associated with the use of morphine, such as nausea and respiratory depression. Ketorolac 30 mg produces equivalent analgesia compared with 10 mg of morphine. Since it is devoid of action on the sphincter of Oddi, it is a useful drug in patients who have pain secondary to biliary spasm. Like any other nonsteroidal anti-inflammatory drug, it does carry the side effect of inhibition of platelet function and increasing the chance of bleeding postoperatively.
70. D. MAC is defined as the dose of an anesthetic at which 50% of patients do not move in response to a surgical incision. Different drugs and physiologic and pathologic states can affect the MAC of an anesthetic. Chronic alcohol use increases the MAC, while acute intoxication decreases it. Respiratory alkalosis does not seem to have any effect. Chronic anemia decreases MAC, but it seems to do so only if hemoglobin level is below 5 gm/dL. Hypothermia decreases the MAC, while hyperthermia increases it.
71. D. All of the drugs mentioned in the question are agonist–antagonist at different opioid receptors except naltrexone, which is a pure antagonist. Use of naltrexone in this patient who has been using heroin for such a long time will precipitate withdrawal symptoms, which include body aches, runny nose, excessive tearing and salivation, diarrhea, mood swings, and, in some cases, high blood pressure, tachycardia, and increased temperature. Severity and duration of these symptoms vary.
72. C. Ketamine causes minimal to no respiratory depression when used to induce general anesthesia. The ventilatory response to carbon dioxide is maintained, and the PaCO2 is unlikely to increase more than 3 mm Hg. It is a potent vasodilator of cerebral vessels, and patients prone to have increased intracranial pressure (ICP) may show a sustained rise in ICP after induction of anesthesia with ketamine despite normocapnia.
Ketamine has bronchodilator activity and is at least as effective as halothane in preventing experimentally induced bronchospasm in dogs. It has been used in subanesthetic doses to treat bronchospasm in the operating room and ICU. It is readily metabolized in the liver by the cytochrome P450 system of enzymes to form norketamine, which is one-fifth to one-third as potent as ketamine.
73. B. Treatment of hypertension in a preeclamptic patient aims at decreasing the risk of cerebral hemorrhage while maintaining and even improving tissue perfusion. Nitroprusside, a potent vasodilator of resistance and capacitance vessels with an immediate but evanescent action, is useful in preventing dangerous elevations in systemic and pulmonary artery blood pressure during laryngoscopy, and is ideal for treatment of hypertensive emergencies. Its infusion can be titrated to effect. Labetalol and hydralazine can be used to provide a longer lasting control of blood pressure but may not be fast enough in their action to control a sudden acute rise of blood pressure that is associated with this condition. Magnesium is primary therapy to prevent seizures in this condition. It is a smooth-muscle relaxant and helps with control of high blood pressure but in itself is not good enough to control the elevation of blood pressure in preeclampsia. Lisinopril is an angiotensin-converting enzyme inhibitor, which is contraindicated during pregnancy because of the risk of fetal abnormalities.
74. B. The response of the nerve to electrical stimulation depends on three factors: the current applied, the duration of the current, and the position of the electrodes. These factors can be modified in different ways to take advantage of the characteristic features of the nondepolarizing neuromuscular blockade: fade and post-tetanic facilitation with high-frequency stimulation. When stimulation is applied at a frequency of ≥30 Hz, the mechanical response of the muscle is the fusion of individual twitch responses. In the absence of neuromuscular-blocking drugs, no fade is present and the response is sustained. During nondepolarizing block, the response achieves a peak and then fades. Higher the frequency, more useful it is to detect residual blockade, although sometimes there may be fade after stimulation with 100 Hz in the absence of a neuromuscular block. On the other hand, with train of four when 2-Hz stimulation is used, the mechanical or electrical response decreases little after the fourth stimulus, and the degree of fade is similar to that found at 50 Hz. Problem with train of four is the difficulty to evaluate by visual or tactile means the difference between the height of first and the fourth twitch. Irrespective of the experience, it is difficult for anesthesiologists to detect train-of-four fade when actual train-of-four ratio is 0.4 or greater, meaning thereby that residual paralysis may go undetected. This shortcoming may be overcome, to some extent by applying two short tetanic stimulations (three impulses at 50 Hz, separated by 750 ms), and by evaluating the ratio of the second to the first response.
75. D. Guillain–Barré syndrome is the most common cause of acute flaccid paralysis. It is an autoimmune disease triggered by bacterial or viral infection. Paralysis leads to proliferation of extrajunctional acetylcholine receptors with risk of hyperkalemia if succinylcholine is used. These patients may show a range of sensitivity to nondepolarizing muscle relaxants from extreme sensitivity to resistance. Use of these agents although is not contraindicated as long as caution is practiced in assuring return of normal muscular power at the end of the procedure before extubation is performed. If the circumstances allow, intrathecal opioids and epidural local anesthetics may actually be a better way to provide anesthesia for these patients.
76. C. Sympathetic stimulation at the time of intubation may cause an exaggerated sympathetic response and needs to be considered in this situation. Blockade of α receptors by labetalol may be helpful under this condition, but its concomitant blockade of β receptors may pose problem. Intense increase in the afterload secondary to exaggerated release of norepinephrine may not be tolerated by the heart that is inhibited by labetalol. Direct vasodilators like nitroglycerine and nitroprusside are more suitable for this situation than a nonselective β-blocker agent. As ketamine can stimulate sympathetic discharge, it is not an appropriate induction agent for this patient. Ephedrine may also increase the release of norepinephrine from the stored site and cause profound hypertension and cardiac dysrhythmias. Propofol does not have any such action, and it is appropriate for use in this case. As mentioned earlier, cocaine inhibits reuptake of norepinephrine into the presynaptic nerve, thus making it accumulate in these nerve endings.
77. C. An acute of episode of cyanosis in a child with history of tetralogy of Fallot signifies more right-to-left shunt because of decreased systemic vascular resistance. Phenylephrine may be an appropriate agent for this situation, as it will increase the systemic vascular resistance through its action on α1 receptors, thus decreasing the shunt. As more blood flows through the lungs before returning to the heart, more oxygen will be available to the peripheral tissues improving the cyanosis.
Oxygen in this situation may not be helpful as not enough of the blood is flowing through the lungs. Other options also may help treat the primary problem. Children with this condition learn to treat these episodes, called “tet spells,” by squatting down, thus increasing their systemic vascular resistance and venous return to the heart.
78. C. Clonidine has been in clinical use for over two decades now. It is a very potent antihypertensive and is very useful to control high blood pressure in some patients with a very resistant kind of disease. Unfortunately, oral dose requires repeated doses, and omission of a dose, as will happen if a long surgical procedure was scheduled, may lead to severe rebound hypertension. Availability of transcutaneous patch has helped decrease this problem. A differential diagnosis in a patient with hypertension in the recovery room should always include possibility of rebound hypertension secondary to omission of a dose of an α agonist like clonidine.
Other antihypertensive agents mentioned in the question do not lead to rebound hypertension, although hypotension during anesthesia associated with perioperative use of drugs causing angiotensin-converting enzyme blockade can be difficult to manage.
79. C. Postoperative nausea and vomiting (PONV) is one of the most disliked side effects of anesthesia and surgery. Efforts to treat it sometimes lead to troublesome side effects which look alarming at the time of presentation but are easy to treat. Dystonic reactions, including tardive dyskinesia, torticollis (commonly called oculogyric crisis), dysphagia, and excessive salivation, are some of the manifestations of this pseudoparkinsonian syndrome. Butyrophenones, phenothiazines, gastrointestinal prokinetics, and lithium are some of the etiologic agents.
Although promethazine can cause these reactions, the incidence is much lower than with metoclopramide. Granisetron is a 5-HT3-receptor antagonist similar to ondansetron. The 5-HT3-receptor antagonists have become the most frequently administered prophylaxis and treatment for PONV due to their efficacy. Central nervous symptoms occur in less than 8% of patients treated with this group of drugs. Intravenous diphenhydramine provides excellent relief of these neurologic symptoms.
80. A. Repeated administration of ketamine may necessitate increased dose to achieve the same effect. This phenomenon could partly be explained by the fact that chronic administration of ketamine stimulates the liver enzymes that metabolize it. It exerts its primary anesthetic and analgesic action through NMDA receptor, although it is found to interact with many other receptors in the central nervous system. Primary site of metabolism of ketamine is liver. It is not significantly bound to plasma proteins and thus is readily available for distribution into the tissues.
81. C. Etomidate cannot be used as an infusion because of its suppressive action on the adrenal gland; otherwise, it would be an ideal sedative agent for procedure that needs moderate sedation as it does not depress respiration even when used in induction doses. It is a potent cerebral vasoconstrictor and causes decrease in cerebral metabolism as well as cerebral blood flow. In comparison to thiopental it increases the excitatory spikes on the EEG and is a good agent for anesthesia for electroconvulsive therapy and mapping for seizure focus if EEG activity needs to be facilitated. An administered dose of etomidate is almost completely metabolized by the liver, and very little of the parent molecule is found in the urine.
82. D. Gabapentin has become a first-line treatment for neuropathic pain. This action is not mediated through GABA receptors as would be expected from the name. Instead, it modulates voltage-gated calcium channels which get activated in an injured nerve. Inhibition of this channel leads to decreased influx of calcium into the nerve cell, decreasing neuronal transmission responsible for causing pain.
Gabapentin has not been found to interact directly with NMDA receptor. Gabapentin’s role in treatment of neuropathic pain has not been linked with any interaction with sodium channel.
83. D. Lipid solubility of a local anesthetic is most closely related to its potency, while pKa determines the onset of action. As a result, more lipid-soluble local anesthetics like tetracaine and bupivacaine are more potent (needing less dose) than less lipid-soluble local anesthetics like lidocaine. The pH at which the charged and uncharged forms of the drug exist in equal concentration is pKa. As it is the uncharged form that crosses the neuronal membrane, local anesthetics with a pKa farther from the physiologic pH have more of the drug in ionized (charged) form delaying their onset of action. This is not the only determinant of the onset of action, though chloroprocaine has a very short onset of action despite having a pKa of 8.7. Reason is that the quantity of the drug injected is so high with chloroprocaine that more of its molecules are available in its uncharged form despite the low percentage of the drug found in uncharged form. Protein-binding of the local anesthetic determines its duration of action as the receptors are proteins, and a drug with a higher affinity for protein will latch on to these receptors longer than a drug with less affinity for protein-binding. Intrinsic property of a drug to cause vasodilatation causes the drug to get absorbed in the systemic circulation, reducing its duration of action at the site of injection compared to a local anesthetic which causes vasoconstriction.
84. A. Etomidate is a carboxylated imidazole. It resembles midazolam in its pharmacokinetics, in that it is water soluble in acidic form and would be useless as an induction agent, except that it changes its characteristics in the body and becomes lipid soluble on exposure to physiologic pH. Unlike propofol, it is not useful for sedation of the patients in the ICU because of its action on adrenal glands. It inhibits 11-β-hydroxylase, thus causing inhibition of conversion of cholesterol to cortisol. Patients experiencing sepsis or hemorrhage, and who might require an intact cortisol response, would be at risk if etomidate is administered to them. Even a single dose may lead to a prolonged depressant effect (4–8 hours) on the adrenal gland. As propofol is a substituted isopropyl phenol, it is very dissimilar in its chemical structure to etomidate. Like other induction agents, awakening from an induction dose of etomidate is secondary to redistribution of the drug. Liver metabolism of etomidate is very complete but not fast enough that that action will lead to awakening from an induction dose of this agent.
85. A. Clopidogrel binds to ADP receptors on the surface of platelets. This action leads to inhibition of activation, aggregation, and degranulation of platelets. Clopidogrel modifies the ADP receptor irreversibly, resulting in its inhibition for the lifetime of the platelet, which is up to 7 days. So recommendation from ASRA is to avoid performing a neuraxial block for 7 days even if only a single therapeutic dose of clopidogrel was used by the patient. Clopidogrel may cause neutropenia, thrombotic thrombocytopenic purpura, and hepatic dysfunction but has not been associated with pancytopenia.
86. C. NMDA receptors have been documented in the spinal cord, and epidural ketamine does have some analgesic action but much less than morphine. Of all the anesthetics available, ketamine maintains the muscle tone the most, and so it does not decrease the duration of action of nondepolarizing neuromuscular-blocking agents. Although in vivo ketamine has been shown to maintain the stroke volume, in vitro studies with isolated myocardial cell show that ketamine leads to decrease in the force of contraction of myocardial cell. In vivo finding is explained by the ability of ketamine to stimulate sympathetic system, which counteracts its myocardial depressant action. This action of ketamine can get unmasked in a patient with chronic congestive heart failure, that is, already using maximum sympathetic activity to maintain his or her cardiac output. Ketamine does not decrease the amplitude of the cortical sensory–evoked potentials.
87. A. True allergic reaction to a local anesthetic is very rare, but is more common with ester local anesthetics compared with amide local anesthetics. Procaine is the only ester local anesthetic among the choices given in this question. All others are amides. So it is probably from procaine.
88. A. Lidocaine has been in use for treating a myriad of pain conditions involving neuropathic pain. Although primary mechanism of its analgesic action may be through blockade of the sodium channel, it acts on many other channels including calcium and G-protein–coupled receptors. So the mechanism of its analgesic action may be more complicated than simple blockade of sodium channel. Although lidocaine has been found to inhibit NMDA receptor in supra clinical levels, activation of this receptor would not lead to analgesia.
89. D. Belladonna alkaloids found in the nature sometimes lead to manifestations of anticholinergic syndrome. Factors that need to be taken into consideration for treatment of this condition include whether there is CNS involvement or not. In this case, it seems that manifestations of CNS involvement are obvious. Neostigmine, pyridostigmine, and edrophonium have quaternary ammonium ion in their chemical structure, making them unable to cross the blood–brain barrier. Physostigmine being a tertiary compound is able to cross this barrier and is able to antagonize the central actions of these anticholinergic agents.
90. D. Many physiologic factors and medications are associated with potentiation of action of neuromuscular blockers. Calcium channel blockers like verapamil lead to decreased sarcoplasmic concentration of calcium, which may potentiate the muscle weakness as well as prolong the duration of action of neuromuscular-blocking agents.
Carbamazepine was originally used as anticonvulsant but has been found to be useful in many other conditions. It is not associated with prolonged action of neuromuscular-blocking agents.
Many antibiotics, notably aminoglycosides, prolong the actions of these drugs, but clindamycin is safe to use and has not been shown to have any deleterious effect when used concomitantly with drugs like vecuronium.
91. C. Remifentanil is metabolized by nonspecific esterases found in blood and tissues. This metabolism is so rapid that action of remifentanil is terminated without the need for redistribution or hepatic extraction. There is no accumulation of the drug in patients with renal failure. Elimination half-life (6 minutes) is not prolonged even after a prolonged infusion. Hypothermia during cardiac bypass does prolong its elimination time up to 20%.
92. C. Dexmedetomidine is an α2-agonist, which acts centrally to inhibit sympathetic nervous system activity. Clonidine belongs to the same group of medicines. Dexmedetomidine actually sometimes is used to treat spasm observed in cerebral palsy patients. Its effect in opioid-induced rigidity is not well studied. Decay time of the serum levels of dexmedetomidine after a short duration of infusion is very fast, but if it used for longer time, for example, 10 hours, as it is sometimes used in intensive care unit setting, the sedative action may take a long time to dissipate. Dexmedetomidine decreases systemic vascular resistance, and that is one of its mechanism by which it may cause a decrease in blood pressure.
93. D. Myotonia is characterized by continued involuntary contraction of a group of muscles. So once triggered, muscles fail to relax. Myotonic dystrophy is the most common form. Succinylcholine can cause severe hyperkalemia and is contraindicated in this condition. Nondepolarizing muscle relaxants may not be able to reverse this spasm. As neostigmine can also trigger myotonic episode, its use for reversal of muscle relaxants is not indicated. For that reason, it is prudent to avoid using longer-acting nondepolarizing agents that may require reversal agents.
Hypothermia can trigger this condition, so precautions need to be taken to avoid it during any anesthetic. Best treatment to relieve the spasm is to inject local anesthetic into the muscle.
94. C. Administration of anticholinesterase agents to reverse the action of nondepolarizing agent allows the acetylcholine levels to build up not only in neuromuscular junction of the skeletal muscle but also at the level of muscarinic receptors. That leads to the problem of bradycardia if not effectively counterbalanced by administration of an anticholinergic agent. Finding the best combination of these agents is of great importance to an anesthesiologist. Older anticholinesterase agent edrophonium causes the cholinesterase activity to increase in cardiac muscarinic receptors, while neostigmine was found to have additional direct action on these cardiac receptors. Despite that finding, neostigmine-induced bradycardia is effectively prevented by administration of anticholinergic agent compared with edrophonium, where this effect is not as predictable. Another factor to consider is the onset of action of these drugs. Atropine and edrophonium are very fast-acting, while neostigmine and glycopyrrolate are slower in onset. As a result, if glycopyrrolate is injected to counteract the cholinergic response induced by edrophonium, the chance of development of bradycardia is greatest with this combination, as glycopyrrolate will take much longer and may not reverse all of the cholinergic effect produced by edrophonium.
95. D. Carcinoid syndrome can be precipitated in the operating room when the carcinoid tumor is manipulated by the surgeon. Cause is the release of massive amount of hormones made by the carcinoid tumor into the systemic circulation. Signs and symptoms during anesthesia may include flushing of head, neck, and upper thorax, bronchospasm, and hypo or hypertension. Many carcinoid tumors contain somatostatin receptors: a gastrointestinal regulatory peptide that reduces the production and release of gastro pancreatic hormone. Somatostatin infusion can avoid and treat the manifestation of this syndrome in the perioperative period. A synthetic analogue: octreotide is used more often in contemporary practice. It is recommended to be started 2 weeks prior to the scheduled surgery and continued in the postoperative period. Ketamine is not indicated in this condition, as it may increase the sympathetic nervous system discharge and worsen the situation. Sevoflurane is helpful to treat bronchospasm acutely but is not specific for this condition and may not be potent enough to treat bronchospasm induced by these hormones. Dexamethasone is not indicated for the acute treatment of bronchospasm, as its onset of action measures in hours and not in minutes.
96. D. This patient seems to be in hypovolemic shock. Body’s response to such a state is to redirect the intravascular volume to vital organs like brain and heart by causing peripheral vasoconstriction through activation of the sympathetic system. Thiopental is a known vasodilator. Mechanism of this action includes barbiturate-induced depression of the medullary vasomotor center and decreased CNS outflow from the CNS. This vasodilatation will cause peripheral pooling of blood. This may cause catastrophic drop in blood pressure, which this patient may not be able to tolerate. Metabolism of thiopental by the liver is slow and does not contribute appreciably to the termination of effect of this drug. Thiopental does have negative inotropic effects on the heart, although this effect is normally masked by baroreceptor-mediated responses.
97. D. Patients with valvular heart disease are sometimes extremely sensitive to abrupt changes in the heart rate. High-dose fentanyl has been shown to cause bradycardia through its effect on the vagus nerve. To some extent, this may be desirable in a patient with stenotic valvular lesion. In case of regurgitant lesions, this may lead to critical decrease in cardiac output. In order to counteract this bradycardia action of the fentanyl, some anesthesiologists like to use a muscle relaxant that causes tachycardia. Pancuronium and an older nondepolarizing muscle-relaxant gallamine were used for this purpose. Effect of pancuronium on the heart rate is elicited at the level of sinoatrial node by blockade of the muscarinic receptors. On the other hand, effect of fentanyl that caused bradycardia was more through central nuclei of the vagus nerve. Carotid baroreceptors and β adrenergic receptor are not involved in induction of tachycardia noticed after administration of pancuronium.
98. D. Different surgical techniques are used to suture the donor heart to the cuff of the recipient heart. In any case, donor sinoatrial (SA) node is severed of its autonomic nervous system connections. As a result, all of the drugs that use SA node and normal conduction system of the heart to produce their cardiac effects fail to produce their effects in a transplanted heart. Although α1 receptors are found in the heart, their stimulation with phenylephrine is not associated with chronotropic effects.
Only drugs that are able to directly stimulate the adrenergic receptors found in the myocardium are useful in treating bradycardia in a transplanted heart. Isoproterenol being a direct β1 stimulant is the drug of choice to treat an episode of bradycardia under these circumstances.
99. C. Propofol infusion syndrome was first described in pediatric intensive care units, but quite a few adult cases have been reported now. Earliest sign of syndrome is metabolic acidosis because of impairment oxidative phosphorylation in the mitochondria, anaerobic metabolism, and accumulation of lactic acid. Cardiac dysfunction is also an early sign, which manifests early on as bradycardia, and right-heart block is very common. Rhabdomyolysis is a hallmark of this condition, and free myoglobin precipitates in the renal tubules, leading to kidney failure. In an established case, the mortality rate is extremely high, in excess of 80%. Higher cumulative dose of propofol over a relatively longer period of time seems to be associated with higher incidence of this condition. This has led to a drop in the popularity of this drug in the pediatric intensive care setting.
100. C. Generally, cerebral blood flow is related to cerebral metabolic rate with factors that decrease cerebral metabolic rate decrease the cerebral blood flow. This coupling effect is preserved during anesthesia, but the degree of the coupling may be altered by anesthetic agents where inhalational agents have relatively higher cerebral blood flow for any degree of cerebral metabolic rate. This variation is different for different inhalational agents and also at different doses of the same agent. At 1.5 MAC, the overall effect of desflurane is cerebral vasodilatation and increased blood flow.
Although nitrous oxide has been shown to have species-specific action on cerebral vasculature, it is clear that in humans, it is a cerebral vasodilator with potential of increasing the cerebral blood flow and intracranial pressure. Phenytoin is an anticonvulsant, which has many central nervous system effects but has not been shown to be a cerebral vasodilator. Pentothal decreases cerebral metabolic rate and is known to preserve the normal coupling between the metabolism and blood flow. So administration of this agent will decrease the cerebral blood flow.
101. A. Anaphylactic reaction during anesthesia is estimated to occur between 1 in 5,000 and 1 in 25,000 cases. Neuromuscular-blocking drugs seem to be the most common agents causing this reaction. Incidence is far too low to determine the relative frequency of occurrence with individual neuromuscular blocker. Latex, antibiotics, and induction agents are much less common etiologic agents in anesthesia. Opioids extremely rarely cause anaphylactic reactions.