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 indirectacting 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-thanexpected 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 Otoluidine 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 antiinflammatory 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.