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.

 

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

B. Opioids

C. Antibiotics

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 reticularactivating 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-maximumrecommended 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 leftventricular filling pressure, thus increasing the cardiac output and blood pressure.