Stoelting Study 2B

Front 1

52. How is placental blood flow affected by the administration of ephedrine?

Back 1

52. Placental blood flow is preserved with the administration of ephedrine. This makes ephedrine the treatment of choice for hypotension in parturients.

Front 2

53. After how many doses of ephedrine does tachyphylaxis become apparent? What are two possible causes of this tachyphylaxis?

Back 2

53. Tachyphylaxis to ephedrine becomes apparent after the first dose. There are thought to be two reasons why the tachyphylaxis results. First, ephedrin may linger on the receptor for a longer period of time than indicated by its clinical effect. Then, when the second dose of ephedrine is administered, there are fewer receptors available to the newly administered ephedrine and the blood pressure response is less pronounced. The second way in which tachyphylaxis may result is by depletion of norepinephrine stores with the first dose, making less norepinephrine available for subsequent ephedrine I doses. (40; 553, 988)

Front 3

54. What is the mechanism of action for phenylephrine? What are its resultant clinical effects?

Back 3

54. Phenylephrine directly stimulates alpha-adrenergic receptors but lacks significant beta-adrenergic activity. Phenylephrine thus increases systemic vasculaMe resistance and blood pressure primarily through venoconstriction without significant constriction of arterial vessels. Clinically, phenylephrine mimics the effects of norepinephrine but is less potent and longer lasting.

Front 4

55. Does phenylephrine primarily stimulate alpha-l receptors or alpha-2 receptors?

Back 4

55. Alpha-l adrenergic receptors are stimulated at lower doses of phenylephrine dose required to stimuhte alpha-2 receptors

Front 5

56. Why might the administration of phenylephrine result in a transient decrease in cardiac output?

Back 5

56. The administration of phenylephrine might result in a transient decrease in cardiac output coincident with the increase in systemic blood pressure. This most likely occurs as a result of the reflex bradycardia that occurs in response to the increase in blood pressure

Front 6

59. What is the mechanism by which antihypertensives decrease blood pressure by acting on the sympathetic nervous system?

Back 6

59. Antihypertensives that act on the sympathetic nervous system to decrease blood pressure do so by affecting the heart, the peripheral vasculature, or both. When antihypertensIves attenuate sympathetic n~rvous stimulation to the heart, parasympathetic nervous system activity at the heart predominates and bradycardia can result

Front 7

60. How is the attenuation of sympathetic nervous system activity by antihypertensives renected clinically?

Back 7

60. Clinically, attenuation of sympathetic nervous sy.tem activity by antihypertensives affects the patient's physiologic capacity to reflexively compenslte for decreases in blood pressure. This may manifest as ortiostatic hypotension. Intraoperatively, the inhibitory effect~ of antihypertensives may manifest as exaggerated decreases in blood }lfessure in response to hemorrhage, positive airway pressure, or sudden changes in body position. (40; 559, 992-994)

Front 8

61. What is the current recommendation for the perioperative medical management of patients on antihypertensive therapy?

Back 8

'he current recommendation for the perioperative medical management of patients on antihypertensive therapy is to continue the prescribed schedule of the antihypertensive throughout the operative period for the optimal control of blood pressure. This includes all types of antihypertensives, irduding calcium channel blockers, beta-adrenergic ra:eptor blockade, and alpha-2 agonists. For those patients on chronic beta-adrenergic blockade therapy who are unable to receive oral medicines, the intravenous administration of a beta blocker, such as esrnolol, can be administered

Front 9

62. What is the mechanism of action of angiotensin-converting enzyme inhibitions in the treatIrent of essential hypertension? Give some examples of this class of drugs.

Back 9

62. Angiotensin converting enzyme inhibitors act as antihypertensives by blocking the conversion of angiotensin I to angiotensin II. This prevents the vasoconstriction and sympathetic nervous system stimulation associated with ,. angiotensin II. Examples of angiotensin converting enzyme inhibilOJs include captopril, enalapril, and lisinopril.

Front 10

63. What are some potential side effects of angiotensin-converting enzyme inhibitors?

Back 10

63. Overall there are very few side effects associated with angiotensin converting enzyme inhibitor therapy, making patient compliance high with this antihypertensive. Potential side effects include an increase in serum potassium levels, cough, upper respiratory congestion, and rhinorrhea. Patients who are espedally at risk of elevated potassium levels are patients on potassium-sparing diuretics or patients with renal insufficiency. Patients with chronic obstructive pulmonary disease may experience an exacerbation of dyspnea and wheezing with angiotensin converting enzyme inhibitor therapy.

Front 11

64. What is the current recommendation for the perioperative medical management of patients on angiotensin-converting enzyme inhibitors?

Back 11

64. The current recommendation for the perioperative management of patients on angIotensin converting enzyme inhibitor therapy is to continue these drugs in the perioperative period. The rebound hypertension, bronchospasm, and metabolic changes that are frequently seen with the discontinuation of other antihypertensive agents have not been noted to occur with the discontinuation of angiotensin converting enzyme inhibitor agents, however.

Front 12

65. What is potential problem during the induction of anesthesia that may be seen in patients who are taking an angiotensin-converting enzyme inhibitor fOJ the treatment of essential hypertension?

Back 12

65. There is some evidence to suggest that patients on angiotensin converting enzyme inhibitors may have a more severe hypotension with the induction of anesthesia than the hypotension seen in patients on other antihypertensive agents. In addition, prolonged hypotension intraoperatively during general anesthesia has been observed in these patients, particularly during operative procedures that involve large fluid shifts. For this reason, some anesthesiologists choose to discontinue angiotensin converting enzyme inhibitor therapy preoperatively.

Front 13

66. Which adrenergic receptor does clonidine act on? How does the administration of clonidine result in a decrease in blood pressure?

Back 13

66. Clonidine acts centrally by stimulating alpha-2 adrenergic receptors. Stimulation of alpha-2 adrenergIc receptors causes a decrease in the outflow of sympathetic nervous system impulses to the periphery. Clinically, the effect of c10nidine to decrease sympathetic nervous system activity results in decreases in cardiac output, systemic vascular resistance, and blood pressure.

Front 14

How does the administration of clonidine affect the patient's anesthetic requirements?

Back 14

67. Small doses of clonidine administered preoperatively result in sedative and! or analgesic effects. This is reflected by a decrease in the minimum alveolar concentration (MAC) of anesthetic required. Sympathetic nervous system responses to direct laryngoscopy and surgical stimulation are attenuated with prior clonidine administration as well.

Front 15

68. What are some of the potential negative effects associated with the initial and chronic administration of clonidine?

Back 15

68. Negative side effects that may accompany the initial administration of c1onidine include sedation, bradycardia, and dry mouth. The most significant adverse effect of chronic clonidine therapy is a rebound hypertensive crisis with abrupt discontinuation of fie drug. Rebound hypertension is thought to result from an abrupt increase in systemic vascular resistance due to the release of catecholamines.

Front 16

69. What is the duration of action of a single dose of clonidine?

Back 16

69. The duration of action of a single dose of c10nidine is 6 to 24 hours. This explains why the administration of clonidine in the preoperative period may result in postoperative sedation.

Front 17

70. What is the role of clonidine in opioid withdrawal?

Back 17

70. Clonidine has been used to suppress symptoms of opioid withdrawal. It is presumed to be effective secondary to its alpha-2 mediated inhibition of sympathetic nervous system activity. (.

Front 18

71. How does c10nidine affect the plasma catecholamine level of a patient with a pheochromocytoma?

Back 18

71. Despite the ability of c10nidine to lower plasma catecholamine levels in hypertensive patients, clonidine does not decrease the amount of circulating catecholamines in a patient wit a pheochromocytoma.

Front 19

72. What is the effect of clonidine injected into the epidural or intrathecal space? What are the benefits and drawbacks to :his route of c10nidine administration?

Back 19

72. Clonidine injected into the epidural or intrathecal space has an analgesic effect. The benefit of this route of administration of clonidine is that, unlike opioids, it does n~t produce respiratory depression, pruritus, or nausea and vomiting. Bradycardia and sedation are the aegative side eifects of epidural or intrathecal clornfuJe administration.

Front 20

76. What is the mechanism by which prazosin lowers blood pressure?

Back 20

76. Prazosin is a selective alpha-l receptor antagonist, with little alpha-2 receptor activity. Because it blocks the activity of norepinephrine at the alpha-l receptor, it acts to lower blood pressure by decreasing systemic vascular resistance.

Front 21

77. What are some potential uses of prazosin? What are two potential side effects associated with the administration of prazosin?

Back 21

77. Potential uses of prazosi.ll include the creatment of essential hypertension, decreasing afterload in pajents with congestive heart failure, and as a preoperative medication in a patient with a pheochromocytoma. Two prominent side effects of prazosin therapy are fluid retentio[ and orthostatic hypertension.

Front 22

78. What is the mechanism by which verapamil lowers blood pressure? What are some potential intraoperative side effects of calcium channel blockers?

Back 22

'8. Verapamil is a calcium channel blocker. Calcium channel blockers have several cardiovascular effects, including decreased heart rate, decreased cardiac contractility, decreased cardiac conduction velocity, and the dilation of cerebral, coronary, and systemic arterioles. Calcium channel blockers used mtraoperatively may have exaggerated effects on blood pressure and myocardial depression when used in combination with inhaled anesthetics. Calcium channel blockers may potentiate the effects of neuromuscular blocking drugs, although this effect is not likely to be noted clinically

Front 23

79. What is; the mechanism by which labetalol lowers blood pressure')

Back 23

79. Labetalol lowers blood pressure through its activity as an antagonist at alpha1 and beta-adrenergic receptor

Front 24

80. What is a potential side effect that may be associated with the administration of labetalol?

Back 24

80. The administration of labetalol may be accompanied by prominent orthostatic hypotension, because both alpha and beta responses to decreases in blood pressure are blocked. Although potential bronchospasm is a concern for patients on beta-blocker therapy, bronchospasm appears to be less likely with labetalol than it is with other nonselective beta-adrenergic receptor antagonists. (

Front 25

81. What is the primary clinical use of beta-l agonists?

Back 25

81. The primary clinical use of beta-l agonistl is to increase heart rate and myocardial contractility. Isoproterenol is a primarily beta-l selective agonist whose clinical uses include its administration to increase the heart rate in a patient after heart transplantation, to act as a chemical pacemaker in a patient with complete heart block, and to decrease pulmonary vascular resistance in a patient with valvular heart disease. The use of beta-l agonists is limited by their potential to cause cardiac dysrhythmias and to increase myocardial I oxygen requirements.

Front 26

82. What is the primary clinical use of beta·2 agonists?

Back 26

82. The primary clinical use of beta-2 agonists is for the treatment of bronchial asthma and premature labor through !heir effects of bronchial and uterine smooth muscle relaxation. Albuterol, a beta- 2 agonist, is the current preferred · treatment of bronchospasm in an anesthetized patient. the administration of albuterol under these conditions is best achieved through the use of a metereddose inhaler during a mechanically producei inspiration. Each metered actuation of aerosol delivers about 90 fLg to the patient. This method of delivery provides for rapid onset and minimizes systemic drug levels. Terbutaline is a , beta-2 agonist tha may be administered subcutaneously for the treatment of ' intraoperative bronchospasm.

Front 27

83. What are some potential adverse effects of the administration of beta-2 agonists?

Back 27

83. Although beta-2 agonists have fewer cardiac effects than beta-l agonists, the administraton of these drugs can lead to a reflex tachycardia either due to beta-2 medi~ted vasodilation md hypotension or by the direct stimulation of

Front 28

84. What is tachyphylaxis to beta agonists attributed to?

Back 28

84. Chronic stimulation of beta-2 receptors leads to a tachyphylaxis, which is attributed to a decreased s.:nsitivity or a decreased number of receptors. The number of receptors in lipid cell membranes is dynamic, such that the number of receptors can become down-regulated in response to specific stimuli. This response is known as tachyphylaxis and can be seen to occur after chronic asthma treatment with beta agonists.

Front 29

85. What is the mechanism by which beta antagonists decrease blood pressure?

Back 29

85. Beta-adrenergic antagonists, or beta blockers, exert several effects. Most beta antagonists have antagonist effects at both beta-l and beta-2 receptors, although with varying degrees of selectivity. Effects of beta-adrenergic antagorusts include decreases in heart rate, cardiac contractility, and cardiac conduction velocity, renin release, lipolysis, bronchoconstriction, and peripheral vasoconstriction. Beta antagonists most likely decrease blood pressure by decreasing cardiac output.

Front 30

86. What are some clinical uses of beta antagonists?

Back 30

i. Beta antagonists are used clinically to decrease blood pressure, to decrease heart rate, for the treatment of myocardial ischemia, for postinfarction manlent, for the treatment of cardiac dysrhytbmias, for thyrotoxicosis man1S prophylaxi; against migraine headaches.

Front 31

87. What are some potential benefits of the administration of beta antagonists?

Back 31

87. Beta antagonist therapy for the treatment of hypertension has several benefits their ability to decrease heart rate and contractility, decrease mvocardilll their ability to decrease heart rate and contractility, decrease myocardial oxygen requirements in addition to decreasing blood pressure. Clinically, in patients with ischemic heart disease, this may manifest as relief of angina pectoris. With regard to beta-adrenergic blockade therapy in the postmyocardial infarction population, several studies have shown that the therapy results in a decrease in mortality and a decrease in the incidence of myocardial reinfarction.

Front 32

88. What are some potential adverse effects associated with beta-adrenergic blockade therapy?

Back 32

88. There are several potential adverse effects associated with beta-adrenergic blockade therapy. Two major adverse effects of this type of therapy are excessive myocardial depression and bronchoconstriction. Myocardial depression may precipitate congestive heart failure in some patients secondary to the decrease in myocardial contractility associated with beta-adrenergic blockade.

Front 33

89. What are some of the signs of excessive drug-induced beta blockade? What is the recommended treatment?

Back 33

89. Signs of excessive drug-induced beta-adrenergic blockade include bradycardia and atrioventricular block. Atropine, a muscarinic antagonist, is the initial treatment of choice in these situations. If the beta blockade persists, the administration of a beta-specific agonist such as isoproterenol or dobutamine is indicated. Large doses of these drugs may be required to reverse the blockade. Another agent that may be useful for reversal of beta blockade is calcium chloride at conventional doses, although the mechanism by which this is effective is not known.

Front 34

90. Which type of beta-adrenergic blocker is best selected for patients needing betablockade therapy who also have a history of bradycardia or depressed left ventricular function?

Back 34

90. In patients with bradycardia or depressed left ventricular function in whom beta-blockade therapy is indicated, drugs that have intrinsic sympathomimetic activity are the most appropriate treatment. Some myocardial depression with volatile anesthetics has been shown to occur, but the combined administration of volatJle anesthetics with beta-adrenergic blockers has not been shown to have clinically significant additive effects.

Front 35

91. Which type of beta-adrenergic blocker is best selected for patients needing betablockade therapy who also have a history of asthma or chronic obstructive pulmonary disease?

Back 35

91. The bronchoconstriction that o.ay accompany beta-2 adrenergic blockade may be detrimental in patients who have a history of asthma or chronic obstructive pulmonary disease. Drugs that are selective for beta-l adrenergic receptors are the most appropriate treatment for these patients when beta blockade therapy is indicated, Examples of beta-l selective drugs inaude esmolol and netoprolol.

Front 36

94. What can result from the abrupt discontinuation of beta-adrenergic blockade?

Back 36

94. Chronic beta-adrenergic blockade thenpy results in an up-regulation of the beta receptors. Abrupt discontinuation of beta-blockade therapy can be associ- I ated with excessive sympathetic nervous system activity from the increased amount of receptors activated with a single stimulus. The enhanced activity may manifest clinically as hypertension, tachycardia, and myocardial ischemia

Front 37

95. Name two peripheral vasodilators commonly used as continuous intravenous infusions In clinical anesthesia practice to decrease systemic blood pressure. What is their mechanism of action?

Back 37

95. Two peripheral vasodilators commonly used as intravenous infusions in clinical mesthesia practice include nitroprusside and nitroglycerin. Nitroprusside is believed to act by both arteriolar and venous dilation, whereas nitroglycerin is believed to act primarily through venous dilation. The mechanism of action for both agents is believed to be through the generation of the intracellular endogenous vasodilator nitric oxide.

Front 38

96. What is a potential negative effect associated with the administration of nitroprusside?

Back 38

96. Two potential negative effects associated with the administration of nitroprusside include cyanide toxicity and methemoglobinemia. The breakdown of nitroprusside in the blood produces cyanide in a dose-dependent manner.

Front 39

97. What is the mechanism of action of adenosine? What is a clinical use of adenosine?

Back 39

97. Adenosine is an endogenorn compound that dilates coronary vessels through an as yet unknown mechanism. It has been postulated to work by increasing levels of cyclic adenosine monophosphate. It is used clinically to treat ! paroxysmal supraventricular tachycardia through its effect of producing a transient block of atrioventricular nodal conduction. (4<

Front 40

98. What is a clinical use of inhaled nitric oxide?

Back 40

98. Inhaled nitric oxide has been used to manage patients with pulmonary hypertension. When used for this purpme it is administered at a dose of 5 to 40 ppm. It acts by vasodilating the pulmonary vasculature and improving arterial > oxygenation. Nitrc oxide is rapidly inactivated when bound to hemoglobin. Because of this, inhaled nitric oxide produces no systerric vasodilation. (44; ,

Front 41

99. What is the mechanism of action of anticholinergics?

Back 41

99. Anticholinergics, including atropine, scopolamine, and glycopyrrolate, are muscanmc antagonists. The mechanism of action of these drugs is to competitively inhibit the action of acetylcholine at cholinergic receptors.

Front 42

100. Which of the anticholinergics has a quaternary ammonium structure? What is its major clinical use in clinical anesthesia?

Back 42

100. Glycopyrrolate has a quaternary ammonium structure that prevents glycopyrrolate from crossing lipid membranes. The effects of glycopyrrolate are therefore limited to peripheral cholinergic receptors. In clinical anesthesia, glycopyrrolate is mostly used to block the muscarinic side effects of the anticholinesterase drugs that are being administered for the reversal of neuromuscular blockade.

Front 43

101. Which of the anticholinergics are tertiary amines?

Back 43

101. Atropine and scopolamine are tertiary amines, making these drugs able to cross lipid membranes such as the blood-brain barrier and placenta. These drugs are therefore able to exert effects centrally and on the fetus of a Parturient

Front 44

102. What is the mechanism of action of anticholinesterases?

Back 44

102. Anticholinesterases act by inhibiting the enzyme acetylcholinesterase, or true cholinesterase. Anticholinesterases inhibit the hydrolysis of acetylcholine at cholinergic receptors after it has been released from the nerve terminal. Consequently, when an anticholinesterase has been administered, acetylcholine accumulates at nicotinic and muscarinic receptor sites and may compete more effectively for those receptors.

Front 45

103. Which of the anticholinesterases are quaternary ammonium structures? What is their major clinical use?

104. Which of the anticholinesterases are tertiary amine structures? What is their major clinical use in the periopmtive period?

Back 45

103. Anticholinesterases that are quaternary ammonium structures and not able to cross lipid membranes such as the blood-brain barrier include neostigmine, pyridostigmine, and edropboniUl1 · These anticholinesterases are used clinically in the I!versal, or antagonism, of muscle relaxation produced by nondepolarizing neuromlBcular Diocking drugs. The quaternary ammonium strucwe limits the action of these drugs to peripheral cholinergic sites such as the neuromuscular junction.

104. An anticholinesterase that is a tertiary amine structure and able to cross lipid membranes is physostigmine. The major clinical use of physostigmine in the perioperative period is the treatment of central anticholinergic syndrome. Central anticholinergic syndrome may manifest as emergence delirium in the postanesthesia care unit after the administration of atropine or scopolamine.