Stoelting Study 2

Front 1

1. What is the most practical method to evaluate autonomic nervous system function at the bedside? What results would suggest autonomic nervous system dysfunction?

Back 1

1. The most practical bedside evaluation of autonomic nervous system function preoperatively is a test for evidence of autonomic nervous system dysfunction. A test for autonomic nervous system dysfunction involves first measuring the blood pressure and heart rate while the patient is in the supine position. The patient then assumes an upright posture. After 5 minutes, blood pressure and heart rate measurements are again taken. A systolic blood pressure decrease of more than 30 mm Hg and the absence of an increase in heart rate indicates that the patient may have autonomic nervous system dysfunction. It implies that the autonomic nervous system does not respond to a decrease in blood pressure by increasing the heart rate, as would be expected from an intact autonomic nervous system.

Front 2

2. What central nervous system structures make up the central autonomic nervous system? What functions do each of these structures control?

Back 2

2. The central autonomic nervous system is made up of the hypothalamus, medulla, and pons. The hypothalamus is responsible for the control of stress lonses, blood pressure, and temperature regulation. The medulla and pons together provide for hemodynamic and ventilatory control.

Front 3

3. The peripheral autonomic nervous system is divided into what two systems? What is the path by which impulses are conducted in both these systems?

Back 3

3. The peripheral autonomic nervous system is divided into the parasympathetic nervous system and the sympathetic nervous system. Both of these systems have myelinated, preganglionic fibers that arise from the central nervous system and synapse on postganglionic fibers. The unmyelinated, postganglionic fibers synapse on the target effector organs.

Front 4

4. What is the function of autonomic ganglia? What neurotransmitter and receptor are involved in the autonorric ganglia?

Back 4

4. A number of cell bodies converge at the autonomic ganglia. This is where synapse between the preganglionic and postganglionic nerve fibers of the peripheral autonomic nervous system occurs. Autonomic ganglia may also serve integrative and processing functions that modulate the synapse. The neurotransmitter relemed at this site is acetylcholine, which acts on nicotinic cholinergic receptors.

Front 5

5. For the parasympathetic nervous system, from where do the preganglionic fibers arise? What neurotransmitter is released by the postganglionic nerve fibers? What receptor type is found at the target organ? How are the postganglionic fibers distributed?

Back 5

5. Preganglionic nerve fibers of the parasympathetic nervous system arise from craniosacral nerves of the central nervous system. The neurotransmitter released by the postganglionic fibers is acetylcholine. Acetylcholine acts on · muscarinic cholinergic receptors at the target, or effector, organ. The distribution of the postganglionic fibers of the parasympathetic nervous system is very selective and discrete. The tenninal ganglia are near the innervated effector organs, resulting in the discrete discharge of impulses. (3

Front 6

6. For the sympathetic nervous system, from where do the preganglionic fibers arise? What neurotransmitter is released by the postganglionic nerve fibers? What receptor type is found at the target organ? How are the postganglionic fibers distributed?

Back 6

6. Preganglionic nerve fibers of the sympathetic nervous system arise from the thoracolumbar nerves of the central nervous system. The neurotransmitter released by the postganglionic fibers is norepinephrine. Norepinephrine acts on adrenergic receptors at the target, or effector, organ. Postganglionic fibers of the sympathetic nervous system are widely distributed throughout the body. The discharge of impulses is generalized, such that a mass reflex response results from stimulation of the sympathetic nervous system

Front 7

7. What are the three classes of adrenergic receptors? What endogenous neurotransmitter primarily stimulates each of these receptors?

Back 7

7. The three classes of adrenergic receptors are the alpha, beta, and dopamine receptors. Alpha- and beta-adrenergic receptors are primarily stimulated by the endogenous neurotransmitter norepinephrine, whereas dopamine receptors are stimulated by the neurotransmitter dopamine.

Front 8

8. How is the pharmacologic response of catecholamines altered by changes in the density and sensitivity of alpha and beta receptors?

Back 8

8. The density and sensitivity of alpha and beta receptors play a role in the degree of phannacologic response seen when these receptors are stimulated by a neurotransmitter. The number of receptors in lipid cell membranes is dynamic, such that receptors can increase in number (up-regulation) or decrease in number (down-regulation) in response to specific stimuli. For example, increased plasma concentrations of norepinephrine result in decreases in the density, or down-regulation, of beta receptors in cell membranes. This down-regulation of receptors decreases the sensitivity of the effector organ to the neurotransmitter. This response is known as tachyphy}axis and can be seen to occur after chronic asthma treatment with beta 1 agonists. Conversely, when beta receptors are chronically blocked, up-regulation of the receptor can result. The increased number of receptors can result in an exaggerated response to minimal stimulation. This explains the rebound tachycardia that can result from discontinuation of a patient's beta-blockade therapy.

Front 9

9. How do alpha-2 receptors exert their physiologic effect when stimulated?

Back 9

9. Alpha-2 receptors are found presynaptically, or on the preganglionic cell that releases norepinephrine. When stimulated, the alpha-2 receptor functions to feedback negatively on the postganglionic cell, inhibiting the subsequent release of neurotransmitter from the cell. Postsynaptic alpha-2 receptors on platelets contribute to platelet aggregation when stimulated.

Front 10

10. How is termination of the action of norepinephrine accomplished?

Back 10

10. Tennination of the action of norepinephrine at its receptor is primarily by its reuptake into the postganglionic nerve ending. Monoamine oxidase is an enzyme m the cytoplasm of the postganglionic cell that acts to deaminate a small amount of the norepinephrine that has been taken up. Most of the norepinephrine, however, escapes deamination and is stored for re-release with subsequent stimulation

Front 11

11. What are the two classes of cholinergic receptors? How is the action of acetycholine terminated at these receptors?

Back 11

· 11. There are two classes of postsynaptic receptors in the parasympathetic nervous system; both cholinergic receptors are stimulated by acetylcholine. The nicotinic type of receptor lies in the autonomic ganglia between the preganglionic cell and the postganglionic cell. Nicotinic receptors are also subtypes of the cholinergic receptor that is found in the neuromuscular junction. The muscarink type of receptor is found at the effector organ and is stimulated by the release of acetylcholine by the postganglionic cells. The action of acetylcholine is terminated at these receptors by its hydrolysis. The enzyme responsible for hydrolyzing acetylcholine at the receptor is acetylcholinesterase, or true cholinesterase.

Front 12

13. Name some examples of catecholamines that are and are not found endogenously. What is their basic chemical structure? Which receptors do they stimulate? What is their clinical use?

Back 12

13. Examples of catecholamines found endogenously include dopamine, norepinephrine, and epinephrine. Isoproterenol and dobutamine are catecholamines that do not occur endogenously. The basic structure of catecholamines is a U1<ll uu 11Ul occur endogenously. The basic structure of catecholammes IS a positions of the ring. Catecholamines stimulate the adrenergic receptors. Clinically, catecholarnines are administered mostly for their cardiovascular effects, usually as intravenous infusions.

Front 13

14. How does the dose of dopamine administered affect its clinical response? Why must dopamine be administered as a contimous intravenous infusion?

Back 13

14. Dopamine stimulates the adrenergic receptor subtypes (dopamine, beta, and alpha) depending on the dose of dopamine being administered. The clinical response to dopamine varies accordingly, depending on which subtype of receptor is primarily being stimulated. At doses between 0.5 and 3.0 J.Lg/kgl min, dopamine receptors are stimulated. Dopamine infusions at a dose of 3 to 10 ILglkglmin result increasingly in beta-adrenergic receptor stimulation. Combined beta- and alpha-adrenergic receptor stimulation by dopamine occurs when it is administered at doses between 10 and 20 f.Lg/kg/min. Alphaadrenergic effects of dopamine predominate at doses greater than 20 J..Lglkgl min. Patients respond variably to dopamine, making it important to titrate its administration to a dose that yields the desired response. The rapid metabolism of dopamine requires that it be administered as a continuous intravenous infusion.

Front 14

15. What clinical situation is dopamine most often used in?

Back 14

15. Dopamine is most often used clinically in patients with symptoms of shock or severe congestive heart failure. Symptoms that are frequently treated with the administration of a dopamine infusion often include a decreased cardiac output, decreased blood pressure, increased left ventricular end-diastolic pressure, and oliguria. Inotropic effects of dopamine increase cardiac output, whereas its effect on redistributing blood flow to the kidneys helps to increase unne output.

Front 15

16. What are the two methods by which dopamine exerts its myocardial inotropic effects?

Back 15

16. Dopamine exerts its myocardial inotropic effects through direct beta-adrenergic receptor stimulation, as well as indirectly by causing the release of endogenous stores of norepinephrine. Clinically, beta-adrenergic receptor stimulation by dopamine manifests as increased myocardial contractility without marked changes in heart rate or blood pressure. When cardiac catecholamine stores are depleted, as in chronic congestive heart failure, the indirect effect of dopamine on the heart is less reliable.

Front 16

18. How does dopamine affect the ventilatory response to hypoxemia?

Back 16

18. Dopamine acts as an inhibitory neurotransmitter at the carotid bodies. This is in part reflected by its interference with the ventilatory response to hypoxemia.

Front 17

19. How does dopamine affect the release of insulin?

Back 17

19. Insulin release is inhibited by dopamine administered at high doses as a result · of the corresponding alpha-adrenergic receptor stimulation. Clinically, this may result in hyperglycemia. (37)

Front 18

20. How should dopamine be prepared? What can result from the preparation of dopamine in alkaline solutions?

Back 18

20. Dopamine should be prepared in a solution of 5% dextrose in water. Dopamine may be inactivated when prepared in solutions that are more alkaline than 5% de~trose in water. (37)

Front 19

21. What does the local extravasation of dopamine result in? How can it be treated?

Back 19

21. The local extravasation of dopamine causes an intense, painful, local vasoconstriction. This localized vasoconstriction can be treated with the local infiltration of phentolamine, an alpha-adrenergic receptor antagonist that opposes the vasoconstrictive action of alpha-l adrenergic receptors. (37)

Front 20

22. Which adrenergic effect of norepinephrine predominates, the alpha or the beta? How may norepinephrine be used clinically?

Back 20

22. Norepinephrine is a neurotransmitter that stimulates both alpha- and betaadrenergic receptors. Endogenously norepinephrine acts to maintain blood pressure by adjusting the systemic vascular resistance via its stimulation of these receptors. Its stimulatory effects on alpha-l adrenergic receptors predominate over its beta-l agonist effects, thereby explaining its primary effect of increasing the systemic vascular resistance. The increase in systemic vascular resistance resulting from its release is reflected by increases in systolic, diastolic, and mean arterial pressures. Norepinephrine may be used clinically to treat refractory hypotension. For example, it may be used intraoperatively to treat refractory hypotension that can occur immediately after ligation of the vascular supply to a pheochromocytoma. Prolonged intravenous infusions of norepinephrine can result in gangrene of the digits, owing to its profound peripheral vasoconstrictive properties. (38; 552-553)

Front 21

23. What are the two methods by which norepinephrine may decrease cardiac output?

Back 21

23. The administration of norepinephrine can result in a decrease in cardiac l by two methods. First, through increasing systemic vascular resistance, afterload is increased. This increases the pressure the heart must overcome to maintain its stroke volume. Second, baroreceptor-mediated reflex bradycardia in response to the increase in blood pressure may contribute to a decrease in cardiac output.

Front 22

24. Which adrenergic receptors are stimulated by epinephrine?

Back 22

24. Epinephrine stimulates alpha-I, beta-I, and beta-2 adrenergic receptors

Front 23

25. How does epinephrine affect systemic vascular resistance?

Back 23

25. Low dose infusions of epinephrine result in vasoconstriction of the skin, mucosa, hepatic, and renal vessels through its stimulation of alpha-l receptors. Stimulation of beta-2 receptors during low-dose epinephrine infusions results in vasodilation of skeletal muscle vessels. The net effect is a decrease in systemic vasculature resistance and redistribution of blood flow to skeletal muscle.

Front 24

26. How does epinephrine affect renal blood flow?

Back 24

26. Epinephrine is a potent renal vascular vasoconstrictor through its alpha-l adrenergic effects. Even without changes in systemic blood pressure, renal blood flow is significantly decreased with the administration of epinephrine.

Front 25

27. How does epinephrine affect the myocardium and myocardial function?

Back 25

27. The administration of epinephrine results in an increase in cardiac output through its beta-l adrenergic effects. Stimulation of beta-l adrenergic receptors by epinephrine increases heart rate, cardiac contractility, and cardiac automaticity. The increase in cardiac automaticity can manifest as cardiac irritability. Premature ventricular contractions are the most frequently seen clinical manifestations of cardiac irritability during epinephrine infusions.

Front 26

28. What are the endocrine and metabolic effects of epinephrine?

Back 26

28. Epinephrine increases metabolic activity through its beta-adrenergic effects and inhibits the release of insulin through its alpha-l adrenergic effects. Together, the stimulation of these receptors by epinephrine results in adipose tissue lipolysis, liver glycogenolysis, and increased circulating levels of glucase, lactate, and free fatty acids. The endogenous release of epirephrine most likely accounts for the hypogIycemia often observed in patients in the perioperative period.

Front 27

29. What are some clinical uses of epinephrine?

Back 27

29. There are several clinical uses of epinephrine. At low doses, epinephrine may be administered in situations of decreased cardiac contractility. The beta-l effects of epinephrine directly increase contractility and cardiac output in those situations. The subcutaneous administration of epinephrine is commonly used in combination with local anesthetics to vasoconstrict the vasculature locally, improving operatng conditions and prolonging the effect of the local anesthetic. The same mechanism accounts for the prolongation of the effect of local anesthetics by epinephrine in the epidunl space. The subcutaneous administration of epinephrine may also be used to treat bronchospasm or to stabilize mast cells as in an allergic reaction. Inhaled racemic epinephrine may be administered to treat airNay edema or bronchospasm. Finally, epinephrine may be administered as a bolus during times of life-threatening allergic reactions, refractory bradycardia, or cardiovascular collapse.

Front 28

30. Which adrenergic receptors are stimulated by isoproterenol?

Back 28

30. Isoproterenol stimulates beta-l and beta-2 adrenergic receptors. Isoproterenol does not have any apparent effect on alpha receptors. (38; 555)

Front 29

31. How does isoproterenol affect the myocardium and myocardial function?

Back 29

31. Isoproterenol exerts its myocardial effects through its stimulation of betaadrenergic receptors. This is consistent with its observed cardiac effects of increased contractility, increased heart rate, increased cardiac output, increased aut)maticity, and an increase in systolic blood pressure . Isoproterenol may decrease coronary Mood low, which can have detrimental effects in patients with ischemic heart disease. This is secrndary to its ability to cause an excessive tachycardia while decreasing diastolic blood pressure. This leads to an increase in myocardial oxygen demand while simultaneously decreasing Its blood flow supply. (38; 555)

Front 30

32. Why is isoproterenol of limited utility in patients with ischemic heart disease?

Back 30

32. Isoproterenol is of limited utility in patients with ischemic heart disease for several reasons. First, the administration of isoproterenol results in tachycardia combined with a decrease in diastolic blood pressure. This results in increases in myocardial oxygen demand while simultaneously decreasing myocardial oxygen delivery. Second, isoproterenol administration is associated with a high incidence of cardiac dysrhythmias due to increased cardiac automaticity. Finally, the beta-2 effects of isoproterenol result in the diversion of blood flow to skeletal muscles. These three events combined limit the utility of isoproterenol in patients with a history of ischemic heart disease.

Front 31

35. What are some clinical uses of isoproterenol?

Back 31

5. Clinical uses of isoproterenol include its administration to increase the heart rate of a patient after heart transplantation and to decrease pulmonary vascular resistance in a patient with valvular heart disease. Isoproterenol has been used to act as a chemical pacemaker in patients with complete heart block but is now no longer included in the American Heart Association's Advanced Cardiac Life Support protocol. (38; 555)

Front 32

36. Which adrenergic receptors are stimulated by dobutamine?

Back 32

36. Dobutamine stimulates beta-l adrenergic receptors without significant effects on beta-2 or alpha receptors. (38;

Front 33

37. What are some of the clinical effects of dobutamine?

Back 33

37. Dobutamine has similar clinical effects as isoproterenol with regard to increases in myocardial contractility and increases in cardiac conduction velocity. Dobutamine has minimal chronotropic or cardiac dysrhythmic effects, however. Clinically, the predominant effect of dobutamine is to increase cardiac output in a dose-dependent fashion. The dose for the infusion of dobutamine for this purpm~ is between 2 and 20 mcg/kglmin.

Front 34

39. What are some clinical uses of dobutamine? Which patients may benefit from simultaneous infusions of dobutamine and dopamine?

Back 34

39. Dobutamine may be useful clinically for patients with congestive heart failure The direct-acting effects of dobutamme are effective in patients such as these The direct-acting effects of dobutamine are effective in patients such as these who have depleted catecholamine stores, and dobutamine is less likely to cause tachycardia or extend the size of an infarct than other catecholamines. Dobutamine may be administered in combination with dopamine in patients who are hypotensive and oliguric, as can occur with cardiogenic shock. The combination of dobutamine and dopamine can increase cardiac output, augment blood pressure, and increase renal blood flow. Prolonged treatment with dobutamine can result in down-regulation of beta receptors, thereby decreasing the effectiveness of dobutamine.

Front 35

38. How does dobutamine affect systemic vascular resistance?

Back 35

38. Dobutamine often decreases systemic vasculature resistance. (38; :

Front 36

42. What are sympathomimetics?

Back 36

42. Sympathomimetics are synthetic drugs whose chemical structure resembles catecholamines. Sympathomimetics have actiors at the adrenergic receptors that are similar to, but less potent than, those of catecholamines. They are often used clinically to reverse the hypotension that car. accompany Spinal, epidural, or general anesthesia. (39; 555

Front 37

43. How are sympathomimetics classified?

Back 37

43. Sympathomimetic; are classified according to the receptors that they selectively stimulate and by their mechanism of action. Sympathomirr:etics may act directly by binding to the Jeceptor to mimic the efftcts of a catecholamine or indirectly by evoking the release of an endogenous catecholamine. (39;

Front 38

44. What are some potential adverse cardiac effects that can result from the administration of sympathomimetics?

Back 38

44. The administration of a sympathomimetic may result in cardiac dysrhythmias or a decrease in cardiac output. Cardiac dysrhytbmias may result from the administration of a sympathomimetic that has beta-l adrenergic effects. A decrease in cardiac output may result from the administration of a sympathomimetic with alpha-adrenergic effects unopposed by beta-adrenergic effects. The mechanism by which the decrease in cardiac output may occur is primarily due to reflex-mediated bradycardia. A compensatory reflex-mediated bradycardia may accanpany the peripheral vasoconstriction and increase in blood pressure caused by alpha·adrenergic receptor stimulation.

Front 39

45. What can result from the administration of a direct-acting sympathomimetic or an indirect-acting sympathomimetic to a patient chronically treated with antihypertensives that decrease sympathetic nervous system activity?

Back 39

45. Patients chronically treated with antihypertensives that decrease sympathetic nervous system activity, for example, beta-adrenergic receptor blockers, may have altered responses to sympathomimetics. When a direct-acting sympathomimetic is administered to these patients the pharmacologic response may be enhanced. this is because of the body's natural response to increase the number of receptors in response to the chronic blockade, so that a given amount of administered sympathomimetic will stimulate a greater number of receptors and exert a greater than normal response. Conversely, when an indirect-acting sympathomimetic is administered to these patients, the pharmacologic response may be decreased. While the sympathomimetic is attempting to elicit a response by endogenous catecholamine release, there is a direct antagorusm of beta-adrenergic activity by the antihypertensive, thereby causing a lesser than normal response

Front 40

46. What can result from the administration of a sympathomimetic to a patient on monoamine oxidase inhibitor or tricyclic antidepressant therapy? When are these patients at the greatest risk of this adverse reaction? How should the anesthetic , technique be altered in these patients?

Back 40

46. Monoamine oxidase inhibitors and tricyclic antidepressants may increase the availability of endogenous norepinephrine. Monoamine oxidase is an enzyme found in the cytoplasm of postganglionic cells that deaminates norepinephrine such that it is unavailable for re-release. Ephedrine, an indirect-acting sympathomimetic, may cause exaggerated blood pressure response, with its administration to these patients.

Front 41

47. What is the current recommendation for the perioperative medical management of patients on monoamine oxidase inhibitors or tricyclic antidepressants?

Back 41

7. The current recommendation for the perioperative medical management of patients on monoamine oxidase inhibitors or tricyclic antidepressants is to continue the medicines as prescribed throughout the perioperative period. The medicines are not believed to introduce an unacceptable anesthetic risk of an adverse drug reaction.

Front 42

48, What is the mechanism of action of ephedrine?

Back 42

48. Ephedrine is primarily an indirect-acting sympathomimetic, with some direct

Front 43

49. What are the cardiovascular effects of ephedrine?

Back 43

49. Ephedrine, like epinephrine, increases systolic and diastolic blood pressures, heart rate, and cardiac output. These effects are primarily mediated through the beta-l adrenergic receptor stimulation that results from the administration of ephedrine. The clinical cardiovascular effects of ephedrine are similar to those of epinephrine but are about 10 times less potent and persist about 10 times longer. Systemic vascular resistance is only minimally altered with ephedrine administration. This is because the effects of peripheral vasculature vasoconstriction due to alpha-adrenergic stimulation are counteracted by the vasodilation of the skeletal muscle vasculature due to beta-2 adrenergic stimulation.

Front 44

50. Why does ephedrine have the potential to elicit cardiac dysrhythmias with its administration?

Back 44

50. Ephedrine has the potential to elicit cardiac dysrhythmias with its administration secondary to its beta-adrenergic stimulatory effects. This potential for cardiac dysrhytbmias increases in the presence of drugs or agents that sensitize the heart to the effects of catecnolamines, such as halothane.

Front 45

51. How are the clinical cardiovascular effects of ephedrine altered in patients with drug-induced beta-adrenergic blockade?

Back 45

51. The cardiovascular effects of ephedrine are primarily due to beta-l receptor stimulation, although ephedrine does have stimulatory effects at alpha-l adrenergic receptors. The admmistration of ephedrine typically manifests clinically as an increase in myocardial contractility and an increase in cardiac I output. Patients on chronic beta-adrenergic blockade therapy, however, may clinically respond to the administration of ephedrine with effects resembling alpha-l adrenergic stimulation.