• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

Card Range To Study



Play button


Play button




Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

41 Cards in this Set

  • Front
  • Back
2. What is the mechanism of action of opioids?
2. Opioids exert their effects through their agonist actions at the opioid receptor. to a receptor, there are at least two mechanisms by which ooioids alter thf". to a receptor, there are at least two mechanisms by which opioids alter the activity of the cell. The main action of opioids appears to be through the interaction with G proteins, resulting in inhibition of the activity of adenylate cyclase and increasing potassium conductance. This ultimately results in hyperpolarization of the cell and leads to a suppression of synaptic transmission. The second mechanism by which opioids may produce their effect is through the interference of calcium ion intracellular transport in the presynaptic cell. This results in interference with the release of neurotransmitter from the presynaptic cell and again suppresses synaptic transmission. Neurotransmitters that are affected by this mechanism of action of opioids include acetylcholine, dopamine, norepinephrine, and substance P.
3. Describe the location, subtypes, and pharmacologic responses of the opioid receptors. What are the primary receptor subtypes for supraspinal and spinal analgesia?
3. Opioid receptors are located in various tissues throughout the central nervous system, including the cerebral cortex, medial thalamus, periaqueductal gray matter, substantia gelatinosa, and sympathetic preganglionic neurons. The five subtypes of opioid receptors are the mu-I, mu-2, delta, kappa, and sigma receptors. Supraspinal analgesia is mediated primarily by the mu receptors, whereas spinal analgesia is mediated primarily by the delta and kappa receptors.
4. What endogenous ligands normally bind to and activate opioid receptors?
4. Endorphins and enkephalins are endogenous ligands that nonnally bind to and activate opioid receptors.
5. How does the affinity of the opioid for the receptor correlate with its potency?
5. The greater the affinity of the opioid for its receptor, the smaller the dose of opioid required to exert a given effect. Therefore, the affinity with which an opioid binds to the opioid receptor directly correlates with its analgesic potency. It also correlates with the opioid molecule's stereochemistry.
6. Where are the opioid receptors located in the spinal cord? .
6. Opioid receptors of the mu, kappa, and delta type are located in the substantia gelatinosa in the spinal cord
7. How do differences in lipid solubility influence the action of epidural opioids?
7. Opioids administered in the epidural space must diffuse across the dura to bind to opioid receptors on the spinal cord. The more lipid soluble the opioid, the more rapid the diffusion across the dura at the sight of injection. In contrast, the less lipid-soluble agents diffuse slowly and have more potential to migrate cephalad in the cerebrospinal fluid. For this reason, epidurally administered fentanyl and sufentanil, which are more lipid soluble than morphine, will tend to have a quicker onset and shorter duration of action and will exert their effects more locally than epidurally administered morphine.
8. How significant is the systemic absorption of opioid after its administration into the intrathecal or epidural space?
8. The systemic absorption of intrathecal opioid is minimal. Opioids administered in the epidural space are significantly absorbed systemically, however, such that the plasma concentration of the opioid is similar to what it would have been if the same dose had been intramuscularly administered.
9. What are some potential side effects of neuraxially administered opioids?
9. Side effects associated with the neuraxial administration of opioids appear to occur in a dose-dependent manner. The side effects are likely due to both the systemic absorption of opioid as well as the effects of opioid in the cerebrospinal fluid. Therefore, some of the potential side effects of neuraxially administered opioids that can potentially occur are similar to those that can occur with the intravenous administration of opioids. These include sedation, nausea and VOll1ltmg, and, most importantly, respiratory depression. Side effects that are more specific to neuraxially administered opioids include pruritus and urinary retention.
10. What is the time course of respiratory depression that may be seen after the administration of neuraxia! opioids? How can it be treated?
10. Clearly the most concerning side effect that may accompany the epidural or spinal administration of opioids is respiratory depression. The patient must be in an environment where he or she can be assessed for at least 24 hours after the administration of the opioid. The assessment must be global, because the patient's ventilatory status is not adequately assessed by respiratory rate alone. In fact, a decrease in the patient's level of consciousness is also an indicator of hypercarbia and respiratory depression. Respiratory depression after the administration of epidural opioids can occur early or be delayed. Early respiratory depression, occurring in the first 2 hours after injection, is thought to be due to vascular uptake and redistribution. Delayed respiratory depression can occur between 6 and 12 hours after injection and is believed to be due to the rostral spread of opioid in the cerebrospinal fluid to the ventilatory centers located in the floor of the fourth ventricle. Respiratory depression should be treated immediately with the support of ventilation by the administration of oxygen and positive-pressure ventilation if necessary. Naloxone, an opioid antagonist, administered in small doses and titrated to effect, may reverse the respiratory depression without reversing the analgesia provided by the opioid.
11. What are some risk factors for respiratory depression after the administration of neuraxial opioids?
11. Risk factors for respiratory depression after the administration of neuraxial opioids include high administered opioid doses, the administration of an opioid with a low lipid solubility, the administration of concurrent intravenous opioids or other intravenous sedatives, the administration of opioids to a patient who lacks tolerance to opioids, and advanced age.
12. How effective is morphine for the relief of pain? What are some other clinical I effects of morphine?
12. Morphine appears to be highly effective for the relief of pain that arises from the viscera, skeletal muscles, and joints. Other clinical effects of morphine include euphoria, sedation, and altered mentation. (n)
13. What is the benefit derived from the administration of opioids minutes before the induction of anesthesia?
13. The administration of opioids minutes before the induction of anesthesia may be beneficial in that it may attenuate the blood pressure and heart rate responses to direct laryngoscopy and intubation of the trachea. It may also contribute to · preemptive analgesia. ('
14. What is preemptive analgesia?
14. Preemptive analgesia has been defined as "antinociceptive treatment that pre- l vents the establishment of altered central processing, which amplifies postoperative pain." Some studies have suggested that an intensely noxious stimulus can result in sensitization of the central nervous system to subsequent painful stimuli, resulting in a level of pain that is subsequently perceived to be higher than it otherwise would have been. Given this, preemptive analgesia describes the phenomenon in which the injection of an opioid before a noxious stimulus results in decreases in the amount of narcotic required after the pain-inducing stimulus for the subsequent control of the pain. For example, the injection of an opioid before painful surgical stimulation may decrease the amount of narcotic needed in the postoperative period for analgesia. (72; 2325)
15. What are the potency, time of onset, and duration of action of opioids dependent on? How rapid is the effect-site equilibration time of morphine relative to the other opioids?
15. The potency of an opioid is related to its affinity for the opioid receptor. The time of onset, or effect-site equilibration time, and duration of action of an opioid are related to its lipid solubility and degree of ionization at physiologic pH. A greater lipid solubility and greater nonionization allow for quicker crossing of the blood-brain barrier, quicker access to the central nervous system to exert its effects, and quicker redistribution to inactive tissue sites. ForI example, morphine has a relatively low lipid solubility and is only 10% to 20% nonionized at physiologic pH, accounting for its relatively prolonged effect-site equilibration time. In fact, less than 0.1% of intravenously administered mor· phine has reached the blood-brain barrier at the time of peak: plasma concentration, which takes 15 to 30 minutes to occur. The intramuscular injection of morphine exerts its peak effect in 45 to 90 minuites.
16. How are opioids cleared from the plasma? Which opioids have active metabolites?
16. Opioids are cleared principally by hepatic metabolism. Morphine is the only opioid that possesses an active metabolite. About 10% of the metabolism of morphine is to the active metabolite morphine-6-glucuronide. Morphine-6glucuronide has analgesic and ventilatory depressant effects and is eliminated by renal excretion. It is more potent at the mu receptor than morphine and has I a similar duration of action. Care must be taken when administering morphine to patients with renal failure because the elimination of the active metabolite of morphine may be prolonged. Morphine's principal metabolite, morphine-3glucuronide, is inactive.
17. "What are the effects of opioids on the cardiovascular system?
17. There are several mechanisms by which the administration of opioids may result in hypotension. These include histamine release, centrally mediated decreases in sympathetic tone, vagal-induced bradycardia, and direct and indirect venous and arterial vasodilation. For example, morphine may result in hypotension primarily due to histamine release or through centrally mediated decreases in sympathetic tone. The release of histamine is most likely to accompany the administration of morphine when high doses of morphine are administered .. rapidly. The effects of morphine on blood pressure may manifest clinically only as orthostatic hypotension in the supine, normovolemic patient. The hypotension as orthostauc nypotenslOn 10 me sup1Oe, normovolemic patient. The hypotension stimulation. Hypertension may accompany the administration of opioids secondary to inadequate dosing of the opioid or to the ill-timed administration of the opioid relative to the stimulus inducing the increase in blood pressure
18. What are the effects of opioids on ventilation?
18. All the fill-receptor agonist opioids produce a dose-dependent depression of ventilation. This is reflected by an increase in the resting PaC02, an increase in the apneic threshold, a decrease in the responsiveness to the ventilatory stimulant effects of carbon dioxide, and a decrease in the hypoxic ventilatory drive. The administration of opioids also affects the rate of breathing and the tidal volume. The mechanism by which these effects of opioids on ventilation occurs is thought to be through the direct depression of the medullary ventilatory centers. Opioids may cause a decrease in the release of acetylcholine neurotransmitter at these centers. When apnea occurs as a result of opioid administration, the patient may spontaneously breathe if directed to do so.
19. What are the effects of opioids on the central nervous system?
19. The administration of opioids results in several central nervous system effects. First, the administration of opioids has been shown to cause modest cerebral vascular vasoconstriction when the Pac02 has been maintained normal under I controlled ventilation. This may also result in modest decreases in cerebral blood flow and intracranial pressure. Opioids are unable to produce a doserelated general depression of the central nervous system typical of other general anesthetics. This is reflected by their inability to produce an isoelectric electroencephalogram. Instead, opioids have a ceiling effect that is not overcome by increasing the administered dose of opioids. Opioids do contribute to the MAC of anesthesia delivered and decrease the amount of volatile agent required to achieve a given anesthetic depth. Opioids are not considered to be true anesthetics, however, because of their inability to reliably produce unconsciousness even in high doses. Finally, the administration of opioids causes miosis through its cortical inhibition of the Edinger-Westphal nucleus.
20. What are the effects of opioids on the thoracoabdominal muscles? How can it be treated?
20. The administration of opioids can result in increased thoracoabdorninal muscle tone, which may result in chest wall stiffness. This "stiff-chest" syndrome can be so severe that the muscle rigidity interferes with ventilation. The impairment of ventilation in these patients has been shown to be primarily due to closure of the vocal cords and not just the rigid chest wall. This syndrome can also result in increases in pulmonary artery pressure and central venous pressure. Although the exact mechanism for this muscle rigidity is not known, it appears to OCcur most frequently when rapid, large boluses of an opioid are initially administered. Termination of the rigidity to allow for ventilation can be aCCOffiplished through the administration of a neuromuscular blocking drug or an opioid antagonist such as naloxone. Prophylaxis against this muscle rigidity can be achieved through the administration of a priming dose of a nondepolarizing neuromuscular blocking drug and the slow, intermittent administration of opioid.
21. What are the effects of opioids on the gastrointestinal system?
21. Among the several effects opioids have on the gastrointestinal system are effects · on gastrointestinal motility, gastric emptying, and biliary smooth muscle tone. Opioids increase tone and decrease propulsive motility in both the small and large intestines. Opioids also increase the gastric emptying time through both central and peripheral effects of the opioid. Centrally, this effect is mediated by the vagus nerve. Peripherally, binding of an opioid to the opioid receptors in the myenteric plexus and cholinergic nerve terminals inhibits the release of acetylcholine at these nerve terminals. Opioids also increase pyloric sphincter tone, further contributing to a delay in gastric emptying. Opioids can cause spasm of biliary smooth muscle, increasing biliary duct pressure. Opioids also increase the tone of the sphincter of Oddi. In patients receiving intraoperative cholangiograms, approximately 3% of patients who have been administered opioids have opioid-induced spasm of the sphincter of Oddi. Together illese can result in an increase in intrabiliary pressure that may manifest as biliary colic or ffilllliC angma pectoris in the awake patient. The clinician can distinguish between opioid-induced biliary colic pain and myocardial ischemia through the administration of naloxone. Naloxone can relieve the pain of biliary colic, but it has no effect on the pain caused by myocardial ischemia. Glucagon also reverses biliary spasm due to opioids. Nitroglycerin has resulted in pain relief in both circumstances, making diagnosis dffiicult
22. What are the effects of opioids on the genitourinary system?
22. Opioids can enhance detrusor and ureteral sphincter tone, leading to urinary retention in some patients. When this occurs there may be the need to catheterize the patient's bladder to drain it.
23. What is the mechanism by which opioids are thought to cause nausea and vomiting?
23. There are several mechanisms by which opioids are thought to cause nausea and vomiting. The primary mechanism appears to be through the direct stimulation of dopamine receptors in the chemoreceptor trigger zone in the area postrema of the medulla.

n addition to this, opioids also increase gastrointestinal I secretions, decrease gastrointestinal tract motility, and prolong gastric emptying time. Other influences of the incidence of nausea and vomiting elicited by the administration of opioids are the age of the patient, female gender, obesity, type of surgery, duration of surgery, a history of gastroparesis, and the administration of nitrous oxide or etomidate.
24. Over what time course does acute tolerance to the analgesic effects of morphine develop? What are some of the characteristics of the opioid withdrawal syndrome in opioid-dependent patients?
24. Tolerance is the need over time to increase the dose of an agent to achieve a · given effect. With analgesic doses of morphine, for instance, after 2 to 3 weeks of administration acute tolerance to its analgesic effects begins to develop. Tolerance to the respiratory depressant effects of opioids may take months to develop. When patients are opioid dependent, the withdrawal of opioids can lead to a typical withdrawal abstinence syndrome within 15 to 20 hours. The syndrome is characterized by diaphoresis, muscle spasms, vomiting, diarrhea, fever, chills, hypertension, tachycardia, and behavioral disturbances. The withdrawal syndrome peaks in 2 to 3 days
25. How do opioids modulate immune function?
25. Opioids have been shown to modulate immune function through the modulation of neutrophil chemotaxis, phagocytic activity, and the secretion of cytokines. · The clinical significance of this is under investigation. C
26. What is the potency of meperidine relative to morphine?
26. Meperidine is about one tenth as potent as morphine.
27. What are some clinical effects of meperidine that are unique to this opioid?
27. Meperidine is unique among the opioids due to its chemical structure, effects on the heart, effects on shivering, and central nervous stimulatory effects of its metabolite. The chemical structure of meperidine resembles atropine, which i may account for its atropine-like effects on the heart. The administration of meperidine may lead to an increase in heart rate and a decrease in myocardial contractility. Meperidine may also lead to mydriasis rather than miosis, again likely due to its atropine-like structure. 1

The metabolite of meperidine, nonneperidine, can produce central nervous stimulation resulting in seizures with its administration. Caution must be taken with the administration of meperidine to patients with renal failure because normeperidine is cleared renally
28. What is the potency of fentanyl relative to morphine? .
28. Fentanyl is 75 to 125 times more potent than morphine.
29. How does fentanyl compare with morphine with regard to its effect-site equilibration time?
29. Fentanyl administered intravenously has a more rapid onset and shorter duration of action than morphine. This reflects its greater lipid solubility. The effect-site equilibration time of fentanyl is about 6.5 minutes. Its shorter duration of action is also reflective of its rapid redistribution to inactive tissue sites, leading to a rapid decrease in the plasma concentration of fentaly
30. How are the effects of fentanyl terminated? How does the context-sensitive halftime of fentanyl compare with other opioids? .
10. The effects of fentanyl are terminated through its redistribution to inactive tissue sites followed by its metabolism by the liver. High intravenous doses of fentanyl or a continuous intravenous infusion can lead to saturation of the inactive tissue sites. This may result in prolonged redistribution, prolonged elimination, and '
31. What are some systemic clinical effects associated with the administration of fentanyl?
31. The administration of fentanyl is associated with a decrease in heart rate. The administration of fentanyl alone leads to little change in systemic blood pressure, whereas its administration after a benzodiazepine may lead to decreases in blood pressure. There are also synergistic effects between fentanyl and benzodiazepines on ventilatory depression and sedation.
33. What is the potency of sufentarul relative to morphine?
33. Sufentanil is 500 to 1000 times more potent than morphine.
34. How does sufentanil compare with the other opioids with respect to its effect-site equilibration time and its context-sensitive half-time? .
34. Sufentanil has an effect-site equilibration time similar to fentanyl. Its contextsensitive half-time is less than that of alfentanil for infusions lasting less than 8 hours, but it is greater than that of remifentanil.
35. What are some systemic clinical effects associated with the administration of sufentanil?
35. Systemic clinical effects associated with the administration of sufentanil include depression of ventilation and bradycardia that appears to be greater than that Produced by fentanyl. Sufentanil in large doses may result in thoracoabdominal muscle rigidity as well.
39. What is the potency of remifentanil relative to morphine?
39. Remifentanil is 250 times more potent than morphine. (
40. How does remifentanil compare with the other opioids with respect to its effect-site equilibration time and its context-sensitive half-time?
40. Remifentanil has an effect-site equilibration time of about 1.4 minutes, which is shorter than that of fentanyl and sufentanil and about equal to that of alfentanil. The context-sensitive half-time of remifentanil is much shorter than that of the other opioids, about 4 minutes. It is also independent of the duration
41. What are some clinical uses of remifentanil?
41. Like alfentanil, the unique pharmacokinetic profile of remifentanil makes it desirable in cases where the response to a brief, intense stimulus requires blunting. It can also be used as maintenance anesthesia when rapid recovery might be desired, as during an intraoperative wake-up test for the evaluation of I · motor nerve integrity during spine surgery. When remifentanil is used as maintenance anesthesia, a longer-acting opioid may need to be administered before patient arousal for analgesia.
42. Name some of the agonist-antagonist opioids. What opioid receptors do these drugs often have strong and weak agonist affinities for?
42. Some of the agonist-antagonist opioids include pentazocaine, butorphanol, nalhave strong affinities for the kappa and delta receptors and only weakly bind have strong affinities for the kappa and delta receptors and only weakly bind the mu receptor.
43 . What are some advantages and disadvantages to the administration of agonistantagonist opioids?
43. The advantage of the administration of agonist-antagonist opioids is that they may only minimally depress ventilation. In addition, they are less prone to being abused secondary to their minimal euphoric effects. Unfortunately, ag- I orust-antagonist opioids have limited analgesic properties. These drugs have a ceiling effect, or a maximal dose above which increasing doses of drug do not provide additional analgesia. This limits their usefulness for the control of pain, making them infrequently used in the perioperative period
44 Name some of the opioid antagonist drugs. What is the mechanism of action of opioid antagonists?
44. Opioid antagonist drugs include naloxone, naltrexone, and nalmefene. These drugs exert their effects by binding to the mu opioid receptor, thereby displacing opioids from the receptor.
45. What is the dose of naloxone for the reversal of undesirable effects of opioids? How should it be administered?
45. In clinical anesthesia practice the administration of naloxone is best achieved with intermittent low doses until the opioid-induced depression of ventilation or pruritus is reversed while leaving a sufficient amount of analgesia for patient comfort. The administration of naloxone for the reversal of undesirable effects of opioids should be done in doses of 1 to 4 f,Lcg/kg. The rapid onset of naloxone allows for rapid, easy titration of the drug to the desired effect. The duration of action of naloxone is brief, about 30 minutes. It is possible that the previously reversed effects of the opioid may recur when the effects of naloxone pass. For this reason it is important to observe the patient for the recurrence of the opioid-induced effects that may necessitate a repeated administration of naloxone. Alternatively, a continuous infusion of naloxone may be administered.
46. What are some of the systemic clinical effects that may be associated with the administration of naloxone?
46. High doses of naloxone administered rapidly can result in rapid awakening with intense pain. Even in the absence of pain the administration of naloxone may result in intense sympathetic nervous system activity with tachycardia, hypertension, pulmonary edema, and cardiac dysrhythmias, including ventricular fibrillation. Caution should be used when administering naloxone for opioid reversal to patients who are at risk of myocardial ischemia.