Opioide Flashcards
1
Q
- Which opioid was the first completely synthetic opioid?
A
- Meperidine was the first completely synthetic opioid. It is a basic phenylpiperidine structure, and the fentanyl congeners are more complex versions of this same skeleton. (123)
2
Q
- In general terms, describe the acid-base status, protein-binding, and ionized state of the opioid class of drugs.
A
- In general, opioids are highly soluble weak bases that are highly protein bound and largely ionized at physiologic pH. These physicochemical properties affect their clinical behavior. (123)
3
Q
- What is the mechanism of action of opioids?
A
- Opioids exert their effects by acting as agonists at opioid receptors. They interact with G proteins to inhibit adenylate cyclase, increase potassium conductance, hyperpolarize the cell, and suppress synaptic transmission. (124)
4
Q
- Describe the locations and classes of opioid receptors.
A
- Opioid receptors are widely distributed in the central nervous system and peripheral tissues. They include the classical µ, κ, and δ receptors, which mediate analgesia and other effects. A fourth receptor, ORL1 (or nociceptin receptor), has also been identified but functions differently. (124)
5
Q
- How are opioids metabolized?
A
- In general, opioids are metabolized in the liver. Some undergo phase I oxidation while others are conjugated, and many of the metabolites are excreted renally. (125)
6
Q
- Which opioids have active metabolites?
A
- Both meperidine and morphine have active metabolites that can accumulate in renal failure; codeine is also metabolized to morphine by CYP2D6. (125)
7
Q
- What are the four key pharmacokinetic behaviors of opioids?
A
- The four key pharmacokinetic behaviors are: (1) latency to peak effect after a bolus (bolus front-end kinetics), (2) time to clinically relevant decay after a bolus (bolus back-end kinetics), (3) time to steady-state during an infusion (infusion front-end kinetics), and (4) time to decay after stopping an infusion (infusion back-end kinetics). (125-126)
8
Q
- What properties of an opioid affect its latency time to peak effect after a bolus injection?
A
- Latency to peak effect is influenced by the opioid’s ionization, protein binding, and lipid solubility. Un-ionized, highly lipid-soluble, and less protein-bound opioids rapidly equilibrate to the effect site. (126)
9
Q
- How is remifentanil different from other opioids when used as a continuous infusion?
A
- Remifentanil rapidly equilibrates to the effect site and is metabolized by non-specific esterases, allowing it to reach steady state quickly without dose accumulation. (127)
10
Q
- State a clinical example of how an opioid bolus latency time to peak effect would influence patient-controlled analgesia (PCA) dosing.
A
- Fentanyl’s rapid onset makes it suitable for PCA because its peak effect occurs before the lockout period ends, reducing the risk of dose stacking. (127)
11
Q
- What is context-sensitive half-time (CSHT)? What are some clinical implications of the CSHT?
A
- CSHT is the time required for the plasma concentration of a drug to decrease by 50% after stopping a continuous infusion; it varies with infusion duration. It guides the choice of opioid for desired recovery characteristics. (127)
12
Q
- What are some therapeutic effects of opioids?
A
- Therapeutic effects include analgesia, sedation, decreased airway irritability, and attenuation of the cough reflex. (128)
13
Q
- What are the effects of opioids on the cardiovascular system?
A
- Opioids generally produce minimal cardiovascular effects. However, fentanyl derivatives may increase vagal tone leading to bradycardia, and in some patients, they may decrease preload and afterload through central depression of vasomotor centers. (129)
14
Q
- What are the effects of opioids on ventilation?
A
- µ-Receptor agonist opioids cause a dose-dependent depression of ventilation, with increases in resting PaCO2, elevation of the apneic threshold, and reduced responsiveness to CO2 and hypoxia. (130)
15
Q
- What are the effects of opioids on the central nervous system?
A
- Opioids produce analgesia, sedation, and miosis without causing a profound general CNS depression. They also decrease the MAC of inhaled anesthetics. (130)
16
Q
- What are the effects of opioids on the thoracoabdominal muscles? How can they be treated?
A
- Opioids may increase thoracoabdominal muscle tone (stiff-chest syndrome), which can impair ventilation. This can be managed by administering a neuromuscular blocking drug or an opioid antagonist like naloxone. (130)
17
Q
- What are the effects of opioids on the gastrointestinal system?
A
- Opioids decrease gastrointestinal motility, delay gastric emptying, and increase the tone of the sphincter of Oddi, leading to ileus and biliary spasm. (130)
18
Q
- What are the effects of opioids on the genitourinary system?
A
- Opioids decrease bladder detrusor tone and increase urinary sphincter tone, which can result in urinary retention. (130)
19
Q
- What is the mechanism by which opioids are thought to cause nausea and vomiting?
A
- Opioids stimulate the chemoreceptor trigger zone in the area postrema, increase GI secretions, slow gastric emptying, and prolong intestinal transit, all contributing to nausea and vomiting. (130)
20
Q
- How do opioids modulate immune function?
A
- Both exogenous and endogenous opioids depress cellular immunity, for example by inhibiting interleukin 2 transcription in activated T cells, which may affect wound healing, infection risk, and cancer recurrence. (130)
21
Q
- What is an example of a pharmacokinetic drug interaction of opioids?
A
- An example is the increased opioid concentration when opioids are administered concurrently with a continuous propofol infusion, possibly due to hemodynamic changes. (130)
22
Q
- What is an example of a pharmacodynamic drug interaction of opioids?
A
- A key pharmacodynamic interaction is the synergistic sedative and ventilatory depressant effects when opioids are combined with sedatives, and their synergistic reduction of MAC when used with volatile anesthetics. (130)
23
Q
- What are some considerations of using opioids in patients with hepatic failure?
A
- In patients with hepatic failure, opioid metabolism may be altered; however, most opioids (except remifentanil) are primarily metabolized by the liver. Severe liver dysfunction can increase sensitivity to opioids. (131)
24
Q
- What are some considerations of using opioids in patients with kidney failure?
A
- Kidney failure is especially important for opioids like morphine and meperidine, whose active metabolites (M6G for morphine and normeperidine for meperidine) may accumulate and cause toxicity. (131)
25
Q
- Does gender have an influence on opioid pharmacology?
A
- Yes; for example, morphine tends to be more potent in women but has a slower onset of action. (131)
26
Q
- Does age have an influence on opioid pharmacology?
A
- Yes; older patients require lower doses of opioids (including remifentanil) due to pharmacodynamic differences and decreased clearance. (131)
27
Q
- How should opioids be dosed in obese patients?
A
- Dosing should be based on lean body mass rather than total body weight, because clearance is more closely related to lean body mass. (132)
28
Q
- What is the active compound of codeine?
A
- Codeine is metabolized in the liver to morphine via CYP2D6; about 10% of Caucasians lack this enzyme and do not obtain a therapeutic effect. (132)
29
Q
- How does the onset time of morphine compare with the other opioids? What are some potential drawbacks of the administration of morphine?
A
- Morphine has a prolonged latency to peak effect and slow CNS penetration due to low lipid solubility and high ionization. Drawbacks include delayed respiratory depression, potential dose stacking, histamine release, hypotension, and accumulation of active metabolites in renal failure. (133)
30
Q
- How does fentanyl compare with morphine with regard to its effect-site equilibration time? What is the potency of fentanyl relative to morphine?
A
- Fentanyl has a more rapid onset (effect-site equilibration time ~6.5 minutes) and is 75 to 125 times more potent than morphine due to its higher lipid solubility. (133)
31
Q
- What are some routes for the administration of fentanyl?
A
- Fentanyl can be administered IV, transdermally, transmucosally, transnasally, and via the pulmonary route. (133)
32
Q
- How are the effects of fentanyl terminated? How does the CSHT of fentanyl compare with other opioids?
A
- Fentanyl’s effects are terminated by redistribution and hepatic metabolism. With high doses or continuous infusions, cumulative effects may occur; compared to alfentanil and remifentanil, fentanyl has a longer context-sensitive half-time. (133)
33
Q
- What are some systemic clinical effects associated with the administration of fentanyl?
A
- Fentanyl can cause bradycardia, sedation, respiratory depression, and synergistic ventilatory depression when combined with benzodiazepines. (133)
34
Q
- What are some clinical uses of fentanyl in anesthesia practice?
A
- Fentanyl is used for perioperative analgesia, as an adjunct to induction and maintenance of anesthesia, to blunt sympathetic responses during laryngoscopy or surgical stimulation, and for preemptive analgesia. (133)
35
Q
- What is the potency of sufentanil relative to morphine?
A
- Sufentanil is significantly more potent than morphine; it is the most potent opioid currently in use in anesthesia practice. (133)
36
Q
- How does remifentanil compare with the other opioids with respect to its effect-site equilibration time and its CSHT?
A
- Remifentanil has a very short effect-site equilibration time and a CSHT of approximately 5 minutes, which is much shorter than that of other opioids and independent of infusion duration, due to its ester structure allowing rapid hydrolysis. (133)
37
Q
- What are some clinical uses of remifentanil?
A
- Remifentanil is used for total intravenous anesthesia (TIVA) in combination with propofol, as a bolus when rapid onset and recovery are needed, and during monitored anesthetic care. (134)
38
Q
- By what mechanism do opioid agonist/antagonists work?
A
- Opioid agonist/antagonists act as partial µ-receptor agonists while competitively antagonizing µ receptors and others, providing analgesia with a ceiling effect and less potential for respiratory depression and dependence. (134)
39
Q
- What are some clinical uses of opioid agonist/antagonists?
A
- They are used in chronic pain management and in opioid-addicted patients because of their reduced potency, ceiling effects, and lower risk of respiratory depression. (134)
40
Q
- What specific risks does tramadol use carry based on its receptor affinity?
A
- Tramadol, due to its weak opioid receptor activity combined with inhibition of serotonin and norepinephrine reuptake, carries a risk of serotonin syndrome, as well as CNS excitability and seizures. (134)
41
Q
- Why does preoperative buprenorphine use complicate perioperative pain management?
A
- Buprenorphine, a high-affinity partial agonist/antagonist, can block the effects of full opioid agonists, making acute pain management more challenging in patients using it chronically. (134)
42
Q
- What role does the opioid antagonist naloxone play in clinical practice? What are some adverse effects of naloxone?
A
- Naloxone is used to reverse opioid-induced ventilatory depression. Adverse effects include precipitating acute withdrawal, nausea, vomiting, tachycardia, hypertension, seizures, and pulmonary edema. (134)
43
Q
- What role does the opioid antagonist naltrexone play in clinical practice?
A
- Naltrexone, when administered orally, undergoes extensive first-pass metabolism and is inactive; however, if opioids containing naltrexone are crushed and injected, naltrexone acts as an antagonist. It is used as a deterrent to opioid abuse. (134)
44
Q
- What are some common clinical indications for the use of opioids in anesthesia practice?
A
- Common indications include postoperative analgesia (often via PCA), balanced anesthesia to reduce volatile agent requirements, and TIVA when used with propofol. (135)
45
Q
- What is the basis of opioid selection in different clinical situations?
A
- Opioid selection is based on pharmacokinetic differences (onset, duration, CSHT) and side-effect profiles (sedation, respiratory depression), with all µ-agonists considered equally efficacious when given in equipotent doses. (135)
46
Q
- What are some concerns regarding opioid use and cancer recurrence?
A
- There is ongoing controversy about the immunosuppressive effects of opioids potentially leading to increased cancer recurrence rates, but studies have shown conflicting results. (136)
