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Questions and Answers
What is a potential consequence of morphine metabolite accumulation in patients with kidney failure?
What is a potential consequence of morphine metabolite accumulation in patients with kidney failure?
What effect does the rapid administration of large doses of certain opioids have on ventilation?
What effect does the rapid administration of large doses of certain opioids have on ventilation?
What unique action does aspirin have compared to other COX inhibitors?
What unique action does aspirin have compared to other COX inhibitors?
What phenomenon may result from prolonged dosing of opioids?
What phenomenon may result from prolonged dosing of opioids?
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How do large doses of opioids affect the neuroendocrine stress response during surgery?
How do large doses of opioids affect the neuroendocrine stress response during surgery?
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What type of analgesic administration strategy has been shown to improve postoperative outcomes?
What type of analgesic administration strategy has been shown to improve postoperative outcomes?
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Which statement about opioid receptors is correct?
Which statement about opioid receptors is correct?
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What can result from the infusion of large doses of remifentanil during surgery?
What can result from the infusion of large doses of remifentanil during surgery?
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What is the primary purpose of multimodal analgesia in postoperative patients?
What is the primary purpose of multimodal analgesia in postoperative patients?
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Which of the following is a characteristic of COX inhibitors regarding their pharmacokinetics?
Which of the following is a characteristic of COX inhibitors regarding their pharmacokinetics?
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How do COX inhibitors primarily exert their effects on pain modulation?
How do COX inhibitors primarily exert their effects on pain modulation?
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Which of the following best describes the relationship between COX inhibitors and cardiovascular effects?
Which of the following best describes the relationship between COX inhibitors and cardiovascular effects?
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What are the typical plasma protein binding characteristics of COX inhibitors?
What are the typical plasma protein binding characteristics of COX inhibitors?
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Which of the following COX inhibitors is specifically formulated for topical application?
Which of the following COX inhibitors is specifically formulated for topical application?
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What happens to acetaminophen at increased doses in the body?
What happens to acetaminophen at increased doses in the body?
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What is a common misconception about multimodal analgesia?
What is a common misconception about multimodal analgesia?
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What is the primary clinical effect of opioids in most medical situations?
What is the primary clinical effect of opioids in most medical situations?
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How do agonist-antagonists differ from full agonists in terms of efficacy?
How do agonist-antagonists differ from full agonists in terms of efficacy?
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What neurotransmitters' release is inhibited by opioid receptor activation?
What neurotransmitters' release is inhibited by opioid receptor activation?
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Which mechanism is NOT affected by opioid receptor activation?
Which mechanism is NOT affected by opioid receptor activation?
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What is a potential side effect of opioid use related to peripheral receptors?
What is a potential side effect of opioid use related to peripheral receptors?
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What characterizes pure opioid antagonists?
What characterizes pure opioid antagonists?
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What pathway is involved in the modulation of pain through opioids?
What pathway is involved in the modulation of pain through opioids?
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Where do opioid receptors exert their greatest effect?
Where do opioid receptors exert their greatest effect?
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Study Notes
Analgesic Agents
- Morphine metabolites (morphine 3-glucuronide and morphine 6-glucuronide) in kidney failure can cause narcosis and ventilatory depression.
- Rapid administration of large opioid doses (fentanyl, sufentanil, remifentanil, alfentanil) can induce chest wall rigidity, making ventilation difficult.
- Prolonged opioid use can cause opioid-induced hyperalgesia, increasing pain sensitivity. General anesthesia with high doses of remifentanil can lead to tolerance, needing higher doses for post-operative analgesia.
- The neuroendocrine response to surgery (measured by hormones like catecholamines, antidiuretic hormone, and cortisol) is inhibited more by opioids than by volatile anesthetics.
- Aspirin irreversibly inhibits COX-1, leading to a nearly one-week duration of clinical effects, including inhibiting platelet aggregation.
Opioids
- Opioids bind to specific opioid receptors (mu, kappa, delta, sigma) throughout the CNS and other tissues, which are coupled to G proteins.
- Opioid receptors' binding of agonists induces effects like membrane hyperpolarisation, inhibiting adenylyl cyclase, activating phospholipase C, inhibiting voltage-gated calcium channels, and activating inwardly rectifying potassium channels.
- Opioid effects vary depending on exposure duration, and tolerance develops impacting opioid responses.
- Opioid receptor types (μ, κ, δ, σ) mediate varied effects (e.g., analgesia, sedation, respiratory depression). Specific agonists bind to specific receptors.
- Opioid receptor activation inhibits presynaptic release and postsynaptic response to excitatory neurotransmitters (like acetylcholine, substance P).
Pharmacokinetics
- Opioids have rapid and complete absorption after intramuscular or subcutaneous injection.
- Fentanyl's low molecular weight and high lipid solubility favor transdermal absorption via patches. Patch absorption is influenced by skin conditions.
- Fentanyl's serum concentration plateaus after 14-24 hours.
- Remifentanil has a very short half-life due to rapid hydrolysis by nonspecific esterases.
- Many opioid metabolites are eliminated by the kidneys.
- Significant amounts of lipid-soluble opioids can be retained in the lungs (first-pass uptake).
Structure-Activity Relationships
- Opioid agonists and antagonists share common structural features.
- Small molecular modifications can convert an agonist into an antagonist.
- Levorotatory (left-handed) opioid isomers are usually more potent than their dextrorotatory (right-handed) counterparts.
Biotransformation
- Opioids are primarily metabolized by the liver's cytochrome P450 system, conjugated via glucuronidation or other metabolic pathways.
- Codeine is a prodrug, activated in the liver to morphine, via CYP2D6.
- Remifentanil is hydrolyzed in the red blood cells by nonspecific esterases
Excretion
- Opioids metabolites are mainly excreted through the kidneys.
- Morphine metabolites (morphine-3-glucuronide, morphine-6-glucuronide) accumulation can be significant with impaired renal function.
Effects on Organ Systems
- Cardiovascular: Opioids can have minimal direct effects on the heart, but higher doses can lead to bradycardia. Histamine release can decrease systemic vascular resistance and blood pressure.
- Respiratory: Opioids significantly depress respiration by altering the respiratory centers, affecting CO2 response and potentially causing apneic periods.
- Cerebral: Opioids influence cerebral oxygen consumption, blood flow, and volume, although effects on ICP are minimal compared to other anesthetics.
- Gastrointestinal: Opioids slow GI motility and may cause constipation, biliary spasm, or sphincter of Oddi contraction.
- Endocrine: Opioids can inhibit hormone release like norepinephrine, antidiuretic hormone and cortisol, in response to surgery.
- Renal: Opioid metabolism and elimination depends on renal function, affecting duration of action for certain opioids.
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Description
This quiz covers the effects and mechanisms of analgesic agents, particularly focusing on opioids and their impact in various clinical scenarios. It explores the consequences of opioid use, including complications in patients with kidney failure and the consequences of rapid administration of high doses. Test your knowledge on how these agents work and their side effects in surgical settings.
