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Anaesthesiology
Opioids
Built from Barash Clinical Anesthesia, 9th Edition
What’s inside
18 sections · 196 slides
Overview
- What this topic covers
- Roadmap of this topic
Background and history
- Scale of current opioid use
- Harms that followed the rise in prescribing
- Education needed for safe opioid prescribing
- Ancient origins of opium
- Milestones in opioid development
- Chemical structures of commonly used opioids
- Fenylpiperidines in anaesthesia
The body's own opioid system
- Components of the endogenous opioid system
- Functions regulated by the opioid system
- Mu receptor subtypes described in rodents
- The endogenous opioid peptides
- Opioid receptors as G-protein-coupled receptors
- Signalling from receptor to effect
- Analgesia and breathing share one pathway
- Opioids acting at more than one receptor
- Multifunctional and biased opioids in development
- Ketamine's action at opioid receptors
Nociception and pain
- Nociception versus pain
- Definition of pain
- Key statements accompanying the pain definition
Classifying the opioids
- Opioids grouped by origin
- Grouping opioids by potency
- Opioid behaviour at the receptor
How opioids relieve pain
- Two effects of opioids on pain
- Pathway from injury to the brain
- Descending inhibitory pathways
- Opioid receptors in the spinal cord
- Evidence that the endogenous system drives analgesia
- Three forms of endogenous opioid analgesia
- Conditioned pain modulation
- Opioids in peripheral inflammatory pain
- The immune system as a source of analgesia
Hyperalgesia and tolerance
- Opioid-induced hyperalgesia
- Mu receptor is not required for hyperalgesia
- Hyperalgesia after remifentanil anaesthesia
- Preventing pain after remifentanil anaesthesia
- Hyperalgesia, tolerance and pseudotolerance
- Cellular basis of tolerance
- Tolerance to respiratory depression develops slowly
- Mechanisms behind opioid tolerance
- Fentanyl tolerance in opioid use disorder
Pharmacokinetics
- Fate of an intravenous opioid dose
- Physical properties that shape opioid kinetics
- Plasma concentration after a bolus
- Volume of distribution and what it predicts
- Context-sensitive half-time
- Why offset of effect is hard to predict
Metabolism and metabolites
- Where and how opioids are broken down
- Three ways metabolism matters clinically
- Lead-in to the interaction table
- Inhibitors and inducers of CYP3A and inhibitors of CYP2D6
- Inhibitors and inducers of CYP3A and inhibitors of CYP2D6 (continued)
- Morphine metabolism and its two glucuronides
- Transport of morphine metabolites
- Morphine in renal failure
- Metabolism of fentanyl and sufentanil
- Why remifentanil is different
- Methadone metabolism and its risks
- Naloxone metabolism
Pharmacodynamics
- Pharmacokinetics versus pharmacodynamics
- What a PKPD model is for
- The effect compartment
- Hysteresis and the equilibration half-life
- The sigmoid Emax model
- Choosing the right population for a model
- Why the EEG is a poor dosing end point
- Clinically relevant C50 values
- Lead-in to the equilibration half-life table
- Estimates of analgesic equilibration half-life for pain relief and respiratory depression
- Estimates of analgesic equilibration half-life for pain relief and respiratory depression (continued)
Titrating opioids to pain relief
- Between-patient variability in morphine need
- Sources of variability in opioid effect
- Reliability of pain scoring
- The case for careful titration
- Titration end points differ before and after surgery
- Morphine dosing figures after surgery
- A practical morphine dosing plan
- Two rules for every postoperative pain plan
- Adjuvants when morphine is not working
The individual opioids
- Fentanyl: potency and speed
- Fentanyl during anaesthesia
- Timing and accumulation of fentanyl
- From high-dose fentanyl to balanced anaesthesia
- Fentanyl in chronic pain
- Other fentanyl delivery routes
- Sufentanil
- Clinical profile of sufentanil
- Remifentanil and breathing
- Variability of remifentanil potency
- Remifentanil and propofol together
- Practical remifentanil infusion advice
- Optimal wake-up after remifentanil-propofol anaesthesia
- Pain after remifentanil fast-track anaesthesia
- Buprenorphine's unusual receptor profile
- Ceiling effect and its clinical uses
- Limits of buprenorphine's safety
- Oliceridine and the utility function
- Utility function validation and limits
Pharmacogenetics
- What pharmacogenetics covers
- CYP2D6 and the metabolizer phenotypes
- Effect of CYP2D6 phenotype on codeine
- A fatal case of codeine in breast milk
- Genotype explanation of the codeine death
- ABCB1 variation and fentanyl toxicity
Opioid-induced respiratory depression
- Scale of the problem
- Brainstem sites of respiratory depression
- Progression of an opioid overdose
- Why a slow injection is safer
- Why monitoring choice hides the effect
- Opioid effects on the upper airway
- Nocturnal hypoxaemia on PCA morphine
- Supplemental oxygen masks hypoventilation
- Opioid-induced muscle rigidity
- Reported incidence of respiratory depression
- The PRODIGY trial definition of an event
- What the high event rate means
- PRODIGY risk factors for respiratory depression
- Risk factors in children
- Utility functions for comparing opioids
- Alcohol added to oxycodone
- Practical advice on combinations
Reversing respiratory depression
- Naloxone as the drug of choice
- Naloxone pharmacology
- Renarcotization
- Titrated naloxone dosing
- Why titration preserves pain relief
- Reversing high-affinity opioids
- Remifentanil and nasal naloxone
- Drawbacks of naloxone
- Respiratory stimulants in development
- Limits of the new stimulants
Monitoring
- Limits of haemodynamic signs as nociception measures
- Signals used by nociception monitors
- The Nociception Level monitor
- Spot checks miss hypoxaemia on the ward
- Arousal failure after repeated apnoea
- Breathing patterns behind the saturation alarm
- Monitors that measure breathing directly
- The integrated pulmonary index
- Wearable continuous monitors
Other side effects
- Range of non-respiratory opioid side effects
- Scale of opioid-induced nausea and vomiting
- Mechanism of opioid-induced nausea and vomiting
- Treating and preventing nausea and vomiting
- Opioid effects on the gut
- Treating opioid-induced bowel dysfunction
- Sphincter of Oddi and biliary effects
- Urinary retention
- Central and peripheral cardiovascular effects
- Clinical cardiovascular consequences
Summary and references
- Key points: mechanism and classification
- Key points: endogenous system and hyperalgesia
- Key points: tolerance and pharmacokinetics
- Key points: metabolism and genetics
- Key points: dosing and titration
- Key points: respiratory safety
- Key points: risk groups and reversal
- Key points: new drugs and other side effects
- References
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- References (continued)
- Barash, Cullen, and Stoelting's Clinical Anesthesia, 9th Edition