Opioid Adverse Effect Management

Aka: Opioid Adverse Effect Management, Opioid Adverse Effect, Narcotic Side Effect, Opioid-Induced Nausea, Opioid-Induced Constipation, Opioid-Induced Hyperalgesia

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II. Indications

  1. Cancer Pain Opioid
  2. Chronic Opioid

III. Approach: Pearls

  1. Many Opioid Adverse Effects are predictable and can be prophylaxed
  2. Consider Opioid intolerance as an opportunity to transition back to Non-Opioid Analgesics

IV. Adverse Effects: Constipation

  1. Tolerance does not develop to constipating effects
    1. Contrast with the tolerance that develops for Analgesic effects
  2. Begin Bowel regime concurrently with Narcotics
    1. See Bowel Regimen in Chronic Narcotic Use
    2. Sample protocol
      1. Polyethylene Glycol solution (Miralax) and
      2. Peristaltic stimulant (senna alkaloid)
      3. Historically, Docusate (Colace) has been used with this combination, but unlikely to add benefit
  3. Consider other Constipation Causes
    1. See Constipation in Cancer
  4. Precautions
    1. Fecal Impaction may present as overflow Diarrhea
    2. Regular stooling for comfort should still be maintained even as intake decreases
    3. Reevaluate Anticholinergic Medications that further provoke Constipation
  5. Refractory cases in cancer patients
    1. Methylnatrexone (Relistor)

V. Adverse Effects: Nausea or Vomiting

  1. See Nausea in Cancer
  2. Types
    1. Initial Nausea when starting medication
      1. Consider Antiemetic for first 3-5 days
    2. Persistent Nausea on starting Opioid (ChemoreceptorTrigger Zone stimulation)
  3. Antiemetics
    1. 5-HT3 Receptor Antagonist (e.g. Ondansetron or Zofran)
    2. Phenothiazines (e.g. Prochlorperazine)
    3. Dimenhydrinate (Dramamine)
    4. Metoclopramide (Reglan)

VI. Adverse Effects: Miscellaneous

  1. Hypogonadism (86% of Chronic Opioid users)
    1. Reduces Testosterone and Estrogen levels
    2. Results in decreased libido, Erectile Dysfunction and irregular Menses
  2. Opioid Analgesic related confusion
    1. Methylphenidate reverses confusion
  3. Opioid reactions
    1. Typically not Allergic Reactions
    2. True Opioid anaphylactic reactions are rare (<1 to 2%)
      1. Avoid all Morphine analogs (e.g. Codeine) if opioid Anaphylaxis history
      2. Avoid semi-synthetics (e.g. Hydromorphone, Hydrocodone, Oxycodone) if opioid Anaphylaxis history
      3. Completely synthetic Opioids (e.g. Fentanyl, Methadone) are safe if opioid Anaphylaxis history
    3. Local Histamine release is common at the Morphine injection site
      1. Presents at localized erythema and Urticaria, Flushing, itching, sweating
      2. Orthostatic Hypotension may occur
      3. More common with Morphine and Codeine than with other Opioids (Fentanyl, Hydrocodone, Oxycodone)
      4. Consider pretreatment with Antihistamine (e.g. Cetirizine)
  4. Opioid induced hyperalgesia or neuroexcitation (Opioid Toxicity response)
    1. May present as hyperalgesia, Allodynia, Delirium. or Myoclonus
    2. Higher risk with high Opioid doses and prolonged, Chronic Opioid use
    3. Masquerades as increasing, often widespread pain and common mistaken approach is to increase Opioid dose
    4. Evaluation
      1. Evaluate for new, organic causes of pain
      2. Consider alternative diagnoses (e.g. Opioid tolerance, Opioid Withdrawal)
    5. Management
      1. Decrease the Opioid dosing gradually (discuss the counterintuitive expected pain improvement)
      2. Consider alternative Opioid sparing agents in acute pain (e.g. Analgesic dose Ketamine)
      3. Consider adjunctive agents for Chronic Pain (e.g. Gabapentin), but risk of potentiating Opioid Overdose
      4. Manage comorbidities (e.g. Major Depression, Anxiety Disorder)
      5. Consider switching to Buprenorphine for Chronic Pain
    6. References
      1. (2023) Presc Lett 30(7): 42
  5. Serotonin Syndrome
    1. Synthetic Opioids (esp. Tramadol, Fentanyl, Methadone, Dextromethorphan) are frequent cause
  6. CNS and Respiratory Depression (high dose)
    1. Additive effects with other CNS Depressants (e.g. Alcohol, Benzodiazepines) and Neuromuscular Blockers
    2. See Opioid Overdose
    3. Risk of death
  7. Psychiatric effects (high dose)
    1. Nightmares
    2. Anxiety
    3. Dysphoria
    4. Major Depression

VII. References

  1. (2018) Presc Lett 25(8)

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