Overview
This lecture covers clinically relevant and board-focused side effects of opioids, including overdose emergencies, reversal agents, drug interactions, and tolerance/addiction concepts.
Opioid Overdose and Respiratory Depression
- Opioid overdose is a medical emergency due to severe respiratory depression, leading to hypoventilation and COâ‚‚ retention.
- Poor ventilation causes respiratory acidosis and altered mental status.
- Pinpoint pupils (miosis) and shallow breathing are classic overdose findings.
- Pain itself acts as a natural antagonist against opioid-induced sedation/respiratory depression.
- Maintain airway patency and provide supplemental oxygen; monitor end-tidal COâ‚‚.
- Narcan (naloxone) is the acute reversal agent administered slowly to avoid sudden withdrawal.
Opioid Reversal Agents
- Naloxone is a competitive antagonist at the mu-opioid receptor with rapid onset but short half-life (30–90 minutes).
- Repeated naloxone dosing (0.4–2 mg IV q2–3 min) may be needed for long-acting opioids; consider infusion for persistent effects.
- Peripherally acting antagonists (e.g., methylnaltrexone) do not cross the blood-brain barrier and are not used for CNS reversal.
- Rapid reversal risks precipitating acute withdrawal and possible non-cardiogenic pulmonary edema.
Side Effects and Drug Interactions
- All patients on opioids develop constipation; tolerance does not develop for this side effect.
- Peripherally acting antagonists (methylnaltrexone, naloxegol) are used for opioid-induced constipation unresponsive to laxatives.
- Opioids can cause smooth muscle spasm (e.g., sphincter of Oddi), worsening pancreatitis or causing urinary retention.
- Certain opioids (demerol, tramadol) can cause serotonin syndrome, especially when combined with SSRIs, notably fluoxetine or paroxetine.
Tolerance, Dependence, and Addiction
- Repeated opioid use leads to tolerance (diminished effect) and physical dependence (withdrawal if stopped).
- Tolerance and dependence are not the same as addiction, which involves compulsive use and psychological craving.
- Withdrawal symptoms include agitation, nausea, diarrhea, yawning, sweating, and pupillary dilation.
- Methadone can be used for opioid rotation and may reduce tolerance development via NMDA antagonism.
Additional Opioid Adverse Effects
- Opioids cause histamine release, leading to itching, vasodilation, and possible hypotension.
- Not all side effects are allergies; most "opioid allergies" are histamine-mediated side effects.
- Opioids depress the cough reflex and can cause nausea/vomiting by stimulating the chemoreceptor trigger zone.
- Dose adjustments may be needed in renal impairment, especially for morphine and hydromorphone.
Key Terms & Definitions
- Naloxone (Narcan) — Opioid antidote; competitive mu-receptor antagonist for rapid reversal of CNS depression.
- Methylnaltrexone — Peripherally acting opioid antagonist used for refractory opioid-induced constipation.
- Tolerance — Reduced drug effect over time, requiring higher doses.
- Physical dependence — Physiological adaptation causing withdrawal on stopping the drug.
- Addiction — Compulsive drug seeking with loss of control despite harm.
- Serotonin syndrome — Life-threatening toxicity from excess serotonin, presenting with confusion, tremor, fever.
- Sphincter of Oddi spasm — Opioid-induced smooth muscle contraction, impairing pancreatic drainage.
Action Items / Next Steps
- Review opioid reversal protocols, side effect management, and relevant drug interactions.
- Study opioid tolerance, dependence, and addiction differences for exams.
- Be familiar with indications for naloxone, methylnaltrexone, and naloxegol.
- Read more on opioid-induced serotonin syndrome and differentiating opioid side effects from allergies.