1. Opioid Medications and Sleep-disorder Breathing (SDB) 1

2. Topics to be covered Opioid pharmacological effects Opioid induced sleep- disorder Breathing Management 2

3. Analgesic Classification 1. Narcotics - no ceiling effect except partial agonists and mixed agonist-antagonist 2. Non-narcotics - NSAIDs/Coxibsceiling effect 3. Adjuvant analgesic or coanalgesics - tricyclic antidepressants - antiepileptics - steroids - Bisphosphonates, calcitonin 3

4. Opiate Receptor Interactions 4 Drug Receptor mukappadeltaSigma* Full Agonists Morphine++++++ Fentanyl++++ + Alfentanil+++ ? Sufentanil*+++++ + Hydromorphone+++ ++ Methadone+++ ++ Meperidine++ Codeine+ Oxycodone+++++ BuprenorphineP---

5. Opiate Receptor Interactions 5 Drug Receptor mukappadeltaSigma* Mixed agonist-antagonists Nalbuphine---+++ Pentazocine-+++ ++ Nalorphine-P +++ Antagonists Naloxone------ Naltrexone------

6. Pharmacology of Opiate Receptors 6 Mu receptor - supraspinal analgesia - euphoria - respiratory depression (mu 2 ? ) - constipation - urinary retention - nausea, vomiting - physical dependence - miosis - lack of response to external stimuli

7. Pharmacology of Opiate Receptors 7 Delta receptor - spinal analgesia - nausea, vomiting Kappa receptor - spinal analgesia - sedation - miosis

8. Control of normal breathing 8 Complex interaction between central respiratory pacemakers and interactions with central and peripheral chemoreceptors and mechanoreceptors Central respiratory pacemaker are located in the pontomedullary reticular formation (rostral ventrolateral medulla oblongata and retrotrapezoid/parafacial respiratory nucleus)

9. Opioids and control of respiration 9 Many opioid receptors are located in the central respiratory pacemakers and chemoreceptors Primary opioid receptors involved in control of respiration are assumed to be u-receptor >> d- receptors >> k-receptors k-receptors have little respiratory depressant activity

10. Opioids induced sleep-disorder Breathing 10 Central apnea during sleep Ataxic breathing during sleep: Biot breathing Obstructive apneas Hypoxemia

11. Treatment of opioid-induced SDB 11 Reduce opioid dose by 50% and use multimodal analgesics Naloxone reversal Choose opioid with less respiratory depression Continuous positive airway pressure (CPAP) support

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