1. Pre-reading about Opioid Analgesia for Children Royal Children’s Hospital Melbourne Australia

2. The use of opium Opium was first discovered in pre- biblical times; derived from the opium poppy Opium was widely used from the middle ages in a medicine known as “tincture of opium” or Laudanum Children's Pain Management Service, RCH, Melbourne

3. What are opioids? All drugs with morphine-like actions are described as opioids Opioids were originally derived from the opium poppy (papaver somniferum) which has 25 alkaloids Only two of these alkaloids have any analgesic action: morphine and codeine Children's Pain Management Service, RCH, Melbourne

4. GlaxoSmithKline supplies ~25% of the world's medicinal opiate needs from opium poppies grown by farmers in Tasmania Children's Pain Management Service, RCH, Melbourne

5. Opioid or Narcotic? Opioid: natural, semi-synthetic and synthetic drugs that relieve pain by binding to opioid receptors in the nervous system Narcotic: obsolete term for opioid, because governments and media use the term loosely to refer to a variety of substances of potential abuse including opioids, cocaine and other substances Children's Pain Management Service, RCH, Melbourne

6. Opiate or Opioid? Opiate: term used to refer to drugs derived from the opium poppy, for example, morphine (thus excluding synthetic opioids such as fentanyl) Opioid: refers to any substance with morphine- like activity including natural, semi- synthetic and synthetic opioids Children's Pain Management Service, RCH, Melbourne

7. How morphine was named In 1805, a German pharmacist (Serturner) isolated an opium alkaloid He named it morphine (after Morpheus, the Greek god of sleep) Children's Pain Management Service, RCH, Melbourne

8. How do opioids work? All opioids bind to opioid receptors Opioid receptors are located in the: peripheral nervous system spinal cord brain When opioids bind to these receptors they affect the transmission of pain signals to the brain Children's Pain Management Service, RCH, Melbourne

9. Opioid receptors There are three main types of opioid receptors: mu (  ) delta (  ) kappa (  ) These receptors have multiple actions Children's Pain Management Service, RCH, Melbourne

10. Mu(  ) opioid receptors The mu receptors are associated with: analgesia side effects Mu receptors are subtyped: mu-1 & mu- 2 Children's Pain Management Service, RCH, Melbourne

11. Action at the mu(  ) receptor Mu-1 receptor is responsible for analgesia Mu-2 receptor is responsible for the opioid side-effects: respiratory depression cardiovascular depression decreased gastrointestinal motility sedation euphoria urinary retention Children's Pain Management Service, RCH, Melbourne

12. Mu-1 specific opioids do not exist The opioid action of all known natural and synthetic opioids at mu receptors is non-specific No opioid has yet been found or developed that acts only on the mu-1 receptor Children's Pain Management Service, RCH, Melbourne

13. Opioid receptor antagonist Naloxone (Narcan TM ) is a pure opioid receptor antagonist Naloxone displaces opioids bound to opioid receptors The duration of action of naloxone is 30- 60 minutes Thus naloxone may wear off before a longer acting opioid and symptoms of opioid toxicity may reappear Children's Pain Management Service, RCH, Melbourne

14. Indications for opioids Pain Intractable diarrhoea Cough Air hunger (end-stage respiratory failure) Children's Pain Management Service, RCH, Melbourne

15. Contraindications to opioids The following are not absolute contraindications, as opioids may be used in small titrated doses: depressed conscious state (relative) head injury (relative) respiratory insufficiency (relative) Children's Pain Management Service, RCH, Melbourne

16. Precautions Neonates: lower doses may be required decreased clearance of opioids and opioid metabolites Children's Pain Management Service, RCH, Melbourne

17. Side effects of opioids Opioid side effects occur regardless of which opioid is used Side effects are usually dose-related Children's Pain Management Service, RCH, Melbourne

18. Side effects of opioids respiratory depression sedation euphoria pinpoint pupils itch muscle rigidity bradycardia (with high doses) vasodilation hypotension urinary retention nausea & vomiting delayed gastric emptying constipation Children's Pain Management Service, RCH, Melbourne

19. Respiratory depression Respiratory depression from opioids is due to the combination of sedation, decreased tidal volume, reduced respiratory rate and a drop in oxygen saturation This results in hypoxia and raised carbon dioxide levels, which leads to further sedation and further respiratory depression Children's Pain Management Service, RCH, Melbourne

20. Different opioid drugs Morphine: pure opioid powerful mu agonist varied formulations (oral, IV/IM/SC) oral immediate release eg Morphine mixture/tabs, Kapanol TM oral sustained release eg MS Contin TM the metabolites are M3G and M6G morphine 3 glucuronide & morphine 6 glucuronide Children's Pain Management Service, RCH, Melbourne

21. Different opioid drugs Codeine: pure opioid mu agonist prodrug (converts to another form) converts to morphine 7-10% of some population groups are unable to convert codeine to morphine, thus get no analgesia effect while others are rapid converters and become sedated. Children's Pain Management Service, RCH, Melbourne

22. Different opioid drugs Pethidine: (rarely used at RCH) synthetic opioid mu agonist metabolite is nor-pethidine pethidine infusions should be avoided due to the concerns of nor-pethidine toxicity Children's Pain Management Service, RCH, Melbourne

23. Different opioid drugs Fentanyl: synthetic opioid mu agonist structurally similar to pethidine short acting, but a lipophilic (fat soluble) drug which may result in accumulation no metabolites Children's Pain Management Service, RCH, Melbourne

24. Different opioid drugs Hydromorphone (Dilaudid TM ): synthetic opioid related to oxycodone and hydrocodone varied formulations (oral, IV/IM/SC, epidural) the metabolites are H3G and H6G hydromorphone 3 glucuronide & hydromorphone 6 glucuronide Children's Pain Management Service, RCH, Melbourne

25. Different opioid drugs Oxycodone: synthetic opioid related to hydrocodone and hydromorphone similar strength to oral morphine sustained release version available Oxycontin TM Children's Pain Management Service, RCH, Melbourne

26. Different opioid drugs Dextropropoxyphene : synthetic opioid weak mu agonist preparations often mixed with other analgesics eg combined with paracetamol as Digesic TM Children's Pain Management Service, RCH, Melbourne

27. Different opioid drugs Methadone : synthetic opioid strong mu agonist very long acting opioid useful for neuropathic pain no metabolites Children's Pain Management Service, RCH, Melbourne

28. Different opioid drugs Tramadol: not a true opioid has opioid and non-opioid properties non-opioid effects are via nor-adrenaline and serotonin pathways active metabolite (M1) has mu receptor affinity Children's Pain Management Service, RCH, Melbourne

29. Misbeliefs about opioids and children ‘Children are more sensitive to opioids’ ‘Infants and neonates do not feel pain’ ‘Pain is character building’ ‘Children have little requirements for opioids’ ‘Children can be easily overdosed’ ‘The use of opioids leads to addiction’ Children's Pain Management Service, RCH, Melbourne

30. Misunderstanding of definitions Confusion about the definitions of addiction, tolerance, withdrawal and the implications for patients are the main reason that opioids are under utilised Children's Pain Management Service, RCH, Melbourne

31. Definitions Addiction: psychological dependence with compulsive drug use, and craving for opioids for effects other than pain relief Tolerance: when increased doses of a drug is needed to produce the same pharmacological effect Children's Pain Management Service, RCH, Melbourne

32. Definitions Withdrawal: a cluster of physiological signs and symptoms, which occur after sudden ceasing of some drugs Dependency: when sudden absence of an opioid produces physical withdrawal syndrome Children's Pain Management Service, RCH, Melbourne

33. Fear of addiction Fear of creating addiction in patients contributes to the under use of opioid analgesics (Ferrell BR et al, J Pain & Sympt Manage, 1992) The risk of addiction for patients having opioids for medical reasons is extremely low Tolerance to an opioid does not mean the patient has an addiction Children's Pain Management Service, RCH, Melbourne

34. Caring for children receiving opioids Accurate documentation Correct dose of opioid Correct and safe delivery of opioid Observation of vital signs Minimal side effects Documented pain scores Adequate analgesia achieved Children's Pain Management Service, RCH, Melbourne

35. Caring for children receiving opioids Monitoring  sedation score  pain score  respiratory effort, rate, depth  oxygen saturation  heart rate Children's Pain Management Service, RCH, Melbourne

36. Combining opioids It is not good practice to administer more than one opioid at a time, as this increases the risk of side effects At RCH we do not administer morphine and codeine together An exception is when long-acting and short- acting formulations of the same opioid are administered for optimal analgesia in patients with severe pain eg MS Contin & morphine mixture OR Oxycontin & oxycodone Children's Pain Management Service, RCH, Melbourne

37. Optimising opioid analgesia The child needs to be comfortable The child needs to be able to breathe deeply/cough without pain The child needs to be able to mobilise freely without being limited by pain Children's Pain Management Service, RCH, Melbourne

38. Optimising opioid analgesia Pre-emptive pain management is important Treat side effects early and adequately Adjunctive analgesia may be required Children should not be sedated Believe the child’s pain assessment Act on assessment Children's Pain Management Service, RCH, Melbourne

39. Children's Pain Management Service The Children's Pain Management Service supervises most patients with opioid infusions at Royal Children's Hospital CPMS can be contacted at all times on pager 5773 Children's Pain Management Service, RCH, Melbourne

40. Finally… Optimal pain management is the right of all patients and the responsibility of all health professionals Children's Pain Management Service, RCH, Melbourne