1. How to use strong opioids in cancer patients
Dr Nicholas Herodotou
Consultant in Palliative Medicine
L&D University Hospital

2. Looking at…
Definition
Strong opioids
How to titrate
Photos

3. What is pain?

5. What patient says it is
‘Unpleasant sensory & emotional experience associated with actual or potential tissue damage’ (Twycross)

6. Pain is multi-dimensional
Physical
Psychological
Social
Spiritual
TOTAL PAIN

7. Evaluating pain

8. Multi-modal approach to pain

9. WHO PAIN LADDER

10. ..A bit about morphine

11. Extracted from opium (exudate derived from seed pods of opium poppy, Papaver Somniferum)
Opium used in Mesopotamia 3400BC as analgesic & anxiolytic
Main constituents of opium are morphine & codeine
Morphine first isolated in 1804 by German pharmacist Friedrich Seturner called it ‘Morphium’ after Morpheus, the Greek god of dreams

12. PAPAVER SOMNIFERUM

13. Opioid receptors & effect of agonistµ1
analgesia, euphoria µ2
constipation, respiratory depression, Κ
spinal analgesic, dysphoria δ
Unknown

14. Use spread when hypodermic needle developed in 1853
Initially used as ‘cure’ for alcohol & opium addiction
Heroin diacetylmorphine (Diamorphine) is a semi- synthetic opioid first synthesised from morphine by acetylation in 1874
Before 1910 heroin used as cough medicine for children (Bayer)-heroin bottle photo!
Still illegal to prescribe diamorphine in USA

15. Issues around strong opiates
Doctrine of double affect
‘Shipman syndrome’
No maximum dosage
Not all opiates are the same
Addiction

16. Strong opioids Morphine (MST, Oramorph, Sevredol) Diamorphine (Heroin)
Oxycodone (Oxycontin & Oxynorm)
Fentanyl
Methadone

17. Strong opioids to use Morphine-1st line Oxycodone-2nd line
Fentanyl-2nd or 3rd line
Diamorphine-SC or syringe driver

18. Morphine, Buprenorphine (partial), Fentanyl, Methadone, Oxycodone
Receptor site
Agonist affect on site μ
Morphine, Buprenorphine (partial), Fentanyl, Methadone, Oxycodone Κ
Oxycodone, Buprenorphine (antagonist) δ
?Methadone, Buprenorphine

19. Weak opioids Dihydrocodeine(DF118) Tramadol Codeine
Co-codamol (Tylex) 30/500
Co-dydramol 10/500

20. Potency ratio of opiates to oral morphine
Codeine
1/10
Tramadol
1/5
Oxycodone 2x
Diamorphine SC 3x
Morphine SC/IM
Methadone
10x
Fentanyl patch
100x

21. Opioid toxicity Agitation & confusion Gastric Stasis Sedation
Myoclonus
Pruritus & allodynia

22. Treating opioid toxicity
Check renal function
Reduce dose of opioid by 1/3, or change opioid, e.g., morphine to oxycodone
Lorazepam 0.5-1mg for anxiety/myoclonus
Alternate route such as Fentanyl patch

23. Morphine Oramorph or Sevredol (rapid release) T1/2 4 hrs
MST (slow release) T1/2 12 hrs
Use as 1st line
Renally excreted, metabolites are morphine-3- glucuronide (M3G) & M6G which accumulate in renal failure
Peak plasma levels min

24. Diamorphine (heroin) Given SC or IM (rarely)
Highly hydrophilic, rapidly absorbed
Peak plasma levels s/c in 5 min
Same T1/2 and renally excreted as Morphine
3x more potent than oral morphine, e.g. 15mg oramorph= 5mg s/c diamorphine

25. Oxycodone (generic)
Semi-synthetic opioid derived from thebaine in 1916
Oxycontin was licensed in USA in 1996 as non- dependant narcotic
Oxynorm (fast acting)T1/2 4 hrs
Oxycontin (slow release), T1/2 12 hrs
NEVER write generic oxycodone on FP10

26. Buprenorphine
Potent partial μ opioid receptor agonist, Κ & δ receptor antagonist
Useful for low-middle pain intensity
Doesn’t suppress gonadal axis so libido maintained
Poorly absorbed orally so sublingual tabs & transdermal patch better bioavailability
Clinical benefit for neuropathic pain syndromes

27. Fentanyl Matrix patch, T1/2 72 hrs-Durogesic stick better
12, 25, 50, 100 mcg/hr patches
‘25’=90mg morphine/24 hrs
Safe in renal failure
Less constipating as lipophilic

28. Fentanyl Useful 2nd line opiate Always write up correct PRN morphine
‘New’ rapid release fentanyl preps:
Effentora, buccal
Abstral, SL
Instanyl, nasal

29. General rules using opioids
Always prescribe a laxative: not lactulose!
Generally don’t get nausea with non-IV
No absolute contraindication

30. Always write up correct PRN morphine dose
Half oral dose when giving SC, e.g. Morphine 10mg PO=5mg morphine SC
Avoid use solely PRN opiates for pain management without titration (see graph)

31. Graph of plasma opiate levels vs time
Twycross

32. Starting strong opioids
If opiate naive start at low dose 5mg 4hrly (on drug chart) or start MST 10mg BD at home
PRN oral morphine (every 4 hrs)
Laxatives!
Total up all morphine requirement in 24 hrs and divide by 2 for MST dose

33. Titration example Regular 5mg 4hrly= 5x6=30mg/24hr
PRN Oramorph needed was 6x5mg=30mg/24 hr
Total morphine needed to control pain is =60mg, so 60/2= 30mg MST BD
Always adjust PRN morphine dose to fit regular morphine, e.g. if on MST 30mg BD, needs Oramorph PRN 10mg written up (1/6 of total 24hr dose)

34. Converting to fentanyl patch
Last MST dose at night
Put patch on in morning and give PRN morphine until pain controlled (upto 8-12 hrs)
If on morphine syringe driver (CSCI), put patch on and keep driver going for 6-hrs at 1/3 reduced dose and then stop
If from patch to CSCI, start driver immediately & take patch off

36. Case scenarios

37. Case scenario 1
80 year old with newly diagnosed metastatic breast cancer. Previously been on Tramadol 100 mg QDS for neuropathic pain in breast & arm, but no longer effective.
What morphine dose would you start her on?
How would you work out the PRN morphine dose?
What else would you include?

38. Solution 1 Tramadol 1/5 strength of morphine, 100x4=400/5
So 80mg morphine/24hrs needed. But if in pain can increase by 1/3 to 100mg/24 hrs or 50mg MST BD
1/6 of total 24 hr morphine dose. So 100/6= 15-20mg Oramorph PRN
A laxative such as co-danthramer or Movicol

39. Case scenario 2
50 year old with metastatic ca lung discharged from hospital to home. Sudden acute deterioration. He was taking MST 300mg Bd for pain relief along with Diclofenac 50mg TDS. He is agitated, sweaty, confused and having myoclonic jerks.
What immediate blood tests are you interested in?
What medication would you alter?
What would you change it to and what dose?
Other drug you could add in?

40. Solution 2 Check U&E to rule out ARF 2nd NSAID (also check corr ca2+)
Stop the NSAID & switch to 2nd line opiate like Oxynorm
Reduce opioid dose by 1/3. 600mg morphine/24hrs= 300mg Oxynorm/24hrs. Reduce by 1/3 down to 200mg Oxynorm/24hrs (remember PRN Oxynorm as well)
BZP such as Lorazepam or Clonazepam for myoclonus

41. Case scenario 3
25 year old with osteosarcoma recently had his MST increased from 100mg BD to 200 mg BD. Now drowsy although pain better controlled.
What would you do?
How would you start a Fentanyl patch?

42. Solution 3
Reduce the dose and add in NSAID for bone pain (check U&E) or switch to 2nd line opioid such as Oxynorm or fentanyl patch
Look at conversion chart, but as general rule, fentanyl patch size/5=4 hrly diamorphine dose. So x3=4hr oral morphine dose. 25 mcg fentanyl patch= mg Oramorph/24 hrs
Patient will therefore need a 100 mcg/hr fentanyl patch
Remember to give correct PRN Oramorph or Oxynorm

43. Case scenario 4 What would you do? What drugs would you use and why?
64 year old with Mesothelioma having uncontrolled neuropathic pain in his right lung. On escalating dose of MST 300mg BD, but having drowsiness, myoclonic jerks & sweats. Now vomiting & unable to take oral medication. He is terminally ill & prognosis of hours-days
What would you do?
What drugs would you use and why?

44. Solution 4
Put on LCP
Start syringe driver(SD) with diamorphine or Oxynorm & midazolam
600/3= 200 mg diamorphine/24hrs into driver or can use Oxynorm 600/2= 300mg PO/24 hrs. Reduce by 1/3 in SD so 200mg Oxynorm.
Give stat doses 2.5-5mg midazolam, put 10 mg in SD but keep giving SC stat doses every 20-30min and titrate up until sedated