1. Opioids and other drugs we use in palliative care
Pharmacy Intro
Opioids and other drugs we use in palliative care

2. Objectives Discuss the role of opioids in end of life care
Discuss the pharmacology and side effects of opioids
Discuss opioid equivalencies and conversions
Review other medications commonly used

3. Deprescribing
It is an art of no little importance to administer medicines properly: but, it is an art of much greater and more difficult acquisition to know when to suspend or altogether to omit them.
Philippe Pinel ( )

4. Role of opioids
Pain is experienced by over 80% of palliative care patients
>60% will have moderate to severe pain
Dyspnea is present in 80% of advanced cancer
95% of COPD patients at the end of life
75% of advanced disease (all comer)

5. Pharmacokinetics of Opioids
All have similar pharmacokinetics
First-order
Conjugated in liver
Excreted in kidney

6. Pharmacokinetics (cont’d)
Onset PO mins
Cmax PO h
SC/IM mins
IV mins
Duration of action
IR 4-5h
LA 8-12h

7. Fentanyl & Sufentanil Onset SL/IN 10-15 mins IV 5 mins
Duration mins
First pass metabolism (if swallowed)
Highly lipophilic (SL/IN)

8. No ceiling for pure opioid agonists
↑dose = ↑analgesic effect (log-linear)
Dose increased until symptom relief or limiting side effects

9. Opioids in Canada

10. Principles of Opioid Dosing
Start with IR dosing
“Start Low and Go Slow”
Dose Q4H regular
Five T1/2 for steady state
Reassess regularly

11. Breakthrough Dose IR 100% of the Q4H dose or 10% of the 24h dose
PO/SL - Q1H
SC Q30min
IV Q10min
For simplicity… all routes are Q1H prn

12. Titration Increase is equal to total 24 hour breakthrough dose
If no response
Increase more rapidly
switch to parenteral

13. Opioid Rotation
Opioid rotation is switching from one opioid to another
Why?
Inadequate analgesia despite appropriate escalation
Intractable/Intolerable side effects
Altered renal/hepatic function
Drug shortages

14. Guide to Opioid Rotation
Use a consistent method
Use the same conversion table
Consider incomplete cross-tolerance, patient variations, limitation of tables

15. Calculate the total daily dose
Convert to new opioid using equianalgesic dose ratio
Decrease dose of new opioid to compensate for incomplete cross tolerance
Fentanyl conversion has incomplete cross tolerance included in table

16. Equianalgesia Dosing
Equianalgesia refers to different doses of two agents that provide approximate pain relief
Does not reflect interpatient variability
Ratio differs in acute and chronic use
Does not use incomplete cross tolerance
Ratios exhibit extremely wide ranges

18. Converting Morphine to Fentanyl

21. Fentanyl Patch For relatively stable pain
Permeates the skin and a depot is formed
12 hrs to develop analgesia
Plasma levels stabilize after 2 sequential applications
Half-life about 17 hours after removal

22. Methadone Opioid agonist (mu, kappa, delta)
N-methyl-d-aspartate (NMDA) antagonist
Inhibits reuptake of serotonin and noradrenalin
Nociceptive and neuropathic pain

23. Analgesic onset mins
Duration hours
T1/ hrs(~30)
Peak hrs
Accumulates in chronic use
Metabolized in liver, eliminated in urine and feces

26. Opioid Side Effects Nausea (50-70%) and Vomiting (15-20%) Sedation
Confusion
Urinary retention
Pruritus
Constipation
Qt with methadone

27. Common Drugs We Use (Our cheat sheet)

29. Bowel Management Senokot 2-4 tabs po od-bid
Lactulose mL po od-bid
Polyethylene glycol g po od-bid
Oral sodium phosphate
Citro-Mag
D & G suppository
Methylnaltrexone 8-12 mg sc eod

30. Bowel obstruction Octreotide 300 mcg sc tid Buscopan 10-20 mg sc tid
Dexamethasone

31. Neuropathic agents Tricyclic antidepressants Gabapentin Pregabalin
Dexamethasone
Carbamezapine
Ketamine

32. Antinauseants Dopamine antagonists Haloperidol 1-2 mg po/sc/iv q4h
Prochlorperazine 5-10 mg po/iv q4h
Metoclopramide 10 mg po/sc/iv q4h
Methotrimeprazine 5-10 mg po/sc q4h
Pro kinetics
Domperidone 10 mg po qid
Metoclopramide
Anticholinergics
Scopolamine (transderm V) 1 patch q3d

33. Antinauseants Histamine antagonists
Dimenhydrinate mg po/sc/iv q4h
Serotonin antagonists
Granisetron 1 mg po/sc/iv q12h
Ondansetron 8 mg po/sc/iv q8h
Other
Dexamethasone
Cannabis

34. End-of-Life Care Sedation Midazolam 2.5-5 mg sc q4h + q1h prn
Methotrimeprazine mg sc q4h + q1h prn
Oral secretions
scopolamine mg sc q1h prn
glycopyrrolate mg sc q1h prn
Crisis Medications (given all at the same time)
Midazolam 5-10 mg sc q10m prn
Methotrimeprazine mg sc q10m prn
Opioid (double dose)

35. ?