1. Opioids and other drugs we use on palliative care
Pharmacy Intro
Opioids and other drugs we use on 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 basics of methadone
Discuss other medications commonly used

3. Objectives (cont’d)
Discuss other medications commonly used

4. Barriers to opioid use Physician Patient
Inadequate training in analgesic practices
Over-reliance on anecdotal experience
Irrational fears of overdosage and addiction (Boston Collaborative survey treated for acute pain... 4 developed addiction)
Focus on diagnostic work-up vs. treatment of symptoms (“Need to know what I’m treating”... might mask what is going on)
Fear of exacerbating hemodynamic instability (ATLS recommends relief of severe pain is important part of management)
Unfounded concerns of masking intra-abdominal pathology (15mg given M v placebo... no pathology masked... may enhance examination by reducing anxiety and increasing cooperation)
Overly suspicious that everyone with chronic pain is an addict
Fear of confrontation with consultants
Patient

5. Why use opioids Pain is experienced by over 80% of patients
Over 60% will be moderate to severe
Dyspnea present in 80% of advanced cancer
95% COPD at end of life
75% of advanced disease (all comers)

6. Opioids in Canada

7. Opioid Pharmacokinetics
All have similar PK (except methadone)
onset of action mins
duration of action 4-5 hrs
LA 8-12hrs

8. Opioid Pharmacokinetics
Fentanyl and Sufentanil
Onset mins
Duration 45 mins
First pass metabolism
Highly lipophilic (SL/IN)

9. Opioid Dosing No ceiling effect ↑dose = ↑analgesic effect (log-linear)
Dose increased until symptom relief or limiting side effects

10. Start with IR dosing
“Start Low and Go Slow”
Q4H
PO = SL = PR
SC/IV = 50% of PO
Reassess regularly

11. Breakthrough Dose IR 50-100% of the Q4H dose or 10% of the 24hr dose
Q1H - PO/SL
Q30Min - SC
Q10Min - IV
For simplicity... all routes are Q1H prn

12. Do Not Use Extended Release Opioid for Breakthrough

13. Titration Increase equal to total 24 hours breakthrough dose
Mild to moderate pain - 50%
If no response
Increase more rapidly
Switch to parenteral

14. Opioid Rotation
Why?
Inadequate analgesia despite appropriate escalation
Intractable/Intolerable side effects
Altered renal/hepatic function
Drug shortages

15. Use a consistent method
Use the same conversion table
Consider incomplete cross-tolerance, patient variations, limitation of tables

16. Equianalgesia Dose Ratio
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

17. Opioid Equivalency Oral (mg) Parenteral (mg) Morphine 10 5 Codeine 100
Morphine: Drug
Oral (mg)
2:1
Parenteral (mg)
Morphine 10 5
Codeine
1:10
100 --
Tramadol
1:5 50
Oxycodone
Hydromorphone
5:1 2 1
Fentanyl
100:1
50 (mcg)
Sufentanil
1000:1
5 (mcg)
Methadone
10:1
Tramacet 37.5mg

19. Fentanyl

20. Morphine BT (mg po) 10 20 30 40 50 80
160
Morphine 24H (mg po)
100
200
300
400
500
800
1600
Fentanyl Transdermal (mcg/h) 25 75
125
Hydromorphone 24H (mg po) 60
240
Hydromorphone BT (mg po) 2 4 6 8 16 24

21. Fentanyl Patch For relatively stable pain
Permeates the skin and a depot is formed
12hrs to develop analgesia
Plasma levels stabilize after 2 sequential patch 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 effect 30-60mins
Duration 4-6hrs
T1/ hrs (~30hrs)
Peak 1.5-3hrs
Large Vd, 80% bioavailability, large protein binding
Accumulates in chronic use
Metabolized in liver, eliminated in urine and feces
Multiple drug interactions

24. Side Effects of Opioids
Nausea (50-70%) and Vomiting (15-20%)
Constipation
Sedation
Confusion
Respiratory depression
Urinary retention
Pruritus
↑ Qt with methadone

25. Other Medications (our cheat sheet)

32. Questions