Opioids and other drugs we use on palliative care Pharmacy Intro Opioids and other drugs we use on palliative care
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
Objectives (cont’d) Discuss other medications commonly used
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 - 12000 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
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)
Opioids in Canada
Opioid Pharmacokinetics All have similar PK (except methadone) onset of action 15-30 mins duration of action 4-5 hrs LA 8-12hrs
Opioid Pharmacokinetics Fentanyl and Sufentanil Onset 10-15 mins Duration 45 mins First pass metabolism Highly lipophilic (SL/IN)
Opioid Dosing No ceiling effect ↑dose = ↑analgesic effect (log-linear) Dose increased until symptom relief or limiting side effects
Start with IR dosing “Start Low and Go Slow” Q4H PO = SL = PR SC/IV = 50% of PO Reassess regularly
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
Do Not Use Extended Release Opioid for Breakthrough
Titration Increase equal to total 24 hours breakthrough dose Mild to moderate pain - 50% If no response Increase more rapidly Switch to parenteral
Opioid Rotation Why? Inadequate analgesia despite appropriate escalation Intractable/Intolerable side effects Altered renal/hepatic function Drug shortages
Use a consistent method Use the same conversion table Consider incomplete cross-tolerance, patient variations, limitation of tables
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
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
Fentanyl
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
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
Methadone Opioid agonist (mu, kappa, delta) N-methyl-d-aspartate (NMDA) antagonist Inhibits reuptake of serotonin and noradrenalin Nociceptive and neuropathic pain
Analgesic effect 30-60mins Duration 4-6hrs T1/2 8-100+ 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
Side Effects of Opioids Nausea (50-70%) and Vomiting (15-20%) Constipation Sedation Confusion Respiratory depression Urinary retention Pruritus ↑ Qt with methadone
Other Medications (our cheat sheet)
Questions