Opioids and other drugs we use in palliative care Pharmacy Intro Opioids and other drugs we use in 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 other medications commonly used

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 (1745-1826)

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)

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

Pharmacokinetics (cont’d) Onset PO 15-30 mins Cmax PO 1h SC/IM 30 mins IV 6 mins Duration of action IR 4-5h LA 8-12h

Fentanyl & Sufentanil Onset SL/IN 10-15 mins IV 5 mins Duration 45 mins First pass metabolism (if swallowed) Highly lipophilic (SL/IN)

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

Opioids in Canada

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

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

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

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

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

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

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

Converting Morphine to Fentanyl

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

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

Analgesic onset 30-60 mins Duration 4-6 hours T1/2 8-100+ hrs(~30) Peak 1.5-3 hrs Accumulates in chronic use Metabolized in liver, eliminated in urine and feces

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

Common Drugs We Use (Our cheat sheet)

Bowel Management Senokot 2-4 tabs po od-bid Lactulose 15-30 mL po od-bid Polyethylene glycol 3350 17-34 g po od-bid Oral sodium phosphate Citro-Mag D & G suppository Methylnaltrexone 8-12 mg sc eod

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

Neuropathic agents Tricyclic antidepressants Gabapentin Pregabalin Dexamethasone Carbamezapine Ketamine

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

Antinauseants Histamine antagonists Dimenhydrinate 25-50 mg po/sc/iv q4h Serotonin antagonists Granisetron 1 mg po/sc/iv q12h Ondansetron 8 mg po/sc/iv q8h Other Dexamethasone Cannabis

End-of-Life Care Sedation Midazolam 2.5-5 mg sc q4h + q1h prn Methotrimeprazine 6.25-12.5 mg sc q4h + q1h prn Oral secretions scopolamine 0.3-0.6 mg sc q1h prn glycopyrrolate 0.2-0.4 mg sc q1h prn Crisis Medications (given all at the same time) Midazolam 5-10 mg sc q10m prn Methotrimeprazine 12.5-25 mg sc q10m prn Opioid (double dose)

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