Pharmacy IntroOpioids and other drugs we use on palliative

care

Objectives

Discuss the role of opioids in end of life careDiscuss the pharmacology and side effects of opioidsDiscuss opioid equivalencies and conversionsReview basics of methadoneDiscuss other medications commonly used

Objectives (cont’d)

Discuss other medications commonly used

Barriers to opioid use

Physician Patient

Why use opioids

Pain is experienced by over 80% of patientsOver 60% will be moderate to severe

Dyspnea present in 80% of advanced cancer95% COPD at end of life75% of advanced disease (all comers)

Opioids in Canada

Opioid Pharmacokinetics

All have similar PK (except methadone)onset of action 15-30 minsduration of action 4-5 hrs

LA 8-12hrs

Opioid Pharmacokinetics

Fentanyl and SufentanilOnset 10-15 minsDuration 45 minsFirst pass metabolismHighly 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 DoseIR50-100% of the Q4H dose or 10% of the 24hr doseQ1H - PO/SLQ30Min - SCQ10Min - IVFor simplicity... all routes are Q1H prn

Do Not Use Extended Release Opioid for Breakthrough

Titration

Increase equal to total 24 hours breakthrough doseMild to moderate pain - 50%If no response

Increase more rapidlySwitch to parenteral

Opioid Rotation

Why?Inadequate analgesia despite appropriate escalationIntractable/Intolerable side effectsAltered renal/hepatic functionDrug 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 reliefDoes not reflect interpatient variabilityRatio differs in acute and chronic useDoes not use incomplete cross tolerance

Opioid Equivalency Morphine: Drug

Oral (mg) 2:1 Parenteral (mg)

Morphine 10 5Codeine 1:10 100 --Tramadol 1:5 50 --Oxycodone 2:1 5 --Hydromorphone 5:1 2 1Fentanyl 100:1 -- 50 (mcg)Sufentanil 1000:1 -- 5 (mcg)Methadone 10:1 1 --

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 50 75 100 125 200 300

Hydromorphone 24H (mg po) 20 40 60 80 100 160 240Hydromorphone BT (mg po) 2 4 6 8 10 16 24

Fentanyl Patch

For relatively stable painPermeates the skin and a depot is formed12hrs to develop analgesiaPlasma levels stabilize after 2 sequential patch applicationsHalf-life about 17 hours after removal

Methadone

Opioid agonist (mu, kappa, delta)N-methyl-d-aspartate (NMDA) antagonistInhibits reuptake of serotonin and noradrenalinNociceptive 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 OpioidsNausea (50-70%) and Vomiting (15-20%)ConstipationSedationConfusionRespiratory depressionUrinary retentionPruritus↑ Qt with methadone

Other Medications (our cheat sheet)

Questions