Pharmacy Intro Opioids and other drugs we use on palliative care.
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Transcript of Pharmacy Intro Opioids and other drugs we use on palliative care.
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Pharmacy IntroPharmacy IntroOpioids and other drugs we use on palliative
careOpioids and other drugs we use on palliative
care
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ObjectivesObjectives
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
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
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Objectives (cont’d)Objectives (cont’d)
Discuss other medications commonly usedDiscuss other medications commonly used
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Barriers to opioid useBarriers to opioid use
PhysicianPhysician Patient
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Why use opioidsWhy 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)
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)
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Opioids in CanadaOpioids in Canada
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Opioid PharmacokineticsOpioid Pharmacokinetics
All have similar PK (except methadone)
onset of action 15-30 mins
duration of action 4-5 hrs
LA 8-12hrs
All have similar PK (except methadone)
onset of action 15-30 mins
duration of action 4-5 hrs
LA 8-12hrs
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Opioid PharmacokineticsOpioid Pharmacokinetics
Fentanyl and Sufentanil
Onset 10-15 mins
Duration 45 mins
First pass metabolism
Highly lipophilic (SL/IN)
Fentanyl and Sufentanil
Onset 10-15 mins
Duration 45 mins
First pass metabolism
Highly lipophilic (SL/IN)
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Opioid DosingOpioid Dosing
No ceiling effect
↑dose = ↑analgesic effect (log-linear)
Dose increased until symptom relief or limiting side effects
No ceiling effect
↑dose = ↑analgesic effect (log-linear)
Dose increased until symptom relief or limiting side effects
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Start with IR dosing
“Start Low and Go Slow”
Q4H
PO = SL = PR
SC/IV = 50% of PO
Reassess regularly
Start with IR dosing
“Start Low and Go Slow”
Q4H
PO = SL = PR
SC/IV = 50% of PO
Reassess regularly
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Breakthrough DoseBreakthrough 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
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
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Do Not Use Extended Release Opioid for BreakthroughDo Not Use Extended Release Opioid for Breakthrough
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TitrationTitration
Increase equal to total 24 hours breakthrough dose
Mild to moderate pain - 50%
If no response
Increase more rapidly
Switch to parenteral
Increase equal to total 24 hours breakthrough dose
Mild to moderate pain - 50%
If no response
Increase more rapidly
Switch to parenteral
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Opioid RotationOpioid Rotation
Why?
Inadequate analgesia despite appropriate escalation
Intractable/Intolerable side effects
Altered renal/hepatic function
Drug shortages
Why?
Inadequate analgesia despite appropriate escalation
Intractable/Intolerable side effects
Altered renal/hepatic function
Drug shortages
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Use a consistent method
Use the same conversion table
Consider incomplete cross-tolerance, patient variations, limitation of tables
Use a consistent method
Use the same conversion table
Consider incomplete cross-tolerance, patient variations, limitation of tables
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Equianalgesia Dose Ratio
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
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
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Opioid EquivalencyOpioid Equivalency
Morphine: Drug
Oral (mg) 2:1 Parenteral (mg)
Morphine 10 5
Codeine 1:10 100 --
Tramadol 1:5 50 --
Oxycodone 2:1 5 --
Hydromorphone 5:1 2 1
Fentanyl 100:1 -- 50 (mcg)
Sufentanil 1000:1 -- 5 (mcg)
Methadone 10:1 1 --
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FentanylFentanyl
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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 80 100 160 240
Hydromorphone BT (mg po)
2 4 6 8 10 16 24
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Fentanyl PatchFentanyl 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
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
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MethadoneMethadone
Opioid agonist (mu, kappa, delta)
N-methyl-d-aspartate (NMDA) antagonist
Inhibits reuptake of serotonin and noradrenalin
Nociceptive and neuropathic pain
Opioid agonist (mu, kappa, delta)
N-methyl-d-aspartate (NMDA) antagonist
Inhibits reuptake of serotonin and noradrenalin
Nociceptive and neuropathic pain
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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
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
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Side Effects of OpioidsSide Effects of Opioids
Nausea (50-70%) and Vomiting (15-20%)
Constipation
Sedation
Confusion
Respiratory depression
Urinary retention
Pruritus
↑ Qt with methadone
Nausea (50-70%) and Vomiting (15-20%)
Constipation
Sedation
Confusion
Respiratory depression
Urinary retention
Pruritus
↑ Qt with methadone
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Other Medications (our cheat sheet)
Other Medications (our cheat sheet)
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QuestionsQuestions