Pharmacy Intro

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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
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
Morphine: Drug
Oral (mg)
Morphine
2:1
Parenteral (mg)
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)
10:1
1
Methadone
--
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
20
40
60
80
100
160
240
2
4
6
8
10
16
24
Hydromorphone 24H (mg
po)
Hydromorphone BT (mg
po)
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

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