1. health and fitness
2. addiction

Yale Interdisciplinary Palliative Care
Educational Project
Pain Management
Drug Therapy Workshop
The Concept of Total Pain
Physical
Psychological
Total Pain
Spiritual
Social
World Health Organization
(WHO) Step Ladder Approach
Severe Pain 7-10/10
Moderate Pain 4-6/10
Mild Pain 1-3/10
ASA, Tylenol,
NSAIDS
Potent opioids (e.g.
morphine) +/non-opioids
Weak opioids +/- nonopioids (e.g. Tylenol #3®)
Clinical Questions #1
Breakthrough pain dosing should be
individualized, but a guide for determining the
initial dose of bolus I.V. medication for a patient
receiving a long acting oral form of morphine is
that the initial breakthrough dose is what
percentage of the total daily long-acting morphine
dose?
a.
b.
c.
d.
10%
20%
50%
100%
Answer #1
a. 10%
Rationale:
10% would be the minimum dose,
Titrated to effect. The range is 1020%
Breakthrough Pain


Patients on long-acting med always need
second, short-acting med, for breakthrough
pain to take Q 4 hours or less.
Generally, dose of breakthrough opioid
should be:
 10% of 24 hour dose of analgesics and
made available Q 2-4 hours.
 Example: MS Contin 60mg q12hrs
breakthrough dose should be immediate
release morphine (MSIR), 10-15 mg Q 2-4
hrs prn.
Clinical Question #2
What is the maximum number of tablets of
hydrocodone/acetominophen 5 mg/500
mg (e.g., Vicodin ®) you can safely
prescribe for a 24 hour period.
a. 4
b. 6
c. 8
d. There is no ceiling dose/maximum
Answer #2
c. 8
Rationale:
4,000mg of acetominophen in 24 hours is
safe for most patients, BUT ceiling dose
may need to be modified significantly or
the drug not used in patients with:



renal or liver disease
history of significant alcohol intake
consider starting at 50% of standard ceiling
dose for elders.
Clinical Question #3
A 40 yr. old women with stage IV ovarian
cancer reports mild to moderate burning
pain in her hands and feet. Ibuprofen has
not been effective. You suggest:
a. A COX-2 inhibitor
b. Topical capsaicin
c. A steroid
d. An adjuvant with activity in
neuropathic pain
Answer #3
d. An Adjuvant with activity in
neuropathic pain
 Pain characterized by sharp,
shooting, electric shocks,
parethesias, dysesthesias, cold
extremities
 Neuropathic pain often responds
poorly to NSAIDs and opioids
Drugs for Neuropathic Pain






opioids
antidepressants
anticonvulsants
local anesthetics
steroids
other
Antidepressants



Tricyclic antidepressants
 Analgesic effects separate from anti-depressant
effects.
 Amitriptyline: most studied, but most side effects
 Nortriptyline & desipramine: better tolerated, less
well studied
SSRIs: little evidence of analgesic effect.
SNRI’s
 inhibit both norepinephrine and serotonin reuptake
 efficacy in neuropathic pain syndromes or pain
associated with depression (duloxetine [Cymbalta®],
venlafaxine [Effexor®])
Anticonvulsants

Agents for neuropathic pain







gabapentin (Neurontin®)
pregabalin (Lyrica®)
clonazepam (Klonopin®)
Other newer agents
Start low, go slow
Watch for side effects
Monitor serum levels, if available
Adjuvants to Opioid Therapy
Adjuvant
Common indication
Alpha agonists
Neuropathic pain
Anticonvulsants
Neuropathic pain
Antihistamines
Nausea, pruritus
Benzodiazepines
Pain w/Anxiety
Bisphosphanates
Bone pain (cancer)
Corticosteroids
Bone pain (cancer)
NSAIDs / COX-2 I
Musculoskeletal pain
Tricyclic antidepressants
Neuropathic pain
Clinical Question #4
A 63 yr. old man with advanced prostate
cancer has been stable on oral morphine
30 mg every 4 hours. He is now NPO and
you are going to switch him to IV
morphine. The correct IV dose is:
a. 4 mg IV q 4 hours
b. 6 mg IV q 4 hours
c. 10 mg IV q 4 hours
d. 30 mg IV q 4 hours
Answer #4
c. 10 mg IV q 4 hours
Rationale:
 Equianalgesic ratio for
morphine is
1 mg IV = 3 mg PO.
 When writing start
time for the first dose,
consider time of last
oral dose.
ORAL
DOSE
(MG)
MED
PARENTERAL
DOSE
(MG)
30
Morphine
10
7.5
Hydromorphone
(Dilaudid
®)
1.5
20
Oxycodone
--
30
Hydrocodone
--
Parenteral Opioids
IV is the route of choice if access
is available.


There is NO indication for IM opioids
(painful, no benefit over SQ route)
All standard opioids can be given SQ, by
either bolus dose or by continuous
infusion.
PCA (basal rate plus a patient initiated
dose) is an effective and well accepted
modality; either IV or SQ.
Parenteral Opioids (cont.)



IV or SQ bolus doses have a shorter
duration of action than oral doses;
typically 1-3 hours.
The peak effect from an IV bolus dose
is 5-15 minutes.
Dose escalation of parenteral opioids
is the same as with oral—always by a
percentage of the starting dose.
Clinical Question #5
Mrs. Jones has advanced cervical cancer. She has
been taking Percocet-5 (2 tablets PRN) for pain
with good effect. The patient is now NPO & is
requiring something for pain. An appropriate
starting dose of PRN IV morphine is
approximately:
a. 2 mg
b. 3 mg
c. 4 mg
d. 5 mg
e. 6 mg
Answer #5
c. 4 mg IV morphine
Rationale:

Most equianalgesic tables use a ratio of 20 mg
po oxycodone = 10 mg IV morphine.

Mathematically, answer is 5 mg IV morphine.
Clinically, account for possible incomplete crosstolerance, so reduce the dose by about 25%50%.

4 mg is a convenient dose of IV morphine. We
might also have rounded down to 3 mg. 4 mg is
almost certainly safe and analgesically
appropriate for opioid non-naïve patient.
Incomplete cross-tolerance


If switching from one opioid to another,
recommended to start the new opioid at
~50% of equianalgesic dose.
Why? :Because the tolerance a patient has
towards one opioid, may not completely
transfer (“incomplete cross-tolerance”) to
the new opioid.
to
from
100%
50%
of new
Opioid
Clinical Question #6
A 69 yr. old patient with metastatic
prostate cancer to the lumbar spine is
taking OxyContin® (sustained release
oxycodone) 100 mg every 8 hours. What
should be the opioid for his breakthrough
pain and at what dose and interval?
a. Oxycodone 30 mg PO every 4 hours
b. Oxycodone 30 mg PO every 8 hours
c. Morphine 10 mg PO every 4 hours
d. Morphine 10 mg IV every 8 hours
Answer #6
a. Oxyocodone 30 mg PO every 4 hours
Rationale:
 In general, keep PRN, short acting opioid the same
drug as the long-acting opioid.
 Starting dose for breakthrough pain is 10% of the
total daily dose (and you can always titrate).
 Here total daily dose = 300 mg, so 10% of this = 30
mg. The PRN interval should never be longer than
the expected analgesic duration (~4 hours in this
case), and can often be less.
Short Acting Opioids
Oral dosing:





onset in 20-30 min
peak effect in 60-90 minutes
duration of effect 2-4 hours
Can be dose escalated or re-administered
every 2-4 hours for poorly controlled pain
General guideline:
Moderate pain: increase 25-50%
 Severe pain: increase by 50-100%

B. Short Acting Opioids
Parenteral or
Oral:




morphine
hydromorphone
(Dilaudid ®)
Codeine
Onset & duration of
action depends on
route administration
Oral only:




oxycodone (Percocet ®
, Tylox ® )
hydrocodone (Vicodin ®
Lortab ®, Lorcet ®)
propoxyphene (Darvon
®, Wygesic ®)
Note: hydrocodone is only
available as a combination
product.
Clinical Question #7
Ms. Nguyen is reporting 7/10 pain now in
her left leg. She had vomited after her
last pain medication, morphine 10 mg IV.
What is your next analgesic order?
a. Dilaudid® (hydromorphone) 1.5 mg IV
b. Fentanyl® Patch 25 mcg/hr q72 hours
c. Dilaudid® 8 mg PO
d. Percocet® 5/325 three tablets
Answer #7
a. Dilaudid® (hydropmorphone) 1.5 mg IV
Rationale:
 With severe pain we need rapid onset option.
 Onset too slow with Fentanyl patch and orals.
 IV morphine plus an antiemetic might be considered,
but easier option - change to another opioid
(different patients have different side effect
responses to various opioids).
 Hydromorphone 1.5 mg IV is approx. equianalgesic
to 10 mg IV morphine.
 As patient currently in severe pain, reducing dose for
potential incomplete cross tolerance not necessary.
Opioid Dose Escalation
Always increase by a percentage of the present dose based
upon patient’s pain rating and current assessment
50-100% increase
25-50% increase
25% increase
Mild pain
1-3/10
Moderate pain
4-6/10
Severe pain
7-10/10
Frequency of dose escalation
The frequency of dose escalation
(oral opioids) depends on the
particular opioid …




Short acting oral: q 2-4 hours
Long acting oral, except methadone:
q 24 hours
methadone: q 72 hours
transdermal fentanyl: q 72 hours.
Clinical Question #8
Mr. MacLean comes to your floor in excruciating pain
(10/10). He receives morphine 4 mg IV, but reports no
relief at all after 15 minutes. The intern or fellow then
orders morphine 6 mg IV. After another 20 minutes the
patient reports that she still has no relief. You note that
the patient is wide awake (no sedation) with continued
10/10 pain. What would you recommend?
a. Tell the patient that the interval between doses is 4
hours and they will have to wait
b. Administer another dose of morphine 6 mg IV in one
hour
c. Administer another dose of morphine 9-12 mg now
d. Call for a pain or palliative care consult
Answer #8
c. Administer another dose of morphine 9-12 mg
now.
Rationale:
 Patient has no unacceptable side effects, so no
immediate reason to change to another drug.
 Patient is in a pain crisis. We should titrate
aggressively (i.e., 50-100% increase in each dose
at approximately 15 minute intervals) until a
response is observed.
 Note:some protocols for pain crisis in cancer
patients suggest that 1-2 doses of ketorolac
(Toradol®) 30 mg IV be considered (if not
otherwise contraindicated) in addition to the opioid.
Clinical Question #9
Ms. Santini, a 45 yr. old woman with colon cancer
metastatic to the liver, had been admitted for
uncontrolled pain. Her pain is now controlled and
stable on PCA morphine of 10 mg/hr. The boluses are
5 mg q15 minutes PRN and work very well but she
rarely needs to use the bolus doses for breakthrough
pain. She is to be discharged home on oral opioids.
What opioid/formulation and what dose would you
recommend?
a. MS Contin 120 mg PO Q 12 hours
b. MS Contin 240 mg PO Q 12 hours
c. MS Contin 360 mg PO Q 12 hours
d. Fentanyl patch 50 mcg Q 72 hours
e. Dilaudid 8 mg PO Q 8 hours
Equianalgesic Doses: Opioid Analgesics
ORAL DOSE
(MG)
ANALGESIC
PARENTERAL
DOSE (MG)
30
Morphine
10
7.5
Hydromorphone
(Dilaudid ®)
1.5
20
Oxycodone
--
30
Hydrocodone
--
Answer #9
c. MS Contin 360 mg PO every 12
hours
Rationale:
 Patient already on morphine, so use same
opioid.
 Using long-acting formulation is the oral
equivalent of a continuous infusion.
 Total daily dose of morphine IV is 240 mg
and the oral equivalent is 720 mg of
morphine, can be given as 360 mg of MS
Contin PO every 12 hours.
C. Long Acting Opioids

Oral




morphine:
 MS Contin®
 Kadian®
 Oramorph SR
oxycodone
 Oxycontin®
 Oxycodone SR
oxymorphone
 Opana SR
methadone

Transdermal


Fentanyl Patch
(Duragesic®) –
Dosing Q 72 hours
Clinical Question #10
What breakthrough pain opioid/formulation would
you recommend for Ms. Santini if she takes MS
Contin 360 Mg Q 12 hours?
a. Morphine elixir 20 mg PO every 2-4 hours PRN
b. Morphine immediate release tablets 40 mg PO
Q 2-4 hours PRN
c. Morphine immediate release tablets 60 mg PO
Q 2-4 hours PRN
d. Morphine immediate release tablets 70 mg PO
Q 2-4 hours PRN
Answer #10
d. Morphine immediate release tablets 70 mg PO
every 2-4 hours PRN.
Rationale:
 Breakthrough pain requires a short-acting formulation.
 Preferable to use same opioid as long-acting.
 PRN initially 10% of the total daily dose = 10% of
720mg = 72mg.
 Dosing interval is q2-3h PRN. We don’t expect that pts
will need to take 12 doses in 24hr (our pain regimen
would be really off).
 If patient requires >5 PRN doses/day, either the PRN
dose needs adjusting or the basal dose or both.
Name one new fact you learned about
the use of narcotics from this presentation
and how you might use it clinically as a Sub- I
References
Portions of this presentation were originally developed by David E. Weissman, MD,
Drew Rosielle, MD, Kathy Biernat, MS and Judi Rehm for:
EPERC
End of Life/Palliative Education Resource Center
And:
Yale Cancer Center Supportive Oncology Program
Connecticut Challenge Survivorship Clinic
Kenneth Miller, MD & Thomas Quinn, APRN
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