Pain Management Drug Therapy Workshop

1
Pain ManagementDrug Therapy Workshop
Yale Interdisciplinary Palliative
Care Educational Project
2
The Concept of Total Pain
3
World Health Organization (WHO) Step Ladder
Approach
Severe Pain 7-10/10
Potent opioids (e.g. morphine) /- non-opioids
Moderate Pain 4-6/10
Weak opioids /- non- opioids (e.g. Tylenol 3)
Mild Pain 1-3/10
ASA, Tylenol, NSAIDS
4
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. 10 b. 20 c. 50 d. 100

5
Answer 1

• a. 10
• Rationale10 would be the minimum dose,
• Titrated to effect. The range is 10-20

6
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.

7
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

8
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.

9
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

10
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

11
Drugs for Neuropathic Pain

• opioids
• antidepressants
• anticonvulsants
• local anesthetics
• steroids
• other

12
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.
• SNRIs
• inhibit both norepinephrine and serotonin
  reuptake
• efficacy in neuropathic pain syndromes or pain
  associated with depression (duloxetine
  Cymbalta, venlafaxine Effexor)

13
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

14
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 anti-depressants Neuropathic pain
15
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

16
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 PAREN-TERAL DOSE (MG)
30 Morphine 10
7.5 Hydro-morphone (Dilaudid ) 1.5
20 Oxycodone --
30 Hydro-codone --
17
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.

18
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 oralalways by a percentage of the
  starting dose.

19
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

20
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
  cross-tolerance, 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.

21
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 50 of new Opioid
from 100
22
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

23
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.

24
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

25
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.

26
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

27
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.

28
Opioid Dose Escalation
Always increase by a percentage of the present
dose based upon patients pain rating and current
assessment
50-100 increase
Severe pain 7-10/10
25-50 increase
Moderate pain 4-6/10
25 increase
Mild pain 1-3/10
29
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.

30
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

31
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.
• Notesome 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.

32
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

33
Equianalgesic Doses Opioid Analgesics
ORAL DOSE (MG) ANALGESIC PARENTERAL DOSE (MG)
30 Morphine 10
7.5 Hydromorphone (Dilaudid ) 1.5
20 Oxycodone --
30 Hydrocodone --
34
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.

35
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

36
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

37
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 dont expect
  that pts will need to take 12 doses in 24hr (our
  pain regimen would be really off).
• If patient requires gt5 PRN doses/day, either the
  PRN dose needs adjusting or the basal dose or
  both.

38
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
39
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
ProgramConnecticut Challenge Survivorship Clinic
Kenneth Miller, MD Thomas Quinn, APRN
40
References cont

• Acute Pain Management Guideline Panel. Acute
  pain management Operative or Medical Procedures
  and Trauma Clinical Practice Guideline. AHCPR
  Publication No. 92-0032. Rockville, MD. Agency
  for Health Care Policy and Research, US
  Department of Health and Human Services, Public
  Health Service, 1992.
• Backonja M, Beydoun, A, Edwards KR, et al.
  Gabapentin for symptomatic treatment of painful
  neuropthy in patients with diabetes mellitus.
  JAMA 19982801831-1836.
• Breitbart W, Chandler S, Eagle B, et al. An
  alternative algorithm for dosing transdermal
  fentanyl for cancer pain. Oncology
  200014695-702.
• Fohr SA. The double effect of pain medication
  separating myth from reality. J Pall Med 1998
  1315-328.
• Jacox A, Carr DB, Payne R, et al. Management of
  Cancer Pain. Clinical Practice Guideline No. 9.
  AHCPR Publication No. 94-0592. Rockville, MD.
  Agency for Health Care Policy and Research, U.S.
  Department of Health and Human Services, Public
  Health Service, 1994.
• Portenoy, RK. Chronic Opioid Therapy in
  Nonmalignant Pain. J Pain Symptom Manage 1990
  5 S46-S62.
• Portenoy, RK. Continuous Infusion of Opioid
  Drugs in the Treatment of Cancer Guidelines for
  Use. J Pain Symptom Manage 19861 223-228.
• Storey P, Hill HH, Jr., St. Louis RH, Tarver EE.
  Subcutaneous infusions for control of cancer
  symptoms. J of Pain Symptom Manage 1990
  533-41.