Introduction to Pain Management: Opioid Pharmacotherapy

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Introduction to Pain Management Opioid
Pharmacotherapy
HERTZBERG PALLIATIVE CARE INSTITUTE
Hertzberg Palliative Care Institute Mount Sinai
School of Medicine
Adapted from The Project to Educate Physicians on
End-of-life Care. Supported by the American
Medical Association andthe Robert Wood Johnson
Foundation
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Objectives By the end of this session, you will
be able to

• Systematically assess pain as a symptom
• Describe the basic principles of opioid
  pharmacotherapy
• Perform simple opioid dose conversions
• Explain the differences among dependence,
  tolerance, and addiction
• Describe the treatment of common opioid side
  effects

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• What are YOUR goals for
• this session?
• What are some specific issues in pain assessment
  and management that YOU would like us to address?

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Case 1

• Mr. A., a 50 year old man with newly diagnosed
  widely metastatic prostate cancer, complains of
  moderate pain in his hips, chest wall, and
  shoulders from bony metastases.
• What questions do you ask?

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Pain assessmentHistory

• Onset
• Provocative or Palliative features
• Quality
• Radiation and Related symptoms
• Severity (intensity and effect on function)
• Temporal pattern

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Pain assessmentPain intensity scales

• Simple Descriptive Pain Intensity Scale
• 0-10 or 0-3 Numeric Pain Intensity Scale
• Visual Analog Scale
• Faces Scale

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Pain assessment Psychosocial assessment

• Meaning of the pain to patient and family
• The patients previous experiences with pain and
  past coping responses.
• The patients knowledge, preferences, and
  attitudes about analgesic options
• Economic impact of pain and its treatment
• Changes in mood secondary to pain

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Types of Pain Nociceptive pain . . .

• Direct stimulation of intact nociceptors
• Transmission along normal nerves
• sharp, aching, throbbing
• somatic
• easy to describe, localize
• visceral
• difficult to describe, localize

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. . . Nociceptive pain

• Tissue injury apparent
• Management
• opioids
• adjuvant / coanalgesics

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Types of Pain Neuropathic pain . . .

• Disordered peripheral or central nerves
• Compression, transection, infiltration, ischemia,
  metabolic injury
• Varied types
• peripheral, deafferentation, complex regional
  syndromes

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. . . Neuropathic pain

• Pain may exceed observable injury
• Described as burning, tingling, shooting,
  stabbing, electrical
• Management
• opioids
• adjuvant / coanalgesics often required

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Case 2

• Mr. B. is a 50 year old man with lung cancer and
  chest wall pain from tumor extension. He is
  taking Percocet 2 tab every 6 hours. The pain is
  not controlled.

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• What is wrong with this regimen?
• Are there questions you would like to ask the
  patient?
• Can you suggest a better regimen?
• How would you assess whether the new regimen is
  working?

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A Simple Approach to Pain Management - The WHO
Analgesic Ladder
Severe
Pain
Strong Opioid
Moderate
Weak Opioid
Mild
Non-Opioid
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Opioid Analgesics

• Opioids used conventionally for moderate pain
  (Step 2)
• codeine, hydrocodone, oxycodone.
• typically combined with non-opioid (e.g. Tylenol
  3, Percocet) which limits dose titration.
• Opioids used conventionally for severe pain (Step
  3)
• morphine, hydromorphone, fentanyl, oxycodone.
• levorphanol, methadone, oxymorphone

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Equianalgesic Dosesof Opioid Analgesics (in mg)

• po / pr Analgesic sc / iv / im
• 200 Codeine 120
• 30 Hydrocodone -
• 7.5 Hydromorphone 2-3
• 30 Morphine 10
• 20 Oxycodone -
• - Fentanyl 0.1-0.25

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Opioids - Principles of Dosing

• Individualize dose by gradual escalation until
  development of adequate analgesia or intolerable
  and unmanageable side effects.
• No therapeutic ceiling effect.
• Around the clock dosing for continuous or
  frequently recurring pain.
• As needed (prn) dosing for dose finding and for
  rescue doses.

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Selecting a Starting Dose

• No prior opioid Begin one of the strong opioids
  at a dose equivalent to 5 - 10 mg of MSO4 IV/SC
  every four hours
• Switching from another opioid Calculate
  equianalgesic dose from standard table, then
• if pain control is good, reduce equianalgesic
  dose by 25-50 to account for incomplete
  cross-tolerance
• if pain control is poor, and side effects not
  severe, reduce equianalgesic dose by 25 or less
• if new drug is methadone, reduce equianalgesic
  dose by 90

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Case 2 continued...

• Following dose titration, Mr. B.s pain comes
  under better control on MS Contin 45 mg po q 8h.
  However he complains that the pain killers
  arent lasting the full eight hours.
• Your response?

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Breakthrough Pain

• Transitory exacerbations of severe pain over a
  baseline of moderate to mild pain
• Reported by 2/3 of cancer patients with
  controlled baseline pain
• Often due to incident pain or end-of-dose
  failure (important to distinguish)

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Opioid Rescue Doses

• Used for breakthrough pain.
• Dose
• Approximately 10 of daily dose equivalent.
• Frequency
• Oral every 1 - 2 hours
• Parenteral every 15 - 30 minutes

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Case 2 continued...

• Mr. B. presents to the Emergency room after
  falling and fracturing his left hip. He is
  currently on MS Contin 90 mg po q 8 hrs standing
  and immediate release morphine 30 mg po q 1 hr
  prn.
• What questions would you ask him?
• What adjustments should be made to his
  medications?

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Opioid Dose Adjustment

• Gradual dose escalation until development of
  adequate analgesia or intolerable and
  unmanageable side effects.
• No ceiling to analgesia and doses may become very
  large.
• Rate of escalation depends on severity of pain.
  Increase dose by 30 -50 for mild to moderate
  pain, 50-100 for severe pain.
• Increase rescue dose as baseline dose is increased

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Case 2 continued...

• Mr. B.s hip fracture is repaired and he returns
  home on his pre-fracture regimen. After a month
  his pain now worsens to the point he is taking
  prn morphine (30 mg) eight times daily.
• Why do you think that there is a need for more
  morphine?

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Tolerance

• Definition A change in the dose-response
  relationship induced by exposure to the drug and
  manifest as a need for a higher dose to maintain
  an effect.
• Develops at different rates to these varying
  effects
• respiratory depression, somnolence, nausea
  analgesia constipation.
• Analgesic tolerance is rarely a problem.
• Opioid doses remain relatively stable in the
  absence of worsening pathology and increased
  opioid requirements after stable periods is often
  a signal of disease progression.

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Case 3

• Ms. C. is a 58 y.o. woman taking hydromorphone 8
  mg po q 4 hrs with good pain control. You want
  to switch to a long-acting preparation.
• What would you use and what dose would you start?

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Case 4

• Mr. D. is taking morphine 600 mg po q 12h. He
  reports complete resolution of his pain following
  radiation therapy and wishes to discontinue his
  morphine.
• What do you advise?

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Dependence

• Definition The development of a withdrawal
  syndrome following dose reduction or
  administration of an antagonist.
• Often develops after only a few days of opioid
  therapy.
• Not a clinical problem if drug is tapered before
  discontinuation.
• Taper by no more than 50 of the dose/day

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Case 5

• Mr. E. is reluctant to begin opioid therapy.
• If I take strong medication now, what will I do
  when things become really bad? Maybe I should
  wait a while.
• What is your advice?

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Barriers to Effective Opioid Therapy

• Patient Barriers
• Save for when its really bad
• Fear of addiction
• Stigma of morphine
• Side effects
• Reluctant to report pain

• Physician Barriers
• Fear of addiction
• Knowledge deficits
• Regulatory oversight
• Analgesia low priority compared to cure

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Case 6

• Ms. F. is reluctant to take opioids. I dont
  want to become an addict.
• What do you say?

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Addiction

• Compulsive Use
• Loss of Control
• Continued Use Despite Harm to Self and Others.

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Addiction

• Risk of iatrogenic addiction in patients with
  pain and no prior history of substance abuse is
  extremely small.
• Need to recognize aberrant drug-related behaviors
  and understand the differential diagnosis for
  this behavior.
• Pseudoaddiction- behaviors that are reminiscent
  of addiction, but are driven by pain and
  disappear with more adequate analgesia.

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Case 7

• Ms. G. is a 72 y.o. woman with metastatic colon
  cancer to liver, s/p resection of her primary
  tumor who complains of worsening abdominal pain
  and watery diarrhea. She is currently taking
  Duragesic 150 mcg/hr patch q 72 hr.
• What question would you ask and what would you
  do?

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Constipation

• Most common adverse effect encountered during
  chronic opioid therapy
• No tolerance developed to this side effect
• Multifactorial
• Prophylactic laxatives are indicated
• PREVENTION IS KEY!

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Constipation Management

• Softeners
• Docusate
• Cathartics
• Senna
• Biscadoyl (Dulcolox)
• Osmotic Laxatives
• Magnesium/aluminum salts
• Lactulose
• Sorbitol
• Enemas
• Fiber- usually not indicated in frail or
  end-of-life patients

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Case 8

• Mr. H. was recently started on morphine for
  painful bony metastases of prostate cancer. He
  complains, Im feeling really nauseated since
  you started me on morphine. I feel that the
  nausea is sometimes worse than the pain. Should
  I stop the morphine?
• How do you respond?

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Nausea and Vomiting

• Common at the start of therapy
• Tolerance typically develops (7 - 10 days)
• Prophylactic administration of antiemetics is not
  necessary
• Select treatment on basis of characteristics

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Opioid-Induced Nausea and Vomiting

• Stimulation of Medullary chemoreceptor trigger
  zone.
• Peak soon after administration
• metoclopramide, neuroleptics
• Enhanced vestibular sensitivity
• vertigo or prominent movement induced nausea
• scopolamine, meclizine
• Increased gastric antral tone
• early satiety, bloating, postprandial vomiting
• metoclopramide

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Case 9

• Ms. I. has recently started on morphine for
  painful bony metastases of breast cancer. Her
  family calls to report that the patient is
  sedated and confused since the start of opioid
  therapy.
• How do you proceed?

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Opioid Side Effects - Sedation and Cognitive
Impairment

• Common with initiation of therapy or dose
  escalation.
• Tolerance usually develops in days-weeks.

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Management of Persistent Opioid Induced Sedation
and Cognitive Impairment

• D/C non-essential centrally acting medications.
• Evaluate and treat other potential causes.
• If analgesia satisfactory, decrease dose by 25.
• If analgesia inadequate or symptoms persist
  despite dose reduction
• trial of psychostimulant (if sedation) or
  neuroleptic (if delirium).
• switch to an alternative opioid.
• trial of other invasive/non-invasive approach to
  decrease systemic opioid requirements.

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When dose-limiting side effects occur with opioid
pharmacotherapy...

• More aggressive treatment of adverse effect(s)
• Opioid-sparing strategies
• Analgesic adjuvants
• Alternate route (e.g. intraspinal)
• Anaesthetic/Neurolytic procedures
• PMR approaches
• Cognitive therapy
• Complementary therapies
• e.g., acupuncture, massage, music therapy
• Opioid rotation

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Adjuvant therapies may be particularly helpful
with...

• Bone pain
• Radiation therapy, steroids, NSAIDs, calcitonin,
  radiopharmaceuticals, bisphosphonates
• Neuropathic pain
• Anticonvulsants, antidepressants, antiarrhythmics

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Summary of Opioid Pharmacotherapy

• By the ladder
• By the mouth
• By the clock
• By the individual