Lec 4: Cancer Pain Management

Question 1

Acute Pain - General

Answer 1

• Normal predicted physiological response to an adverse stimulus
• Result of activation of the pain receptors (nociceptors) at the site of tissue damage.
• Warning signal that something is wrong
• Self-limiting and usually resolves over days to weeks
• Activates sympathetic branch of the autonomic nervous system to produce hypertension, tachycardia, diaphoresis, shallow respiration, restlessness, facial grimacing, guarding behavior, pallor, and/or pupil dilation
• Can be associated with significant physical, psychological, and emotional distress
• Inadequately controlled pain can be a factor in the development of chronic pain
  .
  NOTE: Pain include many dif aspects: physical, emotional, social, adn spiritual

Question 2

Chronic Pain - General

Answer 2

• Intractable pain that exits for 3 or more months and does not resolve in response to
  treatment.
• Can be viewed as its own disease
• Can be affected by physical, environmental, and psychological factors
• May reduce quality of life, well-being, and ability to function over the long-term
• Positive adaptation does not occur
• Does not resolve on its own

Question 3

Classification of Pain
Nociceptive pain (maintained by continual tissue injury) : Somatic pain

Answer 3

SOMATIC PAIN
- Tissue damage to skin, soft tissue, muscle or bone
- Descriptors: aching, gnawing, deep, dull, sharp, stabbing
- Well localized – patients can often point with one finger to the location of their pain

Question 4

Classification of Pain
Nociceptive pain (maintained by continual tissue injury) : Visceral pain

Answer 4

Question 5

Classification of Pain
Non-nociceptive pain: Neuropathic pain

Answer 5

• Injury or inflammation of nerves. Often coexists with somatic or visceral pain
• Descriptors: burning, electric, numb, radiating, lancing, shooting, tingling
• Radicular: single or multiple nerve roots,
  Herpes zoster, sciatica
• Stocking-glove: Fingers and toes
• Diabetic or chemotherapy-induced neuropathy

Question 6

Classification of Pain
Cancer-related bone pain

Answer 6

• Somatic nociceptive and neuropathic
  components
• Deep, aching, localized
• Intensifies with movement and/or weight
  bearing
• Activation of osteoclasts and osteolysis leads
  to pain and hypersensitivity in the bone and
  periosteum
• Cancer within bone marrow causes neuropathic pain and neuroplastic response
• Nerve growth factor is released causing
  central sensitization

Question 7

Pain Assessment Part 1: important acronym to access?

Answer 7

P = palliating/provoking
Q = quality
R = region/radiation
S = severity
T = timing (onset, duration, frequency)
U = YOU (goals, activity level, QOL)

Question 8

Pain Assessment Part 2: Additional questions

Answer 8

Quality:
- What does your pain feel like?
- What words would you use to describe your pain?
.
Region and Radiation:
- Where is your pain?
- Where does the pain start?
- Does the pain move anywhere?
.
Aggravating/Alleviating Factors:
- What makes your pain worse? better?
- What previous treatment have you tried to relieve your pain?
.
Intensity:
- On a scale of 0 to 10, with O being no pain and 10 being the worst pain you can imagine, how much does it hurt right now?
- How does the pain compare with other pain you have experienced?
.
Temporal Characteristics:
- When did your pain start? How often does it occur?
- How long does it last?
.
Functional Impact:
- How does the pain affect your sleep? Your appetite? Your energy level?
- How does the pain affect your mood? relationships?
.
NOTE: use Wong Baker faces to rate pain or numerical rating 0-10

Question 9

When are Opioids Indicated? What are the general steps/ ladder?

Answer 9

When are Opioids Indicated?
- Moderate to severe pain related to cancer or active cancer treatment
- In a 2016 review of oral morphine, the study indicated that 96% of morphine-treated patients achieved the outcome of no worse than mild pain
- Clinicians should discuss goals regarding functional outcomes, shared expectations, and pain intensity, as well as any concerns about opioids (eg. addiction ? use lowest dose?)
- Opioids should be initiated as immediate release and PRN (as needed) to establish an effective dose, with early assessment and frequent titration

Question 10

Fentanyl : importance

Answer 10

• Transdermal, transmucosal, and parenteral formulations
• May only be used in patients receiving at least 60mg oral morphine, 30mg oral oxycodone, 8mg oral hydromorphone, or equivalent daily for at least one week (no need to know specific dose, but know TDF should NOT be used for opiate naïve patients!)

Question 11

Methadone: Importance

Answer 11

• Poorly predictable potency with switch from
  another opiate
• May reverse a component of opioid analgesic tolerance
• Half life can vary from 12 hours to 7 days,
  average is 24 hours and can lead to accumulation
• Multiple drug-drug interaction due to
  metabolism by cytochrome P450 system
• 80% oral bioavailability
• QTc prolongation

Question 12

Cardiac Concerns with Methadone?

Answer 12

• Methadone Should Be Use with caution with other meds that prolong QT interval
  —– Antipsychotics (chlorpromazine, haloperidol)
  —– Antidepressants (citalopram, escitalopram)
  —— Antibiotics (quinolones, macrolides)
  —— Antiemetics (prochlorperazine, ondansetron)
• Low potassium and/or magnesium can increase risk

Question 13

Good/Bad Methadone Candidates

Answer 13

Question 14

Potential Drug Interactions with Methadone

Answer 14

Question 15

Buprenorphine: what is it? / advantages?

Answer 15

What is it?
Mu-opioid partial agonist
— Parenteral for severe acute pain
— Sublingual as opioid agonist therapy
— Transdermal (Butrans®) and transmucosal (buccal film, Belbuca®) for chronic pain
.
Advantages of buprenorphine include:
- Effectiveness in treating a variety of pain syndromes
- Less adverse effects (constipation, cognitive impairment, respiratory depression, immunosuppression, hypogonadism)
- Better safety profile in vulnerable populations (elderly, renal impairment)
- Fewer withdrawal symptoms

Question 16

Starting and Titrating Opioids

Answer 16

• Starting dose depends on frequency and severity of pain, previous experience with
  opiates, recent exposure to opiates, age, body weight, and medical status
• Safest approach is to start low dosage of short acting oral formulation
• Initial dosage should be titrated up until either relief achieved or side effects prevent
  further titration
• Dose usually increased by 25-50% each titration
• Ideally dose escalation should be done at intervals to allow steady state
• Short acting can be used for rapid dose escalation in severe pain

Question 17

Treatment of Breakthrough Pain

Answer 17

• Occurs in 40-80% of cancer patients
• Treated with breakthrough or rescue doses of short acting medication
• Usually 10-20% of the total baseline daily dose prescribed every 2-4 hours
• Titration may be needed to balance efficacy and side effects
• If needed 3 or more times a day, baseline
  (regular scheduled or long-acting dose) may need adjustment

Question 18

Types of Breakthrough Pain, it’s characteristics, and what to do

Answer 18

Question 19

5 A’s – Opioid therapy monitoring tool: Opioid therapy should be monitored by assessing the “5As” of Analgesia therapy - what are they?

Answer 19

1.) Activity: What progress has been made in the patient’s functional goals? (eg. sitting/ standing tolerance, walking ability, ability to preform AoDL)
.
2.) Analgesia: How does the patient rate the following over the last 24 hours?
.
3.) Adverse effects: Has the patient experienced any adverse effects from medication? E.g., constipation, nausea, dizziness, drowsiness
.
4.) Aberrant behaviors: Has the patient been taking medication/s as prescribed? Has the patient exhibited any signs of problematic behaviors or medication abuse/misuse? Has the patient reported lost prescriptions or requested early repeats?
.
5.) Affect: Have there been any changes to the way the patient has been feeling? Is pain impacting on the patient’s mood? Patient depressed or anxious?

Question 20

Sign of under and over medicated

Answer 20

Question 21

Opioid Adverse Effects and Treatments

Answer 21

Question 22

Drug Therapy Monitoring Plan

Answer 22

Question 23

Drug Treatment for Neuropathic Pain
(4 different classes)

Answer 23

1.) Tricyclic antidepressants
- Amitriptyline, nortriptyline, desipramine
- Usual starting dose: 10-25mg PO qhs
- Usual effective dose: 50-150mg PO qhs
.
2.) SNRIs
- Duloxetine 20-30mg PO daily, increase to 60mg PO daily as tolerated (No benefit beyond 60mg PO BID)
- Venlafaxine
.
3.) Calcium channel α2-δ ligands
Modulates the alpha-2-delta protein subunit of the voltage-gated calcium channel; Inhibits calcium influx into the neuron and diminishes neuronal hyperactivity
—- Gabapentin – 100-300mg PO TID ; Titrate 50-100% every 3-7 days; Renal dosing
—– Pregabalin – starting dose 150mg PO daily in 2-3 divided doses; Increase to 300mg/day in 3-7 days, then by 150mg/day every 3-7 days as tolerated; Less titration, greater binding affinity
.
4.) topical products? - no good evidence

Question 24

Drug Treatment for Bone Metastases

Answer 24

1.) Corticosteroids (Dexamethasone, prednisone)
2.) NSAIDs (Diclofenac, ibuprofen, naproxen)
3.) Calcitonin
4.) Bisphosphonates – osteoclast inhibitors ; correct hypercalcemia (Pamidronate, zoledronic acid, ibandronate)
5.) Denosumab – nuclear factor-kappa ligand (RANKL) inhibitor
6.) Radiopharmaceuticals (Strontium-89, Radium-223)

Question 25

What are the 3 types of Difficult to
Treat Pain

Answer 25

1.) Opioid induced hyperalgesia- increasing pain and sensitization caused by complex multifactorial neurobiological factors in a patient who is receiving increasing doses of opioids
.
2.) Opioid-induced tolerance- decreasing efficacy of opioids over time caused by desensitization of antinociceptive opioid pathways
.
3.) Opioid non-responsive pain- types of pain, such as neuropathic pain, ulceration pain, muscle pain, bladder spasm, and rectal tenesmus, that does not usually respond to treatment with opioids

Question 26

More info on: Opioid-Induced Hyperalgesia

Answer 26

• Paradoxical reaction where a patient becomes more sensitive to certain stimuli and may experience pain from ordinarily non-painful stimuli
• Often accompanied by neuroexcitatory signs and symptoms (myoclonus, confusion, hallucinations)
• Case reports typically high dose opioids and most commonly >1000 mg OME
  ➢Treatment: dose reduction, opioid rotation to synthetic opioid, supportive measures

Question 27

Know dosing conversion of these 5 drugs

Answer 27

Question 28

What is the formula used for opioid dose conversions?

Answer 28

Question 29

Assessment for Risk of Misuse: Opioid Risk Tool (ORT)

Answer 29

• 5-item yes/no questionnaire, predicts probability of opioid misuse or abuse
• Asks about family history of substance abuse, personal history of substance abuse, age (16-45 years is a risk factor), history of pre-adolescent sexual abuse, and psychological disease
• Stratifies patients as low, medium or high risk
• Most useful in lower-risk settings, like primary care rather higher risk settings as it is more likely to rule in risk than rule it out and patients may not fully disclose information

Question 30

Assessment for Risk of Misuse: Screener and Opioid Assessment for Patients with Pain (SOAPP)

Answer 30

• 14-item self-report, predicts risk of aberrant drug behavior
• Includes things like antisocial behavior, substance abuse history, doctor/patient relationship, medication-related behaviors, and psychiatric and neuro-biologic need for
  medicine
• Responses on a 5-point Likert scale (possible score range 0-56)
• Using 7 as cut off, has a sensitivity of 91%, specificity of 69%
• Positive predictive value (PPV) of 71% and negative predictive value (NPV) of 90% (7) to
  predict aberrant drug behavior

Question 31

Opioid Access Issues

Answer 31

Question 32

Key Takeaways Regarding Cancer Pain

Answer 32

• Cancer pain is multifactorial therefore a thorough pain assessment is vital to
  developing an appropriate treatment plan
• Opioid therapy is indicated for cancer pain and adjunct analgesics should be used when necessary
• Opioid rotation may be indicated for a variety of reasons and should be approached with caution on an individual basis using a consistent equianalgesic table
• ALWAYS have a bowel regimen in place!!