26 - Cancer Pain Flashcards
Define opioid addiction
- Primary, chronic disease of brain reward, motivation, memory, and related circuitry
- No published reports in cancer px w/ no previous substance abuse hx
Define physical dependence
- Occurrence of abstinence syndrome when the opioid is suddenly stopped
- Fairly common, need gradual withdrawal
Define tolerance
- Decrease in one or more effects of the opioid
- Decreased analgesic effect due to tumour progression
Briefly describe nociceptive pain
- Direct stimulation of intact nociceptors
- Transmission along normal nerves
- Somatic – easy to describe and localize (ex: aching, stabbing, throbbing)
- Visceral – difficult to describe and localize (ex: squeezing, cramping, sharp or dull)
- Tissue injury apparent
Describe neuropathic pain
- Disordered peripheral or central nerves
- Compression, infiltration, ischemia, metabolic injury
- Pain may exceed observable injury
- Less responsive than nociceptive pain
- Poorly responsive syndromes likely have a neuropathic component
- Ex: burning, tingling, sharp, electric shock
Causes of cancer pain
- Cancer itself (75-80%)
- Tumour involvement of the bone (30-70%)
- Tumour involvement of nervous tissue, viscera, blood vessels
- Tx of cancer (15-19%)
- Chemotherapy – peripheral neuropathy, mucositis
- Radiotherapy – plexopathy, pelvic pain
- Post-surgical – neuropathies
- Unrelated to cancer (3-5%)
Tx related neuropathy
- Chemotherapy-induced (cisplatin, oxaliplatin, paclitaxel, thalidomide)
- Surgical
- Phantom limb pain
- Post-mastectomy or post-thoracotomy syndrome
Tx related immunosuppression
- Post-herpetic neuralgia
- Topical compounded cream (combination of topical anesthetic, mu receptor blocker, neuropathic pain med, NMDA blocker) if area is small
- Oral combination of opioid + neuropathic pain med
Codeine – metabolism and CI
- 10% metabolized by CYP2D6 to morphine which is responsible for analgesia
- Due to genetics:
- 5-10% of people will have no analgesic effect
- 1-29% will have a more pronounced effect
- Contraindicated w/ paroxetine, fluoxetine, quinidine, haloperidol
- Contraindicated in renal and liver dysfunction
Morphine – metabolism and CI/ caution
- Hepatic metabolism
- 60% to morphine-3-glucuronide
- 10% to morphine-6-glucuronide (greater analgesic properties and fewer AE)
- 4% to normorphine (non-active, non-toxic)
- Avoid in renal dysfunction and failure
- Use w/ caution in severe liver dysfunction (increase dosing interval from q6h to q8h)
Hydromorphone – metabolism, caution
- Metabolized to hydromorphone 3-glucuronide
- Use w/ caution in severe liver dysfunction
- Increase dosing interval from q6h to q8h
- Dosage conversion from IV to PO is 1:1
When is hydromorphone preferred over morphine?
- Renal failure
- Elderly (> 60 y/o) due to decreased renal function
- Hx of rashes
- Nausea and constipation are a problem
- Sedation is a problem
When is fentanyl preferred over morphine and hydromorphone?
- Elderly (> 60 y/o) due to decreased renal function
- Renal failure and severe liver dysfunction
- Hx of rashes
- When nausea and constipation are a problem
- When sedation is a problem
When should caution be taken w/ fentanyl?
Caution w/ CYP 3A4 inhibitors (clarithromycin, voriconazole, grapefruit) and inducers (dilantin, rifampin, steroids)
Methadone – oral BA, metabolism, MOA, duration of analgesia
- Oral BA > 85%
- Metabolized in liver = no active metabolites
- Blocks NMDA receptors
- Duration of analgesia = 4+ h
Starting doses for IV and PO morphine and hydromorphone for opioid naïve px – moderate pain and frail
- 2.5 mg PO morphine
- 1 mg IV/SC morphine
- 0.5 mg PO hydromorphone
- 0.2 mg IV/SC hydromorphone
Starting doses for IV and PO morphine and hydromorphone for opioid naïve px – severe pain and frail
- 5 mg PO morphine
- 2 mg IV/SC morphine
- 1 mg PO hydromorphone
- 0.5 mg IV/SC hydromorphone
Starting doses for IV and PO morphine and hydromorphone for opioid naïve px – moderate pain and robust
- 5 mg PO morphine
- 2 mg IV/SC morphine
- 1 mg PO hydromorphone
- 0.5 mg IV/SC hydromorphone
Starting doses for IV and PO morphine and hydromorphone for opioid naïve px – severe pain and robust
- 10 mg PO morphine
- 5 mg IV/SC morphine
- 2 mg PO hydromorphone
- 1 mg IV/SC hydromorphone
Who should NEVER get a fentanyl patch?
- Opioid naive px
- < 18 y/o
- For acute pain
Describe bystander apathy
- Belief that others in a group who see the same risks will intervene
- *No pt should ever walk out the door of your pharmacy w/o a face to face instruction on how to use and dispose of fentanyl patches
Titration of opioids for cancer pain
- Correct dose is a compromise between sufficient pain relief, good cognitive function, and acceptable SE profile
- Start low and titrate slowly, elderly metabolize opioids differently due to decreased renal function and hepatic clearance
Guidelines for opioid dose escalation
- Always increase by a percentage of the present dose based upon px pain rating and current assessment
- Mild pain (1-3/10) -> 25% increase
- Moderate pain (4-6/10) -> 25-50% increase
- Severe pain (7-10/10) -> 50-100% increase
PO and IV dose of morphine equal to 100 mg PO codeine
- PO = 10 mg
- IV = 5 mg
PO and IV dose of oxycodone equal to 100 mg PO codeine
- PO = 5 mg
- IV = n/a
PO and IV dose of hydromorphone equal to 100 mg PO codeine
- PO = 2 mg
- IV = 1 mg
PO and IV dose of methadone equal to 100 mg PO codeine
- PO = 1 mg
- IV = n/a
PO and IV dose of fentanyl equal to 100 mg PO codeine
- PO = n/a
- IV = 50 ug
PO and IV dose of sufentanil equal to 100 mg PO codeine
- PO = n/a
- IV = 5 ug
Steps to calculate equianalgesic doses
- Calculate total daily opioid intake (regular and breakthrough doses)
- Convert to morphine equivalents
- Convert from morphine equivalent to new opioid
- Start new product at 50-75% of calculated dosage
- Evaluate frequently for uncontrolled pain and re-titrate, if needed
What is a typical breakthrough dose?
10-15% of daily dose
Fentanyl patch conversion process
- Takes 12-16 h to achieve therapeutic fentanyl serum levels
- Therefore, must provide pt w/ opioid coverage during the conversion period
- Ex: should be given hydromorphone immediate release at time of patch application (whatever the breakthrough dose is calculated as), 4 h after patch application, and 8 h after patch application
- Upon system removal, 17 h or more are required for a 50% decrease in serum fentanyl concentrations
Opioid side effects
- Common = constipation, N, somnolence, mental clouding
- Less common = urinary retention, pruritus, myoclonus, amenorrhea, sexual dysfunction, headache
Opioid induced neurotoxicity (sx and tx)
- Sx = N, twitching/ myoclonus/ seizures, sleeping a lot, change in mental status, delirium, hallucinations, hyperalgesia
- Tx = hydration, change opioid or reduce dose, treat sx (hallucinations, agitation)
- Metabolites cause opioid induced neurotoxicity
Neuropathic pain – pharm options
- Opioids
- Anticonvulsants (gabapentin, pregabalin, carbamazepine)
- Antidepressants (duloxetine, amitriptyline, nortriptyline, venlafaxine, methadone)
- Cannabinoids
Cannabinoid indications (on and off label)
- On-label -> N/V from chemotherapy, chronic pain (neuropathic pain in MS and cancer), anorexia associated w/ HIV/AIDS, drug-resistant epilepsy
- Off-label -> PTSD, anxiety, insomnia, epilepsy, chronic daily headache, inflammatory conditions, neuropathic/ mixed pain
IV dose of codeine equal to 100 mg PO codeine
50 mg
