Pain in Palliative Care: Tx Flashcards
Management of Pain
By the ladder
By the mouth
By the clock
With breakthrough dosing
Individualized for patient
Address all aspects of suffering
Monitor efficacy regularly
Identify and treat underlying causes (if feasible)
Classification of Pain
Using numerical
rating scale (1-10)
(from ESAS-r)
◦ Mild pain (1-3)
◦ Moderate pain (4-6)
◦ Severe pain: 7-10
WHO analgesic ladder
WHO Ladder for Pain Control
Step 1
Mild Pain
Step 2
Moderate Pain
Step 3
Severe Pain
Non-opioids
Acetaminophen
NSAIDS
+/- Adjuvants
Weak opioids
Codeine
Tramadol
+/- Adjuvants
Strong opioids
Morphine
Hydromorphone
◦ Laxatives should be prescribed in most cases (opioids)
◦ Insufficient evidence to support/refute Step 2
opioids (eg. codeine) are superior to NSAIDS
◦ In rapidly progressing pain Step 2 may be omitted
Use low doses of Step 3 analgesics (eg. morphine)
Need to adjust dosing
◦ Geriatrics, and those with decreased cognitive or
organ function.
◦ Opioid tolerant or history of opioid misuse
Oral route is preferred
◦ Easier to administer
◦ Cheaper
◦ No special techniques
required
◦ No specialized pharmacy
◦ No risk of infection
◦ Less painful
May not be possible if:
◦ Malabsorption from gut
Short gut, bowel obstruction
Nausea/vomiting
◦ Patient delirious/unresponsive
By the clock
Continuous pain
or pain which
occurs
frequently,
requires around
the clock
analgesia
Breakthrough Pain
In addition to regular pain most patients
experience pain flares: breakthrough pain
Need prn order in addition to ATC orders
Usually: 10% of daily dose q1h prn
May be associated with a particular activity
◦ Incident pain
Take prn dose before doing that activity
Or daily variation of the pain
◦ Dose when pain increases
if exceed max, neeed reassessment
All Aspects of Suffering
Identify & Treat Underlying
Causes
Address the
physical,
psychological,
spiritual and
social problems
the patient may
be experiencing
If appropriate
◦ Tumors
Palliative
chemotherapy
Palliative
radiation
Palliative surgery
◦Infections
Antibiotics
◦ Constipation
Laxatives
Step 1: Acetaminophen
Used as mild analgesic and adjuvant
Maximum dose (from all sources)
◦ 4000mg/day
Should only be short-term in healthy adults
◦ 3000 mg/day
Long term use in healthy adults (≥ 7 days)
◦ 2000mg /day or avoid
Heavy alcohol use, malnutrition, low body weight,
advanced age, febrile illness, advanced liver disease,
interacting medications
Dose restrictions may limit efficacy
Step 1: NSAIDS
Have traditionally be used for mild cancer pain
Mild analgesic and adjuvant
As effective as weak opioids
Effect in bone pain not as robust as previously
thought: may have benefit in select cases
Adverse effects limit their use particularly in
elderly/frail population.
◦ GI, kidneys, increased bleed risk
Ibuprofen, naproxen, diclofenac (honestly rarely used)
◦ Topical diclofenac is used
Patient Concerns with Opioids
Only used at end of life. With increased survivorship
patients may take these agents for months or years.
Not shown to shorten life when used appropriately.
Very sedating (can’t drive): patients usually
overcome sedation after a few days.
Addiction: Majority of patients do not become
addicted. Dose increases over time may be due to
tolerance. Monitor closely.
If started too early there will be no no options at
the end. Pain does not necessarily increase at the
end of life. Doses can be increased or switch agents
Start Low & Go Slow
When initiating opioids start at lower doses
Dose reduce in presence of frailty or organ
dysfunction
Up-titrate slowly to effect
Monitor for adverse events
◦ Prescribe laxatives to prevent constipation
Naloxone kit (call ambulance)
◦ Patient may have pain crisis if used (immediate)
- controversy for palliative pop, have it for ppl in the house who make help take their opioids for them
Step 2: Codeine
Exhibit a ceiling effect: Maximum effect
Naturally occurring opioid.
~ 1/10 as potent as morphine
Metabolized to morphine
◦ Via CYP 2D6
Genetic polymorphism may alter metabolism
Drug interactions
Dose
◦ Start 8-15 mg
◦ Maximum: 300 to 400 mg
Single agent or combination
Long-acting forms available
Step 2: Tramadol
Weak opioid & inhibitor of norepinephrine &
serotonin reuptake
Liver metabolized
Dose: 50 to 100 mg every 6 hrs
Maximum dose= 400 to 600mg daily
Adverse effects ;
◦ Nausea & dizziness are transient
Care with seizure disorders, raised ICP, hepatic and
renal impairment
Care TCA’s & SSRI’s (lower seizure threshold)
Long-acting formulations available
Not covered by many drug plans
Strong
Opioid Suggested starting dose
Morphine 5 to 10 mg PO q4h atc
Hydromorphone 1 to 2 mg po q4h atc
Oxycodone 2.5 to 5 mg po q4h atc
Fentanyl 25 mcg/h (Do not use 1st –line)
Methadone Dose varies (Do not use 1st line)
Consider dose reductions in the elderly/frail, opioid-naïve patient
Adverse Effects of Opioid
Early/Acute
◦ Usually resolve
Nausea
Sedation
Respiratory depression
Pruritus
Urinary symptoms
◦ Except
Constipation
Late/Chronic
◦ Constipation
◦ Hypogonadism
◦ Neurotoxicity
◦ Tolerance
◦ Addiction
◦ Withdrawal
Fentanyl
Potent (100 x stronger than morphine)
Not active orally
◦ Transdermal patches
◦ Injectable
Intermittent: Incident pain
Rapid onset, short acting
Use 15 minutes prior to aggravating activity
Continuous infusion (subcut or IV)
◦ Sublingual - but very expensive
◦ Intranasal (no commercial product available)
Do not use if opioid-naïve
Not covered by many drug plans
Conversion to Fentanyl Patch
Morphine oral dose
mg/24 hrs
TD Fentanyl
mcg/hr q72h
45-134 25
135-224 50
225-314 75
315-404 100
405-494 125
495-584 150
585-674 175
675-764 200\
12 h to stady state, need to bridge so they dont have pain
Sublingual Fentanyl
Sublingual tablets
◦ Abstral
Buccal tablets
◦ Fentora
Expensive
◦ Not covered by 3rd
parties
◦ Hospital formulary
Compounding
pharmacies
Can use the
injectable
sublingually
50 mcg/mL
Measure dose in
syringe & hold under
the tongue as long
as possible
dosed q8h for the patient
no adjustment for renal failure
methadone as analgesic
Renewed interest
◦ Low cost
◦ Activity against
neuropathic pain
syndromes
◦ ↓ neurotoxicity
Receptors
◦ μ, k & δ (agonist)
◦ NMDA receptors
(antagonist)
◦ Norepinephrine &
serotonin reuptake
Metabolism
◦ CYP 3A4
Induced or inhibited
◦ CYP 1A2
Induced or inhibited
◦ CYP 2D6
Depends on
polymorphism
methadone drug interaction
↓ Methadone ◦ Antiretrovirals Nevirapine Ritonavir ◦ Phenytoin ◦ Carbamazepine ◦ Dexamethasone ◦ Rifampin ◦ Spironolactone ◦ Alcohol/tobacco
↑Methadone ◦ Cimetidine ◦ Omeprazole (not on hospital formulary(◦ Ketoconazole ◦ Fluconazole ◦ SSRI’s ◦ Verapamil ◦ Ciprofloxacin ◦ Macrolides
methadone and ATc interval
Prolongs QTc
interval
Dose related (300-
600mg/day)
Not usually a concern in
palliative patients
Cumulative with other
agents: avoid if possible
◦ Levofloxacin
◦ Fluconazole
◦ Arsenic
methadoe tx advantages
Advantages
◦ Potent and effective
analgesic
◦ Inexpensive
◦ Fewer neuro-toxicities
◦ Long T1/2 (fewer daily
doses)
Neuropathic pain
◦ NMDA receptors
◦ NOR & 5HT
Can be administered to
those highly tolerant to
other agents
Incomplete crosstolerance helps control
intractable pain
Tablets and syrup
commercially available
Methadone as a Co-analgesic
Using low dose methadone in addition to
regular opioid
Does not necessitate full methadone rotation
◦ No hospitalization, rapid initiation, less expertise
required.
Patient does not get the full benefit of
methadone - downside
Difficult to determine origins of toxicities with
more than opioid on board
Ppl unable to do complete methadone rotation
North America 3rd
or 4th line
Europe &
developing
countries often 2nd
line after
morphine
methadone disadvantages
◦ Kinetics unpredictable
Courses for prescribers
◦ Rectal & injectable
forms not
commercially available
Compounding
pharmacies
other receptors involved, not straight conversion
Naloxone Kits
Provide if
◦ Non-compliance
expected
◦ May be taken by others
Explain administration
may precipitate a pain
crisis
Naloxone Kits
* Breathing will change close to death
* Do not mistake for opioid toxicity
* CALL AMBULANCE if administered
if respiratios go down, hold dose and wait as it takes long time towear off
adjuvants used in cancer pain
Acetaminophen
NSAIDS/ASA
Gabapentin & pregabalin ◦ Neuropathic pain
Bisphosphonates ◦ Reduces skeletal events (fractures)
Corticosteroids ◦ Reduce swelling
Anesthetics ◦ Locally for sores ◦ Intrathecal ◦ Ketamine Bursts - large doses for a few days and stop or continious (quite sedating)
Chemo & RT Physiotherapy Psychotherapy
ASA, Acetaminophen, NSAIDs
Used in Step 1
◦ Mild cancer pain
Used in any step as an
adjuvant
Value as adjuvant in
Step 3 (strong opioids)
is questionable
Adverse effects
ASA, Acetaminophen, NSAIDs
* Acetaminophen: Maximum doses. Care in liver mets/failure
* ASA & NSAIDs: Gastric, renal, ↑ bleed risk, corticosteroids
Gabapentin & Pregabalin
Used for neuropathic pain
◦ Gabapentin start at 100 to 300 mg hs and increase
to 900-3600mg/day in 2-3 divided doses
◦ Pregabalin start at 25-75 mg po bid and increase
upto 300 mg po bid
Adverse effects include sedation, cognitive
disturbances, peripheral edema, ataxia &
depression
Do not discontinue abruptly
Antidepressants
Duloxetine start at 30 mg daily and increase
up to 120 mg daily
Venlafaxine has been used but difficult to
discontinue
Tricyclic antidepressants can be useful but can
have profound anticholinergic side-effects
Carbamazepine, valproic acid & phenytoin no
longer recommended as 1st
-line. not used much
Corticosteroids
Useful in bone, neuropathic, & visceral pain
MOA related to their anti-inflammatory
properties
Useful for short courses of therapy (1 to 3
weeks) to manage pain crises
Avoid long-term use use: side effects
◦ Hyperglycemia, Cushing’s syndrome, psychiatric,
agitation, delirium, muscle weakness (reversible on
discontinuation
If long-term use necessary (eg: brain cancer)
use lowest possible dose.
shrink tumours
Dexamethasone
Cortico-steroid of choice
6.7 times more potent than prednisone
Minimum mineralcorticosteroid effects
◦ Less fluid retention
Prednisolone causes less proximal myopathy
than dexamethasone.
8 mg up to qid for severe symptoms
Taper dose if taking for longer than 2 weeks
Increase risk of gastric ulceration if take with
NSAIDS
Bisphosphonates
Clodronate (po), pamidronate (IV), zoledronic
acid (IV)
◦ Hypercalcemia
Pamidronate or zoledronic acid if refractory to
pamidronate
◦ Prevention of skeletal events (fractures)
Reduce risk by up to 30% after 3 months treatment
Multiple myeloma & breast cancer regular
bisphosphonate if extensive bone involvement
May have use in other cancers with bone metastases
Lung, prostate , colon
◦ Bone pain
Short-term (Zoledronic acid for prostate cancer)
Use for bone pain is controversial (& expensive)
A lot of pall pt have low albumin
Must correct
Or can OD by giving hem too much calc supplemetnatio
renal fxn adjustmnet
Use with caution in renal impairment
Clodronante 1600 mg po not well tolerated
◦ 4 large capsules on an empty stomach & no food
for 1 hour post treatment
◦ Cannot lie down after taking meds (prevent
esophagitis)
◦ PO use only for prevention of skeletal events
◦ Clodronate injection (subcut) is no longer available
Other adverse effects include
◦ Flu-like symptoms for a few days post-infusion
◦ Osteonecrosis of mandible reported with
pamidronate and zoledronic acid
used to do it more for multiple myeloma
Other Agents
Ketamine may be of use when traditional
agents have failed
Topical anesthetics (lidocaine) to inflamed
tissue (mouth sores, coccyx ulcers)
Canabinoids (Sativex®) only cannabinoid
indicated in cancer pain has yielded mixed
results in studies
Palliative chemo, radiation, or surgery as
indicated
Non-Pharmacological
Psychosocial support
◦ Psychologist/counselling
◦ Psychiatrist if needed (previous mental illness)
◦ Meditation
Spiritual support
◦ Chaplain
Physiotherapy
Pet therapy
Music therapy
Yoga, Reiki
Acupuncture
