1. THE MODERN MANAGEMENT OF PAIN IN PALLIATIVE MEDICINE

2. ASSESSMENT

3. WHO LADDER Pain NOT controlled STEP 3 STEP 2 Pain NOT controlled
STRONG OPIOIDS
Initial treatment with immediate
release MORPHINE (eg
ORAMORPH/SEVREDOL) 5-10mg* every 4 hours orally and as required for breakthrough pain (* a 2.5mg dose may be enough in elderly or patients with renal impairment)
WEAK OPIOID/
PARACETAMOL
COMBINATION (CO
CODAMOL 30/500) 2 qds
STEP 1
Breakthrough: immediate release
MORPHINE 5mg PRN (eg
ORAMORPH/SEVREDOL
PARACETAMOL
1 gram 4 times daily
+ Stimulant & softening laxatives
eg CO-DANTHRAMER 2 nocte or
DOCUSATE +
BISACODYL
+ Stimulant & softening laxatives
eg CO-DANTHRAMER 2 nocte
Or DOCUSATE +
BISACODYL
+/- ANTIEMETIC eg
HALOPERIDOL 1.5mg od/
METOCLOPRAMIDE 10mg tds
+/- NSAIDs
+/- NSAIDs
+/- adjuvant medication
+/- NSAIDs
+/- adjuvant medication
+/- adjuvant medication

4. MORPHINE Morphine strong opioid of choice for moderate/severe pain
This recommendation decided by:
Availability
Familiarity
Established effectiveness
Simplicity of administration
Relative inexpensive cost
Not based on proven therapeutic superiority over other options
Clinical response to morphine is very variable. Studies have suggested this variability may be related to:
Age
Renal and hepatic function
inducers eg carbamazepine, phenytoin, spironolactone
Concomitant medications steroids → reduced opioid availability
(the importance of cytochrome CYP3A4)
inhibitors eg midazolam, clarithromycin, fluconazole,
cyclizine → reduced opioid availability
Mechanism of pain
Genetic variation

5. OPIOID SWITCHING (ROTATION)
Indications:
Unmanageable side effects or toxicity (consider dose reduction or hydration initially)
Inadequate analgesia
Caution:
Individual variability in the response to different opioids in terms of analgesia and side effects
Need to monitor for possible morphine withdrawal
Fluids may be required if patient is toxic

6. ALTERNATIVE OPIOIDS
Oxycodone (oral, sc)
Hydromorphone (oral, sc)
Fentanyl (transdermal, buccal)
Buprenorphine (transdermal)
Alfentanil (sublingual, sc)
Methadone (oral, sc)

7. DOSAGE ADJUSTMENTS FOR PATIENTS WITH RENAL IMPAIRMENT
Chronic renal disease classified as:
eGFR(ml/min/1.73m2)
Mild
60 – 89
Moderate
30 – 59
Severe
15 – 29
Established
< 15
Doses can be adjusted in 3 possible ways:
By reducing the actual dose
By increasing the interval between doses
By reducing the dose and increasing the interval between doses

8. DOSE ADJUSTMENTS Drug Mild Moderate Severe Paracetamol Normal
Give 6 hourly
Give 8 hourly
NSAIDs (diclofenac)
50-100%
50%
25%
Codeine
100%
75%
8 hourly
12 hourly
Tramadol
Avoid
Morphine, diamorphine
75-100%
Avoid if possible
Oxycodone
Methadone
50-75%
Alfentanil
Fentanyl

9. HEPATIC FAILURE
Metabolism to active or inactive metabolites in the liver
In encephalopathy reduced metabolism and potential for toxicity increased
May need to change to PRN medication

10. BREAKTHROUGH ANALGESIA
Assessment of breakthrough pain, character, aggravating factors etc
Analgesia for treatment of pain or prevention of pain
If on regular opioid analgesic – breakthrough opioid 1/6th total dose of regular opioid (disputed)
1/6th rule not applicable to use of Fentanyl lozenge and probably methadone

11. NEUROPATHIC PAIN
Occurs in approximately 40% of patients with cancer pain
Vast majority of pain mixed
Compared with nociceptive pain, patients with neuropathic pain:
- obtain less pain relief with single dose of analgesics
- are more likely to escalate opioid dose
- are likely to have poorer outcome with treatment
- often obtain less relief with spinal analgesia
There is a lack of evidence for opioids in cancer neuropathic pain (not evidence of lack of effort)

12. MANAGEMENT OF NEUROPATHIC PAIN
Assessment including use of tools, eg LANSS
Medication:
WHO ladder + opioid switching
Amitriptyline
Gabapentin or Pregabalin
Ketamine + Dexamethasone
Methadone
Anaesthetic procedures

13. MODULATION OF OPIOID RECEPTOR MEDIATED EFFECTS
( effectiveness by  efficacy or reducing adverse effects)
2 adrenergic agonists - clonidine – epidural
- no studies of oral clonidine or tizanidine
NSAIDs
NMDA receptor antagonists – Ketamine
CCK antagonists
Gabapentin or pregabalin
NH-1 receptor antagonists
Use of 2 opioids eg Fentanyl + morphine
Methadone + Fentanyl
Methadone + morphine

14. OTHER APPROACHES Other modalities: external beam XRT
unsealed sources eg Sr89
Chemotherapy
Other routes:
Intranasal – alfentanil, fentanyl, diamorphine, morphine oxycodone
Topical – morphine
Other drugs: Complementary:
Baclofen Acupuncture
Bisphosphonates Hypnotherapy