Principles of pain management

By Salahadin A.
 Part I
WHO Analgesic Ladder

Disclaimer: This presentation contains information on the general principles of pain management. This presentation cannot account for
individual variation among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It is
the responsibility of the treating physician, or health care provider, to determine the best course of treatment for the patient. Treat the
Pain and its partners assume no responsibility for any injury or damage to persons or property arising out of or related to any use of these
materials, or for any errors or omissions.
Pain
Objectives

• Define pain management

• Set realistic goal and objectives for treatment of pain
• To administrate medications orally, and regularly by
the clock,
• To select drugs in a stepwise approach ,
• How to use a mix of adjuvants and analgesics
• introduce individualized management case by case
• Describe the mechanisms of analgesic drugs side
effects
• Discuss treatment for mild, moderate, or severe pain
4
Pain management

• Definition of analgesia: Pain

suppression in conscious patient

• Goal of pain management

-Prompt relief of pain,(50% reduction)
-Prevention of the recurrence of pain

5
Realistic Objectives: general well being

• Good sleep at night

• Rest during the day

• Good movement during the day

6
Realistic objective: productivity

· Achieving increased level of physical activity.

· Achieving level of comfort that allow the patient

back to work

· Allowing pain relief so the patient may address

emotional, family and spiritual issues.

7
Realistic Objectives: health care

· Decreasing health care utilization.

· Eliminating or reducing use of

medication
· Allowing a comfortable and peaceful
death process in terminal cases.
8
Principles of Analgesic Use in chronic pain
management

• By the ladder
• By the mouth
• By the clock
• By ‘Individualizing’
• By combination
1- WHO step Ladder

• The WHO analgesic ladder was introduced in 1986

– 3-step ladder for adults
– Updated in 2012 to include 2-step ladder for
children
• Framework for pharmacological management of pain
• 80-90% of patients are effectively treated using the
WHO 3-step approach

http://www.who.int/cancer/palliative/painladder/en/ 10
WHO Analgesic Ladder
Using this ladder 80% of pain can be
controlled
WHO Analgesic Ladder: adults
Step 3
Strong opioid
Step up if pain Step 2 Step up if pain
persists Weak opioid persists Severe pain
or increases
Step 1 or increases
Moderate pain +/- non-opioid
Non-opioid
+/- adjuvant
Mild pain +/- non-opioid
+/- adjuvant
+/- adjuvant

Consider prophylactic laxatives to avoid constipation

12
Adapted by Treat the Pain from World Health Organization http://www.who.int/cancer/palliative/painladder/en/ (accessed 7 November 2013) 12
WHO Analgesic Ladder

· Non-opioid · Weak opioids

Codein
analgesic
Acetaminophen Tramadol
NSAID Hydrocodone

· Adjuvants · Strong opioids

Antidepressants Morphine
anticonvulsants Oxycodone
Steroids Hydromorphone
 others Fentanyl

13
By the Ladder
WHO analgesic ladder Step Ladder

1) Begin with non-opiate, non-steroidal anti-

inflammatory agents (NSAIDS) with or without
adjuvant
2) Add a “weak” opiate, such as codeine,tramadole
(with or without an
adjuvant)orLowdosemorphine
3) Move to a stronger opiate morphine (with or
without an adjuvant)
4-Complementary, non-pharmacologic strategies

5-Interventional strategies

6-go up not sideways

7-going down the ladder

16
2-By the mouth

- convenience
- High serum level
avoided
High serum level avoided:

· When morphine is administered orally its

absorption is the slowest and constant
· so that serum peak level is achieved slowly
· as compared to a sharp rise in intravenous and
erratic one in Intramuscular.
· The latter achieve very rapid and sharp rise
resulting often unintended euphoria which may
18
be risk for development of addiction
 Oral or intravenous dosing
• Intravenous opioid takes effect within 10 min and lasts 3-4 hours
• Oral opioid takes effect within 30 min and lasts about 4 hours

Palliative Care for HIV/AIDS and Cancer

Patients in Vietnam, Basic Training
19
Curriculum: Harvard Medical School,
3-By the Clock vs.
High Dose vs PRN vs.

SIDE EFFECTS: Drowsiness

Morphine dose Too high By the clock

PRN

PA I N
Pain Relief Never
Dosing intervals
If the interval between doses is
longer than the therapeutic effect
of the drug, then pain will recur
before the next dose

Doses should be given regularly,

with intervals determined by the
therapeutic effect of the drug so
that pain does not recur

Palliative Care for HIV/AIDS and Cancer

Patients in Vietnam, Basic Training
Curriculum: Harvard Medical School, 21
Centre for Palliative Care (2007).
4-combination
5-by Combination : Broad spectrum
Analgesic Approach

Non-Opioids Opioids
Codeine (weak)
Paracetamol Morphine (strong)
NSAIDS

This Broad spectrum

Adjuvants Analgesic approach
Corticosteroids Can help us control
Antidepressants
Anticonvulsants
Patients’ pain to NO
antispasmodics Pain at all and option
in our set up
5-individualize
By mouth variation

· In the initial control of any severe

· To do initial dose trial of appropriate morphine
dosing
· Severe vomiting

· Dysphagia

· Non availability of the oral drug

· Inability to swallow such as in dementia 25
By the clock variation

· In renal failure– the dose and frequency should

be reduced
· For breakthrough pain – the drug has to be
given in between the specified intervals
· A double dose at night may be given to avoid
waking up to take medication

26
By the clock variation

· the very old (80+)

· In neonates – half life and clearance are variable

· For dyspnoea, cough management

· patients with evening and night pain only

27
By the ladder variation

· As in morphine trial for quick pain relief and for

assessing the dose requirement
· Stick on to step 2 when morphine is unavailable
· Small dose of Morphine and skipping step 2

· Non opioid is omitted for poor side effect profile

· May use adjuvants as first line if there is

confidence of neuropathic pain
28
Summary

• By the ladder: Use the WHO analgesic ladder. If after

giving the optimum dose an analgesic does not
control pain, move up the ladder; do not move
sideways in the same level
• By the mouth: Use the oral route whenever possible

Beating Pain, 2nd Ed. APCA (2012) 29

Summary
• By the clock: Administer analgesics according
to regular schedule based on duration of
effectiveness rather than “as needed”, except
when titrating dose
• By the patient: The right dose is the one that
relieves pain. Titrate the dose upwards until
pain is relieved or side effects prevent moving
up further
• By combining:

30
review

· Nociception block

· Transduction
· Transmission block
· Modulation

· Perception block

31
· Nociception block: Steroids block arachidonic acid synthesis

· Nociception block : NSAIDs block Prostaglandine synthesis

· Transmission: Alter nerve conduction (e.g. anticonvulsants)

· Modulation: Modify transmission in the dorsal horn (e.g.

opioids and some antidepressants)

· perception/interpretation: Affect the central component and

the emotional aspects of pain(e.g. antidepressants and opioids 32

Step one
No Classification ,NSAIDS Example of Drug

1 Salycylates ASA ,Salsalate

2 Propionic acid Ibuprofen

3 Acetic acid Indometacine, ketrolac,

Diclofenac
4 Enolic acid Meloxicam,piroxicam

5 Fenamenic acid Mefenamine

6 Selective cox 2 Celecoxib , paracetamol

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Step 1 – mild pain: non-opioids

Paracetamol
• Adult dose: 500mg-1g by mouth every 6 hours; maximum
daily dose 4g
• Note: Hepatoxicity can occur if more than the maximum dose
is given per day
• Paracetamol can be combined with an NSAID

Beating Pain, 2nd Ed. APCA (2012) 35

Step 1 – mild pain: non-opioids

Ibuprofen (NSAID)
• Adult dose: 400mg by mouth every 6-8 hours; maximum daily
dose 1.2g
• Give with food and avoid in asthmatic patients
• The maximum dosing limit should be lowered in patients with
liver impairment

Beating Pain, 2nd Ed. APCA (2012) 36

Step 1 – mild pain: non-opioids

Diclofenac (NSAID)
• Adult dose: 50mg by mouth every 8 hours; maximum daily
dose 150mg
• Give with food and avoid in asthmatic patients

Beating Pain, 2nd Ed. APCA (2012) 37

Cautions with NSAIDs

NSAIDs can cause serious side effects, particularly after using for
more than 7-10 days
• Gastro-intestinal (GI) bleeding or renal toxicity
– If GI symptoms occur, stop and give H2 receptor antagonist.
e.g. Ranitidine
• Not for use in patients with renal failure

Beating Pain, 2nd Ed. APCA (2012) 38

Step 2 – moderate pain: weak opioids

Tramadol
• Adult dose: 50-100mg by mouth every 4-6 hours
• Start with a regular dose and increase if no response (dose
limit: 400mg/day)
• Use with caution in epileptic cases, especially if patient is
taking other drugs that lower the seizure threshold
• May cause serotonin syndrome in patients on other
medications containing serotonin

Beating Pain, 2nd Ed. APCA (2012) 39

Step 2 – moderate pain: weak opioids

Codeine
• Adult dose: 30-60mg by mouth every 4-6 hours; maximum
daily dose 240mg
• If pain relief is not achieved with 240mg/day, move to strong
opioid
• Can be combined with Step 1 analgesic
• Give laxative to avoid constipation unless patient has diarrhea
• Genetic variability can lead to variable rates of metabolism
which may make codeine ineffective or lead to excessive side
effects

Beating Pain, 2nd Ed. APCA (2012) 40

Step 2 – moderate pain: weak opioids

Low-dose morphine
• Some palliative care experts recommend using low-dose
morphine in step 2 because it is associated with fewer side
effects compared to other weak opioids

Beating Pain, 2nd Ed. APCA (2012) 41

Step 3 – severe pain: strong opioids

Morphine
• “Gold standard” against which other opioid analgesics are
measured
• When used correctly, patients don’t become dependent or
addicted, tolerance is uncommon, and respiratory depression
doesn’t usually occur

Beating Pain, 2nd Ed. APCA (2012) 42

Step 3 – severe pain: strong opioids

Less commonly used strong opioids (covered in separate lecture)

• Fentanyl
• Oxycodone
• Hydromorphone
• Methadone

Beating Pain, 2nd Ed. APCA (2012) 43

Step 3 – severe pain: strong opioids

Morphine
• Adult starting dose: 2.5–20mg by mouth every 4 hours
depending on age, previous use of opiates, etc.
– Patients changing from regular administration of a Step 2
opioid: 10mg by mouth every 4 hours
– If the patient has experienced weight loss from sickness or
has not progressed onto Step 2 analgesics: 5mg by mouth
every 4 hours
– Frail or elderly patients: 2.5mg by mouth every 6 to 8
hours due to the likelihood of impaired renal function

Beating Pain, 2nd Ed. APCA (2012) 44

Step 3 – severe pain: strong opioids

• Morphine is available as immediate-release or sustained-

release formulations
• Immediate-release
– Dose every 4 hours
– Use to titrate starting dose and treat breakthrough pain

Beating Pain, 2nd Ed. APCA (2012). 45

Step 3 – severe pain: strong opioids

• Sustained-release (or slow-release)

– Dose every 8-24 hours, depending on the formulation
– After determining daily dose with immediate-release
morphine, can change to sustained-release morphine,
being careful to adjust dose as needed to maintain the
total daily dose
• Priority should be given to making immediate-release
formulations available

Beating Pain, 2nd Ed. APCA (2012). 46

Step 3 – severe pain: strong opioids

Morphine
• Increase dose gradually until pain is controlled
• The correct morphine dose is the one that gives pain relief
without side effects: there is no ‘ceiling’ or maximum dose

Beating Pain, 2nd Ed. APCA (2012) 47

Practical Assessment

Asther, a 28 year-old woman with cancer, reports a pain score of 5

out of 10. Which medicines would you consider prescribing?
A. Codeine
B. Tramadol
C. Low-dose morphine
D. Any of the above

If you prescribe low-dose morphine, what is Esther’s starting dose?

2.5mg every four hours

What other prescriptions must be written at the same time?

Laxatives
48
Caution: pethidine

Pethidine is not suitable for patients with chronic pain

• It has a faster onset of action and a shorter duration of action
than morphine and needs more frequent dosing: every 2–3
hours
• Pethidine is metabolised to norpethidine which has side effects
inducing central nervous system excitability including mood
changes, tremors, myoclonus (sudden jerking of the limbs) and
convulsions
• Pethidine was removed from the WHO essential medicines list
in 2003 because it was judged to be inferior to morphine due to
its toxicity on the central nervous system and is generally more
expensive than morphine
Beating Pain, 2nd Ed. APCA (2012); The Selection and Use of Essential Medicines – WHO Technical Report Series, No. 920. 2003. 49
Stopping or changing opioids

• When stopping an opioid, reduce daily dose by 25% each day

to avoid symptoms of withdrawal
• When changing from one opioid to another, be mindful of the
need to convert doses
– Check reference materials or consult an expert

Oxford Textbook of Palliative Medicine (2010) 50

Key treatment principle: prophylactic laxatives

• All patients on opioids are at high risk for constipation, and

laxatives should be ordered unless contraindicated

Beating Pain, 2nd Ed. APCA (2012) 51

 Part II
Adjuvant analgesics or co-analgesics
Adjuvant analgesics or co-analgesics

Adjuvant analgesics, which are also referred to as co-

analgesics, are medicines that are not primarily used for
analgesia. These are medicines that are administered alone or
with NSAIDs and opioids that may:
• Enhance the analgesic activity of the NSAIDs or opioids
• Have independent analgesic activity for certain pain types
(such as neuropathic pain)
• counteract the side effects of NSAIDs or opioids

Beating Pain, 2nd Ed. APCA (2012); Using Opioids to Manage Pain, APCA (2010) 53
Principles in adjuvant therapy

• The use of adjuvants that target neuropathic pain may be

particularly important because such pain may be difficult to
treat with opioids alone
• Adjuvants are also useful for other pains that are only partially
sensitive to opioids such as bone pain, smooth or skeletal
muscle spasms, or pain related to anxiety

Beating Pain, 2nd Ed. APCA (2012); Using Opioids to Manage Pain, APCA (2010) 54
Antidepressants

Used for neuropathic pain, presenting primarily as burning or

abnormal sensations (dysaesthesia)
• Amitriptyline
– Adults: 10-75mg or 0.5-2mg/kg at night then increase
slowly as needed
– Commonly start at 12.5mg at night and then increase to
twice per day as needed
– Response should be evident within 5 days
• If no effect after 1 week, stop the drug

Beating Pain, 2nd Ed. APCA (2012); Using Opioids to Manage Pain, APCA (2010); Introductory Palliative Care Course for Health Care
55
Professionals (Uganda). PCAU/MOH (2013).
Antidepressants

– Side-effects include dry mouth and drowsiness

– Use with caution in the elderly because it may increase
falls
– Use with caution in those with cardiac disease because it
may cause orthostatic hypertension
• Nortriptyline
– May be better tolerated than amitryptyline

Beating Pain, 2nd Ed. APCA (2012); Using Opioids to Manage Pain, APCA (2010); Introductory Palliative Care Course for Health Care
56
Professionals (Uganda). PCAU/MOH (2013).
Anticonvulsant

• Carbamazepine :Adults: start at 100mg twice a

day and can be increased up to 800mg twice a
day
• Phenytoin: 100mg-300 mg daily
• Use Phenytoin and Carbamazepine with caution because of
the rapid metabolism of other drugs metabolised in the liver
and therefore potential drug interactions
• Side effects: drowsiness, loss of muscle coordination (ataxia)
or blurring of vision

57
Anticonvulsants

Use for neuropathic pain; check for drug interactions

• Clonazepam
– Adults: 0.5mg to 2mg once a day
• Sodium valproate
– Adults: 200 mg - 1.2g once a day
• Gabapentin
– Adults: start with 300mg at bedtime and titrate up every 2 or 3 days (300mg
twice per day, then three times per day) until effective or side effects occur
– Usual effective dose is 300-600mg three times a day (maximum dose 1200mg
three times per day)
– Decrease dose in patients with renal insufficiency

Beating Pain, 2nd Ed. APCA (2012); Palliative Care for HIV/AIDS and Cancer Patients in Vietnam, Basic Training Curriculum: Harvard
Medical School, Centre for Palliative Care (2007); Oxford Textbook of Palliative Medicine (2010) 58
Antispasmodics

Use antispasmodics for muscle spasm, e.g. colicky abdominal

pain or renal colic
• Hyoscine butylbromide (Buscopan)
– Adults: start at 10mg three times a day; can be increased
to 40mg three times a day
• Antispasmodics can cause nausea, dry mouth, or constipation

Beating Pain, 2nd Ed. APCA (2012) 59

Muscle relaxants & sedatives

Use these drugs for skeletal muscle spasm and anxiety-

related pain
• Diazepam
– Adults: 5mg orally 2 or 3 times a day
• Lorazepam
– 0.5-2mg oral or intravenous every 3 to 6 hours
• Side effects: can cause drowsiness and ataxia

Beating Pain, 2nd Ed. APCA (2012); Oxford Textbook of Palliative Medicine. (2010) 60
Corticosteroids

Use corticosteroids for bone pain, neuropathic pain, headache due to raised
intracranial pressure, and pain associated with oedema and inflammation
• Dexamethasone
– Adults: 2–4mg per day for most situations
– For raised intracranial pressure, start at 24mg per day and reduce by 2mg each day to
the lowest effective maintenance dose
– For pain from nerve compression, start at 8mg
– For spinal cord compression, start at 16mg

• Prednisolone
– Use when dexamethasone is not available
– A conversion rate of 4mg Dexamethasone to 30mg Prednisolone can be used

Beating Pain, 2nd Ed. APCA (2012) 61

Corticosteroids

• In advanced disease, a corticosteroid may improve

appetite, decrease nausea and malaise, and improve
quality of life
• Side effects include neuropsychiatric syndromes,
gastrointestinal disturbances and immunosuppression
• When stopping a corticosteroid, remember gradually
taper down the dose

Beating Pain, 2nd Ed. APCA (2012) 62

Bisphosphonates

Bisphosphonates are used for the treatment of cancer-related

bone pain
• Pamidronate- 60-90mg slow intravenous infusion every 4
weeks
• Side effects
– Fever and flu-like weakness
– Osteonecrosis of the jaw, although rare, has been
associated with bisphosphonate therapy

Beating Pain, 2nd Ed. APCA (2012) 63

Take home message

• The WHO ladder, an important tool of managing pain, can

effectively treat 80-90% of the patients at this facility
• For non-responsive pain, please refer to a pain specialist

64
Take home messages

• Co-analgesics are important complementary medications in

pain relief
• Used with the correct combinations, co-analgesics can
enhance analgesic effects
• Adjuvants are useful for neuropathic pain and other pains that
are only partially sensitive to opioids such as bone pain,
smooth or skeletal muscle spasms, or pain related to anxiety

65
Thank you
References

• African Palliative Care Association. Beating Pain: a pocketguide for pain management in
Africa, 2nd Ed. [Internet]. 2012. Available from:
http://www.africanpalliativecare.org/images/stories/pdf/beating_pain.pdf
• African Palliative Care Association. Using opioids to manage pain: a pocket guide for
health professionals in Africa [Internet]. 2010. Available from:
http://www.africanpalliativecare.org/images/stories/pdf/using_opiods.pdf
• Amery J, editor. Children’s Palliative Care in Africa [Internet]. 2009. Available from:
http://www.icpcn.org/wp-content/uploads/2013/08/Childrens-Palliative-Care-in-Africa-
Full-Text.pdf
• Kopf A, Patel N, editors. Guide to Pain Management in Low-Resource Settings [Internet].
2010. Available from:
http://www.iasp-pain.org/files/Content/ContentFolders/Publications2/FreeBooks/
Guide_to_Pain_Management_in_Low-Resource_Settings.pdf
• The Palliative Care Association of Uganda and the Uganda Ministry of Health.
Introductory Palliative Care Course for Healthcare Professionals. 2013.

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