Analgesics have a risk associated with their use as with their benefit in the managment of a patient successfully

1. Side effects and toxicity of analgesics
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
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these materials, or for any errors or omissions. Last updated on January 12, 2015

2. Objectives
• Discuss side effects of Step 1, Step 2, and Step 3 analgesics
• Review signs of opioid toxicity
• Describe treatment options of opioid toxicity
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3. Step 1 analgesics: paracetamol
Hepatotoxicity can occur if more than the maximum dose (4g) is
given per day
• Alcohol-dependent and undernourished patients are at a
higher risk
Contraindications:
• Severe hepatic and renal impairment, alcohol dependence,
undernourishment, and glucose-6-phosphate dehydrogenase
deficiency
Beating Pain, 2nd Ed. APCA (2012); Guide to Pain Management in Low-Resource Settings, IASP (2010) 3

4. Step 1 analgesics: NSAIDs
Side effects are usually seen with longer-term use (>7 days)
• Gastro-intestinal (GI) bleeding
– If any GI symptoms develop (dypepsia, epigastric pain),
stop and give H2 receptor antagonist, e.g. Ranitidine
• Renal failure
Contraindications
• Gastrointestinal ulceration, hemophilia, hypersensitivity to
aspirin, thrombocytopenia, young children, pregnancy
(especially third trimester), breastfeeding, and advanced renal
impairment
Beating Pain, 2nd Ed. APCA (2012); Guide to Pain Management in Low-Resource Settings, IASP (2010) 4

5. Step 2 analgesics: weak opioids
Weak opioids are considered very safe, even in patients with
impaired organ function
• Codeine
– Give laxatives to avoid constipation unless patient has
diarrhoea
• Tramadol
– Use with caution in epileptic patients, especially if patient
is on other drugs that lower the seizure threshold
– May cause serotonin syndrome in patients on other
serotonergic medications
Beating Pain, 2nd Ed. APCA (2012); Guide to Pain Management in Low-Resource Settings, IASP (2010) 5

6. Step 3 analgesic: morphine
• When used correctly, problems like dependency, addiction,
tolerance, and respiratory depression are rare
• Opioids are not toxic to any organ
– No contraindications except history of allergic reactions
(rare)
Beating Pain, 2nd Ed. APCA (2012); Guide to Pain Management in Low-Resource Settings, IASP (2010)
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7. Step 3 analgesic: morphine
Constipation is a very common side effect of all opioids and does
not resolve spontaneously
• Laxatives should be prescribed as prophylaxis unless patient
has diarrhoea
• Treat with a stimulant laxative
– i.e. Bisacodyl 5mg at night, increasing to 15mg if needed
Beating Pain, 2nd Ed. APCA (2012) 7

8. Step 3 analgesic: morphine
Nausea and vomiting
• Usually mild and resolves within one week
• Anti-emetics (metoclopramide or haloperidol) can be given
for the first few days of treatment
– Metoclopromide 10mg every 8 hours or haloperidol 1.5mg
once a day
Itching
• Less common
• Treat with chlorpheniramine
Beating Pain, 2nd Ed. APCA (2012), Guide to Pain Management in Low-Resource Settings, IASP (2010)
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9. Step 3 analgesic: morphine
Drowsiness
• Usually resolves within one week
• Advise patients not to perform dangerous tasks or operate
heavy machinery for 2 weeks while they adjust to the
medications
• Patients who have been unable to sleep well due to pain may
initially sleep for long periods once their pain has been
relieved
– These patients should be easily arousable
• If it does not improve, reduce the morphine dose
Beating Pain, 2nd Ed. APCA (2012) 9

10. Step 3 analgesic: morphine
Hepatic and renal impairment
• Not a contraindication for use
• Titrate slowly and carefully to avoid accumulation of
medication or active metabolites
– Consider increasing interval between doses to 6, 8, or even
12 hours
Elderly
• Older people respond well to lower doses
• Consider reducing the dose or increasing the dosing interval
to minimize side effects
Beating Pain, 2nd Ed. APCA (2012); Guide to Pain Management in Low-Resource Settings, IASP (2010)
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11. Opioid toxicity
• Toxic effects of opioids are rare when they are used
in appropriate doses
• Signs include
– Drowsiness that does not improve
– Confusion
– Hallucinations
– Myoclonus (abrupt spasms or muscle twitching)
– Respiratory depression (slow breathing)
– Pinpoint pupils
Beating Pain, 2nd Ed. APCA (2012) 11

12. Opioid toxicity
• If you are concerned that a patient is experiencing toxicity,
reduce the dose by 50% and consider giving parenteral fluids
to increase excretion
• In severe cases, stop the opioid and give Naloxone, an opioid
antagonist
– Naloxone is rarely used and should be used with caution as
it will precipitate pain crisis
• Haloperidol 1.5-5mg at night may help with any hallucinations
or confusion
– Be sure to rule out other causes (such as urinary tract
infection, hypoxia, or side effect of another medication)
Beating Pain, 2nd Ed. APCA (2012), Dr. Kathleen Doyle 12

13. Take home messages
• The use of opioids can cause side effects; with proper use
these side effects can be mediated
• When using opioids, give laxatives to avoid constipation
unless patient has diarrhoea
• When used correctly, patients don’t become dependent or
addicted on morphine
• Opioids are not toxic to any organ
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14. 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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