1. Adjuvants or Co-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 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.

2. Objectives Review different forms of adjuvant or co-analgesic medication Understand adult dosing for each Learn when to utilize them Review potential side effects 2

3. 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) May counteract the side effects of NSAIDs or opioids Beating Pain, 2 nd Ed. APCA (2012); Using Opioids to Manage Pain, APCA (2010) 3

4. 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, 2 nd Ed. APCA (2012); Using Opioids to Manage Pain, APCA (2010) 4

5. 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, 2 nd Ed. APCA (2012); Using Opioids to Manage Pain, APCA (2010); Introductory Palliative Care Course for Health Care Professionals (Uganda). PCAU/MOH (2013). 5

6. 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 6 Beating Pain, 2 nd Ed. APCA (2012); Using Opioids to Manage Pain, APCA (2010); Introductory Palliative Care Course for Health Care Professionals (Uganda). PCAU/MOH (2013).

7. Anticonvulsants Use for neuropathic pain; check for drug interactions Clonazepam – Adults: 0.5mg to 2mg once a day Carbamazepine – Adults: start at 100mg twice a day and can be increased up to 800mg twice 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, 2 nd 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) 7

8. Anticonvulsants 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 Beating Pain, 2 nd Ed. APCA (2012) 8

9. 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, 2 nd Ed. APCA (2012) 9

10. Muscle relaxants 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, 2 nd Ed. APCA (2012); Oxford Textbook of Palliative Medicine. (2010) 10

11. 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, 2 nd Ed. APCA (2012) 11

12. 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 to gradually taper down the dose Beating Pain, 2 nd Ed. APCA (2012) 12

13. 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, 2 nd Ed. APCA (2012) 13

14. 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 14

15. 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. 15