ADJUVANT PAIN MANAGEMENT

Transcription

1 ADJUVANT PAIN MANAGEMENT Bruce H. Chamberlain, MD FACP FAAHPM Palliative Consulting Orem, UT

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3 AAHPM Intensive Board Review Course Using Adjuvant Treatments for Chronic Pain Bruce H. Chamberlain, MD FACP FAAHPM Palliative Consulting Disclosure Information Bruce H. Chamberlain, MD FACP FAAHPM Has disclosed the following financial relationships: research consultant with AstraZeneca and on the Speaker s Bureau for Salix Pharma. Broad Spectrum Pain Management Non-Opioid Analgesics Opioids Adjuvant Interventions

4 Adjuvant Drugs Medications originally developed to treat conditions other than pain that have been found to have pain relieving qualities * Also called co analgesics Various sites and mechanisms of action Many have particular use in neuropathic pain *Cancer-pain.org League Table for Peripheral Neuropathic Pain From Palliative Medicine (Figure 252 1, p. 1423), by TD Walsh, AT Caraceni, R Fainsinger, KM Foley, P Glare (Eds.), 2008, Philadelphia, PA: Elsevier by Elsevier. Reproduced with permission. Adjuvant Treatment Options Antidepressants Anticonvulsants Steroids Systemic Local Anesthetics NMDA antagonists Bisphosphonates External Beam Radiation Radiopharmaceuticals Complimentary and Alternative (CAM) treatments

5 Helpful but NOT Reviewed Here Alpha 2 agonist Capsacian Antispasmodics Antihistamines Question Which of the following antidepressants has NOT been show to have specific efficacy in pain management? 1. Nortriptyline (Aventyl ) 2. Trasadone (Deseryl ) 3. Duloxitine (Cymbalta ) 4. Venlafaxine (Effexor ) How TC Antidepressants Work 1 st Enhance the descending pain inhibitory pathway by blocking presynaptic serotonin +/ norepinephrine uptake Compete with morphine for plasma protein binding sites, 2 nd increasing the MS level Secondary anticholinergic and antihistamine effects in 3 rd some drugs can help with sleep, itch and nausea Analgesic effect occurs sooner and at a lower dose than the antidepressant effect but may still take weeks to be effective

6 Antidepressants: TCA (tricyclic antidepressants) The most documented efficacy Start at mg qhs Secondary amines: nortriptyline, desipramine have fewer side effects Tertiary amines: amitriptyline, i t imipramine, i i doxipine are more sedating and have more sideeffects Yes, they are on the Beer s List max dose mg qhs Antidepressants: Trazadone No documented effect on pain, but is effective for depression and sleep Antidepressants: SSRIs Little data showing efficacy in pain Paroxetine (Paxil ): may be effective for neuropathic pain Fluoxetine (Prozac ): only effective if co morbid depression is present

7 Antidepressants: SNRIs Have shown efficacy in pain especially neuropathic Duloxetine (Cymbalta ): efficacy comparable to gabapentin and pregabalin in neuropathic pain 60 mg/day is best effective dose Venlafaxine (Effexor ): effective in diabetic neuropathy Doses >150 mg/day Milnacipran (Savella ): new old drug much more NE effects, no strong data on better efficacy Dizziness Nausea Dry Mouth Sedation Side Effects Orthostatic Hypotension Antidepressants Anticonvulsants Most clinical experience with: Gabapentin Carbamazepine Phenytoin Valproate Clonazepam Dosing schedule the same as for anticonvulsant indication

8 Anticonvulsants Carbamazepine (Tegretol): chemically related to TCAs. often used for trigeminal neuralgia Side effects (esp. aplastic anemia) make it a second line treatment Gabapentin (Neurontin): is effective and has relatively few side effects (GI, dizziness, sedation). Diabetic neuropathy & post herpetic neuralgia Also has positive effects on mood and sleep 100 to 3600 mg/day Pregabalin (Lyrica): efficacy and pharmacology similar to gabapentin, better kinetics at high doses BID TID dosing vs. TID with gabapentin Better tolerated, easier to titrate to effective doses mg/day Dizziness Nausea Ataxia Sedation Side Effects Fatigue Anticonvulsants Question 76 year old man is admitted with lung cancer and brain mets, you decide to prescribe a course of steroids. Which is the preferred starting drug/dose? 1. Dexamethasone 4 mg po qday 2. Prednisone 40 po mg BID 3. Methylprednisolone 4 mg po QID 4. Dexamethasone 4 mg po QID

9 Steroids Primary effect: Inhibition of the arachidonic acid cascade which inhibits formation of substances which sensitize the peripheral afferent nocioceptor thereby raising the pain threshold Decrease inflammation Beneficial secondary effects: Tumor shrinkage direct antitumor effects Enhanced appetite, weight gain Improved sense of well being Steroids Preferred: Dexamethasone Least mineralocorticoid effect Long acting allows for daily dosing Usual dose: 4 20 mg/day Dose: PO, IV, SQ, epidural Steroid Side Effects: immunosuppression, endocrine effects, psychosis and proximal muscle wasting can occur within 4 6 weeks Immune Suppression Elevated Sugar levels Proximal Muscle Wasting Adrenal Suppression Side Effects Psychosis Steroids

10 Systemic Local Anesthetics lidocaine, mexiletine. Assumed mechanism of action is blocking of sodium channels. Phenytoin, carbamazepine and tricyclic antidepressants also act as sodium channel blockers. Data support for efficacy in non cancer pain* Use is decreasing as experience with ketamine increases Systemic LA References Rowbotham MC, Reisner Keller LA, Fields HL. Both intravenous lidocaine and morphine reduce the pain of post herpetic neuralgia. Neurology 1991;41: Bruera E, Ripamonti C, Brennis C, Macmillan K, Hanson J. A randomized double blind crossover trial of intravenous lidocaine in the treatment of neuropathic pain. J Pain Symptom Manage 1992; 7(3): Question Which of the following is an absolute contraindication to the use of a bisphosphonatae in palliative care? 1. Severe renal impairment 1. Severe renal impairment 2. Severe hepatic impairment 3. Concurrent corticosteroid use 4. None of the above

11 Bisphosphonates Inhibit bone resorption by acting on osteoclasts Used to relieve pain in cancer that has spread to the bones. Medium quality supporting data Pamidronate (Aredia ), Ibandronate (Boniva ) and Zoledronic Acid (Zometa ) are among the most commonly used Concerns: no standardized treatment protocols osteonecrosis of the jaw (<1%) renal impairment Bisphosphonate Benefits The International Mylonma Foundation cites the following benefits: Prevention of further bone damage Reduction of bonepain Better control of hypercalcemia Reduced need for XRT Fewer pathological fractures Improved QOL NMDA Antagonists Methadone Consider in mixed pain syndromes or as an add on to existing opiate regimen Ketamine Increasing utilization by oral and IV/SQ routes Detailed review beyond the scope of this lecture, should not be on the exam Amantadine May be effective in some neuropathic syndromes Starting dose 100 mg bid Dextromethorphan may potentiate opiate effects Dose mg bid in sustained release form Primary side effect is sedation

12 Question Which of the following is true regarding the use of complimentary and alternative medicine in palliative care? 1. There is greater use that is generally reported 2. There are limited supporting data for these interventions 3. The most common CAM intervention is the use of OTC herbal and vitamin supplements 4. All of the above are true Internal Medicine News February 15, 2009 Most Common: Fish oil Glucosamine Echinacea Flaxseed oil or pills remedies Ginseng Chiropractic Massage Yoga Homeopathic Alternative/Complementary Limited supporting data but very low risk, most are low cost and many can be done anywhere or anytime the patient wants A meta analysis found the combination of exercise and psychoeducationalapproachescan approaches can leadto a significant reduction in pain and improvement in functional status for a number of musculoskeletal conditions* *Allegrante JP: The role of adjunctive therapy in the management of chronic nonmalignant pain. Am J Med 1996 Jul 31;101(1A):33S 39S.

13 CAM In Advanced cancer patients enrolled in a phase I trial 88% used at least one CAM modality* 93% pharmacologic: most vitamins Green tea (30%), echinacea (13%), essiac (10%) 53% non pharmacologic: most common are prayer, spiritual practices Patients are often reluctant to discuss CAM use *Hlubocky FJ, Ratain MJ, Wen M. et al. Complementary and alternative medicine among advanced cancer patients enrolled on phase I trials. J Clin Oncol. 2005;23:248 Questions? Please fill out a card for response in the discussion session

14 From Palliative Medicine (Figure 252-1, p. 1423), by TD Walsh, AT Caraceni, R Fainsinger, KM Foley, P Glare (Eds.), 2008, Philadelphia, PA: Elsevier by Elsevier. Reproduced with permission.