Pain Therapeutics Lecture Notes PDF

Pain Therapeu cs PHCY505 Fall 2023 Mary E.D. Yates, PharmD, BCPS [email protected] Pain Unpleasant sensory and emo$onal experience associated with, or resembling that associated with, actual or poten$al $ssue damage 1 Is what the pa$ent says it is 100 million people in the US have chronic pain $50...

Pain Therapeu cs PHCY505 Fall 2023 Mary E.D. Yates, PharmD, BCPS [email protected] Pain Unpleasant sensory and emo$onal experience associated with, or resembling that associated with, actual or poten$al $ssue damage 1 Is what the pa$ent says it is 100 million people in the US have chronic pain $500 – 600 billion annual economic burden (2010 dollars) Greater than: heart disease, cancer, and diabetes Higher prevalence of chronic pain in adults over 65 years old Consequences of pain: mental, physical, social, and economic 1.(IASP) Interna$onal Associa$on for the Study of Pain 2020 2. Gaskin DJ, Richard P. The Economic Costs of Pain in the United States. In: Ins$tute of Medicine (US) Commi?ee on Advancing Pain Research, Care, and Educa$on. Relieving Pain in America: A Blueprint for Transforming Preven$on, Care, Educa$on, and Research. Washington (DC): Na$onal Academies Press (US); 2011. Appendix C. Available from: h?ps://www.ncbi.nlm.nih.gov/books/NBK92521/ 3. omenichiello AF, Ramsden CE. The silent epidemic of chronic pain in older adults. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jul 13;93:284-290. doi: 10.1016/j.pnpbp.2019.04.006. Epub 2019 Apr 17. PMID: 31004724; PMCID: PMC6538291. 4 Uncontrolled Pain E'ects Cough suppression Risk for pneumonia, atelectesis Decreased movement Risk of DVT/PE, cons$pa$on, ileus Tachycardia, Hypertension Increased catabolic demands, muscle breakdown, risk of MI Immunological dysfunc$on decreased healing, increased risk of infec$on Insomnia, anxiety depressive disorder 5 Classifying Pain Type: Nocicep$ve (Soma$c, visceral): result of $ssue injury Mechanical: damage to, in or around the structure of joints (osteoarthri$s, low back disorders, tendini$s) inKammatory: abnormal inKamma$on caused by an inappropriate response by the body’s immune system that causes damage to bone, muscles and car$lage (gout, rheumatoid arthri$s) maladap$ve (neuropathic):caused by nerve irrita$on/damage (neuropathy) centralized (nociplas$c): pain when the central nervous system does not work properly and ampli"ed pain ("bromyalgia, rheumatoid arthri$s) Temporally: Acute versus chronic Severity: Mild, moderate, severe h?ps://www.arthri$s.org/health-wellness/healthy-living/managing-pain/understanding-pain/mechanisms-of-arthri$s-pain 6 Nocicep ve – Soma c Pain arising from skin, bone, joint, muscle, connec$ve $ssue Throbbing Well-localized Sharp Pressure-like Common causes: paper cut, skin contusion, tendoni$s, muscle pain, gout, osteoarthri$s 7 Nocicep ve – Visceral Pain arising from internal organs Di#use; di(cult to localize pain Aching Cramping Common causes: Appendici$s, PUD, bladder distension, dysmenorrhea, gastri$s, acute pancrea$$s 8 Neuropathic Pain arising from impaired processing of pain due to nerve damage Common causes: diabetes, infec$ons (herpes zoster), tumors, autoimmune disease, amputa$on, viruses, toxins (alcohol/drugs) Can evolve from unmanaged nocicepve pain 9 Nociplas c To clinically classify nociplastic pain, patients have to: report pain of at least 3 months duration; report a regional rather than discrete pain distribution; report pain that cannot entirely be explained by nociceptive or neuropathic mechanisms show clinical signs of pain hypersensitivity evoked pain hypersensitivity phenomena: static or dynamic mechanical allodynia heat or cold allodynia Allodynia: pain due to a stimulus that does not normally provoke pain: painful after-sensations after any of the mentioned evoked pain Kosek E., Clauw D., Nijs J., Baron R., Gilron I., Harris R.E., Mico J.A., Rice A.S., Sterling M. Chronic nociplas$c pain a#ec$ng the musculoskeletal hypersensitivity assessments present in the region of pain system: Clinical criteria and grading system. Pain. 2021 doi: 10.1097/j.pain.0000000000002324. 10 Di'eren a ng Pain Representation of "mixed pain" dened as the overlapping of the nociplastic, nociceptive and neuropathic pain 11 Pain Classi-ca on Acute Short in dura$on Las$ng less than 30 days Iden$"able cause Nocicep$ve GOAL: CURE Subacute Lasting 1-3 months Chronic Cancer Pain Long in dura$on (>3 months) Las$ng months to years Nocicep$ve, neuropathic, or mixed Uniden$"able cause Changes to nerve func$on and transmission Associated with cancer or malignancy Includes chronic and acute (breakthrough pain) Cause by the disease, associated treatment, or diagnos$c procedure GOAL: FUNCTIONALITY American Geriatrics Society Panel on Pharmacological Management of Persistent Pain in Older Persons. J Am Geriatr Soc. 2009;57:1331–1346. 12 Pain Assessment Symptoms Subjec$ve May be none or varying Pa$entcentered approach Mental and emo$onal factors alter pain threshold Anxiety, depression, fa$gue, anger, and fear Mood eleva$on, sympathy, distrac$on, and understanding Lab test Rule out vitamin D de"ciency, hypo/hyperthyroidism, and B12 de"ciency Herndon CM, et al. Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw Hill; 2020. 13 Pain Assessment and Reassessment A patient’s self-report of pain is the most reliable pain indicator reliable indicator of pain 14 Clinical Presenta on - Subjec ve Acute Pain Distress Hypertension Tachycardia Diaphoresis Mydriasis (dilated pupil) Pallor Chronic Pain May not present with any no$ceable su#ering More likely to have comorbid condi$ons such as: Anxiety Depression Fa$gue Insomnia 15 Pain Assessment Scales Mild (1-3) Moderate (4-7) This Photo by Unknown author is licensed under CC BY-NC-ND. Severe (8-10) 16 Assessment Tools in Cogni ve Impairment This Photo by Unknown author is licensed under CC BY. 17 AssessmentScales Tools in Cogni ve Impairment Pain Assessment Critical Care Pain Observation Tool (CPOT ) four main dimensions: facial expression body movement, compliance with ventilator muscle tension Each dimension is scored between zero and 2, resulting in a possible total score between zero and 8. A score of zero means no pain whereas scores >2 show pain and the necessity for pain management. Nazari, R. Indian J Crit Care Med.2022 Summer; 26 (4): 472-476 Feldt KS. Pain Manag Nurs. 2000. 1(1):13-21. 18 Goals of Treatment Treat Underlying Condi$ons Decrease Level of care needed by caregiver Reduce Pain Improve Quality of Life Reduce Psychological Stress Individualized Mul$modal Mul$disciplinary Improve/Maintain Level of Physical func$oning Patients (and caregivers) should have realistic expectations 19 Treatment Originally developed for cancer pain currently applied for managing: cancer pain acute and chronic non-cancer painful condi$ons Based on severity of pain Does not include nonpharmacologic approaches New model has a bi-direc$onal approach Pain Intensity World Health Organiza on Analgesic Ladder Anekar AA, Hendrix JM, Cascella M. WHO Analgesic Ladder. [Updated 2023 Apr 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: h?ps://www.ncbi.nlm.nih.gov/books/NBK554435/ 20 Selec ng An Analgesic Regimen: The Pain Trolley Dynamic model Holistic Pain treatments need to follow multimodal approaches (pharmacological and nonpharmacological agents considering intensity of pain, pathophysiology of pain, complexity of symptoms, presence of comorbidities social context the “time” of illness CAM: complimentary and alternative medicine RF: radiofrequency J Pain Res. 2019; 12: 711–714. Published online 2019 Feb 19. doi: 10.2147/JPR.S178910 21 Nonpharmacologic Interven ons Restora$ve Therapy Cold and heat Bracing Massage therapy RICE (rest, ice, compression, elevation) Therapeu$c exercise Transcutaneous electric nerve s$mula$on (TENS) Trac$on Therapeu$c ultrasound (TU) Interven$onal approach Epidural steroid injec$ons (ESIs) Peripheral nerve injec$ons Joint injec$ons Sympathe$c nerve blocks (SNBs) Intrathecal Medica$on Pumps Facet joint nerve block and denerva$on injec$ons Cryoneuroabla$on Radiofrequency abla$on Neuromodula$on Vertebral augmenta$on Trigger points Interspinous process spacer devices Regenera$ve/adult autologous stem cell therapy Behavioral approach Mindfulness Based Stress Reduc$on(MBSR) Behavioral therapy (BT) Cogni$ve behavioral therapy (CBT) Acceptance and commitment therapy (ACT) Emo$onal awareness and expression therapy (EAET) Self-regulatory or psychophysiological approaches Complementary and integra$ve health Acupuncture Massage and manipula$ve therapies Spirituality Yoga Tai chi 22 Acute Pain 23 Se7ngs for Acute Pain Surgery Emergency Room Intensive Care Urgent Care Clinics Outpa$ent Pharmacies 24 Principles of Acute Pain Management Multimodal treatment includes: nerve blocks or epidurals opioids or other analgesics adjunctive medications physical modalities (RICE) rehabilitation Psychosocial interventions: including distraction, meditation, and deep breathing pharmacologic options are only a small part of the solution www.practicalpainmanagement.com/resource-centers/opioid-prescribing-monitoring/medical-management-acute-pain 25 Acute Pain Severity Severity Mild (1-3) Examples Treatment Sinus headache, soreness aRer yard work, super"cial lacera$on RICE, OTC Analgesics (APAP, NSAIDS) Immuniza$on, catheter placement, phlebotomy, super"cial biopsy, simple dental extrac$ons Ice, Buzzy (ice and vibra$on), lidocaine, EMLA (lidocaine, prilocaine topical cream) Opioids Needed? No www.practicalpainmanagement.com/resource-centers/opioid-prescribing-monitoring/medical-management-acute-pain 26 Acute Pain Severity Severity Moderate (4-7) Examples Treatment Opioids Needed? Sprain, strain, simple bone fracture, deep lacera$on Simple outpa$ent surgical procedure, NSAIDs, acetaminophen, RICE No Same-day surgery (arthroscopy, mul$ple dental extrac$ons/ wisdom teeth, laparoscopy, podiatric procedures) NSAIDs, acetaminophen Not likely, at most 6-8 tablets of opioid/acetaminophen combina$on www.practicalpainmanagement.com/resource-centers/opioid-prescribing-monitoring/medical-management-acute-pain 27 Acute Pain Severity Severity Severe (8-10) Examples Treatment Motor vehicle accident, burn, trauma$c amputa$on Surgery, hospitaliza$on, possible intensive care, mul$modal analgesics Arthroplasty, spinal, colorectal, open abdominal surgery requiring hospital stay Mul$modal analgesics Opioids Needed? Yes www.practicalpainmanagement.com/resource-centers/opioid-prescribing-monitoring/medical-management-acute-pain 28 Onset of Ac on for Pain NSAIDS: Analgesic effects are prompt Anti-inflammatory may take ~1-2 weeks The longer acting, the slower the onset of action Reminder: antipyretic Acetaminophen: Analgesic effects: IV 5-10 minutes; PO: < 1 hour Analgesic duration: 4-6 hours No anti-inflammatory properties Immediate-release (Short ac ng opioids) Tmax: 5-15 min (IV), 1-2 hrs (PO) DOA: 1-1.5 hrs (IV), 3-5 hrs (PO/PR) Frequencies: PO: q4 or q6 hours IV: q 1-4 hours Aubrun F, Mazoit J, Riou B. Postoperative intravenous morphine titration. Br. J. Anaesth. 2012; 108(2): 193-201. 29 Acute Pain Treatment Regimens: Back Pain topical NSAIDs may be considered a safe alternative among patients with acute back pain in which oral NSAIDs are contraindicated. trigger point injection (TPI) - may o=er temporary relief of acute back pain secondary to myofascial irritation. Steroids, botulinum toxin, or “dry needling” https://www.emra.org/books/pain-management/back-pain 30 Acute Pain Treatment Regimens: Abdominal Pain Prochlorperazine 10mg IV push, once Droperidol 0.625mg IV push, once Diphenhydramine 25mg IV push, once Dicyclomine 20mg syrup, PO, once OR 20mg PO, once https://www.emra.org/books/pain-management/abdominal-pain 31 Acute Pain Treatment Regimen: Surgery example Pre-opera$ve: Epidural: Bupivacaine (0.1 or 0.2%) Acetaminophen 650 or 975 mg PO x 1 dose Gabapen$n 600mg PO x 1 dose Meloxicam 15mg PO x 1 dose Celecoxib 200mg PO x 1 dose Post opera$ve: (for 120 hours) Acetaminophen 975mg PO q6hrs OR 1000mg IV q 6 hrs (for 24 hrs then reassess) OR if less than 50kg: 15mg/kg IV q6 hrs (for 24 hrs) Meloxicam 15mg PO qday Celecoxib 200mg PO q12hrs Gabapen$n 300mg PO q12hrs Lora$dine 10mg PO qday Ondansetron 4mg ODT PO q6hrs Oxycodone 5mg PO q4hrs, prn, MILD pain (1-3) Oxycodone 10mg PO q4hrs, prn MODERATE pain (4-7) Hydromorphone 0.25mg IV push q20 min, PRN MODERATE pain (4-7) and unable to take PO or failed PO therapy Hydromorphone 0.5mg IV push q20 min, PRN SEVERE (8-10) and unable to take PO or failed PO therapy Promethazine 25mg/mL topical gel, q6hrs PRN nausea Nalbuphine 5mg inj IV push, PRN itching Diphenhydramine 25mg PO q6hrs, PRN itching (if itching unrelieved by nalbuphine) Diphenhydramine 12.5mg IV push q6hrs, PRN itching, if unable to tolerate PO or itching unrelieved by nalbuphine Patient Controlled (PCAs) can also be used; PCAs are not used as often postoperatively; but can Naloxone 0.4mgAnalgesia inj, IV push PRN overseda$on be used in other acute pain conditions (sickle cell crisis, acute cancer pain) MLH ERAS Plan 32 Acute Pain Treatment Regimens: Fractures Long bone fractures (femur, $bia, "bula) or arms (humerus, radius, ulna) Children (< 16yo) o#er: 1. oral ibuprofen, or oral acetaminophen, or both for mild to moderate pain 2. intranasal or intravenous opioids for moderate to severe pain (use intravenous opioids if intravenous access has been established). May see ketamine used Adults o#er: 1. 2. 3. oral acetaminophen for mild pain oral acetaminophen and codeine for moderate pain intravenous acetaminophen supplemented with intravenous morphine $trated to e#ect for severe pain. Notes: Limit NSAIDs to short term use (< 2 weeks) Use intravenous opioids with cau$on in frail or older adults. Do not o#er non-steroidal an$-inKammatory drugs (NSAIDs) to frail or older adults with Na$onal Clinical Guideline Centre (UK). (Non-Complex): Assessment and Management. London: Na$onal Ins$tute for Health and Care Excellence fractures. (risk ofFractures MI, stroke, GI bleed, renal dysfunc$on) (NICE); 2016 Feb. (NICE Guideline, No. 38.) 6, Ini$al pain management. Available from: h?ps://www.ncbi.nlm.nih.gov/books/NBK368141/ 33 Acute Pain Treatment Regimens: Renal Colic Sudden onset of Kank pain Acute obstruc$on of the urinary tract (kidney stones) Ini$al treatments: Lay on the side with pain Fluids Commonly used NSAIDS: ibuprofen 800 mg PO ketorolac 30 mg IV or 60 mg IM diclofenac 50-75 mg IM naproxen 500 mg PO Drug of Choice for severe renal colic: Morphine sulfate https://www.emra.org/books/pain-management/renal-colic-pain 34 Acute Pain: Addi onal Notes Surgery: Pain management often starts PRIOR to surgery Pain is a common problem among patients in ICUs The most common causes of pain in patients in ICU: surgical interventions, posttrauma pain, pain associated with procedures such as arterial line placement chest tube removal airway suctioning wound care * A sedated patient can still feel pain 35 Case/Discussion PY is a 12 yo male who presented to the school nurse’s o(ce complaining of his leR middle "nger hur$ng aRer it was caught in someone’s shirt playing Kag football in PE. The nurse examined his "nger, "nding: Finger to be twisted above the middle joint and bent towards the ring "nger No bruising, no swelling Tender to touch While wai$ng for his parents to come get him, what ac$on can the nurse take? 36 Case/Discussion Xrays are taken in the Emergency room con"rming the nurse’s suspicion of a complete bone break. While wai$ng for the physician to see him, PY is twis$ng his "nger and trying to straighten it manually. He is able to realign his "nger, but it just goes back to the way it was…he appears calm and does not wince or complain of pain, just some aching. What severity level of pain would you say PY is experiencing? The physician prescribes Percocet. Is that needed at this $me? What else could be done? 37 Case/Discussion PY is referred to an orthopedic surgeon for evalua$on and sees the surgeon the following day. The bone is broken and would heal on its own, but would be dis"gured. The surgeon recommends surgery to realign the bone and place 2 pins. PY has surgery: bone realigned, pins placed What pain management would you recommend? And for how long? PY begins physical therapy aRer 1 week of healing, is there any interven$on that can be made? 38 Chronic Pain 39 Chronic Pain Condi ons Medica on Therapies Lower Back Pain: NSAIDs, muscle relaxants, opioids (for severe cases) Head and Neck Pain: NSAIDs, muscle relaxants, tricyclic antidepressants Chronic Postoperative Pain: NSAIDs, opioids (temporarily), nerve blocks Temporomandibular Joint Disorder (TMJ): NSAIDs, muscle relaxants, tricyclic antidepressants Chronic Regional Pain Syndrome (CRPS): NSAIDs, anticonvulsants, opioids Complex Regional Pain Syndrome (CRPS): NSAIDs, anticonvulsants, sympathetic nerve block Irritable Bowel Syndrome (IBS): Antispasmodics, laxatives, tricyclic antidepressants Endometriosis: NSAIDs, hormonal therapy (e.g., birth control pills, GnRH agonists) Chronic Pelvic Pain: NSAIDs, antispasmodics, tricyclic antidepressants Interstitial Cystitis: Bladder analgesics, tricyclic antidepressants, pentosan 40 Opioid pharmacokine cs Extended-release (Long ac ng opioids) Immediate-release (Short ac ng opioids) Tmax: 3 – 9 hrs Tmax: 5-15 min (IV), 1-2 hrs (PO) DOA: 8-24 hrs for oral 72 hrs for patch DOA: 1-1.5 hrs (IV), 3-5 hrs (PO/PR) Frequencies: PO: q12h or qdaily Patch: q72hrs Frequencies: PO: q4 or q6 hours IV: q 1-4 hours 41 Escala ng + De-escala ng Opioid Regimens Increasing regimens NEVER start someone on a long ac$ng opioid! Need to assess short ac$ng usage before you can jus$fy an XR regimen IF pa$ent is eligible for XR formula$on, should account for a “rescue” aka PRN IR med for breakthrough pain (BTP) IR PRN dosage should be ~10-15% of TDD not part of total calcula$on for XR regimen Decreasing regimens Taper more slowly for those on therapy for longer dura$ons because risk of withdrawal 42 Chronic Pain: Addi onal Notes Nonpharmacologic and nonopioid therapies are preferred over opioids Before starting opioids, treatment goals for pain and function should be determined with the patient Discuss benefits and risks and availability of nonopioid therapies with the patient When starting opioids, start with Immediate release formulations Prescribe the lowest effective dose Assess and reassess risks and benefits with doses 50 MME/day and avoid increasing above 90 MME/day – always calculate to determine risk of overdose 43 Case/Discussion 2 ED is a 75yo female with a h/o back surgery. Post surgery and aRer healing, her pain score was 1 of 10. She also has arthri$s in her hands for which she was taking 2 extra strength Bayer Aspirin 4 $mes a day. ED developed a “virus” with nausea and vomi$ng and was unable to eat anything other than bland foods in very small quan$$es. ARer 7 days, she felt be?er, but “relapsed” when she ate some chocolate covered peanuts. What might be happening with ED? Years later, ED has a return of back pain that scores a 4 of 10 most $mes, and some$mes 7 of 10. What op$ons does ED have? 44 Cancer Pain 45 Why Does Cancer Cause Pain Cancer itself can cause pain Type of cancer Stage the more advanced the cancer, more likely to have pain Spinal cord compression: (emergency) back and/or neck pain; can be severe Pain, numbness, weakness Coughing, sneezing, other movements can worsen pain Bone Pain: when cancer spreads to bones Side E#ect from growth factor drugs or colony s$mula$ng factors Aimed at stopping damage to bones (and allevia$ng pain): External radia$on bisphosphonates Treatment for cancer can cause pain Surgical Pain Phantom Pain Peripheral Neuropathy Mouth Sores (mucosi$s and stoma$s) tes$ng https://www.cancer.org/cancer/managing-cancer/side-effects/pain/facts-about-cancer-pain.html; accessed Nov 2023 46 Cancer Pain Treatment Must address both chronic and breakthrough pain Combina$ons of: Long- ac$ng (ER, LA, CR, SR and patch formula$ons) short-ac$ng (IR) opioids NSAIDS, Acetaminophen Adjuvant therapies: neuropathic pain: an$depressants, an$convulsants Bone pain Augment ac$on of opioids S$mulants and amphetamines: Ca#eine, moda"nil, methylphenidate Anxiety: benzodiazepines: lorazepam, diazepam S$mulants and amphetamines: Ca#eine, moda"nil, methylphenidate Nausea and Itching: an$histamines: hydroxyzine, diphenhydramine May develop opioid tolerance or worsening of disease can result in increase in dosage 47 Case/Discussion 3 DT is a 49yo female newly diagnosed with cancer of unknown origin, but has tumors in her stomach, on her spine, and in her liver and lungs. She reports pain of a 10 of 10 and is unable to move due to the pain. She is at home and would like to be able to improve her quality of life: What medica$ons would you recommend for DT? 48 Neuropathic Pain and Fibromylagia 49 Neuropathic Pain Poor response to analgesics Increases with dura$on Versus nocicep$ve pain usually decreases (becomes duller) over $me More likely to have: hyperalgesia allodynia 50 Neuropathic Pain Treatment Algorithm 1st Line (4-6 week trial) 2nd Line (4-6 week trial) Tricylic An$depressants (TCAs) 3rd Line 4th line 5th line* SSRIs Tramadol SNRIs An$convulsants neuromodula$on Opioids Gabapen$noids Combina$ons of 1st line therapies Topicals NMDA Antagonists Bates D, Schultheis BC, Hanes MC, Jolly SM, Chakravarthy KV, Deer TR, Levy RM, Hunter CW. A Comprehensive Algorithm for Management of Neuropathic Pain. Pain Med. 2019 Jun 1;20(Suppl 1):S2-S12. doi: 10.1093/pm/pnz075. Erratum in: Pain Med. 2023 Feb 1;24(2):219. PMID: 31152178; PMCID: PMC6544553. 51 Medica ons for Neuropathic Pain Drug Class Medica on Dosing/Notes Tricyclic An$depressants Nortriptyline & Amitriptyline Star$ng dose: 10-25mg PO QHS Max daily dose: 150mg Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) Duloxe$ne Star$ng dose: 30mg PO daily Max daily dose: 60mg Star$ng dose: 37.5mg PO daily Max daily dose: 225mg Gabapen$noids Gabapen$n Venlafaxine Pregabalin Topicals 5% lidocaine 8% capsaicin* star$ng dose 300mg TID, slow $tra$on up to 600mg TID; max daily dose: 3600mg star$ng dose: 150mg BID or TID Max daily dose: 600mg cream or patch 12 hours on/ 12 o# Max: 3 patches at one $me apply for 60 minutes Avoid in diabe$c neuropathy* Combina$on Therapy Gabapen$noid + TCA Gabapen$noid + SNRI avoid in elderly aim for lower doses of both Weak Mu Opioid agonist &SNRIs Tramadol Star$ng dose: 50mg IR PO BID-QID prn Max daily dose: 400mg 52 Fibromyalgia Widespread soma$c pain and deep $ssue tenderness caused by sensi$za$on of neural pain pathways: “Pain all over” E#ects 2% of the popula$on: (4% women;