Disclosure. Introduction. Objectives. Understanding Pain. Mechanism of Pain 7/25/2015. Management of Chronic Pain Syndromes. 49th Annual Meeting

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1 49th Annual Meeting Management of Chronic Pain Syndromes Anthony Pazanese, PharmD Clinical Pharmacy Specialist Pain and Palliative Care Disclosure I do not have a vested interest in or affiliation with any corporate organization offering financial support or grant monies for this continuing education activity, or any affiliation with an organization whose philosophy could potentially bias my presentation OWNING CHANGE: Taking Charge of Your Profession Objectives Introduction Evaluate various chronic pain syndromes and the pharmacologic treatment options Apply evidence-based practices to the treatment of chronic pain management Critique the treatment of acute pain in chronic pain syndromes Navigate social stigma and challenges of using long term opioids Pain is the single most common reason that patients visit physicians, clinical facilities, and pharmacies Estimated 100 million patients have chronic pain 1/3 of the United States Primary reason for disability claims More prevalent in women and the elderly Up to 25% of nursing home patients with daily pain received no analgesics 25 million patients experience acute pain each year American Academy of Pain Medicine, 2015 Understanding Pain Mechanism of Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (IASP 1979) A subjective experience Substantial variability in intensity Patient description is the most reliable indicator Consider objective parameters as well May not be reliable in chronic pain Transduction Nerve ending activation Transmission Relay of Signals Perception Reduction of transmission Modulation Subjective awareness of pain 1

2 Types of Pain Types of Pain Acute or chronic Chronic pain - persistent or intermittent Malignant or nonmalignant Newer definition of malignant pain extends to pain caused by conditions other than cancer, i.e., any progressive disease that is potentially life limiting (e.g., MS, AIDS, etc.) Etiology: nociceptive or neuropathic Acute pain lasts hours to weeks caused by surgery, trauma, medical procedures prognosis is predictable primary treatment is analgesics under treatment and overtreatment common Chronic pain lasts months to years can be severe and disabling prognosis is unpredictable treatment is multimodal, including analgesics under treatment common Types of Pain Somatic Pain Nociceptive pain Somatic pain: Arises from skin, bone, joint, muscle or connective tissue Visceral pain: Arises from internal organs, mucosal linings Neuropathic Pain Caused by nerve damage Characteristics Typically well-localized Continuous Aching, dull, gnawing, nagging Examples Bone metastasis Mucositis Broken bones Bruises Visceral Pain Neuropathic Pain Characteristics Poorly localized May be referred May worsen with movement or deep inspiration Sharp, stabbing, deep, gnawing, vague, pressure Examples Colon cancer with metastasis Pancreatitis Appendicitis Characteristics Constant Burning, tingling Sharp, shooting, electrical, shocklike Examples Diabetic neuropathy Post-herpetic neuralgia Brachial plexopathy 2

3 Effects of Untreated Pain Untreated pain can Alter neurotransmission signals Modulate pain pathways Make it more difficult to treat pain in the future Lead to chronic pain conditions Other effects include Endocrine/metabolic, respiratory, musculoskeletal, gastrointestinal and immunologic Assessment of Pain Pain Assessment Location Diffuse? Well-localized? Does it radiate? Onset and duration When did the pain start? Any triggering event? Continuous or intermittent? How often does the pain occur? Characteristics or description How would you describe the pain? Pain Assessment Pain characteristics What words would you use to describe your pain? Dull Achy Burning Shooting Pressure Stabbing Deep Sharp Pain Assessment (continued) Intensity of pain Verbal analogue scales On a scale of 0 to 10 (zero being no pain and ten being the worst pain you can imagine), how would you rate your pain right now? What is the worst your pain gets on a scale of 0 to 10? What is the best your pain gets on a scale of 0 to 10? Is your pain zero, mild, moderate or severe pain? Pain Assessment Visual pain intensity scales Numeric rating scale Visual analogue scale (VAS) Simple descriptive scale 3

4 Special Populations Pain Scales in Chronic Pain Pediatrics Geriatrics VAS only validated in acute pain Less telling in chronic pain scales Patients may get stuck on a number Many factors influencing numbers Unable to assess change on daily basis Functional Pain Scales more reliable Impact on function, behavior, mental status Functional Pain Scale Pain Assessment 0 Stay in bed all day. Feel hopeless and helpless about life. 1 Stay in bed at least half the day. Have no contact with the outside world. 2 Get out of bed but don t get dressed. Stay at home all day. 3 Get dressed in the morning. Minimal activity at home. Contact with friends via phone. 4 Simple chores around the house. Minimal activities outside of home two days a week. 5 Struggle but fulfill daily responsibilities. No outside activity. Not able to work. 6 Work limited hours. Limited social activities on weekends. 7 Work a few hours daily. Active at least five hours/day. Simple activities on weekends 8 Work at least six hours daily. Energy for one evening social activity during the week. Active on weekends. 9 Work eight hours daily. Take part in family life. Outside social activities limited. 10 Go to work each day. Normal daily activities each day. Have a social life outside of work. Take an active part in family life. Modifying factors What alleviates or exacerbates the pain Associated signs and symptoms Previous treatments How effective were previous regimens How effective is your current regimen Adverse effects of previous treatment American Chronic Pain Association Pain Assessment A thorough assessment should also include: Medication history Physical assessment Particularly areas of pain Labs Organ function History of substance abuse Personal and family history Psychosocial assessment Up to 50-60% of chronic pain patients have coexisting psychiatric morbidity Pain Assessment Mnemonic to assess pain: PQRST Provoke or palliate What makes pain better or worse? Quality What does the pain feel like? Radiation Does the pain radiate, if so, where? Severity How bad is it? Time When did the pain begin, how long has it lasted? 4

5 Treatment of Chronic Pain Treatment of Chronic Pain Treatment of associated disease state, along with symptom management Multidisciplinary and multimodal Guidelines are somewhat vague Specific treatment flowcharts are not present Pharmacological treatment options are patient specific; based on type of pain and pharmacokinetic profiles Low Back Pain Acute (<4 weeks) Acetaminophen X X Skeletal Muscle X Relaxants Antidepressants X (TCA) Benzodiazepines X X Tramadol, Opioids X X Subacute or Chronic (>4 weeks) Diabetic Peripheral Neuropathy Recommended Drug/Dose Not Recommended Level A Pregabalin mg/day Level B Gabapentin mg/day Oxcarbazepine Sodium Valproate mg/day Lamotrigine Venlafaxine mg/day Lacosamide Duloxetine mg/day Clonidine Amitriptyline mg/day Pentoxifylline Dextromethorphan 400 mg/day Mexiletine Morphine titrated to 120 mg/day Magnetic field treatment Tramadol 210 mg/day Low-intensity laser therapy Oxycodone up to 120 mg/day Reiki therapy Capsaicin 0.075% QID Isosorbide dinitrate spray Electrical stimulation, percutaneous nerve stimulation x3-4 weeks Treatments for Chronic Pain Medication Management Non-Steroidal Anti Inflammatory Drugs (NSAIDs) Acetaminophen Opioids Muscle Relaxants Skeletal vs Smooth Muscle Tricyclic Antidepressants (TCAs) Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) Anticonvulsants Topical Analgesics Treatments for Chronic Pain Botulinum Toxin Injections Epidurals Facet, Nerve, or Intra-articular Blocks Trigger Point Injections Radiofrequency Denervation Surgery Spinal Cord Stimulators Intrathecal Pain Pumps 5

6 NSAIDs NSAIDs Reduce transduction at peripheral nociceptors Effective for musculoskeletal pain Potential risks, especially with long term use COX-1 Increased risk of GI bleed COX 2 Increased risk of MI/TIA Withdrawal of Rofecoxib/Valdecoxib Nephrotoxicity May delay long bone healing But prevents bone spur formation after surgery Thrombocytopenia Opioids Full Mu Agonists Oxycodone Hydrocodone Codeine Morphine Hydromorphone Fentanyl Meperidine Tramadol * Tapentadol * Methadone ** Partial Mu Agonists Buprenorphine Agonists/Antagonists Pentazocine Butorphanol Nalbuphine * Serotonin and Norepinephrine Reuptake Inhibition Opioids Potential for abuse/self harm Negative social stigma Numerous adverse effects Sedation, hypotension, bradycardia, constipation Fentanyl less likely to be effective with obese/cachectic patients Caution against application of heat with fentanyl patches Caution against use of morphine and meperidine in renal failure Expected accumulation of methadone Long Term Use of Opioids No max dose with most full agonists (i.e. morphine)? Opioid induced hyperalgesia Immunosuppression Dose dependent decrease in NK cell, T-cell, and macrophage function with Morphine and Fentanyl Tramadol stimulated immune function Endocrinopathy Decreases in LH, FSH, Testosterone, and Estradiol Sexual dysfunction and low libido Decrease in adrenal function Opioid Endocrinopathy *** P<0.001, **P<0.01, *P<0.05 Rhodin et al,

7 Opioid Endocrinopathy Intrathecal Opioids *** P<0.001, **P<0.01, *P<0.05 Morphine remains the gold-standard for intrathecal analgesia Equianalgesic dose conversions PO to IV morphine 3:1 IV to epidural morphine 10:1 Epidural to intrathecal morphine 10:1 PO to intrathecal morphine 300:1 Doses lessened; adverse effects are comparable Unclear whether will show in UDS Rhodin et al, 2010 Intrathecal Opioids Antispasmodics Baclofen Tizanidine Cyclobenzaprine Carisoprodol Chlorzoxazone Methocarbamol Metaxalone Orphenadrine Kumar et al, 2001 Antispasmodics Smooth Muscle Relaxants All except Baclofen and Tizanidine have strong anticholinergic effects Mechanism of action via general CNS depression Orphenadrine structurally similar to antihistamine Carisoprodol metabolized into meprobamate May show positive for barbiturate on drug screens Tizanidine is an alpha-2 agonist May cause severe hypotension Baclofen associated with confusion when dosed aggressively Intrathecal withdrawal may potentiate seizures Dicyclomine and Hyoscyamine Often effective for acute and chronic abdominal cramping or colic Associated with Crohn s Disease or Colitis Profound anticholinergic effects 7

8 Antidepressants Antidepressants Venlafaxine Duloxetine Milnacipran Amitriptyline Nortriptyline Prevent modulation and perception of pain Effective for neuropathic and chronic musculoskeletal pain 60% of chronic pain patients also have depression Serotonin effect not associated with analgesia Caution with pre-existing history of seizures TCAs have high anticholinergic effects Anticonvulsants Anticonvulsants Gabapentin Pregabalin Act via prevention of modulation of pain GABA analogues Do not affect GABA concentrations Do not bind to GABA receptors Effective for chronic musculoskeletal and neuropathic pain May cause significant peripheral edema Caution in congestive heart failure Dose titration of Gabapentin Topical Anesthetics Diclofenac Patient Cases Lidocaine Capsaicin 8

9 Chronic Lower Back Pain - PR Chronic Lower Back Pain - PR 32 year old male Localized lower back pain resulting from MVC 15 year history of pain PMH significant only for HTN MRI shows facet arthropathy in lumbar spine Negative social history Managed on Oxycodone 5mg PO TID States this is ineffective for him Takes 15mg Oxycodone upon waking up Takes Ibuprofen 800mg q4h during the day Identifies pain score of 8/10 Applying for disability Slight interference with daily activities; unable to work Currently uninsured Describes pain as a constant, sharp, grabbing pain Spasms associated with constant pain Worsened with physical activity Relieved with hot showers Chronic Lower Back Pain - PR Development of Acute Pain Problems with therapy? Ibuprofen use Oxycodone misuse due to prescribed dose not helping Relief with NSAIDs and heat therapy Addition of Meloxicam 15mg daily and Baclofen 5mg TID Baclofen titration to be performed by PCP Instructed to stop taking Ibuprofen Continue Oxycodone 5mg PO TID PRN pain Two months later, PR returns with acute abdominal pain and black stools New regimen not continued by PCP, and continued previous regimen of Ibuprofen and Oxycodone by patient Still with complaints of chronic pain Now with radiation down RLE, to his R knee Evidence of Gastric Ulcer on imaging Disability was approved Now with insurance via disability PR s Acute Pain Radiculopathy - CB Treatment of disease state Initiation of pantoprazole/sucralfate Reinitiation of Baclofen for muscle tightness Avoidance of systemic NSAIDs Although Meloxicam is COX-2 specific, would still avoid Could consider topical Diclofenac to lower back No increase in opioids Treatment of gastric ulcer should provide analgesia Referral to interventional pain management Likely relief from facet blocks 76 year old female complaining of sciatica Lower back pain x 15 years resulting from MVC Radiation down posterior aspect of BLE Tingling and numbness in 4 th and 5 th toes bilaterally Pain described as constant, sharp pain in her back with shooting down legs Had lumbar fusion in 2003 with no relief 9

10 Dermatome Map Radiculopathy CB Current medications Morphine Sulfate ER 30mg BID Morphine Sulfate IR 15mg QID PRN pain PMH HTN Type 2 DM Chronic kidney disease (CrCl 40) Radiculopathy - CB CB s Acute Pain Caution using morphine in renal dysfunction M3G and M6G not dialyzable May lead to respiratory depression and seizures Gabapentin may be a good option for this patient Renally dosed; start at 300mg BID May tolerate gradual weaning of opioids CB is admitted to the hospital complaining of severe chest pain, and is now s/p CABG Morphine doses were slightly weaned outpatient Morphine Sulfate ER 15mg BID Morphine Sulfate IR 15mg BID PRN pain Gabapentin 600mg BID Renal function is unchanged CB s Acute Pain Sickle Cell Disease - DH Temporary increase in morphine would be the easiest solution for management of acute pain Continue ER dose of 15mg BID Increase IR dose to 15mg q4h PRN pain while inpatient Could replace with equivalent dose of IV opioid Continue Gabapentin dose If pain continues at discharge, could send patient home with Rx for IR morphine at higher frequency Follow up with outpatient MD 23 year old male Documented history of sickle cell disease Chronic pain in BLE Described as a generalized dull, aching pain Patient not able to identify any modifying factors Has had inpatient relief with IV hydromorphone Acutely worsens in sickle cell crisis 10

11 Sickle Cell Disease - DH Sickle Cell Disease - DH Uninsured, low income Negative social history Admitted to the hospital about once/year for crisis Currently takes hydrocodone/apap 10/325mg two tablets q4h Pain controlled as long as this is taken Patient wakes up at night to take a dose at 03:30 Complains that he is tired of taking pills Pain controlled with frequent doses of short acting opioids May be appropriate for long acting opioid Uninsured Currently taking 120mg hydrocodone/day Sickle Cell Disease - DH Sickle Cell Crisis - DH Good methadone candidate 5mg PO q8h (8:1 conversion) Patient counseling 1:1 equivalency with morphine in single dose studies Medication accumulation Continue short acting opioid Can likely wean dose as methadone accumulates Admitted to hospital for acute crisis Complains of severely worsened chronic pain Requesting IV hydromorphone States this has helped in the past Requesting IV diphenhydramine States hydromorphone causes itching Current medications Methadone 5mg PO q8h Hydrocodone/APAP 5/325 BID on average Sickle Cell Crisis - DH Fibromyalgia - JC Pain will decrease to baseline with treatment IV Fluids, NSAIDs, and IV opioids Avoid combination of IV opioids with IV diphenhydramine Inpatient treatment Hydromorphone 1mg IV q4h PRN pain Continue Methadone Ketorolac 15mg IV q6h x5 days Diphenhydramine 25mg PO q6h PRN itching 46 year old female complaining of generalized pain secondary to fibromyalgia PMH Fibromyalgia Obesity HTN Dyslipidemia Type 2 DM COPD Depression Smokes 2 PPD; denies EtOH or illicit drug use 11

12 Fibromyalgia - JC Fibromyalgia - JC Pain described as generalized muscle aches Worsened with activity Unable to pinpoint pain to any specific area Worsened with palpation Current pain/psychiatry medications Lexapro 20mg daily Gabapentin 300mg TID Tapentadol 50mg q4h PRN pain (#120 / 30 days) Gabapentin dose likely sub therapeutic Increase to 600mg TID Max dose about 3600mg/day Saturable drug absorption SSRIs have no analgesic properties Could consider changing Lexapro to SNRI Would defer to outpatient psychiatrist if the patient states this has been working well for her Tapentadol may be better than other opioids Norepinephrine reuptake with PRN use? Osteomyelitis - RJ Osteomyelitis - RJ 24 year old male No history of chronic pain Admits to IV use of Hydromorphone 8mg QID Also admits to PO use of alprazolam bars and footballs and carisoprodol UDS positive for marijuana, opioids, barbiturates, benzodiazepines Complains of acute severe lower back pain Treatment will require six weeks of IV antibiotics Unable to discharge due to risk of self-harm Will complete therapy as inpatient Calculated outpatient opioid use based on report 160mg PO morphine equivalents per dose 640mg PO morphine equivalents per day Acute treatment of pain complicated by opioid tolerance and history of drug abuse Osteomyelitis - RJ Use only PO opioids if possible Morphine Sulfate ER 30mg BID Morphine Sulfate IR 30mg q4h PRN pain If IV opioids are needed, consider PCA Lower peaks associated with less euphoria Schedule NSAIDs Ketorolac 15mg IV q6h x 5 days, then Ibuprofen 800mg PO q6h Wean off opioids as tolerated, and avoid discharging with prescription Social Stigma of Opioids 12

13 Epidemiology Substance Use Disorder 52 million people in the United States have abused prescription medications at least once in their lives 12.5 million people abused opioids in million met DSM-IV criteria for abuse or dependence Societal cost: $55.7 billion per year Workplace (46%) Healthcare (45%) Criminal Justice (9%) Birnbaum et al, 2011 The Diagnostic and Statistical Manual of Mental Disorders (DSM) V: Maladaptive pattern of substance use leading to clinically significant impairment or distress with 2 of the following 11 criteria occurring within 12 months: Exceeding recommended dosage or duration Tolerance (need for higher doses to achieve response) Failure to fulfill major role obligations Use in hazardous situations Use despite social and interpersonal problems American Psychiatric Association, 2013 Substance Use Disorder Risk Factors for Abuse Withdrawal Craving or desire for substance Persistent desire to use substance or unsuccessful attempts to reduce or stop use Spending a great deal of time to acquire or use substance Social, occupational, or recreational impairment Personal history of EtOH or drug abuse Family history of EtOH or drug abuse History of physical or sexual abuse Comorbid psychiatric conditions Depression common among chronic pain patients Continuation despite knowledge of harm it can cause Moderate: 2 3 Severe: 4 American Psychiatric Association, 2013 Balancing Opioid Use Lack of Prescriber Education Over-treatment versus under-treatment Concern for patient s pain versus concern for misuse Under-treatment becoming more common Concomitant psychological disease states Concern for patient self-harm Concern for lawsuits Company policies Patient appearance Most internal medicine and family medicine physicians have little to no formal training in pain management Less than 4% of medical schools require a course in pain management Only 16% of medical schools provide an elective Pharmacists are also undereducated regarding pain management Pharmacy schools commonly teach 2-4 hours during a therapeutics course Mezei et al,

14 Case of John Oles We Don t Have It! Walgreens sued due to Vicodin overdose PCP reportedly instructed pharmacy to not fill prescriptions for Vicodin in 2010 Prescriptions no longer written by PCP Patient s mother sued pharmacy Settled for $80 million Cardinal Health fined $34 million in 2012 Failed to report suspicious orders for hydrocodone Occurred in Lakeland, FL distribution center Orders from four pharmacies in Sanford, FL Shipments of controlled substances suspended for two years Led to temporary shortages, and some patients struggling to find pharmacies able to fill their opioids Orders temporarily filled from Mississippi facility War on Pain vs War on Drugs How can we tell whether legitimate prescribing? Prescription Drug Monitoring Programs Most states will require a state license to search Calling MDs with inappropriate or suspicious prescriptions Should I fill this? Requesting early refills Running out early, lost, or stolen prescriptions May be sign of inadequately treated pain Multiple ED prescriptions Does the patient have a PCP, or are they using the emergency department for treatment? Multiple pharmacies Are they being turned down for refills? Should I fill this? Multiple physicians Is the patient able to drive to appointments? Was the patient fired from a previous practice? Ancillary medications Gabapentin and tizanidine vs alprazolam and carisoprodol Payment of cash vs insurance coverage Is the prescriber aware of medication cost? Discuss more cost efficient options with MD Conclusion Thorough assessment is an integral step in treatment of acute and chronic pain Physicians are often undereducated in regards to pain management Treatment for chronic pain management, although evidence based, is largely a grey area Clinical decisions based on pharmacokinetic agents of each medication 14

15 Conclusion Conclusion Opioids are the mainstay of therapy in acute pain, but a multimodal approach is necessary for chronic pain management Opioids will often be less effective than adjuvant medications Pharmacological agents will also target modulation, as well as perception of pain Extensive use of agents targeting neuropathic components of pain Acute pain management may require higher doses due to opioid tolerance Opioid therapy presents with a social stigma, largely due to concern for appropriate use Pain often under-treated Tools do exist to help differentiate drug seekers from legitimate patients Don t make unfair assumptions about patients 49th Annual Meeting Management of Chronic Pain Syndromes Anthony Pazanese, PharmD Clinical Pharmacy Specialist Pain and Palliative Care Anthony.Pazanese@myLRH.org OWNING CHANGE: Taking Charge of Your Profession 15