Medco CE - Topical Pain Management


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  • Immune: Depressed immune response Developmental: behavioral, physiological responses to pain, higher somatization, addictive behavior, anxiety Cognitive: Reduction in mental function, confusion Future Pain: Debilitating chronic pain syndromes Quality of life: Insomnia, anxiety, fear, hopelessness, depression Endocrine: ACTH, cortisol, ADH, epinephrine, norepinepherine, GH, catacholamines, rennin, angiotensin II, aldosterone; ↓ insulin, testosterone Metabolic: Increased catabolic demands; poor wound healing, weakness, muscle breakdown, hyperglycemia Musculoskeletal: Muscle spasm, fatigue, immobility Cardiovascular: heart rate, cardiac output, increased coronary/peripheral/systemic vascular resistance, hypertension Respiratory: ↓ Flows and volumes = atelectasis; ↓cough = sputum retention, infection Gastrointestinal: ↓ gastric and bowel motility Genitourinary: ↓ urine output, urinary retention
  • Acute: treatment outcome predictable. Resolves in days to weeks. Chronic: treatment outcome unpredictable
  • American Pain Society and American College of Rheumatology Capsaicin and methylsalicylate not considered proven to provide much relief vs OA But… Current American Rheumatology guidelines were created prior to the approval of topical NSAID availability in the US
  • Voltaren 1% gel Solaraze 3% gel – only approved for AK actinic keratosis Flector transdermal patch 1.3%
  • Discuss the limitations of those old studies done regarding salicylates and OA Methyl salicylate (BenGay, IcyHot)
  • “ reversible” – nerve fibers re-innervate over a 6 wk period in one small study Zostrix
  • Of note: some nerve regenaration might be irreversible. Some studies of patients who have lost their ability to sense cold
  • Magnesium sacilyate (Doan’s, DeWitt’s, Momentum)- po only Choline magnesium trisalicylate – combo salicylates – po only F&C For external use only: Avoid contact with eyes, eyelids, and mucous membranes. Apply to affected parts only: Do not apply to irritated skin; discontinue use if excessive irritation develops. Consult a physician if pain persists for longer than 7 to 10 days, or if redness is present, or in conditions affecting children younger than 10 years of age. Heat therapy: Do not use an external source of high heat (eg, heating pad) with these agents because irritation and burning of the skin may occur. Protective covering: Applying a tight bandage or wrap over these agents is not recommended because increased absorption may occur. Product List   Print this section RUBS AND LINIMENTSTrade nameDoseform Analgesic Balm-GRXBalm : 14% methyl salicylate, 6% menthol Icy HotBalm : 29% methyl salicylate, 7.6% menthol, white petrolatum EpidermBalm : Isopropyl alcohol, parabens, ureas, menthol, EDTA JointFlexCream : 3.1% camphor, lanolin, aloe, urea, EDTA, glycerin, peppermint oil Capzasin-PCream : 0.035% capsaicin. Alcohols, petrolatum. ArthriCare for Women Silky DryCream : 0.025% capsaicin, parabens, mineral oil ArthriCare for Women Extra MoisturizingCream : 0.025% capsaicin, aloe vera gel, cetyl and stearyl alcohol, parabens ArthriCare for Women Multi-ActionCream : 0.025% capsaicin, 1.25% menthol, 0.25% methyl nicotinate, aloe vera gel, cetyl alcohol, parabens Capzasin-HPCream : 0.1% capsaicin. Alcohols, petrolatum. ArthriCare for Women Ultra StrengthCream : 0.075% capsaicin, 2% menthol, aloe vera gel, cetyl and stearyl alcohol, parabens AxsainCream : 0.25% capsaicin in an emollient base. Lidocaine, benzyl alcohol, cetyl alcohol, white petrolatum. Vicks VapoRubCream : 2.8% menthol, 5.2% camphor, 1.2% eucalyptus oil, cedarleaf oil, cetyl and stearyl alcohol, EDTA, glycerin, urea, parabens, turpentine oil Arthritic HotCream : Methyl salicylate, menthol ZiksCream : 12% methyl salicylate, 1% menthol, 0.025% capsaicin, cetyl alcohol, urea Thera-GesicCream : 15% methyl salicylate, 1% menthol, glycerin, parabens Bengay GreaselessCream : 15% methyl salicylate, 10% menthol, cetyl alcohol, glycerin Pain Bust-R IICream : 17% methyl salicylate, 12% menthol, cetyl and stearyl alcohol ArthriCare for Women NighttimeCream : 30% methyl salicylate, 1.25% menthol, 0.25% methyl nicotinate, glycerin, isopropyl alcohol Arthritis Formula BengayCream : 30% methyl salicylate, 8% menthol, lanolin Icy HotCream : 30% methyl salicylate, 10% menthol Ultra Strength BengayCream : 30% methyl salicylate, 10% menthol, 4% camphor, EDTA, lanolin Panalgesic GoldCream : 35% methyl salicylate, 4% menthol, lanolin, cetyl and stearyl alcohol, mineral oil MyoflexCream : 10% triethanolamine salicylate, cetyl and stearyl alcohol, EDTA Myoflex Extra , Myoflex ArthriticCream : 15% triethanolamine salicylate SportscremeCream : 10% trolamine salicylate, cetyl alcohol, glycerin, parabens, mineral oil AspercremeCream : 10% trolamine salicylate, aloe vera gel, cetyl alcohol, glycerin, parabens, mineral oil MobisylCream : 10% trolamine salicylate, aloe vera gel, cetyl alcohol, urea, glycerin, parabens, mineral oil, sweet almond oil, EDTA Icy Hot Arthritis TherapyGel : 0.025% capsaicin, aloe vera gel, benzyl alcohol, urea, maleated soybean oil, parabens Flexall Quik GelGel : Menthol, methyl salicylate Blue IceGel : 2% menthol. Isopropyl alcohol. Mineral Freez GelGel : 2% menthol. Alcohol. Vanishing Scent BengayGel : 2.5% menthol, urea, isopropyl alcohol Vicks VapoRubGel : 2.6% menthol, 4.8% camphor, 1.2% eucalyptus oil, cedarleaf oil, nutmeg oil, petrolatum, turpentine oil Flexall 454Gel : 7% menthol, aloe vera gel, eucalyptus oil, glycerin, peppermint oil, thyme oil Maximum Strength Flexall 454Gel : 16% menthol, aloe vera gel, eucalyptus oil, glycerin, peppermint oil, thyme oil Flexall Ultra PlusGel : 16% menthol, 10% methyl salicylate, 3.1% camphor, aloe vera gel, eucalyptus oil, glycerin, peppermint oil, thyme oil Icy Hot Chill StickGel : 30% methyl salicylate, 10% menthol, hydrogenated castor oil, stearyl alcohol Myoflex Ice Cold PlusGel : 15% triethanolamine salicylate Therapy Ice GelGel : 2% menthol. Isopropyl alcohol. Absorbine Jr Arthritis StrengthLiquid : Capsaicin, echinacea, calendula, and wormwood extracts Absorbine JrLiquid : 1.27% menthol, echinacea, calendula, and wormwood extracts, wormwood oil Extra Strength Absorbine JrLiquid : 4% menthol, echinacea, calendula, and wormwood extracts, wormwood oil Yager'sLiniment : Camphor, turpentine oil, clove oil Panalgesic GoldLiniment : 55.01% methyl salicylate, 1.25% menthol, 3.1% camphor, emollient oils, alcohol BanalgLotion : 4.9% methyl salicylate, 1% menthol, 2% camphor, parabens, eucalyptus oil Banalg Hospital StrengthLotion : 14% methyl salicylate, 3% menthol, parabens AspercremeLotion : Trolamine salicylate EucalyptamintOintment : 16% menthol, eucalyptus oil, lanolin, mineral oil Original Formula BengayOintment : 18.3% methyl salicylate, 16% menthol, lanolin Absorbine JrPatch : Menthol, camphor, eucalyptus Absorbine Jr Deep Pain ReliefPatch : Menthol, glucosamine, MSM Pain Relieving Bengay PatchPatch : 1.4% menthol. Regular and large sizes. Icy Hot Back Patch , Icy Hot Pop & Peel PatchPatch : 5% menthol. Glycerin. Ultra Strength Bengay Pain Relieving PatchPatch : 5% menthol. Regular and large sizes. Icy Hot Elbow and Wrist Sleeve , Icy Hot Knee and Ankle Sleeve
  • Expected fewer side effects, esp if unable to cross the BBB May be helpful in the repair of damaged skin, as skin activation of the opioid system can influence cell differentiation and apoptosis…
  • Extra notes for my reference Meperidine (Demerol ® ) Not recommended Poor oral absorption Normeperidine is a toxic metabolite Longer half-life (6 hours), no analgesia Psychotomimetic adverse effects, myoclonus, seizures If dosing q 3 h for analgesia, normeperidine builds up Accumulates with renal failure
  • Medco CE - Topical Pain Management

    1. 1. Topical Pain Management for Medco Health Solutions Las Vegas, NV 3/13/11 by Joe Crea [email_address] Crea Healthcare Partnering Powell, OH
    2. 2. Disclosure Information <ul><li>I have the following financial relationships to disclose: </li></ul><ul><li>Honoraria and expenses paid by: </li></ul><ul><li>Medco Health Solutions </li></ul><ul><li>through </li></ul><ul><li>Business Services International, Inc. </li></ul><ul><li>I have no other financial relationships to disclose. </li></ul><ul><li>I will not discuss any investigational uses. </li></ul><ul><li>I will not discuss any off label uses. </li></ul>
    3. 3. Epidemiology <ul><li>> 50 million people are partially or totally disabled due to pain </li></ul><ul><li>70 to 90% of patients with advanced disease from cancer have significant pain that requires the use of opioid drugs. </li></ul><ul><li>Severe, unrelenting pain interferes with patients' quality of life, including their activities of daily living, their sleep, and their social interactions. </li></ul>
    4. 4. Epidemiology (cont.) <ul><li>80% of elderly patients have chronic pain. </li></ul><ul><li>66% have pain in the last month of life </li></ul><ul><li>~ ½ of hospitalized patients with pain are under-medicated. </li></ul><ul><li>Estimated cost of pain is $150 billion per year </li></ul><ul><li>Up to 50% of patients who are taking pain medication do not experience adequate relief </li></ul>
    5. 5. Economics <ul><li>Chronic pain causes 700 million lost work days/year in the U.S. </li></ul><ul><li>> $ 9 billion per year on OTC pain products. </li></ul>
    6. 6. What is Pain? <ul><li>Medical Definition: </li></ul><ul><ul><li>“ Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage.” </li></ul></ul><ul><ul><li>International Association for the Study of Pain, 1979 </li></ul></ul><ul><ul><li>“ An unpleasant sensation induced by noxious stimuli and generally received by specialized nerve endings.” </li></ul></ul><ul><ul><li>CancerWEB, 2011 </li></ul></ul><ul><ul><li>Operative Definition: </li></ul></ul><ul><ul><li>“ Pain is whatever the experiencing person says it is, existing whenever he/she says it does.” </li></ul></ul><ul><ul><ul><li>Margo McCaffery, 1999 </li></ul></ul></ul>
    7. 7. Physiologic Effects of Pain
    8. 8. Pain Behaviors
    9. 9. Presentation of Pain <ul><li>Acute </li></ul><ul><li>Often obvious distress </li></ul><ul><li>Can be sharp, dull, shock-like, tingling, shooting, radiation, fluctuating in intensity, and varying in location ( occur in timely relationship to noxious stimul i) </li></ul><ul><li>Comorbid conditions not usually present </li></ul><ul><li>May see HTN, increased HR, diaphoresis, pallor… </li></ul><ul><li>Chronic </li></ul><ul><li>Can appear to have no noticeable suffering </li></ul><ul><li>Can be sharp, dull, shock-like, tingling, shooting, radiation, fluctuating in intensity, and varying in location ( do NOT occur in timely relationship to noxious stimul i) </li></ul><ul><li>Symptoms may change over time </li></ul><ul><li>Usually NO obvious signs </li></ul>
    10. 10. Four Types of Pain Behaviors <ul><li>Facial/audible expression of distress </li></ul><ul><li>Distorted ambulation or posture </li></ul><ul><li>Negative affect </li></ul><ul><li>Avoidance of activity </li></ul>
    11. 11. Autonomic Response to Pain <ul><li>Grimacing </li></ul><ul><li>Restlessness </li></ul><ul><li>Guarding </li></ul><ul><li>Increased respirations </li></ul><ul><li>Increased heart rate </li></ul><ul><li>Increased blood pressure </li></ul><ul><li>Diaphoresis </li></ul>
    12. 12. Emotions, Coping, and Pain <ul><li>Chronic pain is associated with higher levels of anger, fear, sadness, anxiety and stress, but often fewer observable outward physical changes/signs. </li></ul>
    13. 13. Pain and the Brain
    14. 14. Pain Terminology, Classifications, and Pathophysiology
    15. 15. Pain terms <ul><li>Allogenic substances </li></ul><ul><ul><li>chemicals released at the site of the injury </li></ul></ul><ul><li>Nociceptors </li></ul><ul><ul><li>afferent neurons that carry pain messages </li></ul></ul><ul><li>Referred pain </li></ul><ul><ul><li>pain that is perceived as if it were coming from somewhere else in the body </li></ul></ul>
    16. 16. Pain <ul><li>Pain disorders classified into several categories based upon origin: </li></ul><ul><li>Acute (Nociceptive) </li></ul><ul><ul><li>Somatic </li></ul></ul><ul><ul><ul><li>Superficial (nociceptors of skin) </li></ul></ul></ul><ul><ul><ul><li>Deep [body wall (muscle, bone)] </li></ul></ul></ul><ul><ul><li>Visceral (sympathetic system; may refer to superficial structures of same spinal nerve) </li></ul></ul><ul><li>Chronic </li></ul><ul><ul><li>Malignant (cancer) </li></ul></ul><ul><ul><li>Nonmalignant </li></ul></ul><ul><ul><ul><li>Neuropathic (nerve injury) </li></ul></ul></ul><ul><ul><ul><li>Inflammatory (musculoskeletal) </li></ul></ul></ul><ul><ul><ul><li>Mixed or unspecified </li></ul></ul></ul><ul><ul><ul><li>Psychogenic </li></ul></ul></ul>
    17. 17. Acute Pain <ul><li>Travels into the spinal cord along the appropriate nerve root. </li></ul><ul><li>Nerve root splits into a front division and a back division and carries pain sensation to the CNS (spinal cord and brain). </li></ul><ul><li>Passed to a short tract of nerve cells ( interneurons ), which in turn synapse with a nerve tract that runs to the brain . </li></ul>
    18. 18. Acute Pain <ul><li>Sent out to the rest of the brain, connecting with thinking and emotional centers. </li></ul><ul><li>A modifier pathway from the brain modifies pain at the synapses in the back part of the spinal cord (acute pain is decreased rapidly after tissue injury). </li></ul>
    19. 19. Peripheral Nerve Fibers Involved in Pain Perception <ul><li>A-delta fibers–small, myelinated fibers that transmit sharp pain </li></ul><ul><li>C-fibers–small unmyelinated nerve fibers that transmit dull or aching pain. </li></ul>
    20. 20. Chronic Pain <ul><li>Neuropathic - severe pain disorder that results from damage to the central and peripheral nervous systems. </li></ul><ul><ul><li>Centrally generated </li></ul></ul><ul><ul><li>Peripherally generated </li></ul></ul><ul><li>Inflammatory - results from the effects of inflammatory mediators. </li></ul>
    21. 21. Chronic Pain Conditions <ul><li>Neuralgia </li></ul><ul><ul><li>an extremely painful condition consisting of recurrent episodes of intense shooting or stabbing pain along the course of the nerve. </li></ul></ul><ul><li>Causalgia </li></ul><ul><ul><li>recurrent episodes of severe burning pain. </li></ul></ul><ul><li>Phantom limb pain </li></ul><ul><ul><li>feelings of pain in a limb that is no longer there and has no functioning nerves. </li></ul></ul>
    22. 22. Pain Without Physical Findings <ul><li>Persists long after healing </li></ul><ul><li>May spread and increase in intensity </li></ul><ul><li>May become stronger than was the initial pain from the injury </li></ul>
    23. 23. Pain Assessment and Management
    24. 24. Pain Assessment: PQRST mnemonic <ul><li>P: Precipitating and palliating factors </li></ul><ul><li>Q: Quality </li></ul><ul><li>R: Region and radiation </li></ul><ul><li>S: Severity </li></ul><ul><li>T: Time </li></ul>
    25. 25. Pain Assessment: Instruments <ul><li>Single-dimension </li></ul><ul><ul><li>Visual analog scale </li></ul></ul><ul><ul><li>Verbal numerical scale </li></ul></ul><ul><ul><li>Verbal rating scale </li></ul></ul><ul><li>Multidimensional – assesses the pain as well as the emotional and behavioral effects of the pain. </li></ul>
    26. 26. Pain Assessment: Single-dimension Instruments <ul><li>Visual analog and Verbal numerical scales </li></ul>
    27. 27. Pain Assessment: Single-dimension Instruments <ul><li>Verbal rating scale </li></ul><ul><li>No pain = 0 </li></ul><ul><li>Mild pain = 1-3 </li></ul><ul><li>Moderate pain = 4-6 </li></ul><ul><li>Severe pain = 7-9 </li></ul><ul><li>Worst ever = 10 </li></ul>
    28. 29. WHO Analgesic Ladder
    29. 30. Non-pharmacologic Pain Management <ul><li>Neurostimulation </li></ul><ul><li>TENS </li></ul><ul><li>Acupuncture </li></ul><ul><li>Anesthesiology </li></ul><ul><li>Nerve block </li></ul><ul><li>Surgery </li></ul><ul><li>Physical therapy </li></ul><ul><li>Exercise </li></ul><ul><li>Heat/cold </li></ul><ul><li>Psychological approaches </li></ul><ul><li>Cognitive therapies(relaxation, imagery, hypnosis) </li></ul><ul><li>Biofeedback </li></ul><ul><li>Behavior therapy </li></ul><ul><li>Psychotherapy </li></ul><ul><li>Complementary tx </li></ul><ul><li>Massage, art, music, aroma therapy </li></ul>
    30. 31. Pharmacology of Nociception <ul><li>Four Steps: </li></ul><ul><li>1. Transduction </li></ul><ul><ul><li>NSAIDs, Local Anesthetics & Anticonvulsants </li></ul></ul><ul><li>2. Transmission </li></ul><ul><ul><li>Opioids, NMDA Antagonists </li></ul></ul><ul><li>3. Perception </li></ul><ul><ul><li>Distraction, Relaxation, Imagery </li></ul></ul><ul><li>4. Modulation </li></ul><ul><ul><li>Tricyclic Antidepressants, Opioids, GABA Agonists </li></ul></ul>
    31. 32. Pharmacology of Nociception
    32. 33. Pharmacology of Nociception
    33. 34. Routes of Administration <ul><li>Intramuscular </li></ul><ul><li>Intravenous </li></ul><ul><li>Intraspinal </li></ul><ul><li>Local/Regional blocks </li></ul><ul><li>Oral </li></ul><ul><li>Rectal </li></ul><ul><li>Subcutaneous </li></ul><ul><li>Sublingual </li></ul><ul><li>Transdermal / Topical** </li></ul>
    34. 35. Three Major Classes of Drugs Used to Treat Pain <ul><li>NSAIDs & Acetaminophen </li></ul><ul><ul><li>Peripherally acting </li></ul></ul><ul><li>Opioid Analgesics </li></ul><ul><ul><li>Centrally acting (bind to brain opioid receptors) </li></ul></ul><ul><li>Adjuvant Analgesics </li></ul><ul><ul><li>Affect non-pain conditions (e.g. emotions that can exacerbate pain condition) </li></ul></ul>
    35. 36. Pain Type: Nociceptive (Visceral & Somatic) <ul><ul><li>Non-Opioids – WHO first line </li></ul></ul><ul><ul><ul><li>These agents act peripherally. </li></ul></ul></ul><ul><li>Often used to treat acute pain (e.g. strains, sprains, sore muscles) and OA </li></ul><ul><li>Most topical analgesics fall into this class </li></ul><ul><ul><li>Many are these used in conjunction with oral analgesics (e.g. ASA, APAP, NSAID) </li></ul></ul>
    36. 37. Nociceptive (Visceral & Somatic) <ul><ul><li>Traditional Oral Choices: </li></ul></ul><ul><ul><li>Acetaminophen (Tylenol®) 325-1000 mg q 4-6h </li></ul></ul><ul><ul><li>PO/PR </li></ul></ul><ul><ul><li>Max= 4 gm/day. </li></ul></ul><ul><ul><li>Recommended as first-line </li></ul></ul><ul><ul><li>Salicylates </li></ul></ul><ul><ul><ul><li>Choline/Magnesium Salicylates (Trilisate®) 750-1500mg PO BID (Max= 3 gm/day) </li></ul></ul></ul><ul><ul><ul><li>Aspirin 325-650 mg PO q4h (Max=4 gm/day) </li></ul></ul></ul>
    37. 38. Nociceptive (Visceral & Somatic) <ul><ul><li>Traditional Oral Choices: </li></ul></ul><ul><ul><li>NSAIDs </li></ul></ul><ul><ul><ul><li>Non-selective COX Inhibitors </li></ul></ul></ul><ul><ul><ul><ul><li>e.g. Ibuprofen (Motrin®, Advil®) 200-800 mg po q6h Max=3200 mg/day </li></ul></ul></ul></ul><ul><ul><ul><ul><li>e.g. Naproxen (Naprosyn®) 250-500 mg po BID-TID Max= 1500 mg/day </li></ul></ul></ul></ul><ul><ul><ul><li>COX-2 Selective Inhibitors </li></ul></ul></ul><ul><ul><ul><ul><li>e.g. Celecoxib (Celebrex®) 100-400 mg po QD-BID </li></ul></ul></ul></ul>
    38. 39. Topical NSAIDs, Salicylates, Capsaicin <ul><li>Only considering those commercially available; excludes compounded combinations. </li></ul><ul><li>Trials in the past 5 yrs: </li></ul><ul><ul><li>Diclofenac diethylamine gel </li></ul></ul><ul><ul><li>Diclofenac solution </li></ul></ul><ul><ul><li>Ketoprofen gel </li></ul></ul><ul><ul><li>Ibuprofen cream or gel </li></ul></ul>
    39. 40. Topical Non-Opioids <ul><li>Provide local pain relief </li></ul><ul><li>Many Formulations (cream, gel, oil, patch) </li></ul><ul><li>3 Main Classes: </li></ul><ul><ul><li>1. NSAIDs </li></ul></ul><ul><ul><li>2. Counter-irritants </li></ul></ul><ul><ul><li>a. camphor, eucalyptus, menthol (e.g. IcyHot®, ArthriCare®) </li></ul></ul><ul><ul><li>b. Salicylates (e.g. Aspercreme®) </li></ul></ul><ul><ul><li>3. Capsaicin </li></ul></ul>
    40. 41. Topical vs Oral NSAIDs? <ul><li>NSAIDs : </li></ul><ul><ul><li>considered efficacious for OA pain </li></ul></ul><ul><ul><li>Dose-dependent risk of renal & GI toxicity </li></ul></ul><ul><li>Pharmacology : </li></ul><ul><ul><li>Relieve pain by inhibiting COX </li></ul></ul><ul><ul><ul><li>COX: promotes the formation of inflammatory mediators such as prostacyclin, prostaglandin, and thromboxanes </li></ul></ul></ul><ul><li>Few trials evaluating topical vs. oral NSAIDs </li></ul>
    41. 42. Topical vs Oral NSAIDs <ul><ul><li>European Guidelines: </li></ul></ul><ul><ul><ul><li>Topical NSAIDs preferred over Oral NSAIDs, if: </li></ul></ul></ul><ul><ul><ul><ul><li>Knee or hand </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Few joints involved </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Mild-moderate severity </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Sensitivity to oral NSAIDs </li></ul></ul></ul></ul><ul><ul><li>Why isn’t this the case in the US? </li></ul></ul><ul><ul><ul><li>US Guidelines: list capsaicin and salicylates only. </li></ul></ul></ul><ul><ul><ul><li>Discussion </li></ul></ul></ul>
    42. 43. Topical NSAID: D iclofenac sodium <ul><li>Diclofenac 1% gel </li></ul><ul><ul><li>First Topical NSAID (Rx) </li></ul></ul><ul><ul><li>~$35-$40/100 g tube – for OA </li></ul></ul><ul><li>Diclofenac 3% gel – for actinic keratosis only </li></ul><ul><li>Diclofenac 1.3% patch – for strains, sprains and contusions </li></ul><ul><ul><li>applied to most painful area 2x/day </li></ul></ul><ul><li>Penetrates skin ~ 3-4 mm </li></ul>
    43. 44. Diclofenac 1% gel <ul><li>Oral NSAIDs, but NOT topical NSAIDs have been linked to increased GI, renal, & CV complications & hospitalizations </li></ul><ul><ul><li>Despite low systemic exposure, carries same Black Box warning and safety precautions as oral diclofenac. </li></ul></ul><ul><li>Hand and Knee OA: </li></ul><ul><ul><li>Clinically significant reductions in pain & improvement in physical function </li></ul></ul>
    44. 45. Patient Counseling w/ topical NSAID <ul><li>Gently massage into intact skin – cover entire AA </li></ul><ul><li>Use dosing card (1 per application) to apply the gel. </li></ul><ul><li>Avoid showering/bathing > 1hr after applying </li></ul><ul><li>Avoid external heat and/or occlusive dressings </li></ul><ul><li>Do not cover with clothing/gloves for at least 10 minutes </li></ul><ul><li>Concomitant use of diclofenac gel with oral NSAIDs has not been evaluated; may increase NSAID ADEs. </li></ul>
    45. 46. Topical Diclofenac Dosing <ul><li>Diclofenac gel : </li></ul><ul><ul><li>Lower extremities, including the knees, ankles, and feet: </li></ul></ul><ul><ul><ul><li>Usual Dosage: 4 g to the affected foot, knee, or ankle 4x/day. Max: 16g/d to any single lower extremity joint </li></ul></ul></ul><ul><ul><ul><li>Maximum Dose: 32 g per day, over all affected joints. </li></ul></ul></ul><ul><ul><li>Upper extremities, including the elbows, wrists, and hands: </li></ul></ul><ul><ul><ul><li>Usual Dosage: 2 g to affected hand, elbow, or wrist 4x/day. </li></ul></ul></ul><ul><ul><ul><li>Max Dose: 8 g/day to any single joint of the upper extremities. </li></ul></ul></ul>
    46. 47. NSAID Adverse Effects <ul><li>Highest incidence of adverse events </li></ul><ul><li>Gastropathy </li></ul><ul><ul><li>ASA benefits offset by ADEs </li></ul></ul><ul><ul><li>Provide gastric cytoprotection for NSAIDs, if appropriate. </li></ul></ul><ul><ul><li>Cox-2 selective inhibitors have decreased risk. </li></ul></ul><ul><li>Renal insufficiency </li></ul><ul><ul><li>Maintain adequate hydration </li></ul></ul><ul><li>Inhibition of platelet aggregation </li></ul><ul><ul><li>Assess for coagulopathy </li></ul></ul>
    47. 48. Salicylates (OTC) <ul><li>Derivatives of acetylsalicylic acid (ASA), but different MOA </li></ul><ul><li>MOA : counter-irritant, stimulating pain receptors with the hope of desensitizing them over time. </li></ul><ul><ul><li>Interference with transcription factors and kinases involved in inflammation? </li></ul></ul><ul><ul><li>Do not appear to inhibit COX enzymes. </li></ul></ul>
    48. 49. Salicylates <ul><li>Skin penetration : ~ 3-4 mm </li></ul><ul><li>Use : </li></ul><ul><ul><li>Painful acute conditions </li></ul></ul><ul><ul><li>Not recommendation for chronic pain conditions (poor to moderate efficacy) </li></ul></ul><ul><ul><ul><li>OA may be an exception. </li></ul></ul></ul><ul><ul><ul><li>Very FEW clinical trials published reg. topical salicylate in tx of OA </li></ul></ul></ul><ul><li>Examples: </li></ul><ul><ul><li>Trolamine salicylate (e.g. Aspercreme®) </li></ul></ul><ul><ul><li>Methyl salicylate (e.g. BenGay®, IcyHot®) </li></ul></ul>
    49. 50. Salicylates <ul><li>Safety: </li></ul><ul><ul><li>Have been associated with severe toxicity and death after topical application and intention/unintentional ingestion. </li></ul></ul><ul><ul><li>Like NSAIDs, may increase risk of bleeding; therefore, pharmacointeraction w/ warfarin </li></ul></ul><ul><li>Point: OTC does not necessarily mean safer than Rx! </li></ul>
    50. 51. Capsaicin (OTC) <ul><li>MOA : </li></ul><ul><ul><li>Counterirritant, eventually desensitizing nerves (a result of apparent reversible nerve degeneration) </li></ul></ul><ul><ul><li>Depletion of Substance P and calcitonin gene-related peptide. </li></ul></ul><ul><li>Skin penetration </li></ul><ul><ul><li>Negligible; may be less effective analgesic than salicylates or topical NSAIDs. </li></ul></ul>
    51. 52. Capsaicin <ul><ul><li>Efficacy: </li></ul></ul><ul><ul><ul><li>OA: Clinical trials showed modest benefit in OA pain relief, even after excluding treatment failures from study data analysis. </li></ul></ul></ul><ul><ul><ul><li>Chronic musculoskeletal pain: poor-to-moderate efficacy as monotherapy. May have a role as adjunctive therapy. </li></ul></ul></ul><ul><ul><li>Safety : </li></ul></ul><ul><ul><ul><li>No serious adverse events reported </li></ul></ul></ul><ul><ul><ul><li>Extreme irritation if contact with eye or mucosal tissue. </li></ul></ul></ul><ul><ul><li>Tolerability : </li></ul></ul><ul><ul><ul><li>Effects not immediate; therefore, patients may discontinue prematurely. </li></ul></ul></ul>
    52. 53. Additional Considerations <ul><li>Adherence </li></ul><ul><ul><li>Topical NSAID: 4x/day </li></ul></ul><ul><ul><li>Topical salicylates & capsaicin: prn </li></ul></ul><ul><li>Administration </li></ul><ul><ul><li>Rubbing an already sore joint/painful area? </li></ul></ul><ul><ul><li>Inconvenient? </li></ul></ul><ul><ul><li>Messy? </li></ul></ul>
    53. 54. Agent Pharmacology Efficacy Safety Cost (US$) Topical NSAID Diclofenac gel COX-2 inhibition w/ reduced COX inhibition Penetrates 3-4mm Suitable for OA of knee or hand Effective monotherapy for mild-mod OA of hand or knee Equivalent analgesia to PO NNT for 50% pain reduction: 3 AEs: local Low risk of GI, CV or renal Ses Same Black Box as oral Do not combine w/ other NSAIDs $35-40/100g tube Salicylates Counterirritant – desensitizes pain receptors Modest efficacy in chronic pain No data for OA Adjunct to NSAIDs NNT: 5.3 Excessive use or ingestion can be toxic $6.99 - $8.99/ 57 g tube Capsaicin Counterirritant – desensitizes pain receptors Modest adjunctive tx Minimal as monotx NNT: 8.1 Application site; pain & burning early on $19.99- $22.49/57g tube
    54. 55. Neuropathic Pain <ul><li>Tricyclic Antidepressants : </li></ul><ul><ul><li>First line for non-stabbing pain </li></ul></ul><ul><ul><li>Examples </li></ul></ul><ul><ul><ul><li>Desipramine (Norpramin ® ) </li></ul></ul></ul><ul><ul><ul><li>Nortriptyline (Pamelor ® ) </li></ul></ul></ul><ul><ul><ul><li>Doxepin (Sinequan ® ) </li></ul></ul></ul><ul><ul><ul><li>Imipramine (Tofranil ® ) </li></ul></ul></ul><ul><ul><ul><li>Amitriptyline (Elavil ® ) </li></ul></ul></ul><ul><ul><li>Usual dose: 10-25 mg q HS, titrate up to 150 </li></ul></ul><ul><li>Serotonin/Norepinephrine Reuptake Inhibitor </li></ul><ul><ul><li>Duloxetine (Cymbalta ® ) </li></ul></ul>
    55. 56. Neuropathic Pain <ul><li>Anticonvulsants </li></ul><ul><ul><li>First line for stabbing pain </li></ul></ul><ul><ul><li>Examples </li></ul></ul><ul><ul><ul><li>Gabapentin (Neurontin®) 300-1200 mg TID Up to 6 g/d </li></ul></ul></ul><ul><ul><ul><li>Pregabalin (Lyrica ®) 50-100mg TID </li></ul></ul></ul><ul><ul><ul><li>Carbamazapine (Tegretol®) 200-400 mg QID </li></ul></ul></ul><ul><ul><ul><li>Divalproex Na(Depakote®) 500-2000 mg q HS </li></ul></ul></ul>
    56. 57. Neuropathic Pain <ul><li>Lidocaine transdermal patch </li></ul><ul><ul><li>Only topical for neuropathic pain </li></ul></ul><ul><ul><li>Indicated for post-herpetic neuralgia </li></ul></ul><ul><ul><ul><li>Apply up to 3 patches, only once, for up to 12 hrs. within a 24 hours period </li></ul></ul></ul><ul><ul><ul><li>Apply to cover skin in most painful area </li></ul></ul></ul><ul><ul><li>MOA: Inhibits conduction of nerve impulses </li></ul></ul><ul><ul><li>Penetration: allows for local analgesia, but insufficient to result in complete sensory block. </li></ul></ul><ul><ul><li>Pearl: patches can be cut if done b/f removing release liner </li></ul></ul>
    57. 58. Moving from Peripherally Acting Agents to Centrally Acting: Opioids
    58. 59. Nociceptive Pain (Visceral & Somatic) <ul><li>WHO 2 ND or 3 rd line </li></ul><ul><li>Opioid/non-opioid combinations </li></ul><ul><ul><li>Hydrocodone/APAP (Vicodin ® , Lortab ® ) </li></ul></ul><ul><ul><li>Oxycodone 5 mg /APAP 325mg (Percocet ® ) </li></ul></ul><ul><ul><li>Codeine/APAP (Tylenol with Codeine ® ) </li></ul></ul><ul><ul><li>Propoxyphene/APAP (Darvocet N ® ) </li></ul></ul><ul><li>( Maximum APAP/24hours = 4000 mg) </li></ul>
    59. 60. WHO Analgesic Ladder
    60. 61. Chemical Classes of Opioids <ul><li>PHENANTHRENES </li></ul><ul><ul><li>Morphine </li></ul></ul><ul><ul><li>Codeine </li></ul></ul><ul><ul><li>Hydromorphone </li></ul></ul><ul><ul><li>Hydrocodone </li></ul></ul><ul><ul><li>Oxycodone </li></ul></ul><ul><li>DIPHENYLHEPTANE DERIVATIVE </li></ul><ul><ul><li>Methadone </li></ul></ul><ul><ul><li>Propoxyphene </li></ul></ul><ul><li>PHENYLPIPERIDINE DERIVATIVES </li></ul><ul><ul><li>Meperidine </li></ul></ul><ul><ul><li>Fentanyl </li></ul></ul>
    61. 62. Not recommended . . . <ul><li>Propoxyphene (Darvon®, Darvocet®) </li></ul><ul><ul><li>No better than placebo; low efficacy at commercially available doses. </li></ul></ul><ul><ul><li>Toxic metabolite at high doses. </li></ul></ul><ul><ul><li>Gone in Europe since 2005. </li></ul></ul><ul><li>Mixed agonist-antagonists </li></ul><ul><ul><li>Compete with agonists ->withdrawal </li></ul></ul><ul><ul><li>E.g. pentazocine (Talwin®),butorphanol (Stadol®), nalbuphine (Nubain®) </li></ul></ul><ul><ul><li>Analgesic ceiling effect </li></ul></ul><ul><ul><li>High risk of psychotomimetic ADEs w/ pentazocine, butorphanol </li></ul></ul>
    62. 63. Opioids & The Skin ? <ul><li>New field of interest </li></ul><ul><ul><li>Small RCTs demonstrate effectiveness in chronic pain management </li></ul></ul><ul><li>Growing evidence regarding opioid receptors (OR) in various skin structures </li></ul><ul><ul><li>Peripheral nerve fibers </li></ul></ul><ul><ul><li>Keratinocytes </li></ul></ul><ul><ul><li>Melaninocytes </li></ul></ul><ul><ul><li>Hair follicles </li></ul></ul><ul><ul><li>Immune cells </li></ul></ul><ul><li>Potential Benefits? </li></ul>
    63. 64. Opioids <ul><li>Receptor response on activation: </li></ul><ul><ul><li>Mu : analgesia, respiratory depression, miosis, euphoria, reduced gastrointestinal motility </li></ul></ul><ul><ul><li>Kappa : analgesia, dysphoria, psychotomimetic effects, miosis*, respiratory depression* </li></ul></ul><ul><ul><li>Delta : Analgesia *Less intense than with Mu activation </li></ul></ul>
    64. 65. Opioids <ul><li>Opioids : Immediate release </li></ul><ul><ul><ul><li>Morphine (MS IR®, Morphine Sol. Tabs) Hydromorphone (Dilaudid®) Methadone Oxycodone (Oxy IR®) Oxymorphone (Opana ®) Codeine, hydrocodone, morphine, hydromorphone, oxycodone </li></ul></ul></ul><ul><ul><li>Dose q 4 h & adjust dose daily depending on pain </li></ul></ul><ul><ul><li>Mild-mod pain: increase daily dose by 25-50% </li></ul></ul><ul><ul><li>Mod to severe pain: increase daily dose by 50-100% </li></ul></ul>
    65. 66. Opioids <ul><ul><li>Opioids Sustained Release </li></ul></ul><ul><ul><ul><li>Morphine SR 8-12 hr (MS Contin ® ) </li></ul></ul></ul><ul><ul><ul><li>Oxycodone SR (OxyContin ® ) </li></ul></ul></ul><ul><ul><ul><li>Morphine SR 24 Hr (Avinza ® ) </li></ul></ul></ul><ul><ul><ul><li>Fentanyl Transdermal (Duragesic ® )** </li></ul></ul></ul><ul><ul><ul><li>Oxymorphone ER (Opana ER ® ) </li></ul></ul></ul><ul><ul><li>Long Acting </li></ul></ul><ul><ul><ul><li>Methadone </li></ul></ul></ul>
    66. 67. Opioids <ul><li>Extended-release preparations </li></ul><ul><ul><li>Improve compliance, adherence </li></ul></ul><ul><ul><li>Dose q 8, 12, or 24 h (product specific) </li></ul></ul><ul><ul><li>Do not crush or chew tablets </li></ul></ul><ul><ul><li>May flush time-release granules down feeding tubes </li></ul></ul><ul><ul><li>Adjust dose q 2-3 days (once steady state reached) </li></ul></ul>
    67. 68. Breakthrough Dosing <ul><li>Use immediate-release opioids </li></ul><ul><ul><li>5%–15% of total 24-hour dose </li></ul></ul><ul><ul><li>Offer breakthrough dose after C max reached </li></ul></ul><ul><ul><ul><li>po / pr ≈q 1 h </li></ul></ul></ul><ul><ul><ul><li>Sub-Q, IM ≈q 30 min </li></ul></ul></ul><ul><ul><ul><li>IV ≈ q 10–15 min </li></ul></ul></ul><ul><li>Do NOT use extended-release opioids for breakthrough pain! </li></ul>
    68. 69. Opioid Allergy <ul><li>Anaphylactoid/-ic reactions are the only true allergies. </li></ul><ul><li>Incidence 1:200,000 </li></ul><ul><li>Urticaria (hives) with diffuse rash can be allergies. Needs careful assessment! </li></ul>
    69. 70. Opioid Adverse Effects Common Uncommon Constipation Bad dreams/hallucinations Dry mouth Dysphoria/delirium N/V Myoclonus/seizures Sedation Pruritus/urticaria Sweating Respiratory depression Urinary retention
    70. 71. Constipation from Opioids <ul><li>Occurs with all opioids: </li></ul><ul><li>Pharmacologic tolerance develops slowly or not at all. </li></ul><ul><li>Dietary interventions alone usually not sufficient. </li></ul><ul><li>Avoid bulk-forming agents in debilitated patients. </li></ul><ul><li>Stimulant Laxative + Stool Softener is ideal (e.g. Senna S). </li></ul>
    71. 72. Adverse Effect Management <ul><li>Constipation (prophylaxis or treatment) </li></ul><ul><li>Urticaria </li></ul><ul><li>Senna‐Docusate 1‐2 tabs po hs or bid Bisacodyl 5‐10 mg po daily +/‐ docusate 100 mg po bid </li></ul><ul><li>Hydroxyzine 25‐100 mg q4‐6h prn </li></ul><ul><li>Diphenhydramine 25‐50 mg q6h prn </li></ul>
    72. 73. Respiratory Depression <ul><li>Opioid effects differ between patients </li></ul><ul><li>Pain: a potent stimulus to breathe </li></ul><ul><li>Loss of consciousness precedes respiratory depression </li></ul><ul><li>Rapid pharmacologic tolerance </li></ul><ul><li>Respiratory </li></ul><ul><li>Depression </li></ul><ul><li>Loss of </li></ul><ul><li>Consciousness </li></ul><ul><li>Sedation </li></ul><ul><li>Analgesia </li></ul><ul><li>Pain </li></ul>DOSE
    73. 74. Opioid-Induced Neurotoxicity <ul><li>Patients on morphine or hydromorphone </li></ul><ul><ul><li>Morphine > Hydromorphone </li></ul></ul><ul><ul><li>May continue to have pain with neuro-excitatory side effects. </li></ul></ul><ul><ul><li>Renal insufficiency> Normal renal function </li></ul></ul><ul><ul><li>High dose > low dose </li></ul></ul><ul><li>Further increase of dose exacerbates excitatory behaviors. </li></ul><ul><li>***Can Occur with ALL Opioids at High Doses </li></ul>
    74. 75. Primary Causes of Opioid-Induced Neurotoxicity <ul><li>Depends on both dose and duration of therapy. </li></ul><ul><li>Opioid metabolites </li></ul><ul><ul><li>Oral morphine metabolized in the liver & GI mucosa. </li></ul></ul><ul><ul><li>50% morphine 3-glucuronide (M3G) </li></ul></ul><ul><ul><ul><li>No analgesia </li></ul></ul></ul><ul><ul><ul><li>Neurotoxic side effects </li></ul></ul></ul><ul><ul><li>10% morphine-6-glucuronide </li></ul></ul><ul><ul><ul><li>Analgesic activity </li></ul></ul></ul><ul><ul><ul><li>Longer t ½ than morphine </li></ul></ul></ul>
    75. 76. … ..Opioid-Induced Neurotoxicity <ul><li>Other precipitating factors include: </li></ul><ul><ul><li>Underlying delirium </li></ul></ul><ul><ul><li>Dehydration </li></ul></ul><ul><ul><li>Acute renal failure </li></ul></ul><ul><ul><li>Advanced age </li></ul></ul><ul><ul><li>Psychoactive medications (e.g. BZDs, TCAs) </li></ul></ul><ul><li>Increasing reported incidence as practitioners get more comfortable and aggressive with opioids. </li></ul>
    76. 77. Opioid-Induced Neurotoxicity <ul><li>Early recognition is critical: </li></ul><ul><ul><ul><li>Myclonus –twitching of large muscle groups </li></ul></ul></ul><ul><ul><ul><li>Delirium </li></ul></ul></ul><ul><ul><ul><li>Hallucinations/Seizures </li></ul></ul></ul><ul><ul><ul><li>Rapidly escalating dose requirement </li></ul></ul></ul><ul><ul><ul><li>Hyperalgesia/Allodynia </li></ul></ul></ul><ul><ul><ul><li>Pain “doesn’t make sense”; not consistent w/ recent pattern or known disease. </li></ul></ul></ul>
    77. 78. Treatment <ul><li>Rotate to a structurally dissimilar opioid (i.e. differing receptor affinity profiles or chemical class.) </li></ul><ul><li>Hydration </li></ul><ul><li>Benzodiazepines for neuromuscular excitation </li></ul><ul><li>Behavioral excitation resolves over hours to days with treatment. </li></ul>
    78. 79. Chemical Classes of Opioids <ul><li>PHENANTHRENES </li></ul><ul><ul><li>Morphine </li></ul></ul><ul><ul><li>Codeine </li></ul></ul><ul><ul><li>Hydromorphone </li></ul></ul><ul><ul><li>Hydrocodone </li></ul></ul><ul><ul><li>Oxycodone </li></ul></ul><ul><li>DIPHENYLHEPTANE DERIVATIVE </li></ul><ul><ul><li>Methadone </li></ul></ul><ul><ul><li>Propoxyphene </li></ul></ul><ul><li>PHENYLPIPERIDINE DERIVATIVES </li></ul><ul><ul><li>Meperidine </li></ul></ul><ul><ul><li>Fentanyl </li></ul></ul>
    79. 80. Fentanyl (Duragesic®) is the only topical opioid in U.S. <ul><li>Advantages </li></ul><ul><li>Useful as an alternative to parenteral administration </li></ul><ul><li>May improve compliance/adherence </li></ul><ul><li>For mgmt of persistent moderate – severe pain requiring ATC treatment </li></ul><ul><li>Disadvantages </li></ul><ul><li>Difficult to dose correctly </li></ul><ul><li>Slow onset/offset of action </li></ul><ul><li>Difficult to respond to changing pain </li></ul><ul><ul><li>Dependent on physiological state of patient </li></ul></ul><ul><ul><li>Cachexia </li></ul></ul><ul><ul><li>Fever </li></ul></ul><ul><ul><li>Diaphoresis </li></ul></ul><ul><li>Expensive </li></ul>
    80. 81. Fentanyl <ul><li>Important Considerations: </li></ul><ul><ul><li>ONLY for patients opioid tolerant and requiring a total daily opioid dose of at least fentanyl 25 mcg/h patch </li></ul></ul><ul><ul><ul><li>Tolerant: morphine (or equiv) 60mg/day for > 1wk </li></ul></ul></ul><ul><ul><li>Must evaluate pain control using IR system prior to using extended/modified-release system </li></ul></ul><ul><ul><li>Follow WHO guidelines! </li></ul></ul>
    81. 82. Fentanyl <ul><li>Dosage Titration: </li></ul><ul><ul><li>Starting dose : </li></ul></ul><ul><ul><ul><li>based on daily morphine dose. Generally conservative. </li></ul></ul></ul><ul><ul><li>Dose Increases: </li></ul></ul><ul><ul><ul><li>Increase dose only after 3 days, based on the amt of IR opioid needed for break-through pain in days 2 & 3. </li></ul></ul></ul><ul><ul><ul><li>(45 mg oral morphine: 12.5 mcg/h increase in patch dose) </li></ul></ul></ul><ul><ul><li>New equilibrium: </li></ul></ul><ul><ul><ul><li>May not occur until 6 days after dose increase. </li></ul></ul></ul><ul><ul><ul><li>Wait at least 2 applications before further increasing dose! </li></ul></ul></ul>
    82. 83. Fentanyl Transdermal <ul><li>Criteria for use: </li></ul><ul><ul><li>Not cachectic </li></ul></ul><ul><ul><li>Unable to take PO/PR/SL </li></ul></ul><ul><ul><li>Patient compliance </li></ul></ul><ul><ul><li>Caregiver availability </li></ul></ul><ul><ul><li>Opioid abuse or diversion </li></ul></ul><ul><ul><li>Patient request </li></ul></ul>
    83. 84. Facts & Comparison 4.0. Accessed May 10, 2009 Fentanyl Dose Conversion Chart – ONLY WHEN CONVERTING ORAL TO PATCH & NOT WHEN CONVERTING PATCH TO ORAL!!) Current Analgesic Daily Dose (mg/day) Oral morphine 60 to 134 135 to 224 225 to 314 315 to 404 IM/IV morphine 10 to 22 23 to 37 38 to 52 53 to 67 Oral oxycodone 30 to 67 67.5 to 112 112.5 to 157 157.5 to 202 IM/IV oxycodone 15 to 33 33.1 to 56 56.1 to 78 78.1 to 101 Oral codeine 150 to 447 448 to 747 748 to 1,047 1,048 to 1,347 Oral hydromorphone 8 to 17 17.1 to 28 28.1 to 39 39.1 to 51 IV hydromorphone 1.5 to 3.4 3.5 to 5.6 5.7 to 7.9 8 to 10 IM meperidine 75 to 165 166 to 278 279 to 390 391 to 503 Oral methadone 20 to 44 45 to 74 75 to 104 105 to 134 IM methadone 10 to 22 23 to 37 38 to 52 53 to 67 Recommended fentanyl transdermal system dose Fentanyl transdermal system 25 mcg/h 50 mcg/h 75 mcg/h 100 mcg/h
    84. 85. Cancer Pain <ul><li>Multiple possible etiologies of cancer pain </li></ul><ul><li>Classes of medications other than those traditionally considered “analgesics” used to address these </li></ul><ul><li>As with non-cancer pains, topical analgesics options include: </li></ul><ul><ul><li>lidocaine & capsaicin : neuropathic pain </li></ul></ul><ul><ul><li>fentanyl transdermal : chronic pain </li></ul></ul>
    85. 86. Physical Dependence <ul><li>A process of neuro-adaptation </li></ul><ul><li>Abrupt withdrawal may -> abstinence syndrome </li></ul><ul><li>If dose reduction required, reduce by 25-50% q 2–3 days; avoid antagonists. </li></ul>
    86. 87. Tolerance <ul><li>Reduced effectiveness to a given dose over time. </li></ul><ul><li>If dose is increasing </li></ul><ul><ul><li>suspect opioid tolerance </li></ul></ul><ul><ul><li>disease progression </li></ul></ul><ul><ul><li>psychological/spiritual pain </li></ul></ul>
    87. 88. Addiction <ul><li>Acceleration of abuse patterns onto a primary illness. </li></ul><ul><li>Characteristics: </li></ul><ul><ul><li>psychological dependence </li></ul></ul><ul><ul><li>compulsive use </li></ul></ul><ul><ul><li>loss of control over amount and frequency of use </li></ul></ul><ul><ul><li>loss of interest in pleasurable activities </li></ul></ul><ul><ul><li>continued use of drugs in spite of harm </li></ul></ul>
    88. 89. Pseudoaddiction <ul><li>Drug seeking behavior associated with a person’s need to relieve pain and suffering, not an obsession with the mood altering affects of medication. </li></ul><ul><ul><ul><li>Wesson et al, 1993 </li></ul></ul></ul>
    89. 90. Chronic Pain Medical Issues <ul><li>Physical Exam </li></ul><ul><li>History documenting prescribing rationale </li></ul><ul><li>Pain assessment documentation </li></ul>
    90. 91. Legal Issues <ul><li>Accurate prescription records </li></ul><ul><ul><li>Controlled substance laws </li></ul></ul><ul><ul><li>Schedule II </li></ul></ul><ul><ul><ul><li>Emergency Telephone Prescriptions </li></ul></ul></ul><ul><ul><ul><li>Terminally Ill/Nursing Home Patients Fax prescriptions </li></ul></ul></ul>
    91. 92. Skilled Prescribing <ul><li>Patient –Physician Partnership </li></ul><ul><li>Pain management expectations </li></ul><ul><li>Medication responsibilities </li></ul><ul><li>One physician </li></ul><ul><li>One pharmacy </li></ul>
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