A Pain Management Primer for Pharmacists. Jessica Geiger-Hayes, PharmD, BCPS, CPE Andrea Wetshtein, PharmD, BCPS, CPE

Transcription

1 A Pain Management Primer for Pharmacists Jessica Geiger-Hayes, PharmD, BCPS, CPE Andrea Wetshtein, PharmD, BCPS, CPE

2 Objectives Discuss the differences between somatic, visceral, and neuropathic pain Design a treatment plan for the different modalities of pain

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4 What is Pain? An unpleasant sensory and emotional response associated with actual or potential tissue damage or described in terms of such damage. (IASP) International Association for the Study of Pain. IASP Pain Terminology. Whitten CE, Donovan M, Cristobal K. Treating Chronic Pain: New Knowledge, More Choices

5 What is Pain? Pain is whatever the person says it is -Margo McCaffery

6 Types Acute vs Chronic Nociceptive vs Neuropathic vs Mixed American Pain Foundation:

7 Associated Syndromes Hyperalgesia Increased pain sensitivity to a normally noxious stimulus Allodynia Pain in response to a stimulus which is normally not noxious i.e. blankets, clothing 7

8 Nociception Activation of peripheral nerve receptors by a noxious stimulus Mechanical Pressure Stretch Thermal Chemical

9 Total Pain Physical Symptoms Emotional Psychological Problems Patient with Pain Social Concerns Spiritual Existential Distress

10 How Pain Works 4. Perception Noxious Stimuli 1. Transduction 2. Conduction Modulation happens all along the way 3. Transmission

11 How Pain Works Transduction Conversion of mechanical or chemical stimuli into an electric charge Conduction Impulses from primary nociceptors to the spinal cord Transmission Transmitting nociceptive impulses from the dorsal horn to supra-spinal targets Perception Subjective awareness of pain Modulation Reduction of transmission

12 How Pain Works Excitatory Neurotransmitters Substance P Substance K Glutamate Aspartate Calcitonin gene related peptide Vasoactive intestinal peptide Inhibitory Neurotransmitters Serotonin Norepinephrine Opioids GABA Somatostatin Galanin 12

13 Nociceptive Pain Somatic Pain Skin, soft tissue, bone Easy to describe, localize Described as Sharp Aching Throbbing Visceral Pain Organs Difficult to describe, localize

14 Neuropathic Pain Nervous System Damage Primary lesion Dysfunction Pain may be greater than observable injury Described as: Burning Electrical Shooting Stabbing Tingling Wolf CJ. Ann Intern Med

15 Assessment Precipitating and palliating factors, previous tx Quality Region and radiation Severity Temporal profile U (you) How does the pain affect the patient

16 Patient Case MC is a 56 y.o. male with metastatic NSCLC with new bone metastasis, uncontrolled DM2, and HTN Reports continuous 8/10 generalized pain and 10/10 pain in his L hip which he reports is negatively affecting his ability to take care of his family Described sharp, aching, throbbing pain in his L hip, feels as if his feet are always on fire Current Pain Medications: Oxycodone ER 120 mg PO TID Oxycodone 80 mg PO Q3H prn Gabapentin 300 mg PO TID

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18 Treatment Options 18

19 Treatment options Transduction anti-inflammatories, local anesthetics Conduction opioids Transmission NMDA receptor antagonists, gabapentinoids, antiepileptics, opioids, lidocaine/mexilitine Perception NO DRUGS! THC may play a role here Cognitive behavioral therapy Modulation enhancing descending inhibitory pathway (opioids, TCAs, SNRIs, etc.)

20 Rational Polypharmacy Mechanism-Specific Treatment Multiple targets Brain Descending Inhibition (NE, 5HT) TCA SNRI Tramadol Opioids Peripheral Sensitization (Na + channels) PNS NSAIDs Opioids TCA Lidocaine Spinal Cord Central Sensitization (Ca 2+ channels, NMDA receptors) TCA Gabapentin Opioids 20

21 Medications Affecting Transduction Non-steroidal anti-inflammatories (NSAIDs) Local anesthetics topical lidocaine 21

22 Medications Affecting Conduction Opioids Full Mu Agonists Partial Mu Agonists Agonist/Antagonist Oxycodone Hydrocodone Buprenorphine Pentazocine Codeine Morphine Butorphanol Hydromorphone Fentanyl Nalbuphine Meperidine Tapentadol* Tramadol* Methadone** 22

23 Opioid Receptors Opioid Receptor Class Analgesic Effects Adverse Effects Mu 1 Supraspinal analgesia Euphoria, confusion, dizziness, nausea, low addiction potential Mu 2 Spinal analgesia Respiratory depression, cardiovascular and GI effects, miosis, urinary retention Delta Spinal analgesia Cardiovascular depression, decreased brain and myocardial oxygen demand Kappa Spinal analgesia Dysphoria, psychomimetic effects, feedback inhibition of endorphin system Global J. Pharmacol. 2009; 3(3):

24 Opioids Important to understand potency differences Fentanyl>hydromorphone>oxycodone>morphine/hydrocodone>codeine Side Effect Profile Nausea Vomiting Constipation Confusion Respiratory depression 24

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26 Medications Affecting Transmission NMDA antagonists Methadone Ketamine Anticonvulsants Sodium Channel Blockers Calcium Channel Blockers Lidocaine/mexilitine Opioids 26

27 NMDA Antagonists Methadone Unique pharmacokinetic profile Neuropathic or mixed pain Hyperalgesia/allodynia Ketamine Can decrease opioid requirement Neuropathic or mixed pain Hyperalgesia/allodynia 27

28 Anticonvulsants Medication Recommended Starting Dose Common Side Effects Gabapentin mg QHS Drowsiness, dizziness, edema, Pregabalin 25mg q12h fatigue Topiramate 200mg Q12H Weight loss, agitation, kidney stones, glaucoma Cabamazepine 50mg q12h Skin reactions, hepatotoxicity, hyponatremia, CNS depression Valproic Acid mg BID or Q8H Drowsiness, dizziness nausea, thrombocytopenia, flu-like symptoms, tremor

29 Lidocaine/mexilitine Sodium channel blockade If lidocaine is tolerated, can switch to oral mexilitine 29

30 Medications Affecting Modulation Tri-cyclic antidepressants (TCA) Serotonin and norepinephrine re-uptake inhibitor (SNRI) Opioids 30

31 TCA Medication Recommended starting dose Common Side Effects Amitriltyline 10mg QHS Anticholinergic, sedation, QT prolongation Nortriptyline 10mg QHS Anticholinergic, QT prolongation, sexual dysfunction 31

32 SNRI Medication Recommended starting dose Common Side Effects Venlafaxine 37.5mg daily Nausea. Insomnia or drowsiness Duloxetine 60mg daily Headache, drowsiness, fatigue, nausea 32

33 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 condition Other effects include Endocrine/metabolic, respiratory, musculoskeletal, gastrointestinal and immunologic

34 Barriers Practice Issue Barrier Failure to use more than medications Failure to target mechanism of pain Failure to treat neuropathic pain with adjuvants Reliance on short acting opioids Potential Problems Miss benefits of physical, behavioral and psychological therapies to help retrain the central nervous system Under-treated pain Increased nervous system hypersensitivity Under-treated pain Increased breakthrough, disturbed sleep Opioid tolerance 34

35 References 1. Pasero, C. & McCaffery, M. (2011). Pain Assessment and Pharmacologic Management. St. Louis: Elsevier/Mosby 2. International Association for the Study of Pain. IASP Pain Terminology Whitten CE, Donovan M, Cristobal K. Treating Chronic Pain: New Knowledge, More Choices 4. Backonja M. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA Dec 2;280(21): Benzon, H et al. (2011) Essentials of Pain Medicine: Third Edition. Philadelphia, PA: Elsevier Saunders. 6. Caraceni A. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group. J Clin Oncol Jul 15;22(14): Challapalli V. Systemic administration of local anesthetic agents to relieve neuropathic pain. Cochrane Database Syst Rev Oct 19;(4):CD Dworkin RH. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol Nov;60(11): Ferrini R, Paice JA. How to initiate and monitor infusional lidocaine for severe and/or neuropathic pain. J Support Oncol 2004;2: Finnerup NB. Pain. Algorithm for neuropathic pain treatment: an evidence based proposal Dec 5;118(3): Epub 2005 Oct Finnerup NB, Sindrup SH, JensenTS. The evidence for pharmacological treatment of neuropathic pain. Pain Sep; 150(3): Galer BS. Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study. J Pain Symptom Manage Sep;12(3): Galluzzi KE. Managing neuropathic pain. J Am Osteopath Assoc Nov;107(10 Suppl 6):ES Gilron I. Neuropathic pain: a practical guide for the clinician. CMAJ Aug 1;175(3): Mao J, Chen LL. Systemic lidocaine for neuropathic pain. Pain. 2000;87:7-17. Melissa Vyvey. Steroids as pain relief adjuvants. Can Fam Physician Dec; 56(12): Rowbotham M. Gabapentin for the Treatment of Postherpetic Neuralgia: A Randomized Controlled Trial. JAMA. 1998;280(21): Tauben D. Nonopioid Medications for Pain. Phys Med Rehabil Clin N Am. 2015:26; Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med Mar 16;140(6):