Post on 21-May-2020
A Pain Management Primer for Pharmacists
Jessica Geiger-Hayes, PharmD, BCPS, CPE
Andrea Wetshtein, PharmD, BCPS, CPE
Objectives
• Discuss the differences between somatic, visceral, and neuropathic pain
• Design a treatment plan for the different modalities of pain
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. www.iasp-pain.org/terms-p.html
Whitten CE, Donovan M, Cristobal K. Treating Chronic Pain: New Knowledge, More Choices
What is Pain?
“Pain is whatever the person says it is”
-Margo McCaffery
Types
Acute vs Chronic
Nociceptive vs Neuropathic vs Mixed
American Pain Foundation: http://www.painfoundation.org/learn/publications/files/PainResourceGuide2009.pdf
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
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Nociception
Activation of peripheral nerve receptors by a noxious stimulus
Thermal
Chemical
Mechanical• Pressure• Stretch
Patient with Pain
PhysicalSymptoms
EmotionalPsychological
Problems
SocialConcerns
SpiritualExistential
Distress
Total Pain
How Pain Works4. Perception
3. Transmission
1. Transduction
Modulationhappens all along the way
Noxious Stimuli
2. Conduction
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
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
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Nociceptive Pain
Somatic PainSkin, soft tissue, bone• Easy to describe, localize
Visceral PainOrgans• Difficult to describe, localize
Described as…SharpAchingThrobbing
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. 2004.
Assessment
Precipitating and palliating factors, previous tx
Quality
Region and radiation
Severity
Temporal profile
U (you)• How does the pain affect the patient
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
Treatment Options
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Treatment options
Transduction – anti-inflammatories, local anesthetics
Conduction – opioids
Transmission –NMDA receptor antagonists, gabapentinoids, anti-epileptics, opioids, lidocaine/mexilitine
Perception – NO DRUGS!• THC may play a role here
• Cognitive behavioral therapy
Modulation – enhancing descending inhibitory pathway (opioids, TCAs, SNRIs, etc.)
Rational Polypharmacy
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Brain
Spinal Cord
PNS
Descending Inhibition(NE, 5HT)
Central Sensitization(Ca2+ channels, NMDA receptors)
Peripheral Sensitization (Na+ channels)
NSAIDsOpioidsTCALidocaine
TCAGabapentinOpioids
TCA SNRITramadolOpioids
Mechanism-Specific TreatmentMultiple targets…
Medications Affecting Transduction
Non-steroidal anti-inflammatories (NSAIDs)
Local anestheticstopical lidocaine
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Medications Affecting Conduction
• Opioids
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Full Mu Agonists Partial Mu Agonists
Agonist/Antagonist
Oxycodone Hydrocodone Buprenorphine Pentazocine
Codeine Morphine Butorphanol
Hydromorphone Fentanyl Nalbuphine
Meperidine Tramadol*
Tapentadol* Methadone**
Opioid ReceptorsOpioid Receptor
ClassAnalgesic Effects Adverse Effects
Mu1 Supraspinal analgesia Euphoria, confusion, dizziness, nausea, low addiction potential
Mu2 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):149-53.
Opioids
Important to understand potency differencesFentanyl>hydromorphone>oxycodone>morphine/hydrocodone>codeine
Side Effect ProfileNausea
Vomiting
Constipation
Confusion
Respiratory depression
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Medications Affecting Transmission
• NMDA antagonists• Methadone
• Ketamine
• Anticonvulsants• Sodium Channel Blockers
• Calcium Channel Blockers
• Lidocaine/mexilitine
• Opioids
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NMDA Antagonists
MethadoneUnique pharmacokinetic profileNeuropathic or mixed painHyperalgesia/allodynia
KetamineCan decrease opioid requirementNeuropathic or mixed painHyperalgesia/allodynia
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Anticonvulsants
Medication Recommended Starting Dose
Common Side Effects
Gabapentin 100-300mg QHS Drowsiness, dizziness, edema, fatigue
Pregabalin 25mg q12H
Topiramate 200mg Q12H Weight loss, agitation, kidneystones, glaucoma
Cabamazepine 50mg q12H Skin reactions, hepatotoxicity, hyponatremia, CNS depression
Valproic Acid 125-250mg BID or Q8H Drowsiness, dizziness nausea, thrombocytopenia, flu-like symptoms, tremor
Lidocaine/mexilitine
Sodium channel blockade
If lidocaine is tolerated, can switch to oral mexilitine
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Medications Affecting Modulation
Tri-cyclic antidepressants (TCA)
Serotonin and norepinephrine re-uptake inhibitor (SNRI)
Opioids
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TCA
Medication Recommended starting dose Common Side Effects
Amitriltyline 10mg QHS Anticholinergic, sedation, QT prolongation
Nortriptyline 10mg QHS Anticholinergic, QT prolongation, sexual dysfunction
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SNRI
Medication Recommended starting dose Common Side Effects
Venlafaxine 37.5mg daily Nausea. Insomnia or drowsiness
Duloxetine 60mg daily Headache, drowsiness, fatigue, nausea
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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
Barriers
Practice Issue Barrier Potential Problems
Failure to use more than medications Miss benefits of physical, behavioral and psychological therapies to help re-train the central nervous system
Failure to target mechanism of pain Under-treated pain
Failure to treat neuropathic pain with adjuvants
Increased nervous system hypersensitivityUnder-treated pain
Reliance on short acting opioids Increased breakthrough, disturbed sleepOpioid tolerance
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References
1. Pasero, C. & McCaffery, M. (2011). Pain Assessment and Pharmacologic Management. St. Louis: Elsevier/Mosby2. International Association for the Study of Pain. IASP Pain Terminology. www.iasp-pain.org/terms-p.html
3. 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. 1998 Dec 2;280(21):1831-6.
5. 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. 2004 Jul 15;22(14):2909-17.
7. Challapalli V. Systemic administration of local anesthetic agents to relieve neuropathic pain. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD003345.
8. Dworkin RH. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol. 2003 Nov;60(11):1524-34.
9. Ferrini R, Paice JA. How to initiate and monitor infusional lidocaine for severe and/or neuropathic pain. J Support Oncol 2004;2:90-94.
10. Finnerup NB. Pain. Algorithm for neuropathic pain treatment: an evidence based proposal. 2005 Dec 5;118(3):289-305. Epub 2005 Oct 6.
11. Finnerup NB, Sindrup SH, JensenTS. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010 Sep; 150(3):573-81.
12. Galer BS. Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study. J Pain Symptom Manage. 1996 Sep;12(3):161-7.
13. Galluzzi KE. Managing neuropathic pain. J Am Osteopath Assoc. 2007 Nov;107(10 Suppl 6):ES39-48.
14. Gilron I. Neuropathic pain: a practical guide for the clinician. CMAJ. 2006 Aug 1;175(3):265-75.
15. Mao J, Chen LL. Systemic lidocaine for neuropathic pain. Pain. 2000;87:7-17. Melissa Vyvey. Steroids as pain relief adjuvants. Can Fam Physician. 2010 Dec; 56(12): 1295–1297.
16. Rowbotham M. Gabapentin for the Treatment of Postherpetic Neuralgia: A Randomized Controlled Trial. JAMA. 1998;280(21):1837-1842.
17. Tauben D. Nonopioid Medications for Pain. Phys Med Rehabil Clin N Am. 2015:26;219–248.
18. Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med. 2004 Mar 16;140(6):441-51
19. www.med.ohio.gov
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