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Rational Polypharmacy for Pain

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Rational Polypharmacy for Pain Rational Polypharmacy for the Treatment of Pain Theresa Mallick-Searle, MS, ANP-BC O5 Disclosures Speakers Bureau: Allergan, Lilly, Salix Rational Polypharmacy for the Treatment of Pain Any unlabeled/unapproved uses of drugs or products referenced will be disclosed. Theresa Mallick-Searle, MS, ANP-BC Stanford Health Care, Division Pain Medicine [email protected] @tmallic https://www.linkedin.com/in/theresa-mallick-searle Confidential – For Discussion Purposes Only Objectives clinical indications, contraindications & Explore dosing for common non-opioid analgesics. Describe where analgesics act in the pain pathway. use of medication assisted therapy (MAT) Evaluate in pain management. Confidential – For Discussion Purposes Only Confidential – For Discussion Purposes Only What is Pain? Chronic Pain: Not Simply Acute Pain Lasting Longer “An unpleasant sensory & emotional experience associated with, or resembling that associated with, actual or potential tissue damage.” International Association for Study of Pain (2020) “Pain is a complicated process that involves an intricate interplay of chemicals and signaling on the central nervous system.” Sean Mackey, MD “Whatever the experiencing person says it is, existing whenever he/she says it does.” McCaffery, RN Confidential – For Discussion Purposes Only Confidential – For Discussion Purposes Only 1 Rational Polypharmacy for the Treatment of Pain Theresa Mallick-Searle, MS, ANP-BC O5 Pain Types Categorized by Predominant Etiology The Neuromechanisms of Pain •Fibromyalgia •Restless legs syndrome Peripheral Pain •Interstitial cystitis •Headaches Modulators: •Temporomandibular joint disorder • Histamines • Prostaglandins • Cytokines • Musculoskeletal pain • Bradykinin Sensory • Substance P ►Osteoarthritis and gout Hypersensitivity •Postherpetic neuralgia • Others ►Neck and back pain with / Nociplastic •Diabetic peripheral structural pathology neuropathy Descending ►Rheumatoid arthritis Mixed •Spinal stenosis Neurotransmitters: • Tumor-related • Serotonin •Spinal cord injury nociceptive pain Nociceptive Neuropathic • Norepinephrine •Chemo-induced neuropathy • Endogenous opiates • Others •Back pain • Osteoarthritis • Fibromyalgia •Malignancy pain • Rheumatoid arthritis Confidential7 – For Discussion Purposes Only Confidential – For Discussion Purposes Only MEDICATIONS FOR PERIPHERALLY MEDIATED Non-opioid Analgesics VERSUS CENTRALLY MEDIATED PAIN • Anticonvulsants Cannabinoids • Antidepressants Other: Peripherally Centrally Mediated Pain: Mediated Pain: • Muscle relaxants − Opioid agonist/antagonists • Topical − Tramadol • Acetaminophen • Alpha-2 agonists analgesics/anesthetics • Antihistamines • Anticonvulsants − Buprenorphine • Ca+ channel • NSAIDs • Acetaminophen/NSAIDs − low-dose naltrexone (LDN) • Opioids antagonists mABs (calcitonin gene related • Topical • NMDA • Other adjuvants - sleep peptide – CGRP). anesthetics • Opioids aids, benzodiazepines • TCA/SNRI antidepressants Other – supplements/nutraceuticals Confidential – For Discussion Purposes Only Confidential – For Discussion Purposes Only Polling Question Anticonvulsants Rational Polypharmacy is? First-line therapy in neuropathic/central pain syndromes. a) The best way to justify your The peripheral hyper-excitability is due to a series of use of opioids when the DEA molecular changes at the level of the peripheral nociceptor, agent comes knocking. in dorsal root ganglia, in the dorsal horn of the spinal cord, and in the brain. b) A way to safely and effectively use medications that make sense together in the These changes include: treatment of pain. Abnormal expression of sodium channels c) Part of a multimodal treatment . Increased activity at glutamate receptor sites approach to pain management. Changes in gamma-aminobutyric acid inhibition (GABA-ergic) d) A tag phrase unique to . Alteration of calcium/sodium influx into cells PAINWeek. Confidential – For Discussion Purposes Only Confidential – For Discussion Purposes Only 2 Rational Polypharmacy for the Treatment of Pain Theresa Mallick-Searle, MS, ANP-BC O5 GENERIC USES IN PAIN DOSING CONSIDERATIONS GENERIC (BRAND) USES IN PAIN DOSING CONSIDERATIONS (BRAND) NAMES NAMES gabapentin • Diabetic 600-3600 mg/d- - Sedating, weight gain, peripheral oxcarbazepine Neuropathies 600-2400 mg/d- - Serious dermatological reactions peripheral TID dosing edema, mood instability. (central/peripheral) BID dosing (Stevens-Johnson syndrome). (Neurontin) neuropathy - Growing recreational use. (Trileptal) Similar to - Mood changes, aplastic anemia, • Fibromyalgia - Renal excreted (100% carbamazepine thrombocytopenia, • Post-herpetic unchanged). hypernatremia, monitor -BUN/Cr, neuralgia - Calcium channel modulator CBC w/diff, LFTs. • Other - Sodium channel modulator neuropathies • Restless leg • Headache topiramate Migraine 50-200 mg/d- - Weight loss, cognitive BID dosing dysfunction, renal dosing. (Topamax) - Sodium channel modulator, GABA Same as gabapentin 150-600 mg/d- - Similar to gabapentin (schedule pregabalin agonist, glutamate receptor (less likely in TID dosing V controlled substance, renal antagonist (Lyrica) restless leg or excreted 90% unchanged). headache) - Calcium channel modulator Trigeminal neuralgia 200-1200 mg/d- - Serious dermatological reactions lamotrigine Neuropathies 100-400 mg/d- - Serious dermatological reactions carbamazepine (central/peripheral) BID dosing (Stevens-Johnson syndrome), BID dosing (Stevens-Johnson syndrome). (Lamictal) (Tegretol) - Mood changes, aplastic anemia, - Caution in liver or renal thrombocytopenia, monitor - dysfunction. BUN/Cr, CBC w/diff, LFTs. - Sodium channel modulator, - Sodium channel modulator, decreases presynaptic glutamate GABA receptor agonist, serotonin & aspartate release releasing properties Confidential – For Discussion Purposes Only Confidential – For Discussion Purposes Only Anticonvulsants Anticonvulsants Studied double-blinded, placebo-controlled trials. Neurocognitive . All anticonvulsants appear to have some neurocognitive effects. Pearls: Baseline CBC, CMP, EKG, drug specifics, start low- . Psychomotor reaction time, word finding, memory. go slow, wean off, patient education. Bone disease Suicidality . Increased risk of bone fracture remains unclear, r/t ↑catabolism of Vit. D & FDA analysis of data from 199 clinical trials of 11 ↑PTH, intestinal Ca absorption inhibition, osteoclastic bone resorption stimulation. anticonvulsants showed a risk of suicidal thoughts or behaviors. General risk factors – Female, post-menopausal, Caucasian & Asian, old age, tobacco use, low BMI, low Ca and Vit. D intake. Dermatologic . AED related risk factors – High dose, multiple drug regimens, duration of therapy, chronic illnesses, metabolic acidosis. Stevens-Johnson syndrome, toxic epidermal necrolysis, 90% of cases occur within first 60 days, dose dependent, HLA B*1502 testing recommended (Asian ancestry). Confidential – For Discussion Purposes Only Confidential – For Discussion Purposes Only Antidepressants Antidepressants Co-analgesics in neuropathic/central pain syndromes. Antidepressants may also exert adjunctive therapeutic influences through histamine The explicit way in which antidepressants are effective in pain receptors as well as modulation of sodium management remains unknown, suspected to be channels. multifactorial. Modulate mood and pain perception. Most popular theory is that antidepressants exert their effects on serotonin & norepinephrine, particularly along the descending spinal pain pathways. Confidential – For Discussion Purposes Only Confidential – For Discussion Purposes Only 3 Rational Polypharmacy for the Treatment of Pain Theresa Mallick-Searle, MS, ANP-BC O5 GENERIC (BRAND) CLASS DOSING CONSIDERATIONS GENERIC (BRAND) CLASS DOSING CONSIDERATIONS NAMES NAMES amitriptyline Tricyclic 25-150 mg/d - Uses: DPN, PHN, FM, duloxetine (Cymbalta) Serotonin norepinephrine 60-120 mg/d - Uses: FM, chronic antidepressant (TCA) Once daily dosing migraine. reuptake inhibitors (SNRI) Once daily musculoskeletal (MSK) (tertiary amine) - Anticholinergic symptoms, dosing pain. arrhythmias. - Renal dosing & hepatic - Inhibits serotonin & milnacipran (Savella) 25-200 mg/d- considerations. norepinephrine uptake BID dosing - Similar in terms of efficacy, equally. pharmacodynamics & side effects profile. nortriptyline TCA 25-150 mg/d - Similar to amitriptyline, - Inhibits norepinephrine and (secondary amine) Once daily dosing less sedating. serotonin reuptake in CNS. (Pamelor) - More potent inhibitor of noradrenaline than of serotonin uptake. - Predictable therapeutic window (60-200 ng/ml). venlafaxine SNRIs 75-300 mg/d- - Uses: generalized BID dosing neuropathic pain, Migraine. desipramine TCA 25-300 mg/d - Uses & SE profile similar to - Renal & hepatic dosing (secondary amine) Once daily dosing above, less sedating, more desvenlafaxine (Pristiq) venlafaxine is metabolized 50-100 mg/d adjustments. (Norpramin) activating. to desvenlafaxine Once daily - May effect bleeding time. - Less predictable dosing - Similar in terms of efficacy, therapeutic window (100- pharmacodynamics & side 300 ng/ml). effects profile. - Inhibits reuptake of - Inhibits norepinephrine, serotonin & serotonin & dopamine norepinephrine. reuptake in CNS. - Superior efficacy than amitriptyline. Confidential – For Discussion Purposes Only Confidential – For Discussion Purposes Only Antidepressants Antidepressants Studied double-blinded, placebo controlled trials Cardiovascular Risk: Greater with TCAs duloxetine – FM/DPN/chronic MSK Tachycardia
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