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Formulary Analgesic Medications. Brian Erickson, MD Clinical Assistant Professor, Psychiatry, UVM FAHC Center for Pain Medicine Psychiatry Consultation Service Electroconvulsive Therapy UVM Program in Integrative Health. Acute Pain. Opioids. Codeine morphine Hydrocodone hydromorphone
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FormularyAnalgesicMedications • Brian Erickson, MD • Clinical Assistant Professor, Psychiatry, UVM • FAHC Center for Pain Medicine • Psychiatry Consultation Service • Electroconvulsive Therapy • UVM Program in Integrative Health
Opioids • Codeine morphine • Hydrocodone hydromorphone • Oxycodone oxymorphone • Fentanyl patch • Methadone • Levorphanol • Buprenorphine Freye, E. (2008). Opioids in Medicine: A comprehensive review on the mode of action and the use of analgesics in different clinical pain states. New York: Springer Publishing Co. Smith, H. (2009). Opioid metabolism. Mayo Clinic Proceedings,84(7), 613-624
Codeine “mild opioid” 130 mg = morphine 30 mg May be combined with Tylenol, Butalbital Available in 15, 30, 60 mg Max dose 60 mg q4hr (higher dose not more analgesia, more side effects Half-life 2.9 hr
Codeine • Metabolites: codeine-6-glucuronidate morphine (10%) • Renal excretion • Caution ultra-rapid metabolizers CYP2D6 convert to morphine more rapidly with increased effects • Caution alcohol, benzodiazepines,
Codeine—PracticeAgreement • “Universal Precautions” with opioids • Screen for history of substance abuse • Random drug screens • Lost/stolen scripts not refilled • One pharmacy • Involve family members • Document discussion of risks/benefits
CautionswithOpioids • May cause depression/mania • Constipation, sedation, nausea, myoclonus • Decrease testosterone levels • Methadone – metabolite long half-life; QRS • Opioid-Induced Hyperalgesia • Death – patient, others Krantz, M., Martin, J., Stimmel, B., Mehta, D. & Haigney, M. (2009). QTc interval screening in methadone treatment. Annals of Internal Medicine,150(6), 387-395. Tenant, F. (2009, Nov/Dec). Testosterone replacement in female chronic pain patients. Practical Pain Management. Webster, L. & Dove, B. (2007). Avoiding opioid abuse while managing pain. North Branch, MN: Sunrise River Press.
Ultram (tramadol) Non-opioid– affinity for mu-receptor 10x less than codeine Metabolite o-desmethyltramadol 200x greater affinity that tramadol Inhibits serotonin and norepinephrine re-uptake (similar but less than SNRI) Lower abuse potential than opioids
Tramadol • Available 50 mg tabs • Sustained Release 100mg,200mg,300mg • Dosage: 50 mg q 6hr prn • May use 50 mg qid • Max dose 100mg qid • Studied in osteoarthitis, back pain, others • Side effects: dizziness, nausea, constipation
Tramadol--warnings Seizure risk: reported in recommended dosage range, increased risk combined with TCA, SSRI, SNRI, opioids, MAO-I Serotonin Syndrome: other serotonergic drugs– triptans, neuromuscular activity,autonomic activity, altered mental status
Tramadol—warnings (cont) • Serotonin Syndrome management: --stop agents, iv hydration, consider cyproheptadine Suicide warning—class warning with antidepressants Caution with alcohol, CNS depressants • Pregnancy cat C
Neurontin (gabapentin) • Structure similar to GABA, no known direct activity on GABA receptor • Acts on alpha-2 sub-unit Calcium Channel receptor in spinal cord • Approved for Partial-Complex Seizure,Post-Herpetic Neuralgia, • Used for neuropathic pain, migraine, Fibromyalgia (similar to Lyrica), CRPS
Gabapentin May help anxiety Sleep: enhance slow-wave, help Fibro Not helpful in Bipolar D/O Half-life 5.9 hours Renal excretion, caution renal impairment Side effects: somnolence, peripheral edema, weight gain, cognitive effects
Gabapentin • Available 100mg, 300mg,600mg,800mg • Dosage 100mg hs • 100mg tid, increase by 100mg tid q 3days • Max 800mg two qid • Pregnancy cat C
Flexeril (cyclobenzaprine) Relieves muscle spasm of local origin without interfering with muscle function Not act at neuromuscular junction Mechanism of action unknown, thought to act at brainstem rather than spinal level Similar in structure and effect to tricyclic anti-depressants Half-life 3.2 hrs
Cyclobenzaprine Primarily renal excretion Some hepatic metabolism –caution p450 metabilism, CYP2D rapid metabolizers Caution with TCA, MAO-I Side effects anticholinergic: dry mouth, constipation, urinary retention, vision, cognitive, sedation Caution alcohol, CNS depressants
Cyclobenzaprine • Available 5mg, 10mg • Amrix(cyclobenzaprine extended release),15mg,30mg • Dosage 5mg tid to 10mg tid • Amrix 15mg to 30mg qd
Soma (carisoprodol) Muscle spams, low back pain Mechanism of action unknown Metabolized to meprobamate (carbamate, resembles barbituate) Side effects drowsiness, dizziness, headache, Caution porphyria Caution of CNS agent
Carisoprodol • Available 250mg, 350mg • Dosage 250mg hs • May use 250qid up to 350 qid • Concern for misuse, street value
Compounded Formulations • Topical, sublingual, rectal, nasal delivery avoid systemic side effects, metabolism problems • NSAID—ketoprofen • Neuropathic agents—amitriptyline, gabapentin • Muscle relaxants—MgCl, baclofen • Topical anesthetics—bupivicaine
Compounded formulations (cont) • Intranal Lidocaine—migraines • Rectal baclofen—spasms Naturopaths can’t use Schedule II presently Some insurances will pay for compounds
Adjuvants to Opioids(Nitric Oxide activity) • Oxytocin 10 units q3-6 hr • Helps mood, anxiety, sexual interest • Side effects – fluid retention, vasopressin (Kovacs, 1993) • L-Arginine 1000 mg bid Kovacs (1993). Role of oxytocin in neuroadaptation to drugs of abuse. Psychoneuroendocrinology,19(1), 85-117.