Formulary Analgesic Medications n Brian Erickson MD n

Formulary Analgesic Medications n Brian Erickson, MD n Clinical Assistant Professor, Psychiatry, UVM n FAHC Center for Pain Medicine n Psychiatry Consultation Service n Electroconvulsive Therapy n UVM Program in Integrative Health

Acute Pain

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 q 4 hr (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 CYP 2 D 6 convert to morphine more rapidly with increased effects Caution alcohol, benzodiazepines,

Codeine—Practice Agreement “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

Cautions with Opioids 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 10 x less than codeine Metabolite o-desmethyltramadol 200 x greater affinity that tramadol Inhibits serotonin and norepinephrine reuptake (similar but less than SNRI) Lower abuse potential than opioids

Tramadol • Available 50 mg tabs • Sustained Release 100 mg, 200 mg, 300 mg • Dosage: 50 mg q 6 hr prn • May use 50 mg qid • Max dose 100 mg 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 100 mg, 300 mg, 600 mg, 800 mg • Dosage 100 mg hs • 100 mg tid, increase by 100 mg tid q 3 days • Max 800 mg 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 p 450 metabilism, CYP 2 D rapid metabolizers Caution with TCA, MAO-I Side effects anticholinergic: dry mouth, constipation, urinary retention, vision, cognitive, sedation Caution alcohol, CNS depressants

Cyclobenzaprine Available 5 mg, 10 mg Amrix(cyclobenzaprine extended release), 15 mg, 30 mg Dosage 5 mg tid to 10 mg tid Amrix 15 mg to 30 mg 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 250 mg, 350 mg Dosage 250 mg hs May use 250 qid 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—Mg. Cl, 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 q 3 -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.