Brian Erickson, MD Clinical Assistant Professor,

Psychiatry, UVM FAHC Center for Pain

Medicine Psychiatry Consultation

Service Electroconvulsive Therapy UVM Program in Integrative

Health

Formulary Analgesic

Medications

Acute Pain

OpioidsCodeine morphineHydrocodone hydromorphoneOxycodone oxymorphone Fentanyl patchMethadoneLevorphanolBuprenorphine

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 mgMay be combined with Tylenol, ButalbitalAvailable in 15, 30, 60 mgMax dose 60 mg q4hr (higher dose not more analgesia, more side effectsHalf-life 2.9 hr

CodeineMetabolites: codeine-6-glucuronidate morphine (10%)Renal excretionCaution ultra-rapid metabolizers CYP2D6 convert to morphine more rapidly with increased effectsCaution alcohol, benzodiazepines,

Codeine—Practice Agreement

“Universal Precautions” with opioidsScreen for history of substance abuseRandom drug screensLost/stolen scripts not refilledOne pharmacyInvolve family membersDocument discussion of risks/benefits

Cautions with OpioidsMay cause depression/maniaConstipation, sedation, nausea, myoclonusDecrease testosterone levelsMethadone – metabolite long half-life; QRSOpioid-Induced HyperalgesiaDeath – 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 codeineMetabolite o-desmethyltramadol 200x greater affinity that tramadolInhibits 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-ISerotonin 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 depressantsPregnancy cat C

Neurontin (gabapentin)

Structure similar to GABA, no known direct activity on GABA receptorActs on alpha-2 sub-unit Calcium Channel receptor in spinal cordApproved for Partial-Complex Seizure,Post-Herpetic Neuralgia, Used for neuropathic pain, migraine, Fibromyalgia (similar to Lyrica), CRPS

GabapentinMay help anxietySleep: enhance slow-wave, help FibroNot helpful in Bipolar D/OHalf-life 5.9 hoursRenal excretion, caution renal impairmentSide 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 functionNot act at neuromuscular junctionMechanism of action unknown, thought to act at brainstem rather than spinal levelSimilar in structure and effect to tricyclic anti-depressantsHalf-life 3.2 hrs

CyclobenzaprinePrimarily renal excretionSome hepatic metabolism –caution p450 metabilism, CYP2D rapid metabolizersCaution with TCA, MAO-ISide effects anticholinergic: dry mouth, constipation, urinary retention, vision, cognitive, sedationCaution alcohol, CNS depressants

CyclobenzaprineAvailable 5mg, 10mgAmrix(cyclobenzaprine extended release),15mg,30mgDosage 5mg tid to 10mg tidAmrix 15mg to 30mg qd

Soma (carisoprodol)Muscle spams, low back painMechanism of action unknownMetabolized to meprobamate (carbamate, resembles barbituate)Side effects drowsiness, dizziness, headache,Caution porphyriaCaution of CNS agent

CarisoprodolAvailable 250mg, 350mgDosage 250mg hsMay use 250qid up to 350 qid

Concern for misuse, street value

Compounded Formulations

Topical, sublingual, rectal, nasal delivery avoid systemic side effects, metabolism problemsNSAID—ketoprofenNeuropathic agents—amitriptyline, gabapentinMuscle relaxants—MgCl, baclofenTopical anesthetics—bupivicaine

Compounded formulations (cont)

Intranal Lidocaine—migrainesRectal 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.