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

Opioids

Codeine 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 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—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/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 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.