Pharmacotherapy

• Indications for opioids


  • Acute trauma, postsurgical pain
  • Severe, uncontrolled pain
  • Grey area
• Contraindications for opioids


  • Patients with addiction/abuse history or risk
  • Uncomplicated arthritis
  • "Back pain"
  • Chronic pain - not effective; produces dependence
• Notable side effects of opioids


  • Respiratory depression and death, hypogonadism/low testosterone
  • Do NOT combine with benzodiazepines, as this may cause respiratory depression and death
• Acetaminophen


  Works by inhibiting prostaglandin production (COX enzyme) in the CNS, thus inhibiting pain and fevers centrally
• Acetaminophen dosage


  500-1000 mg ONCE-QID (total max daily dose of 3 or 4g, depending on setting)
• Acetaminophen dose is limited by potential hepatotoxicity
• NSAIDs


  Work by inhibiting COX-1-and/or-COX-2 enzyme, thus reducing inflammation and inflammatory pain
• COX-1


  Produces prostaglandins that protect the stomach lining
• NSAIDs reduce these protective prostaglandins and cause gastric ulcers
• Meloxicam and celecoxib have been developed to act more selectively on COX-2, thus protecting the stomach (theoretically)
• Conditions NSAIDs are effective for


  • Tendonitis, bursitis, arthritis, tenosynovitis, tension headaches, myofascial pain
• It is not advisable to use NSAIDs chronically, due to risk of gastric ulcers and renal disease
• NSAIDs are contraindicated if history/presence of gastric ulcer or AKI/CKD
• Sometimes we ask patients to hold NSAIDs prior to interventional procedures so that proper healing and pro-inflammatory response can take place postprocedurally
• Topical fentanyl


  Patch form discussed in opioids section
• Topical lidocaine gel


  • Comes in various % concentrations, usually 2%
  • Useful for bowel and bladder care in SCI patients
  • Thin spread TOPICALLY BID-TID PRN
• Topical lidocaine patch


  • Comes in various % concentrations, usually (4-5%)
  • Useful for MSK pain, especially neck, back, and shoulder pain; can be cut and divided
  • 1 patch TOPICALLY DAILY
• Don't forget ice and heat!
• Morphine


  • Short or long-acting pain control
  • Acute pain: 5-10 mg PO Q4H PRN
  • Chronic/long-acting pain control: extended-release morphine: 15-60 mg PO Q12H
• Oxycodone


  • Short-acting pain control (sometimes long-acting)
  • Acute pain: 2.5/5/10 mg PO Q4-6H PRN
• Fentanyl


  • Long-acting pain control
  • Acute pain: 25-200 mcg TRANSDERMAL Q72H
• Hydromorphone


  • Short-acting pain control
  • Acute pain: 2 mg PO Q4-6H PRN
• Codeine


  • Short-acting pain control
  • Useful for aborting intractable tension headaches, especially in neurologic disease (stroke)
  • Acute pain: 15-30 mg PO Q4H PRN
• Tramadol


  • Sort of a "step down" from opioids
  • Mu agonist and serotonin-norepinephrine reuptake inhibitor
  • Milder pain medication than most opioids
  • Can cause sedation
  • 25-100 mg PO Q4-6H PRN
• Amitriptyline


  • TCA that inhibits reuptake of serotonin and norepinephrine in the CNS
  • Has antidepressant and anti-neuropathic pain properties
  • Can prolong the QT interval
  • Anticholinergic side effects
  • Can contribute to serotonin syndrome
  • 25-200 mg PO QHS (QHS as it can cause somnolence)
• Gabapentin


  • Blocks L-type Ca2+ channels in the CNS (originally developed as an antiseizure medication)
  • Inhibits synaptic transmission
  • Can cause somnolence, mood stabilization (useful for TBI/mood disorder)
  • 100-1200 mg PO DAILY-TID (900 mg PO QID also possible) (3600 mg maximum daily dose)
• Pregabalin


  • Same mechanism as gabapentin
  • FDA-approved for diabetic neuropathic pain, postherpetic neuralgia, fibromyalgia
• Duloxetine


  • Serotonin-norepinephrine reuptake inhibitor (SNRI)
  • Has both antidepressant and antineuropathic pain properties
  • FDA-approved for diabetic peripheral neuropathic pain and fibromyalgia
  • Useful in mood disorder patients (eg depression) with neuropathic pain
  • 30-60 mg PO DAILY
• Venlafaxine


  • SNRI
  • Similar indications and effects as duloxetine
  • 25 mg PO TID (IMMEDIATE RELEASE) / 375-75-150 mg PO DAILY (EXTENDED RELEASE)
• Carbamazepine


  • Inhibits Na* channels on neurons, thus preventing signal transmission along nerves
  • Useful for trigeminal neuralgia in particular
  • Also useful as a mood stabilizer (TBI patients)
  • 100-200 mg PO BID-QID
• Injectable anesthetic +/- steroid

  • Useful for peripheral nerve-related neuropathic pain
  • The anesthetic works by inhibiting pain fiber sodium channels
  • The steroid works by inhibiting PLA2, thus inhibiting production of arachidonic acid, and by direct neuronal membrane inhibition, thus inhibiting pain fiber signal transmission
• Capsaicin


  • Hot pepper chemical that depletes substance P (substance P helps transmit pain signals)
  • Topical capsaicin is useful for intractable neuropathic pain over a small area (eg. hand)
  • Apply smallest amount necessary to cover the affected area 1-4 times DAILY
• Baclofen


  • Centrally acting GABAβ agonist
  • Inhibits synaptic transmission and the firing of neurons
  • Side effects: sedation, respiratory depression, lower seizure threshold
  • Withdrawal risk: patient becomes "itchy, bitchy, and twitchy"
  • Clearance: renally cleared, so use lower doses in patients with CKD or select another agent
  • Dose: usually start 5 mg PO QHS, titrating up to 20-30 mg TID
• Tizanidine


  • Side effects: sedation, respiratory depression, lower seizure threshold
  • Withdrawal: HTN, tachycardia, anxiety, worsened spasticity
  • Clearance: hepatically cleared, so check LFTs prior to dosing, and monitor ix per week for several weeks to ensure stability before spreading LFTs out over time
  • Dose: usually start 2 mg PO QHS, then increase up to 12 mg TID (36 mg/day)
• Dantrolene


  • Peripherally acting, binds to the ryanodine receptor on the sarcoplasmic reticulum in muscle cells, which then inhibits the influx of Ca2+ from the sarcoplasmic reticulum into the cell
  • No Ca2+ means the muscle can't contract
  • Side effects: sedation, weakness
  • Withdrawal: worsened spasticity
  • Clearance: hepatically cleared, so check LFTs prior to dosing, and monitor Ix per week for several weeks to ensure stability before spreading LFTs out over time
  • Dosing: start 25 mg PO BID, titrating up to 400 mg/day (BID or TID dosing)
• Botulinum toxin injections


  • Inhibit the presynaptic syntaxin, synaptobrevin, and SNAP-25 proteins which are full of neurotransmitters about to be released into the synapse
  • By cleaving these proteins, the toxin prevents neurotransmitter (ACh) from being released
  • This process is called chemodenervation
  • Thus, neurons can't fire, muscles can't contract, and you are paralyzed
  • By focally injecting this into select muscles, we can locally paralyze individual muscles, such as those that are too spastic
  • Black box warning of distant toxin spread, which may cause dysphagia, respiratory depression, so use with caution with existing motor neuron disease such as ALS
  • "3 days, 3 weeks, 3 months" (onset, peak, duration of action)
  • Botulinum toxin is especially useful if you want to avoid systemic medications with systemic side effects
  • Dose: many brands exist, and the dosage per muscle depends on the brand, size of the muscle, degree of spasticity in each muscle, and risk factors for dysphagia and side effects
• Corticosteroids


  • Perform direct inhibition of pain fiber neuronal membranes and inhibit PLA2 enzyme so decrease arachidonic acid and inflammatory mediator production, thereby reducing inflammatory pain mediators
  • Useful for more long-lasting pain relief (aim for 2-3 months of relief)
  • Side effects: hyperglycemia, osteoporosis, metabolic syndrome, thin skin, hypopigmentation of skin
  • Methylprednisolone, triamcinolone, dexamethasone
• Platelet-rich plasma (PRP)


  • Generated when a patient's blood is drawn, spun in the centrifuge machine, and the platelet-rich layer is drawn up into a syringe
  • Out-of-pocket expense in America ($500-1000 per blood draw)
  • Data are gradually being generated demonstrating its utility in regenerating cartilage and repairing partially torn or diseased tendons and ligaments
  • Sometimes used in combination with other regenerative techniques such as percutaneous needle tenotomy or tendon scraping procedures for tendonosis
• Prolotherapy


  • Dextrose is diluted down to a 25% dextrose solution (diluted using sterile water/normal saline/local anesthetic) and injected into damaged tissue (joint, tendon, ligament, over cartilage or labrum)
  • Out-of-pocket expense in America (approximately $125 per injection)
  • Cheaper than PRP
  • Also used in combination with other regenerative procedures