Non opioid Analgesics and Adjuvants migraine by mikeholy


									 Management Strategies for
Headache, Neuropathic Pain,
Back Pain, Fibromyalgia, and
      Myofascial Pain
    Nonpharmacologic Management
            of Headache
•   Diet
•   Exercise
•   Biofeedback/relaxation training
•   Acupuncture
•   Consistent sleep/wake cycles
      Biofeedback: Intervention
• Learning to influence physiologic
   – Electromyography
   – Galvanometry (electrodermal)
   – Temperature
• Shaping of behavior
• Typically includes training in relaxation
    Pharmacologic Management of
   Migraine: Prophylactic Therapies

• Indications
  – 3 headaches/mon with disability or
  – Lack of efficacy with symptomatic therapies
  – Presence of headache types with any risk for
    neurologic injury
• Therapy should be individualized
 Pharmacologic Management of
Headache: Prophylactic Therapies
• Proven types of prophylactic agents include:
    beta-blockers, antidepressants, calcium channel
    blockers, NSAIDs, anticonvulsants,
    methylsergide, and alpha-adrenergic agents
•   Other types of prophylactic agents that have
    been used but whose role has not been as clearly
    established include topiramate and botulinum
     Pharmacologic Management of
    Headache: Symptomatic Therapies
• Stratified, NOT step-care, approach!
• NSAIDs, combination therapies including
    acetaminophen/aspirin/caffeine, or butalbital
    combinations should be used for mild-to-moderate pain
•   Oral/parenteral triptans and dihydroergotamine should be
    used for severe migraine or for those individuals with
    less severe pain but who have not responded to other
•   REMEMBER: overuse of symptomatic therapies can lead
    to an analgesic rebound headache syndrome
Adjuvant Analgesics for Chronic Headache

 •   Beta blockers
 •   Anticonvulsants
 •   Calcium channel blockers
 •   Alpha-2 adrenergic agonists
 •   Antidepressants
 •   Vasoactive drugs
 •   ACE inhibitors
  Neuropathic Pain: Management
• Pharmacotherapy
   – Nonopioid
   – Opioid
   – Adjuvant analgesics
• Interventional
   – Neural blockade (eg, sympathetic nerve blocks)
   – Neurostimulatory techniques (eg, spinal cord
   – Intraspinal infusion
            Neuropathic Pain:
         Pharmacologic Therapies

• Gabapentin, carbamazepine, lamotrigine,
    and newer AEDs
•   Antidepressants
•   Opioid analgesics
•   Lidocaine (transdermal, intravenous [IV]),
•   Alpha-2 adrenergic agonists
Multipurpose Adjuvant Analgesics
Class                Examples
Antidepressants      amitriptyline, desipramine,
                     nortriptyline, duloxetine,
                     venlafaxine, paroxetine, others

Alpha-2 adrenergic   tizanidine, clonidine

Corticosteroids      prednisone, dexamethasone
Multipurpose Adjuvant Analgesics
• Best evidence: 30 amine TCAs (e.g., amitriptyline)
• 20 amine TCAs (desipramine, nortriptyline) better
    tolerated and also analgesic
•   Evidence for the SSNRIs, e.g., duloxetine, and
    little evidence in favor of SSRIs/atypical
    antidepressants (e.g., paroxetine, bupropion,
    others); these are better tolerated yet
Multipurpose Adjuvant Analgesics
Alpha-2 adrenergic agonists
• Clonidine and tizanidine used for chronic pain of
    any type
•   Tizanidine usually better tolerated
•   Tizanidine starting dose 1–2 mg/d; usual
    maximum dose up to 40 mg/d
Adjuvant Analgesics for Neuropathic Pain

   Class               Examples
   Anticonvulsants     gabapentin, pregabalin,
                       valproate, lamotrigine
                       phenytoin, carbamazepine,
                       clonazepam, topiramate,
                       tiagabine, levetiracetam
                       oxcarbazepine, zonisamide

   Local anesthetics   mexiletine, tocainide
Adjuvant Analgesics for Neuropathic Pain

 Class             Examples
 NMDA receptor     dextromethorphan,
  Antagonists      ketamine,

 Miscellaneous     baclofen, calcitonin

 Topical           lidocaine,
                   capsaicin, NSAIDs
Adjuvant Analgesics for Neuropathic Pain
 • Gabapentin or pregabalin commonly
   – Favorable safety profile and positive RCTs in
     PHN/diabetic neuropathy
 • Analgesic effects supported for
   phenytoin, carbamazepine, valproate,
   clonazepam, and lamotrigine
 • Limited experience with other drugs
Adjuvant Analgesics for Neuropathic Pain

 • Local anesthetics
 • Oral therapy with mexiletine, tocainide,
 • IV/SQ lidocaine also useful
 • Useful for any type of neuropathic pain
   Topical Adjuvant Analgesics
• Used for neuropathic pain
  – Local anesthetics
    • Lidocaine patch
    • Cream, eg, lidocaine 5%, EMLA
    • Capsaicin
• Used for musculoskeletal pains
    • NSAIDs
Adjuvant Analgesics for Neuropathic Pain

 Miscellaneous drugs
 • Calcitonin
   – RCTs in CRPS and phantom pain
   – Limited experience
 • Baclofen
   – RCT in trigeminal neuralgia
   – 30–200 mg/d or higher
   – Taper before discontinuation
Adjuvant Analgesics for Neuropathic Pain

 NMDA-receptor antagonists
 • N-methyl-D-aspartate receptor involved in
     neuropathic pain
 •   Commercially-available drugs are analgesic:
     ketamine, dextromethorpan, amantadine
       Adjuvant Analgesics With
          Opioid Interactions

• NMDA antagonists (eg, dextromethorphan,
  ketamine, amantadine)
• Cholecystokinin-B antagonists (eg,
• Ultra-low doses of opioid antagonists
  Neuropathic Pain: Management
• Rehabilitative approaches
• Psychologic interventions
             Sympathetic Block
• Diagnostic
   – Superior cervical (“stellate”) ganglion
   – Lumbar
   – Note need for (but insurers’ reluctance to pay for)
     placebo controls
• Therapeutic
   – CRPS of upper, lower extremity
   – Facial neuralgias
• Technique
   – Local anesthetic
   – Neurolytic
           Spinal Cord Stimulation
• Background: peripheral electrical stimulation for pain
    control since prehistory; recent “gate theory”
•   Retrospective, uncontrolled case series show that SCS
    can reduce intensity of neuropathic pain
•   Biases in existing literature (lack of blinding,
    heterogeneity of interventions/assessments, small
    numbers) confound its interpretation
•   Recent 6-month RCT: “with careful selection of patients
    and successful test stimulation, SCS is safe, reduces pain
    and improves HRQOL in chronic RSD” (Kemler MA, et al.
    N Engl J Med. 2000; N = 36)
        Implanted Pumps for Pain
• Spinal anesthesia ~100 y
• Selective spinal opioid analgesia ~25 y
• Early chronic use of opioid PCEA supplanted by
    intrathecal cannulation
•   Single agents: opioids, local anesthetics,
    NSAIDs, clonidine, cholinomimetics, calcium
    channel blockers, GABA-A and -B, peptides,
    NMDA antagonists, adenosine
•   Combinations: opioid-opioid, opioid-local
    anesthetic, morphine-clonidine…
     Management of Back Pain
• Comprehensive assessment of patients is
  essential to form the appropriate treatment
• In the majority of cases, pharmacologic
  treatment is the main approach.
     Management of Back Pain
• Pharmacologic agents
  – Opioid analgesics
  – Anti-inflammatories
  – Adjuvants and nonopioid analgesics
• Nonpharmacologic therapies
  – Rehabilitative
  – Interventional
 Management of Acute Back Pain
• Overall, 90% of patients will recover within
  2 months without need for any invasive
• The management of acute back pain
  without sciatica or neurologic deficits calls
  for a conservative approach with
  analgesics and no bed rest.
 Management of Acute Back Pain
• With sciatica and no neurologic deficits
  – Conservative management with analgesics
  – Bed rest for 2–3 d
  – Activities as tolerated
  – Neurologic consultation as needed
• With sciatica and positive neurologic deficit
  – Individualized length of rest
  – Analgesics
  – MRI study plus urgent neurologic or emergent
    neurosurgical evaluation, according to progression of
    deficits and symptoms
Nonsteroidal Anti-inflammatory Drugs
• Inhibition of cyclooxygenase activity
• COX-1 and COX-2 drugs
• Toxicity: Cardiovascular, gastrointestinal,
  renal, platelet aggregation
• Multiple drugs
• “Ceiling” dose effect
• Peripheral and central analgesic action
•   Minimal anti-inflammatory action
•   Central analgesia
•   No GI or platelet-aggregation toxicity
•   Serious dose-dependent hepatotoxicity
•   “Ceiling” dose effect
Disabling Back Pain: Opioid Therapy
• Consider opioid responsiveness
• Dosing: Short-acting plus long-acting or
    controlled-release opioid preparations
•   In-hospital dose titration for severe cases: IV
    PCA technique
•   Consider opioid rotation
•   Combine with physical therapy and other
•   Consider cost
Chronic Back Pain: Opioid Therapy
Combination products   Single-entity agents
• Codeine              • Fentanyl
• Oxycodone            • Levorphanol
• Hydrocodone          • Methadone
• Dihydrocodeine       • Morphine
                       • Oxycodone
                       • Oxymorphone
                       • Hydromorphone
                       • Tramadol
   Acute and Chronic Back Pain:
          Opioid Therapy
Short-acting opioids     Long-acting opioids
• Combination products   • Morphine CR
• Hydromorphone          • Oxycodone CR
• Morphine               • Fentanyl CR
• Oxycodone              • Methadone
• Oral transmucosal
  fentanyl               • Levorphanol
• Tramadol
Chronic Back Pain: Opioid Therapy
• Discuss
  –   Addiction
  –   Physical dependence
  –   Tolerance
  –   Side effects
    Nonopioid Adjuvant Analgesics
• Antidepressants
     – TCAs (nortriptyline, amitriptyline,
  –       SSRIs (paroxetine, sertraline, fluoxetine)
  –       SNRIs (duloxetine, venlafaxine)
• Alpha 2-adrenergic agonists
  – Tizanidine, clonidine
TCA = tricyclic antidepressant; SSRI = selective serotonin reuptake inhibitor
Nonopioid Adjuvant Analgesics
   Antiepileptics and antiarrhythmics

– Gabapentin             – Tiagabine
– Pregabalin             – Topiramate
– Carbamazepine          – Oxcarbazepine
– Clonazepam             – Zonisamide
– Valproate              – Mexiletine
– Lamotrigine
Rehabilitative Therapies for Back Pain
 •   Exercises for strength and flexibility
 •   Weight-control management
 •   Behavioral relaxation techniques
 •   Alternative medicine and physiatric
      Interventional Pain Medicine
          and Spinal Surgeries
•   Intrathecal infusion devices
•   Spinal cord stimulator
•   Percutaneous radiofrequency denervation
•   Neurolytic procedures
•   Diskectomy
•   Decompression (laminectomy, foraminotomy)
•   Spinal stabilization
•   Vertebroplasty
Paravertebral (Nerve Root) Injection
• Diagnostic
  – Establish or confirm anatomic mechanism of pain (eg,
    atypical dermatomal distribution in disk disease or
    multilevel foraminal stenosis)
• Therapeutic
  – Deposit local anesthetic plus glucocorticoid via
    paravertebral and/or transforaminal approach
• Technique
  – Fluoroscopy or CT essential to validate, document
    needle placement
  – Radiopaque contrast outlines/tracks root
             Epidural Injection (I)
• Employed for decades using various techniques,
    materials, and patients
    – Poor documentation of diagnosis, pain, technique,
• Limited RCT evidence of efficacy in
    subpopulations, but most reports are case series
•   Techniques (glucocorticoid + local anesthesic)
     – Translaminar
     – Transforaminal
     – Caudal (useful if prior lumbar surgery, scarring)
           Epidural Injection (II)
• Applied for symptomatic relief in
  – Disk protrusion with radiculopathy
  – Spinal stenosis (circumferential or foraminal)
  – Acute pain, local inflammation of vertebral fracture (
    subsequent vertebroplasty)
  – ? Acute herpes zoster, using local anesthetic alone
• May facilitate rehabilitation, avert surgery when
  applied within multidisciplinary framework
           Intra-Articular Injection
• Facet, large joints, sacroiliac most common
• Diagnostic
  – Clarify clinical impression of a “facet syndrome” or “SI
    joint pain”
  – (Facet:) simulate results of potential spinal fusion or
    denervation of medial branch of dorsal ramus
• Therapeutic (local anesthetic + glucocorticoid)
  – Reduce inflammation, pain
  – Increase mobility, facilitate rehabilitation
• Controversy as to efficacy and effectiveness
         Myofascial Pain Syndrome:
• Eliminate the trigger point
    – Trigger-point injections
•   Physical modalities
•   Biofeedback
•   Pharmacotherapy
•   Botulinum toxin
            Trigger-Point Injection I

• Essential criteria
  – Taut band palpable (if muscle accessible)
  – Exquisite spot tenderness of a nodule in a taut band
  – Pressure on tender nodule reproduces pain
  – Range of motion with stretch limited by pain
• Confirmatory observations
  – Visual or tactile identification of local twitch response
  – Local twitch response on needling tender nodule
  – Pain/hyperesthesia in recognized pattern
  – Activity in tender nodule on EMG
            Trigger-Point Injection I

• Essential criteria
  – Taut band palpable (if muscle accessible)
  – Exquisite spot tenderness of a nodule in a taut band
  – Pressure on tender nodule reproduces pain
  – Range of motion with stretch limited by pain
• Confirmatory observations
  – Visual or tactile identification of local twitch response
  – Local twitch response on needling tender nodule
  – Pain/hyperesthesia in recognized pattern
  – Activity in tender nodule on EMG
           Trigger-Point Injection II

• Trigger points may refer pain
   – Toward the periphery (eg, suboccipital, infraspinatus)
   – Proximally or medially (eg, biceps brachii)
   – Locally (eg, serratus posterior inferior)
• Techniques
   – Needle only (no injection)
   – Local anesthetic only
   – Local anesthetic + glucocorticoid (evidence?)
   – Botulinum toxin type A

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