Pharmacological treatment of Pain None Disclosures and Conflict of Interest Dr John F. Flannery Medical Director MSK and Multisystem Rehab Program PMR - FRCPC Objectives At the end of this presentation participants will be able to: List the various pharmacological options for the management of non-cancer pain Describe the main indications and contra-indications of each group of drugs Recall the rationale for choosing a drug based on: 1. The WHO pain ladder adapted for non-cancer pain 2. The 2014 Canadian Pain Society Guideline for pharmacological management of Chronic Neuropathic Pain Case 1 Brittany, 39 yr. old, waitress at a local high-end restaurant 5 months: insidious onset of right shoulder pain, no PHx trauma/dislocation, gradual increase in shoulder pain with overhead activities having increasing difficulties at work ROM preserved, pain with humerus in forward-flexed and internally rotated position Case 1 Think about the? s on the left Case 2 Case 2 Carbamazepine Giuseppe (Joe), 78, retired, DM type 2 for 16 years 5 years numbness of both feet in stocking distribution 6 months of burning, pins and needles, tingling, electric shock like feelings, and hypersensitivity to touch in both hands Impaired fine hand coordination and difficulty with tasks such as opening jars or turning keys Mild cognitive impairment, hypertension, Coronary disease, MI x2, Cr = 140 μmol/litre, benign prostate hypertrophy 1
Case 2 Think about the? s on the left Types of Pain In this lecture, we will focus on: Carbamazepine Nociceptive pain (e.g. shoulder bursitis) Neuropathic pain (e.g. painful diabetic neuropathy) Chronic pain syndrome (e.g. fibromyalgia) What s on the Menu and What are Today's Features and Specials! The Menu Pharmacological Options Non-acidic antipyretic analgesics (e.g. acetaminophen) Acidic antipyretic antiinflammatory analgesics, or non-steroidal antiinflammatory drugs (NSAIDs) Selective Cox-2 inhibitor antiinflammatory Muscle relaxants Antidepressant analgesics Anticonvulsant medications in neuropathic pain Opioids Cannabinoids (e.g. nabilone, medical marijuana) Local anesthetics (e.g. lidocaine patch/injections) Topical analgesics (e.g. capsaicin cream) Steroids Non-acidic antipyretic analgesics (e.g. acetaminophen) Acidic antipyretic antiinflammatory analgesics, or non-steroidal antiinflammatory drugs (NSAIDs) Selective Cox-2 inhibitor antiinflammatory Muscle relaxants Antidepressant analgesics Today s Features Anticonvulsant medications in neuropathic pain Opioids Cannabinoids (e.g. nabilone, medical marijuana) Local anesthetics (e.g. lidocaine patch/injections) Topical analgesics (e.g. capsaicin cream) Steroids Outcome of Goals Vague, Unquantifiable, Irrelevant, Impossible & Untimely Goals leave: Anxiety Uncertainty SMART Goals allow for commitment regarding Decisions Trust Collaboration 2
What is the intention of Tx? The Underlying Intention of Effective Goal Setting Why? How to measure? Trust Rapport Collaboration Goals Don t Do: Homer type Goals DDOOOHHH! Vague Unquantifiable Impossible Irrelevant No time frame SMART Goals Do : SMART Goals S - Specific M Measurable A Attainable/Achievable R Relevant T Time Based (Paracetamol) Indirect inhibitor of cyclooxygenase (in the brain, not peripherically) Excellent antipyretic Lack of serious adverse effects (provided that dose limit is observed). Hepatotoxicity in adults with chronic use >3.2g/day. Careful in elderly and concomitant use of alcohol Combinations: codeine, tramadol, oxycodone Non-steroidal Anti-inflammatory drugs (NSAIDs - Cox1 and Cox 2) All NSAIDs (selective and non-selective) may increase the risk of myocardial infarction and stroke (Bresalier et al 2005). No clear evidence that one is superior Analgesic potency equal to opiates (2-3/10) is least expensive Fluid retention, HTN, renal failure, asthma Risk of GI bleed lowered with PPI, COX-2 Beware if CVD, HTN, liver or kidney disease. APAP: N-acetyl-para-aminopherol 3
NSAIDs Facts Muscle relaxants Fast elimination (1-4 hours) Elimination Low potency High potency Salicylates: aspirin and salicylic acid, Ketoprofen, Diclofenac, Indomethacin, Ketorolac Muscle relaxants Antispasmodics Nonbenzodiazepines: e.g. cyclobenzaprine methocarbamol Benzodiazepines: e.g. diazepam Intermediate elimination (8-12 hours) Slow elimination (12-36 hours) Diflunisal Naproxen Meloxicam, Piroxicam Antispasticity drugs e.g. baclofen, dantrolene botulinum toxin Benzodiazepines have no effect on pain, do not consolidate sleep, can lead to falls, depression, anxiety, & addiction. Antidepressants: Mechanism of Action Analgesic effects independent of antidepressant action Pain inhibiting systems: (S) serotonergic and (N) noradrenergic effects from the brain stem onto the dorsal horn of the spinal cord Tricyclic antidepressants (TCAs): High dose treats depression (200-300 mg/d); Low dose treats sleep cycle disturbance (10-150 mg), consolidates stage IV sleep Antidepressants: Types Tricyclic antidepressants (TCAs): amitriptyline, nortriptyline, Tetracyclic antidepressants: trazodone Selective Serotonin Reuptake Inhibitors (SSRIs): citalopram, paroxetine, fluoxetine Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): venlafaxine and duloxetine Main indications: Antidepressants: Indication Relief of neuropathic pain symptoms: stabbing pain, steady pain and skin sensitivity. approved for fibromyalgia and chronic lowback pain Trazodone (a tetracyclic antidepressant) helps sleep cycle but no evidence for pain. Antidepressants: Contra indications Contra-indications: glaucoma, prostate hypertrophy, prolongation of QT interval, liver function impairment, Contraindication of duloxetine if CrCl < 30 ml/min 4
Anticonvulsants: Mechanism of Action Anticonvulsants: Indication and Types Both epilepsy and neuropathic pain are associated with excess neuronal activity (uncontrolled electrical discharge) Voltage-gated Sodium Channel Blockers: phenytoin, carbamazepine, lamotrigine, topiramate, valproic acid. Non voltage-gated sodium channel blockers: gabapentin and pregabalin (structural analogues of GABA) but exact mechanism of analgesia is unknown presumably modulation of calcium channels. Use: trigeminal neuralgia (carbamazepine), postherpetic neuralgia, painful diabetic neuropathy, post-stroke pain, HIV neuropathy, pain post spinal cord injury, complex regional pain syndrome (CRPS), phantom limb pain : pain reduction is modest (<1/10), helps 15% over placebo benefits and harms are about the same at higher cost than gabapentin. Approved for fibromyalgia Anticonvulsants: Contra-indications Contra-indications: Carbamazepine: hepatotoxicity, AV heart block : kidney problems Choosing an Analgesic Issues to consider Type of pain (anticipated NHx, progressing or regressing) Severity and pattern of pain (level of interference in function, ranking of pain level.) Patient characteristics (what risk factors exist) Patient Choice (which do they think would be helpful) Type of pain Choosing an Analgesic Acute/Chronic; acute on chronic; breakthrough Nociceptive/Neuropathic/Mixed/ Fibromyalgia Nociceptive: muscle, bone, inflammatory, tendinitis Severity and pattern of pain Mild/Moderate/Severe Constant/Intermittent Patient characteristics Liver/Kidney function, allergies, previous experience Sleep abnormality Mood disorder Co-morbidities Risk of opioid overdose (e.g. COPD) or addiction WHO Analgesic Ladder Non-opioid analgesics: aspirin and acetaminophen Adjuvants NSAIDs, antidepressants or anticonvulsants 5
Consensus statement and guideline for pharmacological management of Neuropathic pain from the Canadian Pain Society - 2014 Combining analgesics for chronic pain Pain Neuropathic Nociceptive Moulin et al 2014 Start the Canadian Pain Society Algorithm Start the WHO ladder Algorithm for the pharmacological management of neuropathic pain. *Topical lidocaine (second line for postherpetic neuralgia), methadone, lamotrigine, lacosamide, tapentadol, botulinum toxin; + Limited randomized controlled trial evidence to support add-on combination therapy. TCA Tricyclic antidepressants; SNRI Serotonin noradrenaline reuptake inhibitors Exercise Range of motion/stretching Strengthening Aerobic Relaxation techniques Yoga Pilates Psychological & Education Biofeedback Cognitive behavioural therapy Functional restoration Support groups Manual therapies Massage Manipulation Traction Mobilization techniques Never forget the non-pharmacological options for pain? Physical Modalities Local heat Superficial (hot packs) Deep (ultrasonography or diathermy) Local cold Traction Transcutaneous electrical nerve stimulation (TENS) Percutaneous electrical nerve stimulation Other Ergonomic aids Braces Meditation Acupuncture Shoulder impingment Syndrome Nociceptive Acute None Case 1 Carbamazepine Opioids Case Summary slide Painful diabetic neuropathy Neuropathic Chronic Diabetes Cognitive CVD, HTN Prostate Giuseppe Opioids Could try nortriptyline, but watch prostate symptoms Yes Yes Maybe No, kidney involvement After above meds failed Various pharmacological and non-pharmacological options for the management of non-cancer pain Major groups of drugs: acetaminophen, NSAIDs, Cox2 inhibitors, muscle relaxants, antidepressants and anticonvulsants. Opioids are discussed elsewhere Drug selection is based on type and nature of the pain, its severity of pain, and patient s characteristics and choice Combining analgesics may improve efficacy at lower doses, with fewer side effects than with the use of one agent alone 6
Resources Wall and Melzack s - Textbook of Pain 5 th edition Moulin et al. Pharmacological management of chronic neuropathic pain:revised consensus statement from the Canadian Pain Society. 2014 WHO pain ladder (http://www.who.int/cancer/palliative/painladder/en/) Canadian Opioid Guideline (www.nationalpaincentre.mcmaster.ca/opioid/ ) Demeules et al, Eur J Anesthesiology, 2003. Clinical Pharmacology and rationale of analgesic combinations. 7