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307 Cards in this Set
- Front
- Back
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Epidemiology/Etiology of MS
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2:1 females to males
Diagnosis ~ 15 to 45 years old 400,000 Americans Every week ~ 200 people are diagnosed 2.5 million people worldwide affected Most common in northern European ancestry The incidence decreases the closer you are to the equator Incidence increases above the 37th parallel There is an inverse relationship between MS incidence and 25-hydroxy-vitamin D levels Smoking increases the risk of MS 1st generation family members are at increased risk |
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female:male MS pts.
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2:1 females more like to have MS
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list 3 underlying factors to MS
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infectious agent
genetic predisposition environmental factors they lead to abnormal immunologic response then lead to MS |
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neuropathology of MS
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Demyelination
Reversible Axonal loss Irreversible Immune-mediated damage Disability |
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when is MS damage irreversible?
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axonal loss
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when is MS damage reversible?
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demyelination
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Process of MS diagnosis
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Patient History
Attack consistent with MS symptoms Attack lasts at least 24 hours MRI White matter lesion disseminated in time and space Gadolinium enhancing lesions Atrophy Lumbar Puncture (LP) Oligoclonal bands (IgG) Elevated IgG index Evoked Potentials Visual, delayed but well preserved wave form McDonald Criteria, NMSS |
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primary signs and symptoms of MS
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*Visual complaints/optic neuritis
*Gait problems and falls Paresthesias Pain Spasticity Weakness Ataxia Speech difficulty Psychological changes Cognitive changes *Fatigue Bowel/bladder dysfunction Sexual dysfunction Tremor *Most common signs |
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first attack of MS
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Clinically Isolated Syndrome (CIS)
Radiographically Isolated Syndrome (RIS) |
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List clinical types of MS
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Relapsing-Remitting MS (RRMS) 85%
Primary Progressive MS (PPMS) 10% Progressive Relapsing MS (PRMS) 5% |
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Describe Relapsing Remitting MS
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Most common 85%
Characterized by relapses and remissions RRMS converts to secondary progressive MS (SPMS) at a rate of 2-3%/yr SPMS is characterized by progressive, neurological deterioration with or w/o clinical relapses Median time to conversion is 10 years |
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Desc. Primary Progressive MS
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10%
Progressive disease from onset with occasional plateaus and temporary improvements |
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Desc. Progressive Relapsing MS
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Least common 5%
Least common form of MS Progressive disease from onset, acute relapses with or w/o recovery and progression between relapses |
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Favorable Prognostic factors MS
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Younger age at onset
Female Low relapse rate Sensory symptoms No disability early Normal MRI at onset |
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Unfavorable Prognostic factors of MS
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Older age at onset
Male High relapse rate Early motor or cerebellar symptoms Disability early High T2 lesion load at presentation |
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Immunopathology of MS
KNOW |
T cells activated in periphery -> display adhesion molecules -> activate matrix metalloproteinases -> gain entry into CNS via disrupted blood brain barrier (BBB)
Release of cytokines, upregulation of immune response, BBB opens more Damage to myelin and axons via antibodies, complement proteins, free radicals, cytokines Variable path between patients |
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T-cell plasticity
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Th1 and Th17 considered pathogenic
Th2 and Treg considered protective Th17 and Treg can exhibit “plasticity” In the presence of certain cytokines they can transform into Th1 or Th2 cells |
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BBB function in MS
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The function of the BBB is to establish and maintain homeostasis in the CNS
Longitudinal studies have shown month-to-month fluctuations (30-70%) of enhancing lesions in MS patients before interferon treatment (*treat early!!!) Significant reductions in enhancing lesions were found with both interferon (IFN) beta-1a and 1b and appear to be dose related |
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what is the ultimate goal of MS treatment?
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Delay disease progression
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Goals of MS medication therapy
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Shorten recovery time from exacerbations
Decrease the number/severity of relapses Prevent development of secondary progressive disease Stop the further progression of progressive MS Provide symptomatic modalities Improve quality of life |
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signs of pseudoexacerbation of MS
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Temperature - Heat
Infections - UTIs Stress Emotional Physical |
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what drugs are used for acute exacergation/relapse in MS?
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steroids
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MOA steroids in acute MS tx
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Immunomodulatory:
Reduce the number of T lymphocytes Block gamma IFN Reduce IgG synthesis Inhibit PGE2 (proinflammatory cytokine), etc. |
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Benefit of steroids in acute MS tx
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Reduce the focal defects inflammation/
demyelination) and improve the integrity of the BBB (reduce inflammation & edema) |
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Steroid options for MS
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Methylprednisolone: ~1000 mg iv x 3-5 days
Dexamethasone: 120 mg IV x 5 days (only if shortage of methylprednisolone) Prednisone taper: Inhibit rebound + axis (often not used with short courses of therapy) |
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methylprednisolone MS dose
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1000 mg iv/po x3-5 days
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dexamethasone MS tx
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120 mg iv x 5 da7s
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why use methylprednisolone for MS acute exacerbation?
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Methylprednisolone
Shortens the duration of the acute exacerbation Does not affect progression of the disease High Dose Methylprednisolone New lesions less likely within 6 months of therapy Delays onset of MS with optic neuritis |
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side effects of steroids
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Edema
Insomnia Weight gain Depression Hirsutism Peptic ulcer disease Herpes zoster Axis suppression less common |
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Disease Modifying therapy RRMS
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Relapsing Remitting MS (RRMS)
Interferon beta-1b (Betaseron®) Interferon beta-1a (Avonex®) Interferon beta-1a (Rebif®) Glatiramer acetate (Copaxone®) Efficacy seen at 1 and 2 years |
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disease modifying therapy for refractory MS pts
FDA approved |
Mitoxantrone (Novantrone®)
Natalizumab (Tysabri®) |
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what do IFN beta-1b and IFN beta-1a do?
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MOA: immunomodulating activity, altering the immune response against the myelin sheath
Decrease cell migration into the CNS Overall Effect: Diminish pro-inflammatory response, therefore reducing the inflammation of the CNS Inhibit proliferation of reactive T cells Inhibit antigen presentation Decrease the number of adhesion molecules Decrease T cell production of TNF alpha Induce anti-inflammatory IL-10 Block production of matrix metalloproteinases Enhance Th2 type responses. --Th1 generates gamma interferon --Th2 suppresses Th1 |
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IFN beta-1b (Betaseron, Extavia)
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Produced in Escherichia coli (bacterium)
Mutation of the natural sequence at amino acid position 17 Dose: 250 mcg (8 MIU) SC every other day Storage: Room temperature (no refrigeration due to new formulation) Packaging: Auto-injector, not premixed Cost: $19,632 yearly |
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ROA, dosing freq. IFN beta-1b (Betaseron, Extavia)
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SC every other day
only one that DOESNT need to be refrig |
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IFN beta-1a(Avonex)
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Produced in a mammalian cell line (recombinant)
Identical to human interferon (glycosylated) Dose: 30 mcg (6 MIU) IM once weekly Storage: Refrigerate, ok at room temperature for 30 days Packaging: Pre-filled syringe, 0.5 ml, latex, no graduations on syringe Cost: $18,360 yearly |
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ROA, dosing freq IFN beta-1a(Avonex)
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IM once weekly
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IFN beta-1a(Rebif)
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Produced in a mammalian cell line (recombinant)
Identical to human interferon (glycosylated) Dose: 44 mcg SC 3 times weekly Storage: Refrigerate, ok at room temperature for 30 days Packaging: Pre-filled syringe, 0.5 ml, auto-injector, storage case for travel Cost: $21,163 yearly |
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ROA, dosing freq IFN beta-1a(Rebif)
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SC 3 times weekly
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MS 1st line agents
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IFNs, glatiramer
all used for RRMS and have similar efficacy |
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Glatiramer(Copaxone) ROA, dosing freq
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SC once daily
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Side effects of IFNs
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Flu-like symptoms
Injection site reactions Potential for: Depression - Contraindicated in severely depressed** decrease WBCs/RBCs decreased platelet count increase liver function tests Spontaneous abortions Neutralizing antibodies (Abs) |
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manage side effects of IFNs
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Administer injection at night
Rotate injection sites Dose escalation Ice site/heat Injection at body temperature Clean technique Auto-injector Topical lidocaine Pre-medicate: NSAID or APAP Q4H x 24 hours, then PRN Diphenhydramine 25-50 mg Prednisone (10-30 mg maximum) po daily x 1-3 months rarely used |
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premedication for IFNs
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Pre-medicate:
NSAID or APAP Q4H x 24 hours, then PRN Diphenhydramine 25-50 mg Prednisone (10-30 mg maximum) po daily x 1-3 months |
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what does glatiramer(Copaxone) do?
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MOA: immunomodulating activity
Blocks the binding of MHC class-II products to myelin basic protein (MBP) Overall Effect: Down regulation of the inflammatory and autoimmune responses associated with MS Synthetic polypeptide prepared from four amino acids (L-alanine, L-glutamic acid, L-lysine and L-tyrosine) Dose: 20 mg SQ daily Storage: Refrigerate, ok at room temp. for 7 days Packaging: Pre-filled syringe, 1 ml, auto-injector, storage case for travel, lock box for refrigerator Cost: $19,749 yearly |
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side effects of glatiramer?
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Injection site reactions
Dizziness Flushing Chest tightness Shortness of breath Urticaria Headache Lipoatrophy |
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manage SEs of glatiramer
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Management of side effects for glatiramer acetate (Copaxone®)
Inject at night, rotate sites, ice/heat site, injection at body temperature, clean technique, auto-injector Pre-medicate: Only if needed! NSAID or APAP Diphenhydramine |
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Features of DMTs (Disease Modifying Therapies)
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Decrease relapses by 33%
Decreases number of white matter lesions Decreases number of black holes Long term benefit No acute benefit Treat early 1st attack = Clinically Isolated Syndrome (CIS) |
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DMTs not approved be FDA for worsening/progressive MS
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Not FDA-approved for MS
Rituximab (Rituxan®) Azathioprine (Imuran®) Cyclophosphamide (Cytoxan®) Methotrexate 2.5 mg TIW or 7.5 mg qweek Intravenous gammaglobulin (IVIG®) Mycophenolate (Cellcept®) Methylprednisolone IV pulse therapy |
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DMTs approved by FDA for worsening/progressive MS
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Mitoxantrone (Novantrone®)
Natalizumab (Tysabri®) |
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What does Natalizumab(Tysabri) do?
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Natalizumab (Tysabri®)
Approved for RRMS patients with an inadequate response or intolerance to other MS therapies Partially humanized monoclonal antibody directed at the cell surface adhesion molecule alpha-4 beta integrin (VLA-1) MOA: Attaches to VLA-1 and blocks the interaction with its ligand on CNS endothelium VCAM-1. Activated lymphocytes are denied entry past the BBB. 300 mg IV infusion every 4 weeks Decreases frequency of relapse 50-60%, decreases lesions on MRI 80-90%, and decreases progression of disability Can cause progressive multifocal leukoencephalopathy (PML) 37 reported cases as of February 2010 (>60,000 patients have been treated worldwide) Package insert states PML incidence is 1 in 1000 Patients must be enrolled in TOUCH program |
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what is the BAD rxn from Tysabri/natalizumab
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PML, progressive leukoencephalopathy (viral CNS infection)
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what does mitoxantrone (Novantrone) do?
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12 mg/m2 IV every 3 months
Lifetime max dose 140 mg/m2 Indicated for SPMS, PRMS, and active/worsening RRMS Reduces relapse rate, disability progression, and MRI activity Must do EKG and MUGA prior to each dose Can cause secondary leukemias (1 in 145 patients) |
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why is mitoxantrone rarely used?
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cause secondary leukemias in 1/145 pts
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what does rituximab do?
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Rituximab (Rituxan®)
Not FDA approved for treatment of MS Chimeric murine/human monoclonal antibody targeted against CD20+ B-cells Dose: 1000 mg IV at baseline, then weeks 2, 24, 26, 48, 50, 72, 74, etc Showed promise in RRMS in phase I and II clinical trials Showed no benefit in PPMS in a phase II/III trial |
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what does mycophenolate/Cellcept do?
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Mycophenolate (Cellcept®)
Used for worsening or progressive MS Dose: 250 mg po for 2 weeks, then increase by 250 mg/ day (500 mg total) for 2 weeks, then 750 mg/day (up to 1000 mg/ day) Give 1 hour before or 2 hours after a meal Watch for nausea, vomiting, diarrhea Monitor full chemistry panel and CBC at baseline and months 1, 2, & 3 then quarterly, urine CMV |
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what are some other agents used for progressive MS not used very often?
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Methotrexate
Methylprednisolone IV pulse therapy Azathioprine Cyclophosphamide Intravenous immunoglobulin (IVIG) |
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which DMTs work at the BBB?
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IFN beta
natalizumab |
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symptomatic therapy for visual loss
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IV methylprednisolone (decrease clinical MS within 2 years)
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symptomatic therapy for weakness
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Physical therapy, occupational therapy
Dalfampridine (4-aminopyridine, Ampyra®) MOA: Blocks K+ channels in the excitatory nerve membrane, allowing for more efficient conduction Dose: 10 mg BID First medication FDA approved to treat a symptom of MS Approved to improve walking speed in MS patients Side Effects: Seizures (0.25%), confusion, GI upset |
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symptomatic therapy for spasticity
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Baclofen (Lioresal®)
MOA: GABAb agonist; dorsal horn of the spinal cord Starting Dose: ~5-25 mg po tid (also intrathecal) Side Effects: Confusion, sedation, weakness, hallucinations Abrupt withdrawal: Rebound spasticity, seizures Tizanidine (Zanaflex®) MOA: alpha-2 adrenergic agonist; increases presynaptic inhibition of motor neurons; reduces facilitation of spinal motor neurons Dose: ~ 4 mg Q6-8 hours Side effects: Confusion, hypotension, dry mouth Combination therapy: Can use a lower dose of both medications and they have different MOAs |
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alternative drugs used for MS spasticity
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Dantrolene
MOA: Acts peripherally (directly on skeletal muscles) inhibiting calcium Dose: 25-50 mg daily (max dose of 400 mg daily) Side Effects: Muscle weakness, hepatotoxicity Alternatives: diazepam, clonazepam, gabapentin, pregabalin, tiagabine Marijuana Dronabinol (Marinol®) has been studied, but has not shown benefit over other agents |
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symptomatic therapy for bladder dysfunction: nocturia
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DDAVP
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symptomatic therapy for bladder dysfunction: hyporeflexive bladder(fail to empty)
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Crede maneuver, timed voids, catheterization
Cholinergic Agents: Bethanechol chloride (Urecholine®) |
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symptomatic therapy for bladder dysfunction: sphincter-detrusor dyssynergia (incomplete emptying)
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Prazosin 0.5 mg/d or tamsulosin (Flomax®) 0.4 mg/d (alpha-1 adrenergic blocker) at night to relax the internal sphincter
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symptomatic therapy for bladder dysfunction: hyperreflexive bladder (incontinence)
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Oxybutynin
Ditropan® 10-30 mg PO per day Ditropan XL® 30 mg PO QD Oxytrol® 3.9 mg transdermally twice weekly Tolterodine Detrol® 2 mg PO bid (decrease dose with CYP 3A4 inhibitors) Detrol LA ® 4 mg PO QD Fesoterodine (Toviaz®) 4 to 8 mg QD Darifenacin (Enablex®) 15 mg PO QD Solifenacin (Vesicare®) 10 mg Trospium (Sanctura®) 20 mg bid Not metabolized Other Options: Propantheline, dicyclomine, amitriptyline, imipramine, hyoscyamine, capsaicin bladder irrigation |
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symptomatic therapy for UTI
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Prophylaxis: Bactrim®, Keflex®, Cinobac®, or nitrofurantoin
Can lead to sepsis if not treated |
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symptomatic therapy for sexual dysfxn
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MUSE, Viagra®, Levitra®, Cialis®
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symptomatic therapy for fatigue
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Amantadine (Symmetrel®) 100 mg PO bid
Methylphenidate (Ritalin®) 5-20 mg PO bid-tid Fluoxetine (Prozac®) 10 mg Modafinil (Provigil®) start with 200 mg PO QD and can go up to 400 mg per day Dexedrine |
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symptomatic therapy for central neuropathic pain
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Carbamazepine, TCAs, gabapentin, pregabalin, capsaicin cream
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symptomatic therapy for sensory symptoms
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Trigeminal neuralgia (one of the most common symptoms)
Carbamazepine 200 mg PO bid or tid Burning, itching, L’Hermitte’s sign, face twitching |
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symptomatic therapy for depression and emotional lability
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Depression (25-55%) and emotional lability (10%)
Suicide 7 times higher in MS population TCAs (Amitriptyline 25 to 75 mg/d) SSRIs, SNRIs |
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symptomatic therapy for anxiety and psychosis
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benzos
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NMSS recommendation for MS treatment
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Initiate therapy early
All RRMS patients eligible Continue therapy unless lack of benefit, intolerable side effects, new data suggesting discontinuation, better therapy available, pregnancy Movement from one agent to another should be allowed Okay with most medical conditions |
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RRMS therapies on the horizon: Sphingosine-1-phosphate type 1 receptor (S1P1) agonist
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Novel once daily oral agent; prevents migration of T and B cells out of peripheral lymph nodes
Fingolimod ONO 4641 CS0777 |
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RRMS therapies on the horizon: chemo agents
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cladribine
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RRMS therapies on the horizon: monoclonal antibodies
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Alemtuzumab
Daclizumab Rituximab (anti CD20 |
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RRMS therapies on the horizon: laquinimod
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laquinimod
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RRMS therapies on the horizon: combo therapy
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CombiRx (Avonex + Copaxone)
Estriol plus Copaxone |
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RRMS therapies on the horizon: SPMS
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Dirucotide – Novel antigen based therapy
Induces peptide-specific immunologic tolerance HLA class II defined responder group (HLA DR2, DR4 |
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RRMS therapies on the horizon: Optic neuritis/CIS
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Atacicept
Cladribine |
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RRMS therapies on the horizon: symptomatic tx
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nerispiridine for walking
duloxetine for central neuropathic pain |
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MISC tx for MS with no proven efficacy/benefit
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Bee Venom: Showed no benefit (6/98)
PROCARIN: Transdermal patch for energy; histamine & caffeine (no proven efficacy |
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defn pain
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An unpleasant sensory and emotional experience associated with tissue damage or described in terms of such damage.
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acute vs. chronic pain: location
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defined vs. diffuse/spread out
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acute vs. chronic pain: pt. describes
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simple vs. difficult to describe
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acute vs. chronic pain: duration
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short/limited < 1 mo. vs. ongoing, long term >3 mos
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acute vs. chronic pain: therapy model
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curative vs rehabilitation model
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acute vs. chronic pain: mood of pt
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anxiety,fear vs. depression, frustration, anger
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acute vs. chronic pain: rate of depression
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same as gen. pop vs. 3-4x's gen. pop.
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acute vs. chronic pain: pain tolerance
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usually unaffected vs. decreased, wears person out
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acute vs. chronic pain: impact family relationship
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family/friends helpful/supportive vs. decreased support
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acute vs. chronic pain: impact job
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usually unaffected vs. variable/jeopardized job
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acute vs. chronic pain: impact on function
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imrpove with healing vs. dysfunction over time
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acute vs. chronic pain: response from providers
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fix the problem approach vs. doubt existence/intensity
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acute vs. chronic pain: goal for evaluation
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clarify somatic diagnosis vs. workup endless/fruitless
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acute vs. chronic pain: role of analgesic tx
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pain control while healing vs. improve function, QOL
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Types of pain
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Nociceptive Pain
Neuropathic Pain Mixed Pain Idiopathic Pain Psychogenic Pain |
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Nociceptive pain
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Stimulation of somatic and visceral peripheral nociceptors by stimuli that damage tissue
Has a signaling biologic function Examples - postoperative pain, low back pain, sports/exercise injuries, sickle cell crisis, osteoarthritis, rheumatoid arthritis, fibromyalgia |
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neuropathic pain
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Pain resulting from injury to or dysfunction of the peripheral and/or central nervous system
Does not have any useful biologic function Sensitization, spontaneous pain, evoked pain Examples – postherpetic neuralgia, neuropathic low back pain, peripheral neuropathy, central post-stroke pain, trigeminal neuralgia, complex regional pain syndrome, phantom limb pain |
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mixed pain
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Has both nociceptive and neuropathic components
Example Failed low-back-surgery syndrome Complex regional pain syndrome |
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idiopathic pain
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No underlying lesion found yet, despite investigation
Pain disproportionate to the degree of clinically discernible tissue injury. Chronic pain syndrome |
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psychogenic pain
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No underlying lesion found yet, despite investigation
Presumed psychological or psychiatric origin |
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What is a nociceptor?
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On nerve endings of A-delta and C-fibers
Not spontaneously active Level of stimulation must exceed threshold Distinguish between noxious & innocuous events Distinguish thermal, chemical, or mechanical noxious events Transmit information to the spinal cord Sensitization produces hyperalgesia |
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what is a sensitized nociceptor?
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“Sensitized” with continued stimulation
Decreased threshold Increased intensity and prolonged firing Spontaneous activity (ectopic discharges) |
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Types of periph. nerve fibers
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A Fibers (Fast Transmission)
Alpha - Proprioception (Muscles & Joints) Beta - Mechanoreception (Cutaneous Tissue) Delta - Primary nociceptive neurons C Fibers (Slow Transmission) Primary nociceptive neurons |
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characteristics of A delta fibers
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Small (1-5 µm)
Myelinated Conduct fast 5-25 m/sec |
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characteristics of c fibers
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Very small (< 1µm)
Unmyeliniated Conduct slowly (0.5-2 m/sec) |
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4 major processes of pain pathway:
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transduction
transmission modulation perception |
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transduction
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Conversion of stimuli into electrical action potential by nociceptors
What types of stimuli? Heat or cold Pressure Chemical |
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transmission
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Movement of electrical stimulus information into and through the spinal cord
Two types of fibers A Fibers C Fibers Afferent vs. efferent fibers Fibers come into close proximity as they converge into the spinal cord Cross stimulation can occur referred pain, phantom limb pain |
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modulation
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Modulation of the nerve impulse by in the spinal cord and higher CNS areas
Secondary afferent neurons Gate Cells “Calculate” incoming signals as excitatory or inhibitory Determine which signals propagate to higher CNS |
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what receptors/channels inhibit pain transmission?
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Opioid receptors (μ, κ, δ)
GABA (A and B) Alpha 2 receptors (α2) Blockade of ion channels (Na+, Ca2+) Opening of ion channels (K+) Neuropeptide Y |
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Perception
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Summation of the previous 3 steps
Provides the subjective, emotional experience that accompanies pain. Areas of the brain influenced by pain and involved in the perception of pain: Reticular formation - consciousness Thalamus – relay area Medulla oblongata - cardiac Hypothalamus – sympathetic Limbic system – emotional Cerebral cortex – final step |
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peripheral sensitization pathway
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tissue damage, inflammation, and sympathetic terminals(stimulation) lead to "sensitizing soup" which leads to:
decreased threshold for nociceptor firing, increased intensity and prolonged firing, spontaneous (ectopic) discharges of nociceptors, abnormal accumulation of Na channels |
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Central sensitization
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posterial horn of spinal cord
AMPA, NK1 receptors active in acute pain NMDA usually not activated in acute pain (upregulated in chronic pain) |
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Pain behaviors
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How patients communicate/ demonstrate pain, distress & suffering
Observable manifestations of pain: grimacing sighing moaning splinting posture limits limping c/o pain bradykinesia guarding crying use of cane or crutches taking pain medication visiting the doctor |
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Effects of Chronic Pain
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Decreased function and QoL:
Physical Function --Activities of daily living (ADL) --Sleep disturbances Social Consequences --Relationships --Isolation --Intimacy/sexual activity Psychological Morbidity --Depression --Anxiety --Anger --Loss of self-esteem Societal Consequences --Health care costs --Disability --Lost workdays |
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most common reason for under treated pain?
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failure to assess pain
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Chronic pain assessment
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Collect the data:
Pain history & pain assessment Medical history Psychiatric history Psychological evaluation Physical exam Imaging Laboratory tests Neurophysiologic testing Develop the therapeutic strategy: Multimodality therapy usually needed for chronic pain |
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Benefits of pain assessment
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Establish relationship with patient
Give insight into possible causes or pathophysiology Guide selection of pain treatments Improve pain management Maximize patient comfort, function and quality of life Increase patient satisfaction with care |
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categories of pain treatment
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non opiod analgesics
adjuvant analgesics opiods rehavilatative approaches psychological approaches injection therapies neural blockade implant therapies surgical approachs complementary and alternative medicine approaches lifestyle changes |
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Pain assessment and reassessment: timing
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Initial (baseline)
Regular intervals New report of pain Significant change in report of pain After change in therapy |
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Initial or ongoing pain assessment: characterization of pain
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Location
Description - Onset - Cause - Pattern -Duration - Quality -intensity Effects on function Aggravating/alleviating factors Pain relief Patient expectations and goals Patient satisfaction with treatment |
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pain location
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Describe where the pain is located
Use a body diagram to illustrate the location of areas of pain Is there more than one site of pain |
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pain description: onset, patterns and duration of pain
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ONSET: When did the pain start?
CAUSE: How did the pain start? PATTERN: How often does the pain occur? - Continuous pain - Continuous pain, with “spikes” of increased pain - Intermittent intense pain DURATION CHANGE: Has the pain pattern, duration, or intensity changed? |
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pain desc.: quality of pain
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What does the pain feel like?
Word lists can help to describe the character of the pain: burning, aching, stabbing, throbbing, shooting, tender, dull, squeezing, sharp, throbbing, numb, electric-like, ramping, pressure, gnawing, penetrating, tiring, miserable, exhausting , nagging How the pain feels can be critical to selecting treatment |
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What changes the pain?
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What factors make the pain better? Alleviating Factors?
AND What factors make the pain worse? Aggravating Factors? Examples: Medication Exercise Reclining Physical therapy Sitting Standing Walking Bending Heat Cold Stress Weather Changes Pain relief: Percentage relief? Pain intensity differences? **Needs to be individualized |
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Pain assessment: medications and treatment
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Allergies and adverse reactions
Social drug history --OTCs, vitamins, natural remedies --Caffeine, nicotine, alcohol, marijuana, other illicit drugs Current medications and response/side effects Past medications and reason discontinued Current/past non-pharmacological treatments Patient expectations |
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Pain assessment: difficulties in the elderly
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Short-term memory loss
Impaired cognition Depression Sensory impairment Multiple illnesses Tendency to underreport pain |
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Checklist of verbal pain indicators
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Words expressing pain/discomfort: “ouch”, “that hurts”, cursing during movement, or protesting “stop” or “that’s enough”
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checklist of nonverbal pain indicators
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Vocal Complaints: Nonverbal
Expression of pain not in words, in moans, groans, grunts, cries, gasps, sighs Facial Grimaces/Winces Furrowed brow, narrowed eyes, tightened lips, dropped jaw, clenched teeth, distorted expression Bracing Clutching or holding on to side rails, bed, tray table, or affected area during movement Rubbing Massaging affected area Restlessness Constant/intermittent shifting of position or hand motions, rocking, inability to keep still |
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Assessing pain in cognitively impaired older adults
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Changes in Interpersonal Interactions:
Combative/ aggressive Resisting care Decreased social interactions Socially inappropriate Disruptive Withdrawn Irritability Changes in Mental Status: Irritability or distress Increased confusion Agitation Changes in Activity Patterns/Routines: Sudden cessation of common routines Increased wandering Difficulty sleeping Increase in rest periods Refusing food/appetite change |
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List 1st line agents for neuropathic pain
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Tramadol – mild to moderate pain
Antidepressants Tricyclic antidepressants SNRI antidepressants Anticonvulsants Gabapentin or Pregabalin Capsaicin Lidocaine 5% patch Opioids |
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tramadol MOA
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block reuptake of 5HT and NE,
bind mu receptor |
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tramadol start/max dose
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start 25 mg/day
max 400 mg/day, 300 mg/day if >75 yo |
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tramadol dosing is special pops
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Children: not recommended for patients <16 years
Elderly 65 to 75 years: no dose adjustment* >75 years: do not exceed 300 mg/d in divided doses* Renal impairment Creatinine clearance <30 mL/min 50 to 100 mg q 12 h (max 200 mg/d) Cirrhosis 50 mg q 12 h |
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adv. tramadol 25 mg start dose
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Advantage with the 25 mg/day starting dose
Increase by 25 mg q3d, then 50 mg bid, tid, etc. Fewer patients DC due to dizziness, vertigo, nausea and vomiting |
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side effects tramadol
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Side Effects: dizziness, nausea, constipation, sedation, orthostatic hypotension
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precautions tramadol
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seizure history, cognitive impairment in the elderly
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interactions tramadol
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carbamazepine, drugs that lower seizure threshold, SSRI, MAOI
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monitoring tramadol
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baseline renal & liver function, orthostasis, pain & function
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indications for tramadol
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OA
neuropathic pain painful diabetic neuropathy |
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antidepressants to treat neuropathic pain
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TCA most effective
SNRI DNRI SSRI least effective |
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MOA TCAs in neuropathic (NP) pain
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Tricyclic Antidepressants
decrease Norepinephrine reuptake decreased Serotonin reuptake Sodium channel modulation Analgesic properties are independent of their antidepressant properties |
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TCA start, max dose
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start 10-25 mg hs
max 150 mg/day |
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TCA SEs
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anticholinergic, sedation, sexual dysfunction, orthostatic hypotension, wt gain
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TCA precautions
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cardiovascular disease, urinary retention, glaucoma, seizures, suicide risk, balance problems & cognitive dysfunction in the elderly
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TCA interactions
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cimetidine, antihypertensives, SSRIs, class I antiarrhythmics
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TCA monitoring
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ECG if > 40 yo, hypotension, anticholinergic effects, cognitive function, withdrawal reaction
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TCAs from least to most intense
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desipramine
nortriptyline imipramine doxepin amitriptyline |
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TCA indications
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neuropathic pain
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Duloxetine(Cymbalta) MOA
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SNRI
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Duloxetine(Cymbalta) start, max dose
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start 60 mg/day
max 120 mg/day |
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Duloxetine(Cymbalta) side effects
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anorexia, ataxia, sedation, constipation, dry mouth, hyperhydrosis, nausea, hypertension
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Duloxetine(Cymbalta) interactions
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Drugs that inhibit CYP2D6 (paroxetine, fluoxetine) or
CYP1A2 (ciprofloxacin, cimetidine) may potentiate duloxetine. Duloxetine also inhibits CYP2D6 and may increase the effects of tricyclic antidepressants, phenothiazines, class I antiarrhythmics |
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Duloxetine(Cymbalta) monitoring
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blood pressure, baseline renal & liver function, pain & function
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Duloxetine (Cymbalta) indications
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postherpatic neuralgia
painful diabetic neuropathy fibromyalgia |
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Venlafaxine (Effexor) MOA
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SNRI
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Venlafaxine (Effexor) start, max dose
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IR: start 25 mg bid, max 225 mg/day
XR: start 37.5 mg/day, max 225 mg/day |
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Venlafaxine (Effexor) SEs
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anorexia, anxiety, ataxia, constipation, dry mouth, hyperhydrosis, hypertension, insomnia, nausea, sedation, withdrawal reaction (taper off if electively stopping use).
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Venlafaxine (Effexor) interactions
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antihypertensive medications, venlafaxine is metabolized by cytochrome P450 2D6 & 3A4
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Venlafaxine (Effexor) monitoring
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blood pressure, baseline renal & liver function, pain & function
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venlafaxine(Effexor) indications
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painful diabetic neuropathy
painful polyneuropathy |
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Gabapentin(Neurontin) MOA
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modulation of N-type calcium channels
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Gabapentin(Neurontin) start, max dose
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start 100-300 mg hs tid
max 3600 mg (1200 tid) |
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Gabapentin(Neurontin) SEs
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sedation, dizziness, GI symptoms, weight gain, fluid retention, peripheral edema
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Gabapentin(Neurontin) interactions
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relatively few, antacids
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Gabapentin(Neurontin) monitoring
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baseline creatinine, edema, pain & function
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Gabapentin(Neurontin) precautions
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may exacerbate gait or balance problems, and cognitive impairment in the elderly
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Gabapentin(Neurontin) indications
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neuropathic pain
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Pregabalin (Lyrica) MOA
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modulation Ntype Ca channels
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Pregabalin (Lyrica) controlled?
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yes,
Schedule V controlled substance |
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Pregabalin (Lyrica) SEs
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sedation, dizziness, wt. gain, peripheral edema, blurred vision
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Pregabalin (Lyrica) monitoring
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pain and function
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Pregabalin (Lyrica) start, max dose
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start 150 mg/day
max 300 mg/day (severe 300 mg bid) |
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Pregabalin (Lyrica) indications
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diabetic neuropathy
postherpatic neuralgia fibromyalgia |
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lidocain 5% patch (Lidoderm) MOA
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sodium channel modulation
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lidocain 5% patch (Lidoderm) dosing
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max 3 patches daily for max 12 hours (12 hours off)
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lidocain 5% patch (Lidoderm) precautions
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allergy to amide-type local anesthetics, use only on intact skin
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lidocain 5% patch (Lidoderm) indication
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neuropathic pain
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Capsaicin (Zostrin) MOA
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depletion of substance P, vanilloid receptor neurolytic
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Capsaicin (Zostrin) dosing
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.025-.075% cream tid/qid
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Capsaicin (Zostrin) SE
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burning, tingling, erythema, pruitis, cough, respiratory irritation
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Capsaicin (Zostrin) Precautions
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wash hands, wear rubber gloves if necessary, do not apply to broken skin, moisture enhances burning
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Capsaicin (Zostrin) monitoring
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compliance, burning, pain & function
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Capsaicin (Zostrin indications
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diabetic neuropathy
postherpatic neuralgia *limited effectiveness alone, best when used in conjuction with systemic drugs |
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why use 2nd line agents for neuropathic pain
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Used when there is an inadequate response to the use of 1st line agents alone or in combination
Opioids Used less often Fewer RCT support use More side effects than 1st line agents |
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Bupropion(wellbutrin) in 2nd line treatment NP pain
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Mechanism: dopamine, norepinephrine reuptake inhibitor (DNRI)
Dose: IR: 100 mg bid, may increase to 100 mg tid after one week, maximum dose 150 mg tid. SA: 150 mg q day, may increase to 150 mg bid after one week, maximum dose 200 mg bid. Adequate Trial: 2-3 weeks at maximum tolerated dose. Adverse Effects: insomnia, nausea, avoid in patient with history of seizure disorders Interactions: Monitoring: baseline renal and liver function, pain intensity & function |
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Milnaciprain (savella) in 2nd line treatment NP pain
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Mechanism: serotonin, norepinephrine reuptake inhibitor (SNRI)
Dose: start 12.5 mg q day, usual dose 50 mg bid, maximum dose 100 mg bid. In renal insufficiency (Cr Cl 5-29 ml/min) dose is decreased by 50%. Adequate Trial: 3 weeks Side Effects: nausea, headache constipation, dizziness, insomnia, dry mouth, increase heart rate Adverse Effects: increased blood pressure Interactions: minimal risk, minimal CYP450 hepatic metabolism Monitoring: blood pressure, heart rate, baseline renal function, pain & function *Approved only for fibromyalgia |
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bupropion dose
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IR: start 100 mg bid, max 150 tid
SA: 150 mg/day, max 200 mg bid |
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milnacipran dose
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start 12.5 mg/day, max 100 mg bid
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carbamazepine (Tegretol) in 2nd line tx of NP pain
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Mechanism: sodium channel modulation
Dosing: start 100 mg q day to bid, increase by 100 mg/day q 3-7 days, max. 1000-1500 mg/day Side Effects: sedation, fatigue, ataxia, nausea, vomiting, dizziness, blurred vision Adverse Effects: leukopenia, aplastic anemia, hepatotoxicity, skin reactions, hyponatremia Interactions: tramadol, fluoxetine, propoxyphene, warfarin, oral contraceptives Monitoring: CBC, Na, LFT, rash, mental status, pain & function |
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CBZ dosing
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start 100 mg/day
max 1500 mg/day |
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cbz indications
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trigeminal neuralgi
diabetic neuropathy postherpatic neuralgia |
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Lamotrigiine (Lamictal) in 2nd line tx NP pain
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Mechanism: modulation of sodium channels and N-type calcium channels.
Dosing: start 25 mg q day, increase by 25-50 mg q 7 days, max. 200 mg bid Side Effects: dizziness, constipation, nausea, headache, diplopia, somnolence, ataxia, weakness Precautions: rash, Steven-Johnson syndrome Interactions: carbamazepine, phenytoin, valproate, acetaminophen Monitoring: rash, pain & function |
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Lamotrigiine (Lamictal) dosing
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start 25 mg/day
max 200 mg bid |
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lamotrigine indications
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diabetic neuropathy
trigeminal neuralgia central post stroke pain spinal cord injury HIV neuropathy |
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Oxcarbazepine (Trileptal) 2nd line NP pain tx
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Mechanisms: sodium channel modulation, N-type calcium channel modulation
Dosing: start 75 mg bid or 150 mg hs, increase by 150 to 300 mg/day at weekly intervals, max 600 mg bid Side Effects: dizziness, somnolence Adverse Effects: hyponatremia, rash Interactions: oral contraceptives, felodipine Monitoring: Baseline Na & renal function, mental status, rash, pain & function |
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oxcarbazepine dosing
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start 75 mg bid, max 600 mg bid
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oxcarbazepine indications
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trigeminal neuralgia
diabetic neuropathy refractory neuropathic pain |
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topiramate(topamax) 2nd line tx NP pain
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Mechanisms: sodium channel modulation, effects on GABAA and kinate receptors
Dosing: start 25 q day, increase by 25 mg q7days, max. 100 mg bid Side Effects: somnolence, fatigue, confusion, mental slowing, difficult concentration, paresthesias, dizziness, tremor, weight loss, kidney stones Interactions: carbamazepine, phenytoin, valproate, carbonic anhydrase inhibitors Monitoring: renal function, flank pain, mental status, bicarbonate levels, pain & function |
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topiramate(topamax dosing
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start 25 mg/day
max 100 bid |
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topiramate(topamax indication
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FDA approved migraine HA prophylaxis
low pack pain diabetic neuropathy |
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Baclofen (lioresal) 2nd line tx NP pain
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Mechanism: GABA-B agonist
Dosing: start 5-10 mg q day, increase by 5-10 mg q 3 days, max. 80 mg/day in 3-4 divided doses Side Effects: drowsiness, dizziness, nausea, vomiting, weakness, orthostatic hypotension Precautions: impaired renal function, seizures Interactions: CNS depressants Monitoring: creatinine, orthostasis, withdrawal reaction, pain & function |
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Baclofen (lioresal) dosing
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start 5-10 mg/day, max 80 mg/day 3-4 doses
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Baclofen (lioresal) indications
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trigeminal neuralgia
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Mexiletine (mexitil) 2nd line tx NP pain
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Mechanism: sodium channel modulation
Dosing: start 150 q day, increase by 150 mg every 3-7 days, max. 700 mg/day (10 mg/kg/day) in 3 divided doses Side Effects: nausea, dizziness, tremor, palpitations, headache, seizures, psychosis, proarrhythmia, cardiac conduction disturbances Precautions: CHF, CAD, MI, arrhythmia, liver disease, hypotension Interactions: phenytoin, theophylline, caffeine Monitoring: ECG, BP, pain & function |
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Mexiletine (Mexitil) dosing
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start 150 mg/day
max 700 mg/day |
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Mexiletine (Mexitil) indications
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diabetic neuropathy
periph. nerve injury |
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Clonazepam (Klonopin) 2nd line tx NP pain
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Mechanism: enhances GABA activity
Dosing: start 0.5 mg hs, increase by 0.5 mg q 7 days, max. 4 mg/day in 1-3 divided doses Side Effects: drowsiness, ataxia, dizziness, weakness, fatigue, impaired memory, confusion, respiratory depression, depression Precautions: glaucoma, severe liver disease Interactions: cimetidine, carbamazepine, phenytoin Monitoring: mental status, withdrawal reaction, pain & function |
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Clonazepam (Klonopin) dosing
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start .5 mg hs
max 4 mg/day |
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Clonazepam (Klonopin) indication
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lancinating neuropathic pain
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Clonidine (Catapres) 2nd line NP pain tx
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Mechanism: central alpha-2 agonist
Dosing: Oral: start 0.1 mg q day, increase by 0.1 mg q 7 days, usual max. 0.3 mg/day Transdermal: 0.1 to 0.2 mg, change q 3-7 days Epidural: 300 mcg / 10 ml bolus, 10-50 mcg/hr Side Effects: sedation, dizziness, nausea, dry mouth, bradycardia, hypotension Interactions: TCA, beta blockers, opioids, local anesthetics Monitoring: BP, pulse, pain & function |
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Clonidine (Catapres) dosing
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start .1 mg/day
max .3 mg/day |
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Clonidine (Catapres) indication
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diabetic neuropathy
complex regional pain syndrome |
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APAP and NSAIDs in NP pain
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no adequately studied in neuropathic pain
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antidepressant/anticonvulsant in NP pain
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***DRUGS OF CHOICE***
Titrate one drug at a time Start with agents with lower side effect profile Start low and go slow with dose titration Monitor for intended effect and side effects Use each drug for an adequate trial Combine drugs if necessary |
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Principles of NP pain pharmacotherapys
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Add other neuropathic pain drugs if necessary
Polypharmacy may be necessary for treatment failures Add opioids if necessary. Educate the patient Onset may take days to weeks once effective dose is reached Partial pain relief is the goal Sequential trials of different medications Side effects usually occur before partial pain relief Continue the therapy long-term if: Pain reduction of 30% or more Functional improvement (or stabilized function) Side effect are tolerable/manageable |
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hyperesthesia
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Increased sensitivity to stimulus
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paresthesia
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Abnormal unpleasant sensation such as tingling, pins and needles, numbness
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sysesthesia
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Painful sensation such as burning
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allodynia
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Pain with a non-noxious stimulus such as light touch
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hyperalgesia
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Exaggerated pain response to noxious stimulus
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hyperapathia
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Hyperalgesia that persists after the stimulus has ceased
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deafferentation pain
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Pain in a region of sensory loss
(phantom limb) |
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spontaneous pain
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Lancinating – electric, paroxysmal
Burning – constant, superficial Cramping/aching – deep, musculoskeletal |
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evoked pain
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Hyperalgesia
Allodynia Hyperpathia |
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desc. NP quality of pain
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Burning
Paresthesia Paroxysmal Lancinating Electric like Raw skin Shooting |
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desc. NP cardinal signs and symptoms
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Allodynia: pain from a stimulus that does not normally evoke pain
Thermal Mechanical Hyperalgesia: an exaggerated response to a normally painful stimulus |
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defn diabetic neuropathy
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“Diabetic neuropathy occurs in the setting of diabetes mellitus without other causes for peripheral neuropathy.”
Peripheral nerve damage attributable to diabetes Autonomic nerve damage attributable to diabetes Occurs in 10%-100% of patients with diabetes |
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pathophys. diabetic neuropathy
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High blood glucose levels appear to lead to an inability to transmit signals through nerves.
High blood glucose levels may result in: Metabolic changes—accumulation of sorbitol and a decrease in myo-inositol in nerves Vascular changes—vascular perfusion impaired, vasoconstriction of blood vessels supplying nerves Structure/Function changes—glucose attached to proteins, altering protein structure and function in nerves |
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signs and symptoms of periph. diabetic neuropathy
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Symptoms vary from patient to patient, and may include:
Numbness/insensitivity to touch or pain Extreme sensitivity to touch, even light touch Sharp pains or cramps Burning pain Loss of balance or coordination Loss of reflexes and muscle weakness Organs may also be affected, producing gastroparesis,dizziness, weakness, urinary/sexual dysfunction |
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1st line agents for diabetic neuropathy
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Tramadol – mild-mod pain
Antidepressants Amitriptyline, nortriptyline, imipramine, desipramine Venlafaxine, duloxetine Anticonvulsants Gabapentin, Pregabalin Topical agents Capsaicin Lidocaine patch |
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2nd line agents diabetic neuropathy
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Opioids – after 1st line, if needed
Other antidepressants SSRI Other Anticonvulsants Carbamazepine Phenytoin Others Mexiletine |
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Post herpatic neuralgia defn
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Pain persisting for > 3 months after the onset of
herpes zoster lesions. OTHER DEFINITIONS – used in research Pain continuing for > 1 month after the onset of herpes zoster lesions Pain continuing for > 1 month after the healing of herpes zoster lesions Pain persisting for 6 weeks, 3 months, or 6 months after the crusting of herpes zoster skin lesions |
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pain of post herpatic neuralgia
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Dysesthesia
Constant - deep, aching, bruised or burning Paroxysmal - electrical pain Superficial - sharp, radiating, burning, tender Allodynia Hyperalgesia |
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clinical features of post herpatic neuralgia: distn of pain
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Thoracic dermatomes in majority of patients
Trigeminal (especially ophthalmic division) Lumbar dermatome (10% to 20% of patients) Cervical dermatome (10% to 20% of patients) |
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1st line tx postherpatic neuralgia
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1st line – TCA, gabapentin, pregabalin
Topical agents - capsaicin, lidocaine |
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2nd line tx postherpatic neuralgia
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2nd line – carbamazepine, phenytoin, opioids
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postherpatic neuralgia tx
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Regional and local anesthetic blocks are NOT effective for long-term relief
Neural Stimulation Transcutaneous electrical nerve stimulation (TENS) Spinal cord stimulation (SCS) Surgical procedures for refractory PHN who are suicidal or terminally ill Cordotomy, rhizotomy, sympathectomy |
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post herpatic neuralgia prognosis
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Variable course
Many cases resolve spontaneously Remissions and exacerbations Chronic pain that is difficult to manage Drug discontinuation trials are appropriate in responders to pharmacotherapy |
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trigeminal neuralgia defn
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Sudden, unusual, unilateral, severe, brief, stabbing, recurrent pains in the distribution of one or more branches of the 5th cranial nerve.”
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trigeminal neuralgia pathogenesis
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Primary TGN – no known structural cause
Secondary TGN – pain due to compression or demyelination Central mechanism – spontaneous discharges by disinhibited neurons in the pons Peripheral mechanism – compression of the nerve root by aberrant blood vessels rationale for surgical decompression treatment |
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trigeminal neuralgia
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Face Pain: lips, gums, teeth, cheek, chin
Maxillary & mandibular divisions of trigeminal nerve Nerve supplies sensation to the skin of face and anterior half of the head Fewer cases affect the ophthalmic division Prevalence 3-5/100,000 R>L Female:Male 1.74:1 Increase with age, most common ages 50-70 |
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trigeminal neuralgia presentation
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Unilateral sharp, jabbing, lancinating electrical pain
Day or night but rarely during sleep Pain precipitated by physical triggers Pain attacks lasting a few seconds, pain free in between pain can so frequent as to appear constant Exacerbating and remitting course |
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1st line trigeminal neuralgia tx
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carbamazepine +/- baclofen
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2nd line trigeminal neuralgia tx
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gabapentin, TCAs, opiods, other anticonvulsants
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invasive therapy for trigeminal neuralgia
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Trigeminal nerve block with local anesthetic and steroid
Decompression – place a “cushion” between nerve and aberrant blood vessel, 90% initial success, pain may recur Destructive – radiofrequency, cryotherapy, or alcohol or glycerol to “lesion” the offending nerve branch; higher incidence of side effects and failure |
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trigeminal neuralgia prognosis
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Episodic pain
Pain episodes followed by months to years without pain Drug holidays appropriate in responders to pharmacotherapy |
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Central post stroke pain (CPSP) defn
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DEFINITION: Pain due to a lesion or dysfunction in
the brainstem or brain PREVALENCE – up to 11% of stroke victims ONSET – weeks to years after stroke PATHOGENESIS - Ischemia or hemorrhage Vascular lesions Trauma Neoplasm |
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CPSP presentation
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Pain in a region of abnormal sensory exam (deficit)
unilateral or localized pain deficit in warm/cold or sharpness discrimination may/may not have accompanying motor deficits Dysesthetic burning pain, intermittent stabbing pain Paresthesias squeezing, gnawing, crawling, tingling Allodynia and hyperpathia Autonomic instability changes in cutaneous blood flow in painful area lowered skin temperature Deficits in temperature sensations or sharpness discrimination accompanied by allodynia in presence of a history of stroke make the diagnosis of CPSP likely |
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1st line CPSP tx
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TCA (up to 66% initial response)
TCA + AC or Mexiletine Opioids |
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2nd line CPSP tx
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gabapentin, valproate, carbamazepine,
phenytoin |
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CPSP other treatments
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Peripheral sympathetic blocks (local anesthetic)
Transcutaneous electrical nerve stimulation (TENS) Spinal cord stimulation (SCS) Deep brain stimulation (refractory cases) Surgical – rhizotomy, cordotomy may not provide long-term success |
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why are opiods used to treat pain?
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Opioids relieve the subjective suffering component of pain, without interfering with basic sensations (eg, light touch, pinprick, temperature, position, etc.)
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Chronic pain assessment before starting opioids
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Collect the data:
Pain history & pain assessment Medical history Psychiatric history Psychological evaluation Physical exam Imaging Laboratory tests Neurophysiologic testing Develop the therapeutic strategy: Multimodality therapy usually needed for chronic pain |
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10 steps to universal precautions in pain medicine
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1. make a diagnosis with appropriate differential
2. psychological assessment including risk of addictive disorders 3. informed consent 4. treatment agreement 5. pre/post intervention assessment of pain level and fxn 6. appropriate trial of opiod therapy w/ or w/out adjunctive mediation 7. reassessment of pain score and level of fxn 8. regularly assess the four As of pain medicine 9. periodically review pain diagnosis and comorbid conditions, including addictive disorders 10. documentation |
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what are the 4 As in opioid medicine?
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analgesia
activity adverse effects aberrant behavior |
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phaysical and emotional impact of chronic pain
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Loss of appetite
Sleep disturbance Altered posture Decreased activity Decreased libido Family dysfunction Mood alteration --depression --anxiety Decline in health status Decline in function Decline in quality of life |
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Desired outcomes for chronic pain mgmt
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Maintain / improve function and quality of life
Best possible physical, emotional, and social functioning Increase patient participation in their care Increase the patient’s sense of control Partial pain relief, partial pain control Minimize or manage side effects of treatment Tolerable side effects No aberrant drug-related behaviors |
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what is the MAIN desired outcome for chronic pain mgmt?
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Maintain/Improve QoL and function
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Why is PARTIAL pain relief the goal of chronic pain tx?
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Average relief of pain intensity is 32%.
60% - 70% of patients will report < 50% reduction in pain. Seldom is pain score < 4 recorded. (Turk, Clin J Pain, 2002) Patients confuse pain intensity and pain suffering and may seek increased dose to relieve emotional aspect of pain. Tolerance to mood effects seems to occur more rapidly than tolerance to analgesia. 30-40% of patients do not respond to opioids. |
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Response to chronic opioid pain tx
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Average relief of pain intensity is 32%.
60% - 70% of patients will report < 50% reduction in pain. Seldom is pain score < 4 recorded. (Turk, Clin J Pain, 2002) Patients confuse pain intensity and pain suffering and may seek increased dose to relieve emotional aspect of pain. Tolerance to mood effects seems to occur more rapidly than tolerance to analgesia. 30-40% of patients do not respond to opioids. |
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what is the downside to opioid chronic pain tx?
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Opioid-induced hyperalgesia may develop in high-dose opioid ?? (>200~300 mg daily morphine equivalence).
Characterized by increased sensitivity to pain. Changes in NMDA receptors, neurotoxicity and increased sensitivity associated with tolerance process are possible mechanisms. Endocrine effects can impact mood/psychosocial function. Hypogonadism in males and females Opioid drugs may affect immunity through their neuroendocrine effects, or through direct effects on the immune system. ***Increased pain sensitivity*** |
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when to initiate opioid therapy
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After all other appropriate alternative therapies have failed
Pharmacological Non-pharmacological If the physician and patient decide on a long-term commitment to opioid treatment, then the treatment should be goal-directed and carefully controlled. Opioids used in combination with other modalities |
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Opioid agreement/informed consent
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Details of procedures and expectations between patient and prescriber.
Reminder that opioid treatment is part of total treatment plan. Partial analgesia (30% - 60% pain relief) as treatment goal Improvement in function as treatment goal Limitations on prescribing of opioids. Refill and dose-adjustment procedures. Emergency issues. Prohibited behaviors and grounds for tapering off opioids. Exit strategy |
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exit strategy for opioid treatment
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Agree with patient on criteria for failure of opioid therapy
Common criteria for failure of chronic opioid therapy Lack of significant pain reduction Lack of improvement in function Continued or unmanageable side effects Persistent noncompliance Violation of opioid agreement Document method for tapering off opioids |
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Realistic goals for chronic opioid treatment
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Complete pain relief is not realistic
Reach agreement with patient on individualized goals for treatment Goals must be meaningful and behavior based Common goals: Pain reduction Improved function Improved mood Improved work-related activities |
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clarify functional goals for patient:
realistic behavior based measurable desirable "I" centered |
pain free is not realistic
walking is a behavior can be counted and tracked in a log based on patient motivations patient is in charge of goal achievment, no the provider |
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Function indicators: ADLs
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Bathe or shower myself,
Comb or brush hair, Dress myself, Feed myself, Use the toilet myself |
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patient participation in pain relief health care
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Attend physical therapy appointments,
Attend mental health appointments, Attend/complete substance abuse programs/treatments, Attend individual, couples, family, or group therapy, Take pain medication as instructed, Take mental health medications as instructed, No emergency room visits for chronic pain Practicing stress management & relaxation techniques |
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patient chosen physical activities
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Do home exercises every day,
Walk for ( ) minutes each day, Gradually increase the time walked each day, Go swimming ( ) each week, Engage in sexual activities. |
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patient chosen social activities
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Visit friends, relatives,
Go on family outings, Go out to eat, Go to the movies, Play cards or other games, Participate in a hobby Take a ride in a car or bus, Take a trip, Participate in a recreational activity, Join a club, group or organization, Go to a park or beach. |
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patient chosen work around the home
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--Go grocery shopping,
--Go shopping at the mall, --Prepare a meal, --Wash dishes, --Do the laundry, --Make the bed, --Mow the lawn, --Put groceries away, --Set the table for meals, --Take out the garbage, --Work in the garden --Work on the car --Wash the car --Work on a needed household repair --Help with house cleaning (dusting, sweeping, vacuuming, etc.) |
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function indicators: work related activities
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Continue working
Return to work Train for a new or different job Start a new or different job Become a volunteer |
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WHO Step ladder:
Mild pain |
ASA
Acetaminophen NSAIDs ± Adjuvants |
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WHO Step ladder:
Mod pain |
APAP/Codeine
APAP/Hydrocodone APAP/Oxycodone APAP/Dihydrocodeine APAP/Tramadol Tramadol ± Adjuvants |
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WHO Step ladder:
Severe pain |
Morphine
Hydromorphone Methadone Levorphanol Fentanyl Oxycodone Oxymorphone ± Adjuvants |
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4 classes of opioids:
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morphine
pentazocine meperidine methadone |
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Disadvantages of SA opioids for around the clock pain
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Patient become his own prescriber – anxiety
Patient experiences recurring peaks & valleys of opioid concentration Continues to experience the pain we are trying to control Side effects Withdrawal between doses Conditions patients to euphoria Conditions patients that no euphoria = no analgesia Patient awakens once or twice each night Patient must make the pills last |
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LA opioids, what are they effective for
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Morphine, Oxycodone, Oxymorphone, Fentanyl TDS, Methadone, Levorphanol
Effective for continuous pain (Caldwell et al, 1999; Caldwell et al., 2002; Hale et al., 1999; Lloyd et al., 1992; Peat et al., 1999; Salzman et al., 1999) Smoother pain control Analgesia for the dosage interval |
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advantages of LA opioids
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Analgesia throughout the dosing interval
Less frequent dosing = less focus on pill taking pill taking is a reminder of pain & disability Produce less euphoria Less drug craving and compulsive pill taking People who use drugs compulsively prefer SA opioids (rapid onset/offset drugs) |
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Opioids in NP pain
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Oxycodone CR in post-herpetic neuralgia
Oxycodone CR in diabetic neuropathy Morphine CR in phantom limb pain Morphine CR or Methadone vs TCA in postherpetic neuralgia Levorphanol in varied central and peripheral neuropathic pain syndromes Intravenous fentanyl in neuropathic pain |
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Know how to convert to morphine equivalents
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you will be given the conversions on the exam, just know how to apply them
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methadone dosing for opioid naive patients
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Start with 2.5 mg q12hr
If medically fragile start with 2.5 mg once daily EDUCATE THE PATIENT |
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methadone patient education
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Does not mean the patient is an addict
Three mechanisms of action - compared to one for other opioids Up to 14 days to reach maximum effects – with each dose change Slow accumulation means that it is DANGEROUS to self-increase the dose – danger of respiratory depression or death Most patients with chronic severe pain partial pain relief is the best response achievable. Emphasize improved function as the required outcome. Pain intensity often will not decrease more than 30%. |
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opioid drug selection (LA, SA, etc)
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Long-acting opioid “around-the-clock” (not PRN)
Preferred approach for patients with constant severe pain Long-acting opioid plus short-acting opioid PRN May or may not be appropriate; individualized Rescue doses for break-through or incident pain 10% to 20% of total daily dose |
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opiod dose increases
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Titrated to partial relief (30% relief) or intolerable side effects
Dose increases should be a percentage of the current dosage 20% to 50% increases in daily dose Equal to the daily “rescue” during prior days Less than 20% increases not likely to produce a change in response and can increase pain-related patient anxiety. |
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maximum opioid dose???
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Best support in the literature (randomized trials) of doses up to 180 mg/day of morphine or equivalent
Conservative approach Morphine SA 180 mg/day or equivalent Methadone 40-60 mg/day Higher doses may be appropriate in selected patients Must result in functional improvement No aberrant behaviors |
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mgmt opioid SEs: N/V
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switch opioids, antiemetics
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mgmt opioid SEs: constipation
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Stool softeners;
stimulant laxatives; non-pharmacologic measures; switch opioids |
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mgmt opioid SEs: itching
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Antihistamines;
switch opioids |
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mgmt opioid SEs: endocrine dysfxn
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Monitor; testosterone
replacement; endocrine consultation |
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mgmt opioid SEs: sedation
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Lower dose; switch opioids;
add co-analgesics; add stimulants |
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mgmt opioid SEs: edema and sweating
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Switch opioids
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mgmt opioid SEs: confusion
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Lower dose; switch
opioids |
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mgmt opioid SEs: dizziness
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Antivertigo agents
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tolerance to opioids
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A state of adaptation in which exposure to a drug induces changes that result in a decrease in one or more of the drug’s effects over time.
Require higher doses at same interval Require the same dose more frequently Rarely “drives” dose escalation Does not cause addiction Tolerance to side effects is desirable |
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physical dependence to opioids
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A state of adaptation that is manifest by a drug class specific withdrawal syndrome
Withdrawal syndrome can by produced by: Abrupt cessation Rapid dose reduction Decreasing blood level of drug Administration of antagonist Assumed to be present after a few days of use but highly variable Does not independently cause addiction Avoided by gradual reduction in dose Other drugs cause physical dependence as well Antihypertensives, Antidepressants, Nicotine, Caffeine, etc. |
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pseudoaddiction for opioid use
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Aberrant drug-related behavior as a manifestation of inadequate pain management
Drug-seeking Concerns about availability “Clock-watching” Unsanctioned dose escalation Can be mistaken for addiction Resolves with adequate analgesia |
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Addiction to opioids
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A primary, chronic, neurobiologic disease
Genetic, psychosocial, & environmental factors involved Behavior manifestations include: Craving Impaired control over drug use *Compulsive use despite harm Diagnosed by observance of a pattern of repeated aberrant drug-related behavior |
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signs of a pain patient
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Able to control use of medications
Medications improve function and/or quality of life Will want to decrease medication if side effects are present or troublesome Continue to have concern about the physical problem that causes the pain Follows the agreement for the use of opioids Frequently has medication left over from the previous visit |
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signs of an addict
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Out of control with medications
Medications decrease function and/or quality of life Continues or increases medication despite side effects Unaware of or in denial of any problems related to the pain Does not follow the agreement for the use of opioids Has no medication left over, loses prescription or meds, & always has a “story” Alters route of administration Forges prescriptions Steals medicines |
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checklist for signs of opioid dependence (addiction)
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Frequently runs out early
Multiple dose self-escalations or other noncompliance despite warnings Multiple episodes of prescription loss Angry, demanding, or tearful of not given drug of choice Observed to be intoxicated or in withdrawal Accesses multiple sources of opioids Threatens or harasses staff for immediate appointments Reluctant to try alternatives Decline in function while treated with opioids Concurrent abuse of alcohol or illicit drugs |
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structure for prescribing chronic opioid tx
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1. Assess for risk of drug abuse prior to prescribing opioids.
2. Stratify patients into regimens based on risk level. 3. Monitor patients according to risk level. Use proactive rather than reactive strategies 4. Reassess treatment plans and goals frequently. Adjust as needed Document thoroughly (the 4 A’s). |
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Triage pts. into risk based regimens
(High vs low) |
High addiction risk
Weekly visits and Rxs Only a long-acting opioid Frequent monitoring Urine tests – scheduled and random Pill counts – scheduled and random Low addiction risk Long-acting opioid Short-acting opioid for “breakthrough” pain Less frequent monitoring Monitory, intervene, and adjust treatment regimens proactively |
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chronic OCD
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Chronic for most patients
Comorbid depression, other anxiety d/o, SAD Significantly impaired QOL |
