chronic pain management

85
A National Pain Education Council Program Module 1 Module 1 Progress in Chronic Pain Progress in Chronic Pain Management Management Understanding, Impact, Understanding, Impact, Awareness and Advances Awareness and Advances

Upload: webzforu

Post on 03-Nov-2014

46 views

Category:

Health & Medicine


8 download

DESCRIPTION

 

TRANSCRIPT

Page 1: Chronic pain management

A National Pain Education Council Program

Module 1Module 1

Progress in Chronic Pain ManagementProgress in Chronic Pain Management

Understanding, Impact, Understanding, Impact, Awareness and AdvancesAwareness and Advances

Page 2: Chronic pain management

What is Pain?

PAIN: an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage, or both.

CHRONIC PAIN: persistent or recurrent pain, lasting beyond the usual course of acute illness or injury, or more than 6 months, and adversely affecting the patient’s well-being.

(American Society of Anesthesiologists, 2002; Loeser et al, 2001; Merskey H et al, 1994; Portenoy et al, 1996)

Page 3: Chronic pain management

Pain Classification Schemes

• Anatomy or Body Location (low back pain)

• Duration (acute, chronic)

• Etiology (somatogenic, psychogenic)

• Body System (e.g., myofascial, rheumatic, causalgic)

• Severity (0-10 scale)

• Mechanism (e.g., tissue injury, nervous system injury)

(Loeser et al, 2001)

Page 4: Chronic pain management

Multidimensional Classification of Pain

IASP expert multi-axial classification of chronic pain • Axis I: Regions• Axis II: Systems• Axis III: Temporal Characteristics• Axis IV: Patient’s Statement of Intensity• Axis V: Etiology

Example:

Mild postherpetic neuralgia of T5 or T 6; 6 months’ duration = 303.22eAxis I: Thoracic regionAxis II: Nervous system (central, peripheral, or autonomic); physical

disturbance/dysfunctionAxis III: Continuous or nearly continuous, fluctuating severityAxis IV: Mild severity of 1 to 6 monthsAxis V: Trauma, operation, burns, infective, parasitic (one of these)

(Loeser et al, 2001; Merskey et al, 1994)

Page 5: Chronic pain management

Prevalence and Impact of Chronic Pain on Society

• Chronic pain is one of the most common conditions for which people seek medical treatment

• 35% of Americans suffer from chronic pain

• >50 million Americans are partially or totally disabled by chronic pain

• 50 million workdays are lost per year

• $100 billion is the estimated annual cost in lost productivity, medical costs, and lost income

(American Pain Society, 2001; Gitlin, 1999; Glajchen 2001; Loesser et al, 2001)

Page 6: Chronic pain management

Undertreatment of Chronic Pain

• >40% to 50% of patients in routine practice settings fail to achieve adequate pain relief

• In a recent study of 805 chronic pain sufferers, >50% had to change physicians to achieve relief because the physician:

– was unwilling to treat pain aggressively– did not take the patient’s pain seriously– had inadequate knowledge about pain

treatment

(American Pain Society, 2001; Glajchen, 2001; Lister, 1996; Portenoy, 1996)

Page 7: Chronic pain management

Common Barriers toTreatment of Chronic Pain

Physician-Related• Limited knowledge of pain pathophysiology and assessment skills

• Biases against opioid therapy and overestimation of risks

• Fear of regulatory scrutiny/action

Patient-Related• Exaggerated fear of addiction, tolerance, side effects

• Reluctance to report pain: stoicism, desire to “please” physician

• Concerns about “meaning” of pain (associate increased pain with worsening disease)

System-Related• Low priority given to pain and symptom control

• Limits on number of Rxs filled per month & number of refills allowed• Reimbursement policies

(American Pain Society, 2001; Glajchen, 2001; Lister, 1996; Portenoy RK, 1996; Weinstein et al, 2000)

Page 8: Chronic pain management

Ethnic and Racial Barriers to Treatment

• Language or cultural differences make pain assessment more difficult

• Physicians’ perceptions and misconceptions:

– minority-group patients have fewer financial resources to pay for prescriptions

– higher drug-abuse potential among minority groups

• Patients’ lack of assertiveness in seeking treatment

• Lack of treatment expertise at many sites at which minority-group patients are treated

• Relative unavailability of opioids in some communities

(Bonham, 2001; Glajchen, 2001)

Page 9: Chronic pain management

Evolving Attitudes Toward Opioid Use

Historically, opioids were emphasized in terminally ill patients, and de-emphasized in chronic nonmalignant pain management.

However, from the 1980’s to the present :

• Attitudinal/perceptual changes on opioid use in nonmalignant chronic-pain treatment

• More use of long-term opioid therapy in diverse pain syndromes– slowly growing evidence base– acceptance by pain specialists– acceptance by government and medical associations

– increased reassurance from the regulatory community

(Joranson et al, 2000; Portenoy et al, 1986)

Page 10: Chronic pain management

Recent DevelopmentsIn Pain Management

• Greater understanding of the pathophysiology underlying chronic pain syndromes

• Scientific breakthroughs in molecular biololgy; insight into pain at the molecular level

• Advances in drug therapy (drug delivery technologies)

• Multimodal therapy

• Multidisciplinary teams, shared decision-making that includes patients

• Patients’ rights movement

(JCAHO, 1999; Loeser et al, 2001)

Page 11: Chronic pain management

Recent Organized Support forthe Treatment of Pain

National Organizations Issue Guideines• U.S. Agency for Health Care Policy and Research (HCPR)—1992• U.S. Department of Health and Human Services—1994• AAPM/APS Consensus Statement—1996• American Society of Anesthesiologists—1997• WHO; FSMB—1998• AMA; APS (sickle-cell anemia)—1999

• American Pain Society: Clinical Guideline for Arthritis—2002

State-Led Initiatives• Legislation in form of Intractable Pain Acts (>10 states by 1999)• Guidelines for pain management (>18 states by 1999)• State Cancer Pain Initiatives

(AAPM/APS, 1996; AMA, 2001; ASA, 1997; FSMB, 1998; JCAHO, 1999; WHO, 1996)

Page 12: Chronic pain management

Progress in Chronic Pain Management

Chronic Pain Syndromes:Cancer

Chronic Low Back Pain Osteoarthritis Fibromyalgia

A National Pain Education Council Program

Module 2Module 2

Page 13: Chronic pain management

Cancer Pain

Epidemiology

• Cancer pain is highly prevalent– 30%-50% of those in active therapy

– 75%-90% of those with advanced disease

– approximately 25% of those in nursing homes

(Bernebei et al, 1998; Caraceni et al,1999; Cleeland et al, 1994; Heim et al, 1993; Portenoy, 1994; Portenoy et al, 1992; Serlin et al, 1995)

Page 14: Chronic pain management

Cancer Pain

Inferred Pathophysiology• Nociceptive: deemed consistent with apparent

degree of tissue injury

– Somatic: related to ongoing activation of

somatic primary afferents

– Visceral: related to activation of primary

afferent neurons that innervate viscera

• Neuropathic: sustained by aberrant somatosensory processing in the peripheral nervous system or CNS

(Portenoy, 2000)

Page 15: Chronic pain management

Cancer Pain

Diagnosis: Clinical Considerations

• Acute or chronic

• Nociceptive, neuropathic or mixed pain

– tumor-related (e.g., metastatic bone disease, nerve

compression or infiltration)

– treatment-related (chemotherapy, radiation or

surgery)

– unrelated to cancer or treatment

(Portenoy , 2000; Portenoy et al, 1996)

Page 16: Chronic pain management

Cancer Pain

Principles of Assessment • Pain History

– chronicity– intensity and severity– pathophysiology and mechanism– tumor type and stage of disease– pattern of pain and syndrome

• Physical and Neurologic Examination• Radiographic Findings

(Cleeland CS et al, 1992; Jacox et al, 1994; Portenoy et al, 199; Turk et al, 1994; Wall et al, 1994)

Page 17: Chronic pain management

Cancer Pain

Treatment Considerations

• Identify the cause of the pain• Primary treatment if indicated• WHO ladder combined with etiology-specific therapies

for syndromes– pharmacologic and nonpharmacologic interventions – long-acting + short-acting opoids – adjuvant medications for neuropathic pain– NSAIDs and steroids can be helpful when there is an

inflammatory component to pain

(Jacox et al, 1994)

Page 18: Chronic pain management

04/08/2304/08/23

WHO Guidelines for Cancer Pain

• Step 3: Opioids for moderate-to-severe pain +/- non-opioid +/-adjuvant therapy

• Step 2: Opioids for mild- to-moderate pain +/- non-opioid +/- adjuvant therapy

• Step 1: Non-opioid +/- adjuvant therapy

STEP 1STEP 1

STEP 2STEP 2

STEP 3STEP 3

GOAL:GOAL:Freedom From PainFreedom From Pain

Pain Persists

Pain Persists

(Adapted from Portenoy et al, 1997)

Page 19: Chronic pain management

Epidemiology

• 60%–85% lifetime prevalence

• Second most common complaint to prompt medical evaluation

• Leading cause of long-term work disability

• Most common reason for early Social Security disability in US

• U.S. indirect costs: $33 billion annually

• Disability and costs related to pain, not to the disease process

(Loesser et al, 2001; Wall et al, 1994)

Chronic Low Back Pain

Page 20: Chronic pain management

Chronic Low Back Pain

Pathophysiology

• Activation and sensitization of the nerve root nervi nervorum from root compression/traction

• Sensitization of the nociceptors of the annulus fibrosus, periosteal spinal structures, and ligaments, due to acute inflammation, e.g., status post-trauma

• Hyperalgesia (deep spinal and dermatomal) due to central sensitization

(Loesser et al, 2001)

Page 21: Chronic pain management

Clinical Characteristics

• Preoccupation with pain • Consistently disabled from pain• Depression and anxiety are common • High incidence of psychiatric diagnoses• Drug misuse is common, but addiction

relatively rare

(Wall et al, 1994)

Chronic Low Back Pain

Page 22: Chronic pain management

Diagnosis • History

– medical, psychosocial– pain: location, duration, severity, alleviating/ aggravating

influences

• Physical Examination– posture and range-of-motion evaluation– routine neurologic and vascular exams

• Imaging Studies– X-rays with flexion/extension– MRI– CT in some

(Wall et al, 1994)

Chronic Low Back Pain

Page 23: Chronic pain management

Treatment Considerations

• Analgesic Medications

• Adjuvant Analgesics

• Physical Therapy Approaches

• Neural Stimulation

• Psychologic Management

• Multidisciplinary Pain Centers

(Portenoy et al, 1994)

Chronic Low Back Pain

Page 24: Chronic pain management

Osteoarthritis (Degenerative Joint Disease)

Epidemology

• Most common form of arthritis worldwide

• Occurs most in women and in adults over age 45

• Occurs in 80% of people over 55 years of age

• Affects >40 million people in US (1 in 6)

• 23% experience limitation of activities

• Cost in medical care and lost wages ~$95 billion

(Elders, 2000; Loeser et al, 2001; Merskey et al, 1994)

Page 25: Chronic pain management

Osteoarthritis

Pathophysiology• Progressive loss of articular cartilage

• Chondrocytes produce metalloproteinases that degrade cartilage and cause fissuring, pitting, erosion, and denuded areas

• Subchondral bone thickens and osteophytes, or bone spurs, form

• Synovium thickened (contains moderate amount of lymphocytes, plasma cells)

• Joint capsule and ligaments hypertrophied

(Loesser et al, 2001; Wall et al, 1994)

Page 26: Chronic pain management

Osteoarthritis

Clinical Characteristics• Deep aching pain, poorly localized

• May occur in one or two joints or be generalized

• Pain occurs in involved joint and is relieved by rest

• Joint stiffness in morning and after periods of inactivity

• Aching “night pain” is common

• If pain is severe on activity and asymptomatic at rest, evaluate for neurogenic claudication

(Loesser et al, 2001)

Page 27: Chronic pain management

Osteoarthritis

Diagnosis

• History: age, functionality, degree of pain, stiffness, time of occurrence (e.g., morning, at rest, during activity)

• Physical examination: range of motion, tenderness, bony enlargement of joint

• Laboratory findings: radiograph, CBC, synovial fluid analysis

(Loesser et al, 2001; Manek et al, 2000)

Page 28: Chronic pain management

Osteoarthritis

Treatment Considerations: First, perform a First, perform a comprehensive assessment of pain and functioncomprehensive assessment of pain and function

Mild-to-moderate pain Acetaminophen

Moderate-to-severe pain COX-2 NSAIDS

Severe arthritis pain: COX-2 drugs and non-specific NSAIDs do not provide substantial relief

Opioids

Drug therapy ineffective and function severely impaired

Surgical Treatment

(ACR, 2000; APS, 2002; Manek et al, 2000)

Page 29: Chronic pain management

Fibromyalgia Syndrome

Epidemiology• 4–7 times more common in adult women than in

men; highest prevalence in women 50–60 yrs

• Approximately 2% of general population in U.S. and Canada have symptoms that could meet ACR criteria

• Long-term follow-up studies suggest that fibromyalgia is not a syndrome representing a transition from one disorder to another

(Loesser et al, 2001; Portenoy et al, 1996; Wall et al, 1994)

Page 30: Chronic pain management

PathophysiologyEtiology is unknown: 3 views of pathophysiology have emerged:• Central Nervous System (neurogenic)

– generalized pain– increase in CSF substance P– decrease in serum and CSF serotonin

• Muscle Pathology– decreased oxygen tension and blood flow – abnormal muscle biopsies– weakness

• Psychopathology– anxiety, depression

(Loeser et al, 2001; Portenoy et al, 1996; Wall et al, 1994)

Fibromyalgia Syndrome

Page 31: Chronic pain management

Clinical Characteristics

• Pain (musculoskeletal tenderness)• Lightheadedness, dizziness, syncope• Fatigue• Chronic insomnia; sleep disturbance• Cognitive deficits/short-term memory loss• Depression/anxiety• Numbness, dysesthesia in hands and feet

(Loeser et al, 2001)

Fibromyalgia Syndrome

Page 32: Chronic pain management

DiagnosisBased on the 1990 ACRclassification guidelines:• 1 historical feature + 1 physical finding

• Historical feature = widespread (axial) pain of 3 months or more

• Physical finding = pain in at least 3 of the 4 body segments + a finding of at least 11 tender points on digital palpation of 18 designated tender points

(Merskey et al, 1994; Portenoy et al, 1996; Wall et al, 1994; Wolk M, 2002)

Fibromyalgia Syndrome

Page 33: Chronic pain management

Treatment: A Multidisciplinary Approach

• Patient Education

– reading materials, videos, support groups

• Physical Exercise

– low-grade (muscle stretches, aerobic conditioning)

• Pharmacologic Therapies

– tricyclic antidepressants, NSAIDS, topical capsaicin, opioids*

*Drug therapies have been used with varying degrees of success in treating fibromyalgia.

(Portenoy et al, 1996; Wall et al, 1994)

Fibromyalgia Syndrome

Page 34: Chronic pain management

Pathophysiology of Pain

• Inferred from characteristics, etiology or pathophysiology

• Types

– nociceptive

– neuropathic

– idiopathic

• Therapeutic implications

(Portenoy et al, 1996)

Page 35: Chronic pain management

Pathophysiology of Chronic Pain

• In chronic pain, the nervous system remodels continuously in response to repeated pain signals

– nerves become hypersensitive to pain

– nerves become resistant to antinociceptive system

• If untreated, pain signals will continue even after injury resolves

• Chronic pain signals become embedded in the central nervous system

(Marcus, 2000)

Page 36: Chronic pain management

Peripheral and Central Pathways for Pain

Ascending TractsAscending Tracts Descending TractsDescending Tracts

Cortex

Midbrain

Medulla

Spinal Cord

Thalamus

Pons

(Brookoff, 2000)

Page 37: Chronic pain management

Pain-Sensing System in the Malfunction in Chronic Pain

(Illustration: Seward Hung, 2000)

Acute pain:Pain-sensing signals are initiated in response to a stimulus

• They elicit a pain-relieving response

Chronic pain:Pain signals are generated for no reason and may be intensified

• Pain-relieving mechanisms may be defective or deactivated

Pain Sensing

In chronic pain, pain signals are generated without physiologic significance

Page 38: Chronic pain management

Nociceptive Pain

Presumably results from ongoing activation of primary afferent neurons responding to noxious stimuli

• Pain consistent with degree of tissue injury

• Described as aching, squeezing, stabbing, throbbing

• Subtypes:

– Somatic: related to activation of somatic afferent neurons

– Visceral: related to activation of visceral afferent neurons

(Loeser et al, 2001; Portenoy et al, 1996)

Page 39: Chronic pain management

Neuropathic Pain

• Initiated by a primary lesion in the nervous system; believed to be sustained by aberrant somatosensory processing in the peripheral or central nervous system

• Independent of obvious ongoing nociceptive activation

• Burning, shooting, electrical quality; may be aching, throbbing, sharp

• Subtypes:

– Presumed “central generator”

deafferentation pain (central pain, phantom pain)

Sympathetically-maintained pain

– Presumed “peripheral generator”

Polyneuropathies and mononeuropathies

(Portenoy et al, 1996)

Page 40: Chronic pain management

Idiopathic and Psychogenic Pain

Idiopathic Pain

• Usually exists in the absence of an identifiable physical or psychologic pathology that could account for pain

• Uncommon in patients with progressive illness

Psychogenic Pain

• Presents positive evidence of a predominant psychologic contribution and may be labeled with a specific psychiatric diagnosis

(Loeser et al, 2001; Merskey et al, 1994; Portenoy et al, 1996)

Page 41: Chronic pain management

Therapeutic Modalities for Chronic Pain Management

Assessment

A National Pain Education Council Program

Module 3Module 3

Progress in Chronic Pain Management:Progress in Chronic Pain Management:

Page 42: Chronic pain management

Pain Assessment

• Characterize the pain

• Characterize the disease, relationship between pain and disease and potentially treatable etiologies

• Clarify syndromes and infer pathophysiology

• Determine need for urgent therapy

• Identify other needs

• Develop a therapeutic strategy

(Portenoy et al, 1997)

Page 43: Chronic pain management

Components• History: temporal features, intensity, topography, quality,

exacerbating/alleviating factors• Physical Exam: determine existence of underlying

pathology

• Lab and Radiographic Tests: appropriate to pain syndrome

Assessment Tools• Pain Intensity Scales: VAS, NAS, “faces” scale

• Multidimensional Pain Measures: Brief Pain Inventory, McGill Pain Questionnaire

(Portenoy et al, 1997)

Pain Assessment

Page 44: Chronic pain management

Pain Intensity Rating Scales

• Visual Analogue Scale (VAS)

No painNo pain ----------------------------------- ----------------------------------- Worst painWorst pain

• Categorical Scale

None (0) Mild (1 None (0) Mild (1 – 4) Moderate – 4) Moderate (5 (5 – 6) Severe – 6) Severe (7 – 10(7 – 10) )

• Numerical Rating Scale-------------------------------------------------------------------------------------- 00

No painNo pain

1010Worst pain Worst pain imaginableimaginable

(Cleeland, 1991; Jacox et al, 1994)

Page 45: Chronic pain management

Pain Intensity Rating Scales

• Pain Faces Scale

00

No No hurthurt

22

Hurts Hurts just a just a

little bitlittle bit

44

Hurts a Hurts a little bit little bit moremore

66

Hurts Hurts even even moremore

88

Hurts a Hurts a whole whole

lotlot

1010

Hurts as Hurts as much as much as you can you can imagineimagine

• Brief Pain Inventory

Shade areas of worst painShade areas of worst pain

Put an X on area that hurts mostPut an X on area that hurts most

(Cleeland, 1991; Wong et al, 2001)

Page 46: Chronic pain management

Module 3

Progress in Chronic Pain Management

Therapeutic Modalities for Therapeutic Modalities for Chronic Pain Management:Chronic Pain Management:

TreatmentTreatment

A National Pain Education Council Program

Page 47: Chronic pain management

Therapeutic Optionsfor Chronic Pain Management

• Pharmacotherapy• Rehabilitative Approaches• Psychologic Interventions• Anesthesiological Approaches• Neurostimulatory Techniques• Surgery• Complementary/Alternative Approaches• Lifestyle Changes

(Portenoy et al, 1997)

Page 48: Chronic pain management

Chronic Pain Management: Pharmacotherapy

Analgesics

• Nonopioids

• Adjuvant Analgesics

• Opioids

(Cashman, 1996; Hanks et al, 1998; Galer, 1998; Stein, 1995)

Page 49: Chronic pain management

Nonopioid Analgesics:Acetaminophen

• Minimal anti-inflammatory effect

• Fewer adverse effects than other nonopioid analgesics

• Adverse effects: – renal toxicity

– risk of hepatotoxicity at high doses;

• increased risk with liver disease or chronic alcoholism

• No effect on platelet function

(Gilman et al, 2001)

Page 50: Chronic pain management

Mechanism of Action• Inhibit both peripheral and central cyclo-

oxygenase, reducing prostaglandin formation

• 2 isoforms of COX– COX-1: Constitutive, physiologic– COX-2: Inducible, inflammatory

Nonopioid Analgesics:Nonopioid Analgesics:NSAIDSNSAIDS

Page 51: Chronic pain management

Nonopioid Analgesics:NSAIDS

• Major recent advance: COX-2 selective NSAIDS

• COX-2 selective inhibitors have better GI safety profile; no change in platelet function

• Drug selection should be influenced by drug-selective toxicities, prior experience, convenience, cost

• Great individual variation in response to different drugs

• Use with caution in patients with renal insufficiency, congestive heart failure or volume overload

(Cashman, 1996: Langman et al, 1999; Simon et al, 1999)

Page 52: Chronic pain management

Adjuvant Analgesics

CLASS EXAMPLES

Anticonvulsants gabapentin, valproate, phenytoin,

carbamazepine, clonazepam, topiramate, lamotrigine

Antidepressants amitriptyline, desipramine, nortrip-

tyline, paroxetine, citalopram, others

Local Anesthetics mexiletine

Corticosteroids dexamethasone, prednisone

α-2 Adrenergic Agonists tizanidine

NMDA-Receptor Agonists dextromethorphan, ketamine

Topicals lidocaine, lidocaine/prilocaine, capsaicin

Miscellaneous baclofen, calcitonin

Adjuvant Analgesics for Neuropathic Pain

Page 53: Chronic pain management

Adjuvant Analgesics:Anticonvulsants

Common Characteristics• Most clinical experience: gabapentin, carbamazepine, phenytoin, valproate, clonazepam

• Limited data on efficacy of newer anticonvulsants • Used as an analgesic, dosing schedule is similar to anticonvulsant indication• Large inter-/intra-individual variability in analgesic response

Gabapentin• Usual first-line drug for neuropathic pain• Favorable safety profile• Positive controlled trials in PHN/diabetic neuropathy• No controlled studies in cancer patients• Usual starting dose 100-300 mg/day• Titration to identify responders/nonresponders• Usual effective dose 600-3600 mg/day; higher doses sometimes beneficial

(Galer, 1998; Rosner et al, 1996)

Page 54: Chronic pain management

Adjuvant Analgesics:Antidepressants

• Evidence is best for tricyclics

• SSRI/atypical antidepressants better tolerated

• Proven efficacy for all types of neuropathic pain, but often preferred for continuous dysesthesias

• Analgesic doses for tricyclics is usually less than the antidepressant dose

(Wall et al, 1999)

Page 55: Chronic pain management

Adjuvant Analgesics: Corticosteroids

• Shown to improve pain, appetite, nausea, malaise, quality of life in cancer patients

• In the cancer population, indicated for refractory neuropathic pain, and other indications: bone pain, bowel obstruction, capsular pain, lymphedema, headache

• In non-cancer pain, long-term use is limited to inflammatory conditions

• Usual drugs are prednisone and dexamethasone

(Lucas et al, 2002)

Page 56: Chronic pain management

Adjuvant Analgesics:α-2 Adrenergic Agonists

• Evidence of nonspecific analgesic effects

• Established analgesic effect of epidural clonidine in neuropathic cancer pain

• Tizanidine usually better tolerated (starting dose 1-2 mg/day; usual maximum dose up to 40 mg/day)

(Max et al, 1992; Sindrup et al, 990)

Page 57: Chronic pain management

Adjuvant Analgesics: NMDA-Receptor Antagonists

• N-methyl-D-aspartate receptor involved in neuropathic pain

• Commercially-available drugs in the U.S.: ketamine, dextromethorphan, amantadine

– Ketamine: dissociative anesthetic; can be used p.o. or IV/SC infusion

– Dextromethorphan: antitussive; starting dose 120 mg/day; maximum daily dosage one gram

– Amantadine: starting does 100 mg b.i.d.

(Herry et al, 1995; Nelson et al, 1997; Pud et al, 1998)

Page 58: Chronic pain management

Opioid Therapy: Classes of Opioids

Pure (Full) Agonists: Preferred for Chronic Pain• Bind to opioid receptor(s)• No antagonist activity• No ceiling effect

Agonist-Antagonists • Ceiling effect for analgesia• Can reverse effects of pure agonists

– mixed agonist-antagonists (butorphanol, nalbuphine, pentazocine, dezocine)

– partial agonists (buprenorphine)

Antagonists• Reverse or block agonist effects of pure opioids• Naloxone has been used to treat opioid overdose, addiction

(Jacoxet al, 1994; Portenoy et al, 1996)

Page 59: Chronic pain management

Short-Acting Opioids• Hydrocodone/APAP• Hydromorphone• Morphine• Oxycodone w or w/o

APAP• Oral transmucosal

fentanyl• Tramadol

Long-Acting Opioids• Transdermal Fentanyl• Methadone• Extended-release

morphine• Oxycodone CR

(Lucas et al, 2002)

Opioid Therapy: Drug Selection

Page 60: Chronic pain management

Opioid Therapy: Drug Selection

Advantages of Long-Acting Opioids

• Fewer peaks and troughs

– sustained pain relief

• Dosed less often, improved adherence

• Potentially improved patient satisfaction and quality of life

(Lucas et al, 2002; Weinstein et al, 2001)

Page 61: Chronic pain management

Opioid Therapy:Prescribing Principles

• Drug Selection: Elements to Consider– Severity of pain, previous exposure, availability,

patient’s preference, renal/liver function, cost

• Dose to Optimize Effects

– Fixed schedule (or around-the-clock) vs as-needed dosing; rescue doses

• Treat Side Effects

– Goal: balance between analgesia and side effects

• Manage the Poorly Responsive Patient

– Consider a variety of alternative strategies

(Weinstein et al, 2002)

Page 62: Chronic pain management

Opioid Therapy: Route of Administration

• Oral / Transdermal

• Rectal

• Parenteral (IV, SC)

• Intraspinal (epidural, intrathecal)

(Lucas et al, 2002)

Page 63: Chronic pain management

Opioid Therapy: Dosing

• By-the-clock (fixed-schedule) dosing with long-acting opioid plus an “as-needed” short-acting “rescue” opioid (usually 5%–15% of total daily dose, q 2-3 h prn)

• Baseline dose increases: 25%–100% orequal to “rescue” dose use

• Increase “rescue” dose as baseline dose increases

(American Pain Society, 1998)

Page 64: Chronic pain management

Equianalgesic Table

PO/PR (mg) Analgesic SC/IV/IM (mg)30 Morphine 10

4–8 Hydromorphone 1.5

20 Oxycodone -

20 Methadone 10

- Fentanyl 100 μg/h parenterally and transdermally 4 mg/h morphine parenterally; 1 μg/h transdermally

2mg/24h morphine PO

Page 65: Chronic pain management

Equianalgesic Conversions

Example:

• Patient receiving a total 24-hr dose of morphine 180 mg PO

• What is the equivalent 24-hour dose of PO hydromorphone?

• Morphine 30 mg PO = Morphine 180 mg PO• Hydromorphone 7.5mg PO X

• X = Hydromorphone 45 mg PO (6-8mg PO q 4hr)

• Determine starting dose of new drug based on this calculation

Page 66: Chronic pain management

One 25 mcg/h transdermal

fentanylpatch/3 days

(72 hours)

Conversion Chart for Starting Dose of Transdermal Fentanyl

(Adapted from Duragesic PI, 2001)

Fixed-combination short-acting opioids (6/day):

–Lorcet 5 mg/500 mg–Lortab 5 mg/500 mg–Percocet 5 mg/325 mg–Percodan 5 mg/325 mg–Tylenol + Codeine 30 mg/325 mg–Tylox 5 mg/500 mg–Vicodin 5 mg/500 mg

Long-acting opioids(2/day):– OxyContin 20 mg– MS Contin 30 mg

Multiple patches may be used for doses exceeding 100 mcg/h. Doses up to 6oo mcg/h have been evaluated in clinical trials.

Page 67: Chronic pain management

Opioid Titration

• Dose titration over time is key to successful opioid therapy

• There is no ceiling dose for pure-agonist opioids. Titrate dose upward for maximum pain relief with acceptable side effects

• Consider rescue medication for breakthrough pain

• Responsiveness of an each patient to each drug varies

• If a patient does not respond well on one opioid, it is important to try another (opioid rotation)

(Portenoy et al, 1997)

Page 68: Chronic pain management

Opioid Therapy: Patient Selection

• Thorough Evaluation – pain history – physical exam– coexisting conditions

• Review of Previous Medical/Pain History– any psychological disturbances– chronic pain history

• Substance Abuse History (including alcohol)– remote, recent or ongoing– patient goals/expectations

• consistent with physician’s?• feasible/reasonable?

(Haddox et al, 1997; Portenoy et al, 1996)

Page 69: Chronic pain management

Opioid Therapy:Monitoring Outcomes

Monitoring the 4 A’s

• Analgesia (pain relief)

• Activities of Daily Living (psychosocial functioning)

• Adverse Effects (side effects)

• Aberrant Drug-Taking (addiction-related outcomes)

(American Pain Society, 2002; Passik et al, 2000; Portenoy et al, 1997)

Page 70: Chronic pain management

Opioid Therapy: Managing the Poorly Responsive Patient

If dose escalation increases adverse effects

• Side-effect management

• Pharmacologic strategy to lower opioid requirement

– spinal route of administration

– add nonopioid or adjuvant analgesic

• “Opioid rotation”

– nonpharmacologic strategy to lower opioid requirement

(Mather, 2001)

Page 71: Chronic pain management

Opioid Therapy: Managing the Poorly Responsive Patient

Opioid Rotation• Based on large intra-individual variation in response

to different opioids• Reduce equianalgesic dose by 25%–50% with

provisos:– reduce less if pain severe

– reduce more if medically frail– reduce less if same drug by different route– reduce transdermal fentanyl less (no cutback

from equianalgesic dose)– reduce methadone more: 75%–90%

(Indelicato et al, 2002; Mather, 2001)

Page 72: Chronic pain management

Opioid Therapy:Managing Side Effects

• Common– Constipation– Somnolence, mental clouding

• Less Common– Nausea – Sweating– Myoclonus – Amenorrhea– Itch – Sexual dysfunction– Urinary retention – Headache

(Ahmedzai et al, 1997; Portenoy, 1996)

Page 73: Chronic pain management

Novel Drug Therapies forTreatment of Pain

Central Nociception: Emerging Analgesic Targets

• Excitatory amino acid and NK receptors• N-type Ca++ receptors• N-acetylcholine receptors

• Adenosine (A1) receptors

• Cannabinoid (CB1) receptors

(Pappagallo M)

Page 74: Chronic pain management

Peripheral Nociception:Emerging Analgesic Targets

• Sensory neuron specific Na+ channels (eg, PN3, NAN)• Opioid receptors • Vanilloid receptors• Serotonin receptors• Alpha-adrenergic receptors • Proton-sensitive channels (pH-sensitive)• Nerve–growth-factor receptors (*TrKA, p75)• N- or T-type Ca++ channels• Purine receptors*TrKA = tyrosine kinase

(Pappagallo M)

Novel Drug Therapies forTreatment of Pain

Page 75: Chronic pain management

Chronic Pain Management: Nonpharmacologic Approaches

Anesthetic Approaches

• Neuraxial Drug Administration– opioids, local anesthetics, and/or clonidine

via continuous epidural or intrathecal infusion

• Neural Blockade– temporary block– neurolytic block

(Eisenach et al, 1995; Patt et al, 1998)

Page 76: Chronic pain management

Chronic Pain Management: Nonpharmacologic Approaches

Neurostimulatory Approaches

• TENS (transcutaneous electrical nerve stimulation)• Acupuncture• Dorsal Column Stimulation

Surgical Procedures• Peripheral Nerve Procedures

– peripheral neurectomy– rhizotomy

• CNS Procedures– cordotomy

(Portenoy et al, 1996)

Page 77: Chronic pain management

Chronic Pain Management: Nonpharmacologic Approaches

Psychologic Treatments • Behavioral treatment

• Biofeedback

• Cognitive-Behavioral Treatment

Rehabilitative Approaches• Physical/Occupational Therapy

• Heat/Cold Therapy (diathermy, cryotherapy)

• Prostheses

• Assistive Devices

(Redd et al, 2002)

Page 78: Chronic pain management

Module 4

Progress in Chronic Pain Management

Substance Abuse Issues in Chronic Pain Management

A National Pain Education Council ProgramA National Pain Education Council Program

Page 79: Chronic pain management

The Terminology of Abuse

• Physical Dependence– Abstinence syndrome induced by administration of an antagonist

or by dose reduction

– Usually unimportant if abstinence is avoided

– Assumed to exist after few days’ dosing but actually highly variable

– Does not independently cause addiction

• Addiction – Disease with pharmacologic, genetic, psychosocial elements

– Fundamental features: loss of control, compulsive use, use despite harm

– Diagnosed by observation of aberrant drug-related behavior

(AAPM/APS, 1996; NIDA, 2001; Passik et al, 2000; Portenoy, 1996)

Page 80: Chronic pain management

The Terminology of Abuse

• Tolerance– Diminished drug effect from drug exposure– Varied types: associative vs. pharmacological – Tolerance to analgesia is seldom a problem in the clinical setting:

• Tolerance rarely “drives” dose escalation • Tolerance does not cause addiction

• Pseudoaddiction– Aberrant drug-related behaviors driven by uncontrolled pain– Reduced by improved pain control– Complexities

• How aberrant can behavior be before it is inconsistent with pseudoaddiction?

• Can addiction and pseudoaddiction coexist?

(Passik et al, 1998; Passik et al; Portenoy RK, 1996)

Page 81: Chronic pain management

Risk Assessment for Addiction

Low Addiction Risk • Acute pain • Cancer pain• Patients without abuse background or psychopathology

Chronic Noncancer Pain• Probability of addiction is small

– surveys that include patients with abuse or psychopathology show mixed results

• Predictors of addiction may include– history of substance abuse– Age– personality factors– family dynamics and social factors

(Passik et at, 1998; Passik et al, 1998)

Page 82: Chronic pain management

Diagnosing and MonitoringAberrant Behaviors

Two-Step Monitoring Approach• Step 1: Are there aberrant drug-related aberrant behaviors?

• Step 2: If yes, are these behaviors best explained by the existence of an addiction disorder?

Differential Diagnosis

• Addiction/pseudoaddiction• Other psychiatric disorders (e.g., borderline personality

disorder)

• Mild encephalopathy

• Family disturbances

• Criminal intent

(Passik et at, 1998; Passik et al, 1998)

Page 83: Chronic pain management

Drug-Related Behavior Predictive of Addiction

Probably More Predictive

• Selling prescription drugs• Prescription forgery• Stealing or “borrowing” drug from

another person• Injecting oral formulation• Obtaining prescription drugs from

non-medical source• Multiple episodes of prescription

“loss”• Concurrent abuse of related illicit

drugs• Multiple dose escalations despite

warnings• Repeated episodes of gross

impairment or dishevelment

Probably Less Predictive • Aggressive complaining• Drug hoarding when symptoms

milder• Requesting specific drugs• Acquisition of drugs from other

medical sources• Unsanctioned dose escalation

once or twice• Unapproved use of the drug to

treat another symptom• Reporting psychic effects not

intended by the clinician• Occasional impairment

(Passik et al, 1998)

Page 84: Chronic pain management

Addressing AberrantDrug-Related Behavior

• General Management Principles– know laws and regulations

– structure therapy to match perceived risk

• Proactive Strategies– communicate goals of therapy

– provide written guidelines (treatment contract)

– assess often

• Reactive Strategies– require frequent visits and small quantities of drug

– use of urine toxicologies

– long-acting drugs with no rescue doses– relate to addiction-medicine community (sponsor, program, addiction-

medicine specialist, psychotherapist)

 

(Mironer et al, 2000; Portenoy et al, 1997; Passik et al, 2000)

Page 85: Chronic pain management

Conclusions

• Chronic pain is common and undertreated

• Identify chronic pain patients who would most likely benefit from opioid therapy and use it responsibly

• Implement opioid treatment with a plan for ongoing monitoring

• Assess and monitor pain, side effects, and drug-related behaviors

• Adjust dosage

• Manage side effects