Pain Management in the Primary Care Setting:  A focus

on the appropriate use of Opioids

Dr. Zohra Salehi, PGY 2February 24, 2015

St Josephs Medical Center, Family Medicine

Objectives Overview of mechanism of action of opiates Review trends in opioid use and abuse Discuss step wise approach to pain management including risk assessment

initiation and discontinuation of opioids

Background

Opiates refers to compounds structurally related to products found in opium includes morphine, codeine, and many semisynthetic derivatives. Opos, the Greek word for "juice” Opioids- all (synthetic and semisynthetic); Opiate- naturally

Term narcotic was derived from the Greek word narkotikos, for "benumbing" or "stupor." Although narcotic originally referred to any drug that induced narcosis or sleep, the word has become associated with opioids and is often used in a legal context

Types of Opiates

Long-acting Opioids Fentanyl Transdermal System Methadone Morphine controlled release (CR), sustained

release (SR), extended release (ER) Oxycodone CR Oxymorphone ER

Short-acting Opioids Codeine Hydrocodone Hydromorphone Morphine Oxycodone (alone or in combination with

APAP or ASA) Oxymorphone

Opiate Receptors and effect of AgonistsThe three opioid receptors—δ, μ, and κ are widespread through out the body but have a high density of distribution in the brain and spinal cord.

Mu1, Mu2 Analgesia, Euphoria, Constipation, Respiratory depression

Kappa Spinal AnalgesiaDelta Unknown

Opiate Receptors and effect of Agonists Full agonists (morphine, fentanyl, oxycodone, hydrocodone, methadone)

activate mu receptors, producing analgesia.

Partial Agonist (Buprenorphine) has a strong affinity for mu receptors, but produces mild analgesia that is accompanied by an analgesic ceiling effect. The strong mu receptor affinity blocks additional opioids from binding to the receptor.

Antagonists (naloxone and naltrexone) block mu and kappa receptor activation, preventing analgesia; they are used mostly as reversal agents.

1.Decrease Neuronal Transmitter Release

2.Decrease Impulse Propagation

3. Decreased pain threshold

•Inhibition of adenylyl cyclase activity•Reduced opening of voltage-gated Ca2+ channels•Stimulation of K+ current

Consequences of Opiate Receptor Activation

The loss of effect with exposure to opiates occurs over short- and long-term intervals.

Tolerance: Progressive loss of drug effect over a time interval Time dependent, with changes occurring over short and long term Tolerance develops at different rates (some organs show little tolerance

(miosis), others rapid tolerance (euphoria) Cross tolerance between mu agonists- however this this not always consistent

Consequences of Opiate Receptor Activation Dependance: withdrawal syndrome produced by cessation of drug

exposure. In the CNS, increased adenylyl cyclase, release of excitatory amino acids and cytokines, etc.

- reflected by irritability, loss of energy, hyperalgesia, hypertension, diarrhea, pupillary dilation, dysphoria, piloerection, anticipatory anxiety

Severity dependent upon the dose and duration of drug exposure.

Cravings The craving for alcohol, barbiturates, caffeine, cocaine, opioids, and tobacco, share a

common neuronal pathway that lead to reinforcement.

Drugs that evoke reinforcement appears to sensitize dopaminergic neurons that project ventral tegmental area to the nucleus accumbens.

The peak of dopamine release occurs at the peak drug effects and the degree is related to the rate of dopamine level increases. This relationship accounts for propensity of some drugs to produce dependence. Oral causes less dependence than IV form due to rate at which the drug is distributed to CNS and rate at which dopamine increased in nucleus accumbens. (i.e Inhalation > IV > oral)

Consequences of Opiate Receptor Activation Addiction is a behavioral pattern characterized by compulsive use and time spent obtaining the drug.

Tolerance and dependence does not indicate addiction

Classification of Pain

Psychogenic: pain-associated mood alteration, such as anxiety or depression, because pain is an emotional as well as sensory experience

Somatic pain: typically refers to pain arising from somatic structures, e.g., skin, bones, muscles, and joints. Somatic pain is typically well-localized (“my left finger hurts”) and worsened by palpation or movement of the affected body part.

Neuropathic pain is pain resulting from injury to or as a result of a dysfunction of the central or peripheral nervous system. Examples include spinal cord injury and peripheral diabetic neuropathy. Burning or shooting, hypersensitivity, dermatomal.

Visceral pain typically refers to pain arising from pathology or injury of the visceral organs, such as bowel obstruction or pancreatitis. Poorly localized associated with nausea, vomiting, diarrhea, or constipation.

Epidemiology

In 2011, 4.2 million Americans aged 12 or older (or 1.6 percent) had used heroin at least once in their lives.

According to the CDC, 12 million Americans abused prescription painkillers in 2010, while roughly 15,000 Americans die annually from overdosing on such drugs.

2001 and 2010, the percentage of overall ED visits (pain-related and non–pain-related) where any opioid analgesic was prescribed increased from 20.8% to 31.0%

Trends in Opioid Analgesic Abuse and Mortality in the United States NEJM Jan, 2015

Trends between 2002 and 2013 in the diversion and abuse of all products and formulations of six prescription opioid analgesics: oxycodone, hydrocodone, hydromorphone, fentanyl, morphine, and tramadol. The programs gather data from drug-diversion investigators, poison centers, substance-abuse treatment centers, and college students.

RADARS System programs reported large increases in the rates of opioid diversion and abuse from 2002 to 2010, but then the rates flattened or decreased from 2011 through 2013. The rate of opioid-related deaths rose and fell in a similar pattern

Relationship between the availability of prescription opioid analgesic and the diversion and abuse of these drugs and associated adverse outcomes.

100 people die from drug overdose everyday in the US

http://www.cdc.gov/homeandrecreationalsafety/rxbrief/

http://www.cdc.gov/homeandrecreationalsafety/rxbrief/

Drug Overdose Rates by State, 2008

http://www.cdc.gov/homeandrecreationalsafety/rxbrief/

Groups at highest risk for overdose

Multiple controlled substance prescriptions from multiple providers

• Administration of high daily dosages of prescription

• Low-socioeconomic status population, living in rural areas • Insurance Status -Medicaid are prescribed painkillers at twice the rate of non-Medicaid patients, at 6x risk OD

http://www.cdc.gov/homeandrecreationalsafety/rxbrief/

Guideline Recommendation Department of Health & Mental Hygiene Opioid Prescribing Guidelines

Obtain detail history: pain duration onset quality medication

Comprehensive Family/Medical history Check Drug Monitoring Program Conduct physical exam Urine drug screening for all patients Opioid indication- consider when potential benefits

outweighs harm Start with lowest effective dose possible Avoid benzodiazepine or other depressants

Guideline RecommendationDepartment of Health & Mental Hygiene Opioid Prescribing Guidelines

Urine drug screen- repeat randomly; yearly for low-risks to every 3 months for high risk. (Ask patient their lasts dose)

Written treatment agreement, goal settings, expectations, risk/benefits

Regular follow up visits, assess pain level, adverse events, function Discontinue if signs of misuse Have an exit plan- tapering or referral to detox specialists Explain option of buprenorphine or refer to addiction specialist or

maintenance program

Steps to the Management of Pain with opioids

Screening Assessment

How does the pain feel? Where is the pain? Is it one side? What is the present and past intensity of pain? What is it at it’s best and at it’s worst? When did it begin? Is it consistent or Intermittent? How has your mood affected your daily function? Do you have enough energy to accomplish things during the day? Do you ever feel like giving up?

Assessing Risk Factors & Goals First

RisksConcomitant use of CNS depressantsRecent initiation opioidsMultiple Opioid prescribersMental health disorderMethadone/Substance Abuse Co-morbidities

GoalsBeing completely pain free: Not Achievable

Being able to function (i.e being able to walk etc): Achievable

Opioid Risk Assessment Tool

General Strategy To Initiation

Shared Decision Making Consent agree to open communication with other providers

Consent to Urine Drug Screen Agreeing to integrate other forms of interventions Provide written and verbal instructions to patients

Initiation

Acute Severe Pain: Short term, therapeutic trial Start low dose, titrate cautiously

Moderate-Severe Pain failed to adequately respond to indicated non-opioid and non-drug therapeutic

interventions The potential benefits of OT are likely to outweigh the risks (i.e., no absolute

contraindications) The patient is fully informed and consents to the therapy Clear and measurable treatment goals are established

Absolute Contraindications

Severe respiratory instability Acute psychiatric instability or suicide risk Diagnosed non-nicotine substance use disorder True allergy to opioid agents (cannot be resolved by switching agents) Severe drug-drug interaction QTc interval >500 millisecond for using methadone Active diversion of controlled substances Prior adequate trials of specific opioids that were discontinued due to

intolerance, serious adverse effects that cannot be treated, or lack of efficacy

Outcomes

Pain reduction Complication rates Functional status Quality of life Adverse effects of therapeutic interventions Mortality

Opioid Recommendation

No evidence to recommend for or against the selection of any specific opioid

Transdermal Fentanyl should be avoided on opioid naïve patient Start with lose dose and one medication at a time Initiate bowel regimen to prevent and treat constipation which is

expected with all opioids Insufficient evidence to recommend short versus long acting opioids Avoid use of around the clock, it may contribute to tolerance and

dose escalation

Titration

Adjust the dose of opioid in an individualized and safe manner to achieve satisfactory pain control and a tolerable adverse effect profile.

Only prescribe higher doses in patients with clear improvement in pain and function

Do not increase dose more frequently than every 7 days Titrate one drug at a time Increase dose by 25%-100%; use short acting during process titration If > 200mg equivalent morphine dose is achieved, refer to consultant.

Monitoring

Schedule follow-up visits at least every 2 to 4 weeks after any change in medication regimen

Once every 1-6 months for the duration of the therapy (maintenance)

Monitoring

Urine Drug Screen – diagnostic and accuracy of presence or absence of a drug is well established.

Aberrant behaviors – consider dose adjustment and discontinuation Prescription Drug Monitoring to detect diversion, doctor shopping, etc. Pain Assessment: Ask: "What is your intensity of pain after taking your current

treatment/medication?" How long does your pain relief last after taking your medication?"

Discontinuation

The medication fails to show partial analgesia with incremental dose titration

Trials with different agents provide inadequate analgesia There is other evidence that the pain may not be opioid

responsive Real or potential harms outweigh real or potential

benefits Patient request Behavior to suggest addiction

Cases

Case 1 40-year-old male construction worker who presents with a 9-month history of back

pain that began following a work-related accident. He said that he was lifting a heavy piece of equipment and felt a “pop.” His pain is located in the lower back, buttock and groin area. It occasionally radiates to his left leg and foot. You diagnosed him with lumbar radiculopathy and disc herniation. He was started on an NSAID and continues to have uncontrolled pain. What is your next step in management?

A. Switch to another NSAID or start tramadol B Start Neurontin C. Start Physical therapy, address coping skills D. All above E. A&C

Case 1 40-year-old male construction worker who presents with a 9-month history of back

pain that began following a work-related accident. He said that he was lifting a heavy piece of equipment and felt a “pop.” His pain is located in the lower back, buttock and groin area. It occasionally radiates to his left leg and foot. You diagnosed him with lumbar radiculopathy and disc herniation. He was started on an NSAID and continues to have uncontrolled pain. What is your next step in management?

A. Switch to another NSAID or start tramadol B Start Neurontin C. Start Physical therapy, address coping skills D. All above E. A&C

Low Back Pain

Common and can be difficult to treat.

First Line: NSAIDS Second Line: Muscle Relaxant Self- Care: Remain active, Exercise therapy Psychosocial contributors to pain: depression, anxiety, fear Non-Pharmacological : acupuncture, spine manipulation, rehab

Case 227-year-old male who presents one day following an injury from an accident playing football with friends. He states that he cannot move without experiencing intense pain. You start him on oral NSAIDS and physical therapy. He returns 8 weeks later with unresolved pain. He describes the pain as a “constant aching pain, 7/10” in the middle of his back that worsens during the day. What is your next step in management?A. Order imaging studyB. Make changes in medication and/or physical therapy C. Referring to a pain management specialistD. A&BE. All the Above

Case 227-year-old male who presents one day following an injury from an accident playing football with friends. He states that he cannot move without experiencing intense pain. You start him on oral NSAIDS and physical therapy. He returns 8 weeks later with unresolved pain. He describes the pain as a “constant aching pain, 7/10” in the middle of his back that worsens during the day. What is your next step in management?A. Order imaging studyB. Make changes in medication and/or physical therapy C. Referring to a pain management specialistD. A&BE. All the Above

Case 3

Patient is 64yr female who underwent right total knee replacement. She is complaining of severe pain, 9/10. You get paged to assess the patient. What is your approach to treatment?A. Toradol IV Q6h B. Acetaminophen and Morphine IV Q4 prn Thermal Packs MassageC. Dilaudid IM Q4 prnD. A & BE. A & C

Case 3

Patient is 64yr female who underwent right total knee replacement. She is complaining of severe pain, 9/10. You get paged to assess the patient. What is your approach to treatment?A. Toradol IV Q6h B. Acetaminophen and Morphine IV Q4 prn Thermal Packs MassageC. Dilaudid IM Q4 prnD. A & BE. A & C

Post operative

Multi-modal approach, e.g., combining non-opioid with an opioid medications (i.e. acetaminophen, NSAIDs). While addition of an NSAID usually does not eliminate the need for an opioid, opioid doses can often be reduced, which may potentially reduce opioid side effects.

NSAIDs may be particularly effective against movement-associated pain, while opioids typically are most effective on pain at rest.

Morphine is generally the opioid of choice for acute post-operative pain Intramuscular injections are discouraged, due to erratic absorption Opioids via a PCA pump typically improves analgesia while reducing

doses.

ReferencesGoodman & Gillman The Pharmacologic Basis of Therapeutics. Laurence L. Brunton, Bruce A. Chabner, Björn C. Knollmannaccessmedicine.mhmedical.com/book.aspx?bookid=374

Rising Opioid Prescribing in Adult U.S. Emergency Department Visits: 2001–2010 onlinelibrary.wiley.com/doi/10.1111/acem.12328/abstract

Common elements of in guidelines for prescribing opioids for chronic painwww.cdc.gov/homeandrecreationalsafety/pdf/Common_Elements_in_Guidelines_for_Prescribing_Opioids-a.pdf

Agency for Healthcare Research and Quality. VA/DoD clinical practice guideline for management of opioid therapy for chronic pain. May 2010.

References

Trends in Opioid Abuse and Mortality In United States. Richard C. Dart, M.D., Ph.D., Hilary L. Surratt, Ph.D., Theodore J. Cicero, Ph.D., Mark W. Parrino, M.P.A., S. Geoff Severtson, Ph.D., Becki Bucher-Bartelson, Ph.D., and Jody L. Green, Ph.D. N Engl J Med 2015; 372:241-248

Clou R and Shekelle P. JAMA 2010; 303. 1295-1302

Webster LR et al. Pain Med. 2005; 6:432.