What Pharmacists Need to Know about Pain and its Management

Sukhvir Kaur, PharmD, BCACPContinuing Education at the SNPhA Region III, IV, V Conference

March 11, 2017

Financial Disclosure

• Sukhvir Kaur, PharmD, BCACP has no relevant financial or non-financial relationships in the products or services described, reviewed, evaluated, or compared in this presentation

Learning Outcomes

• Describe chronic pain and the pharmacist’s role in managing a patient with chronic pain• Discuss what the pharmacist’s expectations are in the

management of pain and his/her evolving role• Provide current evidence in treating pain via nonpharmacologic

therapy• Discuss current pharmacologic agents in treating acute and

chronic pain including their place in therapy and their risks• Educate and advocate for patients about effective pain

management strategies

Question 1:

TJ is a 66 YO F who has had a long history of poorly controlled diabetes mellitus II. She was diagnosed with diabetic peripheral neuropathy (DPN) 3 years ago and was started on Gralise. Since that time her health has been slowly declining. Based on the information below, which of the following is a viable option to treat her DPN at this time?BP 118/79 P 72 RR 16 BUN 27 CrCl 29mL/min Glu 143A. LyricaB. NeurontinC. TofranilD. Carbamazepine

Question 2:

TJ is a 16 YO M who comes into your community pharmacy with an injured arm he suffered from football practice this evening. He says it hurts if he tries to move it too much and resting it while applying ice makes it feel better but it is only temporarily. He states that the pain feels like a sharp pain and is localized to the center of his forearm. Upon asking how this pain rates compared to other pains he has felt he states it is 6/10. He says the pain has been pretty consistent since he injured himself at the end of practice about 30 minutes ago. Which of the following statement is CORRECT?A. You must perform a PQRST pain interviewB. This patient may require both opioid and non-opioid treatment after

evaluation by PCPC. This patient can be treated with an OTC NSAID along with rest and applying

ice to the armD. Call 911, this patient need to go the ER immediately

Question 3:

TL is a 35 YO M who was prescribed opioids to treat his lower back pain from an injury suffered on the job a couple months ago. Two weeks after his initial treatment on opioids he came back to the hospital furious that the medication was no longer working for him. His doctor increased the dose at this time. He has continually come back every two weeks complaining that his medication isn’t working and is fed up with having to return every couple of weeks to adjust his pain medication. He is demanding that the doctor starts him on a much higher dose. What type of behavior is this patient displaying?A. Physical dependenceB. ToleranceC. AddictionD. Combative behavior

Individual Activity

• Write down the answer to the following questions• Scenario 1: You had a severe injury and are in acute pain.

1. What therapy would you employ for pain relieve?

• Scenario 2: You suffer from chronic pain and even take opioids and antidepressants around the clock with about 20% pain relief suffer from chronic pain and even take opioids and antidepressants around the clock with about 20% pain relief

1. What nonpharmacologic therapy would you employ for pain relieve?2. What additional pharmacologic therapy would you employ for pain relieve?

The Patient Perspective

The Numbers

• >100 million in US suffer

• Estimated economic burden exceeds 500 billion• Despite all efforts, inappropriately treated leading to â independence

and ADL as well as strain on social relationships, mood and sleep patterns

• Defined as “any pain that persists beyond the anticipated time of healing”• Nociceptive pain or neuropathic pain• International Association for the Study of Pain (IASP) states

that pain is “an unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage”• Highly SUBJECTIVE

Chronic Pain

Causes of Pain

• Help minimize risk for patients using pain medications.• Assess and properly plan to minimize patient risk of Pain Medicine• Proper Pain Assessment to understand pain and provide highly effective

treatment while minimizing risk• Educate the patients of the role of opioids in the treatment of chronic pain

• Help patients live meaningful and productive lives with adequately managed pain

• Monitor patient’s 4 As:• Analgesia• Activities of daily living• Adverse events• Aberrant drug behaviors

Pharmacist’s Role in Chronic Pain Management

CDC Take Pain Management and Pharmacist

Chronic Pain Medications and Dangers

Treatment approaches to Management of Chronic pain

Non-pharmacologic• Acupuncture• Local electrical stimulation including TENS• Brain stimulation• Surgery• Psychotherapy• Relaxation and medication therapies• Biofeedback• Behavior modification• Placebos?

Pharmacologic• NSAIDs• Antidepressants• Anticonvulsants• Topical agents• Cannabinoids• Non-Opioids• Opioids• Intrathecal drug delivery systems

The Goals – Chronic Pain

Improve or maintain the patient’s level of functionalityØ Set goals with the patient for functional improvement,

and document them for future monitoring purposes to determine efficacy

Ø Improving pain and function by ~30% is a success

Current Evidence for Nonpharmacologic therapy in treating Pain

Acupuncture Evidence is conflicting and clinical studies to investigate its benefits are ongoing

Biofeedback Evidence for headache and back pain; Often used in combination without side effects

Chiropractic Evidence for chronic back pain relief

Cognitive-behavioral therapy Strong evidence for chronic pain, postoperative pain, cancer pain, and the pain of childbirth

Counseling Can be of help to learn about the physiological changes produced by pain

Electrical stimulations includingtranscutaneous electrical stimulation (TENS)

Can help reduce pain

Exercise Evidence with chronic pain for overall well being including light to moderate; shown efficacy to relief low back pain

Current Evidence for Nonpharmacologic therapy in treating Pain

Hypnosis Speculated to help a person concentrate and relax or is more responsive to suggestion

Low-power lasers Used by some physical therapists but method is NOT without controversy

Magnets Increasingly popular with athletes to control sport-related pain or other pain conditions

Nerve blocks Interventional to relieve nerve pain and pains related to cancer

Physical therapy and rehabilitation To increase function, control pain and gain recovery

Placebo Employed in studies, work by stimulating the brain’s own analgesics

R.I.C.E.—Rest, Ice, Compression, and Elevation

Temporary muscle or joint injuries

Surgery Limited evidence to show which procedures work best for their indications

Pain Algorithm

Pain relief not adequate, step up therapyALWAYS MONITOR: pain frequency and status, anticipate side effects, properly titrate doses based on patient, PO is

preferred, consider around clock, and PRN regimens for breakthrough or highly variable pain

Identify Pain Source if possibleAssess Pain Severity and Quality using consistent method (Pain Scale: 0-10)

Mild (1-4/10)APAP +/- NSAIDs

Moderate (5-7/10)Combo Opioid + APAP/NSAID

Severe (8-10/10)Opioid analgesics to severity and

patient characteristics

Nonsteroidal Anti-inflammatory Drugs (Nsaids)

Place in Therapy Comments/Concerns

• Acute mild pain or adjuvant in moderate to severe pain

• Effective in the treatment of chronic low back pain as well as chronic pain due to osteoarthritis

• Modest effect in treating lumbar radiculopathy

• The addition of an NSAID to a pain management regiment can have an opioid-sparing effect of between 20-35%

Minimal effect in treating neuropathic pain states

Opioids

Place in Therapy Comments/Concerns• Strong evidence in supporting the short-term use of opiates

in managing BUT long-term use for non-cancer pain is not strong.

• Current recommendations for initiating chronic opiate therapy are intended to better identify patients at risk for abusing and/or misusing opiate medications or from suffering their adverse physical effects. This includes a detailed medical history, psychiatric history, and substance use history as well as establishing a physical diagnosis and the medical necessity for chronic opiate therapy. Urine drug screening as well as establishing an agreement between the provider and patient in which the goals and expectations of the therapy are clearly stated reduces misuse, abuse, or diversion of opiate medications.

• Unwanted adverse effects, such as opioid tolerance, dependence, constipation, respiratory depression, impaired cognitive ability, immune suppression, and opioid-related endocrinopathies, are only some of the known physical alterations associated with the chronic use of opiate medications.

Opioids

• Agents of choice for moderate to severe chronic pain as well as cancer related chronic pain

• Dosing is based on patient’s previous history of opioid analgesic used, the specific patient’s needs, and on the delivery system being utilized.

• Classified by:• Activity at the receptor site • Pain intensity treated • Duration of action (short acting vs. long acting)

Patient Selection

• Patient is experiencing pain despite having a reasonable trial of both non-opioid analgesics and adjuvants

• Severe pain that requires rapid relief

• Patient has contraindication to the use of other analgesics• Opioid regimen should be individualized • Opioid naïve patients should be started on low dose

• In July 2012, FDA requires REMS for all extended release and long acting opioid analgesics.

Commonly Prescribed Opioids

Generic Brand Agonist/antagonist or mixed

Histamine release that would cause N/V/itchiness

Route of Administration

Comments

Morphine Avinza Morphine like Agonist +++ IM, PO, IV, SR, Rectal Drug of choice for severe pain

Hydromorphone Dilaudid, Exalgo Morphine like Agonist IM, PO, IV, rectal Use in severe pain, more potent than morphineREMS program

Oxymorphone Opana Morphine like Agonist IM, IV, SQ, PO Severe pain, immediate with controlled, extended release to stop misuse

Codeine Morphine like Agonist +++ IM, PO CODEINE is metabolized by CYP2D6

Hydrocodone Norco Morphine like Agonist PO most effective when used with aspirin and acetaminophen,

Oxycodone Oxycontin, Oxecta, Roxicodone

Morphine like agonist PO

Meperdine Demerol Meperidine like agonist +++ IM, PO Severe pain, oral is not recommended, should not be used for chronic pain

Commonly Prescribed Opioids

Generic Brand Agonist/antagonist or mixed

Histamine release that would cause N/V/itchiness

Route of Administration

Comments

Fentanyl Sublimaze, duragesic, lazanda, abstral. Actiq, onsolis, fentora, subsys

Meperidine like agonist

IM, transdermal, buccal, transmucosal, sublingual, nasal inhaled

Severe pain, do not use patch in acute pain, always titrate the dose, can be used for breakthrough pain; TM, IN, SL are available through a REMS program.

Methadone Dolophine NMDA antagonistSNRI

IM/IV, PO Reverse opioid tolerance

Naloxone Narcan Antagonist IV

Tramadol Ultram Antagonist Inhibits reuptake of serotonin and ER , used for neuropathic pain

PO Decreased dose in renally and hepatic insufficient patients and elderly.

Tapentadol Nucynta Antagonist PO REMS required.

Administration of Opioids

Frequency Stage of Pain

Around THE CLOCK (QD, BID etc.) Initial stage of pain Persistent chronic pain

As needed (prn) As the painful state subsides and the need for medication is decreased.Also for patients that may present with pain that is intermittent or sporadic in nature.

Around the clock and as needed (conjunction)

When patient experiences breakthrough pain.

Route of Administration

Route of Administration When to Uses

Oral (PO) Mostly commonly used and preferred method in most cases

Continuous IV infusion Postoperative pain

Epidural or intrathecal/ subarachnoid

Control of acute, chronic non-cancer, and cancer pain

Evaluation prior to initiating Opioid regimen

• Before initiating chronic opioid therapy, must assess risk vs. benefit for the patient.

• Based on history, physical examination, assessment of risk of substance abuse, misuse or addiction.

• Personal and family history of alcohol or drug abuse

• Personal history of alcohol or drug abuse may be considered contraindicated for long term opioid therapy.

Definition

• Physical dependence- rapid discontinuation of opioid following prolonged administration, usually one month or longer, will result in withdrawal symptoms such as dysphoria, anxiety, and volatility of mood, as well as physical findings such as hypertension, tachycardia, and sweating.

• Tolerance- is present when increasing amounts of opioid are required to produce an equivalent level of efficacy

• Addiction- is a form of physiological dependence and refers to the extreme behavior patterns that are associated with procuring and consuming the drug.

Major Adverse effects of opioid analgesics

Effect Manifestation

Mood changes Dysphoria, euphoria

Somnolence Lethargy, drowsiness, apathy, inability to concentrate

Stimulation of chemoreceptor trigger zone Nausea, vomiting

Respiratory depression Decreased respiratory rate

Decreased gastrointestinal motility Constipation

Increase in sphincter tone Biliary spasm, urinary retention

Histamine release Pruritus

Tolerance Larger doses for same effect

Dependence Withdrawal symptoms upon abrupt discontinuation

Antidepressants – Place in therapy

• Effectiveness for antidepressants in the treatment of chronic pain disorders with a strong neuropathic component has long been established in the literature

• TCAs (Amitriptyline, imipramine, nortriptyline and desipramine):• Shown to be effective in treating a variety of painful

neuropathic conditions such as diabetic peripheral neuropathy (DPN), postherpectic neuralgia (PHN), painful polyneuropathy, postmastectomy pain, and central poststroke pain

• Analgesic effects are independent of the presence of any changes in depression or mood state.

• Side effects that can be significant include postural hypotension, dry mouth, and sedation for which reason these medications are typically taken at bedtime especially in the elderly population leading to increase risk of fall.

• Duloxetine and venlafaxine• Have shown efficacy in treating

peripheral neuropathic pain and other chronic pain conditions.

• Duloxetine• Treatment of painful DPN,

fibromyalgia, and chronic musculoskeletal pain

• Mood-elevating effects have a significant contribution to the reported decreases in pain scores

Anticonvulsants

Place in Therapy Side effects/concernsCarbamazepine Trigeminal neuralgia but has NOT been shown

to be as effective in treating other neuropathic pain disorders

somnolence, dizziness, and gait disturbanceSerious: SJS, TEN and blood dyscrasias

Valproic acid, oxcarbazepine, topiramate and lamotrigine

Inconsistent evidence of efficacy in treating neuropathic pain

Gabapentin DPN, PHN, painful polyneuropathy, neuropathic cancer pain, central poststrokepain, and spinal cord injury pain

dizziness, somnolence, ataxia, & peripheral edema

Pregabalin *First line for treating neuropathic pain dizziness, somnolence, and ataxia.>peripheral edema

Topical agents

Place in TherapyLidocaine (5% gel or patch) Peripheral neuropathic pain conditions with allodynia as well

as PHN with allodynia

Topical NSAIDs (diclofenac, ibuprofen, and ketoprofen)

Short-term pain relief in the treatment of soft tissue injuries and chronic joint-related pain.

Topical high-dose capsaicin (8%) Effective in providing rapid and sustained pain relief in patients with PHN and painful human immunodeficiency virus (HIV)-associated neuropathies

Cannabinoids

Place in Therapy Mechanism of ActionMedicinal marijuana Neuropathic pain Activation of CB2 receptors on peripheral

inflammatory cells has beenshown to decrease inflammatory cell mediator release, plasma extravasation, and the sensitization of afferent terminal

Facts about Chronic pain and Opioid treatment

• Cost of chronic pain adds up to 635 billion each year.

• It affects over 100 million adults.• About 41% of chronic pain patients reports that their pain is

uncontrolled.

Use of Opioids for the Treatment of Chronic Pain

Legislation and Regulatory Policies Should Limit Inappropriate Prescribing But Should Not Discourage Or Prevent Prescription Of Opioids Where Medically Indicated And Appropriately Managed.Prescription Of Opioids For Chronic, Intractable Pain Is Appropriate When More Conservative Methods Are Ineffective And The Treatment Plan Is Reasonably Designed To Avoid Diversion, Addiction, And Other Adverse Effects. Physicians Should Be Sensitive To And Seek To Minimize The Risks Of Addiction, Respiratory Depression And Other Adverse Effects, Tolerance, And Diversion. However, Some Commonly Held Assumptions About These Issues Need To Be Reviewed. Opioids Should Be Prescribed Only After A Thorough Evaluation Of The Patient, Consideration Of Alternatives, Development Of A Treatment Plan Tailored To The Needs Of The Patient And Minimization of Adverse Effects, And On-Going Monitoring And Documentation.

Use of Opioids for the Treatment of Chronic Pain. American Academy of Pain Medicine. 2013. http://www.painmed.org/files/use-of-opioids-for-the-treatment-of-chronic-pain.pdf. Accessed August 3, 2016

Monitoring of Chronic Pain Management

• Monitoring should occur during each visit

• Documentation of pain intensity, functional status, progress toward therapy goals, side effects and adherence is critical.

Going back to the activity

• You had a severe injury and are in acute pain, what would you employ NOW for pain relieve?

• You suffer from chronic pain and even take opioids and antidepressants around the clock with about 20% pain relief, what would you employ in adjuvant for pain relieve?

Question 1:

TJ is a 66 YO F who has had a long history of poorly controlled diabetes mellitus II. She was diagnosed with diabetic peripheral neuropathy (DPN) 3 years ago and was started on Gralise. Since that time her health has been slowly declining. Based on the information below, which of the following is a viable option to treat her DPN at this time?BP 118/79 P 72 RR 16 BUN 27 CrCl 29mL/min Glu 143A. LyricaB. NeurontinC. TofranilD. Carbamazepine

Question 2:

TJ is a 16 YO M who comes into your community pharmacy with an injured arm he suffered from football practice this evening. He says it hurts if he tries to move it too much and resting it while applying ice makes it feel better but it is only temporarily. He states that the pain feels like a sharp pain and is localized to the center of his forearm. Upon asking how this pain rates compared to other pains he has felt he states it is 6/10. He says the pain has been pretty consistent since he injured himself at the end of practice about 30 minutes ago. Which of the following statement is CORRECT?A. You must perform a PQRST pain interviewB. This patient may require both opioid and non-opioid treatment after

evaluation by PCPC. This patient can be treated with an OTC NSAID along with rest and applying

ice to the armD. Call 911, this patient need to go the ER immediately

Question 3:

TL is a 35 YO M who was prescribed opioids to treat his lower back pain from an injury suffered on the job a couple months ago. Two weeks after his initial treatment on opioids he came back to the hospital furious that the medication was no longer working for him. His doctor increased the dose at this time. He has continually come back every two weeks complaining that his medication isn’t working and is fed up with having to return every couple of weeks to adjust his pain medication. He is demanding that the doctor starts him on a much higher dose. What type of behavior is this patient displaying?A. Physical dependenceB. ToleranceC. AddictionD. Combative behavior

References

• Appropriate Opioid Use. Pharmacist’s Letter. 2015; 31(4):310407.

• ACPA Recourse Guide to Chronic Pain Treatment: An Integrated Guide to Physical, Behavioral and Pharmacologic Therapy. 2016. https://theacpa.org/uploads/documents/ACPA_Resource_Guide_2016.pdf. Accessed August 10, 2016.

• Baumann TJ, Herndon CM, Strickland JM. Chapter 44. Pain Management. In:DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?bookid=689&Sectionid=45310494. Accessed August 16, 2016.

• Beal BR, Wallace MS. An Overview of Pharmacologic Management of Chronic Pain. Med Clin North Am. 2016;100(1):65-79.

• CDC. Opioid overdose. https://www.cdc.gov/drugoverdose/. Accessed January 4, 2017.

• Pain: Hope Through Research. Available at: http://www.ninds.nih.gov/disorders/chronic_pain/detail_chronic_pain.htm#3084_15. Accessed August 5, 2016.

• Use of Opioids for the Treatment of Chronic Pain. American Academy of Pain Medicine. 2013. http://www.painmed.org/files/use-of-opioids-for-the-treatment-of-chronic-pain.pdf. Accessed August 3, 2016