Opioid Chronic Pain

Question 1

A Balancing Act:

Public Health . . .opioid for chronic pain

Answer 1

• A crisis of abuse of prescription opioid medication
• Opioid-Involved Overdose Deaths in New Mexico
– 2017: #17 rank; 16.7 deaths per 100,000
• However ~ 5 years ago NM was ranked #1 in US in accidental OD rates
– Did NM programs for prevention of accidental opioid OD help; or did everyone catch up to us

Question 1

A Balancing Act:

Patient’s Expectations . . . opioid for chronic pain

Answer 1

• Being pain free
• “Magic bullet” medications
• Unlimited supply of medications –> Opioids, possibly gabapentin/pregabalin
• Heavy reliance on medication
• Denial of patient safety concerns

Question 2

A Balancing Act:

Provider Realities

Answer 2

• Previous expose to alcoholism and addiction: 5%-10% of general population
• One addict can effect 7-10 people
• 40% prevalence of current or past substance abuse in patients receiving chronic opioids
• The impact of the CDC Guidelines for Safe Opioid Prescribing, 2016
• Chilling effect; no studies on how this may affect patients
• The challenge (stigma) of prescribing long term opioids
• Substance abuse, misuse and dependence
• Regulatory fears
⇒ clash of provider & patient values

Question 3

Basic Concepts of Prescribing Opioids

Answer 3

• Principles of medication management & prescribing
evidenced based medicine
efficacy and safety
• Use of corticosteroids as an analogy
control symptoms; often not curative
Long term use and high dose dangers

Question 4

CDC Guidelines for Safe Opioid Prescribing (PART 1)

Answer 4

• Primary Care Providers
– Family medicine, Internal medicine
– Physicians, nurse practitioners, physician assistants
• Treating patients >18 years with chronic pain
– Pain longer than 3 months or past time of normal tissue healing
• Outpatient settings
• Does not include active cancer treatment, palliative care, and end-of-life care

Question 5

CDC Guidelines for Safe Opioid Prescribing (PART 2)

• Recommendation #5

Answer 5

– When opioids are started, clinicians should prescribe the lowest effective dosage.
– Clinicians should use caution when prescribing opioids at any dosage, should carefully reassess evidence of individual benefits and risks when increasing dosage to ≥50 morphine milligram equivalents (MME)/day, and should avoid increasing dosage to ≥90 MME/day or carefully justify a decision to titrate dosage to >90
MME/day.

Question 6

Prior to Initiating Opioid Medication . . . what should be done

Answer 6

• Non opioid medication maximized
• Use of screening tests such 
– SOAPP
– ORT
• Controlled Substance Agreement (CSA)
• Review of NMBOP PMP report
• Baseline UDM
• Discuss risks and benefits of using controlled substances w/ patient
• Pause & think

Question 7

Initiating Opioid Medication. . . what to consider

Answer 7

• Complete Critical 1st Assessment
• Start low and go slow
• Start on short acting (SA) opioid
• Reassess in ~ 2 weeks

Question 8

Practical/General Dosage Range Guidelines for Use of Opiates in Chronic Pain
(MED = Morphine Equivalent Dose OR MME = Morphine Milligram Equivalent)

Answer 8

Question 9

Opioid Equianalgesic Doses:

Answer 9

Question 10

PK data for oral opioids

Answer 10

Question 11

PK of Tramadol & Tapentadol. . .

Answer 11

Question 12

Caution with Methadone. . . important things to note

Answer 12

• Variable half-life (8-59 hours) and duration (6-8 hours). . . Dose q 6-12 hours
• Multiple drug interactions. . . Avoid w/ alcohol, azole antifungals, thioridazine
• Can ↑ QTc Interval @ ≈ 100mg/day. . .If ↑ QTc, Decrease dose
• Can accumulate in the elderly
• No changes in dose until 5-7 days after starting methadone

Question 13

Methadone (possible) Equianalgesic Doses:

Answer 13

Question 14

Approximate Fentanyl Patch

Equianalgesic Doses:

Answer 14

Question 15

Fentanyl Patch Cautions. . . Important things to note

Answer 15

• Fentanyl is ≈ 100x > potency than morphine. . .Not for opioid naive patients
• Takes 24 hours before full effect is known, therefore not for breakthrough or acutepain
• Fentanyl is highly lipophilic: caution if ↑ BMI
• Different generic products are not truly interchangeable
• Can only titrate in 3 day increments

Question 16

Reassessment of Opioid Medication Regimen

4 A’s of monitoring opiate therapy

Answer 16

• Analgesia
• activities of daily living
• adverse effects
• aberrant drug-related behaviors

Question 17

Opioid Conversion Examples
.
Patient is on Oxycontin 30mg TID, plus 
Hydrocodone/APAP 7.5/325 TID. What is 
the patient’s total daily opioid dose?

Answer 17

Question 18

Undesired Outcomes of Opioid Use. . .

Answer 18

– Physical Dependence
– Tolerance-larger doses for same effect
– Addiction vs Pseudo-Addiction
– Withdrawal
– Hyperalgesia
– Aberrant Medication Related Behavior

Question 19

Signs/Symptoms Associated with
Aberrant Medication-Related Behavior
• Portenoy and Payne’s Aberrant Behavior. . .

Answer 19

1. Selling prescription drugs
2. Forging prescriptions
3. Stealing drugs
4. Injecting oral formulations
5. Obtaining prescription drugs from non-medical sources
6. Concurrently abusing alcohol/illicit substances
7. Escalating doses on multiple occasions despite warnings
8. “Losing” prescriptions on multiple occasions
9. Repeatedly seeking prescriptions from other providers/ED without informing the provider or after warnings to desist
10. Evidence of deteriorating function due to drug use

Question 20

Urine Drug Monitoring . . . when would it be appropriate?

Answer 20

• Suspected medication related aberrant behavior
• Fear of damaging provider-patient relationship
• Always make sure the test ordered will test for the medication in question
• Always document when patient last took a dose of the medication being tested
• High risk medication, not high risk patents. . .Good data drives good therapy

Question 21

Types of Urine Drug Testing . . .

Immunoassay Presumptive Screen vs. GC-MS or LC-MS/MS Definitive Quantitative

Answer 21

Question 22

Windows of Detection in Urine
.
Indicates how long after administration a person
excretes the drug and/or its metabolite(s) at a
concentration above a specific test cutoff
concentration. . . what are the dates for Amphetamines, THC, Benzodiazepines Opioids, Cocaine (benzoylecgonine metabolite)

Answer 22

Question 23

CDC Guidelines

• Recommendation #4

Answer 23

When starting opioid therapy for chronic pain,
clinicians should prescribe immediate-release
opioids instead of extended-release/long-acting (ER/LA) opioids.

Question 24

Long Acting vs Short Acting Opioid Medication . . . | Since release of CDC Guidelines, there has been movement away from use of LA opioid medication, however:

Answer 24

``` – Since Assume pain at consistent level – Increase adherence – When patient goes for an extended period of time and cannot take a SA opioid; ie: sleep, work – Question of aberrant behavior – > 6 doses of SA opioid/day ```

Question 25

Long Acting vs Short Acting Opioid Medication... benefit of Long Acting?

Answer 25

Question 26

Current Opioid Abuse Deterrent Formulations (ADFs): Advantages and Disadvantages

Answer 26

Question 27

ADF Opioid Medication & Catch 22

Answer 27

* Most ADF products are ER or LA opioid medication & the latest CDC guidelines do not advocate for ER or LA products * All ADF products are brand name products & therefore most insurance co. will not pay for them * Since most insurance co will not pay for ADF products, then these products will not be able to demonstrate post marketing data that these products impacted opioid abuse

Question 28

Use of Buprenorphine for Pain . . . PROs and CONs

Answer 28

``` • Pro – Partial agonist w/ ceiling effect for analgesia & adverse events – Simpler dosing – Less drug-drug interactions – Better safety profile – CIII – More optimal choice for patients that have demonstrated aberrant behavior/addiction – Do not need DEA “X” for CNCP treatment . • Con – If on opioid medication, MAY need to decrease until ≤ 30MME – May not be adequate for severe pain – Insurance obstacles ```

Question 29

Safety of Opioids... things that opioid can do to your body that we need to be careful about . . . GENERAL (3 things)

Answer 29

1. Endocrine system changes 2. Impact of concomitant sleep apnea 3. Opioid hyperalgesia

Question 30

Safety of Opioids | • Endocrine system changes

Answer 30

– Opioids inhibit the release of gonadotropin releasing hormone & corticotropin releasing factor from hypothalmus – Which in turn inhibits the pituitary hormone release of LH, FSH, ACTH & β-endorphins – Resulting in secondary hypogonadism

Question 31

Safety of Opioids | Impact of concomitant sleep apnea

Answer 31

– Opioids cause central sleep apnea by decreasing medullary responsiveness to carbon dioxide levels and thereby worsens obstructive sleep apnea – Compounded by concomitant use of any other CNS depressant; ie: benzodiazepine

Question 32

Safety of Opioids | Opioid hyperalgesia

Answer 32

– Heightened pain perception with opioid use, in the absence of disease progression – Treated by decreasing opioid dose

Question 33

Opioid Medication & Hormonal Changes . . .

Answer 33

Opioids can suppress serum testosterone levels primarily by acting on opioid receptors in the hypothalamus – Decreased release or disruption of the normal plasticity of GnRh secretion – Results in reduction of the release of LH and FSH from pituitary gland and of testosterone or estradiol from the gonad

Question 34

Opioids & Dangerous Medication Combinations: Carisoprodol . . .important to note..

Answer 34

* DO NOT USE CARISOPRODOL (Soma®)!!! * METABOLIZED TO MEPROBAMATE WHICH IS AN ANXIOLYTIC (reduces anxiety) * “HOLY TRINITY” (DEA) = CARSIPRODOL (Soma®) + Benzodiazepine + Opioid = ↑ risk of death drastically!!!

Question 35

Opioids & Dangerous Medication Combinations: Benzodiazepines. . . important to note

Answer 35

– GREATLY INCREASE THE RISK OF ACCIDENTAL OVERDOSE WHEN USED CONCOMMITANTLY W/ OPIOID MEDICATION – AVOID, DON’T USE TOGETHER, STOP USING WITH OPIOID MEDICATION

Question 36

Opioids & Dangerous Drug Combinations

Answer 36

• Benzodiazepines facilitate inhibitory effects of GABA on the respiration at the GABA-A receptor in the medulla • Opioid-induced ventilatory depression results from slowed breathing frequency and reduced tidal volume, & also from a blunted ventilatory responsiveness to hypoxia and hypercapnia • Together these mechanisms can potentiate each other or be synergistic & can be very dangerous very quickly

Question 37

Summary: Gabapentinoids & Opioid Overdose Risk

Answer 37

• Increase in use of gabapentin & pregabalin is most likely due to fallout from CDC Guidelines for Safe Opioid Prescribing • Concomitant gabapentinoids & opioid Rx are significant risk factors for overdose death • Alternatives to gabapentoids need to be recommended for clinicians managing opioid-dependent patients with neuropathic pain or generalized anxiety • Use of gabapentinoids at higher doses should be used with caution in patients concomitantly prescribed opioid medication • Gabapentinoids may suppress respiration &/or decrease opioid tolerance

Question 38

Opioids & Dangerous Drug Combinations: Cyclobenzaprine

Answer 38

• From the New Mexico Department of Health – Cyclobenzaprine was involved in 3% of NM opioid fatal OD – 82% of NM cyclobenzaprine OD fatalities involve opioids

Question 39

Do’s & Don’ts With Opioid Medication . . . the DOs

Answer 39

• DO – Emphasize the importance of sustained improvement in functional levels allowed by opioids – Describe opioids as having potential to “take the edge off” of the pain to allow greater function START with low dose short-acting, perhaps 2-3 tablets per day as needed prn (specify up to maximum of 2-3 tablets per day) - Systemize decision process when filling or refilling opiate Rx - Remove stigma