Opioid Prescriber Education Program Slides

OPIOID PRESCRIBER
EDUCATION PROGRAM
Edward M. Bednarczyk, Pharm.D., FACCP, FAPhA

Director, the Center for Health Outcomes,
Pharmacoinformatics and Epidemiology (cHOPE)
Why are are we (still) here?
OPIOID EPIDEMIC
https://www.cdc.gov/nchs/products/databriefs/db428.htm
Some methods to decrease opioid-related overdoses in NYS
• §80.63 I-STOP Prescription Monitoring Program
• §3332 E-prescribing
• §3216 Mandated insurance coverage for needed inpatient treatment services
• §3309(7) Naloxone co-prescribing law
• §3309-A Prescription pain medication awareness program:
- Require continuing medical education (CME) on pain management by physicians
and other healthcare providers
- Limit initial opioid prescriptions from 30-day supplies to 7-day supplies for acute, non-
cancer pain
- Require pharmacists to provide additional education and counseling to those receiving
opioids
10 NYCRR §80.63, PBH §3332, ISC §3216, PBH §3309 (7)

Prescription pain medication awareness program
• WHAT: Requires at least 3 contact hours of coursework or other training
in:
- Pain management
- Palliative care
- Addiction
• WHO: Prescribers licensed to treat humans and who have a Drug
Enforcement Administration (DEA) number and medical residents
prescribing under a facility DEA number
• WHEN: Prescribers must complete the course work within one year of
DEA registration and once within each three-year period thereafter.
Mandatory training course curriculum
• Training shall include, but is not limited to:
- Pain management
- Appropriate prescribing
- Managing acute pain
- State and federal requirements for prescribing controlled
substances
- Prevention, screening, and signs of addiction
- Response to abuse and addiction
- Palliative medicine
- End-of-life care
Nonjudgmental communication
• Stigma can contribute to patients’ social isolation, Recommended
Terms to Avoid Rationale
Terms
reduced self-esteem, and reluctance to seek treatment
Avoid judging or
- Stigmatizing terms imply a moral judgment and Patient with opioid Addict, drug
defining patient by
use disorder abuser
treat the disorder as a defining personal trait, disorder
contributing to stereotypes and biases Misuse,
harmful/hazardous Avoid moral
• Nonjudgmental communication with patients can Abuse, habit
use, used other judgment or blame
facilitate rapport and collaboration to achieve desired than prescribed
outcomes
Appropriateness
- E.g., “patient with substance use disorder” implies Testing negative
for discussion of
Clean medical condition;
an individual who has a medical condition to be for substance use
avoid bias and
treated shaming
https://nida.nih.gov/nidamed-medical-health-professionals/health-professions-education/words-matter-terms-to-use-avoid-when-talking-about-addiction
Accessed October 28, 2022.
Speaker disclosures
• Edward Bednarczyk: Nothing to disclose
• Karl Fiebelkorn: Nothing to disclose
• Romanth Waghmarae: Averitas Pharma (speaker), Scilex Holding
(speaker)
• Arthur Weissman: Nothing to disclose
• Robert Wahler: Nothing to disclose
LAWS, RULES, AND REGULATIONS
CONCERNING THE PRESCRIBING
OF CONTROLLED SUBSTANCES
IN NEW YORK STATE
Opioid Prescriber Education Program
Karl D. Fiebelkorn, BSPharm, RPh, MBA
Senior Associate Dean
University at Buffalo
School of Pharmacy and Pharmaceutical Sciences
Learning objectives: Law
• List the Federal and New York State (NYS) requirements for prescribing
controlled substances
• Define the NYS Prescription Monitoring Program (PMP) and its purpose
• Describe NYS 7-day rules

Controlled substance schedules
• CI – CV
• Federal Controlled Substance Act
- DEA
- Title 21 Code of Federal Regulations 1300-end
- Title 21 U.S. Code Chapter 13, Subchapter 1 (sections 800-971)
• NYS Controlled Substance Act
- NYS Department of Health Bureau of Narcotic Enforcement (BNE)
- Article 33 Public Health Law
- Part 80 Controlled Substance Regulations
- Part 910 Official New York State Prescription Forms Regulations
Purpose of issuing prescription
§80.65; §910.2; F1306
• A prescription shall be issued by a practitioner for a legitimate medical purpose in
good faith and in the course of their professional practice only
• Responsibility for proper prescribing is upon prescribing practitioner
• Must have a bonafide DEA number and register
- To receive Official New York Prescriptions (abbreviated in this presentation as
ONYSRx)
- Software with NYS BNE
• Corresponding responsibility (and liability) rests with the pharmacist who fills the
prescription
§80.73(e), 80.74(f)
• A pharmacy shall make a good faith effort to verify the identity of any person
accepting delivery or a dispensed prescription for a controlled substance by
requiring such person, if unknown to the pharmacy, to present appropriate
identification
Use of controlled substances in treatment
§80.62; §80.63
• Practitioners may use controlled substances in treating their patients (not for
addiction) when the practitioner regulates the dosage, administers or
prescribes a quantity no greater than that ordinarily recognized by members
of their profession as sufficient for proper treatment
• With limited exceptions, no controlled substances shall be issued prior to
examination of the patient by the practitioner
Use of controlled substances in treatment
§80.62; §80.63
• The parameters for the physical exam may vary to conform to best practices
based on the condition and medication(s) being prescribed
• Once the initial examination has been completed, the frequency and necessity
for future examinations for the same condition will be made by the practitioner
utilizing generally accepted medical standards
Exceptions §80.63
In the temporary absence of the initial prescriber
• If the controlled substance is part of a continuing therapy and the current
prescriber:
- had direct access to the patient’s medical records and such records warrant
continuation, OR
- had direct and adequate consultation with the initial prescriber and both
concur on the continuation
Exceptions §80.63
In the temporary absence of the initial prescriber
• If the patient record is not available, the practitioner shall:
- document the activity for his or her own record, AND
- transmit to the initial prescriber the prescription information
• The initial prescriber shall include the prescription information in the patient’s
record
Exceptions §80.63
• A practitioner may prescribe a controlled substance to their patient after review
of the patient’s record, if:
- The record contains the result of an examination performed by a consulting
physician or hospital and such record warrants the prescribing
Exceptions §80.63
If the patient develops a new condition
• A practitioner may issue a controlled substance prescription prior to performing
an examination if:
- a previously established practitioner/patient relationship exists, AND
- an emergency exists, AND
- the prescription does not exceed a 5-day supply
Types of prescriptions
10 NYCRR Part 910
• Written
- ONYSRx
- Exceptions: Out-of-state prescription written on the authorized blank of that state
- Prescribers not practicing in NYS
- Clinics/hospitals on federal land
- Department of Veterans Affairs
- Tribal Lands
- Military bases (e.g., U.S. Army Fort Drum)
• Verbal
• Electronic
Jane Moneypenny, MD,
Felix Leiter, LPA-987654
1048 Bond Lane
New York, NY 10003
555 007 0001
M C 4 4 4 4 4 4 6 555 007 0002
Auric Goldfinger 8/13/2022
1007 Odd Job Road
Precious NY 66
X
Hydrocodone 5/325
#18
One tab po q4h prn
Felix Leiter, LPA

0
WKP 618 12
Official New York State Prescriptions
• Written types
- Must contain the signature of the prescriber
- Paper
- Security features
- Security touch feature
- Bar code
- Serial number
§910, §80.69
https://www.health.ny.gov/professionals/narcotic/newsletters/docs/pharmacy_update_summer_2009.pdf. Accessed April 4, 2022.
Written Official New York State Prescriptions
§6810(8) NYS Education Law
• Prescriber’s name must be imprinted or stamped legibly and conspicuously on
the blank, with:
- name of the prescriber who signed the prescription
- e.g., hospital/clinic blanks
Prescriptions: Rule of thumb
• Same rules apply to electronic and written prescriptions
• Same rules apply to faxed and verbal prescriptions
- Fax to fax is allowed (telephonic)
- Faxed prescriptions must be on the ONYSRx of the prescriber and signed
prior to faxing
https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/elec_pres_except_disp_clar_4_pharm.htm. Accessed April 4, 2022.

https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/docs/epcs_faqs.pdf. Accessed April 4, 2022.
http://www.op.nysed.gov/prof/pharm/pharmelectrans.htm. Accessed April 4, 2022.
Verbal/faxed prescriptions
§80.67, §80.68, §80.70
• CII, anabolic steroids, benzodiazepines
- Must send follow-up prescription within 72 hours
- Via written ONYSRx or electronic
- Follow-up must state “Authorization for emergency dispensing”
- Pharmacist reports to BNE and DEA if no cover is received
• CIII, CIV (non-benzodiazepines), CV
- Must send follow-up prescription within 72 hours
- Via written ONYSRx or electronic as a follow-up prescription to verbal order
- Practitioner should indicate: “Follow up prescription to oral order”
Persons authorized to issue prescriptions: Verbal
§80.64; F1306
• Federal law allows controlled substance prescriptions to be communicated to a
pharmacist by an employee or agent of the individual practitioner
• NYS says NO!
- Only the prescriber may orally prescribe controlled substances to a
pharmacist in any venue
One drug per blank
§6810(7)
• “No prescription for a drug written in this state by a person authorized to
issue such prescription shall be on a prescription form which authorizes the
dispensing or compounding of any other drug.”
• “No drug shall be dispensed by a pharmacist when such prescription form
includes any other drug.”
One drug per blank
§6810(7)
• Exceptions:
- More than one noncontrolled substance may be written for an inpatient on a
medical order (inpatient) or “patient specific prescription form” residential
health care facility
- Article 28 facilities: General hospitals, nursing homes, residential health
care facility
- Hospitals under §1.03 of the Mental Hygiene Law
- Developmental centers or developmental disabilities services under §13.17
of the Mental Hygiene Law
Internet System for Tracking Over Prescribing (I-STOP)/
Prescription Monitoring Program (PMP)
Controlled substance prescriptions §80.63
• Duty to consult is required prior to prescribing of controlled substance in
schedules CII, CIII, CIV, optional for CV
- Exceptions in §80.63
• May check PMP up to 24 hours in advance
• May be medical marijuana on listing
I-STOP/PMP
• Must document that PMP was checked
- If PMP was not checked, document the reason
- Must be an approved exception as stated in §80.63
• FAQs for PMP
https://www.health.ny.gov/professionals/narcotic/prescription_monitoring/docs/pmp_registry_faq.pdf. Accessed March 30, 2022.

I-STOP/PMP
• Why does the controlled substance prescription that I prescribed
previously not show up on the PMP?
- Data entry error
- Patient lost prescription
- Patient never filled prescription
- Too expensive
- Not covered by insurance
- Patient lost insurance
- Patient filled prescription outside of NYS
I-STOP/PMP
• Why can I not find a patient I know had a controlled substance
prescription filled?
- Depends on format of information entered
- E.g., Pat vs. Patricia vs. Patrice vs. Patty vs. Patti
- Transmission error by the pharmacy
- Wrong practitioner name or DEA number
- May need to contact the pharmacy where the electronic prescription was
sent to clarify
Nursing homes and hospitals
NYS Class 3 and 3a facilities
• If the patient is receiving the medication on premises (on site) where the drug
is consumed, the prescriber is not required to check the PMP
- But must indicate on the chart each time a controlled substance
prescription is ordered in hospital or nursing home
- NPIP: No PMP Institutionalized Patient
• When the patient consumes the medication off premises, consultation of the
PMP is required
https://www.health.ny.gov/professionals/narcotic/prescription_monitoring/. Accessed March 30, 2022.

Patient records
§80.62(b)
• Practitioners shall maintain a written patient record:
- Administration
- Dispensing
- Prescribing of all controlled substances
• Contain sufficient information to justify the diagnosis and warrant the treatment
Patient records
§80.62(b)
• Contain at least the following information:
- patient identification data;
- chief complaint;
- present illness;
- physical examination as indicated;
- diagnosis;
- other data which support the diagnosis or treatment; and
- the regimen including amount, strength, and directions for use of the
controlled substance
7-day supply rule
§3331(5 b,c) July 22, 2016
• A practitioner may not initially prescribe more than a 7-day supply of an opioid
medication for acute pain
• Does not apply to chronic pain such as:
- cancer;
- hospice;
- end-of-life; and
- palliative care
7-day supply rule
§3331(5 b,c) July 22, 2016
• Upon any subsequent consultations for the same pain, the practitioner may
issue, in accordance with existing rules and regulations, any appropriate
renewal, refill, or new prescription for an opioid
• Pharmacists are not required to verify with the prescriber about the condition
being treated.
Written treatment plan
§3331(8)
• No opioids shall be prescribed to a patient initiating or being maintained on
opioid treatment for pain which has lasted more than 3 months or past the
time of normal tissue healing unless the medical record contains a written
treatment plan that follows generally accepted professional or governmental
guidelines
• This does not apply to:
- cancer that is not in remission
- hospice or other end-of-life care
- palliative care
• Treatment plan shall include, but is not limited to:
- Goals for pain management and functional improvement based on the
diagnosis
- Discussion on how opioid therapy will be tapered to lower dosages or
tapered and discontinued if the benefits do not outweigh the risks
- A review with the patient of risks and alternatives to opioids
- Evaluation of risk factors for opioid-related harms
https://www.health.ny.gov/professionals/narcotic/docs/opioid_treatment_plan_letter.pdf
• Documentation and discussions shall be done, at a minimum, on
an annual basis
https://www.health.ny.gov/professionals/narcotic/docs/opioid_treatment_plan_letter.pdf
Naloxone §3309(7)
• With the first opioid prescription to a particular patient each year, the
practitioner must prescribe an opioid antagonist when any of the following are
present:
- History of substance use disorder (SUD)
- High dose or cumulative prescriptions that result in 90 morphine milligram
equivalents or higher per day
- Concurrent use of opioids and benzodiazepine or nonbenzodiazepine
sedatives
Naloxone §3309(7)
• Exceptions include patients in the following settings:
- General hospitals or nursing homes: Article 28
- Mental health facility: Article 31 of Mental Hygiene Law
- Hospice: NYS PBL Article 40 §4002
• Law effective June 28, 2022
Electronic prescriptions
NYS PHL Article 33, §3332
• Note: Federal law states that electronic prescribing of controlled substances
is optional
- New York State = first state to make electronic prescribing mandatory for
both controlled and noncontrolled substances
• Law effective March 27, 2016
§1311.115
• To sign a controlled substance prescription the electronic prescription
application must require the practitioner to authenticate (2 of 3 factors):
1. Something only the practitioner knows
Felony to give password to
- Password or response to a challenge question someone else
2. Something the practitioner is
- Biometric data such as a fingerprint or iris scan
3. Something that the practitioner has
- A device (hard token) separate from the computer to which the
practitioner is gaining access
Electronic prescribing
• Everyone must have their system approved by the DEA and software shall be
registered with the BNE
• FAQs for electronic prescribing

• Created, recorded, transmitted by electronic means
• Issued and validated by the prescriber’s electronic signature
• Electronically encrypted
- Prevent access, alteration, etc.
• Transmitted directly from the prescriber to the pharmacy/pharmacist
http://www.op.nysed.gov/news/advisory-notices.html#electronic. Accessed March 30, 2022.

Electronic prescriptions are not…
• Email
- Not even if encrypted
• Faxing
• Texting
• Social media, etc.
http://www.op.nysed.gov/news/advisory-notices.html#electronic. Accessed March 30, 2022.

Electronic Exceptions
10 NYCRR; Part 910; PHL 281 (3)(a-e)
• There are several exceptions in which a practitioner may issue an ONYSRx
form, oral prescription, or a fax of a manually signed ONYSRx
• Must indicate in the patient’s health record when using an exception
https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/elec_pres_except_disp_clar_4_pharm.htm. Accessed March 30, 2022.

https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/practitioner_notification_requirement.htm. Accessed March 30, 2022.
Exceptions listed in Public Health Law
§281(3) (a-e)
• Temporary technological failure
• Temporary electrical failure
• An approved waiver
• The practitioner reasonably determines that it would be impractical for the patient to obtain
substances prescribed by an electronic prescription in a timely manner and such delay would
adversely impact the patient’s medical condition
- Quantity of the controlled substance not to exceed 5-day supply
• To be dispensed by a pharmacy located outside the state
- Including federal institutions such as Veterans Affairs facilities, Tribal Reservations, U.S. Army Fort
Drum, and U.S. Army West Point
https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/elec_pres_except_disp_clar_4_pharm.htm. Accessed March 30, 2022.
https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/practitioner_notification_requirement.htm. Accessed March 30, 2022.
Commissioner of Health blanket waivers
Effective until March 24, 2024 PHL §281(3)
• The following circumstances allow a practitioner to issue a written ONYSRx or
oral prescription for controlled or non-controlled substances. The practitioner is
not required to indicate the circumstance on the written ONYSRx or oral
prescription:
- Prescriptions with complicated directions
- Compounded prescriptions containing 2 or more products
- Compounded infusion prescriptions
https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/. Accessed April 19, 2023.

Effective until March 24, 2024 PHL §281(3)
• A prescription containing certain elements required by the Federal Food and
Drug Administration (FDA) such as an attachment
• Approved protocols under expedited partner therapy
• Approved protocols under collaborative drug management
• Response to a public health emergency that would allow a non-patient specific
prescription
• Approved research protocol
• A non-patient specific prescription for an opioid antagonist
https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/. Accessed April 19, 2023.
Effective until October 31, 2023 Public Health Law §281(3)
• The following circumstances allow a practitioner to issue a written ONYSRx or
oral prescription for controlled or non-controlled substances:
- To be communicated to a pharmacist serving as a vendor of pharmaceutical
services, by an agent who is a health care practitioner, for patients in
nursing homes and residential health care facilities as defined by Public
Health Law §2801
- A pharmacist serving as a vendor of pharmaceutical services dispensing in
conformity with the above
https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/. Accessed November 17, 2022.

Written or electronic prescriptions
• All pertinent information must be included:
- Patient demographics
- Name, address, age (date of birth), gender (CII’s and benzodiazepines
per 10NYCRR §80.67)
- Prescriber information
- Including name, address, phone, DEA number
- Drug information
- Name, strength, directions, maximum daily dose (MDD)
- NYS dictates one drug per blank (§6807(7))
§6810, §29.7
Electronic prescriptions include:
• Signature (digital)
• Brand or generic
• Prescriber’s NPI number should be on the electronic prescription, a federal
requirement
• Does not include OTCs and herbals/supplements
• Note: An ONYSRx handed to the patient with the notice “electronically signed
by the prescriber” is not electronic
http://www.op.nysed.gov/news/advisory-notices.html#electronic. Accessed January 13, 2022.

§80.67, §80.69, §80.73, §80.74
• All prescriptions for controlled substances must be filled within 30 days of the
date the prescription was issued by the practitioner
• No additional prescriptions (or refills) may be issued by a practitioner to an
ultimate user for the same controlled substance
- Unless/until the ultimate user has exhausted all but a 7-day supply of the
controlled substance
- “7-day rule”
§80.67, §80.69, §80.73, §80.74
• CII, anabolic steroids
- Anabolic steroids are NYS CII and federal CIII
- Maximum 30-day supply
- No refills
• CIV—benzodiazepines
- No refills
- Maximum 5 refills/6 months (if indicated)
Federal versus state law
• The Federal Controlled Substance Act states that a prescriber may issue 3
prescriptions for the same controlled substance at the same time to a patient
- NYS says NO!
- NYS has ‘condition codes’
- The condition or code must be indicated on the prescription
NYS condition codes for controlled substances
§80.67, §80.69, §80.73, §80.74
• May provide up to a three-month supply as determined by the directions for
use for substances used for the treatment of Codes A-E:
Panic disorders Code A

Attention deficit disorders Code B
§80.67, §80.69, §80.73, §80.74
Chronic debilitating neurological Code C

conditions characterized as a
movement disorder or exhibiting
seizure, convulsive or spasm activity
Relief of pain…suffering from Code D
disease known to be chronic and/or
incurable
§80.67, §80.69, §80.73, §80.74
Narcolepsy Code E
Anabolic steroids used to Code F
treat…hormone deficiency states in
males, gynecologic conditions that
are responsive to treatment with
anabolic steroids or chorionic
gonadotropin, metastatic breast
cancer in women, anemia and
angioedema
*May prescribe up to 6-month supply
§80.67, §80.69, §80.73, §80.74
• CII, anabolic steroids, benzodiazepines
- No refills
- 1 refill if indicated
Pharmacy required information sheet
Controlled substances October 22, 2016
• When dispensing a controlled substance, the pharmacist must provide the patient with
information about the:
1. Dangers of misuse and potential risk of substance abuse disorder from prescription-
controlled substances
2. Physical and behavioral warning signs of substance abuse disorder
3. Available alcohol and substance use disorder treatment resources
4. Proper disposal guidelines for unused prescription-controlled substances
• Information must be provided in languages other than English as deemed appropriate by the
NYS Commissioner of Health but shall include the 10 most commonly spoken languages,
aside from English, in the state
• May be provided to the patient electronically if requested by the patient
https://www.health.ny.gov/publications/12022.pdf. Accessed April 4, 2022.
Additional resources
• NYS Bureau of Narcotic Enforcement Website:
- https://www.health.ny.gov/professionals/narcotic/
• NYS Prescription Monitoring Program (PMP) Training:
- https://pharmacy.buffalo.edu/academics/continuing-education/events/the-new-york-state-prescription-
monitoring-program-update.html
• NYS Prescription Monitoring Program Instructional Videos
- Note: Requires Health Commerce System Account
- https://commerce.health.state.ny.us/HCSRestServices/HCSContentServices/docs?docPath=/hcs_Do
cuments/Source/hpn/hpnSrc/C7BBE6FBDA863774E0530547A8C027A9.pdf
PAIN MANAGEMENT,
MANAGING ACUTE PAIN,
APPROPRIATE PRESCRIBING
Romanth Waghmarae, MD, DABA, FACIP, FIPP

Assistant Clinical Professor Anesthesia-McMaster University
Research Assistant Professor-UB SPPS
Learning objectives: Pain management
• Describe the pathophysiology and general approaches for pain
assessment in the ambulatory setting
• Describe approaches for managing acute pain and how they differ from
approaches for managing chronic pain
• Outline evidence-based best practices for appropriate prescribing of

opioid analgesics
Pain management
• Provide safe, multimodal, compassionate care for patients with pain to
optimize their function and quality of life
- Increased caution in the context of the opioid crisis
- Must assess and treat appropriately to prevent harm
• This section will provide an introduction to pertinent pain management topics
in order to help achieve benefits while minimizing potential for harm
Pain
• “An unpleasant sensory and emotional experience associated with, or
resembling that associated with, actual or potential tissue damage.”
Revised International Association for the Study of Pain (IASP) definition, 2020
- Definition valid for acute and chronic pain; applies to all pain conditions
- From the perspective of the one experiencing pain
Raja SN et al. Pain. 2020;161:1976.

Characteristic Acute Pain Chronic Pain
Duration - Time-limited; recent in onset - Long history (i.e., >12 weeks)
(i.e., 4 weeks or less) - Poorly defined onset
- Does not last longer than days to weeks - Duration unknown
Cause - Identifiable—trauma, surgery, acute medical - Persists beyond usual recovery period or occurs
condition, or physiological process along with a chronic health condition
- Nervous system usually intact (e.g., arthritis)
- Serves a useful, protective biologic purpose
Intensity - Variable - Variable

- Subsides with healing - “On” and “off” or continuous
Associated Effects - Psychological problems, e.g., depression are - May affect people to the point that they cannot
short-lived if present at all work, eat properly, take part in physical activity,
or enjoy life
Treatment - Multimodal - Multimodal
- Responds well to non-pharmacological
treatment and/or non-opioid analgesics
Raja SN et al. Pain. 2020;161:1976.

Grichnik KP et al. Mt Sinai J Med. 1991;58:217.
American Chronic Pain Association https://www.theacpa.org/
Acute Pain Processing: Nociception Chronic Pain Pathology
• Recognition and reaction in the brain •Possible neurochemical link between

(interactions of thalamus, sensory cortex, Perception Mental pain and memory. High incidence of
limbic system, reticular activating system) depression, anxiety. Suffering increases
Overload perceived pain.
• Antinociception neurons descend from
Spinal Cord Neuron

brainstem to spinal cord: release chemical
messengers that inhibit transmission of Modulation Loss of •Normally innocuous stimuli become
painful stimuli Nociceptive painful; any movement of tissues causes
pain
Control
• Synaptic transfer of input between neurons Dorsal Horn
via neurotransmitters Transmission
•Repeated pain signals → nervous
Primary Sensory Neuron

Sensitization system changes that intensify pain:
“windup”
• Action potentials pass along neurons Conduction
Damaged •Damaged sensory nerves may send

Nerve constant pain signals
• Noxious stimuli → electrical activity at
sensory nerve endings Transduction
Neurogenic •Increased prostanoid production at pain

• Damaged cells release sensitizing site → allodynia, hyperalgesia →
chemicals Inflammation Noxious stimulus Inflammation generates spontaneous pain
Adapted from Whitten CE et al. Perm J. 2005;9:9.

Pain categorization
Severity Mild vs Moderate vs Severe
Pathophysiology Nociceptive vs Neuropathic vs Mixed
Disease Origin Cancer vs Non-Cancer
Temporal Acute
Chronic
Persistent Intermittent Break-Through

Pain
Adapted from Xiao X et al. Neurosci Bull. 2021;37:405.
Presentation varies across pain states
Neuropathic Pain Nociceptive Pain
Pain initiated or caused Mixed Pain Pain caused by injury to
by a primary lesion or Pain with body tissues
dysfunction in the neuropathic and (musculoskeletal,
nervous system (either nociceptive cutaneous or visceral)
peripheral or central components
nervous system)
Examples Examples
Postherpetic neuralgia Pain due to inflammation
Trigeminal neuralgia Limb pain after a fracture
Painful diabetic neuropathy Examples Joint pain in osteoarthritis
Postsurgical neuropathic pain Low back pain with radiculopathy Postoperative visceral pain
Posttraumatic neuropathy Cervical radiculopathy
Central post-stroke pain Cancer pain Common descriptors
Common descriptors Carpal tunnel syndrome Aching
Burning Sharp
Tingling Throbbing
Hypersensitivity to touch or cold
IASP Pain Taxonomy. McMahon SB et al (eds). Wall & Melzack’s textbook of pain, 6th ed. 2013.
Consequences of lack of knowledge of chronic pain
management
Knowledge Gaps Possible Problems
Miss the benefits of physical, behavioral, and psychological approaches to

Failure to use multimodal approach
train the nervous system and maximize functional recovery
Suboptimal pain control

Failure to target the mechanism of pain
Increased costs when pain control not effective
Failure to treat neuropathic pain with Worsening hypersensitivity of nervous system

adjuvant medications Suboptimal pain control
Increased breakthrough pain, disturbed sleep

Heavy use of short-acting opioids
Development of opioid tolerance
instead of long-acting opioids
Acetaminophen toxicity with opioid/acetaminophen combinations
Whitten CE et al. Perm J. 2005;9:9.

Baseline patient assessment
• Assess
- Clinical history (pain, medical, psychosocial), physical examination (risk
assessment), laboratory and diagnostic criteria
• Determine
- Underlying mechanism of pain
• Characterize
- Pain quality including site and severity
https://www.practicalpainmanagement.com/resources/diagnostic-tests/guide-chronic-pain-assessment-tools. Accessed March 21, 2022.

The PQRSTU mnemonic
• Helpful tool to evaluate patient’s pain symptoms
- Precipitating or Palliative (including medications)
- Quality
- Region or Radiation
- Severity (pain scales)
- Timing or Temporal (onset, time of day, pattern, duration)
- U = “You”— quality of life impact, functioning
Ryan CW. Am Fam Physician. 1996;54:1051. Thomas SA. Phys Med Rehabil Clin N Am. 2003;14:29.
https://www.ems1.com/ems-products/education/articles/how-to-use-opqrst-as-an-effective-patient-assessment-tool-yd2KWgJIBdtd7D5T/. Accessed March 25, 2022.
Evaluation of pain severity
• Every visit Numeric Rating Scale
- Current pain 0 1 2 3 4 5 6 7 8 9 10
- Worst pain in past 7 days No

pain
Moderate
pain
Worst
possible
Adapted from: McCaffery et al. 1989 pain
- Usual or average pain in past 7 days
• Useful bedside pain rating scales Visual Analog Scale
- Numeric rating/visual analog scales No

pain
Worst
possible
- Wong-Baker FACES Pain Rating Scale Adapted from: Haefeli M, Elfering A. 2006 pain
- McGill Pain Questionnaire

• Scales for special populations, e.g., pediatrics, visually impaired
https://www.sralab.org/rehabilitation-measures/numeric-pain-rating-scale. Accessed March 28, 2022. www.wongbakerfaces.org. Accessed March 28, 2022.
Patient evaluation and risk assessment
• For all patients:
- Risk stratification
- Risk assessment
• Many screening tools available to help identify behaviors associated with
risk for misuse and substance use disorder
• If these tools are used, they should be considered in conjunction with
other assessments
Butler SF et al. J Pain. 2008;9:360. Chou R et al. J Pain. 2009;10:113. Dowell D et al. MMWR Recomm Rep. 2022;71:1. Hegmann KT et al. J Occup Environ
Med. 2014;56:e143. Manchikanti L et al. Pain Physician. 2017;20:S3.
I-STOP/PMP. Available at: https://www.health.ny.gov/professionals/narcotic/prescription_monitoring/
Risk assessment screening tools
• SOAPP-R (Screener and Opioid Assessment for Patients with Pain-Revised)
- Risk assessment tool when considering opioids and for continued assessment
when on opioids
- Guide to frequency of monitoring based on risk score
(<12 low, 12-18 moderate, >18 high)
- Consists of 24 self-administered questions
• COMM (Current Opioid Misuse Measure)
- Routine risk assessment of ongoing treatment to screen for drug misuse
- Used to supplement physical exam, patient interview, clinical assessment
- Consists of 17 self-administered questions to identify misuse of opioids
Finkelman MD et al. Pain Med. 2015;16:2344. Butler SF et al. J Pain. 2008;9:360. Butler SF et al. Pain. 2007;130:144.
Mitigation strategies to minimize the risk
of misuse and diversion
• Prevention strategies help prescribers monitor adherence to treatment plans and
minimize the possibility of diversion
• Examples include:
- Pain/opioid management agreement or treatment plans (NYS law §3331(8))
- Patient education
- Routine/random screening: Urine testing, I-STOP/PMP
- Pharmacogenetic testing: Analysis of cytochrome function, if appropriate
- Routine follow-up and reassessment; pill counts if deemed appropriate
Butler SF et al. J Pain. 2008;9:360. Chou R et al. J Pain. 2009;10:113. Dowell D et al. MMWR Recomm Rep. 2022;71:1. Hegmann KT et al. J Occup Environ
Med. 2014;56:e143. Manchikanti L et al. Pain Physician. 2017;20:S3. Volkow ND et al. N Engl J Med. 2016;374:1253.
https://www.healthquality.va.gov/guidelines/Pain/cot/. Accessed January 24, 2023.
https://www.health.ny.gov/professionals/narcotic/prescription_monitoring/. Accessed January 24, 2023.
Understanding urine drug screening
• Component of prescriber-patient opioid management agreement or
treatment plan
• Random versus scheduled
• Frequency varies per patient
• Know the laboratory
• Opioid metabolites— genetic variations in opioid metabolism
• Creatinine concentration
• Interpretation
• Confirmatory testing
Owen GT et al. Pain Physician. 2012;15:ES119.
Acute pain management
• Opioids are not usually warranted for many common acute pain conditions
- First-line treatment: Non-opioid analgesics + non-pharmacologic
E.g., Acetaminophen/nonsteroidal anti-inflammatories +/- adjuvant therapy
• Opioids should be reserved for acute pain where alternative treatments are ineffective or contraindicated
and where acute pain results in severe restriction of ability to function on a day-to-day basis
- Prescribe the lowest effective dose of an immediate-release opioid
- Extended-release formulations of opioids should not be prescribed for the initial treatment of acute pain
- Do not prescribe opioids for longer than necessary
- E.g., ≤3 days often sufficient; >7 days rarely needed
- Opioids should be tapered and discontinued as acute pain improves and resolves, such as in the
postoperative period
Chou R et al. J Pain. 2016;17:131. Dowell D et al. MMWR Recomm Rep. 2022;71:1. Kyriacou DN. JAMA. 2017;318:1655.
Acute pain management—continued
• Educate the patient about potential risks and side effects
• If possible, avoid prescribing opioids in combination with other central nervous system (CNS)
depressants (benzodiazepines, sedative-hypnotics, or skeletal muscle relaxers)
- Per NYS law §3309(7), prescribe naloxone if opioids must be used concurrently with
benzodiazepines or nonbenzodiazepine sedatives
• Patients prescribed opioids for acute pain are at a higher risk of using opioids long-term when
not appropriately monitored and evaluated
• Conducting follow-up:
- Re-evaluation needed if acute severe pain lasts longer than the expected duration
- If opioid therapy continues beyond 30 days for acute pain, discuss whether proceeding with
longer-term treatment is appropriate
Dowell D et al. MMWR Recomm Rep. 2022;71:1. Kyriacou DN. JAMA. 2017;318:1655.
Acute pain: Pharmacologic treatment
• Acetaminophen (APAP)
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Ibuprofen
- Naproxen
• Cyclooxygenase-2 selective NSAIDs → Second-line (cost)
• Full opioid agonists only if opioid combinations (e.g., hydrocodone/APAP)
insufficient to control moderate-to-severe pain
• Tramadol → Second-line for moderate-to-severe pain (less effective than
hydrocodone/APAP)
Blondell RD et al. Am Fam Physician. 2013;87:766.

Chronic non-cancer pain (CNCP) classification:
Neuropathic pain
• First-line pharmacologic treatment options
- Alpha-2-delta ligands (e.g., pregabalin, gabapentin)
- Serotonin-norepinephrine reuptake inhibitors (SNRIs)
- Tricyclic antidepressants (TCAs)
• Second-line treatment options
- Topical agents (e.g., lidocaine, capsaicin)
Attal N et al. Eur J Neurol. 2010;17:1113. Bril V et al. Neurology. 2011;76:1758. ADA Professional Practice Committee. Diabetes Care. 2022;45:S185. Moulin
D et al. Pain Res Manag. 2014;19:328. Finnerup NB et al. Lancet Neurol. 2015;14:162. National Institute for Health and Care Excellence, 2013. Updated
September 22, 2020. https://www.nice.org.uk/guidance/CG173
CNCP classification: Musculoskeletal pain
• Definition: Pain caused by a lesion or disease of the musculoskeletal system including
muscles, ligaments, tendons, cartilaginous structures, and joints. Commonly involves neck,
shoulders, trunk, arms, low back, hips, and lower extremities.
• Description: Tender muscle sites, pain is referred (trigger points)
• Cause/type: By injury or due to occupational repetitive activity, fracture, obstructions,
dislocation, or compression of tissue by tumor, cyst, or bony structure
• First-line pharmacologic treatment options:
- APAP
- NSAIDs
- Topical agents
DiPiro JT et al (eds). DiPiro: Pharmacotherapy a pathophysiologic approach, 12e; chapter 79. 2021. Treede RD et al. Pain. 2015;156:1003. Perrot S et al.
Pain. 2019;160:77.
CNCP classification: Inflammatory pain
• Definition: Pain caused by an inflammatory process (e.g., infection, autoimmune) which is generally
associated with the infiltration of immune cells and tissue damage. Commonly involves neck, shoulders,
trunk, arms, low back, hips, and lower extremities.
• Description: Progressive pain that is sharp or lancinating with or without increased pain with movement
• Pain site may be tender, hot, and red with swelling at the site with a history of injury or known
inflammation
• See specific recommendations/guidelines for rheumatoid arthritis and other individual conditions
• First-line pharmacologic treatment options:
- NSAIDs
- Glucocorticoids
- Topical agents
Fraenkel L et al. Arthritis Care Res (Hoboken). 2021;73:924. Xiao X et al. Neurosci Bull. 2021;37:405.
CNCP: Non-pharmacologic first-line treatment options
• Cognitive-behavioral therapy
• Integrative (e.g., acupuncture, massage)
• Physical therapy
• Patients started on non-pharmacologic and/or non-opioid analgesic
therapies for CNCP should be reassessed for improvement in pain
and/or functional status at 2-4 weeks
Chang KL et al. FP Essent. 2015;432:21. Dowell D et al. MMWR Recomm Rep. 2022;71:1.
Multimodal analgesic approach
• Use of multiple methods can decrease the amount of opioid medications
necessary to relieve pain and can minimize adverse drug reactions
• Thought should be given to patient access to multimodal therapy; tailor
approach to individual needs
• Current consensus guidelines support this approach
• If clinically appropriate, medical cannabis may be another method of treatment
for pain
Chou R et al. J Pain. 2009;10:113. Dowell D et al. MMWR Recomm Rep. 2022;71:1. Manchikanti L et al. Pain Physician. 2017;20:S3.
Patient-centered treatment goals
• Before initiating opioid therapy, consider whether potential improvement in
function/pain outweighs risks to the patient
• Examples of items to discuss jointly with patients when initiating and periodically
during opioid therapy include:
- Realistic benefits and known risks
- Specific, measurable treatment goals
- How opioids will be discontinued if benefits do not outweigh risks
Dowell D et al. MMWR Recomm Rep. 2022;71:1.

Initiating short-acting opioids
• Patients with pain severe enough to require an opioid analgesic despite an
adequate trial of non-pharmacologic and non-opioid therapies should be
evaluated to determine if a short-term trial of a short-acting opioid is
appropriate
• Patients should not expect total pain relief with opioids
• Studies suggest that pain improvement averages <2-3 points on a 0 to 10-point
scale
• Caution with opioid-naïve patients
Chou R et al. J Pain. 2009;10:113. Dowell D et al. MMWR Recomm Rep. 2022;71:1. Hegmann KT et al. J Occup Environ Med. 2014;56:e143.
Manchikanti L et al. Pain Physician. 2017;20:S3. Roxicodone [package insert]. Mallinckrodt; 2017.
Extended-release and long-acting opioids (ER/LA)
• Advantages:
- ER/LA opioids can achieve more consistent control of pain with fewer daily
doses
- May improve adherence
• ER/LA opioids should be reserved for severe, continuous pain
- Not recommended for the treatment of acute pain and should not be used
as the initial opioid for subacute or chronic pain
- Not for intermittent/as-needed use
• Prescribers should not prescribe more than 1 ER/LA opioid at a time for CNCP
ASA/ASRA. Anesthesiology. 2010;112:810. Dowell D et al. MMWR Recomm Rep. 2022;71:1. Hegmann KT et al. J Occup Environ Med. 2014;56:e143.
Manchikanti L et al. Pain Physician. 2012;15:S67. https://www.healthquality.va.gov/guidelines/Pain/cot/. Accessed January 24, 2023.
Checklist for prescribing opioids for CNCP
when considering long-term opioid use
• Set realistic goals for function and pain
• Verify use of non-opioids first
• Discuss risks/benefits with patient (overdose, misuse, opioid use disorder (OUD))
• Evaluate risk of harm or misuse
- Risk factors
- I-STOP/PMP data
- Urine drug screen
- Consider prescribing naloxone – evaluate benefits and legal requirements
• Determine criteria for dose reductions, tapering, stopping (if on low dose), or continuing opioids
• Assess baseline pain and function; schedule initial reassessment
• Prescribe short-acting opioids at lowest effective dose and duration
https://www.cdc.gov/drugoverdose/pdf/pdo_checklist-a.pdf. Accessed March 30, 2022.
Opioids— Mechanism of action for analgesia
• Opioids bind to opioid receptors within CNS and peripheral tissues
- Mu
- Supraspinal analgesia, respiratory depression, euphoria, sedation, ↓ gastrointestinal
motility, physical dependence
- Kappa
- Spinal analgesia, sedation, dyspnea, dependence, dysphoria, respiratory depression
- Delta
- May be responsible for psychomimetic, dysphoric effects
- Sigma
- Psychomimetic effects, dysphoria, stress-induced depression
(no longer considered an opioid receptor)
Trescot AM et al. Pain Physician. 2008;11:S133.

Pure opioid agonists
• Morphine Clinical considerations:
• Codeine • High binding affinity and efficacy at
• Hydrocodone the mu receptor
• Oxycodone • No analgesic dosage ceiling effect
• Hydromorphone • Degree of analgesia is limited by
• Oxymorphone intolerable dose-related adverse
• Methadone effects; there may be diminishing
• Meperidine returns in benefits at higher doses
• Fentanyl
• Levorphanol
DiPiro JT et al (eds). DiPiro: Pharmacotherapy a pathophysiologic approach, 12e; chapter 79. 2021. Dowell D et al. MMWR Recomm Rep. 2022;71:1.
Other opioids
• Tramadol (Ultram®) Clinical considerations:
• Tapentadol (Nucynta®) • Weak agonists at the mu receptor
• Neuropathic pain mechanisms
- Tramadol inhibits reuptake of
norepinephrine and serotonin
- Tapentadol inhibits reuptake of
norepinephrine
Hollingshead J et al. Cochrane Database Syst Rev. 2006;CD003726. Hartrick CT et al. CNS Drugs. 2011;25:359. Blondell RD et al. Am Fam Physician.
2013;87:766.
Buprenorphine
• Partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor
- Exhibits ceiling effect on respiratory depression
- Deaths due to overdose are rare, except with polysubstance use (e.g., alcohol, benzodiazepines)
• There is no established morphine milligram equivalent (MME) conversion
• Approved for OUD and for acute and chronic pain
- For OUD, available as milligram dosing (sublingual tablet, sublingual film)
- For pain, available in microgram dosing (transdermal patch, buccal film)
• DEA letter clarified no restrictions on off-label use of sublingual buprenorphine for pain even at higher
doses (as used in OUD)
Wightman RS et al. J Med Toxicol. 2021;17:10. Paone D et al. Drug Alcohol Depend. 2015;155:298. Heit HA et al. Pain Med. 2004;5:303.
https://mattersnetwork.org/mat-act/. Accessed January 11, 2023.
Changing requirements for prescribing buprenorphine
• Mainstreaming Addiction Treatment (MAT) Act: Signed into law December 29, 2022
- Removes requirement for a separate DEA “X-waiver” to prescribe or dispense buprenorphine for the
treatment of OUD
- Removes limit on the number of patients a practitioner may treat with buprenorphine for OUD
• Medication Access and Training Expansion (MATE) Act: Also signed into law December 29, 2022
- Requires prescribers of controlled medications to receive education on identifying and treating SUD
• See resources below and in supplementary materials for additional details on the MAT Act and related
requirements
- MAT Act: https://www.congress.gov/bill/117th-congress/senate-bill/445
- MATE Act: https://www.congress.gov/bill/117th-congress/house-bill/2067
https://www.health.ny.gov/professionals/narcotic/. Accessed January 24, 2023.

Short-Acting Opioids Special Considerations
Morphine Active metabolite, M6G, may accumulate in renal impairment
Codeine (alone or in Codeine alone is a weak analgesic; more effective in combo with APAP;
combo with APAP) metabolized to morphine
Hydrocodone (in combo Metabolized to active metabolite hydromorphone
with APAP/IBU)
Hydromorphone Dose adjustment in renal and hepatic impairment

Oxycodone (alone or in Use conservative dose initiation in renal and hepatic impairment
combo with APAP)
Oxymorphone Take on an empty stomach at least 1 hour before or 2 hours after a meal
Tapentadol Caution in patients on serotonergic agents; if used in combination with other

CNS depressants, reduce dose of 1 or both agents
Tramadol (alone or in Slower initiation and titration improves tolerability; not recommended for
combination with APAP) patients on serotonergic agents
DiPiro JT et al (eds). DiPiro: Pharmacotherapy a pathophysiologic approach, 12e; chapter 79. 2021.
Drug interaction with opioids
• Pharmacokinetic interactions: Depending on the metabolic pathway, e.g., cytochrome P450 or
glycoprotein inducers or inhibitors
• Alcohol: Pharmacokinetic and pharmacodynamic interactions
• Specific drug-drug interactions
- Examples (not an inclusive list):
- CNS depressants, including benzodiazepines, nonbenzodiazepine sedative-hypnotics,
and alcohol (additional depressant effects seen in combination with opioids)
- Concurrent use with benzodiazepines initially increases risk of opioid-related
overdose by 5-fold
- Agents with serotonergic activity, e.g., monoamine oxidase inhibitors
Solhaug V et al. Scand J Pain. 2017;17:193. Hernandez I et al. JAMA Netw Open. 2018;1:e180919.
https://www.accessdata.fda.gov/drugsatfda_docs/rems/Opioid_analgesic_2018_09_18_FDA_Blueprint.pdf. Accessed April 15, 2022.
Approximate conversion chart for
“equianalgesic” initial doses of opioids
Parenteral PO Conversion to Oral
• Source of equianalgesic data (mg) (mg) Morphine*
• Adjust conversions for incomplete morphine 10 30 N/A
codeine - 200 0.15
cross-tolerance; the “new opioid
hydrocodone - 30 1
is typically dosed substantially oxycodone - 20 - 30 1.5
lower than the calculated MME hydromorphone 1.5 7.5 4
dose…” oxymorphone 1 10 3
methadone 1.5 (3) – 7.5 Variable
• Variable depending on patient-
tramadol - 120 0.1
specific characteristics tapentadol - 100-150 0.4
(i.e., genetics, pharmacokinetics) fentanyl transdermal
- - Per 24 hours: 2.4
(mcg/hr)
McPherson ML. Demystifying opioid conversion calculations. 2009.
*;l j
*Conversion factors may vary by source

Vallejo R et al. Pain Physician. 2011;14:E343. MME: Morphine Milligram Equivalents
Gammaitoni AR et al. Clin J Pain. 2003;19:286.
Morphine Milligram Equivalents (MME)
• Dosages ≥50 MME/day ↑ overdose risk by at least twice the risk of dosages
<20 MME/day
• Caution ≥50 MME/day
- Progressively more likely to result in diminishing returns relative to risks
- Monitor patients frequently
- Discuss reducing dose/tapering opioids
- Consider prescribing naloxone
• Avoid or carefully justify increasing dosage to ≥90 MME/day
https://www.cdc.gov/drugoverdose/pdf/calculating_total_daily_dose-a.pdf
Calculation of MME
• Calculators are available from many sources
- CDC Opioid Guideline Mobile App
- Within the NYS PMP system
https://www.cdc.gov/drugoverdose/pdf/calculating_total_daily_dose-a.pdf. Accessed April 15, 2022.

Opioid side effects
• Respiratory depression • Gastrointestinal
• Central Nervous System - Constipation
- Drowsiness - Nausea
- Dizziness • Cardiovascular
- Sedation - Hypotension
- Hyperalgesia - Bradycardia
- Mood changes - QTc prolongation
• Bladder dysfunction • Sweating
• Pruritus— histamine release • Sexual dysfunction
• Dry mouth
Benyamin R et al. Pain Physician. 2008;11:S105.

Tips for managing side effects
• Nausea and constipation can be minimized using anti-emetics and bowel
regimens
• Many adverse effects spontaneously resolve with continued administration and
development of tolerance
- Exception is constipation— Prophylactic initiation and maintenance of a
bowel regimen is strongly recommended
• Slow titration and use of low opioid doses can help to minimize side effects
Management of opioid-induced constipation
• Softening agents → Little value alone
- Docusate
• Stimulants → Mainstay of therapy
- Senna, bisacodyl
• Osmotics → Additive to stimulants
- Lactulose, sorbitol, polyethylene glycol, glycerin suppositories
• Saline → Cathartics, relieve then adjust
- Magnesium citrate, magnesium hydroxide, magnesium sulfate, sodium phosphates
• Peripherally-Acting Mu-Opioid Receptor Antagonists (PAMORA)
- Naloxegol, methylnaltrexone, naldemedine
Herndon CM et al. Pharmacotherapy. 2002;22:240. Badke A et al. J Palliat Med. 2015;18:799. Badke A et al. J Palliat Med. 2015;18:893. Muller-Lissner S et
al. Pain Med. 2017;18:1837.
FDA boxed warnings for opioids
• Risk of addiction, abuse, and misuse may lead to overdose and death
- Assess risk before prescribing and monitor for development of OUD
- Risk Evaluation and Mitigation Strategy (REMS)
• Serious, life-threatening, or fatal respiratory depression can occur
• Accidental ingestion, especially in children, can result in fatal overdose
• Prolonged use of opioids during pregnancy can result in neonatal opioid
withdrawal syndrome
• Combination use with benzodiazepines increases the risk of respiratory
depression and death
https://www.fda.gov/drugs/information-drug-class/new-safety-measures-announced-opioid-analgesics-prescription-opioid-cough-products-and
Accessed August 31, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/rems/Opioid_analgesic_2018_09_18_FDA_Blueprint.pdf. Accessed October 18, 2022.
Abuse-deterrent opioid products
• Opioid abuse-deterrent formulations (ADFs) are developed with the goal to curb known or
anticipated routes of abuse, e.g., crushing with the intention to inhale
- Labeling as ADF is regulated by the US Food and Drug Administration
• Types of ADF technology:
- Physical/chemical barriers
- Agonist/antagonist combinations
- Aversion
- Delivery system
- New molecular entities and prodrugs
- Combination of the above
- Novel approaches
• Post-marketing data is limited, and consideration should be given to unintended effects such as
increased costs or use of alternative opioids (including heroin) in place of ADFs
https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/abuse-deterrent-opioid-analgesics. Accessed April 15, 2022.

https://www.fda.gov/regulatory-information/search-fda-guidance-documents/abuse-deterrent-opioids-evaluation-and-labeling. Accessed April 15, 2022.
Abuse-deterrent opioids
Product Formulation Approval Date
OxyContin® Oxycodone extended-release tablets Apr. 2010
Hydrocodone extended-release tablets

Hysingla® ER Nov. 2014
• Generic equivalent available
Xtampza® ER Oxycodone extended-release capsules Apr. 2016
Roxybond® Oxycodone tablets Apr. 2017
• Multiple abuse-deterrent opioid products that were previously available have been
discontinued in the U.S.
https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm600788.htm. Accessed October 20, 2022.
Routine assessment in subacute/chronic treatment
• Optimize non-opioid therapies
• Reassess benefits and risks within 1-4 weeks after starting opioid therapy or after dose escalation
- “4 A’s”
- Analgesia
- Activity
- Aberrant behavior (e.g., signs of medication misuse)
- Adverse effects
• After assessing for clinically meaningful improvements in pain and function and weighing that
against risks or harms, determine whether to continue, adjust, taper, or stop opioids
• For continued therapy, reassess benefits and risks at least every 3 months
Manchikanti L et al. Pain Physician. 2012;15:S67. Dowell D et al. MMWR Recomm Rep. 2022;71:1.
https://www.cdc.gov/drugoverdose/pdf/pdo_checklist-a.pdf. Accessed April 15, 2022.
Approaches to inadequate pain relief
• Dosage titration: Slowly ↑ dose to minimize toxicity; find lowest effective dose that
achieves a satisfactory balance between benefits and harm
• Opioid switch/rotation: May help improve efficacy, ↓ side effects, and ↓ dose escalation
in patient with intolerable side effects or inadequate benefit despite dose increases
• Addition or optimization of non-opioid/adjunct agent(s): Addition or dosage increase
of a non-opioid/adjunctive agent can help manage pain through a multimodal approach
and allows for potential decrease in current opioid dose
• Discontinuation of opioid: Assess if the patient is experiencing intolerable adverse
effects, is non-adherent, or is misusing the drug
Manchikanti L et al. Pain Physician. 2012;15:S67. https://www.healthquality.va.gov/guidelines/Pain/cot/. Accessed January 24, 2023.
Reduction/discontinuation of opioid therapy
• Consider tapering to a reduced dose, or tapering and discontinuing, in cases of:
- Severe, unmanageable adverse effects
- Unsafe behaviors, such as serious non-adherence to the treatment plan
- Evidence of opioid misuse or diversion
- Lack of effectiveness to meet treatment goals
- Requests from a patient to discontinue therapy
- Improvement in pain that might indicate resolution of an underlying cause
• In the absence of a life-threatening issue, abrupt reduction/discontinuation is not
recommended
ASA/ASRA. Anesthesiology. 2010;112:810. Dowell D et al. MMWR Recomm Rep. 2022;71:1. Hegmann KT et al. J Occup Environ Med. 2014;56:e143. Manchikanti
L et al. Pain Physician. 2012;15:S67. https://www.cms.gov/About-CMS/Story-Page/CDCs-Tapering-Guidance.pdf. Accessed January 24, 2023.
Risks associated with reducing/discontinuing opioids
• Rapid taper or abrupt discontinuation can lead to significant opioid
withdrawal
• Patients may experience pain exacerbation, psychological distress,
or suicidal ideation
• Patients may resort to other methods of obtaining opioids to address
withdrawal symptoms
- Subsequent risk of overdose due to reduced tolerance
Coffin PO et al. Ann Med. 2022;54:2451. Dowell D et al. MMWR Recomm Rep. 2022;71:1.
https://www.cms.gov/About-CMS/Story-Page/CDCs-Tapering-Guidance.pdf. Accessed January 24, 2023.
Tapering opioid therapy
• Go slowly for safety; an example of a tapering protocol is 10% per month or
slower
- Slow tapering will help to minimize adverse/withdrawal effects, especially
when patients have taken opioids chronically
• Individualize tapering schedule with each patient
• Monitor frequently during taper, e.g., at least monthly
• Consider use of adjuvant agents (e.g., antidepressants, antiseizure
medications)
• Referral for psychosocial support recommended
Manchikanti L et al. Pain Physician. 2012;15:S67. https://www.cms.gov/About-CMS/Story-Page/CDCs-Tapering-Guidance.pdf. Accessed January 24, 2023.
More on opioid tapering
• Taper slow enough to minimize symptoms of withdrawal
• Mild symptoms of opioid withdrawal may last for 6 months after
opioids have been discontinued
• When opioids have been withdrawn, it is advised not to use a
similar opioid or benzodiazepine when treating outpatient
withdrawal symptoms
- Clonidine, lofexidine (Lucemyra™)
Manchikanti L et al. Pain Physician. 2012;15:S67. Lucemyra [package insert]. US WorldMeds, LLC; 2018.
Pediatrics
• Most opioid products are not FDA-approved for pediatric patients
- Refer to specific product labeling
• Refer to a pediatrician for pain management
• For additional information: WHO guidelines on the pharmacological
treatment of persisting pain in children with medical illness
Populations with additional risks/usage considerations
• Patients with sleep-disordered breathing
• Pregnancy
• Renal or hepatic insufficiency
• Age ≥65 years
• Jobs with potentially hazardous tasks/equipment
• Mental health conditions
• Substance use disorder
• Previous overdose
More on assessing risk and harms of opioid use
• Patients should be screened for risk factors for opioid-related harms (including
overdose) before initiating and then periodically during opioid therapy
• Prescribers should review the patient’s controlled substance prescription history in the
state’s Prescription Monitoring Program (PMP)
- The NYS I-STOP is required to be checked when prescribing Schedule II, III, or
IV controlled substances
• For patients utilizing an opioid for chronic pain, toxicology testing should be
considered when initiating therapy and periodically thereafter (at least annually)

More on assessing risk and harms of opioid use—
continued
• Benzodiazepines, when co-prescribed with opioids, increase the possibility of harmful
adverse effects (e.g., respiratory distress, death), as do other CNS depressants
- Consider whether the benefits outweigh the risks when prescribing concurrently
• Regularly assess for signs/symptoms of OUD
- If warranted, strongly encourage patients to seek treatment while providing the
proper tools
- NYS OASAS operates a toll-free, anonymous and confidential service that
helps patients with alcoholism, drug abuse, and gambling problems. The
HOPELINE contact number is 1-877-8-HOPE-NY or text HOPENY.
- Refer and educate about the role of medication for OUD, e.g., buprenorphine
Case 1
• 30-year-old seen for low back pain and spasms
• Has used hydrocodone and carisoprodol (Soma®) for the last 10 years
(started on a visit to the ER)
• MRI: Straightening of lumbar lordosis
• Examination: Benign
• Patient states the medications have allowed them to work for all these years
• Urine drug screen: Presence of opiates
How do you approach this situation?

Case 2
• 50-year-old referred for further management of back pain
• Has had several spine surgeries
• Has been on oxycodone ER (Oxycontin®) 30mg tablets 3x/day and
hydrocodone/APAP 7.5 mg/325 mg 2 tablets per day
• Exam shows positive findings of lumbar radiculopathy and lumbar spine-
restricted ROM
• Requesting same medication although the patient feels it would be better
raising the dose of Oxycontin® and taking 2 hydrocodone/APAP per day
What do you discuss with the patient?

Case 3
• 36-year-old established patient
• Stable on oxycodone/acetaminophen (Percocet®) 10 mg/325 mg 2 tablets per
day for 12 months
• Most recent urine drug screen shows oxycodone, oxymorphone, THC, and
diacetylmorphine
How do you manage this situation?

OPIOID USE DISORDER:
SCREENING, PREVENTION,
AND TREATMENT
Arthur Weissman, MD, FASAM
Assistant Professor, Department of Family Medicine
University at Buffalo
Jacobs School of Medicine and Biomedical Sciences
Learning objectives: Opioid Use Disorder (OUD)
• Identify risk factors for the development of OUD
• Describe screening tools and processes that may be used to identify signs of OUD
• Describe strategies to mitigate the risk of iatrogenic OUD

• Discuss treatment approaches based on whether the patient has chronic pain, OUD,
both, or neither
• Explain harm reduction strategies

Opioid overdose deaths have accelerated
CDC, National Center for Health Statistics (2022). Vital Statistics Rapid Release - Provisional Drug Overdose Data.
Three waves of the rise in opioid overdose deaths
Graphic: https://www.cdc.gov/opioids/basics/epidemic.html
4th wave: Stimulant

+ opioid deaths
Mattson CL et al. MMWR Recomm Rep. 2021;70:202. Ciccarone D. Curr Opin Psychiatry. 2021;34:344.
• Prescription
medications can
be a starting Rx diverted from
Illicit source 27%
friend or relative
point for opioid 32%
use disorder
• Initiation of illicit Own prescription
opioid use with 41%
heroin/fentanyl
has become
more common
Self-reported etiology of opioid use disorder, N = 75
Canfield MC et al. J Addict Med. 2010;4:108

Cicero TJ et al. Addictive Behaviors. 2017;74:63.
Effective, evidence-based treatment for OUD is available
• 3 FDA-approved medications for opioid use disorder (MOUD)

- Buprenorphine
- Methadone
- Naltrexone
• Harm reduction strategies are important
Thomas CP et al. Psychiatr Serv. 2014;65:158.

Fullerton CA et al. Psychiatr Serv. 2014;65:146.
Tanum L et al. JAMA Psychiatry. 2017;74:1197.
Dugosh K et al. J Addict Med. 2016;10:93.
Better outcomes with prevention and early intervention
• Act before there is more damage to
the patient’s life and health
- Early action is more effective and Prevention
more cost-effective &
• Prevention and early intervention are Early
underutilized
Intervention
Save Lives
http://www.clker.com/cliparts/3/2/5/d/1382892910693102057Holdi
ng%20sign.svg.med.png
Compton WM et al. Am J Public Health. 2019;109:S185.

• There is a gap between the need
for treatment and ready access to
treatment
• Prevention, earlier intervention,
harm reduction, and reducing
barriers to treatment are key
Image: https://commons.wikimedia.org/wiki/File:White_pills.jpg
https://nida.nih.gov/about-nida/noras-blog/2019/06/importance-prevention-in-addressing-opioid-crisis. Accessed February 27, 2022.

Prevention: Primum non nocere
• Before prescribing:
- Evaluate risk factors for substance use disorders
- Make an accurate pain diagnosis
- Then, prescribe opioids only if clinically indicated
- Monitor patients carefully going forward
- Avoid prescribing opioids inappropriately and increasing the risk
that patients will develop opioid use disorder
- Observe special care with children and adolescents
https://www.cdc.gov/opioids/healthcare-professionals/prescribing/index.html. Accessed November 10, 2022.
https://www.samhsa.gov/data/sites/default/files/WebFiles_TEDS_SR142_AgeatInit_07-10-14/TEDS-SR142-AgeatInit-2014.pdf. Accessed June 4, 2022.
Evaluate for substance use disorder risk factors
• Adverse childhood experiences (ACEs), physical
and sexual abuse
• Attention-deficit/hyperactivity disorder, conduct
disorder
• Early onset of substance use (especially age ≤14),
including alcohol, tobacco, and cannabis
• Personal history of a SUD
• Genetic predisposition (positive family history)
Caballero MA et al. Child Abuse Negl. 2010;34:576. Webster LR. Anesth Analg. 2017;125:1741.
Charach A et al. J Am Acad Child Adolesc Psychiatry. 2011;50:9. Merikangas KR et al. Arch Gen Psychiatry. 1998;55:973.
Grant BF et al. J Subst Abuse. 1997;9:103. https://nida.nih.gov/publications/research-reports/marijuana/letter-director.
Hingson RW et al. Arch Pediatr Adolesc Med. 2006;160:739. Accessed August 11, 2022.
Genetic predisposition for SUD
• Opioid receptor (OPRM1)

• Dopamine receptor (DRD2)
• Serotonin synthesis
Image: https://commons.wikimedia.org/wiki/File:DNA_orbit_animated.gif
Chen D et al. Drug Alcohol Depend. 2012;123:1.

Smith L et al. Am J Epidemiol. 2008;167:125.
Feinn R et al. Am J Med Genet B Neuropsychiatr Genet. 2005;133B:79.
Prescribe according to best practices
• Check PMP
• Check toxicology
• Limit dosing: lowest effective dose and shortest duration necessary
• Avoid the combination of opioids and CNS depressants, including alcohol and
benzodiazepines
• Harm reduction, e.g., offer naloxone
• Assess outcomes regularly
Argoff CE et al. J Opioid Manag. 2014;10:119.

Chang KL et al. FP Essent. 2015;432:27.
https://www.fda.gov/media/140360/download. Accessed June 3, 2022.
Use special care with young patients
• Information about the risks and benefits of opioid prescriptions for those under
18 is limited
• Adolescents who misuse illicit opioids are at increased risk to misuse
subsequent opioid prescriptions
• Receiving one opioid prescription before high school graduation is associated
with a 33% increase in the risk of later opioid misuse
McCabe SE et al. J Adolesc Health. 2013;52:480.

Miech R et al. Pediatrics. 2015;136:e1169.
Whiteside LK et al. J Adolesc Health. 2016;58:92.
Evaluation should be an ongoing process
• Check medical records and reports
• Screening tools
• Check the PMP (e.g., I-STOP)
• Check toxicology
https://www.cdc.gov/opioids/healthcare-professionals/prescribing/index.html. Accessed November 10, 2022.

Regularly review medical
records and reports
• Emergency department and
hospital admissions
• Diagnostic imaging
• Medications
Screening tools
• Drug Abuse Screening Test (DAST)
• Alcohol Use Disorder Identification Test
(AUDIT)
• Beck Anxiety Inventory (BAI)
• Beck Depression Inventory (BDI)
Skinner HA. Addict Behav. 1982;7:363.

Bohn MJ et al. J Stud Alcohol. 1995;56:423.
Beck AT et al. J Consult Clin Psychol. 1988;56:893.
Beck AT et al. Arch Gen Psychiatry. 1961;4:561.
Check I-STOP
• Required in NYS before issuing a
controlled substance prescription, with
limited exceptions
• Look for red flags:
- Multiple prescribers of controlled substances
- Overlapping prescriptions
- Concurrent benzodiazepines and opioids
https://www.health.ny.gov/professionals/narcotic/prescription_monitoring/docs/pmp_registry_faq.pdf. Accessed April 7, 2022.
https://www.ama-assn.org/system/files/corp/media-browser/public/arc/prescribing-dispensing-controlled-sustances-summary-consensus_0.pdf.
Accessed April 7, 2022.
42-year-old patient requesting evaluation for opioid use disorder
• Using IV heroin/fentanyl
and cocaine
• PMP:
• 1,440 tablets prescribed in
the past year
• No toxicology done
• “Writer”
Check toxicology
• At baseline before prescribing opioids for
6AM
AMP
OP
BAR
MTH
BZO
MTD
COC
ETG
chronic pain,
- and periodically thereafter
• “Point of care” tests
• Immunoassay
• Test for a panel of substances

• Toxicology can give important information
- Counterfeit, adulterated pills
• Should not be punitive or a “gotcha” moment
• Facilitate the discussion with the patient about their substance
6AM
AMP
OP
BAR
MTH
BZO
MTD
COC
ETG
use
• We should not be dismissing patients from care just based on a
toxicology result
• Frequency of testing should be based on clinical judgment
• Observed urine toxicology
- Can be considered if there is a concern about the validity of
the specimen
- Should not be done with every test
- Observed oral fluid screens can be an alternative

Some toxicology specifics
• 6-acetylmorphine (6-AM, AKA MAM) is a specific heroin metabolite
• OPIATE screens usually test positive for morphine, codeine, heroin, and
hydrocodone
• Opiate screens will usually not test positive for the ‘FBOM’:
fentanyl, buprenorphine, oxycodone, or methadone
• The FBOM tests are available as separate screens in the panel
• Alcohol: ethyl glucuronide (EtG) and ethyl sulfate (EtS)
Chyka PA. Substance abuse and toxicological tests. In. Lee M. Basic Skills in Interpreting Laboratory Data. ASHP. 2013.
J Addict Med. 2017;11 Suppl 3:1.
Toxicology is not always straightforward
• False NEGATIVES may be common with benzodiazepine screens (e.g., clonazepam)
• False POSITIVES are common with amphetamines (due to OTC oral decongestants)
• Positives for EtG and EtS may be seen with alcohol exposure in mouthwash and
cooking
- Educate patients to use alcohol-free mouthwash and avoid alcohol in sauces
- Not common with topical exposure (like hand sanitizer)
• Can be clarified with confirmation testing
• Toxicology interpretation is not always straightforward
- Questions? Lab medical director
Toxicology specifics—continued
• Poppy seeds can give a positive OPIATE screen result, but not a positive for 6-
AM
• Trace amounts of morphine and codeine in poppy seeds
• Patients should be cautioned to avoid poppy seeds
• Environmental exposure to cannabis will RARELY produce a positive screen
(except in extreme conditions)
Toxicology specifics—continued
• Drugs with short half-lives (e.g., cocaine, lorazepam, and heroin)
will typically cause screening toxicology to be positive for a few
(i.e., 2 – 4) days
• Drugs with long half-lives (like methadone, cannabis, and
diazepam) may cause screening toxicology to be positive for days
to weeks after prolonged use
Oral fluid toxicology screens
• Similar window of detection compared to urine
(a few days for most drugs)
date
name
• May be more acceptable to some patients than
____________
____________
urine toxicology
• Quantitative results not as accurate, but the
technology is improving
Casolin A. J Anal Toxicol. 2016;40:479.

Confirmation testing
• Screening tests can be sent for
confirmation
• Gas Chromatography Mass
Spectroscopy (GC-MS)
• Accurate, quantitative results
• Not every screen needs to be
sent for confirmation Image: https://commons.wikimedia.org/wiki/File:GCMS_closed.jpg
Casolin A. J Anal Toxicol. 2016;40:479.

Signs of OUD
• There is a continuum from appropriate use of controlled
substances, to non-medical use, to substance use disorders
• Determining where the patient is on that line can be a challenge
DSM-5 criteria • Withdrawal
for opioid use • Control or cut down, failed attempts
disorder • Craving
• Health, continued use despite adverse effects
• Hazardous situations, putting self in
• Activities, giving up normal
• Two criteria over the last year • Amount, using in greater amount (or time) than planned
• Clinically significant • Relationships, continued use despite damage to
impairment or distress • Roles (home, school, work), continued use despite damage
• Tolerance
• Time, spending an inordinate amount
American Psychiatric Association. Diagnostic and
statistical manual of mental disorders, 5th ed. 2013.
DSM-5 criteria • Withdrawal
for opioid use • Control or cut down, failed attempts
disorder • Craving
• Health, continued use despite adverse effects
• Hazardous situations
• Activities, giving up normal
• Two criteria over the last year • Amount, using in greater amount (or time) than planned
• Clinically significant • Relationships, continued use despite damage to
impairment or distress • Roles (home, school, work), continued use despite damage
• Tolerance
• Time, spending an inordinate amount
American Psychiatric Association. Diagnostic and
statistical manual of mental disorders, 5th ed. 2013.
Physical dependence vs. opioid use disorder
• “Dependence” = tolerance and/or withdrawal
• Patients appropriately prescribed controlled substances who do not satisfy DSM criteria for a substance
use disorder may exhibit tolerance to the medication, or withdrawal symptoms with sudden
discontinuation
• Other non-controlled substances also have elements of tolerance and withdrawal (e.g., beta blockers)
• This “physical dependence” ≠ substance use disorder
• SUDs have other bio-psycho-social components
• Patients with physical dependence, if they are inappropriately dismissed from a practice, or threatened
with dismissal, can exhibit behaviors that mimic SUD behaviors
• We should not be dismissing (and abandoning) patients just based on an aberrant toxicology result
https://www.fda.gov/drugs/drug-safety-and-availability/fda-identifies-harm-reported-sudden-discontinuation-opioid-pain-medicines-and-requires-label-changes. April 2019.

Comorbidities
• Chronic pain is common (e.g., up to 64%) in patients with opioid use disorder
• Increasing tolerance may be accompanied by increased pain
(may be opioid-induced hyperalgesia, OIH)
• About half of patients with a substance use disorder will have lifetime
comorbidity with a mental health disorder, and vice versa
Vowles KE et al. Pain. 2015;156:569. Ballantyne JC et al. Clin J Pain. 2008;24:469. Ross et al, Clin Neuropharmacol 2012;35:235. Kelly et al. Soc
Work Pub Health. 2013;28:388. Hser YI et al. J Subst Abuse Treat. 2017;77:26.
Red flags
• Early refill requests
- Tolerance, OIH, increased nociceptive pain?
• Multiple prescriptions from multiple prescribers
• Overlapping prescriptions
• Toxicology results inconsistent with prescribing Image: https://commons.wikimedia.org/w/
• Positive toxicology for alcohol or illicit drugs

index.php?search=red+flag&title=Special:
MediaSearch&go=Go&type=image
Red flags
• I’m late for work/another appointment
• Coordination of care:
- “Let me talk to them first…”
• Functional impairment
Image: https://commons.wikimedia.org/w/index.php?search=
unconscious&title=Special:MediaSearch&go=Go&type=image
How to respond
Brief interventions can save lives
• For a new patient, or those already on opioids, it can be helpful to focus
on SUD factors, and then on the pain situation, and then put them together:
- Decide if the patient has criteria for SUD (yes/no)
- Decide if opioids are indicated (yes/no)
• Perform a brief intervention if necessary
• Some may be treated in your office, for example, with
buprenorphine/naloxone
• Others may need referral to a SUD treatment program
• Discuss harm reduction (e.g. naloxone, referral to a harm reduction program)
https://www.hhs.gov/opioids/prevention/safe-opioid-prescribing/index.html. Accessed April 15, 2022.
Acute pain,
A 16-year-old at increased risk for OUD
jams a finger
while playing • Use rest, ice, compression, and elevation,
basketball • NSAIDS and acetaminophen for pain
• Educate patient and family about the increased
• Requests opioids risk and the need to avoid controlled drugs
• ROM is intact • If opioids are needed:
• Films: no fracture • Lowest dose for shortest duration
(e.g., 3 days, max of 7, depending on the injury)
• Parent has a substance • Make sure parents monitor medication use
use disorder • Discard unused medication
https://www.cdc.gov/acute-pain/postsurgical-pain/index.html. Accessed April 12, 2022.

Is it chronic pain, OUD, both, or neither?
• A practical way to approach a
complex clinical situation
No OUD Probable OUD
• OUD factors? (yes/no) No Chronic Pain No Chronic Pain
• Verified chronic pain for which

opioids are necessary? (yes/no)
No OUD Probable OUD
Verified Chronic Pain Verified Chronic Pain
Richard D. Blondell, MD
Jones KF et al. JAMA Health Forum. 2022;3:e221406.
A 52-year-old is
requesting a refill of No OUD, verified chronic pain
a prescribed opioid
• Monitor pain with an objective scale
• 5 lumbar spine surgeries
• Non-opioid strategies are first line
• Failed back surgery
syndrome (FBSS) • Monitor function
• Toxicology is appropriate • Pill counts
• Takes fewer pills than prescribed • Check PMP at every visit
• Function is intact • Monitor toxicology

A 24-year-old No SUD, no chronic pain
requests refills of
amphetamines, • Possible diversion scenario
alprazolam, and • Get more information
hydrocodone • Consider observed toxicology
• Diagnoses are vague (vs. oral fluid toxicology)
• PMP shows multiple • Coordinate care with other prescribers

prescribers and • Don’t dismiss patient just based on a
overlapping prescriptions toxicology result
• Toxicology is completely • Address concerns with the patient
negative • Consider SUD specialist referral
https://www.ecfr.gov/current/title-21/chapter-II/part-1306#1306.04. Accessed November 10, 2022.

A 42-year-old is SUD concerns, and not an appropriate
situation for long-term opioids for
requesting a refill of chronic pain
hydrocodone for
chronic back pain • Brief intervention
• Non-opioid strategies for pain
• Previous prescriber has retired
• Consider an opioid taper
• Clinically, patient has a lumbar strain
• Consider a transition to
• Imaging is unremarkable
buprenorphine/naloxone for OUD
• Increasing pill use → more pain
• Harm reduction: naloxone, avoid alcohol
• “Borrowing” additional pills from a friend
• Should not dismiss patients based solely on
• Toxicology shows hydrocodone, toxicology results:
oxycodone, and alcohol
- Address illicit drug use and diversion
https://www.uptodate.com/contents/primary-care-management-of-adults-with- - Consider SUD specialist referral
opioid-use-disorder. Accessed April 18, 2022.
A 36-year-old is Probable OUD,
requesting a dose verified chronic pain
increase of • Brief intervention
prescribed opioids • Consider a transition from hydrocodone to
buprenorphine/naloxone
• Has rheumatoid arthritis
- Taper vs. microinduction
with painful joint deformities
• Consider specialist referrals:
• PMP shows scripts • Rheumatology
for hydrocodone only • Pain management
• Toxicology shows hydrocodone, • SUD
fentanyl, and 6-AM (heroin) • Physical therapy, alternative treatments
• Harm reduction: Prescribe naloxone,
consider fentanyl test strips
https://www.uptodate.com/contents/primary-care-management-of-adults-with-opioid-use-disorder. Accessed April 18, 2022.
Approach
• Patients in this situation may be understandably upset, frustrated, and angry:
• Common that they have been dismissed from various practices
• “Nobody listens to me… everybody just tells me I am a drug addict…”
• This can be a challenge
• Don’t label the patient
• “I can see you’ve had a lot of problems with these pills, and they’re not controlling your
pain very well…”
• “I’d like to talk to you about some other options, which I think may control your pain better,
and would probably help with these other problems you’ve been having…"
Brief interventions
• Take a few minutes
• Best evidence is for reducing harmful
alcohol and tobacco consumption
• Some evidence for other drugs
• Useful framework
Image:
• Repeated brief interventions may be more

https://commons.wikimedia.org/w/index.php?search=clock+
5+minutes&title=Special:MediaSearch&go=Go&type=image
effective over time

Beyer FR et al. Alcohol Alcohol. 2019;54:417. Humeniuk R et al. Addiction. 2012;107:957.
Wray JM et al. Nicotine Tob Res. 2018;20:1418. Saitz R. Front Psychiatry. 2014;5:121.
Tait RJ et al. Drug Alcohol Rev. 2003;22:337. Saitz R. JAMA. 2020;323:2263.
Madras BK et al. Drug Alcohol Depend. 2009;99:280. Jonas DE et al. Ann Intern Med. 2012;157:645.
FRAMES: A brief intervention technique
Item Example
Feedback with concern I’m concerned about your opioid use and the risks for your health.
Reinforce responsibility I’d like to make a recommendation, but it’s your decision.
Advise action I recommend that you taper off hydrocodone

and consider a transition to buprenorphine/naloxone.
Menu of options If you don’t want to do that, you could… (give other options).
Express empathy I can appreciate that this must be a difficult thing to talk about.
Support self-efficacy I think you can do this.
Mattoo SK et al. Indian J Psychiatry. 2018;60:S466.

Examples of harm reduction strategies
• Determinations about appropriate medications or modifications
to treatment plans based on clinical judgement and specific
Prescribing to needs of individual
minimize risk • Naloxone
• Buprenorphine
• Fentanyl test strips

• Syringe/needle access (syringe access programs, pharmacies
Other strategies and healthcare providers)
• Refer to other harm reduction providers
Summary
Be careful and do no harm
• Be careful with prescriptions for minors
• Use caution when prescribing amphetamines
• Avoid prescribing benzodiazepines and opioids together
• Avoid long-term benzodiazepine prescribing
• Buprenorphine can now be prescribed for OUD without an X-waiver
• Recognize and respond to red flags
• Avoid stigmatizing language
Takeaways
• Perform a careful clinical evaluation before Offer education on overdose and naloxone when
prescribing opioids prescribing opioids
• NYS law – prescribe naloxone with the first opioid
• Evaluate for SUD risk factors prescription of the year for patients with: history of
• Establish an accurate pain diagnosis substance use disorder; ≥ 90 MME daily;
concurrent use of benzodiazepine or non-
• Decrease the risk of iatrogenic OUD by benzodiazepine sedative hypnotics
monitoring patients carefully • Additional reasons to prescribe naloxone include:
• PMP • Previous overdose history
• Toxicology • Using alcohol or other sedatives
• Household members at risk for accidental
• Intervene early ingestion (children, older adults)
• Offer/refer to harm reduction providers • Any patient taking an opioid
Additional Resources
• CDC 2022 guideline: https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm?s_cid=rr7103a1_w
• ASAM guideline: https://doi.org/10.1097/adm.0000000000000633
• NYSDOH Bureau of Narcotic Enforcement: https://www.health.ny.gov/professionals/narcotic/
• Office of Addiction Services and Supports (OASAS)-Approved Screening, Brief Interventions, and Referral
to Treatment (SBIRT) training: http://www.sbirttraining.com/
• OASAS SBIRT reference page: https://oasas.ny.gov/AdMed/sbirt/index.cfm
• HOPEline: 1-877-8-HOPENY (467369): https://oasas.ny.gov/hopeline
• Avoiding stigmatizing language: https://nida.nih.gov/nidamed-medical-health-professionals/health-
professions-education/words-matter-terms-to-use-avoid-when-talking-about-addiction
Harm Reduction Resources
• NYS Office of Drug User Health: https://www.health.ny.gov/diseases/aids/consumers/prevention/
• Clinical Education Initiative (CEI): https://ceitraining.org/
• Providers Clinical Support System (PCSS) education and training resources: https://pcssnow.org/education-
training/
• NY Expanded Syringe Access Program (ESAP):
https://www.health.ny.gov/diseases/aids/consumers/prevention/needles_syringes/esap/overview.htm
• North American Syringe Exchange Network (NASEN): https://www.nasen.org
PALLIATIVE,
END-OF-LIFE CARE
Robert G. Wahler, Jr., Pharm.D., CPE

Clinical Associate Professor, UB SPPS
Director, Clinical Pharmacy Services, Niagara Hospice
Learning objectives
• Outline principles of and differences between palliative care and
hospice care
• Describe the use of opioids in hospice and palliative care

(e.g., cancer pain, dyspnea, methadone)
Introduction
• 3.38 million deaths/year in the U.S. in 2020
- Approximately 1.55 million under hospice care in 2018
- Median length of service = 18 days (approx. same for the last 15 years)
• Palliative care
- Specialty focused on quality of life (QOL)
- Any serious illness whatever the diagnosis or prognosis – e.g., cancer, heart
failure, chronic obstructive pulmonary disease (COPD), dementia
- Estimated 6 million could benefit from palliative care
• Palliative care teams
- Physicians, nurses, social workers, and spiritual care (chaplaincy)
- Additional support from physician assistants, nurse practitioners, pharmacists,
nutritionists, physical and occupational therapists, and other disciplines as needed
https://www.cdc.gov/nchs/fastats/deaths.htm. Accessed July 11, 2022.
NHPCO Facts and Figures. National Hospice and Palliative Care Organization. 2020.
https://www.capc.org/about/palliative-care/ Accessed September 16, 2022.
https://www.ecfr.gov/current/title-42/chapter-IV/subchapter-B/part-418 Accessed September 16, 2022.
What is palliative care?
• World Health Organization (WHO): “Palliative care improves the quality of life
of patients and that of their families who are facing challenges associated with
life-threatening illness, whether physical, psychological, social or spiritual. The
quality of life of caregivers improves as well.”
https://www.who.int/news-room/fact-sheets/detail/palliative-care. Accessed July 11, 2022.

Palliative care is:
• Appropriate at any stage in a serious illness, and it is beneficial when provided
along with treatments of curative or life-prolonging intent.
• Provided over time to patients based on their needs and not their prognosis
• Offered in all care settings and by various organizations, such as physician
practices, health systems, cancer centers, dialysis units, home health agencies,
hospices, and long-term care providers
• Focused on what is most important to the patient, family, and caregiver(s),
assessing their goals and preferences and determining how best to achieve them
• Interdisciplinary to attend to the holistic care needs of the patient and their
identified family and caregivers
https://www.nationalcoalitionhpc.org/ncp Accessed December 5, 2022.

Kelley AS et al. N Engl J Med. 2015;373:747.
Palliative Care…
IMPROVES QUALITY IS COST-SAVING
• Clarifies goals of care with patients and • Lowers healthcare costs by reducing
families hospital and intensive care unit lengths of
• Relieves pain and suffering via expert stay, readmissions, and pharmacy costs
management of complex physical and • Aligns resources with the priorities and
emotional symptoms needs of patients and families
• Improves patient and caregiver quality of • Reduces healthcare utilization that is
life avoidable, unnecessary, or that does not
• Provides care coordination across settings support or improve patient’s quality of life
and providers • Assists with efficient transitions across
healthcare settings
http://aahpm.org/uploads/advocacy/The_Evidence_for_High-Quality_Palliative_Care.pdf. Accessed December 5, 2022.

https://www.capc.org/about/palliative-care/. Accessed December 5, 2022.
https://www.capc.org/the-case-for-palliative-care/. Accessed January 17, 2023.
• Early palliative care + Standard oncologic care vs.
Standard oncologic care alone
• Better quality of life (mean score on the FACT-L
scale 98.0 vs. 91.5; P=0.03)
• Fewer depressive symptoms (16% vs. 38%,
P=0.01)
• Despite fewer patients receiving aggressive end-
of-life care (33% vs. 54%, P=0.05), median
survival was longer among patients receiving early
palliative care (11.6 months vs. 8.9 months, P=0.02)
FACT-L = Functional Assessment of Cancer Therapy–Lung
Temel et al. NEJM. 2010;363:733.

What is hospice?
• A philosophy and a program that delivers palliative care
- 1982 Medicare Hospice Benefit passed congress
- 1985 → made permanent
• Centers around an interdisciplinary team which provides:
- Expert medical care, pain and symptom management, and emotional
and spiritual support expressly tailored to the patient’s wishes
https://www.nhpco.org/hospice-care-overview/history-of-hospice/. Accessed July 31, 2022.

Hospice interdisciplinary team
• Core disciplines:
- A doctor of medicine or osteopathy (who is an employee of or under
contract with the hospice)
- A registered nurse
- A social worker
- A pastoral care provider or other counselor
• Additional team members:
- Pharmacy
- Bereavement
- Various therapies: occupational, physical, music, pet, etc.
- Volunteers
State Operations Manual, Appendix M - Guidance to Surveyors: Hospice. Rev. 200, February 21, 2020.
https://www.cms.gov/Center/Provider-Type/Hospice-Center. Accessed July 11, 2022.
How does a patient qualify for hospice?
• Medicare benefit
- Terminal illness with a prognosis of six months or less as certified by the attending physician
and the hospice medical director
• Hospice care is provided under:
- Medicare Part A
- Private/public/government health insurance
- Medicaid in most states including NY
- If no payor source → foundations
• Levels of Care
1. Routine home care
2. General inpatient care
3. Continuous home care
4. Respite care
https://www.nhpco.org/wp-content/uploads/NHPCO-Facts-Figures-2020-edition.pdf Accessed December 1, 2022.
https://www.health.ny.gov/health_care/medicaid/program/longterm/hospice.htm Accessed December 1, 2022.
Hospice myths
• Hospice is only for patients with cancer
• A do-not-resuscitate order is required
• A patient cannot have an active automatic implantable cardioverter-defibrillator (AICD)
• A patient cannot have antibiotics, IVs, total parenteral nutrition, or tube feedings
• A patient cannot have chemotherapy or radiation therapy
• A patient cannot have surgery
• A patient cannot live alone or not have a full-time caregiver
• Patients die more quickly than they would otherwise
Murray SA et al. BMJ. 2005;330:1007.
Guo Q et al. J Palliative Care Med. 2012;2:127

Palliative care and hospice
• Palliative care = improving quality of life
for those with serious illness
Palliative care
• Hospice care is a subset of palliative care
- End of life care
• Palliative care outside of hospice:
- Does not require a terminal diagnosis
- Patients do not have to forgo curative Hospice
therapy
PALLIATIVE CARE HOSPICE
• Place • Place
- Hospital - Patient’s home with primary caregiver
- Nursing home - Nursing home
- Community based - Hospice general inpatient unit
- Hospital— less frequent
• Timing • Timing
- No prognostic restrictions - 6-month prognosis
• Payment • Payment
- Emerging models of insurance - Inclusive of interventions related to
coverage diagnosis, including medications
• Treatment • Treatment
- Comfort care in combination with - Comfort care, QOL (not curative, may
curative and/or life-sustaining be life prolonging)
therapy
Kelley AS et al. N Engl J Med. 2015;373:747.
https://www.capc.org/documents/download/867/. Accessed December 1, 2022.
Dickerson D. Eur J Palliat Care. 1999;6:130.
Medication use in Palliative Care
PORTMANTEAU – DESIRABLE PROPERTIES WHO: ANALGESIC ADMINISTRATION
• Multiple therapeutic effects • Be given “by mouth”

• Minimal drug interactions • Be given “by the clock”
• Multiple routes of administration • Be given “for the individual” and
• Favorable adverse-effect profile • Be given with “attention to detail”
• Favorable ceiling effect
• Convenient dosing schedule
• Cost-effective
Dickerson ED. Palliative Care Pocket Consultant, 2nd Ed. Kendall Hunt; 2001.
WHO guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents. World Health Organization; 2018.
WHO's CANCER Pain Ladder For Adults
• “… consistently failed to provide sufficient relief
to 10%–20% of advanced cancer patients with
pain, particularly in cases of neuropathic pain
and pain associated with bone involvement”
Nersesyan H, Slavin KV. Ther Clin Risk Manag. 2007;3(3):381–400.
• Trial compared two-step versus standard X

three-step approach of the WHO analgesic
ladder in patients with cancer
• “No statistically significant difference in time to
stable pain control”
• In 3-step arm, “53% needed to change to a strong
opioid due to ineffective analgesia”
Fallon M et al. Ann Oncol. 2022;33(12):1296-1303.
WHO guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents. World Health Organization; 2018. License: CC BY-NC-SA 3.0 IGO.
Where to start
• Base the initial treatment on the severity of pain the patient reports
- Mild— Non-opioid analgesic
- Moderate— Opioid
- Severe (pain emergency) — Opioid
• Provide prescription
- As needed (PRN) analgesic medication
- “Take the medication if unexpected pain occurs”
- “Call for an appointment to evaluate the pain problem”
• Begin a bowel regimen
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Adult Cancer Pain V.2.2022. © 2022 National Comprehensive Cancer Network, Inc.
The dosing frequency conundrum
Sedation, euphoria, dysphoria
Drug concentration
Relief Relief Relief
Pain returns/hypersensitization
Tolerance develops
2.5 hrs
0 4 8 12
Adapted from Whitten CE et al. Perm J. 2005;9:9.
Post-administration time (hours)
Case CA: Week 1, day 1 hospital admission
• CC: “I’ve been coughing up blood”
• HPI: 58-year-old female recently admitted through the ED with dry, non-productive cough for 2
months, dyspnea on exertion and hemoptysis for 1 week
• PMH: Hypertension, hyperlipidemia, anemia of unknown origin for 1 year
• Current medications: (No known drug allergies)
- Alprazolam 0.5 mg PO TID PRN, atorvastatin 20 mg PO daily, quinapril 20 mg PO daily, folic
acid 1 mg PO daily, ferrous sulfate 325 mg PO TID
• Chest X-ray: Lateral and posterior-anterior views reveal possible mass in right upper lobe
• Bronchoscopy with biopsy: Squamous cell carcinoma
• CT: 2.5 cm x 2 cm right lung mass
• Mediastinoscopy with biopsy: Unresectable Stage IIIB non-small cell lung cancer with metastasis
to contralateral mediastinal nodes
• She reports that her pain is at worst “5/10” and “waxes and wanes throughout the day”; there are
times it’s “unperceivable”. What are her options for pain?
The next step
• “Administer a long-acting opioid on an around-the-clock basis, along with
an immediate-release opioid to be used on an as-needed basis, for
breakthrough pain once the patient’s pain intensity and dose are
stabilized.”
Opioids with long-acting formulations
• Morphine
• Methadone (tablets, liquid)
- The only long-acting liquid available!
• Fentanyl transdermal
• Buprenorphine
• Oxycodone
• Oxymorphone
• Hydromorphone
• Hydrocodone
• Tapentadol
• Tramadol

Breakthrough pain (BTP) medications
• Incident pain vs. end-of-dose failure pain vs. uncontrolled persistent pain
• Which opioid to give? Same as long-acting?
• How much to give? How often to give?
- “Allow rescue doses of short-acting opioids (10% to 20% of the 24-hour total of long-
acting or regularly scheduled oral opioid dose) up to every 3–4 hours PRN.”
- Example: 60 mg extended release (ER) morphine → ~5-10 mg PRN BTP
- “If pain is inadequately controlled, to allow for dose titration, the short-acting opioids
could be given as often as once per hour as needed (if hourly dosing is needed for
more than 3 cycles, reassessment or other intervention is recommended)”
• When to change long-acting medications?
- Patient-dependent
Metastatic bone pain
NSAIDS & COX-2 INHIBITORS CORTICOSTEROIDS
• Pros • Anti-inflammatory
- Useful for mild to moderate pain - Start dexamethasone 2-16
- Adjunctive mg/day (PO or IV)
• Cons - Up to ~30 mg daily
- Ceiling effect • Additional effects:
- Toxicity (especially elderly) - Anti-emetic
- Gastrointestinal - Appetite stimulation
- Renal - Antidepressant effects—
- Cardiac “stimulatory”
- Significant long-term side
effects (mitigated)
Leppert W et al. Curr Pain Headache Rep. 2012; 16:307.
Adjunctive agents (adjuvants, co-analgesics)
• Neuropathic pain
- Brain or spinal cord involvement, symptoms consistent with neuropathic pain
- Residual from cancer therapy
• Misnomer— may be primary intervention
- But often added to opioid regimen
• Failure of one agent not predictive of other drugs failing
• Classes:
- Anticonvulsants
- Tricyclic antidepressants
- Serotonin norepinephrine reuptake inhibitors
- Lidocaine topically
Tramadol
PROS CONS
• Moderate pain • Drug interactions
- Weak mu agonist - Carbamazepine, quinidine,
- M1 - mu agonist TCA, SNRIs, antipsychotics
• Less respiratory depression and SSRIs. (And others)
• Abuse potential - Serotonin syndrome
• Neuropathic pain • Side effects
- Inhibits the reuptake of norepinephrine - Dizziness, GI, constipation
and serotonin in the CNS - Seizure risks
• Extended-release formulation
Dunn KE et al. Front Psychiatry. 2019;10:704. Reines SA et al. Subst Abuse. 2020;14:1178221820930006.
Tramadol Hydrochloride. Micromedex Solutions. http://micromedex.com/. Accessed January 17, 2023.
Tapentadol
PROS CONS
• Moderate/severe pain • Ethanol alcohol (EtOH) – Absolute
- mu agonist contraindication with ER
- Inhibits the reuptake of • Drug interactions
norepinephrine - MAOIs
• Less respiratory depression - TCA, SSRIs, and SNRIs
- < 1% of study patients - Not cytochrome P450 (CYP)
• Abuse potential • Side effects
- Opioid-like
- Seizure risks
Butler SF et al. Pain Med. 2015;16:119.
Tapentadol Hydrochloride. Micromedex Solutions. http://micromedex.com/. Accessed January 17, 2023.
“I can’t swallow tablets anymore”:
• “The least invasive, easiest, and safest route of opioid administration should be
provided to ensure adequate analgesia.”
• Morphine liquid (Roxanol®) 100 mg/5 mL (i.e., 20 mg/mL)
• “Intensol” = concentrated liquid
- Methadone liquid 10 mg/mL
- Hydromorphone liquid 1 mg/mL
- Oxycodone liquid 20 mg/mL
Lugo RA et al. J Pain Palliat Care Pharmacother. 2002;16:5.

Coluzzi P. Journal of Pain and Symptom Management. 1998;16:184.
Opioid routes of administration
NON-PARENTERAL PARENTERAL
• PO/SL/transbuccal • IM
• Inhaled • SQ/IV
• Intranasal - Continuous infusion*
• Rectal • PCA
• Topical • Intrathecal
Case CA: Week 1, day 1 hospital admission
CA contacts you as she is having her next chemotherapy soon and has some questions.
You arrange a telemedicine visit for her.
She appears to be uncomfortable. In a hushed voice, she whispers that she’s in some
pain, but she’s worried about taking the pain medicine. She’s only been using 2-3 doses
per day for pain that gets to 7/10, although she admits that the pain never really goes
away.
The literature from the pharmacy contained all of the side effects including information
about dangers associated with misuse and possibility of dependence.
1. What should you do about her fear of using an opioid?
2. Should she be on a long-acting opioid?
3. What other medications should be prescribed to address the potential side-
effects of opioids?
“Nasty” side effects
• “Adjust opioid doses for each patient to achieve pain relief with an
acceptable level of side effects”
• “Monitor for and prophylactically treat opioid-induced side effects”
- Constipation
- Nausea/vomiting
- Respiratory depression
- CNS depression
Herndon CM et al. Pharmacotherapy. 2002;22:240.
Never forget!
The hand that writes the opioid script

Is the hand that writes the laxative script
Lest it be the hand that performs the disimpaction!
- Dame Cicely Saunders
“I don’t want to get addicted”
FEARS REGARDING OPIOID USE ADDRESSING MISCONCEPTIONS
• In a study, cancer survivors viewed opioids as • Offer psychosocial support
illicit drugs; • Educate patient and
• Media narrative of the opioid epidemic increased family/caregiver regarding pain
negative perception of opioid use for cancer- management and related issues
related pain; • Reevaluate patients at each
• Perceptions of opioids were informed by contact and as needed to meet
experiences of friends and family with an OUD; their goals for comfort and function
• Poor understanding of terminology resulted in
misconceptions of opioid use and addiction;
• Fear of opioid addiction resulted in unrelieved
cancer-related pain and poor QOL
Chavez MN et al. Eur J Cancer Care (Engl). 2022;31:e13582.

Important definitions
• Tolerance: Diminution of ≥1 drug effects (either favorable or adverse effects)
caused by exposure to the drug; may be pharmacologic or associative (related
to learning)
• Physical dependence: Pharmacologic property of some drugs, defined solely
by the occurrence of an abstinence syndrome after abrupt dose reduction,
discontinuation of dosing, or administration of an antagonist drug
• Addiction: The aberrant use of a substance characterized by:
- Loss of control, craving; compulsive use and preoccupation; continued use
despite harm
• Pseudoaddiction: Distress and drug-seeking behaviors that occur in the
context of unrelieved pain. These behaviors subside when analgesia is
achieved.
Weissman DE et al. Pain. 1989;36:363.
Fear of opioids hastening death
• “In conclusion, opioids and sedatives used for symptom control in the
last days are not associated with patient survival.”
Morita et al. J of Pain Symptom Manage. 2001;21(4):282-9.
• “Conclusion: Opioid usage, even at high dosages, had no effect on

survival among advanced cancer patients in a hospice setting.”
Azoulay et al. J Am Med Dir Assoc. 2011;12(2):129-34.
• “…patients who received opioid increases at the end of life did not show
shorter survival than those who received no increases.”
Thorns and Sykes. Lancet. 2000;356(9227):398-9.
Fear of opioids hastening death
• “…unfounded concerns about the possible life-shortening effect of
opioids resulted in less than optimal symptom management in end-of-life
care.”
Bilsen et al. J Pain Symptom Manage. 2006;31(2):111-21.
• “Although published guidelines are available, the research literature

suggests that healthcare providers continue to hold some negative
misconceptions about cancer pain and its treatment.”
Pargeon and Hailey. J Pain Symptom Manage.1999;18(5):358-68.
Dyspnea— General interventions
• Positioning
• Increased air movement via a fan or open window
• Use of bedside relaxation techniques
• Discontinuation of parenteral fluids
• Oxygen is often used but not universally helpful
- Therapeutic trial based on symptom relief, not pulse oximetry
- Titrate to pulse oximetry of 88-92% for COPD with hypoxia
Crombeen AM. Curr Oncol. 2020;27:142.

Yu S et al. J Palliat Med. 2019;22:1603.
Dyspnea— Medications
• Antitussives for cough
• Anticholinergics for secretions
• Anxiolytics for anxiety
• Agents related to specific diseases:
- Diuretics: Congestive heart failure, fluid overload
- Bronchodilators: Asthma, COPD
- Corticosteroids: Mass effect, COPD, asthma, inflammation
- Antibiotics: COPD exacerbation, pneumonia
Palliative care: Overview of cough, stridor, and hemoptysis in adults. Up To Date. https://www.uptodate.com/. Accessed January 17, 2023.
Dyspnea— Opioids
• Help relieve sensation of shortness of breath
• In the opioid naïve patient, low doses of oral (2.5-5 mg) or parenteral
morphine (1-2 mg) provide relief for most patients
• More frequent dosing is more effective than higher doses if dyspnea not
adequately treated
• Generally requires lower doses than necessary for treatment of pain
• “Start low, go slow”
Johnson MJ et. al. Am J Hosp Palliat Care. 2016;33:194.

Rocker G et. al. Thorax. 2009;64:910.
Mechanism of opioids for dyspnea
• Uncertain
• May diminish the chemoreceptor response to hypercapnia and hypoxia
• May cause vasodilation resulting in decreased dyspnea due to the
resulting reduction in preload and pulmonary congestion
• May result in a decrease in anxiety and the subjective sensation of
dyspnea through a central effect
• May treat underlying pain that is causing increased respiratory drive
• Morphine and other short-acting opioids effective; time to onset differs
based upon formulation.
Zebraski SE et al. Life Sci. 2000;66:2221.

Long-acting opioids for dyspnea
• Trial of 48 opioid-naïve COPD patients
- Randomized: 20 mg long-acting morphine or placebo x 4 days
- Significant improvements in subjective dyspnea scores on visual
analog scale
Abernethy et al. BMJ. 2003;327(7414):523-8.
• Long-acting morphine for refractory breathlessness

- 83 patients: COPD, cancer, and interstitial lung
- 62% derived benefit
- Number needed to treat=2, number needed to harm=5
Currow et al. J Pain and Symptom Manage. 2011;42(3):388-99.
Respiratory depression
• A study involving 27 patients (25 cancer, 2 ALS) given opioids for
dyspnea
- 15 opioid-naïve, 12 opioid-experienced
• No significant rise in PaCO2 or fall in PaO2
• All patients had significant symptomatic relief of dyspnea and a reduction
in their respiratory rate
Clemens et al. J Palliat Med. 2008;11(2):204-16.
Expert recommendations
• Low-dose opioids for relief of dyspnea
- American Thoracic Society (ATS)
- American College of Chest Physicians
- American College of Physicians
- National Comprehensive Cancer Network (NCCN)
Lanken PN et al. Am J Respir Crit Care Med. 2008;177:912.

Parshall MB et al. Am J Respir Crit Care Med. 2012;185:435.
Mahler DA et al. Chest. 2010;137:674.
Qaseem et al. Ann Intern Med. 2008;148:141.
Methadone advantages
• Duration of action
- 6-8 hours with single dose; 8-48 hours with chronic dosing
- Methadone should be administered more frequently during the first
days of treatment as ~48 hours may be required to approach steady
state blood levels due to the large volume of distribution
• Pain relief in patients unresponsive to current opioid treatment
• Diminished incidence of side effects
• Opioid agonist plus:
- Noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist
- Norepinephrine or serotonin reuptake inhibition
Ripamonti C et al. Pain. 1997;70:109.
Gourlay et al. Pain. 1986;25:297.
Crews JC et al. Cancer. 1993;72:2266.
Ebert B et al. Biochem Pharmacol. 1998;56:553.
Codd EE et al. J Pharmacol Exp Ther. 1995;274:1263.
Methadone advantages
• Multiple routes of administration • May also be administered rectally,
- PO SL, epidurally, intrathecally, IV, and
- Tablet SC
- 5 mg • Methadone HCl powder for
- 10 mg compounding
- 40 mg (dispersible tablet) - SL: Concentrated drops for
- Solution patients who cannot tolerate large
- 5 mg/5 mL volumes of liquid
- 10 mg/5 mL • Rectal
- 10 mg/mL
- IM - Micro-enema using prepared
- Injection- 10 mg/mL solution
- Compounded suppositories
Methadone Hydrochloride. Micromedex Solutions. http://micromedex.com/. Accessed January 17, 2023.
Methadone dosing (a challenge)
• Caveat: “PRACTITIONERS ARE ADVISED TO CONSULT WITH A PAIN OR
PALLIATIVE CARE SPECIALIST IF THEY ARE UNFAMILIAR WITH
METHADONE PRESCRIBING or if individual patient considerations
necessitate very rapid switching to or from methadone.”*
• Pharmacokinetics
- Absorption: High bioavailability: ~80%, Rapid onset: ~15-45 minutes
- Distribution: VERY LARGE
- Only ~1% of drug in the blood
- Extensive tissue accumulation due to lipophilic properties
- Binds 1-acid glycoprotein (85-90%)
- Variable half-life due to interpatient variability
- Mean = 30.4 +/- 16.3 hours (95% confidence interval)
- Time range to steady state = 70.5 hours-233.5 hours = ~3-10 days
Lugo RA et al. J Pain Palliat Care Pharmacother. 2005;19:13. Gourlay GK et al. Pain. 1986;25:297
*NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Adult Cancer Pain V.2.2022. © 2022 National Comprehensive Cancer Network, Inc
Methadone dosing (a challenge)
• Metabolism and elimination
- Metabolized to inactive metabolites
- Reduces toxicity compared to other opioids
- CYP3A4 substrate
- Inducible metabolism by known enzyme inducing drugs (e.g., phenytoin,
carbamazepine, others)
- Fecal elimination— major, renal excretion— minor
• Ratios of morphine: methadone vary
- Range 3:1 to 20:1
• Consider pharmacokinetic variables
- Naïve: 2.5 mg 2-3 times/day ( PRN)
- Conversion: 5-10 mg 2-3 times/day
- Multiple methods
Ripamonti C et al. Pain. 1997;70:109. Wong E. J Community Hosp Intern Med Perspect. 2012;2.
Methadone monitoring parameters
• Patient must be closely monitored until a methadone steady state concentration has
been attained
- Variable but ~3-10 days
- Educate family regarding how to monitor patient
- Respiratory rate, level of consciousness, arousability, pupillary response
- Once peak serum levels have been obtained, potential problems become less
likely to occur
• QTc prolongation
- Electrocardiogram screening and monitoring
- Concomitant QTc prolongation drugs
Chou R et al. J Pain. 2014;15:321.

Chou R, et al. J Pain. 2014;15:338.
Price LC et al. J Pain Symptom Manage. 2014;48:333.
A “good death”
• Being treated as an individual with dignity and respect
• Being without pain and other symptoms
• Being in familiar surroundings
• Being in the company of close family and/or friends
National Hospice and Palliative Care Organization (NHPCO)

“…means being physically comfortable, at peace in your own home, surrounded by
your loved ones, doing the things you love to do up until the very end.”
Key concepts
• Palliative care → improves overall quality of life
• Team approach
• Palliative care at time of diagnosis
- Simultaneously with curative or life-prolonging therapies
• Opioid use at end-of-life eases both pain and dyspnea
• Methadone is an important tool to address both nociceptive and neuropathic
pain but must be used with caution
Acknowledgements
• Christopher Kerr, M.D., Ph.D.
- Chief Medical Officer, The Center for Hospice and Palliative Care
Thank you!
• To submit the mandatory attestation of course completion using the
Narcotic Education Attestation Tracker (NEAT), please use the link
below:
- https://www.health.ny.gov/professionals/narcotic/mandatory_prescrib
er_education/neat.htm

Opioid Prescriber Education Program Slides

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Opioid Prescriber Education Program Slides

Uploaded by

Copyright:

Available Formats

OPIOID PRESCRIBER

Edward M. Bednarczyk, Pharm.D., FACCP, FAPhA

10 NYCRR §80.63, PBH §3332, ISC §3216, PBH §3309 (7)

• Describe NYS 7-day rules

Auric Goldfinger 8/13/2022

1007 Odd Job Road

Felix Leiter, LPA

https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/elec_pres_except_disp_clar_4_pharm.htm. Accessed April 4, 2022.

https://www.health.ny.gov/professionals/narcotic/prescription_monitoring/docs/pmp_registry_faq.pdf. Accessed March 30, 2022.

https://www.health.ny.gov/professionals/narcotic/prescription_monitoring/. Accessed March 30, 2022.

https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/docs/epcs_faqs.pdf. Accessed April 4, 2022.

http://www.op.nysed.gov/news/advisory-notices.html#electronic. Accessed March 30, 2022.

http://www.op.nysed.gov/news/advisory-notices.html#electronic. Accessed March 30, 2022.

https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/elec_pres_except_disp_clar_4_pharm.htm. Accessed March 30, 2022.

https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/. Accessed April 19, 2023.

https://www.health.ny.gov/professionals/narcotic/electronic_prescribing/. Accessed November 17, 2022.

http://www.op.nysed.gov/news/advisory-notices.html#electronic. Accessed January 13, 2022.

Panic disorders Code A

Chronic debilitating neurological Code C

Romanth Waghmarae, MD, DABA, FACIP, FIPP

• Outline evidence-based best practices for appropriate prescribing of

Raja SN et al. Pain. 2020;161:1976.

Intensity - Variable - Variable

Raja SN et al. Pain. 2020;161:1976.

• Recognition and reaction in the brain •Possible neurochemical link between

• Antinociception neurons descend from

Spinal Cord Neuron

Primary Sensory Neuron

Damaged •Damaged sensory nerves may send

Neurogenic •Increased prostanoid production at pain

Adapted from Whitten CE et al. Perm J. 2005;9:9.

Pathophysiology Nociceptive vs Neuropathic vs Mixed

Disease Origin Cancer vs Non-Cancer

Persistent Intermittent Break-Through

Miss the benefits of physical, behavioral, and psychological approaches to

Suboptimal pain control

Failure to treat neuropathic pain with Worsening hypersensitivity of nervous system

Increased breakthrough pain, disturbed sleep

Whitten CE et al. Perm J. 2005;9:9.

https://www.practicalpainmanagement.com/resources/diagnostic-tests/guide-chronic-pain-assessment-tools. Accessed March 21, 2022.

- Worst pain in past 7 days No

- Numeric rating/visual analog scales No

- McGill Pain Questionnaire

Blondell RD et al. Am Fam Physician. 2013;87:766.

Dowell D et al. MMWR Recomm Rep. 2022;71:1.

Trescot AM et al. Pain Physician. 2008;11:S133.

https://www.health.ny.gov/professionals/narcotic/. Accessed January 24, 2023.

Hydromorphone Dose adjustment in renal and hepatic impairment

Tapentadol Caution in patients on serotonergic agents; if used in combination with other

*Conversion factors may vary by source

https://www.cdc.gov/drugoverdose/pdf/calculating_total_daily_dose-a.pdf. Accessed April 15, 2022.

Benyamin R et al. Pain Physician. 2008;11:S105.

https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/abuse-deterrent-opioid-analgesics. Accessed April 15, 2022.

OxyContin® Oxycodone extended-release tablets Apr. 2010

Hydrocodone extended-release tablets

Xtampza® ER Oxycodone extended-release capsules Apr. 2016

Roxybond® Oxycodone tablets Apr. 2017

Dowell D et al. MMWR Recomm Rep. 2022;71:1.

How do you approach this situation?

What do you discuss with the patient?

How do you manage this situation?

• Describe strategies to mitigate the risk of iatrogenic OUD

• Explain harm reduction strategies

4th wave: Stimulant