Pain Management Part 1 and 2 (12 questions)

What is Pain?

"An unpleasant sensory and emotional experience associated with actual or potential tissue damage."

Chronic Pain Low Risk

+Urine Drug Screen- every 1-2 years +Pain Management Profile- Twice a year (every 6 months) +Use more than 50 mg of Morphine Equivalent Dose If aberrant behaviors are demonstrated, counseling must be done to address them and if the behavior is unchanged, opioid use must be seriously reconsidered

Chronic Pain Medium Risk

+Urine Drug Screen- every 6-12 months +Pain Management Profile- Three a year (every 4 months) +Use more than 50 mg occasionally of Morphine Equivalent Dose +If aberrant behaviors are demonstrated, counseling must be done to address them and if the behavior is unchanged, opioid use must be seriously reconsidered

Pain Pathway Perception affected by

- Cognitive Behavioral Therapy Perception: How your brain actually interprets these incoming signals depends on functions within the higher cortical structures (stress, emotions, etc. can impact perception of pain) Cognitive behavioral therapy can alter Perception

Pain Pathway Transmission affected by

-Opioids - Local anesthetics - Electical nerve stimulation Transmission: Pain sent along A and C fibers to dorsal horn of spinal cord à secondary neurotransmitter release. Lots of things other than pain transmitted as well and can interfere with pain signal

Non-Cancer Chronic Pain: Take-Home Points

1. Pain is NOT a state of opioid deficiency a)Opioids are NOT first-line for chronic non-cancer pain 2. Pain is NOT the 5th vital sign for chronic pain AMA recommended its removal from professional standards 3. Drugs are only part of the solution Opioids should be only be used adjunctly with other non-opioid and non-pharmacologic therapies Cognitive behavioral therapy Relaxation techniques Social stressors Depression Sleep Physical therapy 4. Use assessment tools effectively Pain scores Functionality Depression/PTSD Respiratory depression risk Abuse risk 5. Set realistic goals/expectations for your patients Talk with your patients! What are their goals? Focus on functionality Reassess benefits on regular basis: risks within 1-4 weeks of initiation and at least every 3 months thereafter 6. Patient-provider relationship is the primary determinant of treatment success "Stop trying to cure me and just start listening to me" •David Tauben, MD "It must be recognized, therefore, that the efficacy of [opioids] may relate as much to the quality of the personal relationship between physician and patient as to the characteristics of the patient, dose, or dosing regimen." 7. Set speed limits on long-term opioids Nearing 80-120 mg oral morphine equivalents per day: Take a step back to re-evaluate "Do not prescribe more than an average daily morphine equivalent dose of 120 mg without either the patient demonstrating improvement in function and pain or first obtaining a consultation from a pain management expert." Per CDC:2 Reassess benefits:risks at 50 oral morphine equivalents per day(nervous) Avoid or carefully justify > 90 oral morphine equivalents per day(concern) Acute pain will go over, but Chronic pain do not exceed above 8. Avoid concurrent benzodiazepines or combinations of Benzodiazepines and opioids at all costs! Concomitant respiratory depression Benzodiazepines co-involved in 30% of opioid-related fatal overdoses and increases hospitalizations Very few legitimate indications for chronic benzodiazepines Offer outpatient Naloxone

Prescription opioid volume in billions of milligrams of morphine equivalents dispensed

1992- 25.5 billion 2011- 240.3 billion 2017- 170.8 billion

Choosing the Right Agent For Neuropathic Pain

1st line Antidepressants or Anticonvulsants Amytriplatine or Nortryptaline (TCAs) or Gabapentin (Anticonvulsant) *Carbamazepine (Anticonvulsant) *valproic acid (Anticonvulsant) *topirimate(Anticonvulsant) *lamotrigine(Anticonvulsant) 2nd line Anticonvulsants Pregabalin (Anticonvulsant) *Carbamazepine (Anticonvulsant) *valproic acid (Anticonvulsant) *topirimate(Anticonvulsant) *lamotrigine(Anticonvulsant) 3rd line Venlafaxine or Duloxetine (SNRIs) 4th line Tramadol Adjunct options: Lidocaine patches Capsaicin cream TENS units *Other options (refractory to others): Carbamazepine, valproic acid, topirimate, lamotrigine, mexiletine- may reduce the intensity and frequency of painful muscle cramps and spasms in Amyotrophic lateral sclerosis

Patient Case 3

52 yo M presents to clinic complaining of generalized whole body pain that has been ongoing for several months, and no clear inciting event can be identified Patient denies any history of substance abuse or psychiatric illness Patient is not interested in physical therapy or non-pharmacologic interventions If the physician was considering opioid therapy for this patient, how would you classify this patient's baseline risk for opioid misuse? If opioids are initiated, what other monitoring measures would you recommend? With what frequency?

Patient Case 2

A 68 yo F with chronic low back pain has been prescribed oxycodone 15 mg every 6 hours prn for nearly five years (patient has taken scheduled for the past 2 years) by her PCP, who just retired. Her new PCP is concerned about this opioid regimen given the dose, the lack of non-opioid trials, and the patient's drowsiness during clinic visits. Her PCP would like to taper her off of opioids, and asks for your recommendation: How would you initiate the first step of a taper? What are some signs of withdrawal that you might counsel this patient on? What other non-opioid options could be considered as to facilitate this taper?

Sobering Facts

Actual rate of opioid use disorder closer to 8-12% Higher number will misuse/abuse opioids (21-29%) 80% of heroin abusers begin by using prescription opioids 4-6% of all patients who misuse opioids will transition to using heroin

Opioids in the Hospital

Acutely ill patients often unable to take oral medications IV route commonly utilized Patient-controlled analgesia (PCA) an option Electrical pump that allows the patient to deliver controlled doses of IV opioids to themselves "on-demand" by pressing a button Nursing controlled analgesia is an emerging option at some institutions Advantages Faster patient access to pain medications leading to enhanced pain control Decreased nursing labor in delivering individual doses as needed Decreases risk for oversedation Disadvantages Requires patient to have mental/physical capacity to utilize Patient must be able to recognize pain and press button appropriately Family and friends should NOT press PCA button for patient

1980 NEJM Letter to the Editor

Addiction Rare in patients treated with Narcotics by Jane Porter Hershel Jick M.D. Boston Collaborative Drug Surveillance program Boston University Medical Center Cited 100's of time to justify use of narcotics.

Acute Nocioceptive Pain: Take-Home Points

Adequate treatment of acute pain is essential Decreases risk for development of chronic pain Do NOT use long-acting opioids for acute pain states Strongly reconsider need for opioids once initial tissue damage expected to have healed Prescribe short supplies initially Per 2016 CDC guidelines: "Three days or less will often be sufficient; more than seven days will rarely be needed."

Muscle Relaxants

Adjunct therapy for acute pain related to muscle tension or spasm only Most studied in patients with back pain Benefit mostly due to sedative effects rather than direct effect on the muscles Should NOT generally be used for chronic pain Limited efficacy Tolerance develops to most agents High rate of adverse effects Anticholinergic, sedation, dizziness, increased fall risk Avoid these agents in the elderly or if seizure disorder

Mistake #10 - Making Rapid adjustments to PCA basal dose

Adjusting PCA: Titrate demand dose initially Generally no sooner than 6-8 hours after initiation Time to steady-state Can increase demand dose by 50-100% Can be titrated every 6-8 hours as needed Change basal rate cautiously No sooner than 24 hours after initiation Do not change basal rate more frequently than once daily Do not increase basal rate by more than 100% with each dosing change Small adjustments if elderly, or hepatic/renal dysfunction

Non-Opioid Medications Counterirritants (menthol, camphor, methyl (salicylates)

Advantages (Pros) Low risk for systemic adverse effects Disadvantages (Cons) · Simply masks pain Only effective for localized and relatively superficial pain Formulation · Transdermal Other considerations Apply sparingly · Caution with salicylates products around children

Non-Opioid Medications Lidocaine Patches

Advantages (Pros) Minimal absorption or systemic side effects Disadvantages (Cons) Only effective for localized and relatively superficial pain Formulation · Transdermal Other considerations · Apply sparingly · Caution with salicylates products around children

Opioid Pain Medications Morphine WHO 3

Advantages (Pros) · "Gold standard" opioid · Lower abuse potential than many other potent opioids · Multiple formulations/routes · Inexpensive Vasodilation/histamine release ideal if ACS Disadvantages (Cons) · Renally cleared · Vasodilation/histamine release can cause more hypotension and itching ER formulations not abuse deterrant Formulation PO- IR, ER, & suspension IV, epidural, & intrathecal Other considerations · Should be IV opioids of choice for most patients Consider morphine trial before moving to more potent options

Opioid Pain Medications Oxymorphone WHO 3

Advantages (Pros) · 3 times more potent than morphine · Opana is an abuse deterrent product Disadvantages (Cons) · Higher abuse potential Higher street value Formulation PO- IR & ER IV Other considerations · $$$$ Opana ER voluntarily removed from the market in 2017

Opioid Pain Medications Hydromorphone WHO 3

Advantages (Pros) · 4-5 times more potent than morphine · Exalgo is abuse deterrant product Wide range of formulations and routes Disadvantages (Cons) · Higher abuse potential Higher street value Formulation PO- IR & ER IV, epidural, & intrathecal Rectal Other considerations · Overutilized in EDs and hospitals

Opioid Pain Medications Oxycodone WHO 3

Advantages (Pros) · 50% more potent than morphine · Oxycontin is abuse deterrant product Disadvantages (Cons) · Higher abuse potential · Higher street value Oral formulations only Formulation PO only- IR & suspension Other considerations

Non-Opioid Medications NSAIDS

Advantages (Pros) · Analgesic, antipyretic, and anti-inflammatory · Can be used for wide array of pain times · Multiple formulations/routes · Safe in children OTC form many forms Disadvantages (Cons) Toxicities: · Renal · Bleeding risk · Cardiovascular GI ulceration Formulation PO/IV/transdermal Other considerations · Caution if on ASA, steroids, or blood thinners · Avoid if high risk for toxicities Lower, but non-existent risk for toxicity with transdermal forms

Opioid Pain Medications Codeine WHO 2

Advantages (Pros) · Antitussive · Low abuse potential Not a CII medication- Easier for patients to receive prescription and refill Disadvantages (Cons) · High rate of N/V · "Ceiling" doses due to risk for respiratory depression Formulation PO only Other considerations · Black box warning for use in children · Caution if 2D6 polymorphisms Mostly used for cough or for mild dental procedures

Opioid Pain Medications Tramadol WHO 2

Advantages (Pros) · Can be effective for neuropathic pain (5HT reuptake) · Lower risk for euphoria and abuse than morphine · CV classification- Easier for patients to obtain and refill Inexpensive Disadvantages (Cons) · Risk for serotonin syndrome Can lower seizure threshold Formulation PO only- IR & ER Other considerations · Ideal agent if opioids is needed but high risk for abuse based on patient history

Opioid Pain Medications Tapentadol WHO 2

Advantages (Pros) · Can be effective for neuropathic pain (NE reuptake) and mixed pain states Lower risk for abuse and constipation than morphine Disadvantages (Cons) · CII medication- much more potent opioids than tramadol Higher risk for abuse than tramadol Formulation PO only- IR & ER Other considerations $$$$

Non-Opioid Medications SNRIs (venlafaxine, duloxetine)

Advantages (Pros) · Effective for neuropathic pain · Can be effective for other pain types as well Secondary benefits if anxiety or depression Disadvantages (Cons) · Lots of drug interactions · Prescription only Withdrawal from venlafaxine can be severe Formulation · PO Other considerations Modestly expensive · Caution if hypertension An ideal choice if treating depression and pain concurrently

Non-Opioid Medications Gabapentin

Advantages (Pros) · Effective for neuropathic pain · Can be effective for other pain types as well · Secondary benefits if epilepsy, insomnia, or anxiety Minimal drug interactions Disadvantages (Cons) · Adverse effects: Sedation, weight gain, edema · Saturable absorption · Has abuse potential and mild euphoria · Very slow titration schedule Prescription-only Formulation · PO Other considerations Start low and go slow Great adjunct agent for most acute and chronic pain states

Non-Opioid Medications Pregabalin

Advantages (Pros) · Effective for neuropathic pain · Can be effective for other pain types as well · Secondary benefits if epilepsy, insomnia, or anxiety · Minimal drug interactions Faster titration schedule than gabapentin Disadvantages (Cons) · Adverse effects: Sedation, weight gain, edema · Has abuse potential and mild euphoria · Teratogenic? Prescription-only Formulation · PO Other considerations $$$- Usually a higher tier co-pay for insured patients than gabapentin

Non-Opioid Medications Tricyclic Antidepressants

Advantages (Pros) · Effective for neuropathic pain · Can be effective for other pain types as well · Secondary benefits if insomnia, anxiety, migraines, or depression Inexpensive Disadvantages (Cons) · Anticholinergic adverse effects · Lots of contraindications · Lots of drug interactions Prescription-only Formulation · PO Other considerations Would generally avoid in the very elderly, dementia, epilepsy, BPH, constipation, or unstable cardiac disease

Opioid Pain Medications Fentanyl WHO 3

Advantages (Pros) · Extremely potent opioid · Quick on/off makes it ideal for procedures or acute care settings · Transdermal patch available if PO is not an option · Drug of choice if severe renal/hepatic impairment Disadvantages (Cons) · Patch is not very useful for acute pain · Patch can be very dangerous if misused or misprescribed IR formulations have a short duration of action Formulation Buccal/SL Nasal IV, epidural, & intrathecal Transdermal ER Other considerations · Some products very $$$$ · Dosed in mcg, not mg · Do not cut patches · Patches may not work if low body fat Patches should not be exposed to high heats

Opioid Pain Medications Buprenorphine WHO 2

Advantages (Pros) · Mixed agonist/antagonist Low risk for euphoria, abuse, and withdrawal Disadvantages (Cons) · Ceiling effect for respiratory depression May blunt the effect of other opioids if treating acute on chronic pain (causing withdrawal) Formulation Sublingual Transdermal ER IV Other considerations · Often used in SL form for addiction management · Ideal opioid if high risk for abuse $$$

Opioid Pain Medications Methadone WHO 3

Advantages (Pros) · Multiple mechanisms of action (opioids receptors, NMDA, 5HT) · Very inexpensive · Low risk for hyperalgesia · Low risk for euphoria and abuse Can be effective for neuropathic pain Disadvantages (Cons) · High risk for respiratory depression and death if misused · Variable half-life · Opioid conversions are difficult · Titration is generally very slow · QTc prolongation · Drug interactions Formulation PO IR IV Other considerations · A drug of choice if being treated for opioids addiction · Should only be prescribed if highly skilled in pain/addiction management Only for chronic pain on a scheduled (not prn) basis

Opioid Pain Medications Hydrocodone WHO 3

Advantages (Pros) · Similar potency to morphine · Lower abuse potential than many other potent opioids Disadvantages (Cons) · Most formulations contain APAP- "ceiling dose" & higher risk for hepatotoxicity · Zohydro ER not abuse-deterrent Oral formulations only Formulation PO only- IR, ER, & suspension Other considerations · Now CII Was the most commonly prescribed medication in the US prior to 2014

Non-Opioid Medications Acetaminophen

Advantages (Pros) · Well tolerated and safe · Analgesic and antipyretic · Can be used for wide array of pain times · Multiple formulations/routes · Safe in infants and kids OTC for most forms Disadvantages (Cons) · Hepatoxicity No anti-inflammatory activity Formulation PO/PR/ IV Other considerations · Caution if End-stage liver disease (ESLD), alcoholic, or anticonvulsant use Avoid use of IV APAP -$$$$

Naloxone Access: Pharmacy driven

All 50 states now have specific naloxone access laws Most states have laws that allow outpatient pharmacies to have "standing orders" for naloxone Requires authorized provider agreements Some states, like WY, have statewide pharmacy protocols that allow the same without the provider agreement Either method allows pharmacists to dispense naloxone to: Patients at risk for overdose First responders Employee or volunteer of a harm reduction organization Family member/friend of person at risk for overdose

Monitoring Four A's

Analgesia Activities of daily living Adverse events Aberrant drug-taking behaviors

Escalating Opioid Use Overdose Deaths Involving Opioids

Any Opioid 13.5:100,000 Other synthetic opioids 6.5:100,000 fentanyl and tramadol Heroin 5:100,000 Natural and Semi-Synthetic opioids 4.5:100,000 oxycodone and hydrocodone Methadone 1:100,000

Opioid Withdrawal Symptom Management

Autonomic hyperactivity (chills, piloerection, flushing, inc HR/BP) Clonidine 0.1-0.2 mg TID x 3 days, then BID x 1 day, , then daily x 1 day, then stop Lofexidine (Lucemyra) an alternative Insomnia/restlessness/anxiety Trazodone or diphenhydramine Myalgias/arthralgias- NSAIDs Muscle cramps- cyclobenzaprine Abdominal cramps- Dicyclomine Diarrhea- Loperamide

Opioids are Effective.... Right??

Average reduction in pain scores of 30%, but..... Evidence is there for acute pain Low quality evidence overall for chronic pain Long-term efficacy not well established Mean duration of clinical trials only 4 weeks Minimal impact on quality of life or physical functioning Studies show actually detrimental to QoL, decreased employment, and higher mortality High rate of adverse effects (80%) to opioids

Mistake #6 - Misusing the fentanyl patch

Avoid patch in patients that are: Opioid naïve Having acute pain Have poor pain control Slow titration Have a high fever Have a low body mass Other considerations Heat increases rate of release Hot tubs/baths, heating blankets, direct sunlight Patch disposal Children/animals Slow onset - 24-36 hours to peak effect Conversion from patch to other opioids has not been studied -50% of dose still present in serum 17 hours after removal -After removing patch, slowly titrate up opioids until analgesia Patients should wear a higher dose through 2 applications before any further increase in dosage is made based on average rescue medication needed General rule: if patient needs >3 rescue doses in 24 hours, patch strength should be increased Can calculate amount of rescue medication needed and convert to equianalgesic fentanyl dose Patch strengths: 12, 25, 50, 75, and 100 mcg/hr May need to apply two patches at the same time If titrating up to 37 mcg/hr or using > 100 mcg/hr 20% of patients may require shorter application period of q 48 hours

Muscle Relaxants-Antispasticity agents- Act directly upper motor neurons

Baclofen Pros-Good evidence Cons-Sedation, withdrawal can occur Dantrolene Pros-None Cons Hepatotoxicity limits long-term use

Long-Acting vs. Short-Acting

Benefits of long-acting opioids More consistent control of pain Improved adherence Lower risk of addiction/abuse? Downside of long-acting opioids Longer time to peak effect and steady-state Not very useful for acute pain Systemic effects can continue long after opioid stopped (days) Most concerning in overdose situations Two-fold higher risk for unintentional overdose than short-acting1 More than 5-fold in first 2 weeks after initiation

Wyoming Naloxone Laws

Bill passed in 2017 that allows any licensed pharmacist to prescribe and dispense naloxone to any of the following: Patients who are at risk for an opiate related overdose A person in a position to assist someone who is at risk of an opiate related drug overdose A person who, in the course of their job, may encounter a person experiencing an opiate related drug overdose

Mistake #5 - Ineffective Breakthrough

Breakthrough doses are typically 10-20% of the TDD 120 mg x 0.15 = 18 mg morphine Smallest morphine IR tablet strength is 15 mg Dosing frequency of morphine IR is typically every 4-6 hours New breakthrough regimen: Morphine IR 15 mg every 4-6 hours as needed If patient has to use breakthrough regimen "around-the-clock," likely indicates the need to increase the dose of the long-acting agent Unfortunately, can also indicate abuse as well

Symptoms of Fibromyalgia

Central Chronic headache (Fibro Fog) Sleep disorders Dizziness Cognitive impairment Memory impairment Anxiety Depression Eyes Vision problems Joint of Jaw Dysfunction Skin Various complaints Chest Region Pain Muscular Myofascial pain Fatigue twitches Joints Morning Stiffness Abdomen Pain Stomach Nausea Urinary Problems urinating Female reproductive system Dysmenorrhea Systemic Pain Weight gain cold symptoms multiple chemical sensitivity Widespread pain across multiple "tender points"

CERTA Multimodal Approach

Channels, Enzymes, and Receptors for Targeted Analgesia Channels Sodium channel blockade (lidocaine, anticonvulsants) Calcium channel blockade (gabapentin, pregabalin, magnesium) Enzymes COX 1/2/3 inhibition (NSAIDs, APAP) Receptors Opioid activation (opioids) NMDA blockade (ketamine, magnesium) migraine GABA activation (gabapentin, pregabalin) Dopamine blockade (haloperidol, prochlorperazine, metoclopramide) acute migraine Alpha-2 activation (clonidine, tizanidine) triptans- for migraines

Examples of Steps Taken

Colorado- March 2018 Limitations on opioid day supply for new starts Mandatory use of PDMP prior to first refill Wyoming- July 2017 Emergency Administration of Opiate Antagonist Act Nationwide Over 60 bills related to combating opioid crisis at May 2018 House Energy and Commerce Committee hearings Congress devoted $6 billion to the cause for 2018 & 2019

Pregabalin (Lyrica) Dosing

Common FDA Label Indication, Dosing, and Titration. -Neuropathic pain, diabetes associated or spinal cord injury associated: 50-100 mg po tid -Fibromyalgia: 75-150 mg po bid; may titrate to max 225 mg bid -Postherpetic neuralgia: Initial, 75 mg po bid; may titrate to 300 mg/d; maintenance, 75-150 mg bid or 50-100 mg tid; may titrate to max 600 mg/d Side effects Common (>10%) Dizziness, somnolence, ataxia, headache, peripheral edema Less Common (1-10%) Arthralgia, asthenia, blurred vision, confusion, constipation, diplopia, disturbance in thinking, euphoria, fatigue, incoordination, increased appetite, muscle spasm, tremor, vomiting, weight gain, xerostomia Rare but Serious (<1%) Angioedema

Gabapentin Dosing

Common FDA Label Indication, Dosing, and Titration. -Postherpetic neuralgia: Immediate release, Adults, 300 mg po on day 1, 300 mg bid on day 2, 300 mg tid on day 3, may titrate dose to 1800 mg/d in 3 divided doses; extended release, 300 mg on day 1, 600 mg on day 2, 900 mg days 3-6, 1200 mg days 7-10, 1500 mg days 11-14, and 1800 mg po daily thereafter Off-Label Uses. -Diabetic peripheral neuropathy: Adults, 900-3600 mg/d poRestless leg syndrome: 300 mg po 2 h prior to bedtime -Neuropathic pain: Immediate release, 300 mg po daily, may titrate to 3600 mg po daily Side Effects Common (>10%) Dizziness, somnolence Less Common (1-10%) Ataxia, blurred vision, diarrhea, fatigue, hostile behavior, peripheral edema, nausea, nystagmus, vomiting, weight gain, xerostomia Rare but Serious (<1%) Stevens-Johnson syndrome, suicidal thoughts

Learning Objectives

Communicate realistic goals of pharmacologic therapy to patients with acute and chronic pain Devise strategies to prevent or minimize potential adverse effects of medications used for pain Determine if a patient is an appropriate candidate for opioid therapy Compare and recommend pharmacologic and non-pharmacologic therapies based on patient characteristics/presentation Acute pain Chronic pain Neuropathic pain Titrate opioid doses safely and effectively Recognize signs of aberrant behaviors associated with opioid therapy, and modify therapy based on presence of these behaviors Evaluate appropriateness of pain medication dosing and be able to convert from one opioid to another using equipotent doses Implement strategies to minimize risk for misuse and/or abuse of opioids Be able to respond appropriately to patients with addiction or opioid overdose

Opioid Adverse Effects

Constipation- know this side effect Respiratory depression (no. 1 complication) Sedation Nausea/vomiting Urticaria (hives)- switch opioid or get off opioids Hyperalgesia (increase pain sensitivity)- rare Euphoria Addiction risk Urinary retention Hypotension Long-term use -Hypogonadism -Erectile dysfunction -Immunosuppression

Wyoming Opioid Drug Facts 2014

Counties All had >15 deaths per 100,000 Polk, Campbell, Freemont Natrona, Sweetwater, Unita, Albany and Laramie Wyoming is above the national average in drug poisoning deaths- Age adjusted 19.4 per 100k National Rank in Drug poison deaths is 12th Annual rate of opioid prescriptions dispensed by retail pharmacies was the same with the national average

Muscle Relaxants-Antispasmodics- Central sedating effect only- useful acute phase/not for long term use

Cyclobenzaprine Pros Best clinical evidence Cons Anticholinergic Methocarbamol Pros "Safest" in elderly Cons Urine discoloration Metaxolone Pros Slightly less sedation Cons Expensive Carisoprodol Pros None Cons High abuse potential Orphenadrine Pros Some analgesia, BID Cons Potent anticholinergic

How Do I Switch Between Opioids? Mistake #4 - Failing to account for incomplete cross-tolerance

Determine patient's current daily opioid use (TDD) Long-acting + short-acting + breakthrough 2. Convert TDD into oral morphine equivalents (OME) What is the TDD in OMEs for the following patient? Oxycontin® 40 mg PO BID Oxycodone 5 mg 2-3 tabs every 4 hrs prn Patient reports taking an average of 8 oxycodone tablets per day 3. Determine which opioid to use 4. Account for "incomplete cross-tolerance" Although opioids act on the same receptors, different opioids interact with these receptors with slight differences Generally must reduce anticipated dose by 30-50% to avoid potential overdosing of patient Reduce dose by 50% if: Patient is elderly (>75 yo), extremely frail, or experiencing significant adverse effects Reduce dose by 30% if: Patient has adequate pain control on current regimen May consider no dose reduction if: Patient has severely uncontrolled pain on current regimen Changing to another formulation of the same opioid 5. Calculate the TDD of the new opioid that is equivalent to your OME (after accounting for incomplete cross-tolerance) 6. Divide up the newly calculated total daily dose equivalent into a reasonable dosing regimen split throughout the day Keep in mind: Available dosage strengths Dosing frequency for each formulation 7. Ensure adequate breakthrough pain regimen

Patient Controlled Analgesia ( Hospital PCA order)

Dose, Lock out interval, Basal rate Demand dose (mg or mcg): Dose to be delivered with every push of the PCA button In opioid-naïve patients Hydromorphone 0.1-0.2 mg Morphine 0.5-1 mg Fentanyl 5-10 mcg May need to start with higher doses in opioid-experienced patients Typically 50% of basal rate if basal dose is administered Demand lockout time (minutes): Minimum time between demand doses Lockout times based on time to peak effect: --Typically every 8-10 minutes for hydromorphone and morphine --Every 6-8 minutes for fentanyl given shorter duration of action Basal rate (mg/hr or mcg/hr): Continuous infusion -High risk for oversedation and overdose if basal rate started in opioid-naïve patient -Should ONLY be used in patients who are opioid-experienced

Drug Overdoses a National Epidemic The number who die each year from

Drug overdose 52,404 Car Accidents 37,757 Guns 35,763 HIV 6,465

Gate control theory CLOSES gates

Drugs Counterstimulation Increased interest in activities Intense concentration Relaxation Positive emotions (happiness) Rest and isolation

Chronic Pain

Duration > 3 months Organic Cause Not always present Biologic function Often none Psychologic component Very common Common features Sympathetic hyperactivity, anxiety Depression, insomnia, fatigue, anger, social disruption Goals Improve functionality

Acute pain

Duration Usually < 1 month Organic Cause Common Biologic function Warning signal Psychologic component Uncommon Common features Sympathetic hyperactivity, anxiety Goals Curative

Neuropathic pain:

Dysfunction of peripheral or central nervous system No biological function Descriptive terms: Electric, burning, tingling, numbing, shooting

Opioid Withdrawal

Early Withdrawal Symptoms (first 8-24 hours) Lacrimation/rhinorrhea Yawning Restlessness Insomnia Dilated pupils Piloerection Abdominal pain Myalgia Late Withdrawal Symptoms (1-3 days) Tachycardia Hypertension Fever Nausea/anorexia Extreme restlessness Diarrhea Onset: 6-12 hours after last dose of short-acting (can be delayed to 24-48 hrs if LA such as methadone) Can be more immediate if naloxone given to reverse opioid toxicity Peak of Symptoms is: 24-48 hours

Outpatient Naloxone

Emerging public health initiative Can be administered by bystanders Naloxone HCL- nasal spray 2mg/2mL Evzio (Naloxone)- injection Narcan-Nasal spray 4 mg

Fibromyalgia Treatment Options

First-line treatment is mainly non-pharmacologic Cardiovascular exercise (best data) aerobic exercise Cognitive behavioral therapy Treatment of underlying mood and sleep disorders Second-line treatment is pharmacologic therapy Mainly shown to assist with sleep and overall functionality Some benefit with regards to pain scores TCA usually considered first (amitriptyline has best data) Milnacipran, duloxetine, cyclobenzaprine (similar to TCA) use for sedative, and pregabalin alternatives Tramadol is the only opioid recommended for fibromyalgia Guidelines advise avoiding stronger opioids

Tapering Off Opioids

Generally must slow rate of taper as you get to lower daily doses Rapid tapering -Reduce dose by 25% per day until you reach daily dose equivalent to 45-60 mg of oral morphine equivalents, then decrease by 25% every 3-5 days Gradual tapering -Reduce daily dose by 10-25% every 1-4 weeks

Constipation

Goal: Patient should have a well-formed bowel movement at least every 48 hours Patients who take opioids on a regular (daily) basis should receive a bowel regimen, even if not currently constipated Preferred therapy (consider for all patients on opioids) Ensure adequate dietary fiber 35 grams per day Place the patient on a schedule: Stool softener: Docusate (Colace®) 100 mg daily AND a Stimulant laxative: Bisacodyl (Dulcolax®) 10 mg PO daily OR Sennosides (Senokot®) 8.6 mg PO twice daily Can titrate up to 17.2-34.4 mg (2-4 tablets) twice daily if needed Other medications to consider Maintenance Bulk-form laxatives: Psyllium Osmotic laxatives: Polyethylene glycol, lactulose Acute constipation Bisacodyl suppositories Milk of magnesia Magnesium citrate Tx of Refractory constipation Methylnaltrexone (Relistor®) SQ every other day as needed -Peripheral opioid receptor antagonist that does not cross BBB Lubiprostone (Amitiza®) approved for Opioid-induced Constipation in April 2013 -Intestinal chloride channel activator Naloxegol (Movantik®) approved for Opioid-induced Constipation in September 2014 -Pegylated derivative of naloxone with minimal CNS penetration -Watch for drug interactions that could precipitate withdrawal

Chronic pain and Socioeconomic consequences

Health-care costs increase Disability Lost productivity

Who Should Have Naloxone Available?

History of overdose History of substance use disorder Higher opioid dosages (≥50 MME/day) Concurrent benzodiazepine use

Acute Pain Opioid Alternatives

IV (parenteral) Ketorolac Tromethamine Dicyclomine Hydrochloride Ketamine Hydrochloride Metoclopramide Hydrochloride Magnesium Sulfate Lidocaine Hydrocloride PO Tylenol Extra Strength 500 mg Gabapentin 100 mg

Mistake #10- Failure to Taper Off Opioids When Necessary

Immediate discontinuation (without tapering) may be indicated if patient: -Engages in diversion, prescription forgery, or multi-sourcing (prescribers and/or pharmacies) -Has confirmation of illegal drug use -Overdoses/life-threatening adverse effects Rapid tapering (over days-weeks depending on dose) -Non-adherent to pain contract -Moderate-severe adverse effects Gradual tapering (over months depending on dose) -Opioid-induced hyperalgesia occurs -Lack of efficacy or functional goals not met -Persistent adverse effects despite opioid rotation

Chronic Back Pain Treatment

Inflammatory component NSAIDs- Ibuprofen Naproxen Oral glucocorticoids (Caution) Prednisone Medrol Epidural glucocorticoid injections (not recommended) Prednisolone Neuropathic pain component Anticonvulsants Gabapentin Pregablin Antidepressants Amitriptyline Nortriptyline Duloxetine Venlafaxine Muscle spasm component Muscle relaxants 1st Cyclobenzaprine 2nd Tizanidine Generalized pain APAP Acetaminophen Opioids Tramadol Surgical intervention If symptoms debilitating Severe nerve compression- Motor deficits, bladder/bowel incontinence

Gate control theory OPENS gates

Injury Inappropriate physical activity Focusing on pain Boredom Depression Anxiety/worry Tension/anger

What Works for Chronic Pain? Average reduction in pain scores

Intervention Reduction in Pain Scores % (improvement) Exercise/Physical Therapy 30-60% Cognitive Behavioral Therapy 30-50% Sleep restoration 40% Tricyclic antidepressants 30% Opioids Short term: 30% to 50% Long-term: ???? No data Cannabis 10-30%? Acupuncture 10%

Chronic pain and Emotional functioning

Irritable Angry Anxious Depressed

When to Consider Changing Opioids

Lack of therapeutic response 30% of cancer patients don't respond to morphine Development of adverse effects Change in patient status May not be able to tolerate current formulation Difficulties swallowing, decreased body fat, etc. Cost or insurance Stigma "Methadone is only for drug addicts" "Isn't morphine only for people who are dying?"

Opioid Potency

Less Potent Tramadol* Codeine* More Potent Tapentadol* Hydrocodone/APAP* Morphine Oxycodone Hydromorphone Oxymorphone Methadone Fentany *Note that these four agents have maximum daily doses ("ceiling" doses), while the other opioids do not

Opioid Prescriptions for Chronic Pain and Overdose

Less than 50 mg per day = lower rate of overdose 50 mg or above = higher rate of overdose % overdose rate 1-19 mg/day = ~less than 20% 20-49 mg/day = ~25% 50-99% mg/day = ~70% 100+ mg/day = ~180%

Pain Pathway Stimulation affected by - Chemical - Thermal - Mechanical

Local anesthetics - NSAIDs - Capsaicin Stimulation: Keep in mind that nocioceptors are found throughout the body (internal and external)- Chemical, mechanical, thermal- Tendons, muscles, skin, BVs, viscera

120 mg Morphine Equivalents

MS Contin 60 mg BID Oxycodone 80 mg Oxycontin 40 mg BID Sixteen Percocet 5/325 mg or eight Percocet 10/325 mg tabs Oxymorphone 40 mg Opana ER 20 mg BID (off the market) Hydromorphone 30 mg Exalgo 32 mg daily Fentanyl TDS 50 mcg patch

Medications for Opioid Use Disorder (MOUD)Effectiveness

Methadone All-Cause Mortality Hazard Ratio 0.47 95% CI 0.32 - 0.71 Opioid-related Mortality Hazard Ratio 0.41 95% CI 0.24 - 0.70 Buprenorphine All-Cause Mortality Hazard Ratio 0.63 95% CI 0.46 - 0.87 Opioid-related Mortality Hazard Ratio 0.62 95% CI 0.41 - 0.92 Naltrexone All-Cause Mortality Hazard Ratio 1.44 95% CI 0.84 - 2.46 Opioid-related Mortality Hazard Ratio 1.42 95% CI 0.73 - 2.79

Mistake #7 and #8 - Misusing Methadone

Mistakes Starting methadone at an inappropriate dose 2.5 mg every 6 hours generally a safe starting dose TDD starting is 10 mg Titrating too rapidly Wait seven days after a dosing change before considering dose increase Not educating patient Slow onset and slow titration Side effects likely to present before analgesia Risks involved if not used properly Initiation in a non-compliant patient Self-titration or use for breakthrough pain can be DEADLY Not considering cardiovascular risk Mistake #8 Conversion from another opioid to methadone is highly complex- DO NOT MEMORIZE THIS; FYI only Only a rough estimate and very conservative (see picture)

Opioids: Mitigating Risk for Addication and Abuse

More than 40 people die every day from overdoses involving prescription opioids Since 1999, there have been over 165,000 deaths from overdose related to prescription opioids 4.3 million Americans engaged in non-medical use of prescription opioids in the last month 249 million prescriptions for opioid pain medication were written by health providers in 2013 -enough prescriptions were written for every American adult to have a bottle of pills

Chronic Pain Management Goals

Need to be realistic!! Goal 30% reduction in average pain scores AND Improved quality of life Physical, social, and emotional well-being WITHOUT Causing significant adverse drug-related effects OR Stimulating aberrant drug-related behaviors

Who Receives Benefit from Opioids?

No Significant Benefits of Opioid use Long-term (> 90 days) chronic treatment of nocioceptive pain Widespread soft tissue pain Fibromyalgia Migraines or teansion headaches Pain associated with functional gastrointestinal problems Small to Moderate Benefit Short-term (< 90 days) acute treatment of nocioceptive pain Neuropathic pain-Typically non-opioids would be trialed first, however Chronic cancer pain is the only useful for opioid use

World Health organization (WHO) Pain Ladder 1

Nonopioid Acetaminophen NSAIDS (+-) Adjuvant (anticonvulsants, Antidepressants) Gabapentin (anticonvulsant) Pregabalin (anticonvulsant) Amitriptyline, Nortriptyline-Tricyclic Antidepressants Venlafaxine, Duloxetine-SNRI

Chronic Pain Screening Tools

Objective screening tools DIREScore ABC checklist Atluri and Sudarshan Subjective screening tools SOAPP PDUQp PMQ

Street Prices of Opioids (2019)

Opioid Price per pill Short-acting Hydromorphone IR 4 mg $10 Oxymorphone IR 5 mg $75 Oxycodone IR 10 mg $10 Hydrocodone/APAP 10/325 $5 Morphine IR 15 mg $5 Long-acting Fentanyl TDS patch 50 mcg/hr $50 Morphine SR 30 mg $15 Oxycontin® (new formulation) 20 mg $20 Methadone 10 mg $10

Equivalent Dosing

Opioid and Route Equivalent Dose (mg) Hydrocodone PO 30 mg Morphine PO 30 mg Oxycodone PO 20 mg Oxymorphone PO 10 mg Hydromorphone PO 7.5 mg Morphine IV 10 mg Hydromorphone IV 1.5 mg Fentanyl IV 0.1 mg A patient has taken the following medications over the past 24 hours: Oxycodone 10 mg PO x 4 doses Hydromorphone 1 mg IV x 3 doses Morphine 5 mg IV x 1 dose In oral morphine equivalents, what is the total dose of opioid that this patient has received over the past 24 hours? Oxycodone 10 mg x 4 = 40 mg 20 mg oxycodone = 30 mg PO morphine 40 mg oxycodone = 60 mg PO morphine Hydromorphone 1 mg IV x 3 = 3 mg IV 1.5 mg IV hydromorphone = 30 mg PO morphine 3 mg IV hydromorphone = 60 mg PO morphine Morphine 5 mg IV x 1 = 5 mg IV 10 mg IV morphine = 30 mg PO morphine 5 mg IV morphine = 15 mg PO morphine 60 mg + 60 mg + 15 mg = 135 mg oral (inpatient acute use) morphine equivalents

World Health organization (WHO) Pain Ladder 2

Opioid for Mild to Moderate Pain Tramadol Hydrocodone/APAP Codeine/APAP (+-)Nonopioid Acetaminophen NSAIDS (+-) Adjuvant (anticonvulsants, Antidepressants) Gabapentin (anticonvulsant) Pregabalin (anticonvulsant) Amitriptyline, Nortriptyline-Tricyclic Antidepressants Venlafaxine, Duloxetine-SNRI

World Health organization (WHO) Pain Ladder 3

Opioid for Moderate to Severe Pain Morphine Oxycodone Hydromorphone Fentanyl Methadone (+-)Nonopioid Acetaminophen NSAIDS (+-) Adjuvant (anticonvulsants, Antidepressants) Gabapentin (anticonvulsant) Pregabalin (anticonvulsant) Amitriptyline, Nortriptyline-Tricyclic Antidepressants Venlafaxine, Duloxetine-SNRI

Mistake #3 - Mismanaging bowels

Opioid receptors throughout GI tract Opioid agonists: Reduces gastric motility ("slows down") Decrease stool moisture ("dries out") Constipation occurs in 40-95% of patients on opioids Can occur even after a single dose Only adverse effect that the body does not develop tolerance to Likely to remain a problem while patient remains on opioids Usually requires pharmacological intervention

Pain Pathway Modulation affected by

Opioids - Anticonvulsants - Serotonin/norepinephrine reuptake inhibitors - NMDA Antagonists - APAP - Alpha-2 agonists Modulation: Endogenous and exogenous substances amplify or inhibit the signals along the ascending or descending pathways

Cancer-Related Pain: Treatment

Opioids are first-line for moderate-severe pain related to cancer High-doses are often required (3)Morphine (3)Oxycodone (3)Hydrocodone (3)Hydromorphone (3)Oxymorphone (3)Fentanyl (3)Methadone (caution QTC) (2)Codeine (2)Tramadol (2) Tapentadol (2) Buprenorphine (opioid naive or limited use) Adjuvants often utilized also Inflammation: NSAIDs or glucocorticoids (prednisone or prednisolone or methylprednisolone) Nerve compression: Glucocorticoids Bone pain: NSAIDs, bisphosphonates (Oral clodronate, intravenous (i.v.) pamidronate, and i.v. zoledronic acid), glucocorticoids Bowel obstruction: Anticholinergics (hyoscine butyl bromide or scopolamine), octreotide (mimics natural somatostatin) Neuropathic pain: Anticonvulsants (Gabapentin Pregabalin) antidepressants(Amitriptyline, Nortriptyline, Duloxetine, Venlafaxine) Mucositis: Topical lidocaine (5%) (4% OTC)

Opioid Coversions from 81 step 2

Oxycodone ER 40 mg BID = 40 x 2 = 80 mg/day Oxycodone IR eight 5 mg tabs = 8 x 5 = 40 mg TDD = 80 mg + 40 mg = 120 mg Oxycodone 20 mg = 30 mg oral morphine 120 = X 20 30 120 x 30 = 20X X= 3600/20 X = 180 mg oral morphine equivalents (OME) = 120 mg oral oxycodone 180 ME/30 mg M = 6 x 20 mg oxycodone = 120 mg Opioid and Route Equivalent Dose Hydrocodone PO 30 mg Morphine PO 30 mg Oxycodone PO 20 mg Oxymorphone PO 10 mg Hydromorphone PO 7.5 mg Morphine IV 10 mg Hydromorphone IV 1.5 mg Fentanyl IV 0.1 mg

Amitriptyline Tricyclic Antidepressants

PO Dosing Off-Label Uses. -Chronic pain: 25-100 mg po daily hs; titrate to max 150 mg/d -Polyneuropathy, postherpetic neuralgia, treatment and prophylaxis: 10-25 mg po daily hs; may titrate to max 200 mg/d Common (>10%) Sedation Less Common (1-10%) Blurred vision, confusion, constipation, dizziness, sexual dysfunction, somnolence, urinary retention, weight gain, xerostomia Rare but Serious (<1%) Cardiac dysrhythmia, hepatotoxicity, seizures, suicidal thoughts

Nortriptyline Tricyclic Antidepressants

PO Dosing Off-Label Uses. -Chronic pain: Adults, 10-25 mg once daily at bedtime -Diabetic neuropathy: 10-25 mg po daily, may titrate to 100 mg po daily Common (>10%) Constipation Less Common (1-10%) Blurred vision, confusion, dizziness, headache, sexual dysfunction, somnolence, urinary retention, weight gain, xerostomia Rare but Serious (<1%) Cardiac dysrhythmia, heart block, hepatotoxicity, seizures, suicidal thoughts

Assessing Abuse Risk Low Risk

Pain Definable physical pathology with objective signs and symptoms and clinical correlation with diagnostic testing Psychological disorders Mild or absent Personal or family history of substance/alcohol abuse None Age > 45 yo Pain coping and tolerance Good Motivation Willingness to participate in multimodal therapies

Assessing Abuse Risk Medium Risk

Pain Similar to low-risk, but moderate if significant pain or involvement of >3 regions of the body Psychological disorders Moderate, but well controlled Personal or family history of substance/alcohol abuse None or past history (includes nicotine dependency) Age >45 yo Pain coping and tolerance Moderate Motivation Willingness to participate in multimodal therapies Other qualities Concomitant comorbidities

Assessing Abuse Risk High Risk

Pain Widespread (> 3 areas) without objective signs and symptoms Psychological disorders Severe or uncontrolled Personal or family history of substance/alcohol abuse Active abuse(includes nicotine dependency) Age < 45 yo Pain coping and tolerance Poor Motivation Unwilling to participate in multimodal therapies Other qualities History of aberrant drug-related behaviors

Cancer-Related Pain

Pain can be... Directly related to cancer Bone pain Soft tissue pain Obstructive Bowel Nerves Drug-induced Mucositis Neuropathic Radiation-induced Iatrogenic

Pain Assessment Tools (Scale questions)

Pain intensity and interference 1. In the last month, on average, how would you rate your pain? 0=no pain and 10= pain is as bad as could be (usual pain at times you were in pain) 2. In the last month, how much pain interfered with your daily activities? 0=no interference and 10= unable to care on any activities Question 2 and the face Zap face scale are better than question 1- Vandiver

Gate control theory of pain

Pain is controlled by "gates" in our nervous system Activation of nerves that do not transmit pain signals can interfere with signals from pain fibers and inhibit perception of pain Medications and lifestyle activities to open and close these gates

Mistake #1 - Choosing the wrong opioid

Pain severity: Would not use highly potent opioid unless pain is severe Acute vs. chronic pain: Would not use long-acting formulations for acute pain Maintenance vs. breakthrough dosing: Rapid acting product needed for breakthrough pain Route availability: Is patient able to take oral tablets? Do they have IV access? Substance abuse history: Avoid oxycodone and hydromorphone if high risk for abuse Renal or hepatic dysfunction: Avoid morphine if severe renal dysfunction, methadone if severe hepatic dysfunction. Fentanyl safe in both conditions Cost: MS Contin and methadone least expensive long-acting opioids

Causes of Neuropathic Pain

Painful Diabetic Peripheral Neuropathy (PDPN) Postherpetic Neuralgia (PHN) Radiculopathy Complex Regional Pain Syndrome Phantom Limb Drug-induced HIV-induced Post-stroke Spinal cord/nerve trauma

Patient Selection

Relative contraindications to opioids Respiratory instability at baseline Acute psychiatric instability or suicidal risk History of substance or alcohol abuse History of controlled substance diversion Concomitant use of CNS depressants (benzodiazepines in particular)

Signs of Opioid Overdose

Respiratory depression Miosis Stupor Hepatic Injury from acetaminophen or hypoxemia Myoglobinuric renal failure Rhabdomyolysis Absent of hypoactive bowel souds Compartment Syndrome Hypothermia Possibly presence of one or more fentanyl patches

Mistake #9: Opioid Use in Pregnancy

Risks Neonatal abstinence syndrome -Neurologic, autonomic, and gastrointestinal disturbances Increased prematurity, reduced birth weight and growth parameters Increased risk for birth defects Sudden withdrawal of opioids can result in fetal distress and demise Opioid-dependent women who become pregnant are generally referred to specialist for transition to methadone (buprenorphine an emerging alternative) -Especially if opiate being used is heroin

Management of Adverse Effects

Short-term (first 7-14 days) -Counseling -Avoid other medications with sedating effects -Avoid driving or operating heavy machinery Medications -Antiemetics if nausea/vomiting -Histamine blockers if severe itching -Treatment may worsen sedation, however Monitoring -Repiratory status (pulse ox, resp. rate) -Urinary output -Blood pressure Long-term monitoring -Signs of addiction, abuse, or aberrant behaviors -Sexual dysfunction -Hormone levels

Pain Agreements

Should be considered for all patients receiving chronic opioid therapy Purpose Provide informed consent Foster adherence to treatment program Limit the potential for opioid abuse Improve efficiency of the pain treatment program Common components: Benefits and risks Provider expectations of patient Patient expectations of therapy -Realistic pain goals -When opioids will be stopped

Urine Drug Screening

Should be performed on all patients on chronic opioids at least annually -Quarterly if high risk patient Goal: Identify polysubstance abuse T-HC, benzodiazepines, amphetamines, barbiturates, cocaine, opioids Identify possible diversion Caution! Most standard immunoassays do not detect semisynthetic or synthetic opioids (or their metabolites) -If opioid other than morphine or codeine --Need to order confirmatory gas chromatography

Chronic pain effects on Functional Activities

Sleep disturbances More difficult Work, household chores Less pleasure Leisure activities Less Energy

Neuropathic Pain Treatment

Start with a single agent (one of the 4 talked about) Anticonvulsant or antidepressant Allow for an adequate trial 4 weeks at goal dose Pain relief may take days-weeks after reaching goal dose Side effects may occur prior to pain relief May need to add a second agent after an adequate trial Opioids generally only after other options trialed Continue the agent only if: >30% pain relief Improved functionality Tolerable adverse effects- do not want intolerable effects

Prescription Drug Monitoring Programs (PDMPs)

State-wide electronic database History of all controlled substances filled in the state Fill date, medication, strength, quantity, prescriber, payment method, and pharmacy 49 of 50 states have active state-wide PDMP Should be assessed every time a patient is initiated on an opioid and periodically with long-term use (at least every 3 months) Any licensed prescriber or pharmacist in the state can gain access Aids in detection of opioid abuse and misuse Caveats Many PDMPs are not linked state-to-state VA and mail-order prescriptions may not show up on PDMP

Nocioceptive pain:

Stimulation of peripheral pain receptors Somatic- Musculoskeletal Visceral- Internal (abdominal pain) Has a biological function Warns of impending tissue damage Descriptive terms: Sharp, dull, stabbing, throbbing, aching

Chronic pain and Social Consequences

Strain on Marital and family relegations Intimacy issues Social Isolation

Muscle Relaxants- Antispasticity/antispasmodic combo agents

Tizanidine Pros Fast-acting, some analgesia Cons Hypotension Diazepam Pros Fast-acting, anxiolytic Cons Abuse potential, sedation

Understanding addiction

Tolerance -Physiologic phenomenon Tolerance to: -Analgesia: Days to weeks -Adverse effects (except constipation): > 7 days Dependence -Physiologic phenomenon --Withdrawal symptoms present if drug is abruptly withdrawn Nearly universal among patients receiving repeated doses of opioids for > 7-10 days Addiction (opioid use disorder) -Psychologic phenomenon --Compulsive need to use a medication despite known harms

Opioid Risk Tool

Total Score Risk Category Low risk = 0-3 Moderate risk = 4-7 High risk = > or = to 8 Family Hx of Substance Abuse Alcohol Female (1) Male (3) Illegal Drugs Female (2) Male (3) Prescription Drugs Female (4) Male (4) Personal Hx of Substance Abuse Alcohol Female (3) Male (3) Illegal Drugs Female (4) Male (4) Prescription Drugs Female (5) Male (5) Age (16-45) Female (1) Male (1) History of Preadolescent Sexual Abuse Female (3) Male (0) Psychological Disease Female (2) Male (2) ADD OCD Bipolar Schizophenia Depression Female (1) Male (1)

Mistake #2 - Ineffective or unsafe Initiation and titration

Typical starting doses in opioid-naïve patients Hydrocodone/APAP Oral 5/325 mg - 10/650 mg every 6 hrs as needed Morphine IV 2-4 mg every 4 hrs as needed Oxycodone Immediate-release 5-10 mg every 6 hrs as needed Hydromorphone Oral 2-4 mg every 6 hrs as needed IV 0.4-0.8 mg every 4 hrs as needed Breakthrough dosing in opioid-experienced patients may need to be: Much higher doses (typically 10% of total daily dose) Given more frequently Every 2-3 hours if IV Every 3-4 hours if oral

Methadone for Opioid Addiction

Typically only dispensed from state-licensed outpatient treatment programs Usually under heavy supervision -Patient comes to treatment facility and observed taking their daily dose of methadone (liquid formulation) -Patient only allowed 1-2 "take-home" doses per week for days that the clinic is closed Initial dose should generally not exceed 30 mg once daily -Some patients require 200 mg+ per day

Chronic Pain High Risk

Urine Drug Screen- every 3-6 months Pain Management Profile- Four a year (every 3 months) +Avoid Opioids or use very low doses (10 mg Morphine equivalent dose +Avoid dose escalations +Use > 50 mg Morphine equivalent dose RARELY +Patients displaying aberrant behaviors should be weaned off opiods

Buprenorphine/Naloxone for Opioid Addiction (Suboxone®, Zubsolv®, Bunavail®)

Used by addiction specialists only Must have special training and "X" DEA number to prescribe Special training is 8 or more hours of live or online DATA-approved training Licensed to treat either 30, 100, or 275 patients at a time in a usual office environment Buprenorphine: Lower potential for abuse than pure opioid agonists due to ceiling effect Naloxone added as abuse deterrant- No effect if taken orally or sublingually, but blocks opioid effects if injected Available as sublingual tablet or sublingual orally dissolving film Zubsolv 5.7 mg/1.4 mg tablet Suboxone 8 mg/2 mg tablet Suboxone film 8mg/2mg film Initiated once patient starts to exhibit withdrawal symptoms (at least 6 hrs after last dose) Initiated day 1 in clinic under supervision by prescriber Patient stabilized on once daily dose that can be prescribed as an outpatient Small supplies should be provided without refills

Chronic Back Pain 2

Vertebrae are bones that protect the spinal cord. Forced or locked out of proper position (misaligned) Ligaments and Muscles supportive issues that can be stretched, torn or weakened. Discs are shock absorbers that bulge, rupture or wear down Nerves which carry the bodies messages can get stretched, pinched or irritated

Chronic Back Pain 1

Very common 84% of all adults will have low back pain during their lives Causes Degenerative disc or facet disease Sponylolisthesis "Slipped" disc Herniated disc Spinal stenosis Sciatica- non-steroidal anti-inflamatory Fracture Muscle strain

Upward Titration

WHO titration guidelines: If patient's pain is still: Mild-moderate Increase total daily dose (TDD) by 25-50% Severe Increase TDD by 50-100% Alternatively, can increase the TDD by the same dose of breakthrough opioid required in the prior 24 hours TDD increases of less than 20% unlikely to be effective How quickly should you titrate? Short-acting agents for acute pain Can escalate doses rapidly if patient not responding well Ensure that usual time to peak effect has passed 15-30 minutes for IV, 60-90 minutes for oral Long-acting agents for chronic pain Should generally achieve steady-state at new dose before titrating further Particularly important with fentanyl patches and methadone

Patient Case

We want to switch our patient to MS Contin® because he can no longer afford Oxycontin® Our patient is switching to a different agent, but has adequate pain relief with his current regimen Incomplete cross-tolerance consideration Decrease anticipated OME dose by 30% 180 mg OME x 0.7 (70%) = 126 mg 126 mg OME Do not need any further conversion since we are switching to morphine If switching to any other opioid would need to refer back to equianalgesic chart MS Contin generally dosed every 8-12 hours If BID dosing- 126 mg / 2 = 63 mg BID MS Contin comes as 15, 30, 60, 100, and 200 mg tabs New MS Contin dose: 60 mg BID

National & State Initiatives

White House Response CDC Resources Wyoming Rx Abuse Stakeholders Colorado Consortium for Prescription Drug Abuse Prevention

Naloxone in Overdose Situations

¢Administered IM or IV in acute care settings Support respiration with bag-valve mask before administering Naloxone Initial adult dose = 0.04 mg Initial pediatric dose = 0.1 mg/kg of body weight If an increase in respiratory rate does not occur in 2-3 minutes Administer 0.5 mg of Naloxone If no response in 2-3 minutes Administer 2 mg of naloxone If no response in 2-3 minutes Administer 4 mg of naloxone If no response in 2-3 minutes Administer 10 mg of naloxone If no response in 2-3 minutes Administer 15 mg of naloxone