CLICK TO EDIT MASTER TITLE STYLETHE PAST, PRESENT, AND
FUTURE OF OPIATES
email: [email protected]
Leonard Rappa, PharmD, BCPPBoard Certified Psychiatric Pharmacy Specialist
Professor, Florida A&M UniversityCollege of Pharmacy and Pharmaceutical Sciences
Broward Health Imperial Point, Ft. Lauderdale, Florida
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Recognize signs and symptoms of a drug use disorderUnderstand the severity of opiate addiction and abuse in AmericaAssess the risks of co-prescribing certain medications with opiatesEvaluate prescribing patterns and overdoses specific to FloridaComprehend the significance of opium and its derivatives to
mankindBe able to identify situations in which an opiate blocker should be
recommended or usedIdentify medications used for detoxification and post-detox
Medication Assisted Therapy
OBJECTIVES
CLICK TO EDIT MASTER TITLE STYLEEFFECTS ON SOCIETY#1 national health problem
$80 billion a year in “economic burden” from opioid epidemic in the past
US lifespan is decreasingMore deaths, illness, accidents, disabilities than any other health problemDeath from prescription drug overdoses has replaced car accidents as the leading
cause in adults under 50
DAWN (Drug Abuse Warning Network)http://www.samhsa.gov/data
Opiate addiction & abuse directly correlates with higher doses and longer duration of use
National Center for Health Statistics and National Safety Council
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From the National Institutes of Health (NIH.gov),Centers for Disease Control (CDC.gov), the Substance Abuse and Mental Heath Services Administration (SAMHSA.gov), and the National Institutes of Drug Abuse (DrugAbuse.gov)
$115 billion economic burden to the US in 2017
Cost of treatment reduces overall societal costs
Opiate Use Disorder is a medical disease that is not easily fixed!!!
WHAT DO WE KNOW ABOUT THE OPIOID CRISIS?
CLICK TO EDIT MASTER TITLE STYLEDSM 5 Diagnostic Criteria
OPIOID USE DISORDER (OUD)
Pattern of opioid use leading to significant impairment or distress within a 12-month period: Taking in larger amounts or over a longer period than was intended Desire or unsuccessful efforts to cut down or control use Spending a lot of time to get, use, or recover from use Craving, or a strong desire or urge to use opioids Failure to fulfill major role obligations at work, school, or home Continuing to use despite persistent or recurrent social or interpersonal problems Important social, occupational, or recreational activities are given up or reduced Use in situations that are physically hazardous Continued use regardless of worsened physical or psychological problems Increased tolerance, so need to use more opiate for same effect Opioids are used to relieve or avoid withdrawal symptoms
CLICK TO EDIT MASTER TITLE STYLEGENETICS & SUBSTANCE ABUSE
Genetic traits found – can predispose or protectThousands of genes with some key pathways identifiedhttp://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.0040002
Gene variabilities in drug metabolism
Gene expression and opiate receptor availability
Other common elements:Environmental trauma and stressors contributeHigh mental health comorbidityHigher rates of Antisocial Personality Disorder
CLICK TO EDIT MASTER TITLE STYLETHREE BRAIN REGIONSNucleus Accumbens (NA) Anterior in the mesolimbic systemMediates the positive reward
behaviors
Amygdala (striatum) Mediates the negative or
fear-motivated behaviors
Prefrontal cortex (PFC) Involved in decision making by
assigning stimuli to direct behavioral response
Nat Neurosci 2006;9(11): 1440 – 1441.U.S. Department of Health and Human Services (HHS), Office of the Surgeon General, Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC: HHS, November 2016.
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i ABOUT OPIATES
8
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OPIATE or OPIOID
Resins extracted from seed pod of poppy plantsDrugs derived from the opium poppy
Natural endorphins
Any of several synthetic compoundshaving effects similar to natural opium alkaloids and their derivativesHaving agonist effects at the opioid receptors in the body
WHAT IS AN OPIATE?
CLICK TO EDIT MASTER TITLE STYLEOPIATE RECEPTOR EFFECTS
10
Mu1 (μ1) Analgesia, euphoria
Mu2 (μ2) Constipation, respiratory depression
Kappa()
Supraspinal & spinal analgesia, dysphoria, hallucinations
Delta (,)
Psychotomimetic effects, slowed GI transitAnalgesia through the endorphin, enkephalin, and dynorphin system
CLICK TO EDIT MASTER TITLE STYLEPRESCRIPTION OPIATE CLASSESSchedule I (illegal) II, III, IV, and V
NaturalCodeine (various) (CIII and CV)Morphine (MSContin, Kadian, others) (CII)
SyntheticButorphanol (Stadol®) (CIV)Fentanyl (Actiq®/Duragesic®) (CII)Meperidine (Demerol®) (CII)Methadone (Dolophine®) (CII)Pentazocine (Talwin®) (CIV)Tapentadol (Nucynta/ER) (CII)Tramadol (Ultram/ER) (CIV)
Italics indicate the drug is a mixed agonist/antagonist
CLICK TO EDIT MASTER TITLE STYLEPRESCRIPTION OPIATE CLASSESSchedule I (illegal) II, III, IV, and V
Semi-syntheticBuprenorphine (Suboxone, Subutex®, Butrans®) (CII)Diacetylmorphine (Heroin) (CI - illegal)Hydromorphone (Dilaudid®) (CII)Hydrocodone(Hycodan® / various) (CII)Nalbuphine (Nubain®) (not controlled)Oxycodone (Percodan®, Percocet, Oxycontin) (CII)Oxymorphone (Opana, Numorphan) (CII)
Italics indicate the drug is a mixed agonist/antagonist
CLICK TO EDIT MASTER TITLE STYLEAbuseMisuse or excessive use of anything0.6-8% who receive Rx opiates abuse them35 million have used opioids non-medically
AddictionA chronic brain diseaseHabitual psychological and physiological dependence on a
substance or practice Not using as planned / out of voluntary control
PseudoaddictionIncreased pain forces patient to seek increased doses
DEFINITIONS
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Psychological dependenceDrug craving and drug-seeking behaviors5.7-37.1% show drug-seeking behaviors
Physical dependenceA biological adaptation at the cellular levelResult is tolerance – need more drug to get same result3.1-25% become physically dependent
WithdrawalA syndrome caused by the abrupt cessation of the use of a drug in an
habituated individualWithdrawal effects seen if stoppedPatient appears “drug-seeking” but is not doing it for pleasure
DEFINITIONS
CLICK TO EDIT MASTER TITLE STYLE2017 NATIONAL SURVEY ON DRUG USE AND HEALTH (NSDUH)% OF US POPULATION DRUG BEING MISUSED NOTES
10.6* Any illicit drug Use is significantly increasing8.9* Marijuana Use is significantly increasing1.4 Prescription opiates0.9 Sedatives / tranquilizers0.7 Cocaine Use is increasing in Florida0.6 Stimulants0.5 Hallucinogens
0.2* Methamphetamine Use is significantly decreasing0.2 Inhalants0.2 Heroin Use is increasing
* Indicates a statistically significant change from last year
(Past year use in > 12 y.o) from www.samhsa.gov
CLICK TO EDIT MASTER TITLE STYLECENTRAL CONCEPTS
Mechanism of addiction can be physical, psychological, or both
Abuse liability of a drug may be related to its potency & half-lifeGreater potency = more concentrated effectsDrugs with shorter half-lives wear off quicker and trigger a desire for re-
dosing with the drug
Routes of abuseOral, intravenous, rectal, vaginal, nasal, ophthalmic, and topical
CLICK TO EDIT MASTER TITLE STYLEUSA consumes 30-80% of the world’s opiates Americans consumed 99% of the world’s hydrocodone in 2014#1 dispensed drug in 20144.4% of the world’s population
80% of opiate Rx’s are from 20% of prescribers65% of prescriptions are for acute treatment3-4% are for chronic therapy
DEA has lowered annual production quotas for opiates by 35-46% N Engl J Med 2016;374:1253-63. Pain Physician. 2009 May-Jun 12(3):507-15.Clin J Pain 2014;30:557–564. Pain Physician. (2010). 13, 401-435.International Narcotics Control Board
A PILL FOR EVERY ILL
CLICK TO EDIT MASTER TITLE STYLEPAIN AND ADDICTIONPain and addiction are interrelatedOver 2 million Americans live with addiction to opioids 11-15% of Americans live with daily chronic pain43% of Americans have frequent minor pains
Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999–2016. NCHS Data Brief, no 294. Hyattsville, MD: National Center for Health Statistics. 2017/ CDC. Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: CDC, National Center for Health Statistics; 2016. Available at http://wonder.cdc.gov
Center for Behavioral Health Statistics and Quality. (2017). 2016 National Survey on Drug Use and Health: Detailed Tables. Substance Abuse and Mental Health Services Administration, Rockville, MD.
Nahin RL. Estimates of pain prevalence and severity in adults: United States, 2012. Journal of Pain. 2015;16(8):769-780. GLOBAL COMMISSION ON DRUG POLICY: Drug Control’s Negative Impact on Public Health: The Global Crisis of Avoidable Pain. August 2015.
www.globalcommissionondrugs.org Dowell D, Haegerich T, Chou R, et al. MMWR Recomm Rep 2016;65(1):1-49
NIH website: https://www.nih.govIncident Opioid Use Disorder – 0.7%-16.3%75% of the world has little to no access to opiatesNoble, M et al. Long-term opioid therapy for chronic non-cancer pain: a systematic review and meta-analysis of efficacy and safety, Journal of Pain and Symptom Management 2008;35(2):214–228.
CLICK TO EDIT MASTER TITLE STYLERX PILLS
650,000 prescriptions for opiates dispensed daily
70% of abused Rx’s come from a relative or friend’s RxRx abuse accounts for 25%-30% of all drug abuse May be leftover from unused Rx, sold, or stolenFPDMP - https://flpdm-ph.hidinc.com/fllogappl/bdflpdmqlog/pmqhome.html
Opiate quantities peaked in 2010 at 782 MME* per capita
CLICK TO EDIT MASTER TITLE STYLERX PILLS
Opiate prescriptions peaked in 2012 with 255 mil. Rx’s 83 per every 100 people
21-29% prescribed opioids for chronic pain misuse them 8-12% develop an opioid use disorder
4-6% of prescription opiate abusers transition to heroin
75-80% of today’s heroin abusers began with prescription opiate abuse (NIDA)
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Opioid overdoses are 5 x higher than in 1999
2016 - 42,000 Americans died of opioid overdose
Overdoses increased 30% from July 2016 to Sept. 2017 In 52 areas in 45 statesMidwestern saw opioid overdoses increase 70%Opioid overdoses in large cities increase by 54% in 16 states
OVERDOSES
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CLICK TO EDIT MASTER TITLE STYLE½ of opioid-related deaths involve benzosUS Department of Health and Human Services, Centers for Disease Control
and Prevention, National Center for Health Statistics Risk is 5x greater in first 90 days of a new prescription
17-29% of patients co-prescribed a benzodiazepine 80% from 2001-2013Black Box Warning issued against combination
1 in 5 opioid users also may abuse gabapentinGabapentin use risk of overdose death by 50%Gabapentin was 10th most prescribed drug in 2016https://www.aacc.org/media/press-release-archive/2016/august/study-finds-one-in-five-pain-or-rehab-patients-taking-the-medication-gabapentin-without-prescription. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm518710.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery 8/31/16 BMJ 2017;356:j760 http://dx.doi.org/10.1136/bmj.j760JAMA Network Open 2018;1(2):e180919. doi:10.1001/jamanetworkopen.2018.0919
RISKY CO-PRESCRIBING
CLICK TO EDIT MASTER TITLE STYLEFLORIDA OPIATE STATISTICS
Floridians are 6.4% of US population
At least 16 overdose deaths a day
Opiate-related deaths have 35% from 2015 to 2016*Majority in Manatee CountyBroward & Palm Beach counties have highest # of overdose
deaths from any drug
*According to the FDLE
CLICK TO EDIT MASTER TITLE STYLEFLORIDA PRESCRIBING
2013 – 13.6 million Rxs in FL for opiates70 Rxs for every 100 peopleUS average was 79 Rxs for every 100 people
From 2013 to 2015 – Rxs by 7.3%2015: 63 Rxs for every 100 people
Neonatal Abstinence Syndrome (NAS)6.3 per 1000 in FL vs. 6 per 1000 nationally
CLICK TO EDIT MASTER TITLE STYLEFLORIDA OPIATE STATISTICS
2015 - 670.9 morphine mg equivalents (MME) prescribed per capitaNational average is 642.1 MME
2018 – 549 facilities for substance abuse servicesNational total is 12,284
In FL, 5.3% of drug treatment paid by Medicaid24.2% nationally
CLICK TO EDIT MASTER TITLE STYLEFLORIDA OPIATE STATISTICS
2014 – up to 98% of those in FL needing Addiction Treatment are not receiving it
Syringe Exchange ProgramsOnly 2 in Florida (Miami-Dade county)Not legally permitted in this state
310 nationally
*According to the FDLE
CLICK TO EDIT MASTER TITLE STYLEFLORIDA OPIATE STATISTICSIn 2016 - Opioids were present and/or
cause of death in 5,725 cases22.9 deaths per 100,000
National average is 9.7 deaths per 100,000
2798 pure opiateoverdose deaths14.4 / 100,000National average is
13.3 / 100,000
https://www.drugabuse.gov/drugs-abuse/opioids/opioid-summaries-by-state/florida-opioid-summary
CLICK TO EDIT MASTER TITLE STYLEFLORIDA DEATHS AND TREATMENT FACILITIES
29amfAR Opioid & Health Indicators database http://opioid.amfar.org/FL
Drug-related deaths in FL Facilities that provide MAT
CLICK TO EDIT MASTER TITLE STYLEHIV IN FLORIDA11% of Americans with HIV live in FL
Florida has highest rate of newly diagnosed HIV28 per 100,000 vs. 14.7 nationally (2016) – 90% higher
2015 – 8% of newly diagnosed HIV in FL was from IDU (intravenous drug use)9.1% nationally
2014 – 18.1% of ALL American HIV cases from IDUFlorida was approx. 13%
NIDA (www.drugabuse.gov)
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HISTORY OF OPIATE ADDICTION
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CLICK TO EDIT MASTER TITLE STYLEOPIUM POPPY
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Used around the world for over 5000 years The most important medicine to some societiesAncient Sumerians called it the “joy plant”Rituals, pain, and pleasure
Ancient Minoans (2600-1100 BC) detailed a method for extracting the latex out of the poppy
Ancient Greeks called this latex “opium”
OPIUM‘S BEGINNINGS
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15th Century Brought to China by The British East India Co.
Laudanum – Early 1500s Paracelsus – Swiss-German AlchemistDerived from the Latin verb laudare, to praise10% Tincture of opium (≈ 1% morphine) + EtOHDifferent recipes mixed it with crushed pearls, musk,
amber, saffron, castor, ambergris, mercury, hashish, cayenne pepper, ether, chloroform, belladonna, whiskey, wine, brandy and nutmeg
OPIUM‘S BEGINNINGS
CLICK TO EDIT MASTER TITLE STYLE16th CenturyBrought to America with the pilgrims
17th CenturyThomas Jefferson used it to treat
chronic diarrheaGrew poppies on his estate He remarked that his use was “habitual”
Addiction later recognized when mixed with tobacco
1500 AND 1600’s
CLICK TO EDIT MASTER TITLE STYLE1805 – Morphine isolated from the poppy
by Friedrich Sertürner Named after Greek god of dreams, MorpheusOpium latex ≈ 12% morphineWife later overdosedMerck began marketing it commercially in 1827
1856 - Hypodermic needle inventedGave quick high
Easy to get from catalogs and magazinesHigh rates of addiction after the Civil War (1861-1865)
Exact statistics are unknown
19th CENTURY
CLICK TO EDIT MASTER TITLE STYLE19th CENTURY (cont.)1874 – diacetyl-morphine processed
from morphine by English chemistCharles R.A. Wright
1876 – Opium Dens outlawed in China Town (San Francisco)Fear that Chinese men lured white
women into debauchery
1888 – 15% of Rx’s in Boston were opiates
https://www.forbes.com/sites/carmendrahl/2017/06/12/five-things-heroins-curious-chemistry-history/#4e978528157c
CLICK TO EDIT MASTER TITLE STYLE1890s - Opium imports peaked
Used in most households for coughing, diarrhea, and painMrs. Winslow’s Soothing Syrup
For “fussy” children
In many other “patent” medications
Regulations and laws restricting use were non-existentNo quality control
LATE 19th CENTURY
CLICK TO EDIT MASTER TITLE STYLEBy 1895, 1 in 200 Americans addicted to opiates Mostly by upper to middle class white women
1898 – Bayer’s “less addictive” cough suppressantFor “consumption” and pneumoniaHeroin name means “strong” in German and also refers
to an ancient heroic Greek demigodBayer aggressively marketed it
Producing approximately one ton of heroin annuallyExported heroin to 23 countries within one year“Tolerance” discovered by physicians in 1899
Sears & Roebuck Catalog$1.50 -- 2 vials of heroin + 2 syringes
Aspirin developed by Bayer one year later
LATE 19th CENTURY (cont.)
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By 1905 ≈ 25% males in China were addicted1913 – more heroin addicts than morphine1914 – Harrison Narcotic Tax ActHeroin outlawed Passed because of xenophobiaApocalyptic warnings about various ethnic groups
committing unspeakable acts of murder and mayhemEspecially “seducing” honest white women
EARLY 20th CENTURY
CLICK TO EDIT MASTER TITLE STYLEEARLY 20th CENTURY“Addiction is a moral failing”Government tax stamps needed to
dispense it10,000 doctors arrested in 1st five
yearsStamps were never created or used
1924 – heroin production banned/outlawed
1925 - League of Nations banned nonmedical use of opiates
CLICK TO EDIT MASTER TITLE STYLE1960s – recreational use by the counterculture
and Vietnam VetsSurveys found that 20% of soldiers in Vietnam self-identified as an addict
Janis Joplin overdosed on heroin in 1970 at age 271970s – More xenophobiaHeroin increased crime in inner citiesNixon increased drug laws
1973 –Drug Enforcement Administration (DEA) created
1980 – Article in reported that addiction is rare in treatment of chronic pain
1995 – Oxycontin® heavily marketed Purdue later sued by gov’t in 2007
LATTER 20TH CENTURY
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ILLICIT OPIATES
CLICK TO EDIT MASTER TITLE STYLE“Stepped on”, “scrambled”, or “cut”Diluent is added to a drug to increase volumeDecreases potency to increase profit
Most commonly is lactuloseCan be powdered sugar, corn starch, flour, powdered milk, strychnine,
veterinarian drugs, melamine, anthrax, ground drywall, vitamin C, caffeine, talc, baby formula, nicotinamide (Vit. B3), lidocaine, mannitol, sodium bicarbonateXylazine to cut heroin
A veterinarian-used analog of clonidine (horse tranquilizer)Abused by itself in Puerto Rico
Spiked with other drugs (to mimic or add to the effect)Especially fentanyl 44
DRUG LINGO
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“Nod”Nodding off after injecting heroin
“Chasing the dragon”Trying to achieve the first high ever feltWhen a person melts a drug on tinfoil and then inhales the moving smoke
“Junkie”In New York in the 1920sMorphine & heroin addicts made their livings from salvaging scrap metals
from local junk heaps 45
DRUG LINGO (cont.)
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Diacetyl-morphine is processed from morphine2-4 x more potent than morphine
Most abused and the rapidly acting of the illicit opiatesBlack Tar Heroin (“Brown”/“Muck”)Incomplete acetylation of morphine
Low purity (~30%) brownish heroin
75% of world’s heroin supply originates in Afghanistan
HEROIN (DIAMORPHINE)
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CLICK TO EDIT MASTER TITLE STYLEMexican drug cartels smuggle it to U.S.Dramatic rise in use in last 5+ yearsSince 9/1/11 with PDMP in FLMany former hydrocodone & oxycodone users
HIGH RISK of overdose or deathFirst time use or long-term usersDrug dealers may spike their drugs
with fentanyl or other narcotics toincrease demand and $$An overdose (O.D.) increases demand because it’s considered more
potent
HEROIN
CLICK TO EDIT MASTER TITLE STYLEMade in labs in China & MexicoFentanyl, Sufentanyl, Acetylfentanyl,
Carfentanil, U-47700, W-18Schedule I substances5 to 10,000 x more potent than morphineFentanyl is 80-100 x more potent than morphineDanger: transdermal contact can be fatal!
Used IV or snorted, and can be disguised as, or laced with, heroinSold as “fake Xanax” pills
High risk of respiratory depressionOverdoses can be treated with large & repeated doses of naloxone
(Narcan®/Evzio®)
SYNTHETIC OPIATES
CLICK TO EDIT MASTER TITLE STYLE2010 - Opiate prescriptions peaked 782 Morphine Mg Equivalents (MME) dispensed per capita
2012 - 5% of population > 12 y.o. misused an opiateOperation “Pilluted” – 280 people arrested (5/20/2015)Closed most of Broward County’s pill mills
2016 - 5 billion oxycodone tablets dispensed 116 out of 186 (66%) total fatal overdoses
involve opioidsMANY from illicit fentanylIncrease of 97% from 2015
EARLY 21st CENTURY
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MANAGEMENT OF OVERDOSES
CLICK TO EDIT MASTER TITLE STYLENALOXONE (NARCAN/EVZIO)Available without an Rx in Florida
and most states
Not orally active (IV/IM/SQ/intranasal only)
Binds competitively to opioid receptorsDoes not produce analgesiaUsed to reverse toxic effects of agonist
and agonist–antagonist opioids
Injection Dose: 0.4 to 2mg - can repeat every 2-3 minMay need to repeat doses later (20-60 minutes) Short t1/2 (1.5 hrs)
CLICK TO EDIT MASTER TITLE STYLENALOXONE (NARCAN/EVZIO)Narcan® nasal spray 4mg in 0.1ml $150 for 2 in a box
Auto-injection (Evzio)0.4mg/0.4 mL & 2mg/0.4ml$3800 to $5800 for 2Covered by most insurancesHas voice guidance Comes with training sampler
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CLICK TO EDIT MASTER TITLE STYLE7-hydroxymitragynineTropical evergreen tree in the coffee family
Mitragyna speciosa - Native to SE Asia & Thailand
It is psychoactive, and leaves are chewed to uplift mood and to treat native’s health problems
At low doses, it produces stimulant effectsAlso entheogenic due to indole alkaloids
At high doses, it agonizes of alpha, and mu /delta opiatereceptors and causes euphoriaSold as a natural painkiller at Kava “juice bars”
e.g., Kavasutra (www.kavasutra.com)
KRATOM
CLICK TO EDIT MASTER TITLE STYLENot currently banned, but a “drug of concern”FDA can seize “dietary supplements” if suspect
Can be addictiveHas a recognizable withdrawal syndrome
Effects can last 2-5 hoursOverdoses can be treated with naloxone
Side effects vary from mild to psychosis, respiratory depression, convulsions, hallucinations, and confusion
Krypton: mitragynine & O-desmethyltramadol
KRATOM
CLICK TO EDIT MASTER TITLE STYLEAlso called “Purple drank” and “Lean”Promethazine and codeine cough syrupMixed in to soda with Jolly Ranchers candyUsually combined with alcohol
or other drugs
Referenced in popular music since the late 90’sDJ Screw died of an OD in 2000Lil Wayne hospitalized in 2013
May cause respiratory depression, seizures, death
“SIZZURP”
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OPIATE WITHDRAWAL
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AVOIDING WITHDRAWAL
Some people continue to use to avoid anydistressing withdrawal symptomsMay or may not still
get “high” from the drug use
Opiate withdrawal is rarely fatal!!!Can be extremely
uncomfortable
CLICK TO EDIT MASTER TITLE STYLE↑ BP & ↑ pulse“Flu-like” symptoms:Runny noseNauseaVomiting DiarrheaYawningSneezingWide pupilsTear secretion
OPIATE WITHDRAWAL
Typical effects Sedation IrritabilityAnxietyLack of interestSlurred speechHorripilation Goose bumps “Cold Turkey”
Leg jerks “Kicking” the habit
CLICK TO EDIT MASTER TITLE STYLEDETOXIFICATION
Primary objectiveTo relieve withdrawal symptoms
while the patient adjusts to a drug-free state
Done with or without an opiate substitute
Use C.O.W.S.Clinical Opiate Withdrawal Scale
Wesson DR, & Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs 2003;35(2):253-9.
CLICK TO EDIT MASTER TITLE STYLEShort-term – less than 5 days
1. Abrupt cessation & manage symptoms with clonidine2. Convert dose to buprenorphine & taperBuprenex, Suboxone, Subutex
Long-term – 28, 90, and 180 daysTapering with a long-acting opiate (methadone) or buprenorphine
Naloxone can be used for a “quick detox”Causes instant withdrawal Done under general anesthesiaRapid or Ultra-rapid Opioid Detoxification
DETOXIFICATION
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Due to non-complianceConvert multiple agents (if present) to 1Taper by 25% every 3-7 daysShorter interval for shorter half-life
medication
TAPERING OFF OPIATES
Rapid taper S l o w t a p e rDue to lack of benefit or
side effects / complicationsTaper by 10% per week until
20% of original dose remainsTaper remaining by
5% until off
Augment with non-pharmacologic therapies
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Centrally-acting alpha-2 (α2) agonist
Attenuates the sympathetic response to withdrawali.e., patient’s body doesn’t over-react with physical symptoms
Causes a rapid and significant decrease in withdrawal signs and symptoms
Usual oral dose is 0.1-0.2mg PO Q6hWatch BP!
CLONIDINE (CATAPRES®)
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Available after August 2018
Centrally-acting alpha-2 (α2) agonist (like clonidine)Attenuates the sympathetic response to withdrawal
Available in 0.18 mg tabletsRecommended dose is 3 tablets Q6h for up to 14 days
Causes a rapid and significant decrease in withdrawal signs and symptoms
Watch BP!
LUCEMYRA™ (LOFEXIDINE)
CLICK TO EDIT MASTER TITLE STYLEPercutaneous nerve field stimulatorPNFS placed behind patient’s ear
Reduces the symptoms of opioid withdrawalCan use up to 5 days during acute phase
Affects the Occipital Nerves and Cranial Nerves V, VII, IX and X
N=73 (JAMA. 2018;319(1):14.doi:10.1001/jama.2017.19313)Avg COWS of 20 to 7.5 in 20 min. to 3.1 after 60 minutes to 0.6 after 5 days
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm585271.htm
NSS-2 BRIDGE
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POST-DETOXIFICATION
THERAPIES
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CLICK TO EDIT MASTER TITLE STYLETREATMENTS FOR OPIATE USE DISORDER
Narcotics Addiction Treatment Act of 1974Drug Abuse Treatment Act (DATA) of 2000
AbstinenceOpiates are taperedAn opiate blocker
can be used(Revia®/ Vivitrol® / naltrexone)
Naltrexone was approved in 1984 for opiate addiction
“Harm-reduction” model“Medication Assisted Therapy” MAT
MethadoneSpecialty clinic-based treatmentEvidence-based since the 1950’s
BuprenorphineWith or without naloxonePrescribed by credentialed physicians only
CLICK TO EDIT MASTER TITLE STYLEGUIDELINES FOR TREATMENT
ALL treatments should include psychotherapy and counselingDrugs treat symptoms & should be used as adjunctive treatment
Choice of treatment should be based on level of severity
MAT is not substituting one drug for another
Begin with low doses and continue with the lowest effective doses
Inform patients of sedation, dependence, and potentiation with other CNS agents
Patients must avoid alcohol and other drugs!
CLICK TO EDIT MASTER TITLE STYLEAny prescriber of controlled substances risks
creating an addicted individualAs little as one use of an opiate can spawn an addictionRefill of an opiate Rx doubles the risk of addiction
Only specially licensed professionals can detox and/ortreat the addictionOnly 1 in 20 doctors prescribe MATOnly 1/3 of addiction treatment centers offer MATNaltrexone does not have special licensing requirements
“Harm reduction” model of treatment reduces HIV infections, crime, and risk of deathIncludes providing sterile syringes and/or MAT
TALKING POINTS
CLICK TO EDIT MASTER TITLE STYLEMAT IN A SPECIALTY TREATMENT PROGRAM**Does not include office-based prescribing2015: 17,670 patients in Florida receiving methadone treatmentIncreased from 13,711 (29%) in 2011
2015: 2,922 patients in Florida receiving buprenorphine therapyIncreased from 1,248 (234%) individuals in 2011
Higher doses of MAT lead to better success and overdoses2017 Meta-analysisMethadone treatment reduces all cause mortality by 320%
Overdose mortality decreased by 480%Buprenorphine reduces all cause mortality by 220%
Overdose mortality decreased by 330%
BMJ 2017;357:j1550 http://dx.doi.org/10.1136/bmj.j1550 *According to the FDLE
CLICK TO EDIT MASTER TITLE STYLECompetitive antagonist at opioid receptor sites
Naltrexone Depot (VIVITROL™)**Long-lasting opiate antagonist for monthly use (380mg)
Approved in April 2006 Studies with long-acting depot form Vivitrol™ in Russia demonstrated
extraordinary outcomes regarding drug abstinence, tx. retention, and decreased cravingsVivitrol = buprenorphine + naloxone in efficacy*
n=570 / p=0.44 → no difference*Lancet Online. 11/14/2017 http://dx.doi.org/10.1016/S0140-6736(17)32812-X**Drugs 2002;5(8):835-8**http://www.drugabusesciences.com/products.asp accessed on 3/11/04**http://www.medscape.com/viewarticle/530039 accessed on 4/20/06
NALTREXONE (REVIA®/VIVITROL®)
CLICK TO EDIT MASTER TITLE STYLENot to be used during active withdrawalMust wait 7-14 days post-detox or opioid withdrawal will occur
Oral dose - 50mg po QD or IM dose - 380mg Q4WMonitor for hepatic toxicity, nausea, HA, dizziness, anxiety and
sedationStudies show a reduction in (re-)incarcerations when used with
behavior therapyCompliance and motivation are major factors32-58% successful in compliant patients
Abstinence rates diminish over time
NALTREXONE (REVIA® / VIVITROL®)
Cochrane Database of Systematic Reviews 2003;(2):CD001333. Drug & Alcohol Dependence 1997;47(2):77-86. / Drugs 1988;35(3):192-213.
CLICK TO EDIT MASTER TITLE STYLEUsed as a prescribed opiate substituteMedication is taken orally QD Suppresses withdrawal for 24 to 36 hours and relieves cravingsHalf-life is 15-60 hoursFull mμ agonistCan cause dysphoria and euphoria
Detox: 15-40 mg/day not to exceed 21 daysWithdrawal can be severe & protracted
Maintenance: 20-120 mg/day Facility must be licensed to dispense it!!!Cost savings of $3-4 for every dollar spentIncludes costs of crime and lost productivityCenter for Substance Abuse Treatment. Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) Series 43. HHS Publication No. (SMA) 12-4214. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2005.
METHADONE PROGRAMS
CLICK TO EDIT MASTER TITLE STYLEMixed partial mu opiate agonist &
kappa antagonist (blocks dysphoria)Prescriber MUST be licensed to prescribe itDEA # changes to begin with “X”
Lower risk of abuse vs. methadoneCeiling effect if dosed too highSafer for respiratory depressionCombined with other opiates may cause withdrawal
Usual dose is 4-24mg sublingually daily
BUPRENORPHINE + NALOXONE
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Safe and effective for office-based detox16 mg buprenorphine dailyUp to 21% avoided outside opiates vs. 5.8% on placebo (p<0.001)
Retention rates in programs < methadoneHigh dose buprenorphine may suppress heroin use >
methadoneDoses > 8mg/d have best successQOD dosing also successful
NEJM 2003;349:949-958. / Cochrane Database of Systematic Reviews 2003;(2): CD002207. Addiction 2003;98(4):441-452. / J Neurosci Rural Pract. 2012 Jan-Apr; 3(1): 45–50.
BUPRENORPHINE + NALOXONE
CLICK TO EDIT MASTER TITLE STYLEShort-acting opiate receptor blockerNot used for abstinence but to deter abuseNot orally active (only useful if combination tablets are liquefied
& injected)
Counteracts the effects of opioids and can be used to treat overdoses
Dose: 0.4 to 2 mg/dose IV/IM/subcutaneouslyContinuous infusion: 0.005 mg/kg loading dose followed by
0.0025 mg/kg/hr
NALOXONE COMBINATIONS
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Subutex® (buprenorphine) SL tabs
Buprenorphine + NaloxoneBunavail® buccal filmZubsolv® SL tabletsSuboxone® is a 4:1 ratio of buprenorphine to naloxone
Butrans® and Subsys® are NOT approved
BUPRENORPHINE PRODUCTS APPROVED FOR OPIATE DEPENDENT PATIENTS
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Probuphine® (Buprenorphine implant)320mg in 4 implantable subdermal rods in upper armMust be surgically replaced every 6 monthsDiscontinue after each arm used
Sublocade® monthly SQ depot injectionStart with 300mg x 2 months in abdomenMaintenance is 100mg (up to 300mg) a monthAvailable in pre-filled syringes100mg/0.5ml or 300mg/1.5ml
LONG-ACTING BUPRENORPHINE PRODUCTS
CLICK TO EDIT MASTER TITLE STYLERisk Evaluation and Mitigation StrategiesMethods to reduce severe side effects and bad outcomesMust register a patient before being able to dispense opiate to themSee: http://tirfremsaccess.com and http://www.er-la-opioidrems.com
REMS now applies to ALL opiatesKey messages need to be communicated to patients: Warn patients not to self-administer non-prescribed benzodiazepines or
alcoholKeep out of the sight and reach of childrenKeep their medication safe to protect them from theft Never give to anyone elseAdvise patients that selling or giving away medication is against the law
REMS PROGRAMS
CLICK TO EDIT MASTER TITLE STYLEMedications infused through a spinal pumpZiconotide (Prialt®) solution
An N-type calcium channel antagonist25 mcg/mL & 100 mcg/mL concentrationDelivered by a spinal infusion pumpCan cause cognitive impairment, hallucinations, and changes in mood or consciousness
Baclofen (Gablofen®)Injectable version of Liorisal®A GABA (gamma-aminobutyric acid) agonistUsed for severe spasticity of cerebral or spinal origin90–800 mcg/day dosing
Morphine Sulfate (Infumorph) – preservative-freeOnly 4% reaches the CNSMicro-infused at 0.2–10 mg/day
All incur risks of infection to the CNS
AVAILABLE NON-ADDICTIVE PAIN MEDICATIONS
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ADDRESSING THE CRISIS
81
CLICK TO EDIT MASTER TITLE STYLELegislation to close pill millsPrescription Drug Monitoring Programs (PDMP)Needs full interstate implementation
Increasing access to naloxone for overdosesLegislation to limit prescription quantities
CURRENTLY, WHAT ARE WE DOING?
CLICK TO EDIT MASTER TITLE STYLENEW FLORIDA LEGISLATION – JULY 2018HB13 FS 456.44(3) - Controlled substance prescribingLimits C-II Rx’s for acute pain to a 3-day supplyPatient can get a 7-day supply if medically necessary by writing
“ACUTE PAIN EXCEPTION” on RxRx’s for chronic pain must specify “NONACUTE PAIN”
Patient must be seen by prescriber LESS THAN every 3 monthsPrescribers must complete a 2-hour CE on responsibly prescribing opioidsFlorida’s PDMP will be upgraded for EMR integration
Inter-state collaboration is ultimate goalPrescribers MUST check PDMP before prescribing
Immediately refer patients with signs or symptoms of substance abuse to a board-certified pain management physician, an addiction medicine specialist, or a mental health addiction facility
http://www.leg.state.fl.us/STATUTES/index.cfm?App_mode=Display_Statute&Search_String=&URL=0400-0499/0456/Sections/0456.44.html
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FY 2017 - SAMHSA awarded $485 mil state targeted response grants
2017 - Trump Administration’s Involvement10/26/2017 - declared the opioid crisis a Nationwide Public Health EmergencyNational “Take Back Day” collected 456 tons of expired / unneeded medsINTERDICT Act - Signed on 1/10/2018 against illegally imported fentanylFeb 2018 - the Prescription Interdiction & Litigation task force (PIL)
Attorney General Jeff SessionsTo keep manufacturers and distributors of opioids accountable
Joint Criminal Opioid Darknet Enforcement (J-CODE) TeamFor law enforcement to disrupt online sales of illicit opioids
https://www.whitehouse.gov/briefings-statements/president-donald-j-trump-combatting-opioid-crisis/
RECENT HISTORY
CLICK TO EDIT MASTER TITLE STYLEHEAL INITIATIVEApril 2018 - NIH launched HEAL InitiativeHelping to End Addiction Long-term“Aggressive, trans-agency effort to speed scientific solutions to stem the
national opioid public health crisis”Goals:Improve Treatments for Opioid Misuse and Addiction
Expand therapeutic options for opioid addiction, overdose prevention and reversalEnhance treatments for infants born with Neonatal Abstinence Syndrome (NAS)/
Neonatal opioid withdrawal syndrome (NOWs)Optimize effective treatment strategies for opioid addiction
Enhance Pain Management TherapiesUnderstand the biological underpinnings of chronic painAccelerate the discovery and pre-clinical development of non-addictive pain treatmentsAdvance new non-addictive pain treatments through the clinical pipeline
https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative/heal-initiative-research-plan
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THE FUTURE OF THE OPIOID CRISIS
86
CLICK TO EDIT MASTER TITLE STYLEMore prescriber education Utilizing Risk Reduction Strategies and Pain Treatment Algorithms www.sempguidelines.org
Increase access and insurance coverage (+ Medicare/Medicaid) for detoxification, addiction treatment programs and MAT
Medicaid and insurance companies instituting Pharmacy “Lock-In” ProgramsOne pharmacy / one doctor
Comprehend the genetic component to addictionDeveloping new non-addictive treatments of pain
RESEARCH AND EDUCATION
87
CLICK TO EDIT MASTER TITLE STYLEAPADAZ™
Benzhydrocodone and acetaminophen tabletsA pro-drug that needs to be metabolized to work
Kappa receptor agonists/antagonistsCERC-501, Samidorphan, Difelikefalin, others
Blue-181 by Blue TherapeuticsActs on receptors in the spinal cordSoon to start human trials
BU08028 – an orvinol analogNociceptin/orphanin FQ peptide (NOP) receptor agonist
NKTR-181 by Nektar TherapeuticsLong-acting, selective mu-opioid agonist with low CNS penetration
FUTURE OF PAIN MANAGEMENT
CLICK TO EDIT MASTER TITLE STYLESPRINT endura™ and SPRINT extensa™
SPR TherapeuticsPeripheral nerve stimulation systemLeads are implanted percutaneously
Single or dual leads
Use for up to 60 daysController is Bluetooth enabled
Medical marijuanaEarly studies showing lower doses of opiates needed
https://www.sprtherapeutics.comJAMA Intern Med. Published online April 2, 2018. doi:10.1001/jamainternmed.2018.1007
FUTURE OF PAIN MANAGEMENT
CLICK TO EDIT MASTER TITLE STYLECURRENTLY STILL:
Enough opiates for every American adult to have 52 pills
Drug overdose is the leading cause of death in those < 50 years old
6 in 10 deaths from overdose caused by opiates
>2 million people have an Opioid Use Disorder
Only 20% in treatment & only 1/3 getting MAT
RECAP
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Arizona Department of Health Services (2017). 2016 Arizona Opioid Report. Retrieved Feb. 6, 2018, from azdhs.gov/documents/audiences/clinicians/clinical-guidelines-recommendations/prescribing-guidelines/arizona-opioid-report.pdf
Ali, M., Dowd, W., Classen, T., Mutter, R., and Novak, S. P. (2017). Prescription drug monitoring programs, nonmedical use of prescription drugs, and heroin use: Evidence from the National Survey of Drug Use and Health. Addictive Behaviors,65-77.
American Medical Association (2016). Fact sheet: Physicians' progress to reverse nation's opioid epidemic. Retrieved from ama-assn.org/sites/default/files/media-browser/public/physicians/patient-care/task-force-progress-reversing-opioid-epidemic-aug-2016-update.pdf
ASAM (2015). National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. Retrieved Feb. 6, 2018, from asam.org/docs/default-source/practice-support/guidelines-and-consensus-docs/asam-national-practice-guideline-supplement.pdf
CDC. (2016, March 14). Fentanyl Overdose Data. Retrieved Feb. 6, 2018, from cdc.gov/drugoverdose/data/fentanyl.html CDC. (2017, Aug. 31). Annual Surveillance Report of Drug-Related Risks and Outcomes - United States, 2017. Retrieved Feb. 6, 2018, from
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Kenan, K., Mack, K. A., and Paulozzi, L. J. (2012). Trends in Prescriptions for Oxycodone and Other Commonly Used Opioids, 2000-2010, United States. Open Medicine, 6(2), 41-47.
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The National Safety Council can provide medical experts for medical meetings and conferences. Learn more and submit a speakerrequest at nsc.org/SpeakersBureau.
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