SUD 4: Opioids

SUBSTANCE-RELATED AND ADDICTIVE DISORDERS IV:
DRUG TESTING & THE ACTION OF OPIOIDS, WITHDRAWAL & TREATMENT
Ximena Sanchez-Samper, MD
Instructor Harvard Medical School
Medical Director Spring Hill Recovery Center
Board-Certified Addictions Psychiatrist
xsanchezmd@gmail.com
Question Based Learning

Lecture Modules
• Drug Testing
• The Action of Opioids, Intoxication and Treatment
• Opioid Withdrawal
• Opioid Withdrawal Treatment
Module: Drug Testing
Question: You are employed in an addiction treatment center where the patients are subject to random,
mandatory drug screens as a part of their treatment and/or probation for substance abuse-related
problems or offenses. Which of the following substances cannot be readily detected in an immunoassay
urine drug screen?
A. Marijuana
B. Cocaine
C. Toluene
D. Heroin
E. PCP (Phencyclidine)
Psychiatry Review: Substance-Related and Addictive Disorders IV: Drug Testing & the Action of Opioids, Withdrawal & Treatment
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Types of Drug Tests
• Breath
– Good reflection of the blood alcohol level at time of test
– Available for alcohol only
– Not generally useful in primary care
• Saliva
– Available for alcohol and other drugs
– Reflects blood level of drugs
– Not standardized, “cut-off levels” for positive tests varies between products
• Blood
– Gives accurate assessment of acute intoxication
– More useful in emergency situations than in primary care
• Sweat
– Patch worn for up to 14 days
– High rate of false positives from “environmental contact”
• Hair
– Gives up to 90 day “history” of drug use
– Cannot determine when use occurred
– Ability to “hold” chemicals dependent on hair type
– Marijuana test not considered reliable
• Urine (immunoassays)
– Well studied, standardized, quick, inexpensive
– Multiple drugs screened at once
– Drug concentrations relatively high
– Drugs and metabolites are excreted in the urine for a
period of time after acute intoxication
– Positive results require confirmation
Definitive (Confirmatory) Testing

• Gas chromatography/mass spectrometry (GCMS)
– Gold standard in drug testing
– Highly specific, can be used to confirm positive screen
– Can give quantitative levels
– Can test for substances not detected by a screen
Department of Transportation Protocol
• Patient is required to
– Show picture identification
– Empty pockets/wash hands
• Facility
– No running water
– Toilet water is dyed blue
– Temperature is checked immediately
• “NIDA 5”: marijuana, cocaine, opiates, amphetamines, PCP
Urine Test: Detection Windows
Alcohol Testing
• Alcohol has a short half-life in urine
• Blood alcohol level: determines whether patient is acutely intoxicated or has been drinking recently
• Breath and saliva tests: reflective of the blood alcohol level
• Ethyl glucuronide (ETG): longer half-life and may improve sensitivity up to 5 days
• Carbohydrate Deficient Transferrin (CDT): helps detect HEAVY alcohol consumption
Module: The Action of Opioids, Intoxication and Treatment
Question: Opioid intoxication is generally characterized by which of the following physiologic changes?
A. Pupillary dilation
B. Piloerection
C. Increased blood pressure
D. Depressed respiration
E. Increased body temperature
Opioids
• Natural and synthetic substances with morphine like activity (mu receptor): Used for 6000 years (since
Hippocrates)
• Medical use: Analgesia & Cough suppression
• High addiction potential: can be misused/abused
• Increased potency: leads to increased physical and psychological dependence
• Stigma prevents treatment: Brain disease…NOT a moral issue!
Neurobiology of Opioid Effects

• The spinal cord transmits pain signals from the body. By acting here, opiates block pain messages and
allow people to bear even serious injuries (yellow)
• Opiates change the limbic system to produce increased feelings of pleasure, relaxation and contentment
(red)
• The brainstem controls functions your body does automatically, like breathing or coughing. Opiates can
act on the brainstem to stop coughing or slow breathing (blue)
DOPAMINE
PAIN: The “Fifth Vital Sign”
• Pain was first recognized as the fifth vital sign in the 1990's, giving pain equal status with blood pressure,
heart rate, respiratory rate and temperature as vital signs.
Source: GAO. OxyContin Abuse and Diversion and Efforts to Address the Problem. December 2003. http://www.gao.gov/new.items/d04110.pdf.
Source: http://www.nytimes.com/2007/05/11/business/11drug.html?pagewanted=all&_r=0.
http://www.nytimes.com/2011/09/01/us/01drugs.html?src=me&ref=us.
Development of the Opioid Epidemic Timeline
• 1996: abuse problems begin with OxyContin
• Since 1999: 300% increase in the sales of opioid pain medications in the U.S.
• Corresponding increase in incidence of opioid addiction & patients admitted to treatment increased
dramatically
• 2008: Surge in deaths from prescription opioid overdoses from 3000 deaths in 1999 to 15,000 in 2008:
500% mortality increase!
• Drug Overdose > Car Accidents: CDC classifies opioid overdose as an epidemic (2011)
Source: http://www.cdc.gov/HomeandRecreationalSafety/rxbrief. Centers for Disease Control and Prevention: Injury Prevention and Control Policy
Impact: Prescription Painkiller Overdoses. 2011.
Epidemiology of Opioid Addiction in the US

• Americans (4.6% of the world’s population) consume approximately 80%-90% of the world’s opioid supply
• Americans consume 99% of the world’s supply of hydrocodone (Vicodin)
• In 2012, 259 million prescriptions written for opioids: enough to give every American adult their own
bottle of pills
Source: Substance Abuse and Mental Health Services Administration (SAMHSA) Office of Applied Studies.
Substance Use Treatment Need among Adolescents: 2003-2004. National Survey on Drug Use and Health (NSDUH) 2006. Wang J, Christo PJ. The
influence of prescription monitoring programs on chronic pain management. Pain Physician. May-Jun2009; 12(3):507-15.
Purity vs. Price
Source: https://www.statnews.com/2016/08/03/fentanyl-massachusetts/. http://www.nytimes.com/2016/03/26/us/heroin-fentanyl.html?_r=0.
CDC, NIDA and ASAM Facts & Figures
• Four in five (80%) new heroin users started out misusing prescription painkillers
• 94% of respondents in treatment: chose heroin because prescription opioids were “far more expensive
and harder to obtain & heroin was a cheaper source.”
• Estimated 23% of individuals who use heroin develop opioid addiction.
• 2.1 million Americans meet criteria for OUD
• Drug overdoses killed about 70,000 Americans last year (2018), a record number that reflects a rise of
around 10 percent (higher than peak yearly death totals for HIV, MVAs or gun deaths/homicides)
• CDC estimates 130 Americans die every day from an opioid overdose; 5 PEOPLE PER HOUR
Source: Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: CDC, National Center for Health Statistics; 2017. Available
at http://wonder.cdc.gov. Scholl L, Seth P, Kariisa M, Wilson N, Baldwin G. Drug and Opioid-Involved Overdose Deaths – United States, 2013-2017.
WR Morb Mortal Wkly Rep. ePub: 21 December 2018.
Opioid Intoxication Diagnosis

• Recent opioid use
• Clinically significant problematic behavior (euphoria followed by apathy, dysphoria, psychomotor
agitation/retardation, impaired judgement)
• Pupillary constriction and one or more
– Drowsiness
– Slurred speech
– Impairment in attention or memory
• Not attributable to AMC or another mental disorder
Source: Diagnostic and Statistical Manual of Mental Disorders 5th Ed. DSM-5. American Psychiatric Association.
Opioid Intoxication Treatment
Module: Opioid Withdrawal
Question: Which of the following is not a symptom of opioid withdrawal?

A. Increased body temperature
B. Depressed respiration
D. Piloerection
E. Pupillary dilation
“Quitting Cold Turkey” and…
“Kicking the Habit”
Module: Opioid Withdrawal Treatment
Question: Which of the following statements is true in reference to starting Buprenorphine?

A. It should be started when the patient is intoxicated with an opiate
B. It should be started when objective evidence of opiate withdrawal is evident
C. It should be started at the time the patient consumes heroin
D. It should only be administered at hs
E. It should be administered orally/PO
Symptom Management
• Headache, muscle pain, joint or bone pain: Ibuprofen 600-800 mg q6-8h or acetaminophen 650 mg q4h
• Muscle spasm: Quinine sulfate 325 mg q 6h prn
• Anxiety: Hydroxyzine 25-50 mg or lorazepam 1-2 mg or chlordiazepoxide 2-5 mg q6-8h
• Insomnia: Lorazepam 2 mg or chlordiazepoxide 25 mg or trazodone 50-100 mg or doxepin 10-20 mg
• Abdominal cramps: Dicyclomine 10-20 mg q6h
• Nausea: Phenergan 25 mg PO/IM q6h or metoclopramide 20 mg q6h
• Loose stool: Bismuth subcarbonate 30 cc or Imodium 2 mg after each loose stool, up to 8 doses total
Clonidine
• Decreases sympathetic outflow ➔suppresses autonomic mediated symptoms
– Presynaptic noradrenergic a2 agonist
• Side effects: Drowsiness and orthostatic
• Oral dosing
– Day 1-4: 0.1-0.2 mg q 4 hr (up to 1.2 mg qd)
– Day 5-completion: reduce by 0.2 mg qd until done
• Transdermal weekly patch (0.2 mg daily equivalent)
– Give 1, 2, or 3 patches based on weight
Opioid Classification
• Full agonists
– Morphine
– Heroin
– Oxycodone
– Fentanyl
• Partial agonist
– Buprenorphine (Subutex; Suboxone)
• Antagonists
– Naloxone (Narcan)
– Naltrexone (Oral Revia or IM Vivitrol)
Partial vs. Full Opioid Agonist
Methadone
• Synthetic opioid agonist
– Acute opioid withdrawal in detox centers
– Opioid replacement therapy: most researched treatment (1970s)
• Better treatment retention rates
• Reduces morbidity and mortality
• Curbs spread of infectious disease
• Works best if programs are numerous, accessible, and flexible
• Approved in pregnancy
Source: *Mattick et al. 2003. **Single, 2000.
Buprenorphine
• Long-acting, potent, partial (mu) agonist
• Mixed agonist/antagonist (kappa)
• Less euphoria… less addictive than full agonists
• Can substitute for a full opioid agonist and alleviate symptoms of withdrawal and cravings
• Can be prescribed by physicians who complete brief training and obtain a waiver
• Good first choice for adolescents and young adults
• Pregnancy Category C: MOTHER study
Goals
1. Suppress withdrawal 2. Attenuate euphoria
3. Minimize/eliminate cravings
4. Decrease overdose risk
Buprenorphine Displaces or Blocks Other Opioids

• Buprenorphine has a high affinity for mu receptors and can displace bound opioids
• Other opioids cannot bind to the receptor if buprenorphine is there
Buprenorphine Pharmacologic Properties

• Quick onset of action (100 vs. 150 min), slow dissociation rate, less frequent dosing (option of alternative
day dosing)
• Side effects
– Paragraphs
– Nausea, constipation
– Monitor LFT’s
• Drug-drug interactions: CYP 3A4 metabolism
– Decrease dose if on azoles or protease inhibitors
Buprenorphine Formulations
• Sublingual (Addiction treatment only)
• Sublingual tabs and film (Suboxone):
Bup/Naloxone 4:1
• Sublingual tabs (Subutex): Bup mono
product
• Sublingual tabs (Zubsolv, generic): Bup/Naloxone
• Buccal Film: Bunavail (Buprenorphine/Naloxone)
• Subdermal Implant: Probuphine (Buprenorphine)
• Injectable SubQ Formulation: Sublocade (Buprenorphine
extended release)
• Transdermal (Pain Only): Butrans patch (Buprenorphine)
Buprenorphine Formulations
• Combo tablet/film buprenorphine 4 mg + naloxone 1 mg ratio: Suboxone
* 2 mg (2 mg/0.5 mg) * 4 mg (4 mg/1 mg)
* 8 mg (8 mg/2 mg) * 12 mg (12 mg/3)
• Mono tablet/film buprenorphine: Subutex
* 2 mg * 4 mg
* 8 mg * 12 mg only for pregnancy or naloxone allergy
– M.D. waiver needed for X DEA (8 hrs ASAM training)
– Apply to SAMHSA to increase from 30 patient limit to 100
– After 100 x 1 yr, can apply to increase to 275 patient limit
Buprenorphine-Naloxone: Suboxone
• Poor oral bioavailability (extensive first pass metabolism)
• Must be administered sublingually
• With sublingual Suboxone, only the buprenorphine is absorbed,
NOT the naloxone
• Naloxone is a safety feature: Opioid antagonist
• If Suboxone is injected, patient goes into withdrawal
• Eliminates IV use: Decreases transmission of HCV/HBV/HIV and
decrease diversion risk
Benefits of Office-Based Buprenorphine Treatment

• Good first choice for adolescents
• Confidential, safe and effective treatment provided in a doctor’s office
• Methadone approved for >18 y.o. only
• Fits lifestyle: No daily clinic visits or out-of-town, costly residential treatment
• Allows for parental involvement/support
• Psychosocial therapies/random urine testing
• Improves functional status: More time for school, work, family and other activities
Source: *Mattick et al. 2003; Single, 2000.
Naltrexone XR (IM) Vivitrol

• 250 opioid addicted subjects in Russia
• Half remained in treatment at end of 6 m
• 36% of Naltrexone – treated patients remained in treatment x 6 months
without using drugs vs. 23% in placebo group
• High cost limits use but some insurance companies cover it as a medical
benefit
• 380 mg IM monthly on alternating buttocks
• Also FDA approved for Alcohol Use D/O
Answer Key
Question: You are employed in an addiction treatment center where the patients are subject to random,
mandatory drug screens as a part of their treatment and/or probation for substance abuse-related
problems or offenses. Which of the following substances cannot be readily detected in an immunoassay
urine drug screen?
A. Marijuana
B. Cocaine
C. Toluene
D. Heroin
E. PCP (Phencyclidine)
Answer Explanation
• Inhalants are generally not assessed along with routine urine drug screening, thus detection relies on
clinical judgment, conducting a thorough history and a detailed physical examination
• Often, abnormal nontoxicological laboratory results (i.e. elevated liver enzymes) can also indicate a
suspicion of inhalant abuse
• Some of the laboratory tests which are commonly been done for a patient presenting with acute inhalant
intoxication (or suspected inhalant use) include a CBC, electrolytes, phosphorous, and calcium levels, an
acid-base assessment, hepatic and renal profiles, and cardiac/muscle enzyme analysis
• Requesting specific urine drug testing can sometimes be useful when benzene, toluene, or a similar agent
has been chronically abused, because major urinary metabolites (phenol and hippuric acid, respectively)
are detectable when there has been a high level of use
Source: Broussard LA. The role of the laboratory in detecting inhalant abuse. Clin Lab Sci. 2000;13:205–9. Anderson CE, Loomis GA. Recognition and
prevention of inhalant abuse. Am Fam Physician. 2003;68:869–74.
Question: Opioid intoxication is generally characterized by which of the following physiologic changes?
A. Pupillary dilation
B. Piloerection
D. Depressed respiration
E. Increased body temperature
Answer Explanation
• Due to their effect on the brainstem, opioids in high doses can cause respiratory depression and death
• An opioid overdose can be identified by a combination of three signs and symptoms referred to as the
“opioid overdose triad.” The symptoms of the triad are
– Pinpoint pupils
– Unconsciousness
– Respiratory depression
• Combining opioids with alcohol and sedative medication increases the risk of respiratory depression and
death, and combinations of opioids, alcohol and sedatives are often present in fatal drug overdoses
Source: Paulozzi L, Weisler R, Patkar A. A national epidemic of unintentional prescription opioid overdose deaths: how physicians can help control it. J
Clin Psychiatry 2011;72:589-592 Okie S. A flood of opioids, a rising tide of deaths. N Engl J Med 2010;363:1981-1985[Erratum, N Engl J Med
2011;364:290.].
Question: Which of the following is not a symptom of opioid withdrawal?
A. Increased body temperature
B. Depressed respiration
D. Piloerection
E. Pupillary dilation
Answer Explanation
• Either of the following may be present during OPIOID WITHDRAWAL
– Cessation or reduction in opioid use
– Administration of opioid antagonist after period of opioid use
• Three or more of the following
– Dysphoric mood
– Nausea or vomiting
– Muscle aches
– Lacrimation or rhinorrhea
– Pupillary dilation, piloerection or sweating
– Diarrhea
– Yawning
– Fever
– Insomnia
• Significant distress or impairment in functioning
• Not AMC or another mental disorder
Source: Diagnostic and Statistical Manual of Mental Disorders 5th Ed. DSM-5. American Psychiatric Association.
Question: Which of the following statements is true in reference to starting Buprenorphine?

A. It should be started when the patient is intoxicated with an opiate
B. It should be started when objective evidence of opiate withdrawal is evident
C. It should be started at the time the patient consumes heroin
D. It should only be administered at hs
E. It should be administered orally/PO
Answer Explanation
• The Buprenorphine Induction Phase is the medically monitored startup of Buprenorphine treatment
performed in a qualified physician’s office or certified OTP (Opioid Treatment program) using approved
buprenorphine products
• Buprenorphine is administered sublingually (not PO) when a person with opioid dependency has
abstained from using opioids for 12 to 24 hours and is in the early stages of opioid withdrawal opioids in
their bloodstream
• It is important to note that buprenorphine can bring on acute withdrawal for patents who are not in the
early stages of withdrawal and who have other opioids in their bloodstream
Source: Fiellin D.A., Rosenheck R.A., Kosten T.R. Office‐based treatment for opioid dependence: Reaching new patient populations. American Journal
of Psychiatry. 2001;158(8):1200–1204. [PubMed: 11481150] Fudala P.J., Bridge T.P., Herbert S., Williford W.O., Chiang C.N., Jones K., Collins J., Raisch
D., Casadonte P., Goldsmith R.J., Ling W., Malkerneker U., McNicholas L., Renner J., Stine S., Tusel D. Buprenorphine/Naloxone Collaborative Study
Group. Office‐based treatment of opiate addiction with a sublingual‐tablet formulation of buprenorphine and naloxone. New England Journal of
Medicine. 2003;349(10):949–958.
End of Lecture

SUD 4: Opioids

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SUD 4: Opioids

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SUBSTANCE-RELATED AND ADDICTIVE DISORDERS IV:

DRUG TESTING & THE ACTION OF OPIOIDS, WITHDRAWAL & TREATMENT

Question Based Learning

Module: Drug Testing

Definitive (Confirmatory) Testing

Urine Test: Detection Windows

Neurobiology of Opioid Effects

Epidemiology of Opioid Addiction in the US

Source: https://www.statnews.com/2016/08/03/fentanyl-massachusetts/. http://www.nytimes.com/2016/03/26/us/heroin-fentanyl.html?_r=0.

Opioid Intoxication Diagnosis

Opioid Intoxication Treatment

Question: Which of the following is not a symptom of opioid withdrawal?

“Quitting Cold Turkey” and…

“Kicking the Habit”

Module: Opioid Withdrawal Treatment

Question: Which of the following statements is true in reference to starting Buprenorphine?

Partial vs. Full Opioid Agonist

Buprenorphine Displaces or Blocks Other Opioids

Buprenorphine Pharmacologic Properties

Benefits of Office-Based Buprenorphine Treatment

Naltrexone XR (IM) Vivitrol

Question: Which of the following statements is true in reference to starting Buprenorphine?

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