Addiction Medicine - Substances of Abuse

INTENSIVE UPDATE AUGUST 24 - 26, 2018 & BOARD REVIEW Loews Chicago O’Hare Hotel Rosemont, IL

INNOVATIVE • COMPREHENSIVE • HANDS-ON

Bradley J. Miller, DO, FAAFP

The American College of Osteopathic Family Physicians is accredited by the American Osteopathic Association Council to sponsor continuing medical education for osteopathic physicians.

The American College of Osteopathic Family Physicians designates the lectures and workshops for Category 1-A credits on an hour-for-hour basis, pending approval by the AOA CCME, ACOFP is not responsible for the content.

Substances of Abuse

ACOFP Intensive Update and Board Review in Osteopathic Family Medicine

Bradley J. Miller, DO, FAAFP Williamsport Family Medicine Residency

Objectives

• Define Addiction • Review current statistics and disease burden of substance abuse in the United States. • Review DSM V criteria for substance use disorders • Review specific substances of abuse (opioids, alcohol, nicotine, MJ) and accepted behavioral and pharmacologic treatments

1 What Is Addiction: ASAM Definition1

Short Definition of Addiction Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. This is reflected in an individual pathologically pursuing reward and/or relief by substance use and other behaviors.

Without treatment or engagement in recovery activities, addiction is progressive and can result in disability or premature death.”

1. American Society of Addiction Medicine. http://www.asam.org/docs/publicy-policy- statements/1definition_of_addiction_long_4-11.pdf?sfvrsn=2; accessed April 13, 2012

What is addiction? Characteristics of Chronic Disease • Chronic, ie no known cure; must be managed over time – long-lasting chemical changes in the brain regardless of detoxification • Relapsing – with and without treatment, craving and compulsive, pathological pursuit of substance can return • Progressive – gets worse over time; high fatality rates for addiction specifically

2 The evolution of dopamine reward…

• The midbrain of the human is almost identical to that of an amphibian. – All animals have the same basic reward wiring. – Behaviors that are rewarding: • Warm Body • Eating  Full Belly • Reproductive activity – The brain provides a reward of “well being” to reinforce these behaviors that are positively associated with SURVIVAL. • 2. Physiologic Range of reward is on a scale of 1-50. Food  Sex • 3. Supra-physiologic range of reward with drugs and alcohol. – Range of 50-10,000. – DEEP IMPRINT for Reward behaviors = Difficult to forget

Courtesy Dr. Darryl Inaba Pharm.D. CADC III

3 What is addiction?

*National Institute of Drug Abuse: https://www.drugabuse.gov/publications/drugs-brains-behavior-science-addiction/drugs-brain

National Trends

Center for Behavioral Health Statistics and Quality. (2015). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health (HHS Publication No. SMA 15-4927, NSDUH Series H-50). Retrieved from http://www.samhsa.gov/ data/

4 DSM-V Substance Related Disorders

– Nomenclature helps define SUD as a continuum and removes confusion regarding dependence with “addiction”

– Disorder, Severity (based on # of specific criteria for substance), Category

– Matches ICD-10 approaches to categorization “Alcohol Use Disorder, severe, in withdrawal” “Opioid Use Disorder, moderate, intoxication” “Gambling Use Disorder, severe, unspecified”

Question

An intoxicated patient is brought to the emergency department. Ocular examination reveals mydriasis. This patient was most likely using which of the following substances?

(A) alcohol (B) cocaine (C) opioids (D) PCP (E) sedatives

5 Opioids

Types of Opiates/Opioids

• Natural opiates: • Synthetics • Morphine • Oxycodone • Methadone • Codeine • Fentanyl • Opium • Buprenorphine (partial • Semi-synthetics agonist) • Heroin • LAAM • Hydromorphone • Propoxyphene • Hydrocodone • Pentazocine • Butorphanol (agonist/antagonist) • Fentanyl • Dextromethorphan (agonist/antagonist) • Naloxone (pure opiate antagonist) • Naltrexone (pure opiate antagonist)

6 Common scenario

• Acute pain  prescription for opioid  Addiction – Post-surgery – Accident – Sports injury – Medical condition • One of the major causes of opioid addiction is the use of legitimately prescribed opioid medications

Chronic, Non-Malignant Pain Summary (CNMP)

• Use of opioids for too long greatly increases risk of: – Acute pain becoming chronic, non-malignant pain (CNMP) – Hyperalgesia (greater sensitivity to pain) – Hyperkatifeia (dysphoria; chronic negative emotional states) – Addiction

7 Common scenario

• Risk is higher for: – Family history of SUD (genetics) – Individual history of SUD – Depression/Anxiety/Other MH disorders – PTSD – Childhood trauma/chronic problematic environment – Adolescents

National Trends

8 National Trends

National Trends

Source Where Pain Relievers Were Obtained for Most Recent Nonmedical Use among Past Year Users Aged 12 or Older: 2011-2012

Substance Abuse and Mental Health Services Administration, Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013

9 Drugs Involved in U.S. Overdose Deaths* - Among the more than 64,000 drug overdose deaths estimated in 2016, the sharpest increase occurred among deaths related to fentanyl and fentanyl analogs (synthetic opioids) with over 20,000 overdose deaths. Source: CDC WONDER

Why are opioid medications used to treat opioid addictions?

• Long-term (permanent?) changes to opioid receptor system.

• Changed receptors may require an opioid to function normally.

• Opioid treatment medications reduce symptoms; promote remission.

• Long-term (at least 2 years, for some, lifelong) medication treatment works best.

10 Why are opioid medications used to treat opioid addictions? • Research has consistently and repeatedly found that opioid medication-assisted treatment, compared to no treatment or abstinence: – Reduces drug use – Reduces overdose and mortality – Reduces crime – Reduces costs to society – Improves functioning and quality of life • In a high percentage of cases, when medication stops, symptoms return, and overdoses and fatalities can increase, even with ongoing behavioral intervention

Opiate Addiction Pharmacologic Interventions

• Opiate Agonists – Methadone

• Partial Agonist, Partial agonist/antagonist – buprenorphine – buprenorphine/naloxone

• Antagonist – Naltrexone (Vivtrol®)

11 Medication Treatments for Opioid Use Disorder

Conceptual Representation of Opioid Effect Versus Log Dose for Opioid Full Agonists, Partial Agonists, and Antagonists Full Agonist: (high intrinsic activity) (Oxycodone, Heroin, Methadone)

Potentially Lethal Dose

Partial Agonist: (low intrinsic

Opioid EffectOpioid activity) (Buprenorphine)

Antagonist: (no intrinsic activity) Log Dose (Naloxone/Naltrexone) Nutt&Langford, 2008, Brit Jl Pharm

Methadone • Full opiate agonist • Tightly blocks two subset opioid receptor • Well studied for decades • Safe in pregnancy • Must be administered at a federally licensed treatment facility • Abuse potential • Very long half life

• CAUTION: can cause QT prolongation

12 Naltrexone (Vivitrol®) • Naltrexone is a opiate antagonist • Tightly blocks mu opioid receptors • FDA approved for treating alcohol dependence and opiate dependence – Decreases cravings in patients who abuse alcohol • Comes in oral and IM depot formulations – oral used to trial naltrexone prior to committing to IM – IM- (Vivitrol®) – depot formulation that is given monthly. If patients use opiates while on, no high. • CAUTION: Will cause opiate withdrawal • BLACK BOX WARNING-acute hepatic toxicity

Buprenophine

• Partial agonist/antagonist of the mu opioid receptor – Binds to and activates the receptor – Decreases cravings – Null overdose potential (w BZDs) – Partial agonists have a “ceiling effect:” • larger doses do not produce greater highs-- has a very low risk of abuse and overdose.

13 Question

Which of the following has an amount of alcohol consistent with a “standard drink”?

A. One Long Island Iced Tea B. 1 shot (1.5 ounces) of whiskey C. One 16 ounce beer D. One martini (3 ounces of vodka) E. There is no standard drink definition, every alcoholic beverage is a standard drink

Alcohol Use Disorder

14 National Trends - ETOH

USPSTF • Alcohol Misuse, Screening and Behavioral Counseling Interventions in Primary Care – Adults – The USPSTF recommends that clinicians screen adults aged 1 years or older for ETOH misuse and provide persons engaged in risky or hazardous drinking with brief behavioral counseling interventions to reduce misuse – Grade B Recommendation

15 Alcohol • What is Low-Risk Drinking?: • Females < 7 drinks per week < 3 drinks per occasion

• Males < 14 drinks per week < 4 drinks per occasion

• Adults over 65 years of age < 7 drinks per week < 3 drinks per occasion

Standard Drink = 14 Grams of ETOH

One 12oz. Can/Bottle of Beer

A single shot (1.5 oz.) of distilled spirits (gin, vodka, rum, etc…)

A glass of wine (5 oz.) or a small glass of sherry

16 Alcohol Withdrawal Syndromes

SYNDROME ONSET/DURATION FEATURES OTHER

Within 6-12 hours of Insomnia, Consistent from one Minor drinking tremulousness, episode to next anxiety, headache, Withdrawal diaphoresis, GI upset, palpitations Withdrawal Within 48 hours of last Tonic-clonic Usually single episode drink 3% of AUD patients Seizures Between12-24 and Usually visual but can Often mistaken for Alcohol resolve between 36-48 be aural or tactile Delirium Tremens Specific not global Hallucinations clouding of sensorium

Begin 48-72 hours Hallucinations, Occurs 5% of pts in Delirium Duration 1-5 days disorientation, withdrawal tachycardia, HTN, low Mortality rate of 5% Tremens grade fever, agitation, and diaphoresis

AUD - FDA Approved Tmts

MEDICATION PHARMACOLOGY DOSING COMMENTS

Naltrexone - Pure opioid antagonist 50 mg PO daily CAN CAUSE OPIOID - Revia ®(PO) - Blunts pleasurable OR WITHDRAWAL (no effects of alcohol and - Vivitrol ® (IM 380 mg IM Q 4 opioids for 7-10 days) reduces cravings wks (after 3 day Depot) - Reduces relapse and oral trial) BBW – can cause number of drinking days acute hepatic toxicity Acamprosate -Structural analog of 666 mg PO TID Adjust dose if diarrhea - Campral® GABA -Decreases excitatory -Works best with very neurotransmission during engaged patients withdrawal Disulfuram Deterrent- causes 500 mg Q AM Avoid ALL alcohol - Antabuse® flushing, nausea, containing products vomiting, tachycardia, (mouthwash) dyspnea, HA, blurred vision, vertigo and anxiety Must be abstinent 15-30 minutes after from ETOH >12 hrs ingestion of ETOH

17 Treatment

• Inpatient vs outpatient

• For all patients: 1. Thiamine 100mg oral/IV daily (before glucose containing fluids to avoid Wernicke encephalopathy) 2. Folate 1 mg oral for 3 days

Indications for inpatient alcohol detoxification

Indications for inpatient alcohol detoxification - History of severe withdrawal symptoms - History of alcohol withdrawal seizures or DTs - Multiple past detoxifications - Other medical or psychiatric illness - Recent high levels of alcohol consumption - Lack of reliable support network - Pregnancy

Myrick,H. Treatment of alcohol withdrawal. Alcohol Health and Research World, 1998, Vol.22 Issue 1, 38-46.

18 Treatment

Clinical Institute Withdrawal Assessment Revised Scale (CIW-Ar)

<10: Very mild withdrawal 10-15: Mild withdrawal 16-20: Modest withdrawal >20: Severe withdrawal

Smith,M. Management of alcohol intoxication and withdrawal. Principles of Addiction Medicine. 4th edition. 559-572.

Question

The “five A’s Model” for treating tobacco abuse and dependence include all of the following except

A – Ask about tobacco use on every patient B – Advise to quit C – Assess willingness to made a quit attempt D – Assist in the quit attempt E – Arrange for nicotine support group

19 Nicotine

Nicotine

• Tobacco is the chief avoidable cause of illness and death in our society • Accounts for more than 435,000 deaths/yr • 45 million smokers in the United States – 70% of them want to quit – 20 million attempt to quit each year, unaided – only 4-7% are successful

20 USPSTF • Tobacco Smoking Cessation: Behavioral and Pharmacotherapy Interventions – Adults who are not pregnant. – The USPSTF recommends that ask all adults about tobacco use, advise them to stop using tobacco, and provide behavioral interventions and US FDA- approved pharmacotherapy for cessation to adults who use tobacco – Grade A Recommendation

USPSTF • Tobacco Smoking Cessation: Behavioral and Interventions – Pregnant Women. – The USPSTF recommends that clinicians ask pregnant women about tobacco use, advise them to stop using tobacco, and provide behavioral interventions for cessation to adults who use tobacco – Grade A Recommendation

21 USPSTF • Tobacco Use in Children and Adolescents, Primary Care Interventions. – The USPSTF recommends that primary care clinicians provide interventions, including education and brief counseling, to prevent initiation of tobacco abuse among school-aged children and adolescents – Grade B* Recommended (previous grading system)

Dependence nicotine>heroin>cocaine>alcohol>caffeine among users

Difficulty achieving (alcohol=cocaine=heroin=nicotine)>caffeine abstinence

Tolerance (alcohol=heroin=nicotine)>cocaine>caffeine

Physical alcohol>heroin>nicotine>cocaine>caffeine withdrawal severity

Deaths nicotine>alcohol>(cocaine=heroin)>caffeine

Importance in (alcohol=cocaine=heroin=nicotine)>caffeine user's daily life

Prevalence caffeine>nicotine>alcohol>(cocaine=heroin)

22 The “5 A's” Model for Treating Tobacco Use and Dependence

• Ask about tobacco on every patient • Advise to quit. • Assess willingness to make a quit attempt. • Assist in quit attempt • Arrange follow up

FDA Approved

• Nicotine Replacement Therapy (NRT) -Patch (OTC) -Gum (OTC) -Lozenge (OTC) -Oral Inhaler (Rx) -Nasal Spray (Rx) • Non-Nicotine Medications -Varenicline (Chantix, Rx) -Bupropion Hydrochloride (Rx)

23 NRT Medications

• Use high enough dose • Scheduled dosing better than PRN • Can be combined with Bupropion • Don’t combine with Varenicline • Can be combined with each other • Have very few contraindications • Have no drug-drug interactions

NRT Comparisons DELIVERY DOSING PROs CONs 7, 14, 21 Mg patches -Good compliance Slow onset Patch ON in AM, OFF in PM -Continuous delivery Skin irritation -OTC Insomnia -Initial dose depends on # cigs per day 2mg or 4mg per piece -Flexible dosing (every Need to use correctly Gum 1-2 hours, up to 24 Nausea, heartburn, pieces/day) Must CHEW AND PARK -Keeps mouth busy mouth and throat (buccal absorption) -OTC burning. - Good for oral Taste tobacco users 2mg or 4mg per Flexible dosing (every Need to use correctly Lozenge lozenge 1-2 hours up to May cause insomnia, Based on time to first 20/day) some nausea, cigarette Keeps mouth busy hiccups, heartburn, Suck don’t chew /park OTC coughing 1-2 doses/hour Rapid delivery through Rx needed Nasal Spray Dose = 1 spray/nostirl nasal mucosa Nasal irritation, Flexible dosing rhinitis, watery eyes, (40/day) coughing

24 Non-Nicotine Pharmacotherapy

• First-line non-NRT medications • FDA approved -Bupropion (Zyban/Wellbutrin) -Varenicline (Chantix) • Others (nortriptyline, clonidine)

Bupropion Hydrochloride • Dopamine and norepinephrine (noradrenaline) effects • Reduces cravings, withdrawal • Improved abstinence rates in trials • Less weight gain while using • Start 7-10 days prior to quit date • Continue 7-12 weeks or longer ( > 6 months)

25 Bupropion Precautions • Contraindicated: seizure disorder, eating disorders, electrolyte abnormalities, MAO use – OK with SSRIs • NOT dangerous to smoke while taking • Monitor blood pressure • Side effects: – Insomnia (40%) – Dry mouth – Headaches – Rash

Varenicline (Chantix)

• Action at 42 nicotine receptor • Partial agonist/antagonist • Releases lower amounts of dopamine into brain than smoke – Reduces withdrawal – Not as addictive as smoke • Blocks nicotine from binding to receptor – Prevents reward of smoking

26 Varenicline (Chantix)

• In 2008 FDA added a warning regarding the use of varenicline noting that depressed mood, agitation, changes in behavior, suicidal ideation, & suicide have been reported in patients attempting to quit smoking while using varenicline .

• FDA recommends that: 1. Patients tell their healthcare provider about any history of psychiatric illness prior to starting this medication 2. Clinicians monitor patients for changes in mood and behavior when prescribing this medication

Electronic Nicotine Delivery Systems (ENDS) • Introduced into US in 2007 • 3 M teens use e-cigs • FDA reg 2016 – Covers all tobacco and vaping products and components – Required warning label about addictive nature of nicotine and that product is made from tobacco – Must be 18 or older to purchase • Solvents used to dissolve nicotine are irritants and may be carcinogenic

27 Electronic Nicotine Delivery Systems (ENDS)

• E-cigs vs. placebo – helped with abstinence from smoking traditional cigs 30 days or less but not long term • Surpasses all other forms of tobacco in youth population • Flavors that might appeal to younger age group (chocolate, bubble gum…)

28 Question

Which of the following is the most commonly abused illicit drug in the US?

A – lorazepam B – cannabinoids (marijuana) C – opiates (heroin and pain medication) D – alcohol E – cocaine

Marijuana

29 Marijuana

• Marijuana is the most commonly abused illicit drug in the United States

• Long-term marijuana abuse can lead to addiction; – compulsive drug seeking and abuse despite its known harmful effects upon social functioning – Long-term marijuana abusers trying to quit report irritability, sleeplessness, decreased appetite, anxiety, and drug craving, all of which make it difficult to quit

National Institute on Drug Abuse (NIDA) Website; http://www.nida.nih.gov/infofacts/costs.html

30 Marijuana • Effects of Use

– Physiologic – HR, RR, orthostasis,  appetite – Neurocognitive - impairment of ST memory, judgement, motor coordination – Impaired driving • #1 reported illicit drug in adolescent fatalities – Amotivational syndrome – mental slowing,  planning,  judgement, apathy – Impaired cognition - ability to learn, attention/concentration, abstract reasoning and decision making, memory – Physical health - resp function infections, strokes – Mental health – long term use  anxiety, depression, psychosis

31 References

• “Creating Opportunities for Reducing Alcohol Related Harm in the Veteran Community; Session 6: Brief Intervention.” Version 2.3. Department of Veterans’ Affairs, Australia. December 2002

• Thomas Babor, John Higgins-Biddle. Brief Intervention for Hazardous and Harmful Drinking-A Manual for Use in Primary Care. World Health Organization, Department of Mental Health and Substance Dependence. 2001

• Gentilello et al. “Alcohol Interventions in a Trauma Center as a Means of Reducing Risk of Injury Recurrence”. Annals Surgery 1999;230:473-483

• 2012 National Survey on Drug Use and Health (NSDUH) sponsored by the U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration (SAMHSA), Office of Applied Studies (OAS). http://www.oas.samhsa.gov/nsduh/2k6nsduh/2k6Results.cfm#Ch1

• National Institute on Drug Abuse (NIDA) Website; http://www.nida.nih.gov/infofacts/costs.html

• Gold, MS and Aronson, MD. Treatment of Alcohol Use and Dependence. In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2008.

• Weinhouse, GL. Alcohol Withdrawal Syndromes. In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2008.

• Motivational Interviewing: Resources for clinicians, researchers and trainers. Interaction Techniques.http://www.motivationalinterview.otg/clinical/interaction.html

• Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. May 2008.

• American Academy of Family Physicians. Studies Suggest E-Cigarettes Don't Aid Long-term Smoking Cessation: American Family Physician. http://www.aafp.org/news/health-of-the-public/20150605e-cigstudies.html , June 2015