Heroin, Fentanyl and Other Opioids. Steve Hanson

Transcription

1 Heroin, Fentanyl and Other Opioids Steve Hanson

2 Heroin/Opiates

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4 Neurotransmitter-receptor interactions To transmit instructions to cells, neurotransmitters interact with their receptors. receptor neurotransmitters

5 Neurotransmitter Action Release of NT Reuptake Receptor

6 Brain Changes

7 This is Your Brain on Drugs 7

8 Opiates Increase DA Release

9 % of Basal Release HEROIN MORPHINE hr Time After Morphine Source: Di Chiara and Imperato

10 What Drugs Do Agonists Increase NT activity Produce more NT Block Reuptake Mimic NT s Antagonists Decrease NT activity Block NT s Decrease NT s Mixed Ceiling effect

11 Opiates Dates to 4,000 BC Mimics endorphin activity Natural - Opium, morphine, codeine Semi-synthetic- Heroin, Dilaudid Synthetics - Darvon, Demerol, Fentanyl

12 Modern History Off and on use through until the 60 s Man with the Golden Arm Vietnam war soldiers using heroin 1970 s increased prevalence urban areas Treatment programs Methadone Maintenance / Therapeutic Communities 1980 s Hard to find substitutes 1990 s resurgence 2010 s epidemic

13 Heroin Chic

14 Opiates Heroin more potent % - <10% in 70 s Younger age group - High School Users start with snorting - IV within 12 months Withdrawal painful - not deadly

15 NATURALOPIATES OPIUM MorphineCodeineThebaine

16 Semi-synthetics Morphine Heroin Dilaudid

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18 Synthetics Demerol Fentanyl Methadone Darvon

19 Opiates Fat solubility Heroin high rush Morphine lower longer onset Heroin metabolized into morphine Morphine metabolized by the liver Metabolite is 10-20X more powerful Detectable in urine for 2-4 days

20 The Action of Heroin (Morphine)

21 Tolerance Rapid tolerance with continued use Initial dose of 50mg/day can go to 500mg/day in as little as 10 days Cell sensitivity thought to be the tolerance mechanism.

22 Opiates & Reward Pathway

23 Opiates Increase DA Release

24 Agonists, Mixed and Antagonists

25 Effects Analgesia - change in pain perception Euphoria - intense Sedation - on the nod Respiratory depression Cough suppression Nausea/vomiting Constipation Heroin Withdrawal Pain Depression Alert Rapid breathing Coughing Nausea/vomiting Diarrhea 3-5 days

26 Addiction/Dependency Cycle Opioids trigger reward system euphoria leads to continued use addiction Withdrawal symptoms are significant regular use to avoid withdrawal - dependence

27 Addiction vs. Dependency

28 Natural History of Opioid Dependence

29 Potency Factors by Weight Morphine 1 Heroin 3 Codeine 0.1 Dilaudid 8 Demerol 0.05 Fentanyl

30 Potency NIDA

31 Heroin usage patterns Highly addictive and dependence producing Significant tolerance up to 35X Increased cost Tolerance management (Tx, jail, etc.) Mixing with other opiates and other drugs (speedballing/cocaine)

32 Prescription Opiates

33 OxyContin

34 OxyContin Oxycodone synthesized from thebaine (part of opium) OxyContin 1995 Crush the tablet for quicker high Oral, snort, inject Percocet oxycodone & acetaminophen Percodan oxycodone & aspirin

35 Vicodin

36 Vicodin Hydrocodone and acetaminophen Lorcet, Lortab Schedule III high psychological/medium physical Pain and post-surgical use (pain)

37 Drug Overdose Rate Higher than Motor Vehicle Death Rate 5/22/ Source: CDC

38 Drug Poisoning Deaths Involving Opioids: USA,

39 Heroin Death Rate Male vs. Female

40 Heroin-related deaths highest among aged 25-44

41 Treatment Traditional Recovery Based/NA Naltrexone - Antagonist/Blocker Opiate Maintenance Tx withdrawal management Methadone- daily Buprenorphine/Suboxone Methadone to abstinence models

42 What is effective treatment? Pharmacotherapy Methadone Buprenorphine Naltrexone Recovery Support AA, NA, SMART Recovery Recovery Coaches Psychosocial Interventions CBT, MI, CM

43 Detox Detox: Medical risk with opioid withdrawal is low, while discomfort is very high Inpatient Outpatient Only recommended during 2 nd trimester of pregnancy if mother is invested Otherwise methadone stabilization is in best interest of mother and fetus

44 Levels of Care Inpatient rehabilitation 5-21 days length of stay Focus on medical/psychiatric stabilization May initiate Suboxone for opiates Community residence (halfway houses) Supportive living environment 3-12 months

45 Levels of Care Intensive Residential Supportive environment therapeutic community Longer term stays 6-24 months Focus on rehabilitation/sober living skills Outpatient Intensive outpatient

46 Federal Position Drug courts that receive federal dollars will no longer be allowed to ban the kinds of medication-assisted treatments that doctors and scientists view as the most effective care for opioid addicts, Botticelli announced in a conference call with reporters. (Michael Botticelli ONDCP Director) "We've made that clear: If they want our federal dollars, they cannot do that. We are trying to make it clear that medication-assisted treatment is an appropriate approach to opioids. (Pamela Hyde, SAMHSA s Administrator) 5/22/

47 BJA Grants Applicants must demonstrate that the drug court for which funds are being sought will not: 1.deny any appropriate and eligible client for the drug court access to the program because of their medically necessary use of FDA-approved medication assisted treatment (MAT) medications (methadone, injectable naltrexone, non-injectable naltrexone, disulfiram, acamprosate calcium, buprenorphine) that is in accordance with an appropriately authorized physician's prescription; and 2.mandate that a drug court client no longer use medically necessary MAT as part of the conditions of the drug court if such a mandate is inconsistent with a physician's recommendation or prescription. Under no circumstances may a drug court judge, other judicial official, or correctional supervision officer connected to the identified drug court deny the use of these medications when medically necessary and when available to the clients and under the conditions described above. 5/22/

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49 Pharmacological Approaches Goals Provide: relief from withdrawal symptoms, prevent drugs from working, reduce craving, aversive reactions These actions are helpful in reducing relapse and increasing retention in programs

50 Does Treatment Work? Medications + psychosocial therapy both benefit brain function and recovery. Each affects different parts of brain and in opposite ways. PET scans adapted and retouched from Goldapple et al. 2004

51 Pharmacological Approaches Methadone Opiate addiction reduces craving, mediates withdrawal symptoms, helps restore normal functioning Buprenorphine (Suboxone) similar to methadone, may be prescribed by an MD with special training)

52 Pharmacological Approaches Naltrexone (Vivitrol) stops opiates from working, changes alcohol action for some reduction in relapse 30 day dose. Baclofen possible reduction in cocaine cravings

53 Patient Needs Diabetes Some can control with diet Some can control with medication Some are insulin dependent Without adequate treatment - many will die Opiod Addicts Some can quit on own Some can remain abstinent with regular treatment Some need ORT Without adequate treatment - many will die

54 Methadone Effectiveness Gunne & Gronbladh, 1984 Methadone H H H H H H H H H H H H H H H H H Baseline Regular Outpatient Rx. H H H H H H H H H H H H H H H H H

55 Methadone Effectiveness Gunne & Gronbladh, 1984 Methadone P H H H H After 2 Years No Methadone P P H 1 H H H H 2 H H H H H 3 H H D D 1- Sepsis & endocarditis 2- Leg amputation 3- Sepsis

56 Methadone Effectiveness Gunne & Gronbladh, 1984 Methadone P H H H After 5 Years No Methadone P P D P D D D D

57 Retention in treatment Heilig, Lancet 2003 Centers for Disease Control (2011)

58 Buprenorphine A tragic appendix: Mortality Heilig, Lancet 2003 Placebo BPN Dead 4/20 (20%) 0/20 (0%)

59 Vivitrol Long Acting Injectable Helps with compliance Non-Addicting

60 Is Vivitrol THE ANSWER? 2015 Vermont Review Research is limited. FDA approval based on a single 6 month trial in Russia. Health Risk Liver toxicity, Death (51 from ) Overdose Risk upon termination Effective for Some still to be defined

61 Is naltrexone (XRN) effective? 1. XRN vs. Placebo RCT (Lancet 2011) a.setting: Russia; Funder: Alkermes b.enrolled patients post-detoxification ( 7 days since last use) c.outcome: XRN: retention; opioid free weeks; cravings 2. XRN vs. Usual Care RCT (NEJM 2016) a.setting: USA; Funder: NIDA; Alkermes donated XRN b.enrolled justice-involved pts preference for opioid free tx c.outcome: XRN: time to relapse (10.5 weeks vs 5.0 weeks) 3. Two Comparative XRN vs. Bupe Studies (2017)

62 XRN vs. Bupe 1. XRN vs. Bupe RCT (Tanum, JAMA 2017) a.setting: Norway; Funder: RCN; Alkermes allowed comments b.recruited; sent for detoxification; then enrolled/analyzed c.232 recruited 165 included (51 refused; 6 failed detox) d.outcome: XRN and Bupe similar in reducing opioid use 2. XRN vs. Bupe RCT (Lee, Lancet 2017) a.setting: USA; Funder: NIDA; Indivior donated Suboxone b.recruited; stratified; analyzed both per-protocol and ITT c.itt: Bupe>XRN; 28% of XRN vs. 6% bupe never started TX d.pp: Of those who started, relapse rates similar for both

63 XRN vs. Bupe Patients less likely to successfully start naltrexone than bupe. Naltrexone group 72% successfully inducted Buprenorphine group 94% successfully inducted Patients not inducted on medication Patients successfully inducted Slide courtesy of NYC DOHMH

64 XRN vs. Bupe Naltrexone group 72% successfully inducted 28% of patients in XRN arm experienced early relapse. Of the patients able to complete detox & start treatment, relapse rates between XRN & Bupe were similar at 24 weeks. Patients not inducted on medication Patients successfully inducted

65 NARCAN - Overdose Reversal Kits 5/22/

66 Summary 1. Opioid addiction is a chronic condition associated with multiple harms, including fatal overdose, and that requires ongoing social support and medical care. 2. Drug possession/use and crime committed to pay for drugs and prevent opioid withdrawal result in frequent criminal justice exposure. 3. Treatment exists and is effective at reducing harms of opioid addiction. Medications for Addiction Treatment (MAT) such as methadone & buprenorphine have the strongest evidence base, with emerging evidence to support naltrexone in highly motivated patients. 4. Ultimately, all treatment options should be available to patients and decision regarding treatment modality should be made between patient and health care provider.