Pharmacology of Opiates. Steve Hanson Associate Commissioner NYS OASAS
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1 Pharmacology of Opiates Steve Hanson Associate Commissioner NYS OASAS
2
3 Neurotransmitter-receptor receptor interactions To transmit instructions to cells, neurotransmitters interact with their receptors. receptor neurotransmitters
4 Neurotransmitter Action Release of NT Reuptake Receptor
5 ENDORPHINS Endogenous Morphine Response to Pain Morphine Receptor sites Enkephalins found in tears
6 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
7 Opiates Dates to 4,000 BC Mimics endorphin activity Natural - Opium, morphine, codeine Semi-synthetic- Heroin, Dilaudid Synthetics - Darvon, Demerol, Fentanyl
8 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
9 Heroin Chic
10 Why would people use Heroin? Take the best orgasm you ve ever had Multiply it by a thousand. And you re still nowhere near it.
11 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
12 NATURAL OPIATES OPIUM Morphine Codeine Thebaine
13 Semi-synthetics Morphine Heroin Dilaudid
14
15 Synthetics Demerol Fentanyl Methadone Darvon
16 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
17 The Action of Heroin (Morphine)
18 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.
19 Addiction/Dependency Opioids trigger reward system euphoria leads to continued use addiction Withdrawal symptoms are significant regular use to avoid withdrawal - dependence
20 Opiates & Reward Pathway
21 Opiates Increase DA Release
22 Opiate Effects Analgesia - change in pain perception Euphoria - whole body orgasm Sedation - on the nod Respiratory Depression - OD Cough Suppression Nausea/vomiting Constipation
23 Pain Depression Alert Rapid Breathing Coughing Nausea/Vomiting Diarrhea 3-5 days Withdrawal
24 Addiction vs. Dependency
25 Potency Factors by Weight Morphine 1 Heroin 3 Codeine 0.1 Dilaudid 8 Demerol 0.05 Fentanyl
26 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)
27 Treatment Traditional Recovery Based/NA Naltrexone - Antagonist/Blocker Opiate Maintenance Tx withdrawal management Methadone- daily Buprenorphine/Suboxone Methadone to abstinence models
28 Pharmacology of Methadone Charles W. Morgan, M.D., FASAM, FAAFP, DABAM Acting Medical Director New York State Office of Alcoholism and Substance Abuse Services Medical Director John L. Norris Addiction Treatment Center NYS Office of Alcoholism and Substance Abuse Services
29 What is Methadone? Methadone is a synthetic opioid analgesic synthesized in 1937 by German scientists Max Bockmühl and Gustav Ehrhart who were searching for an analgesic that would be easier to use during surgery and also have low addiction potential. (Dolophine) Although chemically unlike morphine or heroin, methadone also acts on the opioid receptors and thus produces many of the same effects. Chemically, methadone is the simplest of the opioids.
30 Methadone introduced in USA Methadone was introduced into the United States in 1947 by Eli Lilly and Company as an analgesic. Since then, it has been best known for its use in treating narcotic addiction, though it has also been used to managing chronic pain due to its long duration of action and very low cost
31
32 Heroin Addiction: a Metabolic Disease Vincent P. Dole, MD and Marie E. Nyswander, MD
33 Heroin addiction is a brain disease Mary Jeanne Kreek, MD
34 Endorphin mechanism of action Mu Receptor Endorphin Lock & Key
35 Methadone Opioid full agonist: the more you give the more the effect Mu Receptor Opiate Addiction
36 Examples of Opioids: Heroin Morphine Hydromorphone Buprenorphine Fentanyl Meperidine Oxycodone Hydrocodone Tramadol
37 Methadone stabilizes the brain so that treatment can occur.
38 Methadone Recovery Methadone itself is not the treatment for Opioid Dependence; it merely helps to achieve the condition for treatment to be effective.
39 METABOLISM Converted in liver Recirculation Excreted by liver and kidney Highly protein-bound
40 Main Methadone Metabolite EDDP 2 ethylidene 1, 5 dimethyl, 3,3 diphenylpyrreline Inactive Implications for UDS
41 Drugs that interact with Methadone INH (decreased or increased methadone levels) HIV Antivirals (increased or decreased methadone levels, new data) Dilantin (decreased methadone levels) St. John s Wart (decreased methadone levels) Antihistamines (severe constipation) Prozac (increased methadone levels) Azithromycin (cardiac) Ciprofloxin (cardiac) ACE Inhibitors (cardiac) Diuretics (cardiac) Buprenorphine (withdrawal) Carbamazepine (decreased methadone level)
42 Drugs that interact with Methadone Clozapine (sedation) Erythromycin (sedation, cardiac) Tricyclics (sedation) Ginseng (sedation) Risperdal (sedation) Trazodone (sedation) Depakote (sedation) Baclofen (sedation) Phenobarbital (sedation) Chamomile (sedation) Ethanol (sedation, death) Benzodiazepines (sedation, death) Cytochrome P450 System
43 Why people say they use heroin I use it to feel normal I I always felt different... and then I took my first... and suddenly I felt like I thought everyone else had been feeling all along.
44 Methadone is an opiate used to treat Opiate Dependence Duration of action Heroin short Methadone long (half-life of about 24 to 30 hours)
45 Optimal Dose (Blocking Dose) Average Dose Blocks withdrawal Blocks mu receptors Blocks effects of heroin mg per day Nyswander & Dole Less than mg per day not effective
46 Methadone Myths 1. Rots teeth 2. Gets into your bones 3. It s harder to withdraw from methadone. 4. It s more dangerous than heroin. 5. Harms your liver 6. Harms your immune system 7. Leads to use of other drugs 8. Lower doses are better. 9. Causes sedation 10. Pregnant women should detox from methadone. 11. Mothers cannot nurse their babies. 12. All babies born to mothers on methadone will go through withdrawal. 13. Methadone doses should be low for pregnant women.
47 Side Effects Constipation Sedation Urinary Retention Prolonged QTc interval and other cardiac and BP effects Decreased libido Drug interactions Respiratory depression Nausea/vomiting Pulmonary edema Opioid induced androgen deficiency NAS
48 Lifetime Lifetime Lifetime Lifetime Duration of Treatment with Methadone Detoxification Detoxification Detoxification Detoxification to
49 Safe use of methadone PA/SAMSHA/CSAT/IRETA Conference Recent Deaths related to improper usage during the treatment of pain Careful induction Concomitant use of other medications Patient education
50 Methadone is the most regulated Prescribed medication in the U.S State (OASAS) Federal Local Methadone FDA DEA
51 Who s appropriate for Methadone Maintenance 1 year of opiate dependence Current physiological dependence At least 18 years of Age Exceptions for pregnancy Exceptions for individuals being released from incarceration Priorities for pregnant and HIV positive people
52 Regulations Admission Criteria Take Homes Guest Dosing Communication/Documentation
53 Buprenorphine Treatment of Opioid Addiction Andrew Kolodny, M.D. Chief Medical Officer Phoenix House Foundation New York, NY
54 How to Pronounce Buprenorphine BUEW PRE NOR FEEN 54
55 Suboxone = buprenorphine + naloxone 55
56 Buprenorphine Treatment Partial agonist Weaker effects Safer to use Long duration of action Lower risk of overdose death
57 Full Opioid Agonists
58 Buprenorphine- A Partial Agonist
59 Buprenorphine Diversion Some docs are prescribing irresponsibly Has significant street value Black market use of often therapeutic Patient seeking treatment often acknowledge having tried already tried it Does not appear to be popular among opioid naïve teens or as a party drug 59
60 Buprenorphine as Contraband in Correctional Settings 60
61 Buprenorphine Treatment Unlike methadone, prescribed by doctors Patients can take it temporarily as a detoxification agent Patients can be maintained on it without an arbitrary time limit
62 Retention in treatment Heilig, Lancet 2003 Remaining in treatment (nr) Detoxification Maintenance Treatment duration (days)
63 Buprenorphine RCT A tragic appendix: Mortality Heilig, Lancet 2003 Placebo BPN Dead 4/20 (20%) 0/20 (0%)
64 Summary We are in the midst of an epidemic of opioid addiction To reduce overdose deaths, crime, infection diseases and other problems, we must rapidly expand access to effective treatment. 64
Opiates Heroin/Prescription Steve Hanson Opiates Dates to 4,000 BC Mimics endorphin activity Natural - Opium, morphine, codeine Semi-synthetic- Heroin, Dilaudid Synthetics - Darvon, Demerol, Fentanyl Modern
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