Opioids- Indica-ons, Equivalence, Dependence and Withdrawal Methadone Maintenance (OST) Paul Glue

Transcription

1 Opioids- Indica-ons, Equivalence, Dependence and Withdrawal Methadone Maintenance (OST) Paul Glue

2 Scope Pharmacology of Opioids Equivalence Dependence and Withdrawal Methadone Maintenance (OST)

3 3 Opioid receptor classes Mu: supraspinal analgesia (µ1), euphoria, resp depression (µ2), physical dependence, miosis, cons-pa-on, seda-on Kappa: spinal analgesia, miosis, seda-on Delta: analgesia Endogenous ligands Enkephalins Endorphins Dynorphins

4 Mu receptor agonists ac-va-ng mu receptor decreased camp levels decreased glutamate and substance P release decreased neuronal excita-on decreased pain signal sensi-vity and transmission

5 Mu ligands Agonists Strong morphine, heroin, methadone, pethidine, fentanyl, alfentanil etc Moderate oxycodone, codeine Par-al agonist buprenorphine Antagonists naloxone, naltrexone Natural: (opiates) opium; morphine; Synthe-c: (opioids) heroin; methadone; etc...

6 Indica-ons Moderate severe pain Breathlessness in pallia-ve care

7 Opioid equivalence (pallia-ve care) hup://

8 Opioid abuse and dependence Pharmacology: µ opioid agonism Acute effects: analgesia; euphoria (depends on route of administra-on); nausea, cons-pa-on, seda-on, dizziness; respiratory depression; pruri-s, cons-pa-on, hypotension Tolerance Development: rapid for euphoria; also (but slower) tolerance to seda-ve, analgesic, resp. depressant, nausea s/e dose escala-on to injectable/smoked opioids; less with oral/long t½ drugs Dependence: differen-ate physical dependence (e.g. in pa-ents with cancer pain) vs. full dependence syndrome in opioid addicts cancer pa-ents will tolerate slow down--tra-on and stopping of opioids without desire to reinstate drug use

9 hat opioids are available in NZ no heroin Opioid Dependent est 10-26,000 adults Sellman et al % Morphine; 50% Methadone Adamson & Sellman 1998 Robinson et al 2011

10 IDMS Chris Wilkins, Massey Yearly survey of drug use in NZ major centres hup:// Colleges/College%20of%20Humani-es%20and %20Social%20Sciences/Shore/reports/IDMS %202013%20report.pdf? 6908B6F2215DE C0938DC08

11 Where is it all coming from? Methadone OST services Morphine, oxycodone, DHC chronic pain prescribers Doctor shopping doctor decep-on/manipula-on forged prescrip-ons Occasionally Hospice inheritance ; veterinary supplies; robberies,etc Prescrip<on drug misuse: issues for primary care Sheridan & Butler (2008) University of Auckland

12 Opioid withdrawal symptoms Resembles a severe flu-like illness. Onset within 30-36h of last methadone dose Peaks at ~36-72h aper this Craving and risk of further use + ++ during this -me May persist as milder state for weeks aperwards

13 OWS Measurement scales e.g. COWS

14 Opioid Withdrawal unpleasant but not life threatening -me course depends on opioid (5-10 days/heroin; 2-3wks/ methadone) early withdrawal: drug craving; restlessness, irritability; hyperalgesia; GI symptoms (nausea, vomi-ng, diarrhoea, cramps); myalgia; dysphoria, anxiety, insomnia; autonomic overac-vity (tachycardia, swea-ng, dilated pupils), yawning late withdrawal: anxiety, insomnia, craving, cyclical weight changes main risk restar-ng opioid use Withdrawal treatment op-ons: nothing (cold turkey) managed detox required if further drug treatment is planned

15 Opioid withdrawal PD Noribogaine study (CPDD 2016) Placebo group (l) had mean 14h between last dose of morphine and resump-on of opioids associated with increased COWS scores Note increase in COWS by ~6 points Pupil diameter increased ~1mm N 180mg N 120mg n Placebo l N 60mg

16 (1) Withdrawal to abs-nence Withdrawal op-ons clonidine (α2-agonist 150mcg BID - effec-ve against sympathe-c NS symptoms) plus loperamide (peripheral opioid agonist - effec-ve against GI symptoms) no effects on myalgia or craving symptoms Very low success rate for sustained abs-nence (2) Transfer to therapeu-c opioid with subsequent dose reduc-on: based on cross tolerance of opioid agonists switch from short-ac-ng street opioid to long-ac-ng legal opioid e.g. test dose of methadone 20mg and observe effects - usual daily dose range 40-80mg/day establish transfer dose and then reduce by 20%/day Very low success rate for sustained abs-nence

17 OST (3) Long term opioid subs-tu-on: Ra-onale: Major complica-ons of chronic opioid use are social and legal; physical complica-ons are 2 o to illicit nature of opioid use; avoid by providing pharmaceu-cal grade non-iv opioids under supervision; generally once stabilized pa-ents do not tend to escalate doses; facilitates involvement with psychological/social services most successful strategy in management of opioid dependence Rx - full or par<al opioid μ agonists - all class B/C controlled drugs: methadone 20-80mg/day (oral - daily) buprenorphine 8-32mg/day (sublingual; t1/2 > 24h - may give on alternate days;?safer in overdose than methadone) Suboxone (buprenorphine/naloxone 4:1 combo - 8/2-32/8mg/day sublingual) (EU) 7 heroin subs-tu-on trials completed

18 NZ MoH OST guidelines publications/nz-practice-guidelines-opioid-substitution-treatment-apr14-v2.pdf

19 (4) Opioid antagonists: Opioid antagonists: Naltrexone /day (long ac-ng orally ac-ve μ antagonist) or Vivitrex depot injec-on no effects on craving or protracted withdrawal symptoms - however blocks agonist effects not effec-ve for most heroin addicts; main pa-ents are highly mo-vated white collar addicts (e.g. physicians; nurses; pharmacists)