Treatment options in Opioid Dependence. Dr Kevin Stoloff

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1 Treatment options in Opioid Dependence Dr Kevin Stoloff

2 Today opiates/opioids history of use mechanism of action intoxication/ withdrawal neurobiology of addiction treatment options

3 opiates vs opioids Derivatives of opium eg heroin and morphine All substances, natural or synthetic (pethidine, fentanyl etc), that act at mu - opioid receptors in brain

4 Opium poppy

5 Opium Opium is a complex chemical cocktail containing sugars, proteins, fats, water, meconic acid, plant wax, latex, gums, ammonia, sulphuric and lactic acids, and numerous alkaloids, most notably morphine (10%- 15%), codeine (1%-3%), noscapine (4%-8%), papaverine (1%-3%), and thebaine (1%-2%)

6 Heroin On the illicit market, opium gum is filtered into morphine base and then synthesized into heroin.

7 Short history Persia, Egypt and Mesopotamia. first known written reference to the poppy appears in a Sumerian text dated around 4,000 BC. Homer conveys its effects in The Odyssey

8 Short history Popular in Egyptian civilizations Opium bought on streets of Rome 8th Century AD spread to India, Arabia,China 16 th C Laudenum created by Paracelsus; essentially tincture of morphine: created witches brew when he added this to henbane, crushed pearls, and frogspawn 19 th C laudenum in British Pharmacy s

9 Short History Youngsters introduced to pleasures of opiates at mothers breasts; baby-minders and parents found babies happy and docile Godfrey's Cordial Street's Infants' Quietness, Atkinson's Infants' Preservative, Mrs Winslow's Soothing Syrup.

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14 Thomas De Quincy Whereas wine disorders the mental faculties, opium introduces amongst them the most exquisite order, legislation and harmony. Wine robs a man of selfpossession; opium greatly invigorates it...wine constantly leads a man to the brink of absurdity and extravagance; and, beyond a certain point, it is sure to volatilize and disperse the intellectual energies; whereas opium seems to compose what has been agitated, and to concentrate what had been distracted....a man who is inebriated...is often...brutal; but the opium eater...feels that the diviner part of his nature is paramount; that is, the moral affections are in a state of cloudless serenity; and over all is the great light of majestic intellect... Confessions of an opium- eater (1821)

15 Samuel Taylor Coleridge "In Xanadu did Kubla Khan A stately pleasure-dome decree Where Alph, the sacred river, ran Down to a sunless sea I would build that dome in air, That sunny dome, those caves of ice! And all who heard should see them there, And all should cry, Beware! Beware! His flashing eyes, his floating hair! Weave a circle round him thrice, And close your eyes with holy dread, For he on honey-dew hath fed, And drunk the milk of Paradise."

16 And Opium wars Advent of hypodermic syringes and upper classes in Europe and America injecting morphine opiates.net God s own medicine by Sir William Osler

17 Neurobiology of addiction

18 Endogenous opioids

19 Intoxication At above pain-relieving does occupation of mu-receptors gives very intense brief euphoria (a rush ), followed by a profound sense of tranquility, (may last several hours), followed by drowsiness

20 Dependence early on in addiction, intoxication alternates with normal functioning later, euphoria absent, and alternates between withdrawal, and lack of withdrawal

21 Withdrawal?

22 Inputs to Mesolimbic dopamine pathway of reward amygdala Nucleus Accumbens Emotional learning ie fear, reward, pleasure, cues assoc with pleasure pleasure Enkephalin (opioid) 5HT GABA cannabinoid VT

23 Mesolimbic dopamine pathway of reward Reactive reward system amygdala Nucleus Accumbens Emotional learning ie fear, reward, pleasure, cues assoc with pleasure pleasure VT Repeated exposure, this system pathologically learns to trigger drug-seeking behaviour in response to int/ ext cues

24 Mesolimbic dopamine pathway of reward Reflective reward system Reactive system regulated by top-down reward system involving regions of pre-fontal cortex Should I be doing This Is it worth it? Let me weigh it all up? H. C. Connections to NA including CSTC loops Nucleus Accumbens

25 Mesolimbic dopamine pathway of reward Reactive reward system Yes, emotional memories of pleasure are being triggered, find drugs now Amygdala? Nucleus Accumbens Am I detecting anything rewarding related to previous drug experience? Reward circuitry HIJACKED, cannot base decisions on consequences VT

26 Take drugs or not to take drugs? Reflective pathway (will power) Reactive pathway (temptation) In addiction, balance is disturbed

27 Heroin in RSA Main illicit opioid Statistics from inpatient treatment centres 8 to 23% in 2008 heroin primary 76% are repeat treatment seekers Mostly smoked 6 to 18% report ivi % black/african increasing ie 65% Gauteng; 73% NR

28 Medical model Aim for abstinence from all opioids In clinical practice, short-term success for total abstinence is low eg in 1 study, 34% relapsed within 3 days, 45% within a week, and 60% within 90 days Abstinence assoc with completing programs, and aftercare

29 options Rapid detoxification from all opiates, and relapse prevention Harm reduction method, which is substitute opioid prescribing international trends

30 Medications used Methadone Buprenorphine (Subutex) Suboxone

31 Rapid detoxification 7 to 21 days Graded lowering of opioid dose Use opioid substitution medication (methadone or bubrenorphine), and/ or symptomatic treatment (for mild dependence)

32 Aspects to consider Identification and motivation Detoxification Management of co-morbid medical and mental health problems Relapse prevention

33 About detoxification Using substitution medication, need to start with enough to alleviate withdrawal symptoms, without intoxication (baseline dose usually worked out in first 3 days) Thereafter, gradual reduction of dose Non-substitute medications include alpha-2 agonist, clonidine (blocks sympathetic hyperarousal), but not muscle aches, dysphoria, craving Buscopan, paracetamol, immodium, diazepam

34 Relapse prevention Psychosocial: various, including CBT, relapseprevention therapy, 12-step programs like NA Pharmacological: Naltrexone opioid antagonist (blocker), can be injected, implanted or taken orally. Was not available except on case-by-case basis but now oral naltrexone has become availabe Risks: overdose, and precipitate withdrawal

35 Susbtitute opioid prescribing Some unable to give up, so intervention to reduce harm till ready Harm reduction strategies popular internationally due to chronic relapsing nature, and poor results of rapid detox Cochrane: proven effectiveness, and methadone maintenance Rx reduces morbidity (incl HIV risk, incarceration and other substance use), and mortality, and increases retention in care

36 Methadone Until recently, only physeptone (cough mixture at 2mg/5ml so inaccurate dispensing Now equity elixir is available in RSA 2mg/ml Full mu-opioid agonist, and therefore toxicity/ overdose possible given daily QTc prolongation Metabolized CYP2B6/3A4P450 PI s in HIV toxicity, and Rifampicin and anti-covulsants can cause withdrawal Benzo s/ alcohol

37 Buprenorphine (Subutex) Partial mu-receptor agonist with low intrinsic activity but high R affinity (so if heroin added, diff to displace) Ceiling effect so reduces risk of toxicity, so reduces overdose risk Can precipitate withdrawal in highly dependent

38 Suboxone Buprenorphine thought to have low abuse potential but still happening So developed buprenorphine-naloxone combo as deterrent to injecting of buprenorphine

39 Suboxone Naloxone S/L absorbtion poor, buprenorphine good, so S/L will not precipitate withdrawal; but if ivi, nalaxone absorbed well, and highly unpleasant but safe withdrawal precipitated 4:1 orally is equally effective for SOT

40 Cape Town Stikland Hospital inpatient detoxification 1 week; Suboxone 1 st line, equity methadone 2 nd line Both have been applied for at district/ secondary hospital level (obstetrics, psychiatry etc) OST clinic Above not registered as substitute drugs in RSA but because detox outcomes poor, offer a Monday morning OST Clinic, but patients have to pay privately for meds

41 Cape Town Crescent Clinic, Kenilworth Clinic and others do detox Some private practitioners provide substitution therapy

42 References Weich, L et al, (2009). South African Guidelines for the Management of Opioid Dependence: Update 2009; S African Med Journal, Jan 2010 South African Community Epidemiology Network on Drug Use (SACENDU)- updarte June The plant of joy opiates.net Google images

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