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36 Cards in this Set
- Front
- Back
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Opium & derivatives |
- opium poppy: opium comes drom the poppy plant Papaver Somniferum (god of sleep) - not same as garden variety - morphine comes from plant (diffuclt to synthesize) - opiates come from the poppy (opium, morphine, codeine, thebaine). - opiods is the poppy ones plus the synthetics |
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Describe the history of opium outside north america |
- 1513 Portuguese control trade from Calcutta to Canton and introduced smoking pipe to china, began to trade opium for silk, spices, etc - 1600s Dutch, French and British involved in opium trade with China- opium dens flourish in China. This became a serious problem. - 1796 - chinese Empereror banned opium but illegal transport from the birtish, french etc didnt stop - 1838 Chinese govt seizes British opium , beginning first OPium Wat - 1842 China surrenders, cedes Hong Kong tp British, but refuses to legalize opium - 1856-60 second OPium war between china and britian/france- treaty imposes legalized opium in china -1900- 13.5 million chinease opium addicts |
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Describe the history of opium in north america |
- 1852-70- large chinese immigration to work on railroads, brought opium - 1861-63 morphine was extensively used during the US civil war- morphine isolated, invention of syringe = large number of dependent men. “ soldier disease” meant being morphine dependency - 1878-1885 approx 60% of opiate addicts in US were middle class women buying legal opiates - dependence was 4.6/1000 vs 2/1000 now - scheduled in Canada following narcotic Control Act -Aspirin was producer of heroine, marketed as a cough sedative. Aspirin used to be only available by prescription, but heroine free samples |
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three types of drugs used for reliefe of pain : analgesics |
1) opioids (opiate, narcotic) analgesics 2) Non-opioid (non-narcotic) angalgesic-anti-inflammatory analgesics NSAIDS 3) Analgesic adjuvants: antidepressants, anticonvulsants, NMDA-antagonists, Tetrahydrocannabinol (Sativex) |
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look at this chart |
Morphine: standard dose = 10 mg intramuscular, 60 mg orally. hald life =6 hrs, but analgesia is 4-5 hrs duration Methadone is more potent than morphine and has a duration of 18-24 hrs |
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What are some pure agonists/ antagonists, mixed and partial? |
- in a chronic addict, opiate receptors are full, if you give them an antagonist like naltrexone, they go into immediate withdrawal- this is used to save people form overdose- on partial agonist, like buprenorphene, if they try to inject heroin, there will be no effect of the heroin |
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Pharmakokinetics of morphine |
- poorly absorbed orally - when abused, either smoked or injected - slowly crosses BBB - achieves same levels in fetus as mother - for chronic pain, morphine can be delivered firectly into spinal fluid via a pump - avoids sig levels in blood stream (post surgery) - Morphine is metabolized to an active metabolite: morphine-6-glucuronide -Both have half-lives of about 3–5 hours - Patients with impaired renal function accumulate the active metabolite and can become toxic - Urine screening: metabolites can be detected for 2–3 days |
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Pharmacodynamics of morphine |
AnalgesiaEuphoria (tranquil drowsiness) Diminishment of sexual desire Sedation and anxiolysis (tingling sensation, feeling of warmth in lower abdomen) Respiratory depression Cough suppressionMiosis |
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Read the 2 case presentations |
DO IT |
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Describe personality disorders. What are the two types? |
- inflexible, distressing impairments in emotion regulation - ASPD and BPD are really comorbid with alcohol ASPD: lack of remorse, conduct disorder prior, reckless, aggressive, impulsive, violation of others rights BPD: unstable and intense relationships, impulsive, affective instability, chronic feelings of emptiness, fear of abandonment, suicide/self harm |
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Criteria for BPD |
5 or more criteria -frantic efforts to avoid abandonment - unstable intense relationships - identity disturbance - unstable mood - emptiness - cant control anger - recurrent suicide /self harm - paranoid ideation or dissociative symptoms - impulsivity |
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Multiple problems related to combo of alcohol and heroin (7) |
- sever physical dependence (withdrawal symptoms including seiures, restlessness, pain, potential for grand mal seizures) - abnormal thinking (disorientation, loss of sense of reality) - aggressiveness, excessive sedation, confusion - coordination problems - depression - memory loss of recent events - nervousness/irritability |
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Prescription opioid Dependence |
- 15-21% canadians sed prescription opioids in the past year -oxycotin abuse up 3.8%-55.4% 200-2004 - number of treatment admissions for opioids doubled in two years , deaths up 242% - Nova Scotia started a program fro doctors over prescribing opiates - more prescription opioids deaths in US 1999-2010 than heroin, cocaine, benzos - Fentanyl’s popularity has risen as the availability of other opiates like Oxy has declined- Canada and US - regulations are tightening and opium drug companies are under pressure to crease tamper-proof drugs, and this has caused a major resurgence of heroin abuse in NA |
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what is the largest producer of opium? consumer? |
Australia is the largest producer (37% of global production) Afghanistan is the largest illegal growing country; - Canada is the largest consumer of opiates/morphine (medical purposes) in the world!! 812mg per capita. There are a lot of pain patients addicted to opiates. But becoming too restrictive withn these people is dangerous bc they need the meds |
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Describe early treatment of opiate addiciotn |
- legislations to limit availability started in 1910 in canada NCA - in US physicians were allowed to prescribe, but gvt tried to prosecute - 1918 govt in us established treatment clinics - morphine and other drugs were prescribed for opiate addicts . This can be considered the 1st wave of opiate maintenance programs. These were discontinued in 1923 - after 1923 there were only prison-like hospitals involving drug-free cold turkey detox - 1963 Dole and Nyswander started studying methadone- oral and suppressed withdrawal symptoms with a single daily dose. After 6 days of regular methadone doses they will get to a steady state - this means no withdrawal AND opiate receptors should be occupied so that you wont het a rush from any additional heroin that you take - early reports of this therapy indicated that there could be a considerable amount of rehabilitation of opiate addicts following regular methadone admin |
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What are the stats like for heroin detox? |
- outcomes were very poor - regardless of the detox method- non-oiiate, methadone, sedatives, still have VERY high (like 80-90+%) readdiction rates, many fail to complete program Why has detox from opiates generally been so unsuccessful? - protracted withdrawal? - cue-induced craving and conditioned withdrawal symptomatology - hyperalgesia - high prevalence of comorbidity (personality disorders?) - Very poor preparation and rehab prior to detox. As shown by Stimmel et al, longer term outcomes improves significantly with appropriate treatment strategies |
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Stimmel et al 1977 results |
Overall outcome at 2 years follow-up: - 28% abstinence rate - however noted different outcomes in relation to length of prior treatment in methadone maintenance - 13% discharged for other reasons - 21% voluntarily went through treatment against advice of treatment staff - 83% abstinence rate at 2 years of follow-up for those who had completed maintenance programs prior to detoxification! - going to maintenance programs first, allowed them to slowly shift their social environment, day-to-day life away from drugs and towards support systems |
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What are the criteria Stimmel et al says you need to have in order to complete methaDone maintenance? |
- consistent negative urine analysis of ALL drugs- ability to express needs, insight - developing longterm goals - increased frustration- tolerance - stable homelife, ability to establish meaningful relationships - resources for spending time in more meaningful ways - improvement of or stability in vocational status Conclusion: results suggest that at least one year of stable methadone maintenance is needed before detox is attempted. Patient needs to have achieved a degree of work and social stability prior to detox. - the field has not paid attention to this. They go right from methadone into detox then back on to streets. |
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What are the 3 main current options for Treatment of Opiate Dependence |
-> detoxification (abstinence-oriented, as part of comprehensive treatment program): switch to longer acting opioid (like methadone) and then taper drug dosage on an inpatient or outpatient basis (1-12 weeks) Combined with group and individual psychosocial treatments ->Ultra-Rapid Detox (not recommended, poor outcomes) : detox under general anesthesia and naloxone IV (veryyy painful, money-making) Subjective withdrawal scores were really high but it didnt improve treatment retention -> Harm Reduction: - needle exchanges - safe injection sites - opiate substitution on long acting oral opiates (methadone maintenance, LAAM, buprenorphone (suboxone)) - IV heroin substitution (HAT studies such as NAOMI) |
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Harm Reduction |
- focuses on those policies, programs, interventions that seek to minimize adverse consequences of sub use without requiring an individual to discontinue sub use- we cant accept or reject these base don their ideological perspective, but on their effectiveness |
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Dole and Nyswanders findings on methadone
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The principal effects of daily oral methadone dosing in MM treatment (80-120 mg/day) were: - Relieved narcotic cravin - gSuppressed opiate abstinence syndrome for 24-36 hrs -Blocked the effects of administered heroin - Patients on MM developed tolerance to the euphoria, sedation, or other narcotic effects of methadone - They also developed tolerance to the analgesic properties of methadone - Aimproved physical health, decreased HIV risk behaviourslower crime rate, higher rates of employmentoverall better quality of life |
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According to Dole and Nyswanders, what is necessary for successful methadone maintenance |
higher methadone doses (> 80 mg/day) a flexible dosing policy (e.g. work with patients concerns) a well trained staff, low staff turnovera non-confrontational therapeutic approach with an attempt to develop trusting relationshipsclear policies and procedures, flexible take-out policies |
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What are the advantages of methadone? (harm reduction therapy) |
oral administration long half-life high bioavailability low costoccupies opiate receptors and blocks effects of heroin suppresses withdrawal symptoms disengages addict from IV drug use and conditioned cues |
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Heroin Assisted Therapy HAT (harm reduction therapy) |
- NAOMI north american opiate medication initiative- 8 million dollar study. Phase 3 trial in Vancouver + Mtl. the participants had to have failed methadone 2 times. - using heroine as the substitution agent for opiate addiction. They come in, are given a dose, and shoot up. 27% received supplements of methadone (they couldnt get through the night without the withdrawal. This is a serious confounding factor, but they overlooked that) - lets give heroine addicts heroine - wont be cut with anything, reduce infection rates, reduce criminality- but you have to go and shoot up 3 times a day- not very practical - retention in treatment (they said that this was if you stayed in ANY treatment not just this one- high drop out rate) + 20% reduction on illicit drug use or crime (what is this stat? 20% drop is ot clinically meaningful, seems like they just randomly picked it) - the people in the heroine group was still using illicit heroine and cocaine |
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What are the implications of HAT study? |
•Results biased due to design and analysis - high drop-out from MMT •biased criteria for determining retention and outcome •treatments confounded (HAT group also received methadone) •high cost, specialized injection rooms, security •requires on site medical supervision, unlike MMT •high polysubstance abuse in most IDU populations – increased risk for seizures, overdoses and poor outcomes •multiple daily visits to the HAT site – implications for rehabilitation? employment?•little information on psychological status, and differential outcome for patients with concurrent mental disorders |
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What is the problem of knowledge translation and how does it relate to this? |
why does knowledge not transfer from research to clinics |
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Which factors influence treatment failure for opiate dependence? describe study one: addictions unit protocols |
- Separated them by those addicted to opiates and sedative-hypnotics - opiates user are younger, little bit older when they start using, so fewer years of problem use before treatment. Much more likely to be using multiple substances - opiate users had more personality disorders, 64% had chronic pain conditions, MANY had both PD and Chronic pain - opiates calm emotions AND physical pain! - The no PD group completed treatment very well in both groups - the cluster B BPD group did not do very well in the opiate group - Why? emotional discomfort! dealing with their affective instability - main predictors of treatment drop-out: opiate dependence, IV drug use (more attachment to drug), Cluster B PD diagnosis** people not taking into consideration personality disorders is according to the prof one of the major reasons so many addicts fail treatment |
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Which factors influence treatment failure for opiate dependence? Describe study two: looked at baseline, detox, 3 months after |
- quant: addiction severity, mood, withdrawal, craving, pain sensitivity (Von frey test (allodynia), algometer pressure test, McGill Pain questionnaire, highly sensitive persons scale) Hypothesis: detox would be associated with higher physical distress and emotional dysreg in patients with PD. Also, PD will experience greater difficulty toleratinf withdrawal symptoms (somatic symptoms and emotional) and this will lead to more dropout - Cluster B PD were more severe addicts, showed greater psychiatric severity - no PD had lower objective withdrawal severity (like blood pressure, tearing etc), but those with cluster B PD had much higher scores. So they may be more miserable but they are also more OBJECTIVELY symptomatic than other patients- PD had much more anger/hostility, and more depression So these PD patients are both subjectively and objectively more symptomatic than other patients- They are also much more likely to relapse (full= 78% partial 87%) |
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What are the profs conclusions from her studies? |
- patients with BPD are more likely to receive prescription opioids and to develop sub use disorder. and also 30% of pain patients have a BPD. These people need more monitoring! - patients with opioid, dep, chronic pain and PD experience sign difficulty tolerating detox and show poor long term outcomes - this is maybe due to lack of focus on comorbidity with PDs by the treatment industry- weak clinical linkages with psychiatry and addiction services : problem of knowledge translation |
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What are two theories of opioid dependence? Are they adequate? |
1) follow regular use, individuals become physically dependent on opiates thus they must continue use in order to avoid the fear, distress and pain of withdrawal. BUT this doesnt take into account why they started and doesnt explain adequately the development of the disorder. Note that in this case detox should solve the abuse pattern, but this isnt the case. Most opiate addicts are using more opiates than are necessary to just suppress withdrawal symptoms! It isnt just about overcoming pain/physical dependence 2) In some people opiates relieve preexisting painful affective states. Maladaptive coping response. BUT while opiate addicts have high comorbidities with things like PD, there is not evidence of a low endorphin state. It is the pleasure that accounts for most of the addicts! |
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Naloxone + overdose |
- must be injected, to prevent overdose, takes 5 minutes to take effect, allows respiratory functions to come back up -There are now take-home naloxone programs in 13 provinces in canada. It was removed from the prescription drug list, so that you can carry it with you in case of overdose |
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What is the developmental model of addiction? |
1) Pre-drug motivation factors: riskfactors (environmental, family, genetics (like alpha2 subunit of GABA- produces more excitatory response to alcohol), childhood adversity, mental illness, availability) 2) drug taking + drug effects 3) pavlovial conditioning (setting, who you are with, time of day, etc) 4) instrumental cinsitioning- the act of taking the drug reinforce the other behaviours along with it- getting drug, taking it, context, etc 5) post-drug motivation : conditioned responses, conditioned drive states…. 6) post-drug motivational states- withdrawal symptoms! fear of withdrawal, uncomfort ** Genes could affect the responses to drugs, the rate of tolerance, likelihood of developing physical dependence and severity of withdrawal |
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Positive reinforcer |
A positive reinforcer is an event subject or stimulus that increases the behaviour that preceded it. The act of taking a drug us reinforced by the primary positive effects of the drug like reduced anxiety, mood alteration, rush. Long term use may see a shift to unpleasant mood states etc that are relieved briefly following each self-administration |
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Student presentation: GluR23Y |
- repeated morphine admin induces endocytosis of AMPARS containing GluR2 - important in the acquisition of memory - GluR23y blocks endocytosis of the AMPARs- can this block the aquitistion and reinstatement of CPP - inhibits acquisition of CPP and reinstatement, but NOT expression of CPP Possibility of clinical use - can take before you take the opiate meds to prevent forming opiate related cues, or after abstinence to get relief from cues |
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Student presentation: GLT-1 & synaptic glutamate spillover |
- GLT-1 takes glu from synapse to be recycled- downregulated in chronic heroin use= more glu in synapse, less uptake into vesicles ...slipover effect- cause action potential on another neuron or same - is this linked to heroin relapse? - trained rats to SA heroine, gave Ceftriaxone- upregulates GLT-1 upon extinction - ceftriaxone restored Glutamate uptake in heroin rats and abolished the spillover effect, reduced cue-induced reinstatement |
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What are opiate addicted kids like? |
Neonatal Abstinence syndrome- high pitched crying is most significant symptom, along with sweating, low-grade fevers, diarrhea - smaller weight, head, length - mean gestation time is shorter than for other babies - long term neurodevelopmental outcomes like working memory updating deficits, motor deficits and delays in milestones, less social engagement, attention - treatment is buprenorpnrene (treatment shorter than with methadone) with Clonidine as an adjunct - if they adopted the kids away from heroin parents, they functioned relatively normally |
