Presentation on theme: "به نام خداوند جان و خرد كزو برتر انديشه بر نگذرد"— Presentation transcript:
1به نام خداوند جان و خرد كزو برتر انديشه بر نگذرد Opioids WithdrawalDiagnosis & ManagementDr Gholam Reza KheirabadiAssistant Professor of psychiatryIsfahan University of Medical Sciences
2Addiction and Dependence Drug addiction: is a condition in which an individual has lost the power of self-control with reference to a drug and abuses the drug to such an extent that the individual, society, or both are harmed.Dependence: refers to a state resulting from habitual use of a drug, where negative physical withdrawal symptoms result from abrupt discontinuation.The key is that addiction results when the reward pathways in the brain are stimulated by drug use thereby causing dependence due at least in part to psychological reasons.Dependence implies need of the drug to avoid withdrawal symptoms, not to gain a reward response in all cases. Palliative care patients do not experience a “high” when taking an opioid and are therefore not considered to be addicted.
3ToleranceTolerance, describes the need for a drug user to administer larger and larger doses of the drug to achieve the same psychoactive effect.When the body's chemical equilibrium is upset, as in habitual drug-taking, the body sets up oppositional processes to restore itself. More of the drug is needed to overcome these efficient corrective processes.While considerable debate exists about the mechanisms of opioid tolerance, two factors have been isolated with a degree of certainty.Receptor Downregulation- Opioid receptors in the body are actively reduced due to overexposure to opioids. This can also have an effect on endogenous opioid peptide function (i.e. regular functioning of endorphins)Antiopiates- Chemicals like neuropeptide FF, orphanin FQ/nociceptin, and Tyr-W-MIF-1 have all been found to block the function of opioids. This activity is due to the fact that these drugs can block g-protein activity.
4Opioids produce their effect by acting at the opioid receptors in the nervous system -opioid receptor most importantAgonistsbind to the receptor and stimulate physiological activityPartial agonistsbind to the receptor but do not produce maximum stimulationAntagonistshave no intrinsic pharmacological effect, but bind to the receptor and can block the action of an agonist
7Source: NSW Department of Health (2007) NSW Drug and Alcohol Withdrawal Clinical Practice Guidelines
8Dependence (DSM IV-TR) 3 occurring at any time in the same 12 month period:ToleranceWithdrawalOpioids taken in larger amounts or longer than intended.Persistent desire or unsuccessful attempts to cut down or control use.A great deal of time is spent in activities necessary to obtain opioids, use opioids, or recover from their effects.Important social, occupational, or recreational activities are given up or reduced because of opioid use.Opioid use is continued despite knowledge of harms caused or exacerbated by opioids.
9Factors affecting drug abuse & dependence UserEnvironment
11Role of assessment Assessment serves two key functions: To ascertain valid information in order to identify the most suitable management plan;To engage the patient in the treatment processEstablishing rapport with the patientFacilitating treatment plans
12Stages of change modelPre-contemplation: People do not have major concerns regarding their drug use and are not interested in changing behaviourContemplation: People aware that there are both benefits and problems arising from their drug use, and are weighing up whether or not to make changes - or what those changes should beAction: People are implementing strategies in order to changeMaintenance: holding onto the behaviour changesRelapse: can be volitional, or triggered by physical, emotional, social factors
13Some authors recognise a preparation stage before the action stage RELAPSEMAINTENANCE&DetoxificationACTIONCONTEMPLATIONA version of this diagram will be included in the online publication: Proude et al (2009) The Treatment of Alcohol ProblemsA Review of the Evidence. Commonwealth Department of Health and Aging, Canberra.Some authors recognise a preparation stage before the action stageIn this diagram the pre-contemplation stage is merged with relapseProude, E (2009), unpublished data
14Principles of effective treatment Long duration of treatmentAdequate dose of medicationQuality of therapeutic relationshipPsycho-social supports for the patientRegular review, supervision & monitoringParticipation in counsellingEnvironment, family, friends, employmentBio-psycho-social model for chronic condition
15Methadone Full agonist at - opioid receptor Onset min after dose, Peak after ~ hrsLong-acting: t1/2= hrs: one dose / dayOpioid toxicity with too much methadone: sedation, respiratory depression, death1 dose of 20-40mg can kill childRepeated doses of 30–40mg can kill an adult (opiate naïve)1 dose of 70mg can kill an adult (opiate naïve)Widespread diversion & methadone related deaths where no supervision (e.g. UK)Daily supervised dispensing at clinics / pharmaciesHenry-Edwards et al (2003) Clinical Guidelines and Procedures for the Use of Methadone in the Maintenance Treatment of Opioid Dependence. Commonwealth Government of Australia, Canberra.Henry-Edwards et al (2003) Clinical Guidelines and Procedures for the Use of Methadone in the Maintenance Treatment of Opioid Dependence.
16Principles of methadone dosing InductionRequire slow induction (‘start low & go slow’)20-30mg / day & increase dose by 5-10mg every 1-3 days until reach target dose (over 2-6 weeks)MaintenanceDoses of 20 – 40mg prevent opiate withdrawalDoses >60mg most effective in reducing heroin useWithdrawalGradual dose reductions (at rate of 10mg / month)Henry-Edwards et al (2003) Clinical Guidelines and Procedures for the Use of Methadone in the Maintenance Treatment of Opioid Dependence. Commonwealth Government of Australia, Canberra.Henry-Edwards et al (2003) Clinical Guidelines and Procedures for the Use of Methadone in the Maintenance Treatment of Opioid Dependence.
17MEHTADONE Stabilization on Methadone: -Initial dose: A:10-20mg→ if withdrawal persist → Repeat the dose( 2 hours later ) [ no more than 40mg during first day].B: Calculation of equivalent withdrawal suppressing dose of methadone?(Methadone is 3time potent than morphine).C: Add 10mg/2-3day or week( different for outpatient V.S inpatient detoxification?)up to final stabilization(more gradual and upper final dose in outpatient setting).
18Buprenorphine Partial agonist at the opioid receptor - Low intrinsic activity only partially activates receptorsHigh affinity for the receptorBinds more tightly to receptors than other opioidsDeveloped in 1980s as analgesic
19Safety Aspects of BPN Less risk of overdose c/w full opiate agonists Less respiratory depression & sedation than methadoneBPN ‘tolerated’ by individuals with low levels of opiate dependenceSailing effectsPotential concerns re: safetyBPN related deaths reported in combination with other sedatives (EtOH, BZDs) … BUT less of a concern than other opiates (e.g. methadone, heroin)
20Clinical Pharmacology Sublingual tablets0.4, 2 & 8 mg tablets available3 to 10 minutes to dissolveTime courseOnset: 30–60 min, peak: 1–4 hoursDuration of action dose-related (1 dose / day)Side effectsTypical for opioid class: less sedating than methadoneWithdrawal syndromeMilder than full agonistsLintzeris et al (2006) National clinical guidelines and procedures for the use of buprenorphine in treatment of opioid dependence. Commonwealth Government of Australia, Canberra.Lintzeris et al (2006) National clinical guidelines and procedures for the use of buprenorphine in treatment of opioid dependence.
21Overview BPN Doses Induction Delay first dose of BPN until early opiate withdrawalCommence 4 to 8 mg dailyFrequent & rapid dose increases possible (by 2 to 8mg/day)MaintenanceDaily doses: 8 – 16mg (max 32mg) required initiallyAlternate day dosing possible for many clientsWithdrawalMore rapid dose reductions possible than methadone(e.g. 2 – 4 mg / week usually well tolerated)Lintzeris et al (2006) National clinical guidelines and procedures for the use of buprenorphine in treatment of opioid dependence. Commonwealth Government of Australia, Canberra.Lintzeris et al (2006) National clinical guidelines and procedures for the use of buprenorphine in treatment of opioid dependence.
22Buprenorphine-naloxone tablet (Suboxone®) Sublingual tablet in 4:1 ratio (BPN:NLX)Naloxone (antagonist) poorly absorbed sublingually & inactiveNaloxone produces antagonist (withdrawal) effects if tablet injected by heroin userEnables take-away doses with greater convenience for patients & less risk of tablet misuse
23TramadolMechanism: serotonin & nor-epinphrin reuptake inhibitor(Parent compound) + µ agonist(metabolize compound-desmethyltramadol).Withdrawal control with mg for modest and 600 mg for sever withdrawal)Seizure in high doses CNS suppressant Using with B.Z & seretonergic syndrome with SSRI.
25Mechanism & Sideffects It has specificity towards the presynaptic alpha-2 receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels, and inhibits the release of norepinephrine (NE). The net effect is a decrease in sympathetic toneThis drug may cause drowsiness, lightheadedness, dry mouth, dizziness, or constipation. Clonidine may also cause hypotension. It can also cause inhibition of orgasm in women
26ClonidinePatient stabilized on low dose of opioids (30 – 40 Methadone/ day).starting dose 0/1 – 0/3.*Maximum dose (1/mg/day) In outpatient & mg/day In hospitalized patients.*Adjusting Dose based On Hypotension & sedation.Contraindication: acute or chronic cardiac disease, Renal & metabolic disease, Hypotension).
27Clonidine More effective in: =stabilization on Methadone. =good Relationship with therapist.Effective in suppressing of : Sweating, cramps, nusea, vomiting and diarrheaIneffective In suppressing of (Muscle aches – Lethargy – Insomnia – restlessness and Craving).Non – effective on relapse after complete detoxification.Facilitation of detoxification of Methadone Maintained patients & subsequent stabilization on naltrexone.
28When should we stop substitution treatment? Chronic condition needs long term treatmentPremature cessation of treatment usually results in relapse to dependent heroin useConsider ending treatment when:No illicit drug use for months / yearsStable social environmentStable medical / psychiatric conditionsPatient ‘has a life’ that does not revolve around drugsPatient informed consentWhen do we stop anti convulsants/antidepressants?