Presentation on theme: "به نام خداوند جان و خرد كزو برتر انديشه بر نگذرد Opioids Withdrawal Diagnosis & Management Dr Gholam Reza Kheirabadi Assistant Professor of psychiatry."— Presentation transcript:
به نام خداوند جان و خرد كزو برتر انديشه بر نگذرد Opioids Withdrawal Diagnosis & Management Dr Gholam Reza Kheirabadi Assistant Professor of psychiatry Isfahan University of Medical Sciences
Addiction 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.
Tolerance Tolerance, 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. 1.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) 2.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.
Opioids produce their effect by acting at the opioid receptors in the nervous system – -opioid receptor most important Agonists –bind to the receptor and stimulate physiological activity Partial agonists –bind to the receptor but do not produce maximum stimulation Antagonists –have no intrinsic pharmacological effect, but bind to the receptor and can block the action of an agonist
7 Source: NSW Department of Health (2007) NSW Drug and Alcohol Withdrawal Clinical Practice Guidelines
Dependence (DSM IV-TR) 3 occurring at any time in the same 12 month period: 1.Tolerance 2.Withdrawal 3.Opioids taken in larger amounts or longer than intended. 4.Persistent desire or unsuccessful attempts to cut down or control use. 5.A great deal of time is spent in activities necessary to obtain opioids, use opioids, or recover from their effects. 6.Important social, occupational, or recreational activities are given up or reduced because of opioid use. 7.Opioid use is continued despite knowledge of harms caused or exacerbated by opioids.
Factors affecting drug abuse & dependence Drug User Environment
Withdrawal Management (Detoxification)
Role 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 process –Establishing rapport with the patient –Facilitating treatment plans
Stages of change model Pre-contemplation: People do not have major concerns regarding their drug use and are not interested in changing behaviour Contemplation: 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 be Action: People are implementing strategies in order to change Maintenance: holding onto the behaviour changes Relapse: can be volitional, or triggered by physical, emotional, social factors
PREPARATION RELAPSE MAINTENANCE & Detoxification MAINTENANCE & Detoxification ACTION CONTEMPLATION Some authors recognise a preparation stage before the action stage In this diagram the pre-contemplation stage is merged with relapse Proude, E (2009), unpublished data
Principles of effective treatment Long duration of treatment Adequate dose of medication Quality of therapeutic relationship Psycho-social supports for the patient –Regular review, supervision & monitoring –Participation in counselling –Environment, family, friends, employment Bio-psycho-social model for chronic condition
Methadone Full agonist at - opioid receptor Onset min after dose, Peak after ~ hrs Long-acting: t 1/2 = hrs: one dose / day Opioid toxicity with too much methadone: sedation, respiratory depression, death –1 dose of 20-40mg can kill child –Repeated 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 / pharmacies Henry-Edwards et al (2003) Clinical Guidelines and Procedures for the Use of Methadone in the Maintenance Treatment of Opioid Dependence.
Principles of methadone dosing Induction –Require 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) Maintenance –Doses of 20 – 40mg prevent opiate withdrawal –Doses >60mg most effective in reducing heroin use Withdrawal –Gradual 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.
MEHTADONE 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).
Buprenorphine Partial agonist at the opioid receptor - Low intrinsic activity only partially activates receptors High affinity for the receptor -Binds more tightly to receptors than other opioids -Developed in 1980s as analgesic
Safety Aspects of BPN Less risk of overdose c/w full opiate agonists –Less respiratory depression & sedation than methadone –BPN ‘tolerated’ by individuals with low levels of opiate dependence –Sailing effects Potential concerns re: safety –BPN related deaths reported in combination with other sedatives (EtOH, BZDs) … BUT less of a concern than other opiates (e.g. methadone, heroin)
Clinical Pharmacology Sublingual tablets –0.4, 2 & 8 mg tablets available –3 to 10 minutes to dissolve Time course –Onset: 30–60 min, peak: 1–4 hours –Duration of action dose-related (1 dose / day) Side effects –Typical for opioid class: less sedating than methadone Withdrawal syndrome –Milder than full agonists Lintzeris et al (2006) National clinical guidelines and procedures for the use of buprenorphine in treatment of opioid dependence.
Overview BPN Doses Induction Delay first dose of BPN until early opiate withdrawal Commence 4 to 8 mg daily Frequent & rapid dose increases possible (by 2 to 8mg/day) Maintenance Daily doses: 8 – 16mg (max 32mg) required initially Alternate day dosing possible for many clients Withdrawal More 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.
Buprenorphine-naloxone tablet (Suboxone ® ) Sublingual tablet in 4:1 ratio (BPN:NLX) Naloxone (antagonist) poorly absorbed sublingually & inactive Naloxone produces antagonist (withdrawal) effects if tablet injected by heroin user Enables take-away doses with greater convenience for patients & less risk of tablet misuse
Tramadol Mechanism: 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.
Mechanism & 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 tonepresynapticvasomotor brainstem calcium norepinephrine This drug may cause drowsiness, lightheadedness, dry mouth, dizziness, or constipation. Clonidine may also cause hypotension. It can also cause inhibition of orgasm in women hypotension
Clonidine Patient 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).
Clonidine More effective in: =stabilization on Methadone. =good Relationship with therapist. Effective in suppressing of : Sweating, cramps, nusea, vomiting and diarrhea Ineffective 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.
When should we stop substitution treatment? Chronic condition needs long term treatment –Premature cessation of treatment usually results in relapse to dependent heroin use Consider ending treatment when: –No illicit drug use for months / years –Stable social environment –Stable medical / psychiatric conditions –Patient ‘has a life’ that does not revolve around drugs –Patient informed consent When do we stop anti convulsants/antidepressants?