Download Withdrawal

‫به نام خداوند جان و خرد‬
‫كزاین برتر اندیشه 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
100
Size of Opiate Agonist Effect.
.
Full Agonists: Heroin, morphine,
methadone, codeine
0
Threshold for respiratory
depression
Partial Agonists: Buprenorphine
Antagonists: Naltrexone, naloxone
Drug Dose
Opioid effects & withdrawal
Opioid effects
•
•
•
•
•
•
•
•
Analgesia
Sedation
Euphoria
Pinpoint pupils
Low BP, PR, RR
Dry skin, mouth, ↑urine
Constipation, ↑bowel action
Nausea, vomiting
Opioid withdrawal
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
ACTION
PREPARATION
MAINTENANCE
&
Detoxification
CONTEMPLATION
RELAPSE
• 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 30 - 60 min after dose, Peak after ~ 2 - 6 hrs
Long-acting: t1/2= 24-30 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 13 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 than full opiate
agonists
– Less respiratory depression & sedation than
methadone
– BPN ‘tolerated’ by individuals with low levels of
opiate dependence
– Sailing effects
• Potential concerns: safety
– BPN related deaths reported in combination
with other sedatives (EtOH, BZDs) … BUT
less of a concern than other opiates (e.g.
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 compounddesmethyltramadol).
• Withdrawal control with200-400mg for
modest and 600 mg for sever withdrawal)
• Seizure in high doses CNS suppressant
Using with B.Z & seretonergic syndrome
with SSRI.
2
α2 Agonists
- Clonidine
-Lofexidine (Less Hypotensive)
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 tone
• 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
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 &
1.5-2.0mg/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?