Title: Drug prevention and treatment
1Drug prevention and treatment
- Part I
- Pleven October 2004
2Structure of the presentation
- Introduction to addiction problems
- Tolerance
- Dependence
- Addiction
- Drugs (overview)
- Opiates XTC
- Opiates
- From neurobiology to clinical management
- Treatment
- Relapse prevention (AAA)
3Addictions
4Introduction
- Tolerance
- Dependence
- Addiction
- Craving
- relapse
5Tolerance and dependence not pathological
6Adaptations
- Tolerance
- innate
- aquired
- Pharmacokinetic
- Pharmacodynamic
- behavioral
- Cross sensitisation
- Behavioral sensitisation (inverse tolerance)
7Adaptations (2)
- Dependence
- Withdrawal syndrom
- Loss of control
- addiction
8Drugs overview
9 Opioïdes
- Opioïdes (opiacés)
- Héroïn
- Morphine
- Methadone
- Codeine
10Ecstasy
- MDMA
- Produits apparentés
- DMMA
- PMA
- TMA
- DDPR
- 2 CB
- MDMA adjuvants ecstasy
11Ecstasy
- Stimulant
- Hallucinogen
- Conséquence possible
- toxicity
- Hepathic saturation
- Intoxication
- Acute hepathitis
12cannabis
- Cannabis sativa
- 400 composants
- 60 cannabinoids
- Delta 9 THC
- Delta 8 THC
- Synthetic Cannabinoids
13A reality Polydrug abuse
14Why polydrug use
- Tolerance
- Personnality
- Sensation seeking
- Synergic actions (learning)
- genetic (sensitivity)
15Opiates
16Nicotine or caffeine withdrawal ?
17Evaluation
- Drogues
- Others drugs (alcohol, medications, )
- Medical problems
- Psychiatric problems
- Psychological context
- Familial context
- Social context
- Interventions, existing network
18Opiacés et opioides
- Natural (opium)
- Synthetic (methadone)
- Semi-synthetic (heroin)
19Opiates - Objectives
- Opiate detoxification
- Harm reduction
- substitution
- MASS
- Controlled heroin deliverance
20Polydrug use
- Complete detoxification
- long term programm
- Step by step
21Others therapeutic objectives
- Medical problems
- (HIV, hépatitis C,)
- Psychiatric comorbidities
- Psychological revalidation
- Social revalidation
- Familial reconstruction - restructuration
22GPs
- Methadone prescription maintenance, withdrawal
- Medical problems
- The center of the patients life
23Substitution objectives
- Stop illegal drugs
- Harm reduction
- Psycho-social revalidation, quality of life
- long term to stop opiate
24Substitution
- General principles
- evaluation
- Global strategy
- Family , psychology,
- Long term
25Méthadone (1)
- Indications
- Opiates Substitution (héroïn, codéin,)
- Stabilisation
- Withdrawal
- Heroin ? methadone ? detoxification
26Méthadone (2)
- opiate receptors agonist
- Effects
- Euphoria (possibilité dabus)
- Sedation
- Analgésia
- decrease gastro-intestinal motility,
- Nausea,
- Cough relieving
27Méthadone (3)
- Surdosage
- Sedation -gt coma
- Respiratory depression
- Hypothermia
- Hypotension
- Hypoglycémia
- Surdosage treatment
- Antagonist naloxone (Narcan) IV, 1 amp de
0.4mgr (2 hours ok !) - Watch for 24 - 36 hours
- Multiple intoxications !!!
28Méthadone (4)
- Per os
- t1/2 15 heures
- Plasmatic peak 2 - 6 hours,
- Slow increase, efects from 12 to 24 hours
- Hepatic degradation, renal elimination, cross the
placenta barrier , through breast milk
29Méthadone side effetcs
- sedation, euphoria, incoordination
- Constipation
- Sweating
- Memory problems
- Libido modifications
30Methadone substitution
-
- Opiate dependance
- No emergency !!!
- Avoid abuses specific pharmacy, weekly or dayly
intake.
31Methadone substitution results
- Retention rate 50 à 80
- effetcs
- Nothing lt 3 mois
- Quality of life between 6 and 24 mois
- In general
- 1/3 OK
- 1/3 abstinence and relapses
- 1/3 no effetcs
32Opiate detoxification
- From neurobiology to clinical practice
33Chemical sedation psychiatry
- 1944 Sargant Slater
- We must be prepared to give the patient what he
needs when it is clear that he needs it, and not
be dissuaded by illusory dangers. Especially is
this the case when psychotherapy and
environmental readjustment have failed to produce
substantial benefits
34Rapid antagonis induction (RAI)
- General principles
- History
- Actuality
- Clinical applications worldwide
- First application in Belgium - 1998 (Brugmann
Hospital - Brussels) - Development of pre-clinical models
35Addicted Rats
- Staircase regimen
- 10 to 100 mg/kg in 3 days
- 3 times/day at 9-12-17
- Third day at 17 experiment (detox)
- Chloral hydrate
- Midazolam
- ketamine
36design
nalox
nalox
saline
2 hours
nalox
nalox
Chloral Hydrate
2 hours
nalox
nalox
Chloral hydrate
4 hours
37Chloral hydrate
38Conclusions (1)
- Do not suppress withdrawal
- Temporary overshadowing
- Signs can reappear even being potentiated
- Different effects on central and peripheral
systems - Residual effect of anesthetic agent ?
39 Design
nalox
nalox
saline
nalox
nalox
nalox
Midazolam
nalox
nalox
nalox
Ketamine
nalox
2 hours
4 hours
40midazolam or ketamine
41Conclusions (2)
- Interference in withdrawal expression
- Each anesthetic interfere specifically
- Residual effect or complex pharmacological
interactions ? - If residual effect decreased doses decreased
residual effects
42midazolam or ketamine (dose 75)
43Conclusions (3)
- Dosage reduction 75
- Interference of withdrawal signs
- Anesthetic-specific and dose dependent
- Not compatible with residual effect
- Pharmacological basis ?
44Hypothesis
- Interactions with endogenous opiates
- Naloxone ? increase endorphines
- Endogenous opiates more competitive
- Increase dosage to block exo/endo opiates
- Anesthetic agents ? interactions with opiates
receptors - GABA agonists
- NMDA antagonists
45Hypothesis 2
- Interference with excitatory amino acids
- Noradrenergic storm
- Internal mechanism (cellular adaptations)
- K channels decreased activity
- External mechanism
- Excitatory input
- Glutamate from nucleus paragigantocellularis
- Anesthetics agents and glutamate
- GABA agonist and NMDA antagonist decrease
glutamate liberation
46Addicted rats and relapse
- Morphine in water
- 8 days
- 0,1-- 0,2 -- 0,3 -- 0,4 -- 0,5- 0,5 0,5 0,5
- Detoxification procedures
- ? free choice paradigm
- Water vs. water morphine (0,5 mg/ml)
- Why forced conditioning before free choice
paradigm.
47Relapse evaluation
48Design
Free choice paradigm opiate vs water 30 days
Control Naloxone Midazolam naloxone Ketamine
naloxone
detoxification
49Detoxification procedure and relapse rate
50Naltrexone and relapselate vs early induction
51Conclusions
- Procedure do not interfere with relapse rate
- Naltrexone interfere with relapse rate
- Early induction better than late induction
- Opiate receptor blockade
- Inverse agonist ?
52Final analysis
- Anesthetic agents useful in interference of
withdrawal signs - Pharmacological exponations
- Narcosis obviously not required
- Whatever the procedure naltrexone is the key
issue for post-detoxification - Early induction is associated with better outcome
53References
- Streel al. (2000) Life Sci. 67 2883-2887
- Streel al. (2001) Life Sci. 70 517-522
- Streel al. (2001) Add. Biol. 6 385
- Streel Verbanck (2003) Add. Biol. 8 123-128
54limitations
- The purpose is to detoxify human not rats
- Anonym reviewer
55Withdrawal in humans after RAI
56The problem is not to stop, but not to start
again
57Biology and psychology
- Biology
- Craving
- Risk of relapse
- If drug intake ? reinstatement of biological
dependence
- Psychology
- Craving
- Need to learn how to stay abstinent
- Detoxification procedure is to fast
58Learning the language of abstinence
- Antagonist assisted abstinence
- (AAA)
59Learning foreign language analogy
- To learn English
- England ? immersion method
- Fast and Effective
- Once you learn the new language you can switch
from one to another - To learn new habits without drugs
- Immersion ?
- A place without drugs ?
- Sooner or later the patients will have to face
drug reality - A place where drug has no effect
- This place does not exist !
- Create such a place
60A place where drug has no effect pharmacology
- The opiate receptor
- G-protein coupled
- Agonists and antagonists
- opiate receptor blockade
- Opiate receptor antagonists
- Naltrexone
- Nalmefene
- Per os
- Implants
61A place where drug has no effects Psychology
- Learn English in England
- Need to communicate
- Want to communicate
- You cant ? Learn
- Opiate receptor blockade
- Need to take drugs
- Want to take drugs
- Drugs have no effects
- Have to learn
62Antagonist assisted abstinence
- Combination of pharmacology and counseling
63Antagonist assisted abstinence
- Pharmacology
- Receptor blockade
- Test the blockade
- Technical relapse
- No drug effect
- Psychology
- Maintenance stage
- Develop new habits
64Pharmacology reinforce the effectiveness of
psychological follow-up
65Antagonist assisted abstinence
- Naltrexone
- Per os (50 mg/Day)
- Implants
- 3 6 months
- Avoid early relapses
- Increase psychotherapy effectiveness
66Last but not least
- A short note on opiate management in children
67Opiate withdrawal in children
68 69(No Transcript)
70Paediatric Intensive Care UnitH.U.D.E.R.F
- Medico-surgical unit
- 15 beds
- Neonates and childrenlt18 years
- Cardiac surgery 40
71Sufentanil
- 1000 x more powerful than morphine
- Fast action delay 3-4 minutes
- Short action time 30 minutes-1 hour
- Less cardiovascular effects ( cardiac surgery)
Sufenta
72Tolerance and Withdrawal
- Tolerance decrease in a drugs effect over
time or need to
increase dose to achieve the same effect - Withdrawal physical signs and symptoms
occuring when a sedative or
analgesic agent is stopped in a patient
physically tolerant - Physical dependence need to continue a sedative
or analgesic agent to prevent withdrawal
73Sedation in cardiac surgery
- Continuous IV opioids Sufentanil
- Continuous IV benzodiazepine Midazolam
- Prolonged infusions 48 hours to 21 days
WITHDRAWAL
74- How to recognise a child with withdrawal syndrome
? - How to differentiate withdrawal from pain ?
75(No Transcript)
76Activation of sympathetic system
77Gastro-intestinal manifestations
78Central Nervous System
79Paediatric Scoring Systems of Withdrawal
- Describe and quantify the patients symptoms
- Assess the need of treatment
lt 3 months FINNEGAN
? 3 months PAEDIATRIC ABSTINENCE SCORE
80Neonatal Abstinence Score
81Validation of a paediatric abstinence score
- DESIGN Prospective clinical trial
- PATIENTS 28 patients aged 3 months to 15 years
(average 13 months) - Continuous infusion of sufentanil gt 5
day (2 patients excluded unrelated
medical complications) - METHODS Sufentanil interrupted abruptly if
infusion lasted lt 216 hours and tapered
if infusion lasted gt 216 hours (9 days) - Withdrawal scoring system
based medical literature - Nursing team observations
every 3 hours during the first day and
every 6 hours over the following 48 hours - Medical team clinical
observations concomitantly and
indenpendtly, withdrawal treatment with
oral methadone
82Validation of a paediatric abstinence score
- RESULTS
- Underlying conditions cardiac surgery 22
severe
pneumonia 3
near-drowning 1 - Incidence of withdrawal 21 patients (71)
- Cumulative dose of sufentanil mean 260 ?g/kg
(63-1244) - Lenght of sufentanil infusion mean 247 hours
( 120-495) - Associated sedative or analgesic drugs
midalozam infusion (25/26)
clonidine (5/26)
ketamine (1/26)
paracetamol
(26/26) -
83Validation of a paediatric abstinence score
84Validation of a paediatric abstinence score
85Treatment of withdrawal
GOAL OF THE THERAPY patient not agitated
or distressed, sleeping between feeding not
too much sedated, but with signs of mild
withdrawal
- METHADONE
- starting dose 0.1 mg/kg every 6 hours
- increasing dose 0.05 mg/kg/dose
- NURSING
- reduction of the stimuli
- swaddling
- presence of the parents
86CONCLUSION
- Opioïd withdrawal is a real problem in PICU
- Paediatric abstinence score is an
- appropriate tool to identify withdrawal
(validation) - Methadone is an effective treatment for
children