Drug prevention and treatment - PowerPoint PPT Presentation

1 / 86
About This Presentation
Title:

Drug prevention and treatment

Description:

Clinical applications worldwide ... Development of pre-clinical models. Addicted Rats. Staircase regimen. 10 to 100 mg/kg in 3 days ... – PowerPoint PPT presentation

Number of Views:103
Avg rating:3.0/5.0
Slides: 87
Provided by: Str76
Category:

less

Transcript and Presenter's Notes

Title: Drug prevention and treatment


1
Drug prevention and treatment
  • Part I
  • Pleven October 2004

2
Structure of the presentation
  • Introduction to addiction problems
  • Tolerance
  • Dependence
  • Addiction
  • Drugs (overview)
  • Opiates XTC
  • Opiates
  • From neurobiology to clinical management
  • Treatment
  • Relapse prevention (AAA)

3
Addictions
4
Introduction
  • Tolerance
  • Dependence
  • Addiction
  • Craving
  • relapse

5
Tolerance and dependence not pathological
6
Adaptations
  • Tolerance
  • innate
  • aquired
  • Pharmacokinetic
  • Pharmacodynamic
  • behavioral
  • Cross sensitisation
  • Behavioral sensitisation (inverse tolerance)

7
Adaptations (2)
  • Dependence
  • Withdrawal syndrom
  • Loss of control
  • addiction

8
Drugs overview
  • Opiates - XTC

9
Opioïdes
  • Opioïdes (opiacés)
  • Héroïn
  • Morphine
  • Methadone
  • Codeine

10
Ecstasy
  • MDMA
  • Produits apparentés
  • DMMA
  • PMA
  • TMA
  • DDPR
  • 2 CB
  • MDMA adjuvants ecstasy

11
Ecstasy
  • Stimulant
  • Hallucinogen
  • Conséquence possible
  • toxicity
  • Hepathic saturation
  • Intoxication
  • Acute hepathitis

12
cannabis
  • Cannabis sativa
  • 400 composants
  • 60 cannabinoids
  • Delta 9 THC
  • Delta 8 THC
  • Synthetic Cannabinoids

13
A reality Polydrug abuse
14
Why polydrug use
  • Tolerance
  • Personnality
  • Sensation seeking
  • Synergic actions (learning)
  • genetic (sensitivity)

15
Opiates
16
Nicotine or caffeine withdrawal ?
  • Pause

17
Evaluation
  • Drogues
  • Others drugs (alcohol, medications, )
  • Medical problems
  • Psychiatric problems
  • Psychological context
  • Familial context
  • Social context
  • Interventions, existing network

18
Opiacés et opioides
  • Natural (opium)
  • Synthetic (methadone)
  • Semi-synthetic (heroin)

19
Opiates - Objectives
  • Opiate detoxification
  • Harm reduction
  • substitution
  • MASS
  • Controlled heroin deliverance

20
Polydrug use
  • Complete detoxification
  • long term programm
  • Step by step

21
Others therapeutic objectives
  • Medical problems
  • (HIV, hépatitis C,)
  • Psychiatric comorbidities
  • Psychological revalidation
  • Social revalidation
  • Familial reconstruction - restructuration

22
GPs
  • Methadone prescription maintenance, withdrawal
  • Medical problems
  • The center of the patients life

23
Substitution objectives
  • Stop illegal drugs
  • Harm reduction
  • Psycho-social revalidation, quality of life
  • long term to stop opiate

24
Substitution
  • General principles
  • evaluation
  • Global strategy
  • Family , psychology,
  • Long term

25
Méthadone (1)
  • Indications
  • Opiates Substitution (héroïn, codéin,)
  • Stabilisation
  • Withdrawal
  • Heroin ? methadone ? detoxification

26
Méthadone (2)
  • opiate receptors agonist
  • Effects
  • Euphoria (possibilité dabus)
  • Sedation
  • Analgésia
  • decrease gastro-intestinal motility,
  • Nausea,
  • Cough relieving

27
Méthadone (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 !!!

28
Méthadone (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

29
Méthadone side effetcs
  • sedation, euphoria, incoordination
  • Constipation
  • Sweating
  • Memory problems
  • Libido modifications

30
Methadone substitution
  • Opiate dependance
  • No emergency !!!
  • Avoid abuses specific pharmacy, weekly or dayly
    intake.

31
Methadone 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

32
Opiate detoxification
  • From neurobiology to clinical practice

33
Chemical 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

34
Rapid antagonis induction (RAI)
  • General principles
  • History
  • Actuality
  • Clinical applications worldwide
  • First application in Belgium - 1998 (Brugmann
    Hospital - Brussels)
  • Development of pre-clinical models

35
Addicted 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

36
design
nalox
nalox
saline

2 hours
nalox
nalox
Chloral Hydrate
2 hours
nalox
nalox
Chloral hydrate
4 hours
37
Chloral hydrate
38
Conclusions (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
40
midazolam or ketamine
41
Conclusions (2)
  • Interference in withdrawal expression
  • Each anesthetic interfere specifically
  • Residual effect or complex pharmacological
    interactions ?
  • If residual effect decreased doses decreased
    residual effects

42
midazolam or ketamine (dose 75)
43
Conclusions (3)
  • Dosage reduction 75
  • Interference of withdrawal signs
  • Anesthetic-specific and dose dependent
  • Not compatible with residual effect
  • Pharmacological basis ?

44
Hypothesis
  • 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

45
Hypothesis 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

46
Addicted 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.

47
Relapse evaluation
48
Design
Free choice paradigm opiate vs water 30 days
Control Naloxone Midazolam naloxone Ketamine
naloxone
detoxification
49
Detoxification procedure and relapse rate
50
Naltrexone and relapselate vs early induction
51
Conclusions
  • Procedure do not interfere with relapse rate
  • Naltrexone interfere with relapse rate
  • Early induction better than late induction
  • Opiate receptor blockade
  • Inverse agonist ?

52
Final 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

53
References
  • 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

54
limitations
  • The purpose is to detoxify human not rats
  • Anonym reviewer

55
Withdrawal in humans after RAI
56
The problem is not to stop, but not to start
again
  • Relapse prevention

57
Biology 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

58
Learning the language of abstinence
  • Antagonist assisted abstinence
  • (AAA)

59
Learning 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

60
A 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

61
A 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

62
Antagonist assisted abstinence
  • Combination of pharmacology and counseling

63
Antagonist assisted abstinence
  • Pharmacology
  • Receptor blockade
  • Test the blockade
  • Technical relapse
  • No drug effect
  • Psychology
  • Maintenance stage
  • Develop new habits

64
Pharmacology reinforce the effectiveness of
psychological follow-up
65
Antagonist assisted abstinence
  • Naltrexone
  • Per os (50 mg/Day)
  • Implants
  • 3 6 months
  • Avoid early relapses
  • Increase psychotherapy effectiveness

66
Last but not least
  • A short note on opiate management in children

67
Opiate withdrawal in children
68

69
(No Transcript)
70
Paediatric Intensive Care UnitH.U.D.E.R.F
  • Medico-surgical unit
  • 15 beds
  • Neonates and childrenlt18 years
  • Cardiac surgery 40

71
Sufentanil
  • 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
72
Tolerance 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

73
Sedation 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)
76
Activation of sympathetic system
77
Gastro-intestinal manifestations
78
Central Nervous System
79
Paediatric Scoring Systems of Withdrawal
  • Describe and quantify the patients symptoms
  • Assess the need of treatment

lt 3 months FINNEGAN
? 3 months PAEDIATRIC ABSTINENCE SCORE
80
Neonatal Abstinence Score
81
Validation 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

82
Validation 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)

83
Validation of a paediatric abstinence score
84
Validation of a paediatric abstinence score
85
Treatment 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

86
CONCLUSION
  • 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
Write a Comment
User Comments (0)
About PowerShow.com