125. Opiate Addiction – Forensic Science

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125. Opiate Addiction – Forensic Science

125. Opiate Addiction – Forensic Science

 

 

CATEGORY: Medical & Medicine – 500 Courses

COURSE NUMBER: 125

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Syllabus

Foreword by Albert D. Fraser …………………………………………………….. v
Preface …………………………………………………………………………………….. vii
Contributors …………………………………………………………………………….. xv
CHAPTER 1
Pharmacology of High-Dose Buprenorphine
Pierre Marquet………………………………………………………………………………. 1
1. Introduction ……………………………………………………………………………………………. 1
2. Pharmacokinetic Properties……………………………………………………………………… 1
2.1. Absorption and Bioavailability …………………………………………………………. 1
2.2. Distribution …………………………………………………………………………………….. 3
2.3. Metabolism ……………………………………………………………………………………… 5
2.4. Excretion ………………………………………………………………………………………… 5
3. Pharmacodynamic Properties …………………………………………………………………… 5
4. Administration Schedules………………………………………………………………………… 8
5. Clinical Effects of Buprenorphine ……………………………………………………………. 8
6. Conclusion …………………………………………………………………………………………….. 9
References …………………………………………………………………………………………………. 9
CHAPTER 2
Controlled Drug Administration Studies
of High-Dose Buprenorphine in Humans
Marilyn A. Huestis ………………………………………………………………………. 13
1. Introduction ………………………………………………………………………………………….. 13
2. Bioavailability ………………………………………………………………………………………. 14
3. Dose-Effect Profiles ……………………………………………………………………………… 16
4. Abuse Liability …………………………………………………………………………………….. 16
5. Toxicity ……………………………………………………………………………………………….. 19
6. Safety and Abuse Liability of High-Dose Intravenous Buprenorphine ………. 21
7. Conclusion …………………………………………………………………………………………… 23
References ……………………………………………………………………………………………….. 24

CHAPTER 3
High-Dose Buprenorphine for Treatment of Opioid Dependence
Eric C. Strain ………………………………………………………………………………. 29
1. Introduction ………………………………………………………………………………………….. 29
2. Buprenorphine Solution vs Tablets…………………………………………………………. 30
3. Efficacy of Buprenorphine vs Placebo: Clinical Trials …………………………….. 31
3.1. Summary of Placebo-Controlled Studies………………………………………….. 34
4. Efficacy of Buprenorphine vs Other Medications:
Clinical Trials ………………………………………………………………………………………. 34
4.1. Summary of Studies Comparing Buprenorphine
to Other Medications ……………………………………………………………………… 44
5. Safety and Side Effects of Buprenorphine ………………………………………………. 44
6. Summary and Conclusions …………………………………………………………………….. 45
Acknowledgment ……………………………………………………………………………………… 47
References ……………………………………………………………………………………………….. 47
CHAPTER 4
Foreseeable Advantages and Limits
of Buprenorphine-Naloxone Association
Michel Mallaret, Maurice Dematteis, Celine Villier,
Claude Elisabeth Barjhoux, and Chantal Gatignol ……………….. 51
1. Introduction ………………………………………………………………………………………….. 51
2. Advantages of Buprenorphine-Naloxone Association ………………………………. 52
2.1. Advantages of Opiate-Naloxone Association: Lessons of the Past ……… 52
2.1.1. Epidemic of Pentazocine and Tripelennamine Abuse
in the United States………………………………………………………………. 52
2.1.2. Epidemic of Analgesic Buprenorphine Abuse in New Zealand … 53
2.2. Buprenorphine and Naloxone:
A Complex and Controversial Pharmacology …………………………………… 53
2.3. Clinical Aspects …………………………………………………………………………….. 54
2.3.1. Pharmacokinetic/Pharmacodynamic Advantages
of Associated Naloxone in BupNx Combination …………………….. 54
2.3.2. Sublingual Naloxone in BupNx Tablets Does Not Decrease
Buprenorphine Effects………………………………………………………….. 55
2.3.3. Sublingual Naloxone in BupNx Tablets Does Not Decrease
Blockade Effects of Buprenorphine
in Opioid-Dependent Patients ……………………………………………….. 55
2.3.4. Sublingual Naloxone in BupNx Tablets Does Not Precipitate
Withdrawal Symptoms in Opioid-Dependent Patients …………….. 56
2.3.5. Is the BupNx Combination Effective for Detoxification
or Treatment of Depressive Symptoms
in Opioid-Dependent Patients? ……………………………………………….. 56

2.3.6. What Is the Abuse Liability of Intravenous BupNx Combination
in Nonopioid-Dependent and Opioid-Dependent Patients? ………. 56
2.3.7. Intravenous Naloxone May Decrease Respiratory Depression
by Buprenorphine ………………………………………………………………… 58
2.3.8. What Will Be the Epidemiological Consequences and Potential
Economic Impact of the Use of BupNx Combination? ………………. 59
3. Limits of Buprenorphine-Naloxone Association ……………………………………… 59
3.1. Potential Risk of Inefficacy of Naloxone in BupNx Combination ………. 59
3.2. Abuse Liability of Intravenous BupNx Combination:
Low But Still Possible …………………………………………………………………….. 60
3.3. Adverse Buprenorphine Reactions and Sublingual BupNx Combination…. 60
3.3.1. Respiratory Depression ………………………………………………………… 61
3.3.2. Involuntary Overdoses………………………………………………………….. 62
3.3.3. Experimental Buprenorphine Hepatotoxicity ………………………….. 62
3.4. Specific Risks in Office-Based Treatment (BupNx Combination)
of Opiate Dependence …………………………………………………………………….. 63
4. Conclusion …………………………………………………………………………………………… 63
References ……………………………………………………………………………………………….. 64
CHAPTER 5
Buprenorphine Maintenance Treatment in Primary Care:
An Overview of the French Experience
and Insight Into the Prison Setting
Marc Deveaux and Jean Vignau …………………………………………………..69
1. Introduction ………………………………………………………………………………………….. 69
2. Implementation of BMT Through French Primary Care System ……………….. 70
2.1. A Late But Considerable Concession to Harm Reduction Paradigm …… 70
2.2. Legal Framework of Therapeutic Use of Buprenorphine …………………… 70
2.2.1. Essential Landmarks of French Health Services ……………………… 70
2.2.2. Opioid Maintenance Treatments ……………………………………………. 71
3. Observable Effects of French Policy ………………………………………………………. 72
3.1. Is BMT Accessible and Acceptable? ……………………………………………….. 72
3.2. Is BMT Safe? ………………………………………………………………………………… 72
3.2.1. Data from Preregistration Studies ………………………………………….. 73
3.2.2. Data from French Experience ……………………………………………….. 74
3.3. Is BMT Effective in Controlling Opiate Addiction and Preventing
Subsequent Relapses? …………………………………………………………………….. 75
4. Prison …………………………………………………………………………………………………… 76
4.1. Drug Addicts in French Prisons ………………………………………………………. 76
4.2. Legal Framework of BMT in Prison ………………………………………………… 76
4.3. Procedures in Loos-lez-Lille Prison…………………………………………………. 77
5. Conclusion …………………………………………………………………………………………… 78
Acknowledgments…………………………………………………………………………………….. 79
References ……………………………………………………………………………………………….. 79

CHAPTER 6
Buprenorphine as a Viable Pharmacotherapy in Australia
John H. Lewis……………………………………………………………………………… 83
1. Introduction ………………………………………………………………………………………….. 83
2. Buprenorphine………………………………………………………………………………………. 84
3. National Evaluation of Pharmacotherapies for Opioid Dependence …………… 86
4. Conclusion …………………………………………………………………………………………… 86
Acknowledgments…………………………………………………………………………………….. 87
References ……………………………………………………………………………………………….. 87
CHAPTER 7
Separative Techniques for Determination of Buprenorphine
Vincent Cirimele …………………………………………………………………………..89
1. Introduction ………………………………………………………………………………………….. 89
2. Determination of Buprenorphine in Blood ………………………………………………. 90
3. Determination of Buprenorphine in Urine ……………………………………………….. 96
4. Determination of Buprenorphine in Biological Tissues ……………………………. 99
5. Determination of Buprenorphine in Hair…………………………………………………. 99
6. Conclusion …………………………………………………………………………………………. 106
References ……………………………………………………………………………………………… 106
CHAPTER 8
Buprenorphine-Related Deaths
Pascal Kintz ……………………………………………………………………………….109
1. Introduction ………………………………………………………………………………………… 109
2. Forensic Aspects …………………………………………………………………………………. 110
3. Buprenorphine Fatalities ……………………………………………………………………… 110
4. Conclusion …………………………………………………………………………………………. 115
References ……………………………………………………………………………………………… 116
CHAPTER 9
Pharmacology of Opiates During Pregnancy and in Neonates
Pierre Marquet……………………………………………………………………………119
1. Introduction ………………………………………………………………………………………… 119
2. Perinatal Pharmacokinetics of Opiates ………………………………………………….. 119
2.1. In Utero ………………………………………………………………………………………. 119
2.1.1. Transfer Through Placenta and Distribution in Fetus …………….. 119
2.1.2. Transfer Through Blood-Brain Barrier…………………………………. 120
2.2. Postnatal ……………………………………………………………………………………… 120

3. Perinatal Pharmacodynamics of Opiates ……………………………………………….. 120
3.1. Opioid Receptors and Development of Embryos …………………………….. 120
3.2. Perinatal Effects of Exogenous Opiates………………………………………….. 121
3.2.1. On Development ………………………………………………………………… 121
3.2.2. On Opioid System………………………………………………………………. 122
4. Maintenance Treatments During Pregnancy ………………………………………….. 122
References ……………………………………………………………………………………………… 123
CHAPTER 10
Case Study of Neonates Born to Mothers
Undergoing Buprenorphine Maintenance Treatment
Pierre Marquet, Pierre Lavignasse, Jean-Michel Gaulier,
and Gérard Lachâtre …………………………………………………………..125
1. Introduction ………………………………………………………………………………………… 125
2. Clinical Findings…………………………………………………………………………………. 126
2.1. Neonates Included………………………………………………………………………… 126
2.2. Questionnaire and Toxicological Survey of Mothers ………………………. 126
2.3. Neonates’ Outcomes …………………………………………………………………….. 130
3. Toxicological Investigations ………………………………………………………………… 130
3.1. Materials and Methods …………………………………………………………………. 130
3.2. Results ………………………………………………………………………………………… 131
4. Discussion ………………………………………………………………………………………….. 133
5. Conclusion …………………………………………………………………………………………. 134
Acknowledgments…………………………………………………………………………………… 135
References ……………………………………………………………………………………………… 135
CHAPTER 11
Buprenorphine and Pregnancy:
A Comparative, Multicenter Clinical Study
of High-Dose Buprenorphine vs Methadone Maintenance
Claude Lejeune, Sandrine Aubisson, Laurence Simmat-Durand,
Fabrice Cneude, and Martine Piquet …………………………………..137
1. Introduction ………………………………………………………………………………………… 137
2. Materials and Methods ………………………………………………………………………… 138
3. Results ……………………………………………………………………………………………….. 139
4. Discussion ………………………………………………………………………………………….. 143
5. Conclusion …………………………………………………………………………………………. 145
Acknowledgments…………………………………………………………………………………… 145
References ……………………………………………………………………………………………… 145
Index……………………………………………………………………………………………………………………. 147

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