Methadone Jin Bai amp Stephen Bogert 1 Introduction to Methadone Identity Structure and Uses amp Abuses Identity Belongs in the opioid family Synthetic opioid High oral bioavailability ID: 743097
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Slide1
Opioid Epidemic: Uses, Abuses, and Innovation:
Methadone
Jin Bai & Stephen BogertSlide2
1.
Introduction to Methadone
Identity, Structure, and Uses & AbusesSlide3
Identity
Belongs in the opioid family
Synthetic opioid
High oral bio-availability
2Opioid receptor agonist2Long half-life2
1
Hasan, P.; Williams, J. Basic Opioid Pharmacology: An Update. British Journal of Pain,
2012
,
6.1
, 11-16.
2
Grissinger, M. Keeping Patients Safe From Methadone Overdoses.
Pharmacy and Therapeutics
,
2011
,
36-8,
462-466Slide4
StructureSlide5
Uses & Abuses
Treatment of opioid addiction
3,4
Maintenance therapy
3Administered via clinics3Highly regulated4Addiction occurs through negligence3Abuse occurs by accident
3,4
No true dosage guidelines
5
3
American Addiction Center. What to Know about Methadone Clinics.
AAC
, <www.americanaddictioncenters.org/methadone-addiction/clinic-facts> (accessed 11 March, 2018)
4
CDC. Methadone Overdose.
CDC
, < www.cdc.gov/vitalsigns/MethadoneOverdoses> (accessed 6 March, 2018)
5
Trafton, J.;
Minkel
, J.; Humphreys, K.
Determineing
Effective Methadone Dose for Individual Opioid-Dependent Patient.
PLoS
Medicine,
2006
,
3-3,
e80.Slide6
2.
Making Methadone
Preparation, Synthesis, and Analytical DataSlide7
6
Schultz, E. Reaction of
Aminoaklylhalides
and
Diphenylacetonitrile. J. Am. Chem. Soc,
1947,
69
, 188.
7
Brode, W. Rearrangement of the 1,2-dimethylaminochloropropanes.
J. Am. Chem.
Soc
,
1947
,
69,
724.8Schultz, E. The Structures of Amidone. J. Am. Chem. Soc, 1947, 69, 2454-2459.9Easton, N. Synthesis and Confirmation of the Amidone Structure. J. Am. Chem. Soc, 1947, 69, 2941-2942.10Barnett, C. Modification of Methadone Synthesis Process Step. US PAT, 1947, 4-084, 211.Slide8
6
Schultz, E. Reaction of
Aminoaklylhalides
and
Diphenylacetonitrile. J. Am. Chem. Soc,
1947,
69
, 188.
7
Brode, W. Rearrangement of the 1,2-dimethylaminochloropropanes.
J. Am. Chem.
Soc
,
1947
,
69,
724.8Schultz, E. The Structures of Amidone. J. Am. Chem. Soc, 1947, 69, 2454-2459.9Easton, N. Synthesis and Confirmation of the Amidone Structure. J. Am. Chem. Soc, 1947, 69, 2941-2942.10Barnett, C. Modification of Methadone Synthesis Process Step. US PAT, 1947, 4-084, 211.Slide9
6
Schultz, E. Reaction of
Aminoaklylhalides
and
Diphenylacetonitrile
.
J. Am. Chem.
Soc
,
1947,
69
, 188.
7
Brode, W. Rearrangement of the 1,2-dimethylaminochloropropanes.
J. Am. Chem.
Soc
, 1947, 69, 724.8Schultz, E. The Structures of Amidone. J. Am. Chem. Soc, 1947, 69, 2454-2459.9Easton, N. Synthesis and Confirmation of the
Amidone
Structure.
J. Am. Chem.
Soc
,
1947
,
69,
2941-2942.10Barnett, C. Modification of Methadone Synthesis Process Step. US PAT, 1947, 4-084, 211.
sp
2
C:H
C:::N
aromatic C::C
sp
2
C:H
aromatic C::C
C
::O
C:NSlide10
3.
Mechanism of Methadone
Function and PerformanceSlide11Slide12
Functionality
Competitive inhibition
11
Maintenance
Eliminates highs and lows11Absence of euphoria11
11
Anderson, I.; Kearney, T. Use of Methadone.
West J Med.,
2000
,
172.1,
43-46Slide13
Performance
High oral-bioavailability
Long duration
High efficacy
1212Marsch, L. The Efficacy of Methadone Maintenance Interventions in Reducing Illicit Opiate Use, HIV Risk Behavior and Criminality: a Meta-Analysis. SSA,
1998
,
93-4
, 515-532.Slide14
Oral Bio-availability
Onset Effect
Avg. Half-life
Typical Duration
Codeine
70-90%
45-60m
Prodrug
4-6h
Pethidine
40-60%
20-40m
4h
2-4h
Morphine
30-40%
30-45m
3h
3-4h
Oxycodone
60-80%
45-60m
3.5h
4-6h
Hydrocodone
60-80%
45-60m
3.5h
4-6h
Hydromorphone
24%
30m
2.6h
2-3h
Oxymorphone
10%
20-40m
1.3h
3-4h
Levorphanol
50%
20-40m
11-16h
4-8h
Methadone
80%
60-90m
22h
6-12h
Fentanyl
10-15%
10-20m
3.5h
1-2h
Buprenorphine
10-15%
60m
36h
4-12h
Tramadol
70%
60-90m
6.5h
4-6h
Tapentadol
30-40%
30-45m
4.5h
2-4hSlide15
4.
The Good & Bad of Methadone
Merits and Deficiencies of MethadoneSlide16
“Prevent any appearance of euphoria”
11
“There was a gradual onset of action of orally administered methadone”
13
“Prevent[
ing
] opiate withdrawal symptoms…and minimizing the craving”
11
11
Anderson, I.; Kearney, T. Use of Methadone.
West J Med.,
2000
,
172.1,
43-46
13
Institute of Medicine. Federal Regulation of Methadone Treatment. NAP,
1995
,
1
, 1-112.Slide17
High addiction rate
3
Lack of euphoria
11
Negligence leads to addiction
3
3
American Addiction Center. What to Know about Methadone Clinics. AAC, <www.americanaddictioncenters.org/methadone-addiction/clinic-facts> (accessed 11 March, 2018)
11
Anderson, I.; Kearney, T. Use of Methadone.
West J Med.,
2000
,
172.1,
43-46Slide18
Buprenorphine:
An alternative?
Better half-life and duration
14
Poorer performance14Clear-headed feeling14Higher cost14Not orally available14
14
Whelan, P.;
Remski
, K. Buprenorphine vs Methadone Treatment: A Review of Evidence in Both Developed and Developing Worlds.
J
Neurosci
Rural
Pract
,
2012
,
3-1,
45-50.Slide19
Summary
Used in treatment of opioid addiction
Effective receptor agonist and competitive inhibitor
High duration and efficacy
Produces no euphoria
High addiction rateSlide20
QUESTIONS