Opioid Epidemic Uses Abuses and Innovation Methadone Jin

Opioid Epidemic: Uses, Abuses, and Innovation: Methadone Jin Bai & Stephen Bogert

1. Introduction to Methadone Identity, Structure, and Uses & Abuses

Identity × Belongs in the opioid family × Synthetic opioid × High oral bio-availability 2 × Opioid receptor agonist 2 × Long half-life 2 1 Hasan, P. ; Williams, J. Basic Opioid Pharmacology: An Update. British Journal of Pain, 2012, 6. 1, 11 -16. M. Keeping Patients Safe From Methadone Overdoses. Pharmacy and Therapeutics, 2011, 36 -8, 462 -466 2 Grissinger,

Structure

Uses & Abuses × Treatment of opioid addiction 3, 4 × Maintenance therapy 3 × Administered via clinics 3 × Highly regulated 4 × Addiction occurs through negligence 3 × Abuse 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/Methadone. Overdoses> (accessed 6 March, 2018) 5 Trafton, J. ; Minkel, J. ; Humphreys, K. Determineing Effective Methadone Dose for Individual Opioid-Dependent Patient. PLo. S Medicine, 2006, 3 -3, e 80.

2. Making Methadone Preparation, Synthesis, and Analytical Data

6 Schultz, E. Reaction of Aminoaklylhalides and Diphenylacetonitrile. J. Am. Chem. Soc, 1947, 69, 188. W. Rearrangement of the 1, 2 -dimethylaminochloropropanes. J. Am. Chem. Soc, 1947, 69, 724. 8 Schultz, E. The Structures of Amidone. J. Am. Chem. Soc, 1947, 69, 2454 -2459. 9 Easton, N. Synthesis and Confirmation of the Amidone Structure. J. Am. Chem. Soc, 1947, 69, 2941 -2942. 10 Barnett, C. Modification of Methadone Synthesis Process Step. US PAT, 1947, 4 -084, 211. 7 Brode,

6 Schultz, E. Reaction of Aminoaklylhalides and Diphenylacetonitrile. J. Am. Chem. Soc, 1947, 69, 188. W. Rearrangement of the 1, 2 -dimethylaminochloropropanes. J. Am. Chem. Soc, 1947, 69, 724. 8 Schultz, E. The Structures of Amidone. J. Am. Chem. Soc, 1947, 69, 2454 -2459. 9 Easton, N. Synthesis and Confirmation of the Amidone Structure. J. Am. Chem. Soc, 1947, 69, 2941 -2942. 10 Barnett, C. Modification of Methadone Synthesis Process Step. US PAT, 1947, 4 -084, 211. 7 Brode,

C: : : N aromatic C: : C sp 2 C: H C: N 6 Schultz, E. Reaction of Aminoaklylhalides and Diphenylacetonitrile. J. Am. Chem. Soc, 1947, 69, 188. W. Rearrangement of the 1, 2 -dimethylaminochloropropanes. J. Am. Chem. Soc, 1947, 69, 724. 8 Schultz, E. The Structures of Amidone. J. Am. Chem. Soc, 1947, 69, 2454 -2459. 9 Easton, N. Synthesis and Confirmation of the Amidone Structure. J. Am. Chem. Soc, 1947, 69, 2941 -2942. 10 Barnett, C. Modification of Methadone Synthesis Process Step. US PAT, 1947, 4 -084, 211. 7 Brode, C: : O

3. Mechanism of Methadone Function and Performance

Functionality × Competitive inhibition 11 × Maintenance × Eliminates highs and lows 11 × Absence of euphoria 11 11 Anderson, I. ; Kearney, T. Use of Methadone. West J Med. , 2000, 172. 1, 43 -46

Performance × High oral-bioavailability × Long duration × High efficacy 12 12 Marsch, 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.

Oral Bio-availability Onset Effect Avg. Half-life Typical Duration Codeine 70 -90% 45 -60 m Prodrug 4 -6 h Pethidine 40 -60% 20 -40 m 4 h 2 -4 h Morphine 30 -40% 30 -45 m 3 h 3 -4 h Oxycodone 60 -80% 45 -60 m 3. 5 h 4 -6 h Hydromorphone 24% 30 m 2. 6 h 2 -3 h Oxymorphone 10% 20 -40 m 1. 3 h 3 -4 h Levorphanol 50% 20 -40 m 11 -16 h 4 -8 h Methadone 80% 60 -90 m 22 h 6 -12 h Fentanyl 10 -15% 10 -20 m 3. 5 h 1 -2 h Buprenorphine 10 -15% 60 m 36 h 4 -12 h Tramadol 70% 60 -90 m 6. 5 h 4 -6 h Tapentadol 30 -40% 30 -45 m 4. 5 h 2 -4 h

4. The Good & Bad of Methadone Merits and Deficiencies of Methadone

× “Prevent[ing] opiate withdrawal symptoms…and minimizing the craving” 11 × “Prevent any appearance of euphoria” 11 × “There was a gradual onset of action of orally administered methadone” 13 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.

3 American × High addiction rate 3 × Negligence leads to addiction 3 × Lack of euphoria 11 Addiction Center. What to Know about Methadone Clinics. AAC, <www. americanaddictioncenters. org/methadoneaddiction/clinic-facts> (accessed 11 March, 2018) 11 Anderson, I. ; Kearney, T. Use of Methadone. West J Med. , 2000, 172. 1, 43 -46

Buprenorphine: An alternative? × Better half-life and duration 14 × Poorer performance 14 × Clear-headed feeling 14 × Higher cost 14 × Not orally available 14 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.

Summary × Used in treatment of opioid addiction × Effective receptor agonist and competitive inhibitor × High duration and efficacy × Produces no euphoria × High addiction rate

QUESTIONS