(66) 2 Methyl-AP-237 Overdose: A Case Report

INTRODUCTION
Synthetic opioids have contributed to the opioid epidemic in numerous countries1. Some synthetic opioids may be more lethal due to respiratory depression that is refractory to antagonists1. Deaths from synthetic opioid use are increasing in the US2 in part from easy accessibility including the internet.
We present a case of overdose in a patient who procured online Bucinnazine (AP-237, 1-butyryl-4-cinnamylpiperazine, a potent synthetic opioid analgesic that is used in China to treat cancer-related pain but his de-identified sample detected 2 Methyl-AP-237.

2 Methyl-AP-237 is a novel synthetic opioid, a methyl derivative of Bucinnazine.
Bucinnazine has a similar analgesic potency to morphine but a shorter duration of action and is associated with tolerance and dependence, sedation, bradycardia, hypotension and apnea3. It can be ingested, inhaled, vaped or used by intravenous or intramuscular injection3. It has also been identified in recreational abuse in China3.
Fatal and non-fatal overdose from 2 Methyl-AP-237 have been reported recently in the United States4. Both 2 Methyl-AP-237 and Bucinnazine are not controlled substances in the United States and can be legally purchase via the internet3.
CASE REPORT
A 42 year old male with history of Crohn’s disease, depression, anxiety and severe opioid and benzodiazepine use disorders was brought to the ED by EMS after an accidental overdose. He was initially found apneic by his mother who administered 2 doses of 4 mg intranasal Narcan. EMS administered an addition 4mg Narcan dose after finding him hypoxic with a O2 saturation of 30%. He improved and on arrival to ED was lethargic, alert, oriented and no longer hypoxic. He admitted using 50 g of AP-237 (Bucinnazine) that he purchased online and an unknown quantity of“Xanax” prior to admission. He denied suicidality.
Urine drug screening was positive for cocaine and benzodiazepine but not opioids. Alcohol, Tylenol and salicylate levels were negative. He also had a creatinine of 1.38, venous blood gas pH of 7.35 and PCO2 of 58.
Emergency staff consulted pharmacy and poison control who were unfamiliar with the pharmacokinetic properties of this synthetic opioid. He was admitted for monitoring. 4 hours later, he developed acute hypoxic respiratory failure with a respiratory rate of 7 and aO2 saturation of 86%. 6L oxygen nasal cannula and a naloxone IV infusion was started and titrated from 0 .8 to 1.2mg/h with clinical improvement. The Naloxone drip was successfully tapered over the next 14 hours and he was discharged on third day of admission.
De-identified blood, serum, and urine samples were sent to the University of California San Francisco Clinical Toxicology and Environmental Biomonitoring (CTEB) Laboratory, which confirmed presence of 2-Methyl AP-237 in plasma and urine.

Discussion:
2 Methyl-AP-237 and Bucinnazine, are synthetic opioids that are currently not scheduled in the United States, can be easily procured and undetected by urine drug screening.
When combined with benzodiazepine, 2 Methyl-AP-237 may cause life-threatening acute opioid overdose with apnea which can be reversed using extended duration IV naloxone infusion.

References
REFERENCES
1. Synthetic Opioids. Beardsley PM, Zhang Y. Handb Exp Pharmacol. 2018;252:353-381

2. Fentanyl, fentanyl analogs and novel synthetic opioids: A cpmprehensive review. Armenian P, Vo KT, Barr-Walker J, Lynch KL.Neuropharmacology. 2018 May 15;134(Pt A):121-132

3. Michigan Poison Center, Fact Sheet: Bucinnazine

4. https://www.deadiversion.usdoj.gov/dea_tox/announcements/2-Methyl_AP-237.pdf#search=bucinnazine

Diversity, Equity, and Inclusion
Educating people in my program that addiction/substance use disorder can impact anyone irrespective of race, religion and socioeconomic status.
Providing support to all irrespective of race, religion and socioeconomic status.