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2. Novel Synthetic Opioids: Clinical Manifestations, Diagnosis,
and Treatment
David A. Gorelick, M.D., Ph.D., DLFAPA
Professor of Psychiatry
University of Maryland School of Medicine

3. Novel Synthetic Opioids
Euphoria
More available
Relaxation
Lower cost
Nondetectability on drug screening tests
Sedation
Pichini, S., R. Solimini, et al. (2018). "Acute Intoxications and Fatalities from Illicit Fentanyl and Analogues: An Update." Ther Drug Monit 40(1):

4. Immediate Adverse Effects
Stupor
Confusion
Dizziness
Slow and shallow breathing
Pupillary constriction
Orthostatic hypotension
Agitation
Nausea
Constipation
Urinary retention or urgency
Itching
Pichini, S., R. Solimini, et al. (2018). "Acute Intoxications and Fatalities from Illicit Fentanyl and Analogues: An Update." Ther Drug Monit 40(1):

5. Novel Synthetic Opioids Overdose
Coma
Cyanosis
Foaming of the mouth
Respiratory depression
Pulmonary edema
Chest wall rigidity
Bradycardia
Gurgling breath sounds
Hypotension
Ileus
Pichini, S., R. Solimini, et al. (2018). "Acute Intoxications and Fatalities from Illicit Fentanyl and Analogues: An Update." Ther Drug Monit 40(1):

6. Nonfentanyl Synthetic Opioids (MT-45)
Dry eyes
Dermatitis
Elevated liver enzymes
Possibly due to another drug or contaminant
Pichini, S., R. Solimini, et al. (2018). "Acute Intoxications and Fatalities from Illicit Fentanyl and Analogues: An Update." Ther Drug Monit 40(1):

7. Opioid intoxication syndrome
Diagnosis and Treatment
Routine drug screen
Opioid intoxication syndrome
Response to naloxone
History
Collateral
informants
Drug
samples
Packaging
Paraphernalia

8. Routes of Administration
Form
Administration
Intranasal
Powder
Injection
Tablet or capsule
Oral
Blotter paper
Transdermal
Patch
Fairbairn, N., P. O. Coffin, et al. (2017). "Naloxone for heroin, prescription opioid, and illicitly made fentanyl overdoses: Challenges and innovations responding to a dynamic epidemic." Int J Drug Policy 46:

9. Synthetic Opioids Street Names
Apache
China White
China Girl
China Town
Dance Fever
Tango & Cash
Synthetic Heroin
Green Jollies
Street Oxy
Image:

10. US Drug Enforcement Administration (DEA)
US National Institute on Drug Abuse (NIDA)

11. Respiratory depression Opioid Intoxication and Overdose
Sedation or stupor
Respiratory depression
Opioid Intoxication
and Overdose
Alcohol
Pupillary constriction
Slurred speech
Benzodiazepines vs
Other sedative-hypnotics

12. Confirmation of Intoxication
Naloxone
Partially reversed
Reverses intoxication syndrome
Mixed overdose with sedative-hypnotics

13. Naloxone: Specific Treatment
Mu receptor
Reverses intoxication
Goal
Prompt reversal of life-threatening manifestations 
Fairbairn, N., P. O. Coffin, et al. (2017). "Naloxone for heroin, prescription opioid, and illicitly made fentanyl overdoses: Challenges and innovations responding to a dynamic epidemic." Int J Drug Policy 46:

14. Naloxone Dosing Liquid solution Single dose autoinjector
Multidose nasal atomizer
Single dose nasal spray
0.4 mg/mL
2.0 mg
1 mg in 1 mL dose
0.4 or 2.0 mg in 0.1 mL
Fairbairn, N., P. O. Coffin, et al. (2017). "Naloxone for heroin, prescription opioid, and illicitly made fentanyl overdoses: Challenges and innovations responding to a dynamic epidemic." Int J Drug Policy 46:

15. Naloxone Dose to Treat Novel Synthetic Opioid Intoxication
2 mg (injected)
4 mg (intranasal) OR
May need to be repeated at 2 to 3 min intervals
Dose up to 10 mg to 20 mg
Dose and interval based on patient’s response
Goal: Respiratory rate 8 to 10 breaths/min
Fairbairn, N., P. O. Coffin, et al. (2017). "Naloxone for heroin, prescription opioid, and illicitly made fentanyl overdoses: Challenges and innovations responding to a dynamic epidemic." Int J Drug Policy 46:

16. Administer naloxone as soon as possible.
Monitor for at least 2 hours:
Vital signs
Naloxone re-administration 
Oxygen
Intravenous fluids
Evaluate for opioid use disorder and
long-term treatment.
Strongest risk factor is a prior overdose
Fairbairn, N., P. O. Coffin, et al. (2017). "Naloxone for heroin, prescription opioid, and illicitly made fentanyl overdoses: Challenges and innovations responding to a dynamic epidemic." Int J Drug Policy 46:

17. Synthetic Opioid Use Withdrawal
Similar to, but more intense than, cessation of conventional opioids 
The risk of withdrawal increases if the patient has developed tolerance.
Acute withdrawal can be precipitated by naloxone.
Gowing, L., R. Ali, et al. (2017). "Buprenorphine for managing opioid withdrawal." Cochrane Database Syst Rev 2: CD

18. Synthetic Opioid Withdrawal Syndrome
Dysphoria
Anxiety
Irritability
Depression
Suicidal ideation
Insomnia
Muscle and bone aches
Chills and fever
Gowing, L., R. Ali, et al. (2017). "Buprenorphine for managing opioid withdrawal." Cochrane Database Syst Rev 2: CD

19. Synthetic Opioid Withdrawal Syndrome
Sweating
Piloerection
Diarrhea
Abdominal cramps
Lacrimation
Rhinorrhea
Pupillary dilation
Yawning
Gowing, L., R. Ali, et al. (2017). "Buprenorphine for managing opioid withdrawal." Cochrane Database Syst Rev 2: CD

20. Treatment of Withdrawal
Methadone
Long-term treatment of opioid use disorder
Buprenorphine
Mu receptor
Short-term treatment for opioid withdrawal
Gowing, L., R. Ali, et al. (2017). "Buprenorphine for managing opioid withdrawal." Cochrane Database Syst Rev 2: CD

21. Clinical Management Observation and monitoring
Supportive and symptomatic measures
Antidepressants if:
Intravenous fluids for dehydration
Depression persists more than several days
Acetaminophen for pain or headache
Known, independent, comorbid mood disorder

22. Substance Use Disorder
10%-30%
Opioid users
Develop opioid use disorder ?
Novel synthetic opioid users
Continued use of the substance despite suffering adverse consequences from such use 
Nielsen, S., B. Larance, et al. (2016). "Opioid agonist treatment for pharmaceutical opioid dependent people." Cochrane Database Syst Rev(5): CD

23. No formal diagnosis in DSM-5 or ICD-10
Diagnosis is made by generalizing from the criteria for opioid and other substance use disorders.
Nielsen, S., B. Larance, et al. (2016). "Opioid agonist treatment for pharmaceutical opioid dependent people." Cochrane Database Syst Rev(5): CD

24. Treatment of Synthetic Opioid Use Disorder
Long-term buprenorphine or methadone for:
Pharmaceutical opioid analgesic substance use disorder
Semisynthetic opioid
substance use disorder
Nielsen, S., B. Larance, et al. (2016). "Opioid agonist treatment for pharmaceutical opioid dependent people." Cochrane Database Syst Rev(5): CD

25. Key Points
Overdose can cause life-threatening coma and respiratory depression, thus 
requiring immediate treatment. 
Intoxication can be distinguished from other designer drug intoxication by pupillary constriction and prompt response to naloxone.
Naloxone at an initial dose of 2 mg (injected) or 4 mg (intranasal) is the indicated treatment for synthetic opioid overdose.
Novel synthetic opioid withdrawal or use disorder may be treated with buprenorphine or methadone.

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