Although CPHCS is only available by prescription in the United States, its widespread abuse suggests easy access to this drug. In April 2014, Actavis, the pharmaceutical company that produces a promethazine/codeine product known as the “champagne of sizzurp,” made a bold decision to cease all production and sales of the product in direct response to the widespread media attention and glamorization of CPHCS. In its announcement, the company cited its “commitment to being a partner in the fight against prescription-drug abuse.”6 Despite Actavis’ cessation of manufacturing CPHC, at least four other companies continue to sell similar formulations.
What are the dangers of CPHCS use?
The effects produced by CPHCS are described as euphoric, which may be attributable to both codeine and promethazine. Codeine, or 3-methyl morphine, is an inactive opioid agonist and prodrug that requires metabolic activation via O-demethylation to morphine by CYP2D6. Onset of action occurs 30 to 45 minutes after ingestion, while peak effects are reached within 1 to 2 hours and last approximately 4 to 6 hours.7 Since approximately 5% to 7% of the white population lack CPY2D6 function, these individuals will experience no analgesic or euphoric effects from codeine.8 However, ultra-rapid CYP2D6 metabolizers can produce significant and potentially life-threatening concentrations of morphine.
Adverse effects of recreational codeine use are similar to that of any opioid and include central nervous system (CNS) depression, miosis, and hypoactive bowel sounds, with severe toxicity marked by coma, respiratory depression, hypotension, bradycardia, and/or death due to respiratory arrest. Aspiration pneumonitis and rhabdomyolysis are complications of impaired airway protection and prolonged immobility. Opioid-induced ototoxicity, resulting in either temporary or permanent hearing loss, is a rare complication, described largely in case reports.9 (See Emerg Med. 2012;44[11]:4-6).
Promethazine hydrochloride contributes to the unique effects experienced by the recreational user and likely acts synergistically with codeine to augment CNS depression. Both a histamine H1-receptor antagonist and the muscarinic dopamine (D2)-receptor antagonist promethazine is included in prescription cough syrups to produce its antihistamine, antiemetic, and sedative properties.7 It is well absorbed from the gastrointestinal (GI) tract with more limited oral bioavailability due to the first-pass effect. Onset of action occurs within 20 minutes of administration, and the duration of effect is approximately 4 to 6 hours. Adverse effects of promethazine include variable CNS effects, from obtundation to agitated delirium, and are often accompanied by anticholinergic effects such as hyperthermia, dry flushed skin, mydriasis, hypoactive bowel sounds, and urinary retention. Neurological manifestations, likely mediated by dopamine blockade, include muscle rigidity, athetosis, hyperreflexia, and other upper motor neuron signs. Severe toxicity can produce coma, respiratory depression, seizure, and/or death.
What are the treatment strategies?
Management of patients with CPHCS toxicity, as with all poisoned patients, begins with rapid evaluation and stabilization of the airway, breathing, and circulation. The benefits of GI decontamination are likely to be outweighed by the risks engendered by CNS depression. While supportive care is the mainstay, targeted therapies may include naloxone for the treatment of opioid-induced respiratory depression and physostigmine, when contraindications have been ruled out, for the reversal of the anticholinergic toxidrome.
Conclusion
The patient was admitted to the intensive care unit where he was treated for aspiration pneumonitis, acute respiratory distress syndrome, rhabdomyolysis, and acute renal failure. His hearing loss and tinnitus resolved. He was extubated on hospital day 9 and discharged from the hospital on day 14.
Dr Laskowski is a medical toxicology fellow in the department of emergency medicine at New York University Langone Medical Center. Dr Nelson, editor of “Case Studies in Toxicology,” is a professor in the department of emergency medicine and director of the medical toxicology fellowship program at the New York University School of Medicine and the New York City Poison Control Center. He is also associate editor, toxicology, of the EMERGENCY MEDICINE editorial board.