Case Studies in Toxicology: Sippin’ on Some “Sizzurp”

Case

A 19-year-old man was found unresponsive by his girlfriend. They both attended a party the previous night where a number of people were drinking alcohol and cough syrup to get “high.” When emergency medical technicians arrived at the patient’s house, they administered naloxone, which somewhat improved the patient’s level of consciousness; oxygen was also delivered via facemask.

Upon arrival to the ED, the patient complained of hearing loss and tinnitus. His initial vital signs were: blood pressure, 99/60 mm Hg; heart rate, 110 beats/minute; respiratory rate, 20 breaths/minute; temperature, 96.8°F. Oxygen saturation was 80% on room air. On examination, he was lethargic but responsive to voice and oriented to time, place, and person. His pupils were pinpoint; his hearing was decreased bilaterally; his breathing was shallow, with rales audible at both lung bases; his bowel sounds were hypoactive; and his skin was warm and moist. The rest of the examination was otherwise unremarkable.

What cough and cold products are commonly abused with the intent to get high?

Hundreds of nonprescription pharmaceutical products—each with the potential for misuse or abuse—are available to consumers in retail stores and online. These products can be classified by expected clinical effect, which helps clinicians with the diagnosis and management of these patients (Table).

Of the antitussive products currently available over the counter (OTC), those that contain dextromethorphan have the widest abuse potential. Referred to as “dex,” “DMX,” or “tuss,” this drug is widely abused among adolescents and young adults due to its easy availability. In therapeutic doses, dextromethorphan suppresses cough via the medullary cough center. Ingesting dextromethorphan at higher doses, a practice referred to as “Robo tripping,” can produce hallucinations and a dissociative state marked by alterations in consciousness and impaired motor control. Dextromethorphan is a structural analog of ketamine and phencyclidine, which accounts for their similar clinical effects.

Codeine

Codeine is another drug added to various cough medications for its antitussive properties. An opioid, it acts centrally to suppress cough and has mild analgesic properties. It is available only by prescription in the United States, but can be purchased as an OTC product in other countries. Recently, it has come into the media spotlight as the starting product to make “Krokodil” (see Emerg Med. 2014;46[2]:76-78).

Case Continuation

While undergoing his workup in the ED, the patient became increasingly lethargic with persistent hypoxia. Although initially
responsive to naloxone, his respirations became more labored, requiring intubation. Prior to intubation and while awake, the patient mentioned that he was drinking “sizzurp” the evening prior. He denied the use of other drugs or of having any suicidal intent. A postintubation chest X-ray revealed a left-sided retrocardiac infiltrate consistent with aspiration pneumonitis.

What is sizzurp?

Sizzurp is a slang term used to describe a beverage that is most frequently comprised of fruit-flavored soda, codeine/promethazine hydrochloride cough syrup (CPHCS), and hard candy (classically a Jolly Rancher).¹ This combination is ingested by the user with the intent of achieving a unique high—attributable to the combined effects of codeine, an opioid, and promethazine, an antihistamine (with antipsychotic properties). According to user reports, CPHCS induces a deep sense of euphoria, relaxation, and a slowed sense of time.² Additional slang terms used to describe this product include “lean,” “purple drank,” “purp,” “drank,” “syrup,” “barre,” and “Texas tea.”

According to one source, purple drank originated in Houston, Texas around the 1960s, when blues musicians would combine dextromethorphan with beer.³ Over time, the recipe was modified, and by the 1980s, when purple drank was adopted by hip-hop musicians from the same Houston neighborhoods, the name sizzurp took hold.

In the 1990s, one Houston-based hiphop artist, DJ Screw, developed a genre of music called “chopped and screwed,” inspired by the CPHCS high and notable for its slowed-down tempo that fit the sedation and decreased motor activity induced by the drug. As chopped and screwed music became popularized, so too did the recreational use of CPHCS. In 2000, “Sippin’ on Some Sizzurp,” a hit song by southern hip-hop group Three Six Mafia, introduced CPHCS to more mainstream hip-hop audiences.

Despite the CPHCS-related deaths of a number of hip-hop musicians, including DJ Screw, as well as the arrests of professional
football players linked to abusing the drug, CPHCS continues to be glorified by a number of hip-hop and pop musicians.

Unfortunately, media attention of these events often has the paradoxical effect of promoting use among adolescents and young adults, and CPHCS has become a drug of choice for black adolescents in many Texas communities.⁴ However, one study attempting to define a purple drank user profile among college students at a large public university in the southeastern United States revealed that use was most prevalent among urban male youth primarily from Hispanic, Native American, and white ethnic backgrounds—challenging the notion that it is confined to the black community.⁵

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.

Case

A 19-year-old man was found unresponsive by his girlfriend. They both attended a party the previous night where a number of people were drinking alcohol and cough syrup to get “high.” When emergency medical technicians arrived at the patient’s house, they administered naloxone, which somewhat improved the patient’s level of consciousness; oxygen was also delivered via facemask.

Upon arrival to the ED, the patient complained of hearing loss and tinnitus. His initial vital signs were: blood pressure, 99/60 mm Hg; heart rate, 110 beats/minute; respiratory rate, 20 breaths/minute; temperature, 96.8°F. Oxygen saturation was 80% on room air. On examination, he was lethargic but responsive to voice and oriented to time, place, and person. His pupils were pinpoint; his hearing was decreased bilaterally; his breathing was shallow, with rales audible at both lung bases; his bowel sounds were hypoactive; and his skin was warm and moist. The rest of the examination was otherwise unremarkable.

What cough and cold products are commonly abused with the intent to get high?

Hundreds of nonprescription pharmaceutical products—each with the potential for misuse or abuse—are available to consumers in retail stores and online. These products can be classified by expected clinical effect, which helps clinicians with the diagnosis and management of these patients (Table).

Of the antitussive products currently available over the counter (OTC), those that contain dextromethorphan have the widest abuse potential. Referred to as “dex,” “DMX,” or “tuss,” this drug is widely abused among adolescents and young adults due to its easy availability. In therapeutic doses, dextromethorphan suppresses cough via the medullary cough center. Ingesting dextromethorphan at higher doses, a practice referred to as “Robo tripping,” can produce hallucinations and a dissociative state marked by alterations in consciousness and impaired motor control. Dextromethorphan is a structural analog of ketamine and phencyclidine, which accounts for their similar clinical effects.

Codeine

Codeine is another drug added to various cough medications for its antitussive properties. An opioid, it acts centrally to suppress cough and has mild analgesic properties. It is available only by prescription in the United States, but can be purchased as an OTC product in other countries. Recently, it has come into the media spotlight as the starting product to make “Krokodil” (see Emerg Med. 2014;46[2]:76-78).

Case Continuation

While undergoing his workup in the ED, the patient became increasingly lethargic with persistent hypoxia. Although initially
responsive to naloxone, his respirations became more labored, requiring intubation. Prior to intubation and while awake, the patient mentioned that he was drinking “sizzurp” the evening prior. He denied the use of other drugs or of having any suicidal intent. A postintubation chest X-ray revealed a left-sided retrocardiac infiltrate consistent with aspiration pneumonitis.

What is sizzurp?

Sizzurp is a slang term used to describe a beverage that is most frequently comprised of fruit-flavored soda, codeine/promethazine hydrochloride cough syrup (CPHCS), and hard candy (classically a Jolly Rancher).¹ This combination is ingested by the user with the intent of achieving a unique high—attributable to the combined effects of codeine, an opioid, and promethazine, an antihistamine (with antipsychotic properties). According to user reports, CPHCS induces a deep sense of euphoria, relaxation, and a slowed sense of time.² Additional slang terms used to describe this product include “lean,” “purple drank,” “purp,” “drank,” “syrup,” “barre,” and “Texas tea.”

According to one source, purple drank originated in Houston, Texas around the 1960s, when blues musicians would combine dextromethorphan with beer.³ Over time, the recipe was modified, and by the 1980s, when purple drank was adopted by hip-hop musicians from the same Houston neighborhoods, the name sizzurp took hold.

In the 1990s, one Houston-based hiphop artist, DJ Screw, developed a genre of music called “chopped and screwed,” inspired by the CPHCS high and notable for its slowed-down tempo that fit the sedation and decreased motor activity induced by the drug. As chopped and screwed music became popularized, so too did the recreational use of CPHCS. In 2000, “Sippin’ on Some Sizzurp,” a hit song by southern hip-hop group Three Six Mafia, introduced CPHCS to more mainstream hip-hop audiences.

Despite the CPHCS-related deaths of a number of hip-hop musicians, including DJ Screw, as well as the arrests of professional
football players linked to abusing the drug, CPHCS continues to be glorified by a number of hip-hop and pop musicians.

Unfortunately, media attention of these events often has the paradoxical effect of promoting use among adolescents and young adults, and CPHCS has become a drug of choice for black adolescents in many Texas communities.⁴ However, one study attempting to define a purple drank user profile among college students at a large public university in the southeastern United States revealed that use was most prevalent among urban male youth primarily from Hispanic, Native American, and white ethnic backgrounds—challenging the notion that it is confined to the black community.⁵

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.

Case

A 19-year-old man was found unresponsive by his girlfriend. They both attended a party the previous night where a number of people were drinking alcohol and cough syrup to get “high.” When emergency medical technicians arrived at the patient’s house, they administered naloxone, which somewhat improved the patient’s level of consciousness; oxygen was also delivered via facemask.

Upon arrival to the ED, the patient complained of hearing loss and tinnitus. His initial vital signs were: blood pressure, 99/60 mm Hg; heart rate, 110 beats/minute; respiratory rate, 20 breaths/minute; temperature, 96.8°F. Oxygen saturation was 80% on room air. On examination, he was lethargic but responsive to voice and oriented to time, place, and person. His pupils were pinpoint; his hearing was decreased bilaterally; his breathing was shallow, with rales audible at both lung bases; his bowel sounds were hypoactive; and his skin was warm and moist. The rest of the examination was otherwise unremarkable.

What cough and cold products are commonly abused with the intent to get high?

Hundreds of nonprescription pharmaceutical products—each with the potential for misuse or abuse—are available to consumers in retail stores and online. These products can be classified by expected clinical effect, which helps clinicians with the diagnosis and management of these patients (Table).

Of the antitussive products currently available over the counter (OTC), those that contain dextromethorphan have the widest abuse potential. Referred to as “dex,” “DMX,” or “tuss,” this drug is widely abused among adolescents and young adults due to its easy availability. In therapeutic doses, dextromethorphan suppresses cough via the medullary cough center. Ingesting dextromethorphan at higher doses, a practice referred to as “Robo tripping,” can produce hallucinations and a dissociative state marked by alterations in consciousness and impaired motor control. Dextromethorphan is a structural analog of ketamine and phencyclidine, which accounts for their similar clinical effects.

Codeine

Codeine is another drug added to various cough medications for its antitussive properties. An opioid, it acts centrally to suppress cough and has mild analgesic properties. It is available only by prescription in the United States, but can be purchased as an OTC product in other countries. Recently, it has come into the media spotlight as the starting product to make “Krokodil” (see Emerg Med. 2014;46[2]:76-78).

Case Continuation

While undergoing his workup in the ED, the patient became increasingly lethargic with persistent hypoxia. Although initially
responsive to naloxone, his respirations became more labored, requiring intubation. Prior to intubation and while awake, the patient mentioned that he was drinking “sizzurp” the evening prior. He denied the use of other drugs or of having any suicidal intent. A postintubation chest X-ray revealed a left-sided retrocardiac infiltrate consistent with aspiration pneumonitis.

What is sizzurp?

Sizzurp is a slang term used to describe a beverage that is most frequently comprised of fruit-flavored soda, codeine/promethazine hydrochloride cough syrup (CPHCS), and hard candy (classically a Jolly Rancher).¹ This combination is ingested by the user with the intent of achieving a unique high—attributable to the combined effects of codeine, an opioid, and promethazine, an antihistamine (with antipsychotic properties). According to user reports, CPHCS induces a deep sense of euphoria, relaxation, and a slowed sense of time.² Additional slang terms used to describe this product include “lean,” “purple drank,” “purp,” “drank,” “syrup,” “barre,” and “Texas tea.”

According to one source, purple drank originated in Houston, Texas around the 1960s, when blues musicians would combine dextromethorphan with beer.³ Over time, the recipe was modified, and by the 1980s, when purple drank was adopted by hip-hop musicians from the same Houston neighborhoods, the name sizzurp took hold.

In the 1990s, one Houston-based hiphop artist, DJ Screw, developed a genre of music called “chopped and screwed,” inspired by the CPHCS high and notable for its slowed-down tempo that fit the sedation and decreased motor activity induced by the drug. As chopped and screwed music became popularized, so too did the recreational use of CPHCS. In 2000, “Sippin’ on Some Sizzurp,” a hit song by southern hip-hop group Three Six Mafia, introduced CPHCS to more mainstream hip-hop audiences.

Despite the CPHCS-related deaths of a number of hip-hop musicians, including DJ Screw, as well as the arrests of professional
football players linked to abusing the drug, CPHCS continues to be glorified by a number of hip-hop and pop musicians.

Unfortunately, media attention of these events often has the paradoxical effect of promoting use among adolescents and young adults, and CPHCS has become a drug of choice for black adolescents in many Texas communities.⁴ However, one study attempting to define a purple drank user profile among college students at a large public university in the southeastern United States revealed that use was most prevalent among urban male youth primarily from Hispanic, Native American, and white ethnic backgrounds—challenging the notion that it is confined to the black community.⁵

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.