Prescription opioids account for about a third of all deaths from opioid use, and they sometimes have numerous adulterants that are doled out to unsuspecting users. Pure cocaine and heroin are rarely available on the street these days, with many additives and contaminants used to increase the amount of the substance sold and to produce symptoms similar to those of the pure drug.
Likewise, unadulterated opioids are rarely available to drug users, and it is quite amazing how many nonopioid contaminants can be found in these substances. The number of overdose deaths increased from 23,500 in 2002 to 70,200 in 2017, and opioid deaths increased fourfold, from 11,900 in 2002 to 47,600 in 2017. (MMWR Morb Mortal Wkly Rep. 2018;67:1419; https://bit.ly/3eiTdOK; Centers for Disease Control and Prevention. December 2018.) Many of these deaths were related to the user unknowingly using adulterated or tainted street drugs.
The Emerging Role of Toxic Adulterants in Street Drugs in the U.S. Illicit Opioid Crisis
Singh VM, Browne T, Montgomery J Public Health Rep.
The rate of opioid overdose deaths rose from 42,000 in 2016 to 47,600 in 2017, a 13 percent increase in just one year. Deaths from cocaine and the number of overdose deaths related to prescription opioids, however, have remained relatively constant. A total of 28,400 of the estimated 38,000 opioid deaths in 2018 involved non-methadone synthetic opioids; the most common was illicitly manufactured fentanyl.
Fentanyl as an adulterant was largely responsible for the increased number of deaths, but the presence and danger of multiple toxic adulterants are also important issues in opioid-related deaths. Importantly, the number of deaths from prescription opioids was and still is declining. About 60 percent of opioid-related deaths now are due to non-methadone synthetic opioid adulterants. This is a marked 45 percent increase from the previous year, highlighting the fact that manufactured opioids have become the main driver of the nation's opioid crisis.
Fentanyl and fentanyl analogs are produced in clandestine laboratories rather than commercial pharmaceutical laboratories. Synthetic opioids have been detected in about 60 percent of opioid-related deaths. Ninety percent of those who died from opioids in Florida had nonopioid toxic components in their system at autopsy. Illicit fentanyl is clearly complicating and amplifying the death rate from opioids. It is sold on the street as a powder and mixed with heroin and other less potent opioids.
Fentanyl and other added lethal adulterants often go undetected and unreported because current toxicology laboratories are unable to identify them. Suspected but unidentified adulterants can lead to renal and liver problems, blood disorders, infectious diseases, respiratory depression, and cardiac arrest. An additional pharmacologically active substance was found in 97 percent of street drug samples in Vermont and in 89 percent of those in Kentucky. As many as nine additional components were identified in these samples. It would not be uncommon to find as many as 11 additional components in the systems of those who died of drug overdose at autopsy.
Obviously, failure to recognize or identify toxic adulterants will hinder timely and appropriate treatment and could even interfere with life-saving measures. The presence of multiple pharmacologically active components in street drugs is simply amazing. The table demonstrates the amazing number of components found in street drugs seized as cocaine in Kentucky and Vermont in 2017.
Determination of Cutting Agents in Seized Cocaine Sample Using GC-MS, GC-TMS and LC-MS/MS
Fiorentin TR, Fogarty M, et al.
Forensic Sci Int.
The authors of this study attempted to quantify cocaine and cutting agents in 116 samples of cocaine using sophisticated laboratory methods. The analysis was done at the NMS Laboratories in Willow Grove, PA, probably the most advanced toxicology laboratory in the country. NMS uses gas chromatography-mass spectrometry and other state-of-the-art tests not generally available to clinicians.
The testing was done specifically to evaluate for cocaine, levamisole, benzocaine, phenacetin hydroxyzine, theophylline, acetaminophen, and caffeine. Cocaine was the only compound in only 17 percent of samples billed as cocaine. The most common cutting drug was levamisole, found in 80 percent of all samples. The percentage of levamisole in the samples was occasionally as high as 75 percent. This is one of many articles showing that street drugs are nowhere near what is advertised. Many agents are added to give a CNS effect or produce an effect that the user would identify as that of the sought-after illicit compound.
Complications from adulterants can be significant. Cardiac arrest and other cardiac complications have been well described from quinine and quinidine used to cut heroin sold to IV drug users. (J Gen Intern Med 2012;27:1722; https://bit.ly/3r9fNi2.)
Levamisole has increasingly been found in street cocaine as an adulterant (Clin Pharmacol Ther. 2010;88:408), and this may have led to the withdrawal of the drug from the U.S. market. Levamisole was approved by the U.S. Food and Drug Administration as an immunomodulator, a chemotherapy adjuvant, and an anthelmintic medication. Toxicology laboratories will not routinely assay for levamisole. The purpose of adulterating street cocaine with levamisole is not known. It has been speculated that it is added to potentiate the effects of cocaine. There have also been reports of the metabolism of levamisole to aminorex in racehorses. Aminorex and related compounds, specifically 4-methylaminorex, or “ice,” have high abuse potential because of their amphetamine-like pharmacological activity, but the intended role of levamisole in street cocaine remains unclear.
Cardiac Complications of Unwitting Co-injection of Quinine/Quinidine with Heroin in an IV Drug User
Phillips KA, Hirsch GA, et al.
J Gen Intern Med.
This article emphasizes the omnipresence of unusual products used to cut street drugs and some of the bizarre complications encountered by the unwary drug user. Clinicians in an ideal world would be able to quickly identify contaminants and be equipped to deal with the accompanying complications, but this is clearly not possible given the many adulterants used by drug dealers. The clinicians in this case identified the presence of quinine/quinidine in a street drug sold as heroin.
The purity of heroin sold in Baltimore in 2019 ranged from an amazingly low zero to 36 percent, according to the Baltimore office of the DEA. Adulterants included acetaminophen, caffeine, diphenhydramine, methorphan, alprazolam, quetiapine, chloroquine, diltiazem, cocaine, procaine, lidocaine, quinine/quinidine, phenacetin, and thiamine.
The authors reported the case of an asymptomatic 31-year-old man participating in a drug research study who was found to have an accelerated atrioventricular junctional rhythm on an ECG performed before the study. This patient had a complicated medical history, including IV heroin dependence, hepatitis C, and tobacco dependence. He was taking methadone (100 mg/day) but had no symptoms on initial evaluation. His vital signs and initial laboratory tests were normal, and a drug screen was positive for methadone.
A transthoracic echocardiogram showed minimal abnormalities, including an ejection fraction of 50%-55%, mild tricuspid regurgitation, and trace pulmonary and mitral regurgitation. The most common cause of accelerated junctional rhythm is digitalis toxicity, but it can be caused by a number of other medications and conditions.
A GC/MS analysis of the patient's urine identified codeine/morphine, methadone, acetaminophen, and quinine/quinidine. Methadone is associated with bradycardia, palpitations, hypotension, faintness, and syncope. Note that a urine GM/MS toxicology test cannot differentiate between quinidine and quinine, but that differentiation is not clinically required for the emergency physician. The accelerated atrioventricular junctional rhythm reported in this case has not been associated with methadone.
Quinine/quinidine was the second most common adulterant in heroin in Baltimore and was found in 64 percent of samples in 2009-1010. Quinine/quinidine as an adulterant produces a bitter heroin-like taste, and the hypotensive rush produced can mimic a heroin rush. Both characteristics are used by drug buyers to identify heroin on the street by tasting a small drug sample, an activity often seen on TV shows. An amazing number of adulterants have been found in street drug samples throughout the country. Levamisole was found in 62 percent of cocaine-positive urine samples in 2009. Why levamisole would be used as a cutting agent for cocaine is confusing. It can cause agranulocytosis, ear lobe necrosis, and laboratory findings of antiphospholipid syndrome. (Find additional discussion about the toxicology of levamisole in EMN. 2019;41:16; http://bit.ly/2osdXN6 and EMN. 2014;36:1; https://bit.ly/3B59FfB.)
Eighty-three percent of street drug samples collected in Vermont contained five or more components, and 15 percent contained nine or more. Eighty-nine percent of samples collected in Kentucky contained one additional pharmacologically active component, and 32 percent had five or more additional components.
No significant clinical complications were noted, and this patient did not stop using heroin, but he did decrease his use. An ECG repeated three days later showed sinus bradycardia with a period of atrioventricular dissociation plus slight junctional acceleration, which occurred at a slower rate than in earlier ECGs. A cardiologist confirmed that this change reflected an improvement in the rate and rhythm. The patient's decreased heroin use presumably resulted in decreased unwitting co-injection of quinine/quinidine, accompanied by a dose-related improvement in ECG parameters.
This case illustrated an accelerated junctional rhythm that may have resulted from a drug or drugs unwittingly injected during intravenous heroin use. Drug adulterants may produce arrhythmias or other medical complications, as well as toxicity from unsuspected drug-drug interactions. Quinidine alone has more than 135 major interactions. (See common ones in the table.) When treating patients who use illicit drugs, physicians should look beyond the known drugs of abuse for adulterants and diluents to determine possible etiologies of cardiac and other medical complications. Clinicians should also be aware that standard urine toxicology tests do not detect diluents and adulterants, and that tests such as a urine GC/MS should be performed if the clinical picture warrants it.
Obviously, given the tremendous number of adulterants and substitutions found in street drugs, it is impossible for the clinician to identify all such interventions to street drugs. It seems like few street drugs are exactly as advertised, and clandestine activities by drug dealers will only increase. Exactly how far the clinician should go in pursuing these issues is a puzzle.
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Dr. Robertsis a professor of emergency medicine and toxicology at the Drexel University College of Medicine in Philadelphia. Read his past columns athttp://bit.ly/EMN-InFocus.