Contributed by Rachel Vanderschelden, MD and Kenichi Tamama, MD, PhDFINAL DIAGNOSIS
Rhabdomyolysis and acute kidney injury secondary to cocaine and synthetic cathinone intoxication
DISCUSSION
This patient’s clinical presentation is not atypical of cocaine intoxication alone. However, his urine drug screen showed positivity for pentylone, a novel psychoactive substance (NPS) which is part of the synthetic cathinone class.
Novel psychoactive substances (NPS) are synthetic recreational drugs, often modeled after natural compounds and lacking therapeutic significance. In the United States, these substances began emerging at a high rate in the early 2000s, partially as a response to decreased availability of 3,4-Methylenedioxymethamphetamine (MDMA) 1. In fact, they are often distributed as MDMA or other established recreational drugs. There is often a lag time between first appearance of these drugs and passage of restrictive legislation. Therefore, new drugs of this class are frequently being developed to replace restricted substances. Synthetic cathinones, colloquially referred to as "Bath Salts", are derivatives of a natural alkaloid found in the shrub Catha edulis. To date, there are over 150 known synthetic cathinones, and new cathinones are continually being developed 2,3. The overwhelming majority of synthetic cathinones are used for recreational purposes, however there are some therapeutic examples, such as the antidepressant bupropion 4.
Chemically, cathinones are β-keto derivatives of amphetamines, and may be consumed by swallowing, snorting, smoking, or injecting (Figure 1). Effects on the brain are complex and vary greatly depending on the substituent of each particular cathinone. Different cathinones produce effects similar to methamphetamine, cocaine, or benzodiazepines. The most common mechanism of action is through interaction with monoamine transporters (MATs), inhibiting uptake of dopamine, norepinephrine, or serotonin at DATs, NETs, and SERTs, respectively 5,6,7. A study of one of the most commonly abused cathinones, 3,4-methylenedioxypyrovalerone (MDPV), showed that it inhibited dopamine reuptake in a fashion similar to that of cocaine with approximately 10 times the efficacy and potency 8.
Detection of synthetic cathinones has posed a challenge for toxicology laboratories. In most clinical settings, drug screening is initially performed using a qualitative or semi-quantitative immune-based assay panel. These immunoassays utilize antibodies to the target drug, and have the advantage of being rapid, relatively simple to use, widely available, and able to detect multiple drugs within the same class. However, immunoassays have limited sensitivity and specificity, and therefore results must be confirmed by definitive testing methods such as mass spectrometry coupled with either liquid or gas chromatography (LC-MS or GC-MS, respectively) 9. The detection of novel synthetic drugs is difficult for many reasons. Although some synthetic cathinones might cross-react with commercial immunoassays due to their structural similarities with amphetamine and phencyclidine, they do not lead to predictable immunoassay results. Thus, they must be definitively analyzed by LC-MS or GC-MS against a library of emerging drugs, which requires establishment of the chemical structure and expected metabolites. This also requires additional procedures such as an extraction step. In this case, the patient’s immunoassay panel was entirely negative. However, both LC-high resolution MS and GC-MS results confirmed the presence of both benzoylecgonine and pentylone.
The most recent DEA National Drug Threat Assessment lists eutylone as the most frequently reported synthetic cathinone in current use 10. Pentylone, a positional isomer of eutylone, may be indistinguishable from eutylone by LC-high resolution MS or LC-quadrupole time of flight mass spectrometry (LC-qTOF-MS), as the ion fragments for pentylone identification are shared with eutylone. But eutylone was ruled out by gas chromatography-mass spectrometry (GC-MS) analysis, confirming the identification of pentylone in this specimen. A recent study of eutylone and its structural isomers showed that they both display a "hybrid" effect on transporter activity, with inhibitory and releasing effects. Both eutylone and pentylone display potent inhibition of DAT, NET, and SERT. Additionally, they display partially releasing action at SERT 11.
The symptoms of eutylone and pentylone intoxication include tachycardia, hyperthermia, hypertension, euphoria, and agitation. Less commonly, paranoia, convulsions, hallucinations, rhabdomyolysis, acute kidney failure, and death have been reported 2. In addition to supportive treatment, patients may require physical restraints in the case of severe combativeness, and psychiatric monitoring in the case of homicidal and/or suicidal ideation. As recreational cathinone use continues occur at a high rate, it is important that clinicians are aware of presenting signs of intoxication so that they can monitor for serious manifestations such as kidney injury and rhabdomyolysis.
REFERENCES
ACKNOWLEDGEMENTS
We thank Todd Rates, Jacqueline A. Rymer, and the UPMC Special Chemistry staff for their technical assistance.
Contributed by Rachel Vanderschelden, MD and Kenichi Tamama, MD, PhD
  |
