Aminorex associated with possible idiopathic pulmonary hypertension in a cocaine user

Karch, Steven B.; Defraia, Beatrice; Messerini, Luca; Mari, Francesco; Vaiano, Fabio; Bertol, Elisabetta

doi:10.1016/j.forsciint.2014.03.028

Cited by 27 publications

(27 citation statements)

References 21 publications

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“…Interestingly, studies in horses show that levamisole is metabolized to aminorex (152), which has a well-established link to pulmonary arterial hypertension. There is one case report of possible PAH in a cocaine user who was known to have ingested cocaine containing levamisole (153); however there are a number of confounders present in this case. While there is a strong rationale behind the levamisole-aminorex-PAH connection, more research is needed to establish whether there is a causal link with PH.…”

Section: Levamisolementioning

confidence: 79%

Drug- and toxin-induced pulmonary arterial hypertension: Current state of the literature

Ramírez

Thomas

Anderson

et al. 2020

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Drug- and toxin-induced pulmonary arterial hypertension (PAH) is an increasingly important sub-group of group 1 pulmonary hypertension (PH). In the last 60 years, we have seen the rise and fall of numerous prescription and illicit agents that have caused severe and deadly outbreaks of PAH. Currently, drugs and toxins are classified into “possible” and “definite” risk factors for PAH. While the exact mechanisms and pathogenesis of drug- and toxin-induced PAH are currently unknown, novel clinical and basic science studies are beginning to unravel the biologic factors and genetic underpinnings responsible for disease development. The clinical management of affected patients can be challenging as it is often difficult to identify patients early and demonstrate causality between drugs and PAH. Given the recent trends in drug utilization and development, it is highly likely that we will continue to identify new agents capable of causing pulmonary vascular disease. We must keep a high index of suspicion in order to identify patients and new compounds deemed definite or likely risk factors for PAH. Practicing pharmacovigilance, raising awareness, and working in tandem with PH patient associations and drug regulatory agencies may ultimately be our most effective strategy in preventing the next deadly outbreak of drug- and toxin-induced PAH.

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Section: Levamisolementioning

confidence: 79%

Drug- and toxin-induced pulmonary arterial hypertension: Current state of the literature

Ramírez

Thomas

Anderson

et al. 2020

gcsp

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“…Furthermore, few hair testing methods were published, always in combination with cocaine [7,[9][10][11].…”

Section: Resultsmentioning

confidence: 99%

“…The older hair, more porous, could have incorporated more drug when compared to the proximal segments [12]. A review of the literature on levamisole in hair showed few publications [7,[9][10][11]. Single cases were reported except a study with fifty cases from Fucci et al [11].…”

Section: Resultsmentioning

confidence: 99%

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Poisoning of a child by levamisole: Evidence by hair testing

Jamey

Kintz

Raul

2015

Toxicologie Analytique et Clinique

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“…The fact that this conversion occurs at all raises the possibility that levamisole administration might, ultimately, result in human PAH. Our group described one cocaine abuser with PAH who had aminorex detected in his urine and hair (16). But, because cocaine can cause PAH in its own right, any causal relationship remains speculative.…”

Section: Contextmentioning

confidence: 99%

Levamisole, Aminorex, and Pulmonary Arterial Hypertension: A Review

Karch¹,

Vaiano²,

Bertol³

2015

Razavi Int J Med

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Context: An epidemic of aminorex-associated pulmonary arterial hypertension (PAH), resulting in multiple fatalities, occurred in the 1970s ending only after the drug was removed from the market. In 2009, when it was found that horses de-wormed with the anthelmintic levamisole, metabolized that drug to aminorex, the same drug that caused the 1970s outbreak of PAH. The discovery would not have been cause for concern except to horseracing enthusiasts, who feared horse doping. However, at about the same time the relationship between levamisole and aminorex was discovered, cocaine cartels began adulterating cocaine with levamisole. The rationale for adulterating cocaine with levamisole remains to be established. The purpose of this short review article is to discuss possible reasons for levamisole contamination, new discoveries about the human pharmacokinetics of aminorex, and the possible relationship between aminorex and pulmonary arterial hypertension in man. Evidence acquisition: Medline contents, as well as estimates published by the U.S. drug enforcement agency (DEA), US state department, and the European monitoring center for drugs and drug abuse (EMCDDA) were reviewed and relevant articles retrieved. There is uniform agreement among the various monitoring agencies analyzed.Results: Approximately 70 percent of the U.S. cocaine supply and 40 percent of the European cocaine supply is contaminated with levamisole. Aminorex has the same binding affinities for serotonin and other neurotransmitters as amphetamine. As serotonin is considered to be an important factor in the development of PAH, the possibility of another epidemic of aminorex-induced PAH, this time among cocaine abusers, seems real, and threatening. Conclusions:The results of the first human pharmacokinetic studies of aminorex were first characterized in 2013. The results suggest that while humans could produce aminorex from levamisole, they probably do not convert very much. Even though cases of PAH have been reported in cocaine users, the latest pharmacokinetic studies suggest that very little aminorex is actually produced from the ingested levamisole, probably not enough to cause PAH. However, since both cocaine and aminorex can cause PAH the situation remains unclear. the lack of a clear answer is partially the development of an insidious pulmonary hypertension, producing subtle and non-specific symptoms in its early stages.

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Aminorex associated with possible idiopathic pulmonary hypertension in a cocaine user

Cited by 27 publications

References 21 publications

Drug- and toxin-induced pulmonary arterial hypertension: Current state of the literature

Drug- and toxin-induced pulmonary arterial hypertension: Current state of the literature

Poisoning of a child by levamisole: Evidence by hair testing

Levamisole, Aminorex, and Pulmonary Arterial Hypertension: A Review

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