Fatalities, Cerebral Hemorrhage, and Severe Cardiovascular Toxicity After Exposure to the New Psychoactive Substance 4-Fluoroamphetamine: A Prospective Cohort Study

Hondebrink, Laura; Lonkhuyzen, Johanna J. Nugteren–van; Rietjens, Saskia J.; Brunt, Tibor M.; Venhuis, Bastiaan J.; Soerdjbalie‐Maikoe, Vidija; Smink, B. E.; Riel, Antoinette van; Vries, Irma de

doi:10.1016/j.annemergmed.2017.07.482

Cited by 29 publications

(18 citation statements)

References 20 publications

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“…However, unlike other halogenated stimulants, such as 4-fluoroamphetamine, 4-chloroamphetamine never achieved popularity as a designer drug, possibly because of its well-documented neurotoxicity. Nevertheless, the widely used 4-fluoroamphetamine has been associated with various mild-to-moderate adverse effects (e.g., agitation, severe headache, anxiety, confusion, tachypnea, hypertension, tachycardia, chest pain, electrocardiographic abnormalities, and nausea) and severe adverse effects (e.g., coma, convulsions, cerebral hemorrhage, inverted takotsubo cardiomyopathy, myocardial infarction, and fatalities following cardiac arrest) (Hondebrink et al 2018). A detailed review of amphetamine toxicity, including toxicological pathways that involve the formation of reactive species, the depletion of antioxidants, and microglial activation, was previously published (Carvalho et al 2012).…”

Section: Adverse Effects Of Amphetaminesmentioning

confidence: 99%

Designer drugs: mechanism of action and adverse effects

2020

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Psychoactive substances with chemical structures or pharmacological profiles that are similar to traditional drugs of abuse continue to emerge on the recreational drug market. Internet vendors may at least temporarily sell these so-called designer drugs without adhering to legal statutes or facing legal consequences. Overall, the mechanism of action and adverse effects of designer drugs are similar to traditional drugs of abuse. Stimulants, such as amphetamines and cathinones, primarily interact with monoamine transporters and mostly induce sympathomimetic adverse effects. Agonism at l-opioid receptors and c-aminobutyric acid-A (GABA A) or GABA B receptors mediates the pharmacological effects of sedatives, which may induce cardiorespiratory depression. Dissociative designer drugs primarily act as N-methyl-D-aspartate receptor antagonists and pose similar health risks as the medically approved dissociative anesthetic ketamine. The cannabinoid type 1 (CB 1) receptor is thought to drive the psychoactive effects of synthetic cannabinoids, which are associated with a less desirable effect profile and more severe adverse effects compared with cannabis. Serotonergic 5-hydroxytryptamine-2A (5-HT 2A) receptors mediate alterations of perception and cognition that are induced by serotonergic psychedelics. Because of their novelty, designer drugs may remain undetected by routine drug screening, thus hampering evaluations of adverse effects. Intoxication reports suggest that several designer drugs are used concurrently, posing a high risk for severe adverse effects and even death.

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Section: Adverse Effects Of Amphetaminesmentioning

confidence: 99%

Designer drugs: mechanism of action and adverse effects

2020

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“…The same rank order has also been described for the potency of 4-FA to induce monoamine release (EC50 values of 28 nM (NE), 52 nM (DA), and 939 nM (5-HT) (Wee et al 2005). Cardiotoxicity and hyperthermia are typical symptoms of sympathomimetic intoxication associated with 4-FA use, and severe headache has been increasingly reported (Hondebrink et al 2017). Cerebral hemorrhage and severe cardiovascular toxicity were diagnosed in several cases of severe or fatal intoxications (Wijers et al 2017;Hondebrink et al 2017).…”

Section: -Fluoroamphetamine 4-fluoromethamphetamine and Nethylamphementioning

confidence: 75%

“…4-FA is a popular NPS and described by users to induce a mixture of amphetamineand MDMA-like effects, which include stimulation, euphoria and empathy (Linsen et al 2015;Hondebrink et al 2017). Despite the entactogenic properties reported for 4-FA, which are typical for MDMA-like substances, 4-FA has been included in this section due to its DAT/SERT ratio above a value of 1 (Wee et al 2005;Rickli et al 2015a;Eshleman et al 2017).…”

Section: -Fluoroamphetamine 4-fluoromethamphetamine and Nethylamphementioning

confidence: 99%

“…Cardiotoxicity and hyperthermia are typical symptoms of sympathomimetic intoxication associated with 4-FA use, and severe headache has been increasingly reported (Hondebrink et al 2017). Cerebral hemorrhage and severe cardiovascular toxicity were diagnosed in several cases of severe or fatal intoxications (Wijers et al 2017;Hondebrink et al 2017). 4-FA exhibits moderate affinity for the α2A adrenoceptor and shows weak to moderate binding affinity or activation potency at the 5-HT1A-, 5-HT2A-, 5-HT2B-, and 5-HT2C receptors.…”

Section: -Fluoroamphetamine 4-fluoromethamphetamine and Nethylamphementioning

confidence: 99%

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Pharmacology of MDMA- and Amphetamine-Like New Psychoactive Substances

Simmler

Liechti

2018

New Psychoactive Substances

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New psychoactive substances (NPS) with amphetamine-, aminoindan-, and benzofuran basic chemical structures have recently emerged for recreational drug use. Detailed information about their psychotropic effects and health risks is often limited. At the same time, it emerged that the pharmacological profiles of these NPS resemble those of amphetamine or 3,4-methylenedioxymethamphetamine (MDMA). Amphetamine-like NPS induce psychostimulation and euphoria mediated predominantly by norepinephrine (NE) and dopamine (DA) transporter (NET and DAT) inhibition and transporter-mediated release of NE and DA, thus showing a more catecholamine-selective profile. MDMA-like NPS frequently induce well-being, empathy, and prosocial effects and have only moderate psychostimulant properties. These MDMA-like substances primarily act by inhibiting the serotonin (5-HT) transporter (SERT) and NET, also inducing 5-HT and NE release. Monoamine receptor interactions vary considerably among amphetamine- and MDMA-like NPS. Clinically, amphetamine- and MDMA-like NPS can induce sympathomimetic toxicity. The aim of this chapter is to review the state of knowledge regarding these substances with a focus on the description of the in vitro pharmacology of selected amphetamine- and MDMA-like NPS. In addition, it is aimed to provide links between pharmacological profiles and in vivo effects and toxicity, which leads to the conclusion that abuse liability for amphetamine-like NPS may be higher than for MDMA-like NPS, but that the risk for developing the life-threatening serotonin syndrome may be increased for MDMA-like NPS.

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“…A case series of 33 intoxicated patients with 4-FA (4-fluoroamphetamine) showed that eight had important complications, including two deaths, four cerebral hemorrhages, two instances of Takotsubo's cardiomyopathy, one myocardial infarction, and one acute heart failure [112].…”

Section: Synthetic Amphetamine Derivativesmentioning

confidence: 99%

New Drugs of Abuse and Cardiovascular Function

Locatelli¹,

Lonati²,

Petrolini³

2020

Brain and Heart Dynamics

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Over the past decade, several new chemical compounds (the so-called NPS, new or novel psychoactive substances) have been synthesized and placed on the abuse market. About a thousand agents are known and monitored by supranational and national agencies because they cause new intoxication, prolonged health adverse effects, and addiction. Synthetic cannabinoids, cathinones, ketamines, new phenethylamines, and other molecules are today readily available at low cost. The high potency of these compounds, the important effects on the cardiovascular and central nervous systems, the still little knowledge about the prolonged health consequences, together with the hope to identify contrastable mechanisms of toxicity, have conquered

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Fatalities, Cerebral Hemorrhage, and Severe Cardiovascular Toxicity After Exposure to the New Psychoactive Substance 4-Fluoroamphetamine: A Prospective Cohort Study

Cited by 29 publications

References 20 publications

Designer drugs: mechanism of action and adverse effects

Designer drugs: mechanism of action and adverse effects

Pharmacology of MDMA- and Amphetamine-Like New Psychoactive Substances

New Drugs of Abuse and Cardiovascular Function

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