N-Benzylphenethylamine derivatives are 5-HT2A receptor agonists with hallucinogenic properties, including NBOMe (N-(2-methoxybenzyl)-2-(3,4,5-trimethoxyphenyl)ethan-1-amine) and NBOH (2-(((2,5-dimethoxyphenethyl)amino)methyl)phenol). We reported here the case of a 23-year-old man who presented a serotoninergic syndrome and a loss of consciousness following the consumption of a powder labelled as 25I-NBOH. Toxicological analyses of biological samples were carried out using a liquid chromatography high-resolution mass spectrometry. Two new psychoactive substances were identified and confirmed with certified reference materials: 25E-NBOH (2-(((4-ethyl-2,5-dimethoxyphenethyl)amino)methyl)phenol) and MDPHP (1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-yl)hexan-1-one). Pharmaceuticals administered to the patient during his medical care were found in plasma and urine. 25E-NBOH and MDPHP concentrations were respectively at 2.3 ng/mL and 3.4 ng/mL in plasma, and 25.7 ng/mL and 30.5 ng/mL in urine. 25I-NBOH (2-(((4-iodo-2,5-dimethoxyphenethyl)amino)methyl)phenol) was specifically searched in both samples and was not detected. These results are discussed along with a literature review on human cases of exposure to N-benzylphenethylamine derivatives. Using molecular networking approach, we propose the first 25E-NBOH metabolism study using authentic biological samples (plasma and urine). We described seven metabolites (M1 to M7), including two phase I (m/z 330.172; m/z 288.160) and five phase II metabolites (m/z 464.191, m/z 478.207, m/z 492.223, m/z 508.218; m/z 396.156). The M6 (m/z 492.223) was the most intense ion detected in plasma and urine and could be proposed as a relevant 25E-NBOH consumption marker. Overall, we described an original case of 25E-NBOH poisoning and identified metabolites that could potentially be used as consumption markers to detect 25E-NBOH intoxications with a higher confidence level and probably a longer detection window.

Self-medication is a part of the self-care practices carried out by the elderly in their environment. The aim of this case report is to show how the self-medication of fluoxetine and dimenhydrinate in an older adult can induce serotoninergic and cholinergic syndromes, showing symptoms such as nausea, tachycardia, tremor, loss of appetite, memory loss, decreased vision, falls, and increased urination. An older adult who has been diagnosed with arterial hypertension, dyslipidemia, diabetes mellitus, and a recent diagnosis of essential thrombosis is the subject of this case report. After the analysis of the case, cessation of fluoxetine was recommended to avoid withdrawal symptoms, therefore decreasing the need for dimenhydrinate and the medicines used for dyspepsia. After the recommendation, the patient showed an improvement in the symptoms. Finally, the comprehensive evaluation process of the medication in the Medicines Optimization Unit achieved the detection of the problem and improved the patient\'s health condition.

BACKGROUND: Drug-Drug Interactions (DDIs) represent a common problem in clinical practice during drug treatments. DDIs can both induce the development of adverse drug reactions or reduce the clinical efficacy of each drug.
OBJECTIVE: The main objective of this review was to analyze the pharmacokinetic and pharmacodynamic DDIs in cocaine consumers, focusing the interest on their clinical implications.
METHODS: The PubMed, Embase and Cochrane library databases were searched for articles published until January 10, 2017. Secondary search included articles cited in reference lists identified by the primary search. Papers were deemed eligible if they included any form of words: \"adverse drug reaction\", \"drug interactions\", \"poly-therapy\", \"cocaine\", \"systemic diseases\".
RESULTS: In this review, the nodal points treated concern: i) cocaine biochemical metabolism described for both, inactive benzoylecgonine and ecgonine methyl esters and norcocaine active metabolites. We provided evidences of concepts deriving from rat/mice experimental studies speculating a translation approach to human in order to treat cocaine overdose. ii) Drug-drug interactions, which come out from clinical evidences as the case of CYP450 family enzyme inhibitors or inductors modulating cocaine toxicity. Particularly, we highlighted the lack of knowledge concerning cocaine and CYP3A4 inhibitors (such as ketoconazole, nefazodone, erythromycin, and clarithromycin). We recorded the worst association of cocaine and beta-blockers by direct and indirect action, particularly at postsynaptic levels on dopamine and norepinephrine reuptake, sympathetic activation and increase of heart rate, blood pressure and cardiovascular toxicity. Cocaine also induces increase in serotonin synaptic activity leading to the development of a serotoninergic syndrome when used with drugs that affect serotonin pathway. Genetic (i.e. glutathione peroxidase-1 deficiency) and epigenetic factors (i.e. microRNAs) may be involved in drug-drug interactions in cocaine-users are also being introduced.
CONCLUSIONS: DDIs represent an important potential complication in cocaine users in clinical setting. The knowledge of DDIs can also be used to select treatments for patients, thus optimizing clinical response and minimizing toxicity.