[Cannabinoids and emesis: new evidences, new questions].
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Antiemetics↗
Biomedical subjects
Sergio Abanades
Publications and source records attributed to Sergio Abanades.
Gamma-hydroxybutyrate (GHB) in humans: pharmacodynamics and pharmacokinetics.
Despite gamma-hydroxybutyrate (GHB) therapeutic uses and the increasing concern about its toxicity, few studies have addressed GHB dose-related effects under controlled administration and their relationship with its pharmacokinetics. The study design was double-blind, randomized, crossover, and controlled. As a pilot pharmacology phase I study, increasing doses of GHB were given. Single oral sodium GHB doses (40, 50, 60, and 72 mg/kg) were administered to eight volunteers. Plasma and urine were analyzed for GHB by gas chromatography-mass spectrometry. Physiological effects, psychomotor performance, and subjective effects were examined simultaneously. GHB produced dose-related changes in subjective effects as measured by questionnaires and VAS. GHB showed a mixed stimulant-sedative pattern, with initially increased scores in subjective feeling of euphoria, high, and liking followed by mild-moderate symptoms of sedation with impairment of performance and balance. Mean peak GHB plasma concentrations were 79.1, 83.1, 113.5, and 130.1 mug/L for 40, 50, 60, and 72 mg/kg, respectively. GHB-mediated physiological and subjective effects were dose dependent and related to GHB plasma concentrations. GHB urinary excretion was mainly related to administered doses. GHB-mediated subjective and physiological effects seem dose dependent and related to GHB plasma concentrations. Results suggest a high abuse liability of GHB in the range of dose usually consumed.
Cross-Over Studies↗
Quantification of the plant-derived hallucinogen Salvinorin A in conventional and non-conventional biological fluids by gas chromatography/mass spectrometry after Salvia divinorum smoking.
A gas chromatography method with mass spectrometric detection is described for the determination of Salvinorin A, the main active ingredient of the hallucinogenic mint Salvia divinorum. The method was validated in plasma, urine, saliva and sweat using 17-alpha-methyltestosterone as internal standard. The analytes were extracted from biological matrices with chloroform/isopropanol (9:1, v/v). Chromatography was performed on a 5% phenyl methyl silicone capillary column and analytes were determined in the selected ion monitoring mode. The method was validated over the concentration range 0.015-5 microg/mL plasma, urine and saliva and 0.01-5 microg/patch in the case of sweat. Mean recoveries ranged between 77.1 and 92.7% for Salvinorin A in different biological matrices, with precision and accuracy always better than 15%. The method was applied to the analysis of urine, saliva and sweat from two consumers after smoking 75 mg plant leaves to verify the presence of the active ingredient of S. divinorum in human biological fluids as a biomarker of plant consumption. Salvinorin A was detected in urine (2.4 and 10.9 ng/mL) and saliva (11.1 and 25.0 ng/mL), but not in sweat patches from consumers.
Body Fluids↗
[Club drugs: old medicines as new party drugs].
During the last few years the term club drugs has been used for defining an heterogeneous group of chemical substances in permanent evolution, that are consumed for recreational purposes. These substances have been extensively used, firstly by the Rave culture and later by the so called Club culture. These movements are characterized by the search of amplified sensations, by means of the combination of electronic music, marathon dancing and substance abuse. After years with a predominating consumption of designer amphetamines in these groups, it seems that the use of another type of substances is increasing, fundamentally drugs with hallucinogenic effects. This review focus in four of these substances; ketamine, dextromethorphan, nitrous oxide and gamma-hydroxybutyric acid (GHB, liquid ecstasy), and includes a discussion of their pharmacology, recreational use, adverse effects and patient management. These drugs are, at he same time, drugs of abuse and medicines with concrete indications in therapeutics, with an important increase of their consumption in the last few years. The Rave and Club cultures are also described.
Designer Drugs↗
Reversible coma secondary to cefepime neurotoxicity.
OBJECTIVE: To describe a case of cefepime neurotoxicity associated with acute renal failure that resulted in nonconvulsive status epilepticus. CASE SUMMARY: A 66-year-old woman with acute myeloid leukemia had fever on the third day of the initial chemotherapy cycle. Empiric antibiotic treatment with cefepime 2 g every 8 hours was started; fluconazole and vancomycin were subsequently added due to the persistence of fever. Ten days after initiation of cefepime, the patient developed acute renal failure followed by altered consciousness (Glasgow coma scale 6) associated with nonconvulsive status epilepticus. Cefepime was discontinued. Epileptiform activity in the electroencephalogram disappeared with clonazepam, and the patient regained consciousness 48 hours after cefepime withdrawal. DISCUSSION: Acute renal impairment combined with the use of cefepime may account for nonconvulsive status epilepticus. An objective causality assessment revealed that the adverse event was probably due to cefepime. Cefepime's neurotoxic effects derive from high serum concentrations resulting from decreased renal clearance, increased unbound antibiotic, and blood-brain barrier dysfunction during uremia. CONCLUSIONS: The combination of cefepime treatment and acute renal failure may induce drug-related neurotoxicity. Nonconvulsive status epilepticus frequently passes unnoticed in severely ill patients without a history of epilepsy. This disorder should be included in the list of potential causes of coma. In this patient, early detection of nonconvulsive status epilepticus and withdrawal of the antibiotic resulted in full recovery.
Acute Kidney Injury↗
Olive oils high in phenolic compounds modulate oxidative/antioxidative status in men.
The aim of the present study was to evaluate whether olive oils high in phenolic compounds influence the oxidative/antioxidative status in humans. Healthy men (n = 12) participated in a double-blind, randomized, crossover study in which 3 olive oils with low (LPC), moderate (MPC), and high (HPC) phenolic content were given as raw doses (25 mL/d) for 4 consecutive days preceded by 10-d washout periods. Volunteers followed a strict very low-antioxidant diet the 3 d before and during the intervention periods. Short-term consumption of olive oils decreased plasma oxidized LDL (oxLDL), 8-oxo-dG in mitochondrial DNA and urine, malondialdehyde in urine (P < 0.05 for linear trend), and increased HDL cholesterol and glutathione peroxidase activity (P < 0.05 for linear trend), in a dose-dependent manner with the phenolic content of the olive oil administered. At d 4, oxLDL after MPC and HPC, and 8-oxo-dG after HPC administration (25 mL, respectively), were reduced when the men were in the postprandial state (P < 0.05). Phenolic compounds in plasma increased dose dependently during this stage with the phenolic content of the olive oils at 1, 2, 4, and 6 h, respectively (P < 0.01). Their concentrations increased in plasma and urine samples in a dose-dependent manner after short-term consumption of the olive oils (P < 0.01). In conclusion, the olive oil phenolic content modulated the oxidative/antioxidative status of healthy men who consumed a very low-antioxidant diet.
8-Hydroxy-2'-Deoxyguanosine↗
Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition.
MDMA (3,4-methylenedioxymethamphetamine, ecstasy) is a widely misused psychostimulant drug abused among large segments of the young population. Pharmacologically it displays effects related to amphetamine-type drugs and a set of distinctive effects (closeness to others, facilitation to interpersonal relationship, and empathy) that have been named by some authors "entactogen" properties. MDMA is a potent releaser and/or reuptake inhibitor of presynaptic serotonin (5-HT), dopamine (DA), and norepinephrine (NE). These actions result from the interaction of MDMA with the membrane transporters involved in neurotransmitter reuptake and vesicular storage systems. The most frequent effects after MDMA/ecstasy administration are euphoria, well-being, happiness, stimulation, increased energy, extroversion, feeling close to others, increased empathy, increased sociability, enhanced mood, mild perceptual disturbances, changed perception of colors and sounds, somatic symptoms related to its cardiovascular and autonomic effects (blood pressure and heart rate increase, mydriasis), and moderate derealization but not hallucinations. Acute toxic effects are related to its pharmacologic actions. The serotonin syndrome (increased muscle rigidity, hyperreflexia, and hyperthermia), among others, is characteristic of acute toxicity episodes. MDMA metabolism is rather complex and includes 2 main metabolic pathways: (1) O-demethylenation followed by catechol-O-methyltransferase (COMT)-catalyzed methylation and/or glucuronide/sulfate conjugation; and (2) N-dealkylation, deamination, and oxidation to the corresponding benzoic acid derivatives conjugated with glycine. The fact that the polymorphic enzyme CYP2D6 partially regulates the O-demethylenation pathway prompted some expectations that subjects displaying the poor metabolizer phenotype may be at higher risk of acute toxicity episodes. In this metabolic pathway a mechanism-based inhibition of the enzyme operates because the formation of an enzyme-metabolite complex that renders all subjects, independently of genotype, phenotypically poor metabolizers after the administration of 2 consecutive doses. Therefore, the impact of CYP2D6 pharmacogenetics on acute toxicity is limited. One of the interesting features of MDMA metabolism is its potential involvement in the development of mid- to long-term neurotoxic effects as a result of progressive neurodegeneration of the serotonergic neurotransmission system.
Adrenergic Uptake Inhibitors↗
Guidelines for anecdotes might include more information.
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Adverse Drug Reaction Reporting Systems↗