Sample records for sympathomimetics

  1. Prevalence of Rhabdomyolysis in Sympathomimetic Toxicity: a Comparison of Stimulants. (United States)

    O'Connor, Ayrn D; Padilla-Jones, Angie; Gerkin, Richard D; Levine, Michael


    Synthetic cathinones have emerged as popular drugs of abuse and produce sympathomimetic toxicity. It is unknown if rhabdomyolysis occurs more frequently following the use of synthetic cathinones compared to other stimulants. This retrospective study sought to determine the prevalence of rhabdomyolysis in patients with sympathomimetic toxicity and compare rates among patients using specific agents. Patients greater than 14 years of age with sympathomimetic toxicity and detection of a stimulant agent in urine via gas chromatography-mass spectroscopy (GC-MS) were included. Patients were excluded if clinical sympathomimetic toxicity was not present, a serum creatine kinase (CK) was not measured, or urine GC-MS was not performed. Rhabdomyolysis and severe rhabdomyolysis were defined as CK > 1000 and 10,000 IU/L, respectively. Prevalence of rhabdomyolysis and severe rhabdomyolysis were reported. Logistic regression was performed to determine the relative effect in single-agent exposures of a synthetic cathinone compared to other sympathomimetics on rhabdomyolysis. A secondary outcome, a composite endpoint defined as need for mechanical ventilation, renal replacement therapy, development of compartment syndrome, or death, was also analyzed. One hundred two subjects met inclusion criteria; median age (IQR) was 32 (25-42) years with a range of 14-65 years; 74 % were male. Rhabdomyolysis occurred in 42 % (43/102) of subjects. Patients whose sympathomimetic toxicity could be ascribed to a single agent were considered for further statistical analysis and placed into four groups: methamphetamine (n = 55), synthetic cathinone (n = 19), cocaine (n = 9), and other sympathomimetic (n = 6). In 89 subjects with single stimulant exposure, the prevalence of rhabdomyolysis was as follows: synthetic cathinone, 12/19 (63 %); methamphetamine, 22/55 (40 %); cocaine, 3/9 (33 %); and other single agent, 0/6 (0 %). The occurrence of severe rhabdomyolysis (CK > 10

  2. Pharmacotherapy of intraocular pressure: part I. Parasympathomimetic, sympathomimetic and sympatholytics. (United States)

    Costagliola, Ciro; dell'Omo, Roberto; Romano, Mario R; Rinaldi, Michele; Zeppa, Lucia; Parmeggiani, Francesco


    Elevated intraocular pressure (IOP) has been recognized as the major risk factor for the development of glaucoma and a wide range of options are now available to reduce it: medical treatment, laser, filtering, or cyclodestructive surgery (alone or in combination). All these modalities act by decreasing eye pressure and, thereby, protecting the optic nerve head from a mechanic direct and/or vascular indirect insult. Topical medical therapy represents the first-choice treatment and, in most cases, it effectively controls IOP, avoiding the occurrence of further optic nerve damage. All medications lower IOP in two main ways: decreasing the production of aqueous humour or by increasing its outflow from the eye. Consequently, antiglaucoma drugs either suppress aqueous humour formation (beta-adrenergic antagonists, carbonic anhydrase inhibitors, and alpha-2-adrenergic agonists) or raise aqueous humour outflow throughout the conventional (e.g., pilocarpine) or uveoscleral (prostaglandin FP receptor agonists, and prostamides) route. In addition, fixed and unfixed combinations of antiglaucoma compounds have also been available for patients requiring more than one type of medication. This review, which is part one of two (please see Expert Opinion on Pharmacotherapy 10 (17)) briefly considers the characteristics of sympathomimetic, sympatholytics and parasympathomimetic commonly employed in the medical treatment of glaucoma, mainly the primary open-angle form, focusing the discussion on the clinical evidence supporting the use of these three classes of compound.

  3. Use of sympathomimetic drugs leads to increased risk of hospitalization for arrhythmias in patients with congestive heart failure

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    Bouvy, M L; Heerdink, E R; De Bruin, M L


    discharge diagnosis of CHF, we identified 149 cases with a readmission for arrhythmias, and compared these in a nested matched case-control design with 149 controls from the remainder of the cohort with no hospital readmission for any cardiac cause. Conditional logistic regression was used to calculate...... sympathomimetic drug was associated with an increased risk of admission for arrhythmia (odds ratio, 4.0; 95% confidence interval, 1.0-15.1). For systemic sympathomimetic drugs, the corresponding odds ratio was 15.7 (95% confidence interval, 1.1-228.0). CONCLUSIONS: The results of this study strongly suggest...... an increased risk of hospitalization for arrhythmias in patients with CHF treated with sympathomimetic drugs. Sympathomimetics should be given under close surveillance to patients with CHF....

  4. Sympathomimetic amine therapy found effective for treatment of refractory chronic complex regional pain syndrome (reflex sympathetic dystrophy). (United States)

    Check, J H; Cohen, R


    To determine if treatment with sympathomimetic amines could improve the pain from complex regional pain disorder (CRPD) which was keeping a woman from trying to conceive her second child. Dextroamphetamine sulfate was prescribed. Within a short length of time the woman's wrist pain considerably improved to the point that she is ready to try in vitro fertilization once again to have a second baby. Though sympathomimetic amines are used by some reproductive endocrinologists for unexplained infertility and unexplained recurrent miscarriages, the most common use by the gynecologist is for pelvic pain. Despite the thought by some clinicians and researchers that the etiology for CRPD may be related to sympathetic nervous system hyperactivity (and thus sympathomimetic amines could theoretically exacerbate the symptoms), in fact, the treatment with dextroamphetamine sulfate may turn out to be a new and possibly the most effective, least risky, and least expensive treatment to date for CRPD.

  5. Transient sixth cranial nerve palsy following orgasm abrogated by treatment with sympathomimetic amines. (United States)

    Check, J H; Katsoff, B


    To describe a unique disorder where a transient 6th nerve palsy leading to diploplia following orgasm developed in a 28-year-old woman. This coincided with a weight gain of 100 pounds in a short time without a corresponding change in dietary habits. She was treated with the sympathomimetic amine dextroamphetamine sulfate. Indeed she immediately responded to treatment with dextroamphetamine sulfate sustained release capsules with complete resolution of the episodes of 6th nerve palsy following orgasm. The main importance of this case is that it suggests that orgasm causes a transient generalized decrease in sympathetic nervous system activity and that the achievement of an orgasm may require an increase in the sympathetic nervous system activity.

  6. Sympathomimetic Activity of a Hoodia gordonii Product: A Possible Mechanism of Cardiovascular Side Effects

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    Orsolya Roza


    Full Text Available Hoodia gordonii, a popular appetite suppressant, is widely used as an ingredient in many food supplements despite the fact that supporting scientific evidence is scarce. Recently alarming side effects of H. gordonii products (increased blood pressure and elevated pulse rate have been reported. The aim of our study was to elucidate the underlying mechanism of these symptoms. A H. gordonii-containing product was tested for sympathomimetic activity. Isolated organ experiments on rat uterine rings revealed smooth muscle relaxant effect with a substantial component mediated through β-adrenergic receptors. Chromatographic comparison of the analyzed product and authentic plant material confirmed that the herbal product contained Hoodia spp. extract, and its cardiovascular effects may be linked to the compounds of the plant.

  7. Sympathomimetic effects of chronic methamphetamine abuse on oral health: a cross-sectional study. (United States)

    Rommel, Niklas; Rohleder, Nils H; Koerdt, Steffen; Wagenpfeil, Stefan; Härtel-Petri, Roland; Wolff, Klaus-Dietrich; Kesting, Marco R


    Methamphetamine, a highly addictive sympathomimetic stimulant, is currently widely abused worldwide and has been associated with devastating effects on oral health, resulting in the term "meth mouth". However, "meth mouth" pathology is primarily based on case reports with a lack of systematic clinical evaluation. Therefore, we have conducted a systematic study to investigate (1) the pharmacological impact of methamphetamine on oral health with regard to saliva function, including the parameters saliva flow rate and total saliva production (ml/5 min) and the buffering capacity of saliva; (2) the contribution of the symptoms of bruxism and muscle trismus to potential oral health damage. We assessed the data of 100 chronic methamphetamine abusers and 100 matched-pair comparison participants. Primarily, we conducted an anamnesis with all methamphetamine abusers with regard to saliva dysfunctions, jaw clenching and pain in the temporomandibular joint. Subsequently, in the first part of the clinical enquiry, we tested the saliva flow rate and the total saliva production (ml/5 min) by using the sialometry method and the buffer capacity of saliva by determining the pH-value. In the second part of the clinical enquiry, we evaluated bruxism symptoms with respect to generalized tooth attrition, dentine exposure and visible enamel cracks and examined a potential muscle trismus by measuring the maximal opening of the mouth. The majority of methamphetamine abusers reported a dry mouth (72 %) and jaw clenching (68 %). Almost half of all methamphetamine abusers experienced pain in the temporomandibular joint (47 %). With regard to the clinical findings, methamphetamine abusers showed significantly lower total saliva production (ml/5 min) (p  0.05). The sympathomimetic effects of chronic methamphetamine abuse may lead to dry mouth and extensive bruxism and therefore can increase the risk for caries decay, periodontal lesions and tooth wear. Furthermore, a significant

  8. Human cardiovascular response to sympathomimetic agents during head-down bed rest: the effect of dietary sodium (United States)

    Williams, W. J.; Stuart, C. A.; Fortney, S. M.; Pietrzyk, R. A.; Chen, Y. M.; Whitson, P. A.


    Changes in sympathoadrenal function and cardiovascular deconditioning have long been recognized as a feature of the physiological adaptation to microgravity. The deconditioning process, coupled with altered hydration status, is thought to significantly contribute to orthostatic intolerance upon return to Earth gravity. The cardiovascular response to stimulation by sympathomimetic agents before, during, and after exposure to simulated microgravity was determined in healthy volunteers equilibrated on normal or high sodium diets in order to further the understanding of the deconditioning process.

  9. EPR study of complex formation between copper (II) ions and sympathomimetic amines in aqueous solution

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    Preoteasa, E.A. [Inst. of Atomic Physics, IFIN, Bucharest (Romania); Duliu, O.G.; Grecu, V.V. [Bucharest, Univ. (Romania). Dept. of Atomic and Nuclear Physics


    The complex formation between sympathomimetic amines (SA): adrenaline (AD), noradrenaline (NA), dopamine (DA), ephedrine (ED) and p-tyramine (pTA), and Cu(II) ion in aqueous solution has been studied by X-band EPR at room temperature. Excepting pTA, all investigated SA yielded two types of complexes in different pH domains. All complexes consistent with a ligand fields having a distorted octahedral symmetry, i.e., hexacoordination of Cu(II). The covalence coefficient calculated from the isotropic g and A values has shown strong ionic sigma-type ligand bonds. A structural model with the Cu(II) ion bound by four catecholic O(hydroxy) atoms for the low pH complexes of AD, NA and DA is proposed. For the high pH complexes of the former compounds as well as for both Ed complexes, the authors suppose Cu(II) bound by two N (amino) and two O (hydroxy) atoms. The spectra are consistent to water binding on the longitudinal octahedron axis in all compounds excepting the high pH complex of Ed, where OH2- ions are bound. Possible implications for the SA-cell receptors interactions are discussed.

  10. Effect of hindlimb suspension on cardiovascular responses to sympathomimetics and lower body negative pressure (United States)

    Overton, J. Michael; Tipton, Charles M.


    To determine whether hindlimb suspension is associated with the development of cardiovascular deconditioning, male rats were studied before and after undergoing one of three treatment conditions for 9 days: (1) cage control (n = 15, CON), (2) horizontal suspension (n = 15, HOZ), and (3) head-down suspension (n = 18, HDS). Testing included lower body negative pressure administered during chloralose-urethan anesthesia and graded doses of sympathomimetic agents (norepinephrine, phenylephrine, and tyramine) administered to conscious unrestrained animals. Both HDS and HOZ were associated with a small decrease in the hypotensive response to lower body negative pressure. The HOZ group, but not the HDS group, exhibited augmented reflex tachycardia. Furthermore, both HDS and HOZ groups manifested reduced pressor responses to phenylephrine after treatment. These reductions were associated with significantly attenuated increases in mesenteric vascular resistance. However, baroreflex control of heart rate was not altered by the treatment conditions. Collectively, these results indicate that 9 days of HDS in rats does not elicit hemodynamic response patterns generally associated with cardiovascular deconditioning induced by hypogravic conditions.

  11. [Specific detection of urinary sympathomimetic amines for control of anti-doping by gas chromatography-mass spectroscopy]. (United States)

    Franceschini, A; Duthel, J M; Vallon, J J


    A specific, sensitive and reliable gas chromatography-mass spectrometry (GC-MS) technique for detection of sympathomimetic amines following urinary extraction is proposed. Amphetamine, phentermine, ephedrine, mephenorex, methylphenidate, benzphetamine, clobenzorex and internal standard (fenfluramine) are extracted from urines at pH 7.0 using elution by chloroform-isopropanol on C18 cartridges. Derivatization followed by GC-MS analysis allows identification of these drugs founded on relative retention times and mass spectra. The quantitation limit for derivatizable drugs was found to be 200 ng/ml and 500 ng/ml for underivatizable drugs.

  12. Arousal and stability - The effects of five new sympathomimetic drugs suggest a new principle for the prevention of space motion sickness (United States)

    Kohl, R. L.; Calkins, D. S.; Mandell, A. J.


    Sympathomimetic agents are frequent components in antimotion-sickness drug combinations because of their usefulness in counteracting the sedation caused by stressful motion or resulting from the administration of other antimotion-sickness drugs. The noradrenergic neurochemistry of the brain's arousal-attentional systems prompted us to evaluate the efficacy of five new sympathomimetic drugs and to further define the role of arousal in susceptibility to motion. Subjects were orally administered methamphetamine (20 mg), phenmetrazine (25 mg), phentermine (37.5 mg), methylphenidate (20 mg), or pemoline (75 mg) 2 h prior to taking a Staircase Profile Test. All of the drugs increased resistance to stressful coriolis stimulation by 80-120 percent. Methylphenidate and pemoline showed fewer side effects. These findings, interpreted in conjunction with the documented inefficacy of most anticholinergic and antihistaminergic drugs tested to date, suggest that sympathomimetic drugs or a generalized state of arosusal can inhibit the development of motion sickness.

  13. Nasal Resistance Is Elevated in People with Tetraplegia and Is Reduced by Topical Sympathomimetic Administration. (United States)

    Gainche, Laura; Berlowitz, David J; LeGuen, Mariannick; Ruehland, Warren R; O'Donoghue, Fergal J; Trinder, John; Graco, Marnie; Schembri, Rachel; Eckert, Danny J; Rochford, Peter D; Jordan, Amy S


    Obstructive sleep apnea (OSA) is common in individuals with tetraplegia and associated with adverse health outcomes. The causes of the high prevalence of OSA in this population are unknown, but it is important to understand as standard treatments are poorly tolerated in tetraplegia. Nasal congestion is common in tetraplegia, possibly because of unopposed parasympathetic activity. Further, nasal obstruction can induce OSA in healthy individuals. We therefore aimed to compare nasal resistance before and after topical administration of a sympathomimetic between 10 individuals with tetraplegia (T) and 9 able-bodied (AB) controls matched for OSA severity, gender, and age. Nasal, pharyngeal, and total upper airway resistance were calculated before and every 2 minutes following delivery of ≈0.05 mL of 0.5% atomized phenylephrine to the nostrils and pharyngeal airway. The surface tension of the upper airway lining liquid was also assessed. At baseline, individuals with tetraplegia had elevated nasal resistance (T = 7.0 ± 1.9, AB = 3.0 ± 0.6 cm H 2 O/L/s), that rapidly fell after phenylephrine (T = 2.3 ± 0.4, p = 0.03 at 2 min) whereas the able-bodied did not change (AB = 2.5 ± 0.5 cm H 2 O/L/s, p = 0.06 at 2 min). Pharyngeal resistance was non-significantly higher in individuals with tetraplegia than controls at baseline (T = 2.6 ± 0.9, AB = 1.2 ± 0.4 cm H 2 O/L/s) and was not altered by phenylephrine in either group. The surface tension of the upper airway lining liquid did not differ between groups (T = 64.3 ± 1.0, AB = 62.7 ± 0.6 mN/m). These data suggest that the unopposed parasympathetic activity in tetraplegia increases nasal resistance, potentially contributing to the high occurrence of OSA in this population. © 2016 American Academy of Sleep Medicine

  14. Hyperresponsiveness of the airways following exposure of guinea-pigs to racemic mixtures and distomers of beta 2-selective sympathomimetics. (United States)

    Mazzoni, L; Naef, R; Chapman, I D; Morley, J


    Allergic bronchospasm in sensitized guinea-pigs was totally suppressed by acute subcutaneous infusion of rac-salbutamol (0.69 microgram/kg per min) for salbutamol induced a progressive susceptibility to inhaled antigen so that, by 48 h, animals collapsed and died following inhalation of antigen. In anaesthetized animals, acute infusion of rac-salbutamol (1.67 micrograms/kg per min) suppressed airway obstruction, an effect that can be attributed to beta 2-adrenoceptor activation by the eutomer (R-salbutamol). Acute intravenous infusion of the distomer (S-salbutamol) (1.67 micrograms/kg per min) induced hyperresponsiveness to histamine without having any effect upon airway calibre. It is suggested therefore that subcutaneous infusion of rac-salbutamol initially abrogates the bronchoconstrictor response to antigen because the bronchodilator action of the eutomer predominates over hyperreactivity attributable to the distomer. Conversion from protection to susceptibility was not determined by reduced beta 2-adrenoceptor activation since animals could be protected from a lethal response to antigen by inhalation of rac-isoprenaline or by subcutaneous injection of rac-salbutamol. The seeming progressive loss of efficacy of R-salbutamol may result from disproportionate accumulation of S-salbutamol if, as in man, there is stereospecific metabolism of R-salbutamol. The capacity of S-salbutamol to evoke hyperresponsiveness is shared by S-isoprenaline and S-terbutaline and, as has been shown previously for rac-isoprenaline, the capacity of S-salbutamol to elicit hyperresponsiveness was not evidenced following section of the vagus nerves. No mechanism has yet been established which might account for this property of S-salbutamol or for other S-enantiomers of sympathomimetics.

  15. Novel kinetic spectrophotometric method for estimation of certain biologically active phenolic sympathomimetic drugs in their bulk powders and different pharmaceutical formulations. (United States)

    Omar, Mahmoud A; Badr El-Din, Khalid M; Salem, Hesham; Abdelmageed, Osama H


    A simple, selective and sensitive kinetic spectrophotometric method was described for estimation of four phenolic sympathomimetic drugs namely; terbutaline sulfate, fenoterol hydrobromide, isoxsuprine hydrochloride and etilefrine hydrochloride. This method is depended on the oxidation of the phenolic drugs with Folin-Ciocalteu reagent in presence of sodium carbonate. The rate of color development at 747-760nm was measured spectrophotometrically. The experimental parameters controlling the color development were fully studied and optimized. The reaction mechanism for color development was proposed. The calibration graphs for both the initial rate and fixed time methods were constructed, where linear correlations were found in the general concentration ranges of 3.65×10 -6 -2.19×10 -5 molL -1 and 2-24.0μgmL -1 with correlation coefficients in the following range 0.9992-0.9999, 0.9991-0.9998 respectively. The limits of detection and quantitation for the initial rate and fixed time methods were found to be in general concentration range 0.109-0.273, 0.363-0.910 and 0.210-0.483, 0.700-1.611μgmL -1 respectively. The developed method was validated according to ICH and USP 30 -NF 25 guidelines. The suggested method was successfully implemented to the estimation of these drugs in their commercial pharmaceutical formulations and the recovery percentages obtained were ranged from 97.63%±1.37 to 100.17%±0.95 and 97.29%±0.74 to 100.14±0.81 for initial rate and fixed time methods respectively. The data obtained from the analysis of dosage forms were compared with those obtained by reported methods. Statistical analysis of these results indicated no significant variation in the accuracy and precision of both the proposed and reported methods. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Novel kinetic spectrophotometric method for estimation of certain biologically active phenolic sympathomimetic drugs in their bulk powders and different pharmaceutical formulations (United States)

    Omar, Mahmoud A.; Badr El-Din, Khalid M.; Salem, Hesham; Abdelmageed, Osama H.


    A simple, selective and sensitive kinetic spectrophotometric method was described for estimation of four phenolic sympathomimetic drugs namely; terbutaline sulfate, fenoterol hydrobromide, isoxsuprine hydrochloride and etilefrine hydrochloride. This method is depended on the oxidation of the phenolic drugs with Folin-Ciocalteu reagent in presence of sodium carbonate. The rate of color development at 747-760 nm was measured spectrophotometrically. The experimental parameters controlling the color development were fully studied and optimized. The reaction mechanism for color development was proposed. The calibration graphs for both the initial rate and fixed time methods were constructed, where linear correlations were found in the general concentration ranges of 3.65 × 10- 6-2.19 × 10- 5 mol L- 1 and 2-24.0 μg mL- 1 with correlation coefficients in the following range 0.9992-0.9999, 0.9991-0.9998 respectively. The limits of detection and quantitation for the initial rate and fixed time methods were found to be in general concentration range 0.109-0.273, 0.363-0.910 and 0.210-0.483, 0.700-1.611 μg mL- 1 respectively. The developed method was validated according to ICH and USP 30 -NF 25 guidelines. The suggested method was successfully implemented to the estimation of these drugs in their commercial pharmaceutical formulations and the recovery percentages obtained were ranged from 97.63% ± 1.37 to 100.17% ± 0.95 and 97.29% ± 0.74 to 100.14 ± 0.81 for initial rate and fixed time methods respectively. The data obtained from the analysis of dosage forms were compared with those obtained by reported methods. Statistical analysis of these results indicated no significant variation in the accuracy and precision of both the proposed and reported methods.

  17. Adverse effects of sympathomimetic drugs in a group of adolescents


    Jerí, F. Raúl; Departamento de Medicina, Sección de Neurología, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Carbajal, Carlos; Departamento de Medicina, Sección de Neurología, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Sánchez M., César; Departamento de Medicina, Sección de Neurología, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú


    Clinical observations of 35 youths who used hallucinogenic drugs for two to four years are mostly present . The proportion of males was three times compared to women , almost all households were from well integrated and belonged to a higher socio- economic level or medium . The drugs used were marijuana , LSD , barbiturates , mescaline , afetamina , methaqualone and alcohol, in various combinations . All of these young people showed signs of psychological disturbance , personality disorders g...

  18. Phenylephrine postconditioning increases myocardial injury: Are alpha-1 sympathomimetic agonist cardioprotective?

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    Iordanis Mourouzis


    Full Text Available Objective: We studied effects of phenylephrine (PHE on postischemic functional recovery and myocardial injury in an ischemia-reperfusion (I-R experimental model. Materials and Methods: Rat hearts were Langendorff-perfused and subjected to 30 min zero-flow ischemia (I and 60 min reperfusion (R. During R PHE was added at doses of 1 μM (n = 10 and 50 μM (n = 12. Hearts (n = 14 subjected to 30 and 60 min of I-R served as controls. Contractile function was assessed by left ventricular developed pressure (LVDP and the rate of increase and decrease of LVDP; apoptosis by fluorescent imaging targeting activated caspase-3, while myocardial injury by lactate dehydrogenase (LDH released during R. Activation of kinases was measured at 5, 15, and 60 min of R using western blotting. Results: PHE did not improve postischemic contractile function. PHE increased LDH release (IU/g; 102 ± 10.4 (Mean ± standard error of mean control versus 148 ± 14.8 PHE (1, and 145.3 ± 11 PHE (50 hearts, (P < 0.05. PHE markedly increased apoptosis. Molecular analysis showed no effect of PHE on the activation of proapoptotic c-Jun N-terminal kinase signaling; a differential pattern of p38 mitogen activated protein kinase (MAPK activation was found depending on the PHE dose used. With 1 μM PHE, p-p38/total-p38 MAPK levels at R were markedly increased, indicating its detrimental effect. With PHE 50 μM, no further changes in p38 MAPK were seen. Activation of Akt kinase was decreased implying involvement of different mechanisms in this response. Conclusions: PHE administration during reperfusion does not improve postischemic recovery due to exacerbation of myocardial necrosis and apoptosis. This finding may be of clinical and therapeutic relevance.

  19. Phenylethylamine and tyramine are mixed-acting sympathomimetic amines in the brain. (United States)

    Knoll, J; Miklya, I; Knoll, B; Markó, R; Rácz, D


    On the helical strip of a capacitance vessel, the pulmonary artery of the rabbit, phenylethylamine (PEA) and tyramine act solely via displacement of noradrenaline from their storage sites and this effect is inhibited by desmethylimipramine (DMI). In contrast, on a resistance vessel, the perfused central ear artery of the rabbit, PEA enhances stimulation induced contractions in 0.2-0.8 microgram/ml concentration [catecholaminergic activity enhancer (CAE) effect], and increases smooth muscle tone (noradrenaline displacing effect) in 4-6 micrograms/ml concentration. This latter effect only is blocked by DMI. Tyramine acts similarly and is more potent than PEA. On the isolated brain stem PEA, tyramine and (-)methamphetamine are, in the presence of cocaine and DMI, highly potent enhancers of stimulation induced release of 3H-noradrenaline, 3H-dopamine and 3H-serotonin. Compounds with specific CAE effect in the brain, (-)deprenyl and 1-phenyl-2-propylaminopentane [(-)PPAP], antagonize tetrabenazine-induced depression of performance of rats in the shuttle box. PEA and tyramine, which are rapidly metabolized in vivo, are ineffective in this test up to 40 mg/kg, whereas (-)methamphetamine, the stable PEA derivative, is highly effective. Compounds with CAE effect enhance at low concentrations the slow inward Ca2+ current in the sino-auricular fibers of the frog heart and inhibit it in high concentration. PEA and tyramine enhance Ca2+ influx from 0.05 to 4 micrograms/ml and inhibit it in 8 micrograms/ml. In conclusion, PEA and tyramine stimulate primarily coupling of action potential to transmitter release in the catecholaminergic neurons in the brain and displace catecholamines in higher concentration only.

  20. Anti-rhinovirus-specific activity of the alpha-sympathomimetic oxymetazoline. (United States)

    Koelsch, Stephan; Tschaikin, Marion; Sacher, Fritz


    Oxymetazoline (CAS 2315-02-8, OMZ, Nasivin) known as the active ingredient in nose drops and sprays demonstrates excellent efficacy in the treatment of rhinitis symptoms that are mainly caused by Rhinovirus infections. To elucidate possible modes of action, the antiviral activity of OMZ was studied in vitro on human pathogenic viruses. No in vitro effects were detected against enveloped RNA viruses, Parainfluenza Virus and Respiratory Syncytial Virus and against Adenovirus, a non-enveloped DNA-virus. In contrast, OMZ showed a specific inhibition of Human Rhinovirus (HRV). Analysis of production of HRV-14 and HRV-39 after treatment of infected HeLa cells using plaque-reduction assay and virus titration showed a strong dose-dependent antiviral activity of OMZ. Additional data demonstrated that OMZ did also directly affect HRV-14 infectivity in a dose-dependent manner. Analysis of a cell-protective effect of OMZ showed that pre-treatment of HeLa cells decreased virus adsorption as well as virus replication. Furthermore, OMZ induced a down-regulation of ICAM-1 expression on Tumor Necrosis Factor-alpha (TNF-alpha)-stimulated HeLa cells and human umbilical vein endothelial cells. Taken together, these results show that OMZ besides its vasoconstrictive action also possesses potent antiviral and anti-inflammatory activities. Therefore, OMZ does not only reduce rhinitis symptoms but additionally offers a causal therapeutic approach.

  1. Caffeine and other sympathomimetic stimulants: modes of action and effects on sports performance. (United States)

    Jones, Gareth


    Stimulants, illegal and legal, continue to be used in competitive sport. The evidence for the ergogenic properties of the most potent stimulants, amphetamines, cocaine and ephedrine, is mostly insubstantial. Low doses of amphetamines may aid performance where effects of fatigue adversely affect higher psychomotor activity. Pseudoephedrine, at high doses, has been suggested to improve high intensity and endurance exercise but phenylpropanolamine has not been proven to be ergogenic. Only caffeine has substantial experimental backing for being ergogenic in exercise. The mode of action of these stimulants centres on their ability to cause persistence of catecholamine neurotransmitters, with the exception of caffeine which is an adenosine receptor antagonist. By these actions, the stimulants are able to influence the activity of neuronal control pathways in the central (and peripheral) nervous system. Rodent models suggest that amphetamines and cocaine interact with different pathways to that affected by caffeine. Caffeine has a variety of pharmacological effects but its affinity for adenosine receptors is comparable with the levels expected to exist in the body after moderate caffeine intake, thus making adenosine receptor blockade the favoured mode of ergogenic action. However, alternative modes of action to account for the ergogenic properties of caffeine have been supported in the literature. Biochemical mechanisms that are consistent with more recent research findings, involving proteins such as DARPP-32 (dopamine and cAMP-regulated phosphoprotein), are helping to rationalize the molecular details of stimulant action in the central nervous system.

  2. Intranasal oxytocin reduces provoked symptoms in female patients with posttraumatic stress disorder despite exerting sympathomimetic and positive chronotropic effects in a randomized controlled trial. (United States)

    Sack, M; Spieler, D; Wizelman, L; Epple, G; Stich, J; Zaba, M; Schmidt, U


    Posttraumatic stress disorder (PTSD) is a severe psychiatric disease accompanied by neuroendocrine changes such as adrenergic overdrive and hence an elevated cardiovascular morbidity. Current pharmacotherapeutic options for PTSD are less than suboptimal, necessitating the development of PTSD-specific drugs. Although the neuropeptide oxytocin has been repeatedly suggested to be effective in PTSD treatment, there are, to our knowledge, only three studies that have assessed its efficacy on the intensity of PTSD symptoms in PTSD patients - among them one symptom provocation study in male veterans. To evaluate for the first time how oxytocin influences the intensity of provoked PTSD symptoms and, furthermore, cardiac control in female PTSD patients, we assessed their psychic and cardiac response to trauma-script exposure with and without oxytocin pretreatment in a double-blind randomized placebo-controlled study. We used a within-subject design to study 35 female PTSD patients who received oxytocin and placebo in a 2-week interval. Furthermore, we performed a small pilot study to get an idea of the relation of the stress-modulated endogenous oxytocin levels and heart rate - we correlated oxytocin serum levels with the heart rate of 10 healthy individuals before and after exposure to the Trier Social Stress Test (TSST). Intranasal oxytocin treatment was followed by a reduction of provoked total PTSD symptoms, in particular of avoidance, and by an elevation in baseline and maximum heart rate together with a drop in the pre-ejection period, a marker for sympathetic cardiac control. Furthermore, we found a positive correlation between endogenous oxytocin levels and heart rate both before and after TSST challenge in healthy control subjects. This study provides the first evidence that oxytocin treatment reduces the intensity of provoked PTSD symptoms in female PTSD patients. The small size of both samples and the heterogeneity of the patient sample restrict the generalizability of our findings. Future studies have to explore the gender dependency and the tolerability of the oxytocin-mediated increase in heart rate. This randomized controlled trial was retrospectively registered at the German Trials Register (DRKS00009399) on the 02 October 2015.

  3. Mecanismos de cardiotoxicidad: antineoplásicos, anti-inflamatorios no esteroideos, antipsicóticos, cocaetileno y simpaticomiméticos Mechanisms of cardiotoxicity: antineoplastics, nonsteroidal anti-inflammatory drugs, antipsychotics, cocaethylene and sympathomimetics

    Directory of Open Access Journals (Sweden)

    Lukas Salazar


    Full Text Available La interacción constante del organismo humano con diferentes sustancias, que incluso en muchas ocasiones se consideran inofensivas, tiene un alto impacto sobre todos los sistemas, siendo el cardiovascular uno de los más afectados. Por lo tanto, es vital reconocer los mecanismos por los cuales estas sustancias ejercen su efecto tóxico sobre este sistema, bien sea afectando la estabilidad de membrana y la función contráctil o generando disfunción de organelos intracelulares y estrés oxidativo. Numerosos estudios han descubierto efectos lesivos de sustancias, como la clozapina y las catecolaminas, que han tenido amplio uso durante largos años. En la actualidad aún se realizan investigaciones que buscan esclarecer los mecanismos cardiotóxicos de medicamentos de formulación común, entre ellos antineoplásicos y anti-inflamatorios no esteroideos (AINE, así como de sustancias de uso habitual que causan adicción, tales como alcohol, cocaína y cocaetileno, su metabolito activo.The constant interaction of the human body with different substances that are even in many cases considered harmless has a high impact on all systems, being the cardiovascular system one of the most affected. Therefore, it is vital to recognize the mechanisms by which these substances exert their toxic effect on this system, either affecting the membrane stability and the contractile function, or generating intracellular organelles dysfunction and oxidative stress. Numerous studies have found that drugs which have been widely used for many years such as clozapine and catecholamines, have harmful effects. Research is still being done seeking to clarify the cardiotoxic mechanisms of drugs commonly formulated, including anticancer and non steroidal anti-inflammatory drugs (NSAIDs, as well as commonly used substances that cause addiction, such as alcohol, cocaine and cocaethylene, its active metabolite.

  4. Epinephrine Injection (United States)

    ... in a class of medications called alpha- and beta-adrenergic agonists (sympathomimetic agents). It works by relaxing ... This branded product is no longer on the market. Generic alternatives may be available.

  5. Enhancement of drug detection and identification by use of various derivatizing reagents on GC-FTIR analysis. (United States)


    Phenylpropanolamine (PPA) is a relatively common non-prescription sympathomimetic amine. As such, it is frequently detected during forensic analysis. The presence of phenylpropanolamine can be confirmed by using Gas Chromatograph-Fourier Transform In...

  6. Thunderclap headache and reversible segmental cerebral vasoconstriction associated with use of oxymetazoline nasal spray. (United States)

    Loewen, Andrea H S; Hudon, Mark E; Hill, Michael D


    Oxymetazoline is a sympathomimetic amine found in over-the-counter nasal decongestants. We report a case of chronic use of nasal oxymetazoline associated with thunderclap headache due to reversible segmental intracranial vasoconstriction.

  7. Thunderclap headache and reversible segmental cerebral vasoconstriction associated with use of oxymetazoline nasal spray


    Loewen, Andrea H.S.; Hudon, Mark E.; Hill, Michael D.


    OXYMETAZOLINE IS A SYMPATHOMIMETIC amine found in over-the-counter nasal decongestants. We report a case of chronic use of nasal oxymetazoline associated with thunderclap headache due to reversible segmental intracranial vasoconstriction.


    African Journals Online (AJOL)

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    )-pyridinones and their 2-imino ... synthesis of milrinone analogues as a series of nonglycosidic, non-sympathomimetic, cardiotonic .... from dimethoxyacetophenone and ammonia adds to the aldol condensation product of the aldehyde and ...

  9. Fetal heart rate changes following maternal administration of a nasal decongestant. (United States)

    Baxi, L V; Gindoff, P R; Pregenzer, G J; Parras, M K


    Repeated use of a long-acting sympathomimetic amine in the form of a nasal spray was associated with a nonreactive nonstress test and late decelerations in a patient at 41 weeks of gestation. Six hours after the last dose, these changes gradually disappeared.

  10. Disodium Cromoglycate (Lomudal) in Asthma with Emphasis on ...

    African Journals Online (AJOL)

    The value of DSCG in facilitating reduction of corticosteroid and sympathomimetic therapy for asthma is emphasized. Some practical points in the use of DSCG are listed. Disodium cromoglycate is safe and efficacious in allergic bronchial asthma and is a very useful adjunct in the therapy of this common, potentially serious ...

  11. Semen-like urethral discharge during the use of mazindol

    NARCIS (Netherlands)

    van Puijenbroek, E P; Meyboom, R H

    Two case reports are described of male patients experiencing a semen-like urethral discharge during micturition, suspected to be induced by mazindol. Mazindol has an indirect sympathomimetic action and is known to cause urogenital side effects such as urinary retention and testicular pain. It is

  12. Pulmonary oedema after hexoprenaline administration in preterm ...

    African Journals Online (AJOL)

    Despite the widespread use of ,a-sympathomimetic agents for preterm labour there appears to be a limited appreciation of the need for cardiovascular monitoring in the mother. Four patients in whom pulmonary oedema developed during tocolysis with hexoprenaline are described and the aetiological factors and ...

  13. [Pharmacological prophylaxis of vestibulo-autonomous syndrome (motion sickness) in model investigations]. (United States)

    Shashkov, V S; Iasnetsov, V V; Shashkov, A V; Il'ina, S L; Galle, R R; Sabaev, V V; Potapov, M G


    The authors summarize results of multiyear investigations at the Institute of Biomedical Problems of induced motion sickness and development of prophylactic medicaments representing various classes of biologically active substances (choline blocking agents, sympathomimetics, antihistamines etc.) prescribed singularly or in an combination based on the knowledge of MS-provoking inter-receptor interactions and therapeutic effects of drugs.

  14. Pulmonary oedema after hexoprenaline administration in preterm ...

    African Journals Online (AJOL)


    May 18, 1991 ... Complications associ~ted with the use of j:l-sympathomimetic agents in preterm labour have been reviewed by Benederti.1. Pulmonary oedema, myocardial ischaemia, cardiac arrhythmia, cerebral vasospasm, hypotension, hyperglycaemia and hypo- kalaemia have all been reponed. Pulmonary oedema is ...

  15. Semen-like urethral discharge during the use of mazindol. (United States)

    van Puijenbroek, E P; Meyboom, R H


    Two case reports are described of male patients experiencing a semen-like urethral discharge during micturition, suspected to be induced by mazindol. Mazindol has an indirect sympathomimetic action and is known to cause urogenital side effects such as urinary retention and testicular pain. It is suggested that seminal discharge may be added to this list.

  16. Artificial Neural Networks and Concentration Residual Augmented ...

    African Journals Online (AJOL)

    Methoxyphenoxy) - 1, 2 - propanediol] is an alpha - adrenergic sympathomimetic agent which stimulates alpha - adrenergic receptors, producing pronounced vasoconstriction [3]. The combination of the four drugs is used for treating bronchial spasm and as antitussive. The UV absorption spectra of the four drugs display.

  17. Herbal Energizers: Speed By Any Other Name. (United States)

    Jenkins, Andrew P.

    This guide focuses on over-the-counter (OTC) stimulants sold to high school aged athletes and dieters as "herbal energizers," food supplements, and fatigue reducers. While advertising often makes them appear healthful and harmless, all of these stimulants belong in the class "sympathomimetic amines," so called because they…

  18. A Serious Adverse Effect of Pseudoephedrine Used For Common Cold Treatment : Ventricular Arrhythmia

    Directory of Open Access Journals (Sweden)

    Cenk Aypak


    Full Text Available Common cold is one of the frequently seen disease in childhood. Pseudoephedrine hydrochloride (PEH is a sympathomimetic drug which is widely used for treatment of common cold as a decongestant on children. The aim of this case report is, to draw attention to serious adverse effects of PEH treatment. [Cukurova Med J 2013; 38(3.000: 506-510

  19. [Tolerance and effectiveness of oxymetazoline and xylometazoline in treatment of acute rhinitis]. (United States)

    Dorn, M; Hofmann, W; Knick, E


    Local alpha-sympathomimetics in hydrous solution are well known in the therapy of acute rhinitis and sinusitis. However, added preservatives like benzalkonium chloride have a negative effect on compatibility. A total of 307 patients with acute rhinitis entered the study. The treatment with oxymetazoline with preservative, oxymetazoline without preservative and xylometazoline with preservative was evaluated. This randomised, double-blind, multi-centered, verum-controlled tolerance study confirmed that the local sympathomimetics oxymetazoline and xylometazoline are well tolerated in the treatment of acute rhinitis. When evaluated according to the parameters "feeling of dryness in nasal mucosa" and "burning sensation", the Nasivin sanft 0.05% spray, which contains the active agent oxymetazoline without preservatives, proved to be considerably superior to preparations containing the preservative benzalkonium chloride. Preparations without preservatives should be the preferred choice of treatment for acute rhinitis.

  20. The effect of some commercially available antihistamine and decongestant intra-nasal formulations on ciliary beat frequency. (United States)

    Su, X Y; Li Wan Po, A


    The effects of azelastine (0.1%) nasal spray (Rhinolast) on ciliary beat frequency are investigated and compared with those of oxymetazoline hydrochloride (Vicks Sinex), xylometazoline (Otrivine) and ephedrine hydrochloride (0.5%). It is shown that all four formulations exert a ciliotoxic effect. The antihistamine (azelastine) and the two long-acting alpha sympathomimetic decongestants (xylometazoline and oxymetazoline) had comparable effects which were milder than those observed with ephedrine, the less specific alpha and beta sympathomimetic agent. The results suggest that the intranasal application of all four products should be restricted to short-term therapy. Oral antihistamine therapy and not topical therapy should still be the first-line therapy for antihistamine-responsive rhinitis until non-ciliotoxic formulations can be developed.

  1. PCBs Alter Dopamine Mediated Function in Aging Workers (United States)


    58.23 % Women 39 41.03 % 73 49.32 % a Number of observations varies across characteristics due to missing values. b Cardiovascular drugs (Class 24...inhibitors. c CNS active medications include: antihistamines , sympathomimetic agents, beta- adrenergic blocking agents, angiotensin-converting enzyme...comprehensive medical history, including use of over-the- counter and prescription drugs , as well as (if applicable) female reproductive histories

  2. Illicit drug use in late pregnancy associated with stillbirth and eclampsia


    Scott, Katherine; Fagermo, Narelle; Callaway, Leonie; Lust, Karin


    We present the case of a 20-year-old student with an undiagnosed pregnancy who had taken ecstasy and LSD (lysergic acid diethylamide). Twenty-four hours later she delivered a stillborn term infant, and subsequently developed eclampsia with seizures, hypertension and proteinuria. Illicit drug use is relatively common in women of child-bearing age in Australia, and is a risk factor for adverse obstetric outcomes. Ecstasy (MDMA [3,4-methylenedioxymethamphetamine]) is a sympathomimetic amine, sim...

  3. The Dietary Supplement Ephedrine - Should It Be Banned?


    Kim, Paul


    Ephedrine is a sympathomimetic, which stimulates the sympathetic nervous system and increases the rate and strength of heart contractions. Presently, it is an immensely popular ingredient in dietary supplements (over three billion servings a year in 1999) known for its ability to decrease body weight and body fat. However the side effects of the ephedra alkaloids have not gone without notice. Annals of Internal Medicine in March 2003 found that 64% of all the adverse reactions such as stroke,...

  4. A trial of clenbuterol in bronchial asthma. (United States)

    Anderson, G; Wilkins, E


    Clenbuterol is a beta 2-sympathomimetic bronchodilator. In a double-blind cross-over trial in 19 asthmatic patients with reversible airways obstruction, oral administration of both clenbuterol (40 microgram) and salbutamol (4 mg) caused significantly greater increased in peak expiratory flow rate (PEFR) than placebo, that of clenbuterol lasting longer. The patients' subjective assessment also suggested the relief of their symptoms by the active drugs. Side-effects were minimal. PMID:341407

  5. The monoamine oxidase type B inhibitor rasagiline in the treatment of Parkinson disease: is tyramine a challenge? (United States)

    Chen, Jack J; Wilkinson, Jayne R


    Rasagiline is an irreversible monoamine oxidase type B (MAO-B) inhibitor indicated for the treatment of the signs and symptoms of idiopathic Parkinson disease as initial monotherapy and as adjunct therapy to levodopa. Pharmacologic inhibition of monoamine oxidase type A (MAO-A), but not MAO-B, poses a risk of the "cheese effect," a hypertensive response to excess dietary tyramine, a biogenic sympathomimetic amine. Tyramine challenge studies, conducted to characterize rasagiline selectivity for the MAO-B enzyme and tyramine sensitivity, demonstrate that rasagiline, when used at the recommended dose, is selective for MAO-B and is not associated with heightened tyramine sensitivity. This conclusion is also supported by safety results from large clinical trials of rasagiline in Parkinson disease involving 2066 rasagiline-treated patients who did not require dietary tyramine restriction per protocol. In late 2009, US labeling for rasagiline was modified to state that dietary tyramine restrictions are not ordinarily required when rasagiline is administered at recommended doses. In addition, because rasagiline has been demonstrated to be selective for MAO-B at the approved dose of up to 1 mg/d, contraindications regarding concomitant use with sympathomimetic amines, use of sympathomimetic vasopressors in conjunction with general or local anesthesia, and use in patients with pheochromocytoma also were removed.


    Directory of Open Access Journals (Sweden)

    S. N. Avdeykin


    Full Text Available Objective: to evaluate the efficiency of transpulmonary thermodilution (TPTD for the choice of measures to correct hemodynamics in patients with severe nosocomial pneumonia (NP. Subjects and methods. The investigation enrolled 107 NP patients admitted to an intensive care unit (ICU. Group 1 patients were intensively treated in accordance with a protocol for hemodynamic correction during early goaldirected therapy for sepsis. In Group 2, infusion thera py and sympathomimetic agents were prescribed depending on the results of TPTD. Results. Patients in both groups did not differ in the examined clinical and laboratory indicators. On day 1 of intensive therapy, in Group 2 (a TPTD controlled intensive treatment group the prescription of sympathomimetic drugs was virtually twice more active than in Group 1; and the value of positive hydrobalance was, twice less. In 5 days, the frequency of use of sympathomimetic agents had no intergroup differences and, in 7 days became less in Group 2 patients. After the therapy patients in Group 2 did not require substantial amounts of infusion and great positive hydrobalance, resulting in lower central venous pressure (CVP values. After 5 days of intensive therapy, the positive hydrobalance in Group 2 patients was 5 times less and on day 7 this indicator became negative. There were no intergroup differences in CVP on day 1; however, this indicator was higher in Group 1 patients from day 2 to the end of the followup period. At days 5—7, Group 2 patients exhibited elevated SvO2 values and hypolactatemia. At day 3, the SOFA severity was somewhat higher in Group 2 than in Group 1, then substantially reduced and on days 5—7 it was 2—2.5 scores lower in Group 2 than in Group 1. The mortality in ICU was 49% and 33% in Groups 1 and 2, respectively (χχ2=3.899; pConclusion. The determination of infusion amounts and indications for the use of sympathomimetic drugs on the basis of the integrated assessment of global

  7. [Acute poisoning with weight-loss dietary supplement falsely suggesting the use of amphetamine]. (United States)

    Łukasik-Głebocka, Magdalena; Sommerfeld, Karina; Tezyk, Artur; Zielińska-Psuja, Barbara


    We report a case of abuse of weight-loss dietary supplement in 27-year-old man, with characteristic for amphetamine sympathomimetic symptoms and positive analysis of this drug in the urine by immunoassay method (FPIA; Axsym, Abbott). However positive result was not confirmed by liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). The patient ate nine tablets of the Thermal Pro with declared composition of caffeine (250 mg), bitter orange (200 mg), beta-phenylethylamine (100 mg), willow bark (75 mg), Cayenne pepper (40 mg), 1,3-dimethyloamyloamine (DMAA, 35 mg), gooseberry extract (20 mg), bergamot orange (20 mg), black pepper (5 mg), after two-month period of regular consumption at dose of 2-3 capsules per day. After 4 hours, during admission to the Department of Toxicology, patient manifested typical sympathomimetic symptoms: anxiety, agitation, pale skin, sweats, tachycardia 120/min, mydriasis. Following the outcome of detecting amphetamine/methamphetamine in the patient's urine at 2377 ng/mL concentration using FPIA method, drug intoxication was suspected. It was considered that the ingestion was intentional or unconscious of adulterated dietary supplement. In view of the strong opposition of the patient, who denied any use of psychoactive substances, it was decided to re-examine collected speciments. The liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) method did not confirm the presence of amphetamine in the patient's blood and urine. Based on the composition of dietary supplements for substances which could be responsible for the positive amphetamine result in urine by FPIA method and available literature data, it was concluded that the substances that may react in the immunoassay could be dimethylamyloamine (DMAA, geranamine) or bitter orange components. False positive urinalysis towards amphetamine/methamphetamine by immunoassay and presence of sympathomimetic effects may contribute to a false diagnosis of this drug

  8. Positioning new pharmacotherapies for COPD

    Directory of Open Access Journals (Sweden)

    Barjaktarevic IZ


    Full Text Available Igor Z Barjaktarevic,1 Anthony F Arredondo,1 Christopher B Cooper1,2 1Department of Medicine, 2Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Abstract: COPD imposes considerable worldwide burden in terms of morbidity and mortality. In recognition of this, there is now extensive focus on early diagnosis, secondary prevention, and optimizing medical management of the disease. While established guidelines recognize different grades of disease severity and offer a structured basis for disease management based on symptoms and risk, it is becoming increasingly evident that COPD is a condition characterized by many phenotypes and its control in a single patient may require clinicians to have access to a broader spectrum of pharmacotherapies. This review summarizes recent developments in COPD management and compares established pharmacotherapy with new and emerging pharmacotherapies including long-acting muscarinic antagonists, long-acting β-2 sympathomimetic agonists, and fixed-dose combinations of long-acting muscarinic antagonists and long-acting β-2 sympathomimetic agonists as well as inhaled cortiocosteroids, phosphodiesterase inhibitors, and targeted anti-inflammatory drugs. We also review the available oral medications and new agents with novel mechanisms of action in early stages of development. With several new pharmacological agents intended for the management of COPD, it is our goal to familiarize potential prescribers with evidence relating to the efficacy and safety of new medications and to suggest circumstances in which these therapies could be most useful. Keywords: COPD phenotypes, once-daily inhalers, fixed-combination inhalers, long-acting muscarinic antagonist, LAMA, long-acting β-2 sympathomimetic agonist, LABA

  9. Generation Z: Adolescent Xenobiotic Abuse in the 21st Century. (United States)

    Eggleston, William; Stork, Christine


    NMDA receptor antagonists include the prescription medication ketamine, the illicit xenobiotics PCP, MXE, and other novel PCP analogs, and the OTC medication DXM. The NMDA receptor antagonist most commonly abused by adolescents in the United States is DXM. These xenobiotics cause dissociative effects by non-competitively inhibiting the action of glutamate at the NMDA receptor. Additionally, these agents modulate the actions of monoamine neurotransmitters, agonize opioid receptors, and inhibit nitric oxide synthase. Patients typically present with sympathomimetic and neuropsychiatric clinical manifestations after abuse of NMDA receptor antagonists. Treatment is generally symptomatic and supportive. Interventions include benzodiazepines, propofol, fluids, antiemetics, aggressive cooling, and respiratory support.

  10. The confounding effect of the development of idiopathic orthostatic edema and thyrotoxcosis on weight fluctuation related to effects on free water clearance in a woman with long-standing surgically induced panhypopituitarism and diabetes insipidus. (United States)

    Check, J H; Weidner, J


    To evaluate the effect of idiopathic orthostatic edema and the effect of thyrotoxicosis on weight fluctuation and fluid retention in the presence of surgically induced panhypopituitarism and diabetes insipidus controlled with hormone replacement. Dextroamphetamine sulfate was used for weight gain when no other etiologic factor was found. Methimazole was used when weight loss occurred when serum T4 and free T4 indicated thyrotoxicosis. Sympathomimetic amine therapy very effectively controlled the weight gain and methimazole controlled the weight loss. Hypopituitarism and diabetes insipidus controlled with hormone replacement do not protect against fluid retention from idiopathic edema.

  11. Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man

    DEFF Research Database (Denmark)

    Astrup, A; Bülow, J; Madsen, J


    was estimated by measurements of leg blood flow and arteriovenous oxygen difference. The perirenal adipose tissue blood flow increased approximately twofold, whereas the local temperature increased approximately 0.1 degrees C on an average. Assuming that man possesses 700 g of BAT with a similar thermogenic...... skeletal muscle, approximately 50% of the increase in oxygen consumption induced by ephedrine may take place in skeletal muscle. It is concluded that skeletal muscle is a tissue of importance with respect to the thermogenic effect of sympathomimetics in man, whereas the results do not support a major role...

  12. Acute neurotoxicology of drugs of abuse. (United States)

    Traub, S J; Levine, M D


    Many substances can affect the central nervous system, and may cause patients to become critically ill. Acute central neurotoxicologic syndromes associated with drugs of abuse are usually caused by an overdose of sedative-hypnotic agents (including alcohol) or opioids, withdrawal from sedative-hypnotic agents, or an overdose of anticholinergic or sympathomimetic agents. Clinical findings are often syndromic, making physical examination the most important diagnostic tool in the approach to the patient with an unknown ingestion. Treatment focusses on supportive care as the most important intervention for all such patients, augmented by antidotal therapy when appropriate. © 2017 Elsevier B.V. All rights reserved.

  13. No effect of Pindolol on postural hypotension in type 1 (insulin-dependent) diabetic patients with autonomic neuropathy. A randomised double-blind controlled study

    DEFF Research Database (Denmark)

    Dejgård, A; Hilsted, J


    of this therapy we performed a double-blind placebo controlled cross-over study with Pindolol (15 mg/day). Eight Type 1 (insulin-dependent) diabetic patients with autonomic neuropathy and signs and symptoms of orthostatic hypotension (systolic blood pressure decrease greater than 30 mm Hg when standing......Orthostatic hypotension is one of the most troublesome symptoms in diabetic autonomic neuropathy. Some reports have suggested Pindolol - a beta-adrenoceptor antagonist with intrinsic sympathomimetic activity - to be effective in the treatment of this condition. In order to elucidate the value...

  14. The Effect of Topical Anesthesia on Pharmacological Mydriasis in Diabetic Patients Depends on the Presence of Retinopathy

    DEFF Research Database (Denmark)

    Clausen, Susanne; Jørgensen, Christina Mørup; Bek, Toke


    for retinopathy and whether the effect depends on the presence of retinopathy. Methods: Thirty-six patients attending a screening programme for diabetic retinopathy were randomized to receive local anesthetic eye drops on one eye, followed by instillation of both a sympathomimetic and a parasympatholytic eye drop...... in patients during screening for diabetic retinopathy, but pupil size before and after the intervention depends on the presence of retinopathy.......Abstract Purpose: Instillation of topical anesthetics with or without preservatives in normal persons has been shown to enhance the effect of mydriatic eye drops. The purpose of the present investigation was to study whether a similar effect can be observed in diabetic patients screened...

  15. First-Trimester In Utero Exposure to Methylphenidate

    DEFF Research Database (Denmark)

    Dideriksen, Dorthe; Pottegård, Anton; Hallas, Jesper


    Methylphenidate is a centrally acting sympathomimetic used for the treatment of attention deficit/hyperactivity disorder (ADHD) in children and adolescents and for narcolepsy in adults. Despite the growing use among adult women, no reliable data on the prevalence of use during pregnancy have been......, The Collaborative Perinatal Project and the Swedish Birth Registry were evaluated. Excluding three case-reports, a total of 180 children exposed to methylphenidate in utero during first trimester were identified, among whom 4 children with major malformations were observed. Methylphenidate exposure during pregnancy...

  16. Amphetamine, mazindol, and fencamfamin in narcolepsy. (United States)

    Shindler, J; Schachter, M; Brincat, S; Parkes, J D


    Twenty patients with the narcoleptic syndrome were treated separately with dexamphetamine sulphate tablets 10 and 30 mg, Dexedrine Spansules 10 mg, mazindol 4 mg, and fencamfamin hydrochloride 60 mg daily. Each drug was given for four weeks and the effects compared. In these dosages the reported frequency of attacks of narcolepsy was roughly halved with each treatment, dexamphetamine 30 mg daily being only slightly more potent than 10 mg. The subjective effects of Dexedrine tablets and Spansules could not be distinguished by most patients. Effects on mood, alertness, and sympathomimetic side effects were largely inseparable with all these drugs, but a decrease in appetite was not reported by patients with narcolepsy. PMID:2859077

  17. Determination of l-methamphetamine: a case history. (United States)

    Wyman, John F; Cody, John T


    Methamphetamine was detected in a 77-year-old male who had a history of congestive heart failure. Using a modification of a previously reported method, trifluoroacetyl-l-prolyl chloride was used to derivatize sympathomimetic amines to allow separation and identification of individual enantiomers. The l-enantiomer of methamphetamine and a trace amount of l-amphetamine were found in blood and urine specimens from this case. Further investigation revealed the decedent had bronchial asthma and regularly used a Vicks Inhaler, which contains l-methamphetamine as the active ingredient.

  18. Dependency of cerebral blood flow upon mean arterial pressure in patients with acute bacterial meningitis

    DEFF Research Database (Denmark)

    Møller, Kirsten; Larsen, Fin Stolze; Qvist, Jesper


    OBJECTIVE: Patients with acute bacterial meningitis are often treated with sympathomimetics to maintain an adequate mean arterial pressure (MAP). We studied the influence of such therapy on cerebral blood flow (CBF). DESIGN: Prospective physiologic trial. SETTING: The Department of Infectious...... Diseases, Copenhagen University Hospital, Denmark. PATIENTS: Sixteen adult patients with acute bacterial meningitis. INTERVENTION: Infusion of norepinephrine to increase MAP. MEASUREMENTS: During a rise in MAP induced by norepinephrine infusion, we measured relative changes in CBF by transcranial Doppler...... bacterial meningitis, CBF autoregulation is impaired. With recovery from meningitis, the cerebral vasculature regains the ability to maintain cerebral perfusion at a constant level despite variations in MAP....

  19. Improved patient selection for TAH implantation. (United States)

    Loisance, D; Dubois Rande, J L; Deleuze, P; Benvenuti, C; Dervanian, P; Brunet, S; Hillion, M L; Castaigne, A; Cachera, J P


    Patient selection and optimal timing for implantation are unsettled issues in candidates for a bridge to cardiac transplantation. A prospective evaluation of a strategy based on enoximone (E) given IV, in addition to sympathomimetic drugs, permitting to buy time, and delay by hours or days the decisions, has been performed from 1985 to 1988. Thirty-four patients in cardiogenic shock with hemodynamical criteria for TAH implantation have been included: Cl was 1.8 +/- 0.2 L/min/m2 PCWP 29 +/- 7 mmHg, diuresis less than 20 ml/hr. The protocol permitted to postpone decisions of implantation in 30 cases. The 4 unresponsive patients were implanted immediately with TAH (3) or VAD (1). Three were transplanted, two successfully. For 30, time given permitted discovery of hidden contraindications to transplantation in 17 patients. In 13, indication for transplantation was confirmed and performed in 11 within 6 hrs to 8 days (survival 64%). In two, sudden deterioration led to an unsuccessful TAH implantation. Multifactorial analysis showed that a 50% rise in Cl together with a 50% drop in PCWP, a 50% drop in PVR 30 min after IV E has a high predictive value of survival. These data suggest that enoximone IV bolus given in addition to maximal sympathomimetics to patients in cardiogenic shock reduces by 88% the need for TAH or VAD. It also permits a better selection of the candidates.

  20. Blood pressure and heart rate effects following a single dose of bitter orange. (United States)

    Bui, Linda T; Nguyen, DiemThuy T; Ambrose, Peter J


    The ingredients of numerous "ephedra-free" dietary supplements used for weight loss include bitter orange, which contains sympathomimetic alkaloids such as synephrine. Due to the similarity in chemical structure to ephedrine and the potential sympathomimetic effects of synephrine, it is hypothesized that bitter orange may increase blood pressure (BP) and heart rate (HR). To determine the effects on BP and HR after a single dose of bitter orange in healthy adults. In a prospective, randomized, double-blind, placebo-controlled, crossover study, 15 young, healthy, adult subjects received either a single dose of Nature's Way Bitter Orange--a 900 mg dietary supplement extract standardized to 6% synephrine--or matching placebo, with a one week washout period. Systolic BP (SBP), diastolic BP (DBP), and HR were measured at baseline and every hour for 6 hours after administration. SBP after bitter orange was significantly increased versus placebo at hours 1-5 (p bitter orange, DBP after bitter orange was significantly increased versus placebo at hours 4 and 5 (p bitter orange versus placebo for hours 2-5 (p bitter orange versus placebo in young, healthy adults.

  1. Pharmacological profiling of zebrafish behavior using chemical and genetic classification of sleep-wake modifiers (United States)

    Nishimura, Yuhei; Okabe, Shiko; Sasagawa, Shota; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Tanaka, Toshio


    Sleep-wake states are impaired in various neurological disorders. Impairment of sleep-wake states can be an early condition that exacerbates these disorders. Therefore, treating sleep-wake dysfunction may prevent or slow the development of these diseases. Although many gene products are likely to be involved in the sleep-wake disturbance, hypnotics and psychostimulants clinically used are limited in terms of their mode of action and are not without side effects. Therefore, there is a growing demand for developing new hypnotics and psychostimulants with high efficacy and few side effects. Toward this end, animal models are indispensable for use in genetic and chemical screens to identify sleep-wake modifiers. As a proof-of-concept study, we performed behavioral profiling of zebrafish treated with chemical and genetic sleep-wake modifiers. We were able to demonstrate that behavioral profiling of zebrafish treated with hypnotics or psychostimulants from 9 to 10 days post-fertilization was sufficient to identify drugs with specific modes of action. We were also able to identify behavioral endpoints distinguishing GABA-A modulators and hypocretin (hcrt) receptor antagonists and between sympathomimetic and non-sympathomimetic psychostimulants. This behavioral profiling can serve to identify genes related to sleep-wake disturbance associated with various neuropsychiatric diseases and novel therapeutic compounds for insomnia and excessive daytime sleep with fewer adverse side effects. PMID:26578964

  2. Alterations in Ca2+-dependent and Ca2+-independent release of catecholamines in preparations of rat brain produced by ethanol treatment in vivo

    International Nuclear Information System (INIS)

    Lynch, M.A.; Pagonis, C.; Samuel, D.; Littleton, J.M.


    Compared to preparations from control animals, superfused striatal slice preparations from brains of rats treated chronically with ethanol released a significantly greater fraction of stored [ 3 H] dopamine on depolarisation in 40 mM K + . Similarly, the electrically-evoked release of [ 3 H]-norepinephrine from cortical slices and of [ 3 H]-dopamine from striatal slices is also increased, although with this mechanism of depolarisation the change is significant only in the case of [ 3 H] norepinephrine release. In contrast to this tendency to enhancement of Ca 2+ -dependent depolarisation-induced release, a reduced fraction of stored [ 3 H]-catecholamines was released from these preparations by the indirect sympathomimetics tyramine and (+)-amphetamine. The catecholamine release induced by these indirect sympathomimetics is largely independent of external Ca 2+ and the results are interpreted as suggesting that chronic alcohol treatment changes the distribution of catecholamine neurotransmitters between storage pools in the nerve terminal which do or do not require Ca 2+ entry for release

  3. The use of appetite suppressants among health sciences undergraduate students in Southern Brazil. (United States)

    Zubaran, Carlos; Lazzaretti, Rubia


    To investigate the prevalence of appetite suppressant use among health sciences students in Southern Brazil. Undergraduate students (n=300) from seven health science undergraduate courses of the Universidade de Caxias do Sul completed a questionnaire about the use of substances to suppress appetite. A significant percentage (15%; n=45) of research participants used appetite suppressants at least once in their lives. The most commonly used substances were sympathomimetic stimulant drugs (5%), including amfepramone (3.3%) and fenproporex (1.7%). The lifetime use of appetite suppressants was more prevalent among Nursing (26.7%) and Nutrition (24.4%%) students. There was no reported use of appetite suppressants among medical students. The use of appetite suppressants was significantly more prevalent among women. The majority of those who used these substances did so under medical recommendation. Most of users took appetite suppressants for more than 3 months. Lifetime use of appetite suppressants was substantial, being sympathomimetic stimulant drugs the most commonly used agents. Students enrolled in Nursing and Nutrition courses presented a significantly higher prevalence of lifetime use of appetite suppressants.

  4. Sympathetic activity of S-(+-ketamine low doses in the epidural space

    Directory of Open Access Journals (Sweden)

    Slobodan Mihaljevic


    Full Text Available BACKGROUND AND OBJECTIVES: S-(+-ketamine is an intravenous anaesthetic and sympathomimetic with properties of local anaesthetic. It has an effect of an analgetic and local anaesthetic when administered epidurally, but there are no data whether low doses of S-(+-ketamine have sympathomimetic effects. The aim of this study was to determine whether low doses of S-(+-ketamine, given epidurally together with local anaesthetic, have any effect on sympathetic nervous system, both systemic and below the level of anaesthetic block. METHODS: The study was conducted on two groups of patients to whom epidural anaesthesia was administered to. Local anaesthesia (0.5% bupivacaine was given to one group (control group while local anaesthesia and S-(+-ketamine were given to other group. Age, height, weight, systolic, diastolic and mean arterial blood pressure were measured. Non-competitive enzyme immunochemistry method (Cat Combi ELISA was used to determine the concentrations of catecholamines (adrenaline and noradrenaline. Immunoenzymometric determination with luminescent substrate on a machine called Vitros Eci was used to determine the concentration of cortisol. Pulse transit time was measured using photoplethysmography. Mann-Whitney U-test, Wilcoxon test and Friedman ANOVA were the statistical tests. Blood pressure, pulse, adrenaline, noradrenaline and cortisol concentrations were measured in order to estimate systemic sympathetic effects. RESULTS: 40 patients in the control group were given 0.5% bupivacaine and 40 patients in the test group were given 0.5% bupivacaine with S-(+-ketamine. Value p < 0.05 has been taken as a limit of statistical significance. CONCLUSIONS: Low dose of S-(+-ketamine administered epidurally had no sympathomimetic effects; it did not change blood pressure, pulse, serum hormones or pulse transit time. Low dose of S-(+-ketamine administered epidurally did not deepen sympathetic block. Adding 25 mg of S-(+-ketamine to 0

  5. Impact of concomitant medication use on myocardial 123I-mIBG imaging results in patients with heart failure. (United States)

    Jacobson, Arnold F; White, Susan; Travin, Mark I; Tseng, Carol


    Medications that interfere with sympathetic neuronal norepinephrine uptake and storage, such as neuropsychiatrics (NP) and sympathomimetic amines, are most likely to affect cardiac uptake of iodine-123 metaiodobenzylguanidine (I-mIBG). The present study examined these and other medications reported to affect I-mIBG uptake using measurements of cardiac I-mIBG uptake on the heart failure (HF) patients in the ADMIRE-HF extension (X) study. Baseline concomitant medications taken by the 961 HF patients were categorized into five groups: calcium channel blockers, NP medications, β agonists and sympathomimetics, α antagonists, and other antihypertensives. NP medications were further subcategorized into those expected to have high and low impact on norepinephrine transporter (NET) function. Myocardial I-mIBG heart/mediastinum (H/M) uptake ratios on 4 h planar images were compared among the groups. Impact of medication group on the prognostic value of the H/M ratio for all-cause (AC) and cardiac death during a median 2-year follow-up was also examined. A total of 283 (29%) patients were using at least one calcium channel blocker, NP medication, or β agonist or sympathomimetic. These patients had a lower mean H/M ratio than the other study patients (1.42±0.20 vs. 1.45±0.20; P=0.022). However, the 2-year AC mortality rates in the two groups were the same [11.3% (95% confidence interval: 7.5-15.2%) vs. 11.8% (95% confidence interval: 9.2-14.4%)]. In terms of medication categories, there were no significant differences in the mean H/M ratios between patients who did and did not use NP medications, β agonists, calcium channel blockers, and α antagonists. Across all categories, patients with H/M ratio greater than or equal to 1.60 had lower AC and cardiac mortality. Patients using higher potency (for NET inhibition) NP medications had significantly lower H/M ratio values, but the prognostic significance of H/M ratio greater than or equal to 1.60 was unchanged. Only a

  6. The clinical toxicology of metamfetamine. (United States)

    Schep, Leo J; Slaughter, Robin J; Beasley, D Michael G


    hydroxylation producing 4-hydroxymetamfetamine and N-demethylation to form amfetamine. Metamfetamine is excreted predominantly in the urine and to a lesser extent by sweating and fecal excretion, with reported terminal half-lives ranging from ∼5 to 30 h. Clinical features. The clinical effects of metamfetamine poisoning can vary widely, depending on dose, route, duration, and frequency of use. They are predominantly characteristic of an acute sympathomimetic toxidrome. Common features reported include tachycardia, hypertension, chest pain, various cardiac dysrhythmias, vasculitis, headache, cerebral hemorrhage, hyperthermia, tachypnea, and violent and aggressive behaviour. Management. Emergency stabilization of vital functions and supportive care is essential. Benzodiazepines alone may adequately relieve agitation, hypertension, tachycardia, psychosis, and seizure, though other specific therapies can also be required for sympathomimetic effects and their associated complications. Metamfetamine may cause severe sympathomimetic effects in the intoxicated patient. However, with appropriate, symptom-directed supportive care, patients can be expected to make a full recovery.

  7. The effects of acebutolol and metoprolol on walking distances and distal blood pressure in hypertensive patients with intermittent claudication

    DEFF Research Database (Denmark)

    Svendsen, T L; Jelnes, Rolf; Tønnesen, K H


    The effects of acebutolol (with intrinsic sympathomimetic activity (ISA] and metoprolol (without ISA) on arm blood pressure, ankle systolic blood pressure, claudication distances (CD) and maximal walking distances (MWD) were compared in patients with essential hypertension and intermittent...... claudication. Fourteen patients participated in a long-term, open, randomized cross-over study. After randomization the patients received either acebutolol, 200 mg b.i.d., or metoprolol, 100 mg b.i.d. After eight weeks the drugs were shifted and after another eight weeks they were withdrawn. Arm and ankle...... blood pressure, CD and MWD were determined before randomization and after 4, 8, 12 and 16 weeks, and again 4-6 weeks after withdrawal of the drugs. The arm blood pressure was reduced by 20/13 mmHg after acebutolol and by 22/21 mmHg after metoprolol. In spite of a significant decrease in arm blood...

  8. Present and Future: Pharmacologic Treatment of Obesity

    Directory of Open Access Journals (Sweden)

    Mariela Glandt


    Full Text Available Obesity now presents one of the biggest health problems of our times. Diet and exercise are best for both prevention and treatment; unfortunately, both require much discipline and are difficult to maintain. Medications offer a possible adjunct, but their effect is modest, they are limited by side effects, and the weight loss lasts only as long as the drug is being taken, since as soon as treatment is stopped, the weight is regained. Sibutramine, a sympathomimetic medication which was available for long-term treatment, is the most recent of the drugs to be withdrawn from the market due to side effects; in this case it was an increased risk of cardiovascular events. This paper reviews those medications which are available for treatment of obesity, including many of those recently taken off the market. It also discusses some of the newer treatments that are currently being investigated.

  9. [Methylphenidate and secondary Raynaud's phenomenon]. (United States)

    Iglesias Otero, M; Portela Romero, M; Bugarín González, R; Ventura Victoria, M A


    Raynaud's phenomenon is a clinical disease characterized by episodic attacks of vasoconstriction of the arteries and arterioles of the extremities such as fingers and toes, sometimes the ears and nose, in response to cold or emotional stimuli. A classic attack is the pallor of the distal extremity, followed by cyanosis and redness, accompanied by paresthesia, usually as heat. When it occurs without apparent cause is called primary Raynaud's phenomenon. When associated with other disease, is called secondary Raynaud's phenomenon. The secondary table is associated with increased frequency of rheumatic diseases of collagen. They can also present certain drugs that cause vasoconstriction, such as ergotamine, beta-adrenergic antagonists, contraception and sympathomimetic drugs. Regarding the latter, we present a case of Raynaud's phenomenon secondary to methylphenidate in a 14 years. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  10. Amphetamine-type medicines: a review of pharmacokinetics, pharmacodynamics, and toxicological aspects. (United States)

    Mariotti, Kristianee C; Rossato, Luciana G; Fröehlich, Pedro E; Limberger, Renata P


    Amphetamine-like drugs are sympathomimetic agents with marked central and peripheral stimulant properties. Despite the street illegal drugs such as amphetamine and ecstasy, some amphetamine-like compounds are also legally marketed under medical prescription in the treatment of attention deficit-hyperactivity disorder (methylphenidate) and obesity/overweight (fenproporex and diethylpropione). However, similar with what happens with their illicit analogues, therapeutic amphetamine-like drugs also share important toxicological risks. Although methylphenidate is considered the first choice in the treatment of attention deficit-hyperactivity disorder, its high popularity among teenagers and children is raising concern in the medical community. Regarding weight-loss purposes, the use of amphetamine-like compounds are very controversial, though. Thus, the present review will address pharmacokinetic, pharmacodynamic, and toxicological aspects of amphetamine-like compounds used with therapeutic aims.

  11. Pupil dilation with intracameral lidocaine during phacoemulsification: Benefits for the patient and surgeon

    Directory of Open Access Journals (Sweden)

    Nikeghbali Aminollah


    Full Text Available Topical and/or intracameral administration of anticholinergic and/or sympathomimetic mydriatic agents which are usually used for pupillary dilation during cataract surgery, have some disadvantages such as slow onset of dilation and adverse ocular and systemic effects. We evaluated intracameral injection of preservative-free 1% lidocaine without using any preoperative or intraoperative mydriatics to induce pupil dilation in 31 consecutive eyes scheduled for phacoemulsification cataract extraction and intraocular lens implantation. Pupil diameter was measured before and 90 sec after intracameral lidocaine injection. After intracameral lidocaine injection, the mean pupil diameter was significantly greater than the baseline measurement (P< 0.001. No additional mydriatics were needed up to the end of the operations. Intracameral preservative-free lidocaine 1% has a rapid and effective mydriasis that could be a safe alternative to topical and intracameral mydriatics in phacoemulsification.

  12. Cardiovascular effects of methamphetamine in dogs treated chronically with the amine. (United States)

    Vidrio, H


    Methamphetamine is one of a group of sympathomimetic amines that lower blood pressure upon chronic administration to hypertensive dogs. To determine whether tolerance to the cardiovascular effects of these drugs could play a role in their antihypertensive action, acute blood pressure responses to oral d-methamphetamine were determined in trained conscious renal hypertensive dogs at weekly intervals during treatment with the drug for 2 months. Responses were also obtained in similarly treated normotensive dogs and in normotensive and hypertensive animals receiving l-methamphetamine. Pressor responses to d-methamphetamine in hypertensive dogs remained unchanged throughout treatment, while in all other cases they diminished gradually. Only the dextro isomer reduced blood pressure chronically in the hypertensive group. It was concluded that tolerance is not involved in the antihypertensive effect of methamphetamine and that, considering the stereo specificity of this effect, residual lowering of blood pressure might involve formation of a false mediator metabolite of the amine.

  13. Methamphetamine Ingestion Misdiagnosed as Centruroides sculpturatus Envenomation

    Directory of Open Access Journals (Sweden)

    Joshua Strommen


    Full Text Available The authors present a case report of a 17-month-old female child who ingested a large amount of methamphetamine that looked very similar clinically to a scorpion envenomation specific to the southwestern United States by the species Centruroides sculpturatus. The child was initially treated with 3 vials of antivenom specific for that scorpion species and showed a transient, though clinically relevant neurologic improvement. Her clinical course of sympathomimetic toxicity resumed and she was treated with intravenous fluids and benzodiazepines after blood analysis showed significant levels of d-methamphetamine. This case report is to specifically underline the clinical confusion in discerning between these two conditions and the realization of limited and/or expensive resources that may be used in the process.

  14. Methamphetamine Ingestion Misdiagnosed as Centruroides sculpturatus Envenomation (United States)

    Strommen, Joshua; Shirazi, Farshad


    The authors present a case report of a 17-month-old female child who ingested a large amount of methamphetamine that looked very similar clinically to a scorpion envenomation specific to the southwestern United States by the species Centruroides sculpturatus. The child was initially treated with 3 vials of antivenom specific for that scorpion species and showed a transient, though clinically relevant neurologic improvement. Her clinical course of sympathomimetic toxicity resumed and she was treated with intravenous fluids and benzodiazepines after blood analysis showed significant levels of d-methamphetamine. This case report is to specifically underline the clinical confusion in discerning between these two conditions and the realization of limited and/or expensive resources that may be used in the process. PMID:25649670

  15. [Role of pneumotachography in the diagnosis and assessment of treatment effectiveness in bronchial dystonia in respiratory tract diseases of dust etiology]. (United States)

    Levitskaia, V L


    Flow-volume values and their changes in response to salbutamol and methacin inhalations were studied with the help of a pneumotachograph in 69 patients with anthracosilicosis stage I, and in 70 patients with chronic dust bronchitis stages I and II. Pneumotachography was shown to extend diagnostic potentialities in the detection of ventilation insufficiency in patients with dust pulmonary pathology, making it possible to determine not only a degree but also a site of obstructive disorders. Disorders of the sympathetic and parasympathetic bronchial innervation and associated biochemical mechanisms were important in the mechanism of bronchospasm development. Pneumotachography was recommended in combination with bronchospasmolytic drugs of sympathomimetic and cholinolytic action for elucidation of the mechanism of disorders of the bronchial tone, a choice of adequate therapy and assessment of its efficacy.

  16. Immediate haemodynamic effects of a novel partial agonist, beta 1-adrenoceptor blocking drug ICI 141,292 after intravenous administration to healthy young volunteers and patients with ischaemic heart disease

    DEFF Research Database (Denmark)

    Bonde, J; Svendsen, T L; Lyngborg, K


    decreased approximately 8% following all three doses of ICI 141,292 and 14.9% after atenolol 5 mg. No changes in blood pressure were observed under resting conditions after any of the drugs. In six patients with ischaemic heart disease the intrinsic sympathomimetic activity following intravenous...... were administered intravenously. The attenuation in exercise induced tachycardia varied between 16.0 and 21.2% (P less than 0.01). A significant reduction in blood pressure could be demonstrated following all three doses of ICI 141,292 and atenolol during exercise. At rest in the sitting position HR....... No significant changes were observed in mean arterial blood pressure, stroke volume or total peripheral resistance whereas an increase in supine resting mean pulmonary arterial pressure of 3.4 mm Hg (P less than 0.05) could be demonstrated. ICI 141,292 seems to be a potent (at least five times as potent...

  17. Effects of beta-adrenergic blockers on drug-induced tremors. (United States)

    Iwata, S; Nomoto, M; Fukuda, T


    We studied the effect of various kinds of beta-adrenergic blockers on oxotremorine-, harmaline- and thyrotropin-releasing hormone (TRH)-induced tremors in mice. To investigate what property of beta-blockers plays the main role in suppressing tremor, we employed five beta-blockers (propranolol, atenolol, butoxamine, pindolol, and arotinolol). All drugs suppressed oxotremorine-induced tremors but none reduced harmaline-induced tremors. Even though TRH-induced tremors were decreased significantly only by propranolol and high doses of arotinolol, all drugs had a tendency to reduce the tremor. We concluded that neuropharmacological mechanisms underlying to harmaline-induced tremors were different from those of TRH- and oxotremorine-induced tremors and that features of beta-blockers (beta 1- or beta 2-selectivity, intrinsic sympathomimetic activity, and membrane stabilizing activity) did not primarily contribute to the suppression of tremors.

  18. Ketamine in adult cardiac surgery and the cardiac surgery Intensive Care Unit: An evidence-based clinical review

    Directory of Open Access Journals (Sweden)

    Michael Mazzeffi


    Full Text Available Ketamine is a unique anesthetic drug that provides analgesia, hypnosis, and amnesia with minimal respiratory and cardiovascular depression. Because of its sympathomimetic properties it would seem to be an excellent choice for patients with depressed ventricular function in cardiac surgery. However, its use has not gained widespread acceptance in adult cardiac surgery patients, perhaps due to its perceived negative psychotropic effects. Despite this limitation, it is receiving renewed interest in the United States as a sedative and analgesic drug for critically ill-patients. In this manuscript, the authors provide an evidence-based clinical review of ketamine use in cardiac surgery patients for intensive care physicians, cardio-thoracic anesthesiologists, and cardio-thoracic surgeons. All MEDLINE indexed clinical trials performed during the last 20 years in adult cardiac surgery patients were included in the review.

  19. [Cardiovascular complications of hypertensive crisis]. (United States)

    Rosas-Peralta, Martín; Borrayo-Sánchez, Gabriela; Madrid-Miller, Alejandra; Ramírez-Arias, Erick; Pérez-Rodríguez, Gilberto


    It is inexorable that a proportion of patients with systemic arterial hypertension will develop a hypertensive crisis at some point in their lives. The hypertensive crises can be divided in hypertensive patients with emergency or hypertensive emergency, according to the presence or absence of acute end-organ damage. In this review, we discuss the cardiovascular hypertensive emergencies, including acute coronary syndrome, congestive heart failure, aortic dissection and sympathomimetic hypertensive crises (those caused by cocaine use included). Each is presented in a unique way, although some patients with hypertensive emergency report non-specific symptoms. Treatment includes multiple medications for quick and effective action with security to reduce blood pressure, protect the function of organs remaining, relieve symptoms, minimize the risk of complications and improve patient outcomes.

  20. Administration of supplemental L-tyrosine with phenelzine: a clinical literature review (United States)

    Hinz, Marty; Stein, Alvin; Cole, Ted; Ryan, Patricia


    The subject of this literature review is the alleged relationship between L-tyrosine, phenelzine, and hypertensive crisis. Phenelzine (Nardil®) prescribing information notes: “The potentiation of sympathomimetic substances and related compounds by MAO inhibitors may result in hypertensive crises (see WARNINGS). Therefore, patients being treated with NARDIL should not take […] L-tyrosine […]”. Interest in the scientific foundation of this claim was generated during routine patient care. A comprehensive literature search of Google Scholar and PubMed revealed no reported cases of hypertensive crisis associated with concomitant administration of L-tyrosine and phenelzine. Review of current US Food and Drug Administration nutritional guidelines relating to ongoing phenelzine studies reveals no mention and requires no consideration of L-tyrosine ingestion in combination with phenelzine. This paper is intended to provide an objective review of the science to then allow the reader to formulate the final opinion. PMID:25092999

  1. Recent Advances in Methamphetamine Neurotoxicity Mechanisms and Its Molecular Pathophysiology

    Directory of Open Access Journals (Sweden)

    Shaobin Yu


    Full Text Available Methamphetamine (METH is a sympathomimetic amine that belongs to phenethylamine and amphetamine class of psychoactive drugs, which are widely abused for their stimulant, euphoric, empathogenic, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, METH produces persistent damage to dopamine and serotonin release in nerve terminals, gliosis, and apoptosis. This review summarized the numerous interdependent mechanisms including excessive dopamine, ubiquitin-proteasome system dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression, inflammatory molecular, D3 receptor, microtubule deacetylation, and HIV-1 Tat protein that have been demonstrated to contribute to this damage. In addition, the feasible therapeutic strategies according to recent studies were also summarized ranging from drug and protein to gene level.

  2. Acute myocardial infarction associated with dietary supplements containing 1,3-dimethylamylamine and Citrus aurantium. (United States)

    Smith, Triston B; Staub, Brian A; Natarajan, Gayathri M; Lasorda, David M; Poornima, Indu G


    We describe the case of a previously healthy 22-year-old man who presented with anginal chest pain and was diagnosed with a non-ST-elevation myocardial infarction. For 3 weeks, he had been ingesting the dietary supplements Jack3d® (principal ingredient, 1,3-dimethylamylamine) and Phenorex™ (principal ingredient, Citrus aurantium) daily, before undertaking physical activity. Coronary angiograms revealed a proximal left anterior descending coronary artery thrombus with distal embolization. A combined medical regimen led to resolution of the thrombus. Three months later, the patient was asymptomatic with no evidence of ischemia. The primary ingredients in the sympathomimetic supplements taken by our patient are controversial in the medical community and have been individually associated with adverse cardiac events. There are no safety data on their simultaneous use. We discuss other reports of adverse effects associated with these supplements and recommend that the relevant safety guidelines be revised.

  3. Use of anti-obesity drugs among college students. (United States)

    Martins, Maria do Carmo de Carvalho e; Souza Filho, Manoel Dias de; Moura, Felipe Scipião; Carvalho, Juliana de Sousa Ribeiro de; Müller, Marina Costa; Neves, Rebeka Valença; Mousinho, Patrícia Coelho; Lima, Iúri Paz


    To evaluate the use of anti-obesity drugs among students attending a public university. This was a cross sectional random study of 664 college students. Drug use, socioeconomic, and anthropometric variables were observed. Body mass index (BMI) and waist circumference (WC) were classified according to World Health Organization criteria. Current or previous use of anti-obesity drugs was reported by 6.8% of students. Amphetamine and sympathomimetic amines (40.5%) were the most commonly used drugs. Among those who reported use of anti-obesity agents, 62.2% were female. Only 31.1% of medications were prescribed by doctors. Mean BMI and WC were higher among students reporting the use of such drugs, but 47% of them were classified as eutrophic by BMI, and 76.5% had normal WC measure. The use of anti-obesity drugs among college students is of concern, particularly due to the high proportion of drug use without indication or prescription.

  4. Mirtazapine-induced acute angle closure

    Directory of Open Access Journals (Sweden)

    Nilay Kahraman


    Full Text Available Acute angle closure (AAC is an ocular emergency with symptoms including blurred vision, eye pain, headache, nausea, vomiting and reddening of the eye those results from increased intraocular pressure. This clinical condition can lead to permanent damage in vision, thus causing blindness by generating progressive and irreversible optic neuropathy if left untreated. There are several reasons of AAC, including several types of local and systemic medications; mainly sympathomimetics, cholinergics, anti-cholinergics, mydriatics, anti-histamines, antiepileptics like topiramate, tricyclic and tetracyclic antidepressants, serotonin reuptake inhibitors, antipsychotics, sulfa-based drugs and anticoagulants. Mirtazapine, a noradrenergic and specific serotonergic antidepressant, is an atypical antidepressant with a complex pharmacological profile. This case report describes a patient with major depressive disorder, who experienced AAC after the first dosage of mirtazapine treatment, and highlights the importance of close monitoring of individuals under antidepressant treatment particularly immediately after initiation of the drug.

  5. Emergency department management of priapism [digest]. (United States)

    Podolej, Gregory S; Babcock, Christine; Kim, Jeremy


    Priapism is a genitourinary emergency that demands a thorough, time-sensitive evaluation. There are 3 types of priapism: ischemic, nonischemic, and recurrent ischemic priapism; ischemic priapism accounts for 95% of cases. Ischemic priapism must be treated within 4 to 6 hours to minimize morbidity, including impotence. The diagnosis of ischemic priapism relies heavily on the history and physical examination and may be facilitated by penile blood gas analysis and penile ultrasound. This issue reviews current evidence regarding emergency department treatment of ischemic priapism using a stepwise approach that begins with aspiration of cavernosal blood, cold saline irrigation, and penile injection with sympathomimetic agents. Evidence-based management and appropriate urologic follow-up of nonischemic and recurrent ischemic priapism maximizes patient outcomes and resource utilization. [Points & Pearls is a digest of Emergency Medicine Practice].

  6. Successful Management of Chylothorax With Etilefrine: Case Report in 2 Pediatric Patients. (United States)

    Muniz, Gysella; Hidalgo-Campos, Jennifer; Valdivia-Tapia, Maria Del Carmen; Shaikh, Nader; Carreazo, Nilton Yhuri


    Chylothorax is defined as the accumulation of chyle within the pleural space. Originally described in 1917 by Pisek, it is the most common cause of pleural effusion in the neonatal period. The leading cause of chylothorax is laceration of the thoracic duct during surgery, which occurs in 0.85% to 6.6% of children undergoing cardiothoracic surgery. Few authors of reports in the literature have looked at etilefrine, a relatively unknown sympathomimetic, as an option for the medical treatment of chylothorax. In this case report, we review the clinical course of 2 infants with type III esophageal atresia who developed chylothorax after thoracic surgery and were successfully treated with intravenous etilefrine after failing initial dietary and pharmacological management. Copyright © 2018 by the American Academy of Pediatrics.


    Directory of Open Access Journals (Sweden)

    E.Yu. Radtsig


    Full Text Available The article discusses mechanisms of occurrence and clinical course of children's acute rhinitis. It shows that traditionally, topical decongestants are used for curing acute rhinitis — a group of medications including sympathomimetics and selective ?1-adrenoceptor agonist. At the same time it is known that long time usage of decongestants is accompanied with serious side reactions (paresis of vessel walls of nasal mucous, medicament rhinitis, ETC. Besides, the poisoning frequency is high, especially among infants and younger school age children. An alternative curing method for acute rhinitis is an inhalation with volatile oils complex with bactericidal and bacteriostatic activity. Accordingly, this complex can be recommended as a safe and efficient means for curing and prophylaxis of acute rhinitisKey words: children, acute rhinitis, topical decongestants, volatile oils.

  8. Clenbuterol Hydrochloride. (United States)

    Al-Majed, Abdulrahman A; Khalil, Nasr Y; Khbrani, Ibraheem; Abdel-Aziz, Hatem A

    Clenbuterol (Broncodil and trade) is a direct-acting sympathomimetic agent with mainly beta-adrenergic activity and a selective action on β2 receptors (a β2 agonist). It has properties similar to those of salbutamol. It is used as a bronchodilator in the management of reversible airways obstruction, as in asthma and in certain patients with chronic obstructive pulmonary disease. The uses, applications, and the synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum are all produced. This profile also includes the monograph of British Pharmacopoeia, together with several reported analytical methods including spectrophotometric, electrochemical, chromatographic, immunochemical methods, and capillary electrophoretic methods. The stability, the pharmacokinetic behavior, and the pharmacology of the drug are also provided. © 2017 Elsevier Inc. All rights reserved.

  9. Immediate haemodynamic effects of a novel partial agonist, beta 1-adrenoceptor blocking drug ICI 141,292 after intravenous administration to healthy young volunteers and patients with ischaemic heart disease

    DEFF Research Database (Denmark)

    Bonde, J; Svendsen, T L; Lyngborg, K


    were administered intravenously. The attenuation in exercise induced tachycardia varied between 16.0 and 21.2% (P less than 0.01). A significant reduction in blood pressure could be demonstrated following all three doses of ICI 141,292 and atenolol during exercise. At rest in the sitting position HR...... decreased approximately 8% following all three doses of ICI 141,292 and 14.9% after atenolol 5 mg. No changes in blood pressure were observed under resting conditions after any of the drugs. In six patients with ischaemic heart disease the intrinsic sympathomimetic activity following intravenous....... No significant changes were observed in mean arterial blood pressure, stroke volume or total peripheral resistance whereas an increase in supine resting mean pulmonary arterial pressure of 3.4 mm Hg (P less than 0.05) could be demonstrated. ICI 141,292 seems to be a potent (at least five times as potent...

  10. Falsely elevated plasma metanephrine in patients taking midodrine. (United States)

    Emms, Holly; Farah, George; Shine, Brian; Boot, Chris; Toole, Barry; McFadden, Martin; Lam, Leo; Ou, Zong-Quan; Woollard, Gerald; Madhavaram, Hima; Kyle, Campbell; Grossman, Ashley B


    Plasma metanephrines have become the biochemical test of choice for suspected phaeochromocytomas and paragangliomas in many institutions. We encountered two separate cases of significantly elevated plasma metanephrines in patients taking midodrine, a sympathomimetic drug used in the treatment of severe postural hypotension, in the absence of a diagnosis of phaeochromocytomas and paragangliomas. Upon stopping midodrine treatment, plasma metanephrine concentrations returned to normal in both patients. To explore the hypothesis that midodrine or its metabolite desglymidodrine might interfere with the metanephrines assay, we tested the interaction of midodrine with metanephrine assays from two different centres. High-performance liquid chromatography tandem mass spectrometry on plasma samples and on methanolic extract of midodrine demonstrated co-elution of the metabolite desglymidodrine with metanephrine. We conclude that patients taking midodrine may have falsely elevated plasma metanephrine as a result of analytical interference, and clinicians need to be aware of this problem.

  11. The pharmacology of 1-phenyl-2-propylamino-pentane (PPAP), a deprenyl-derived new spectrum psychostimulant. (United States)

    Knoll, J; Knoll, B; Török, Z; Timár, J; Yasar, S


    The peculiar tyramine uptake inhibitory effect of (-)deprenyl prompted structure-activity relationship studies aiming to develop new spectrum central nervous system stimulants which are devoid of MAO inhibitory potency and operate de facto as indirectly acting, nonreleasing sympathomimetics. Of the derivatives synthesized for this purpose, 1-phenyl-2-propylaminopentane (PPAP) was selected as the reference substance and its pharmacological spectrum is presented. PPAP is taken up by the catecholamine axon terminal membrane and the vesicular membrane but it is devoid of catecholamine-releasing property. As a result, PPAP is, by interference, a potent inhibitor of the uptake of indirectly acting sympathomimetic releasers and of the catecholamine transmitters. This was proved, on the one hand, by measuring the uptake of [14C]PPAP into the catecholaminergic axon terminals and the inhibition of the uptake of [3H]noradrenaline and [3H]dopamine by PPAP in the rat brain, and, on the other hand, on the pulmonary artery strip of the rabbit and, in vivo, using the rat nictitating membrane as a detector. PPAP increases motility at 2 mg/kg and, in contrast to amphetamine, inhibits it at very high doses (50 mg/kg) only. A two-sided antagonism in the motility-increasing effect between PPAP and amphetamine and, more pronounced, between PPAP and mazindol was detected. PPAP is substantially less effective in inducing stereotyped behavior than either amphetamine or methamphetamine. PPAP facilitates learning and retention, is highly potent in antagonizing the tetrabenazine-induced depression in behavioral tests and is very effective in the forced swimming test. Whereas amphetamines facilitate performance in a very narrow range of low doses, which turns, at a modest elevation of the dose, into the opposite effect, PPAP improves performance within a reasonably broad dose range. Based on the peculiar pharmacological profile of PPAP, its potential usefulness in depression, in Alzheimer

  12. Orthostatic hypotension in patients, bed rest subjects, and astronauts (United States)

    Lathers, C. M.; Charles, J. B.


    Orthostatic hypotension after even short space flights has affected a significant number of astronauts. Given the need for astronauts to function at a high level of efficiency during and after their return from space, the application of pharmacologic and other treatments is strongly indicated. This report addresses the clinical problem of orthostatic hypotension and its treatments to ascertain whether pharmacologic or physiologic treatment may be useful in the prevention of orthostatic hypotension associated with space flight. Treatment of orthostatic hypotension in patients now includes increasing intravascular volume with high sodium intake and mineralocorticoids, or increasing vascular resistance through the use of drugs to stimulate alpha or block beta vascular receptors. Earlier treatment used oral sympathomimetic ephedrine hydrochloride alone or with "head-up" bed rest. Then long-acting adrenocortical steroid desoxycorticosterone preparations with high-salt diets were used to expand volume. Fludrocortisone was shown to prevent the orthostatic drop in blood pressure. The combination of the sympathomimetic amine hydroxyamphetamine and a monoamine oxidase inhibitor tranylcypromine has been used, as has indomethacin alone. Davies et al. used mineralocorticoids at low doses concomitantly with alpha-agonists to increase vasoconstrictor action. Schirger et al used tranylcypromine and methylphenidate with or without a Jobst elastic leotard garment or the alpha-adrenergic agonist midodrine (which stimulates both arterial and venous systems without direct central nervous system or cardiac effects). Vernikos et al established that the combination of fludrocortisone, dextroamphetamine, and atropine exhibited a beneficial effect on orthostatic hypotension induced by 7-day 6 degrees head-down bed rest (a model used to simulate the weightlessness of space flight). Thus, there are numerous drugs that, in combination with mechanical techniques, including lower body negative

  13. Metabolic consequences of beta-adrenergic receptor blockade for the acutely ischemic dog myocardium

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    Westera, G.; Hollander, W. den; Wall, E.E. van der; Eenige, M.J. van; Scholtalbers, S.; Visser, F.C.; Roos, J.P.


    In an experimental study in 50 dogs the myocardial uptake of free fatty acids (FFAs) after beta-blockade was determined using radioiodinated heptadecanoic acid as a metabolic tracer. All 4 beta-blockers used (metoprolol, timolol, propranolol and pindolol) lowered the uptake of FFAs in the normal canine heart. Uptake of FFAs was also diminished after coronary artery occlusion per se, but administration of beta-blockers exerted little additional influence on the uptake of FFAs. This observation was qualitatively parallelled by the uptake of /sup 201/Tl in concomitant experiments. Plasma FFA levels were increased by pindolol (non-selective with intrinsic sympathomimetic activity), not changed by metoprolol (a cardioselective betablocking agent) and lowered by timolol and propranolol (both non-selective compounds). The extent of ischemic tissue, as reflected by uptake of iodoheptadecanoic acid and /sup 201/Tl, was diminished by metoprolol but not by other beta-blockers. Regional distribution of both tracers, as shown in the endo-epicardial uptake ratios, was hardly influenced by beta-blockade, except for a small increase of /sup 201/Tl uptake in non-occluded endocardium. Uptake of /sup 201/Tl as well as of iodoheptadecanoic acid in the ischemic area was increased by metoprolol, timolol and propranolol and decreased by pindolol. We conclude that beta-blocking agents confer different effects on myocardial uptake and metabolism of FFAs which might possibly be related to their different inherent properties.

  14. 75 deaths in asthmatics prescribed home nebulisers. (United States)

    Sears, M R; Rea, H H; Fenwick, J; Gillies, A J; Holst, P E; O'Donnell, T V; Rothwell, R P


    The circumstances surrounding the deaths of 75 asthmatic patients who had been prescribed a domiciliary nebuliser driven by an air compressor pump for administration of high dose beta sympathomimetic drugs were investigated as part of the New Zealand national asthma mortality study. Death was judged unavoidable in 19 patients who seemed to have precipitous attacks despite apparently good long term management. Delays in seeking medical help because of overreliance on beta agonist delivered by nebuliser were evident in 12 cases and possible in a further 11, but these represented only 8% of the 271 verified deaths from asthma in New Zealanders aged under 70 during the period. Evidence for direct toxicity of high dose beta agonist was not found. Nevertheless, the absence of serum potassium and theophylline concentrations and of electrocardiographic monitoring in the period immediately preceding death precluded firm conclusions whether arrhythmias might have occurred due to these factors rather than to hypoxia alone. In most patients prescribed domiciliary nebulisers death was associated with deficiencies in long term and short term care similar to those seen in patients without nebulisers. Discretion in prescribing home nebulisers, greater use of other appropriate drugs, including adequate corticosteroids, and careful supervision and instruction of patients taking beta agonist by nebuliser should help to reduce the mortality from asthma.

  15. Effect of the alkaloid (-)cathinone on the release of radioactivity from rabbit atria prelabelled with 3H-norepinephrine

    International Nuclear Information System (INIS)

    Kalix, P.


    In certain countries of East Africa and the Arab Peninsula, fresh leaves of the khat shrub are used as a stimulant. The effect of the plant material can be explained by the presence of the phenylalklamine alkaloid (-)cathinone in the leaves, since this substance has been shown to have an amphetamine-like releasing effect on CNS tissue prelabelled with 3 H-dopamine. Characteristically, the chewing of khat is accompanied by sympathomimetic effects, especially at the cardiovascular level. To test whether these might be due to release of neurotransmitter from adrenergic nerve endings, the effect of (-)cathinone on the efflux of radioactivity from isolated rabbit atrium tissue prelabelled with 3 H-norepinephrine was investigated. It was found that, at concentrations below 1 μM, (-)cathinone caused an immediate increase of efflux. The effect was dose-dependent and was potentiated by pretreatment of the rabbits with reserpine. Preincubation of the tissue with desipramine and cocaine prevented the induction of release by (-)cathinone. The results indicate that the alkaloid (-)cathinone has an amphetamine-like releasing effect on noradrenergic nerve endings and they suggest that the cardiovascular symptoms observed during khat consumption are due to release of neurotransmitter from physiologicl storage sites

  16. A little "dab" will do ya' in: a case report of neuro-and cardiotoxicity following use of cannabis concentrates. (United States)

    Rickner, Shannon S; Cao, Dazhe; Kleinschmidt, Kurt; Fleming, Steven


    The use of marijuana and cannabis concentrates is increasing, especially following decriminalization in several states. Psychosis and cardiotoxicity have been reported following cannabis use; however, myocardial injury from "dabbing" has not yet been reported. We report a case of hyperthermia, tachycardia, hypertension, severe agitation, neuro-, and cardiotoxicity following the use of "dabs" where there is concomitant confirmatory biological and sample testing. A 17-year-old athletic man developed agitation requiring sedation and intubation for safety, with peak systolic blood pressures in the 190s and hyperthermia (to 102 °F). He developed elevated serum troponins with persistent tachycardia despite sedation and no clear non-intoxicant etiology. It was discovered that the patient had recently been "dabbing"; an exhaustive search of his home found a sample of the "dabs" which was analyzed along with a comprehensive urine drug screen by tandem liquid mass spectroscopy (t-LCMS) for confirmation. Tetrahydrocannabinol (THC) has been increasingly associated with agitation and cardiotoxicity, while cannabidiol (CBD) has been associated with neuroprotective, inhibitory states. We propose that increasing concentrations of THC as well as THC:CBD ratios seen in cannabis concentrates such as "dabs" may cause agitation and end-organ damage through sympathomimetic and serotonergic pathways.

  17. Consumption of dietary supplements containing Citrus aurantium (bitter orange)--2004 California Behavioral Risk Factor Surveillance Survey (BRFSS). (United States)

    Klontz, Karl C; Timbo, Babgaleh B; Street, Debra


    Following the marketing ban of ephedra-containing supplements in April 2004, many manufacturers substituted the herb Citrus aurantium for ephedra and marketed the products as "ephedra-free" supplements. Extracts of C. aurantium contain synephrine, a sympathomimetic alkaloid. To determine the prevalence of consumption of dietary supplements containing C. aurantium in California during 2004. We used the 2004 California Behavioral Risk Factor Surveillance Survey to determine the prevalence of consumption of dietary supplements containing C. aurantium in California during 2004. Two percent (n = 70) of the 4140 survey respondents reported taking a dietary supplement containing C. aurantium in the previous year. Reasons stated included energy enhancement, weight loss, and appetite suppression. Compared with nonusers, users were more likely to report being single, aged 18-34 years, and Hispanic; consuming 3 or more alcoholic drinks on days that they imbibed; and having a heavier body mass index. Among the 5 users who reported experiencing an adverse event that they attributed to the supplement, 3 indicated that the severity was mild. Given that supplements containing ephedra were banned in April 2004, the results from this study may serve as a baseline estimate against which future studies of the use of C. aurantium products may be compared.

  18. Accidental poisoning in childhood: five year urban population study with 15 year analysis of fatality. (United States)

    Pearn, J; Nixon, J; Ansford, A; Corcoran, A


    Patterns of accidental poisoning in children are changing dramatically. A five year population study (1977-81) was undertaken in urban children from Brisbane (population 1 000 000). A total of 2098 children were poisoned during this period with only one fatality, which represents a dramatic reduction in mortality. Over the past 15 years (1968-82) 13 children have died from accidental poisoning from this population, and two were murdered with drugs. A study of secular trends has indicated that peak incidence occurred in 1979, and the rate has been falling progressively since. The current age corrected rate of poisoning is 393 per 100 000 children per year (0-5 year olds). The rank order of poisons, drugs, and chemicals causing hospital admission and death is: petroleum distillates 13%; antihistamines 9%; benzodiazepines 9%; bleach and detergents 7%; and aspirin 6%. The ratio of fatalities to ingestions requiring hospital admission was calculated to give an index of a practical danger of noxious agents to which children are currently exposed and the rank order is: cardiotoxic drugs, one fatality to 25 ingestions; tricyclic antidepressants, one to 44; sympathomimetic drugs, one to 54; caustic soda, one to 68; aspirin, one fatality to 350 ingestions. Accidental poisoning of children leading to death has been reduced because patterns of drug prescriptions have changed, packaging of dangerous drugs has been made safer, and substances such as kerosene have been coloured blue.

  19. Transient left ventricular dysfunction due to coronary spasm after spinal anesthesia with bupivacaine - a case report. (United States)

    Elikowski, Waldemar; Małek-Elikowska, Małgorzata; Słomczyński, Marek; Horbacka, Karolina; Bartkowski, Jarosław; Kalawski, Bartosz


    Bupivacaine is a long-acting local anesthetic (LA) used for cutaneous infiltration, peripheral nerve blocks, epidural and spinal anesthesia. However, its application may result in cardiovascular complications such as: hypotension, bradycardia, cardiac arrest and toxic myocardial injury. The authors describe a 53-year-old male with a history of cigarette smoking, admitted for an elective inguinal hernia surgery. Before surgery, the patient received subarachnoid injection of bupivacaine (20 mg). After the operation, he developed transient hypotension. Blood pressure returned to normal after gelofusine infusion; no sympathomimetics were administered. The male denied chest pain; however, ECG showed ST segment elevation coexisting with left ventricular anterolateral hypokinesia and decreased longitudinal strain in echocardiography. A significant increase in troponin I level was suggestive rather of myocardial infarction than of takotsubo cardiomyopathy. Urgent coronary angiography revealed left anterior descending artery spasm, which remitted after intracoronary nitroglycerin injection. Normalization of ECG and echocardiography was observed within a few days. The authors indicate that the presented atypical adverse effect of bupivacaine manifested itself with delay and that coronary spasm proceeded without angina. A close observation of the patient after anesthetic procedure with LA should be extended over the postoperative period.

  20. [The characteristics of using visken in middle-aged and elderly patients with arterial hypertension]. (United States)

    Tokar, A V; Iena, L M; Kozymenko, T M; Shyshkina, O S


    Effect of three-week treatment with visken on renal and central haemodynamics, renin-angiotensin-aldosterone system (RAAS) and metabolism of electrolytes was studied in 88 elderly and old patients 45 of whom had hypertonic disease (HD) in the second stage and 43 suffered from atherosclerotic (isolated systolic) hypertension (AH). Visken is a highly effective hypotensive beta-adrenoblocker with partially retained sympathomimetic activity. It may be administered as monotherapy to elderly patients with HD as well as to the old and elderly with SH regardless of initial state of systemic and renal haemodynamics. The drug makes blood pressure fall due to its diuretic effect and decrease of general peripheral vascular resistance. It improves renal blood circulation, reduces renal vascular resistance, enhances compromised glomerular filtration but exert no influence upon RAAS. Efficacy of visken diminishes with age. This phenomenon is conditioned by increased refractivity rate and more frequent adverse effects in the old with HD. Latent heart failure, disorders of cardiac rhythm and conductivity (even if mentioned in anamnesis) as well as hypokalemia are contraindications to visken.

  1. Anti-hypotensive treatment and endothelin blockade synergistically antagonize exercise fatigue in rats under simulated high altitude.

    Directory of Open Access Journals (Sweden)

    Daniel Radiloff

    Full Text Available Rapid ascent to high altitude causes illness and fatigue, and there is a demand for effective acute treatments to alleviate such effects. We hypothesized that increased oxygen delivery to the tissue using a combination of a hypertensive agent and an endothelin receptor A antagonist drugs would limit exercise-induced fatigue at simulated high altitude. Our data showed that the combination of 0.1 mg/kg ambrisentan with either 20 mg/kg ephedrine or 10 mg/kg methylphenidate significantly improved exercise duration in rats at simulated altitude of 4,267 m, whereas the individual compounds did not. In normoxic, anesthetized rats, ephedrine alone and in combination with ambrisentan increased heart rate, peripheral blood flow, carotid and pulmonary arterial pressures, breathing rate, and vastus lateralis muscle oxygenation, but under inspired hypoxia, only the combination treatment significantly enhanced muscle oxygenation. Our results suggest that sympathomimetic agents combined with endothelin-A receptor blockers offset altitude-induced fatigue in rats by synergistically increasing the delivery rate of oxygen to hypoxic muscle by concomitantly augmenting perfusion pressure and improving capillary conductance in the skeletal muscle. Our findings might therefore serve as a basis to develop an effective treatment to prevent high-altitude illness and fatigue in humans.

  2. Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias (United States)

    O'Leary, Michael E; Hancox, Jules C


    Cocaine is a highly active stimulant that alters dopamine metabolism in the central nervous system resulting in a feeling of euphoria that with time can lead to addictive behaviours. Cocaine has numerous deleterious effects in humans including seizures, vasoconstriction, ischaemia, increased heart rate and blood pressure, cardiac arrhythmias and sudden death. The cardiotoxic effects of cocaine are indirectly mediated by an increase in sympathomimetic stimulation to the heart and coronary vasculature and by a direct effect on the ion channels responsible for maintaining the electrical excitability of the heart. The direct and indirect effects of cocaine work in tandem to disrupt the co-ordinated electrical activity of the heart and have been associated with life-threatening cardiac arrhythmias. This review focuses on the direct effects of cocaine on cardiac ion channels, with particular focus on sodium, potassium and calcium channels, and on the contributions of these channels to cocaine-induced arrhythmias. Companion articles in this edition of the journal examine the epidemiology of cocaine use (Wood & Dargan [1]) and the treatment of cocaine-associated arrhythmias (Hoffmann [2]). PMID:20573078


    Directory of Open Access Journals (Sweden)

    P. G. Shchvartz


    Full Text Available Neurogenic hyperactiv e bladder in different clinical variations is a characteristic com plication of restorativ e and residual periods of ischemic stroke and an important diagnostic criterion in vascular dementia. Mechanisms of formation of individual symptoms included in this syndrome is due to ischemic damage to cortical, subcortical and brainstem (the nucleus of Barrington centres of urination and associative areas of the brain, and the functional dissociation of these structures due to demyelination of the Central conductors of the afferent and efferent impulses. As a result of deficit of cerebral effects (such as brake and activating, is a violation of the implementation of the reflexes of urination (including carrying out continence, ongoing spinal (sympathetic, parasympathetic and somatic. The article presents a new concept of formation of the syndrome of hyperactive bladder on the basis of violations of the implementation of the 4 reflexes of urination, which provides the normal retention of urine and are responsible for the accumulation function of the bladder. First we analyzed the main point of application of drugs of anticholinergic and sympathomimetic actions in the reflexes of urination and mechanisms of restoration of function of the lower urinary tract in patients with acute and chronic v ascular diseases of the brain.

  4. Epidemiological analysis of alcohol and drug use as risk factors for psychotic experiences. (United States)

    Tien, A Y; Anthony, J C


    Clinical and laboratory studies link alcohol and other drug use to the occurrence of psychotic experiences, but epidemiologic evidence has been lacking. In this study, the quantitative relationships between alcohol or other drug use and psychotic experiences were examined by analysis of prospective data from 4994 adult household residents sampled in a multisite survey of mental disorders in the population, the NIMH Epidemiologic Catchment Area Program. After control for sociodemographic factors and preexisting psychiatric conditions, the risk for onset of self-reported delusions or hallucinations was observed to be greater for daily users of marijuana or cocaine and for users of anxiolytics or sympathomimetics compared with nonusers. After control for daily cocaine use and alcohol disorder, the risk of onset of psychotic experiences for daily users of marijuana was double that for nonusers. Alcohol disorder in men was associated with eightfold risk and in women with threefold risk. Baseline depressive episodes, manic episodes, agoraphobia, and obsessive-compulsive disorder also were associated with increased risk of onset of psychotic experiences.

  5. Alpha-blockade and vasodilatation induced by nipradilol, arotinolol and labetalol in pithed rats. (United States)

    Nakagawa, Y; Nakahara, H; Chin, W P; Imai, S


    In pithed rats two recently-introduced beta-blockers, nipradilol and arotinolol, as well as labetalol shifted the pressor dose-response curve for phenylephrine to the right. Labetalol and arotinolol did not modify the pressor dose-response curve for clonidine, while nipradilol induced a definite rightward shift. These results indicate that labetalol and arotinolol are selective alpha 1-blockers, while nipradilol is a non-selective one. In addition, all the three beta-blockers produced complex changes in the blood pressure in pithed rats. A fall of the diastolic blood pressure induced by labetalol and nipradilol was preceded by a slight rise, while arotinolol produced a fall at lower doses and a rise at higher ones. The hypotension by labetalol was abolished after propranolol, while the hypertension was suppressed by prazosin, indicating that labetalol has an intrinsic beta- and alpha 1-sympathomimetic effect. The hypertension and the hypotension produced by nipradilol and arotinolol persisted even in the presence of propranolol and prazosin or propranolol and yohimbine.

  6. Comparison of Prophylactic Infusion of Phenylephrine with Ephedrine for Prevention of Hypotension in Elective Cesarean Section under Spinal Anesthesi: A Randomized Clinical Trial. (United States)

    Moslemi, Farnaz; Rasooli, Sousan


    Spinal anesthesia is an accepted technique in elective cesarean sections. However, hypotension, resulted from sympathectomy is a common problem, especially in pregnant women. Prevention of this complication by sympathomimetic agents is of potential clinical significance. The aim of this study is to compare the effect of prophylactic infusion of Phenylephrine versus Ephedrine in the prevention of hypotension during spinal anesthesia in elective cesarean section. Eighty-three patients were enrolled in this study and randomly divided into three groups. Group Ph received phenylephrine infusion, group E received ephedrine infusion while group P were delivered placebo. Vital signs (blood pressure, heart rate, and arterial oxygen saturation) were recorded throughout the surgery. Maternal and neonatal perioperative complications were also controlled and recorded. There was an insignificant difference in demographic data between the groups. Systolic and diastolic blood pressures were higher in the phenylephrine group than control, but not higher than the ephedrine group. Maternal dysrhythmias were more common in ephedrine and phenylephrine groups than the control group. Vomiting was more common in ephedrine group (Pcomplication for mother or her fetus. IRCT2012120911700N1.

  7. Here today, gone tomorrow…and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines. (United States)

    Rosenbaum, Christopher D; Carreiro, Stephanie P; Babu, Kavita M


    Despite their widespread Internet availability and use, many of the new drugs of abuse remain unfamiliar to health care providers. The herbal marijuana alternatives, like K2 or Spice, are a group of herbal blends that contain a mixture of plant matter in addition to chemical grade synthetic cannabinoids. The synthetic cathinones, commonly called "bath salts," have resulted in nationwide emergency department visits for severe agitation, sympathomimetic toxicity, and death. Kratom, a plant product derived from Mitragyna speciosa Korth, has opioid-like effects, and has been used for the treatment of chronic pain and amelioration of opioid-withdrawal symptoms. Salvia divinorum is a hallucinogen with unique pharmacology that has therapeutic potential but has been banned in many states due to concerns regarding its psychiatric effects. Methoxetamine has recently become available via the Internet and is marked as "legal ketamine." Moreover, the piperazine derivatives, a class of amphetamine-like compounds that includes BZP and TMFPP, are making a resurgence as "legal Ecstasy." These psychoactives are available via the Internet, frequently legal, and often perceived as safe by the public. Unfortunately, these drugs often have adverse effects, which range from minimal to life-threatening. Health care providers must be familiar with these important new classes of drugs. This paper discusses the background, pharmacology, clinical effects, detection, and management of synthetic cannabinoid, synthetic cathinone, methoxetamine, and piperazine exposures.

  8. Emerging drugs of abuse. (United States)

    Nelson, Michael E; Bryant, Sean M; Aks, Steven E


    Many new emerging drugs of abuse are marketed as legal highs despite being labeled "not for human consumption" to avoid regulation. The availability of these substances over the Internet and in "head shops" has lead to a multitude of emergency department visits with severe complications including deaths worldwide. Despite recent media attention, many of the newer drugs of abuse are still largely unknown by health care providers. Slight alterations of the basic chemical structure of substances create an entirely new drug no longer regulated by current laws and an ever-changing landscape of clinical effects. The purity of each substance with exact pharmacokinetic and toxicity profiles is largely unknown. Many of these substances can be grouped by the class of drug and includes synthetic cannabinoids, synthetic cathinones, phenethylamines, as well as piperazine derivatives. Resultant effects generally include psychoactive and sympathomimetic-like symptoms. Additionally, prescription medications, performance enhancing medications, and herbal supplements are also becoming more commonly abused. Most new drugs of abuse have no specific antidote and management largely involves symptom based goal directed supportive care with benzodiazepines as a useful adjunct. This paper will focus on the history, epidemiology, clinical effects, laboratory analysis, and management strategy for many of these emerging drugs of abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. New drugs of abuse. (United States)

    Rech, Megan A; Donahey, Elisabeth; Cappiello Dziedzic, Jacqueline M; Oh, Laura; Greenhalgh, Elizabeth


    Drug abuse is a common problem and growing concern in the United States, and over the past decade, novel or atypical drugs have emerged and have become increasingly popular. Recognition and treatment of new drugs of abuse pose many challenges for health care providers due to lack of quantitative reporting and routine surveillance, and the difficulty of detection in routine blood and urine analyses. Furthermore, street manufacturers are able to rapidly adapt and develop new synthetic isolates of older drugs as soon as law enforcement agencies render them illegal. In this article, we describe the clinical and adverse effects and purported pharmacology of several new classes of drugs of abuse including synthetic cannabinoids, synthetic cathinones, salvia, desomorphine, and kratom. Because many of these substances can have severe or life-threatening adverse effects, knowledge of general toxicology is key in recognizing acute intoxication and overdose; however, typical toxidromes (e.g., cholinergic, sympathomimetic, opioid, etc.) are not precipitated by many of these agents. Medical management of patients who abuse or overdose on these drugs largely consists of supportive care, although naloxone may be used as an antidote for desomorphine overdose. Symptoms of aggression and psychosis may be treated with sedation (benzodiazepines, propofol) and antipsychotics (haloperidol or atypical agents such as quetiapine or ziprasidone). Other facets of management to consider include treatment for withdrawal or addiction, nutrition support, and potential for transmission of infectious diseases. © 2014 Pharmacotherapy Publications, Inc.

  10. Comparison of Prophylactic Infusion of Phenylephrine with Ephedrine for Prevention of Hypotension in Elective Cesarean Section under Spinal Anesthesi: A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Farnaz Moslemi


    Full Text Available Background: Spinal anesthesia is an accepted technique in elective cesarean sections. However, hypotension, resulted from sympathectomy is a common problem, especially in pregnant women. Prevention of this complication by sympathomimetic agents is of potential clinical significance. The aim of this study is to compare the effect of prophylactic infusion of Phenylephrine versus Ephedrine in the prevention of hypotension during spinal anesthesia in elective cesarean section. Methods: Eighty-three patients were enrolled in this study and randomly divided into three groups. Group Ph received phenylephrine infusion, group E received ephedrine infusion while group P were delivered placebo. Vital signs (blood pressure, heart rate, and arterial oxygen saturation were recorded throughout the surgery. Maternal and neonatal perioperative complications were also controlled and recorded. Results: There was an insignificant difference in demographic data between the groups. Systolic and diastolic blood pressures were higher in the phenylephrine group than control, but not higher than the ephedrine group. Maternal dysrhythmias were more common in ephedrine and phenylephrine groups than the control group. Vomiting was more common in ephedrine group (P<0.05. In addition, the fifth-minute Apgar score of neonates was higher in phenylephrine and ephedrine groups than the control group (P<0.05. Neonates of phenylephrine group had less acidosis than the other groups. Conclusion: Prophylactic infusion of phenylephrine can effectively decrease spinal anesthesia related hypotension without any significant complication for mother or her fetus. Trial Registration Number: IRCT2012120911700N1

  11. Correlation of phenylpropanolamine bioavailability with gastrointestinal transit by scintigraphic monitoring of 111In-labeled hydroxypropylmethylcellulose matrices

    International Nuclear Information System (INIS)

    Feely, L.C.; Davis, S.S.


    Two controlled-release hydroxypropylmethylcellulose (HPMC) matrix formulations, a single-unit and a multiple-unit system, have been evaluated in human volunteers. Both formulations contained the sympathomimetic drug phenylpropanolamine hydrochloride and each was radiolabeled with 111 Inbound Amberlite IR 120 ion-exchange resin. The formulations were administered to each of six healthy male volunteers and gastrointestinal (GI) transit was monitored using a gamma camera. Serum samples were taken at set time intervals and assayed for phenylpropanolamine content, thus allowing blood drug levels to be correlated with the position of the dosage form in the GI tract. The multiple-unit system emptied from the stomach gradually over a period of about 180 min, when administered after a light breakfast, whereas the single-unit dosage forms had extremely variable gastric emptying times (range, 60 to greater than 570 min). However, both formulations provided prolonged phenylpropanolamine blood levels. The differences in the blood profiles obtained with the two formulations were attributed to variations in their in vitro release rates and not to any differences in their GI transit times

  12. Meth Mouth—A Growing Epidemic in Dentistry?

    Directory of Open Access Journals (Sweden)

    Andreas Pabst


    Full Text Available In the past two decades, the synthetic style and fashion drug “crystal meth” (“crystal”, “meth”, chemically representing the crystalline form of the methamphetamine hydrochloride, has become more and more popular in the United States, in Eastern Europe, and just recently in Central and Western Europe. “Meth” is cheap, easy to synthesize and to market, and has an extremely high potential for abuse and dependence. As a strong sympathomimetic, “meth” has the potency to switch off hunger, fatigue and, pain while simultaneously increasing physical and mental performance. The most relevant side effects are heart and circulatory complaints, severe psychotic attacks, personality changes, and progressive neurodegeneration. Another effect is “meth mouth”, defined as serious tooth and oral health damage after long-standing “meth” abuse; this condition may become increasingly relevant in dentistry and oral- and maxillofacial surgery. There might be an association between general methamphetamine abuse and the development of osteonecrosis, similar to the medication-related osteonecrosis of the jaws (MRONJ. Several case reports concerning “meth” patients after tooth extractions or oral surgery have presented clinical pictures similar to MRONJ. This overview summarizes the most relevant aspect concerning “crystal meth” abuse and “meth mouth”.

  13. Direct and indirect cardiovascular actions of cathinone and MDMA in the anaesthetized rat. (United States)

    Alsufyani, Hadeel A; Docherty, James R


    The stimulants cathinone (from Khat leaves) and methylenedioxymeth-amphetamine (MDMA) produce adrenoceptor mediated tachycardia and vasopressor actions that may be the result of direct receptor stimulation, actions on the noradrenaline transporter, and/or displacement of noradrenaline from nerve terminals. Effects of cathinone or MDMA were compared with those of the indirect sympathomimetic tyramine. Male Wistar rats were anaesthetized with pentobarbitone for blood pressure and heart rate recording. Some rats were sympathectomised by treatment with 6-hydroxydopamine. In the anaesthetised rat, cathinone, MDMA and tyramine (all 0.001-1 mg/kg) produced marked tachycardia, tyramine produced marked pressor responses and MDMA produced small pressor responses. The tachycardia to cathinone and MDMA was almost abolished by propranolol (1mg/kg). Pretreatment with cocaine (1mg/kg) did not significantly affect the tachycardia to cathinone or MDMA, but reduced the response to tyramine. However, in sympathectomised rats, the tachycardia to cathinone or MDMA was markedly attenuated, but the tachycardia to tyramine was only partially reduced. Blood pressure effects of tyramine and MDMA were also markedly attenuated by sympathectomy. The results demonstrate firstly that cocaine may not be the most suitable agent for assessing direct versus indirect agonism in cardiovascular studies. Secondly, the use of chemical sympathectomy achieved the desired goal of demonstrating that cardiac β-adrenoceptor mediated actions of cathinone and MDMA are probably largely indirect. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. A contemporaneous finding of fenproporex in a polydrug suicide. (United States)

    Bell, R R; Crookham, S B; Dunn, W A; Grates, K M; Reiber, T M


    Fenproporex is a sympathomimetic agent with a pharmacological profile similar to that of amphetamine. It is available in many countries throughout the world, but it is currently not available in the United States. Because of its stimulant effects, it has a great potential for abuse. To the best of our knowledge, there have been no literature reports of blood or serum concentrations found in therapeutic, toxic, or fatal cases. We report a case where fenproporex was a finding in the death of a young adult. Blood, urine, and gastric contents were analyzed. The following drug concentrations were found: 0.90 mg/L (inferior vena cava blood), 1.2 mg/L (urine), and 120 mg total (gastric) for fenproporex and 0.084 mg/L (inferior vena cava blood), 0.94 mg/L (urine), and 0.14 mg total (gastric) for amphetamine. In addition to the fenproporex, other medications detected and their blood concentrations found in this case were H diazepam (0.54 mg/L), nordiazepam (0.46 mg/L), diphenhydramine (0.12 mg/L), and gamma hydroxybutyric acid (GHB) (1100 mg/L).

  15. Validation and application of a liquid chromatography-electrospray ionization mass spectrometric method for determination of mazindol in human plasma and urine. (United States)

    de Oliveira, Marcella Herbstrith; Ferreira, Pâmela Cristina Lukasewicz; Carlos, Graciela; Salazar, Fernanda Rodrigues; Bergold, Ana Maria; Pechansky, Flavio; Limberger, Renata Pereira; Fröehlich, Pedro Eduardo


    Even after removal of some stimulants, like fenproporex, amfepramone and mazindol, from Brazilian market, the use of these substances is still high, especially by drivers. Mazindol is the second most used anorectic agent in the world acting as an indirect sympathomimetic agonist, having stimulatory action on central nervous system. Plasma is a good matrix to monitor since it reflects the psychomotor effects of these drugs, but unlike urine has an invasive collection; drug levels and detection time are quite low. The method involved a liquid-liquid extraction of the samples and a LC-MS analysis was fully validated. Method was used to analyze samples of urine and plasma collected from health volunteers in a period of 24h. Metabolite of mazindol was synthesized using alkaline conditions. After validation the method proved to be adequate to analyze samples collected from health volunteers. Method was linear in the concentration range of 0.1-10ng/mL (r=0.9982) for plasma and 5-50ng/mL (r=0.9973) for urine. Analysis of the samples showed that mazindol can be detected after 1h of administration and that concentration levels in urine were always higher than in plasma. Mazindol metabolite was detected only in urine. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Can MDMA play a role in the treatment of substance abuse? (United States)

    Jerome, Lisa; Schuster, Shira; Yazar-Klosinski, B Berra


    A wider array of treatments are needed for people with substance abuse disorders. Some psychedelic compounds have been assessed as potential substance abuse treatments with promising results. MDMA may also help treat substance abuse based on shared features with psychedelic compounds and recent reports indicating that MDMAassisted psychotherapy can reduce symptoms of PTSD. Narrative reports and data from early investigations found that some people reduced or eliminated their substance use after receiving MDMA, especially in a therapeutic setting. MDMA is a potent monoamine releaser with sympathomimetic effects that may indirectly activate 5-HT2A receptors. It increases interpersonal closeness and prosocial feelings, potentially through oxytocin release. Findings suggest that ecstasy, material represented as containing MDMA, is associated with deleterious long-term effects after heavy lifetime use, including fewer serotonin transporter sites and impaired verbal memory. Animal and human studies demonstrate moderate abuse liability for MDMA, and this effect may be of most concern to those treating substance abuse disorders. However, subjects who received MDMA-assisted psychotherapy in two recent clinical studies were not motivated to seek out ecstasy, and tested negative in random drug tests during follow-up in one study. MDMA could either directly treat neuropharmacological abnormalities associated with addiction, or it could indirectly assist with the therapeutic process or reduce symptoms of comorbid psychiatric conditions, providing a greater opportunity to address problematic substance use. Studies directly testing MDMA-assisted psychotherapy in people with active substance abuse disorder may be warranted.

  17. Development and validation of impurity-profiling UPLC method for the determination of sodium cromoglicate and tetryzoline hydrochloride: Application on rabbit aqueous humor. (United States)

    Lotfy, Hayam M; Saleh, Sarah S; Hassan, Nagiba Y; Salem, Hesham


    Sodium cromoglicate (SCG), antihistaminic agent, and tetryzoline hydrochloride (TZH), a sympathomimetic agent, are formulated together as an ophthalmic preparation. An ultra-performance liquid chromatographic method with UV detection (UPLC-UV) was developed and validated for the quantitative determination of SCG and TZH in rabbit aqueous humor. Due to the instability of both SCG and TZH under alkaline conditions, the UPLC method was applied for their determination in the presence of their possible degradation impurities. The separation was performed using C18 column (1.7μm particle size) and isocratic elution system with methanol: 1% o-phosphoric acid (65: 35, v/v).The optimum flow rate was 0.5ml/min and the detection was done at 230nm. The suggested method was validated in compliance with the ICH guidelines and was successfully applied for determination of sodium cromoglicate (SCG) and tetryzoline HCl (TZH) as prepared synthetically in laboratory mixtures, and in the presence of their alkali-induced degradation impurities. The suggested method was effectively applied the determination of spiked rabbit aqueous humor samples as well as commercial pharmaceutical formulation. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Effects of acute administration of mazindol on brain energy metabolism in adult mice. (United States)

    Gonçalves, Cinara Ludvig; Scaini, Giselli; Rezin, Gislaine Tezza; Jeremias, Isabela Casagrande; Bez, Gisele Daiane; Daufenbach, Juliana Felipe; Gomes, Lara Mezari; Ferreira, Gabriela Kozuchovski; Zugno, Alexandra Ioppi; Streck, Emilio Luiz


    Mazindol is a sympathomimetic amine, widely used as an anorectic agent in the treatment of obesity. This drug causes psychostimulant effects because of its pharmacological profile similar to amphetamine, acting like a monoamine reuptake inhibitor. However, the mechanisms underlying the action of mazindol are still not clearly understood. Swiss mice received a single acute administration of mazindol (0.25, 1.25 and 2.5 mg/kg, ip) or saline. After 2 h, the animals were killed by decapitation; the brain was removed and used for the evaluation of activities of mitochondrial respiratory chain complexes, Krebs cycle enzymes and creatine kinase. Acute administration of mazindol decreased complex I activity only in the hippocampus. Complex IV activity was increased in the cerebellum (2.5 mg/kg) and cerebral cortex (0.25 mg/kg). Citrate synthase activity was increased in the cerebellum (1.25 mg/kg) and cerebral cortex (1.25 mg/kg), and creatine kinase activity was increased in the cerebellum (1.25 mg/kg). We suggest that the inhibition of complex I in the hippocampus only and activation of complex IV, citrate synthase and creatine kinase occurs because of a stimulus effect of mazindol in the central nervous system, which causes a direct impairment on energy metabolism.

  19. Clenbuterol - regional food contamination a possible source for inadvertent doping in sports. (United States)

    Guddat, S; Fußhöller, G; Geyer, H; Thomas, A; Braun, H; Haenelt, N; Schwenke, A; Klose, C; Thevis, M; Schänzer, W


    The misuse of the sympathomimetic and anabolic agent clenbuterol has been frequently reported in professional sport and in the livestock industry. In 2010, a team of athletes returned from competition in China and regular doping control samples were taken within the next two days. All urine samples contained low amounts (pg/ml) of clenbuterol, drawing the attention to a well-known problem: the possibility of an unintended clenbuterol intake with food. A warning that Chinese meat is possibly contaminated with prohibited substances according to international anti-doping regulations was also given by Chinese officials just before the Bejing Olympic Games in 2008. To investigate if clenbuterol can be found in human urine, a study was initiated comprising 28 volunteers collecting urine samples after their return from China. For the quantification of clenbuterol at a low pg/ml level, a very sensitive and specific isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed using liquid/liquid re-extraction for clean-up with a limit of detection and quantification of 1 and 3 pg/ml, respectively. The method was validated demonstrating good precision (intra-day: 2.9-5.5 %; inter-day: 5.1-8.8%), accuracy (89.5-102.5%) and mean recovery (81.4%). Clenbuterol was detectable in 22 (79%) of the analyzed samples, indicating a general food contamination problem despite an official clenbuterol prohibition in China for livestock. Copyright © 2012 John Wiley & Sons, Ltd.

  20. Rhabdomyolysis Secondary to Clenbuterol Use and Exercise. (United States)

    Grimmer, Nicole M; Gimbar, Renee Petzel; Bursua, Adam; Patel, Meet


    The literature regarding rhabdomyolysis secondary to illicit drug use is sparse. Clenbuterol is a bronchodilator approved for veterinary use, which in high doses can increase protein deposition and lipolysis similarly to anabolic steroids, and is thereby abused for bodybuilding and weight loss effects. Clenbuterol has previously been described in case reports to be cardiotoxic, with patient presentations similar to overdoses of sympathomimetic substances, but reports of rhabdomyolysis are limited to a single case series in horses. We report the first case of rhabdomyolysis secondary to clenbuterol in a human. Our patient used clenbuterol for muscle-building effects in addition to exercise for multiple days prior to presentation. The patient's chief complaint at Emergency Department (ED) presentation was discolored urine. Workup for rhabdomyolysis was initiated, and an initial creatine kinase was measured at 122,933 units/L. Our patient's rhabdomyolysis was successfully treated with supportive therapy, and the patient was eventually discharged to home with no identifiable disability. The patient's kidney function remained at baseline, and no acute kidney injury was experienced secondary to rhabdomyolysis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients presenting to the ED may have been unintentionally exposed through cutting of illicit substances or through intentional use in bodybuilding. Clenbuterol has well-described cardiotoxic effects, and we report the additional toxicity of rhabdomyolysis with its use. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Effects of MDMA on body temperature in humans (United States)

    Liechti, Matthias E


    Hyperthermia is a severe complication associated with the recreational use of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy). In this review, the clinical laboratory studies that tested the effects of MDMA on body temperature are summarized. The mechanisms that underlie the hyperthermic effects of MDMA in humans and treatment of severe hyperthermia are presented. The data show that MDMA produces an acute and dose-dependent rise in core body temperature in healthy subjects. The increase in body temperature is in the range of 0.2-0.8°C and does not result in hyperpyrexia (>40°C) in a controlled laboratory setting. However, moderately hyperthermic body temperatures >38.0°C occur frequently at higher doses, even in the absence of physical activity and at room temperature. MDMA primarily releases serotonin and norepinephrine. Mechanistic clinical studies indicate that the MDMA-induced elevations in body temperature in humans partially depend on the MDMA-induced release of norepinephrine and involve enhanced metabolic heat generation and cutaneous vasoconstriction, resulting in impaired heat dissipation. The mediating role of serotonin is unclear. The management of sympathomimetic toxicity and associated hyperthermia mainly includes sedation with benzodiazepines and intravenous fluid replacement. Severe hyperthermia should primarily be treated with additional cooling and mechanical ventilation. PMID:27626046

  2. Bath Salts Abuse Leading to New-Onset Psychosis and Potential for Violence. (United States)

    John, Michelle E; Thomas-Rozea, Crystal; Hahn, David

    Bath salts have recently emerged as a popular designer drug of abuse causing significant hazardous effects on mental health and physical health, resulting in public health legislation making its usage illegal in the United States. To educate mental health providers on the effects of the new designer drug bath salts, including its potential to cause psychosis and violence in patients. This is a case report on a 40-year-old male with no past psychiatric history who presented with new-onset psychosis and increased risk for violence after ingesting bath salts. In addition, a literature review was performed to summarize the documented effects of bath salts abuse and the current U.S. public health legislation on bath salts. The presented case illustrates a new-onset, substance-induced psychotic disorder related to bath salts usage. The literature review explains the sympathomimetic reaction and the potential for psychotic symptoms. To discuss the physical and psychological effects of bath salts, treatment options for bath salts abuse and U.S. legislation by Ohio state law to current U.S. federal law that bans production, sale, and possession of main substances found in bath salts. It is important for mental health providers to be aware of bath salts, understand the physical and psychiatric effects of bath salts and be familiar with current legislative policy banning its usage. Lastly, bath salts abuse should be in the differential diagnosis where psychosis is new onset or clinically incongruent with known primary presentation of a psychotic disorder.

  3. Antidepressant-like effect of Hoodia gordonii in a forced swimming test in mice: evidence for involvement of the monoaminergic system

    Directory of Open Access Journals (Sweden)

    M.C.O. Citó


    Full Text Available Hoodia gordonii is a plant species used traditionally in southern Africa to suppress appetite. Recently, it has been associated with a significant increase in blood pressure and pulse rate in women, suggesting sympathomimetic activity. The present study investigated the possible antidepressant-like effects of acute and repeated (15 days administration of H. gordonii extract (25 and 50 mg/kg, po to mice exposed to a forced swimming test (FST. Neurochemical analysis of brain monoamines was also carried out to determine the involvement of the monoaminergic system on these effects. Acute administration of H. gordonii decreased the immobility of mice in the FST without accompanying changes in general activity in the open-field test during acute treatment, suggesting an antidepressant-like effect. The anti-immobility effect of H. gordonii was prevented by pretreatment of mice with PCPA [an inhibitor of serotonin (5-HT synthesis], NAN-190 (a 5-HT1A antagonist, ritanserin (a 5-HT2A/2C antagonist, ondansetron (a 5-HT3A antagonist, prazosin (an α1-adrenoceptor antagonist, SCH23390 (a D1 receptor antagonist, yohimbine (an α2-adrenoceptor antagonist, and sulpiride (a D2 receptor antagonist. A significant increase in 5-HT levels in the striatum was detected after acute administration, while 5-HT, norepinephrine and dopamine were significantly elevated after chronic treatment. Results indicated that H. gordonii possesses antidepressant-like activity in the FST by altering the dopaminergic, serotonergic, and noradrenergic systems.

  4. β1-Adrenoceptor autoantibodies from DCM patients enhance the proliferation of T lymphocytes through the β1-AR/cAMP/PKA and p38 MAPK pathways.

    Directory of Open Access Journals (Sweden)

    Yunhui Du

    Full Text Available Autoantibodies against the second extracellular loop of the β(1-adrenergic receptor (β(1-AA not only contribute to increased susceptibility to heart failure, but also play a causative role in myocardial remodeling through their sympathomimetic-like effects that are induced upon binding to the β(1-adrenergic receptor. However, their role in the function of T lymphocytes has never been previously investigated. Our present study was designed to determine whether β(1-AA isolated from the sera of dilated cardiomyopathy (DCM patients caused the proliferation of T cells and the secretion of cytokines.Blood samples were collected from 95 DCM patients as well as 95 healthy subjects, and β(1-AA was detected using ELISA. The CD3(+T lymphocytes were selected separately through flow cytometry and the effect of β(1-AA on T lymphocyte proliferation was examined by CCK-8 kits and CFSE assay. Western blotting was used to analyze the expressions of phospho-VASP and phospho-p38 MAPK.β(1-AA enhanced the proliferation of T lymphocytes. This effect could be blocked by the selective β(1-adrenergic receptor antagonist metoprolol, PKA inhibitor H89, and p38 MAPK inhibitor SB203580. Furthermore, the expression of the phosphorylated forms of phospho-VASP and phospho-p38 MAPK were markedly increased in the presence of β(1-AA. β(1-AA also inhibited the secretion of interferon-γ (IFN-γ while promoting an increase in interleukin-4 (IL-4 levels.These results demonstrate that β(1-AA isolated from DCM patients binds to β(1-AR on the surface of T cells, causing changes in T-cell proliferation and secretion through the β(1-AR/cAMP/PKA and p38 MAPK pathways.

  5. Clinical evaluation of carbon-11-phenylephrine: MAO-sensitive marker of cardiac sympathetic neurons. (United States)

    Raffel, D M; Corbett, J R; del Rosario, R B; Gildersleeve, D L; Chiao, P C; Schwaiger, M; Wieland, D M


    The sympathomimetic drug phenylephrine recently has been labeled with 11C for use in PET studies of cardiac sympathetic innervation. Previous reports using isolated perfused rat heart models indicate that phenylephrine is metabolized by intraneuronal monoamine oxidase (MAO). This report compares the imaging characteristics, neuronal selectivity and kinetics of (-)-[11C]phenylephrine (PHEN) to the structurally similar but MAO-resistant analog (-)-[11C]-meta-hydroxyephedrine (HED), an established heart neuronal marker. Fourteen healthy volunteers were studied with PET and PHEN. Ten had paired studies with HED; four of the 10 were scanned a second time with each tracer after oral administration of desipramine, a selective neuronal transport blocker. Hemodynamic and electrocardiographic responses were monitored. Blood levels of intact radiotracer and radiolabeled metabolites were determined from venous blood samples taken during the PET study. Myocardial retention indices for both tracers were calculated. No hemodynamic or electrocardiographic effects were observed with either tracer. PHEN showed reduced myocardial retention at 50 min compared to HED; however, image quality and uniformity of distribution were comparable. PHEN cleared from myocardium with a mean half-time of 59 +/- 5 min, while myocardial levels of HED remained constant. PHEN metabolites appeared in the blood approximately three times faster than HED metabolites. Desipramine pretreatment markedly reduced (> 60%) myocardial retention of both PHEN and HED. PHEN provides PET images of human heart comparable in quality and uniformity to HED. Like HED, PHEN localizes in the sympathetic nerves of the heart. However, the more rapid efflux of PHEN, that is likely mediated by MAO, may provide information on the functional status of cardiac sympathetic neurons unobtainable with HED.

  6. Pharmacological bridge to cardiac transplantation. (United States)

    Loisance, D; Dubois Rande, J L; Deleuze, P H; Hillion, M L; Duval, A M; Tavolaro, O; Romano, P; Castaigne, A; Tarral, A; Cachera, J P


    From September 1985 to August 1988, 32 patients were referred from various intensive care units throughout Paris for urgent cardiac transplantation or for a mechanical bridge to transplantation. At time of admission, under maximal sympathomimetic therapy, the cardiac index (CI) was 1.81 +/- 0.26 l/min per m2, the pulmonary capillary wedge pressure (PCWP 31 +/- 7 mmHg), systemic vascular resistances (SVR) 2053 +/- 469 dynes s cm-5. In 25, diuresis was less than 25 ml/h. Five were anuric. Prior to any final decision, a new inotropic agent, enoximone, was infused in addition to previous treatment as a 10 min bolus iv 1.5-2 mg/kg every 8 h. In 3, the situation further deteriorated, leading to a Jarvik 7-70 implantation within 12 h. In 29 however, within 3 h, the Cl increased to 2.69 +/- 0.56 as SVR dropped to 1410 +/- 453 and PCWP to 18 +/- 7. Diuresis increased to more than 100 ml/h in all. This permitted an indepth evaluation of the transplant candidates leading to contraindications to transplantation in 16. Nine patients could be weaned off iv enoximone. Four of these are still living (NYHA class III) with a follow up of 6-17 months. In 11, transplantation was performed within 2 days. Four died within a month, 2 with multiple organ failure. One patient died after 5 months. Six are back to normal life, NYHA class I (follow up 10 months-2.5 years). This protocol suggests that in patients with extreme heart failure, immediate survival may be increased by iv enoximone therapy, permitting a better selection of the recipients, more efficient pre-transplantation intensive care and consequently a decrease in the indications for a temporary mechanical bridge to a staged transplantation.

  7. Enoximone improves selection of candidates for urgent cardiac transplantation. (United States)

    Loisance, D; Benvenuti, C; Dubois Randé, J L; Deleuze, P; Castaigne, A; Cachera, J P


    Immediate cardiac transplantation, or urgent implantation of devices for mechanical support of the failing heart, has been shown to be effective as life-saving procedures in patients with cardiogenic shock unresponsive to maximal sympathomimetic treatment. The intravenous administration of enoximone in these patients, in addition to previous inotropic support, should permit a 'buying of time' strategy, leading to a reduction in the need for complex, invasive and costly techniques, such as artificial hearts. In addition, it should permit improved selection of candidates for cardiac transplantation. A prospective study was started in 1985 to obtain data on the haemodynamic and clinical efficacy of intravenous enoximone in these critically ill patients, and to determine the time gained for evaluation of the need for urgent transplantation. Cardiac index rose from 1.82 +/- 0.26 litres/minute/m2 to 2.67 +/- 0.56 litres/minute/m2 after 30 minutes, while pulmonary capillary wedge pressure decreased from 29.9 +/- 7 mm Hg to 18.0 +/- 7 mm Hg (n = 30). This early beneficial effect waned progressively after 6 hours. Prior to the next intravenous infusion at 8 hours, cardiac index was 2.07 +/- 0.53 litres/minute/m2 and pulmonary capillary wedge pressure was 25 +/- 8.5 mm Hg. Only four patients could not wait for a biological graft and had to be implanted with a complete artificial heart (3 patients), or a ventricular assist device (1 patient). In all, 30 patients improved and their increased survival allowed a re-evaluation for cardiac transplantation itself; 13 were rapidly (1.7 days; range 0.5-5) confirmed as good candidates. As a whole, this strategy compares favourably with the results of a strategy based on mechanical bridging alone.

  8. Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord

    Directory of Open Access Journals (Sweden)

    Elizabeth A Gozal


    sympathomimetic function.

  9. Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants. (United States)

    Chacur, M; Longo, I; Picolo, G; Gutiérrez, J M; Lomonte, B; Guerra, J L; Teixeira, C F P; Cury, Y


    The ability of Lys49 and Asp49 phospholipases A(2) (PLA(2)), from Bothrops asper snake venom, to cause hyperalgesia was investigated in rats, using the paw pressure test. Intraplantar injection of both toxins (5-20 micro g/paw) caused hyperalgesia, which peaked 1h after injections. Incubation of both proteins with heparin, prior to their injection, partially reduced this response. Chemical modification of Asp49 PLA(2) with p-bromophenacyl bromide (p-BPB), which abrogates its PLA(2) activity, also abolished hyperalgesia. Intraplantar injection of a synthetic peptide corresponding to the C-terminal sequence 115-129 of Lys49 PLA(2), caused hyperalgesia of similar time course, but varying magnitude, than that induced by the native protein. In contrast, a homologous peptide derived from the Asp49 PLA(2) did not show any nociceptive effect. Hyperalgesia induced by both PLA(2)s was blocked by the histamine and serotonin receptor antagonists promethazine and methysergide, respectively, by the bradykinin B(2) receptor antagonist HOE 140 and by antibodies to tumor necrosis factor alfa (TNFalpha) and interleukin 1 (IL-1). Pretreatment with guanethidine, atenolol, prazosin and yohimbine, inhibitors of sympathomimetic amines, or with indomethacin, inhibitor of the cyclo-oxygenase pathway, reduced Lys49 PLA(2)-induced hyperalgesia without interfering with the nociceptive activity of Asp49 PLA(2). The hyperalgesic response to both myotoxins was not modified by pretreatment with celecoxib, an inhibitor of the cyclo-oxygenase type II, by zileuton, an inhibitor of the lipoxygenase pathway or by N(g)-methyl-L-arginine (LNMMA), an inhibitor of nitric oxide synthase. These results suggest that Asp49 and Lys49 PLA(2)s are important hyperalgesic components of B. asper venom, and that Lys49 and Asp49 PLA(2)s exert their algogenic actions through different molecular mechanisms.

  10. 1,5-Dimethylhexylamine (octodrine) in sports and weight loss supplements: Natural constituent or synthetic chemical? (United States)

    Wang, Mei; Haider, Saqlain; Chittiboyina, Amar G; Parcher, Jon F; Khan, Ikhlas A


    In the past years, there has been a mounting trend toward the addition of sympathomimetic stimulants in sports and weight loss supplements sold in the US and claimed to be from natural constituents. The latest among those pharmaceutical stimulants is 1,5-dimethylhexylamine (1,5-DMHA or octodrine), an ingredient in newly introduced sports and weight loss supplements with its 'natural' origin being cited from Aconitum or Kigelia plants. In order to validate the natural existence of 1,5-DMHA, two GC/MS methods were developed. One method involved using thick film megabore capillary columns to analyze the underivatized 1,5-DMHA. The second method was to determine enantiomeric distribution of 1,5-DMHA. Fifteen Aconitum or Kigelia plant samples originating from various locations were analyzed, and none of them contained 1,5-DMHA within the limit of detection (25 ng/mL) of the method. In contrast, although 1,5-DMHA was listed on the labels or website for all the 13 dietary supplements, only four products were found to contain this compound, with the highest quantity being reported as 112 mg per serving size. This is equivalent to more than three times the highest pharmaceutical dose established in Europe. The enantiomeric ratios of 1,5-DMHA in these products were determined to be between 0.9-1.0 (expressed as peak area ratio of one enantiomer over another), suggesting racemic nature. Interestingly, two byproducts from 1,5-DMHA synthesis were identified in commercial supplements containing 1,5-DMHA, indicating that 1,5-DMHA indeed originated from a poor quality source. Overall, the significant amount of 1,5-DMHA observed in the supplements, the enantiomeric distribution and the presence of the synthetic byproducts all suggested the synthetic origin of 1,5-DMHA in the commercial products. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Continuous Renal Replacement Therapy and Extracorporeal Membrane Oxygenation in Cardias Surgery

    Directory of Open Access Journals (Sweden)

    S. V. Kolesnikov


    Full Text Available Objective: to analyze the combined use of extracorporeal membrane oxygenation (ECMO and continuous renal replacement therapy with switching into the ECMO circuit in cardiac surgical patients over 18 years of age and to reveal predictors of a fatal outcome in this combination of auxiliary organ support techniques. Materials and methods. The retrospective cohort study postoperatively used a combination of ECMO and continuous renal replacement therapy in 27 cardiac surgical patients aged over 18 years with severe cardiopulmonary insufficiency concurrent with acute kidney lesion. In all cases, the continuous renal replacement therapy circuit was switched into the line after an ECMO pump. The end points of the study were the duration of dialysis-dependent acute renal failure, the frequency of complications, and hospital mortality. Results. In all cases with a favorable outcome, the duration of continuous renal replacement therapy was 3 days longer than that of ECMO. There were no cases of recovery if the duration of continuous renal replacement therapy was shorter than that of ECMO and the duration of the latter was more than 10 days. The duration of sympathomimetic support (>3.5 days was shown to be an independent and significant predictor of death (AUC 0.99; CI 99.9%, 0.96—1.0 in the patients receiving continuous renal replacement therapy and ECMO. It was established that the number of inotrophic drugs (>2 and the highest lactate level (>1.99 mmol/l could be used to predict hospital mortality in patients with acute kidney injury and severe cardiopulmonary insufficiency (AUC 0.85 and 0.86; sensitivity/specificity 0.83/0.67 and 0.86/0.67, respectively.Conclusion. The concurrent use of ECMO and continuous renal replacement therapy in severe cardiac surgical patients with potentially reversible cardiopulmonary insufficiency and acute kidney injury is a sound and complementary combination of auxiliary organ support techniques.  

  12. Evidence for an association between tako-tsubo cardiomyopathy and bronchial asthma: retrospective analysis in a primary care hospital. (United States)

    von Blotzheim, Leonardo Glutz; Christen, Stefan; Wieser, Stephan; Ulrich, Silvia; Huber, Lars C


    We investigated the prevalence of bronchial asthma in patients with Tako-Tsubo Syndrome (TTS). This retrospective case-series study was conducted in a primary care hospital in Zurich, Switzerland. Data of all patients with newly diagnosed TTS (2002 - 2012) were assessed electronically by the use of ICD-10. Asthma prevalence was compared to published epidemiologic data. Bronchial asthma is characterized by airway inflammation and, during attack, release of endogenous catecholamines. Sympathomimetic drugs are the mainstay of treatment for asthma patients. Likewise, catecholamine mediated diffuse microvascular myocardial dysfunction seems to be of critical importance for the development of TTS. 20 cases of TTS were identified. 90% were female, showed a median age of 70±13y [25y - 90y], an apical and/or midventricular ballooning pattern with preserved basal function and a median initial LVEF of 34±9% [25% - 55%]. 65% of patients underwent coronary angiography to rule out significant coronary artery disease. Hypertension was present in 45% of patients, 35% were smokers, none was suffering from diabetes. Prevalence of asthma in patients with TTS was significantly higher compared to the normal population (25% vs. 7%, p=0.012). In 30% of the TTS patients an iatrogenic cause for development of TTS was identified. Prevalence of asthma was significantly higher in patients with TTS compared to epidemiologic data from an age-matched population. Phenotypes of patients developing obstructive ventilatory disease and TTS might share common pathogenic mechanisms beyond the use of bronchodilatators. In addition, we identified other iatrogenic etiologies in patients with TTS.

  13. Serotonergic and adrenergic drug interactions associated with linezolid: a critical review and practical management approach. (United States)

    Ramsey, Tasha D; Lau, Tim Ty; Ensom, Mary Hh


    To describe the evidence for serotonergic and adrenergic drug interactions with linezolid and discuss clinical management strategies. A literature search of PubMed (1947-November 2012), MEDLINE (1946-November 2012), EMBASE (1974-November 2012), and International Pharmaceutical Abstracts (1970-November 2012) was conducted using the terms linezolid, drug interaction, serotonin syndrome, serotonin toxicity, sympathomimetic, serotonergic agents, and adrenergic agents. Citations of retrieved articles were also reviewed. English-language articles describing coadministration of serotonergic or adrenergic agents with linezolid to humans were included. Studies published only in abstract form were excluded. One prospective study, 6 retrospective studies, and 24 case reports were identified describing a serotonergic or adrenergic drug interaction. Incidence of serotonin syndrome in patients on linezolid and serotonergic agents ranged between 0.24% and 4%. Serotonergic agents determined to have probable (according to the Horn Drug Interaction Probability Scale) linezolid interactions in case reports included meperidine, citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, and venlafaxine. Serotonergic agent dose and duration of coadministration with linezolid did not appear to influence the occurrence of serotonin syndrome. Adrenergic medication coadministration was associated with a possible drug interaction as determined by the Horn Drug Interaction Probability Scale but did not appear to result in clinically significant drug interactions with linezolid. Linezolid-associated serotonergic drug interactions occur more commonly than adrenergic interactions. Serotonergic interactions considered probable according to the Horn Drug Interaction Probability Scale do not appear to correlate with drug dosage; time of onset ranges from serotonergic agent cannot be avoided, clinicians should be aware of the symptoms and management of serotonergic toxicity; close

  14. Mephedrone (4-methylmethcathinone; 'meow meow'): chemical, pharmacological and clinical issues. (United States)

    Schifano, Fabrizio; Albanese, Antonio; Fergus, Suzanne; Stair, Jackie L; Deluca, Paolo; Corazza, Ornella; Davey, Zoe; Corkery, John; Siemann, Holger; Scherbaum, Norbert; Farre', Magi'; Torrens, Marta; Demetrovics, Zsolt; Ghodse, A Hamid


    Recently, those substances deriving from the active ingredient of the Khat plant, cathinone, have been rising in popularity. Indeed, 4-methylmethcathinone (mephedrone; 'meow meow' and others) has been seen by some as a cheaper alternative to other classified recreational drugs. We aimed here at providing a state-of-the-art review on mephedrone history and prevalence of misuse, chemistry, pharmacology, legal status, product market appearance, clinical/management and related fatalities. Because of the limited evidence, some of the information here presented has been obtained from user reports/drug user-orientated web sites. The most common routes for mephedrone recreational use include insufflation and oral ingestion. It elicits stimulant and empathogenic effects similar to amphetamine, methylamphetamine, cocaine and MDMA. Due to its sympathomimetic actions, mephedrone may be associated with a number of both physical and psychopathological side effects. Recent preliminary analysis of recent UK data carried out in 48 related cases have provided positive results for the presence of mephedrone at postmortem. Within the UK, diffusion of mephedrone may have been associated with an unprecedented combination of a particularly aggressive online marketing policy and a decreasing availability/purity of both ecstasy and cocaine. Mephedrone has been recently classified in both the UK and in a number of other countries as a measure to control its availability. Following this, a few other research psychoactives have recently entered the online market as yet unregulated substances that may substitute for mephedrone. Only international collaborative efforts may be able to tackle the phenomenon of the regular offer of novel psychoactive drugs.

  15. Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects. (United States)

    Dolder, Patrick C; Müller, Felix; Schmid, Yasmin; Borgwardt, Stefan J; Liechti, Matthias E


    3,4-Methylenedioxymethamphetamine (MDMA) is used recreationally and investigated as an adjunct to psychotherapy. Methylphenidate and modafinil are psychostimulants that are used to treat attention-deficit/hyperactivity disorder and narcolepsy, respectively, but they are also misused as cognitive enhancers. Little is known about differences in the acute effects of equally cardiostimulant doses of these stimulant-type substances compared directly within the same subjects. We investigated the acute autonomic, subjective, endocrine, and emotional effects of single doses of MDMA (125 mg), methylphenidate (60 mg), modafinil (600 mg), and placebo in a double-blind, cross-over study in 24 healthy participants. Acute drug effects were tested using psychometric scales, the Facial Emotion Recognition Task (FERT), and the Sexual Arousal and Desire Inventory (SADI). All active drugs produced comparable hemodynamic and adverse effects. MDMA produced greater increases in pupil dilation, subjective good drug effects, drug liking, happiness, trust, well-being, and alterations in consciousness than methylphenidate or modafinil. Only MDMA reduced subjective anxiety and impaired fear recognition and led to misclassifications of emotions as happy on the FERT. On the SADI, only MDMA produced sexual arousal-like effects. Only MDMA produced marked increases in cortisol, prolactin, and oxytocin. In contrast to MDMA, methylphenidate increased subjective anxiety, and methylphenidate and modafinil increased misclassifications of emotions as angry on the FERT. Modafinil had no significant subjective drug effects but significant sympathomimetic and adverse effects. MDMA induced subjective, emotional, sexual, and endocrine effects that were clearly distinct from those of methylphenidate and modafinil at the doses used.

  16. Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine. (United States)

    Dos Santos, Rafael G; Valle, Marta; Bouso, José Carlos; Nomdedéu, Josep F; Rodríguez-Espinosa, José; McIlhenny, Ethan H; Barker, Steven A; Barbanoj, Manel J; Riba, Jordi


    Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting β-carboline alkaloids that render DMT orally active. The tea, obtained from Banisteriopsis caapi and Psychotria viridis, has traditionally been used for religious, ritual, and medicinal purposes by the indigenous peoples of the region. More recently, the syncretistic religious use of ayahuasca has expanded to the United States and Europe. Here we conducted a double-blind randomized crossover clinical trial to investigate the physiological impact of ayahuasca in terms of autonomic, neuroendocrine, and immunomodulatory effects. An oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight) was compared versus a placebo and versus a positive control (20 mg d-amphetamine) in a group of 10 healthy volunteers. Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects that were absent after amphetamine. Both drugs increased pupillary diameter, with ayahuasca showing milder effects. Prolactin levels were significantly increased by ayahuasca but not by amphetamine, and cortisol was increased by both, with ayahuasca leading to the higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased, whereas natural killer cells were increased. Maximum changes occurred around 2 hours, returning to baseline levels at 24 hours. In conclusion, ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation, and a time-dependent modulatory effect on cell-mediated immunity. Future studies on the health impact of long-term ayahuasca consumption should consider the assessment of immunological status in regular users.

  17. Muscle cramps and elevated serum creatine phosphokinase levels induced by beta-adrenoceptor blockers. (United States)

    Imai, Y; Watanabe, N; Hashimoto, J; Nishiyama, A; Sakuma, H; Sekino, H; Omata, K; Abe, K


    We have assessed the propensity of beta-adrenoceptor blockers to cause muscle cramps and to raise the serum creatine phosphokinase (CPK) level in 78 patients with essential hypertension. After a control period, a beta-adrenoceptor blocker without intrinsic sympathomimetic activity (ISA; propranolol, metoprolol or arotinolol) was administered for three months. Thereafter, the patients were randomised to receive a beta-adrenoceptor blocker with ISA (pindolol or carteolol) for three months or a beta-adrenoceptor blocker without ISA for a further three months. This pattern was continued until all beta-adrenoceptor blockers had been given. At the end of each period, CPK and CPK-MB levels were measured. Of the 78 subjects, muscle cramps occurred in 27 during treatment with pindolol and 32 during treatment with carteolol. No complaints were made by subjects treated with propranolol and arotinolol, but muscle cramps were reported in 2 treated with metoprolol. While muscle cramps were caused both by pindolol and carteolol in 16 subjects, they were caused by either of these drugs in the remainder of the subjects. Muscle cramp occurred mainly in the calves when the patients were in bed at night. Serum CPK and CPK-MB levels increased significantly during treatment with pindolol (control period vs pindolol, CPK = 96 vs 133, CPK-MB = 14 vs 18 or carteolol (CPK = 117, CPK-MB = 18 while the levels during treatment with propranolol, arotinolol and metoprolol did not change from those in the control period.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Pharmacotherapy of binge-eating disorder: a review. (United States)

    Goracci, Arianna; di Volo, Silvia; Casamassima, Francesco; Bolognesi, Simone; Benbow, Jim; Fagiolini, Andrea


    The purpose of this article is to provide a comprehensive review of pharmacotherapy for binge eating disorder, including new therapeutic approaches such as centrally acting sympathomimetics, nootropics, lisdexamfetamine, and substance abuse treatment agents such as acamprosate, sodium oxybate, baclofen, and naltrexone. The study was conducted by searching the MEDLINE database using the keywords "binge eating disorder," "obesity," and "pharmacological therapy."All available studies on each drug dating from 1988 to the present were considered, focusing mainly on randomized controlled trials (RCTs). Other types of studies were considered when no RCTs were found. We drafted separate tables for open-label studies (), RCT (), and retrospective studies (). Each study is detailed by the number of subjects, additional design considerations, doses, results, additional main comparators, and study limitations. The data emerging from this study seem to show that, at least in the short term, some specific medications within the classes of antidepressants, anticonvulsants, and antiobesity agents may prove promising in achieving the main objectives in the treatment of binge eating disorder: reducing the frequency of binge eating, reducing weight, and improving the associated psychopathology. The major limitation in interpreting these results is the short duration of the studies and the lack of adequately sized trials, or trials including patients with medical comorbidities.Good results are being obtained with new combinations of drugs and with substance abuse treatment agents. Although the precise nature of the relationship between substance use disorders and binge eating disorder remains to be clarified, the evidence suggests that treatments recognized as effective for substance use disorders may be useful as novel treatments for binge eating disorder. This field of research remains open to future studies with more precise methodological approaches and more detailed parameter

  19. [What illegal substances are used by sportsmen? a study in Midi-Pyrénées Doping Preventing Medical Centre (AMPD-MP)]. (United States)

    Senard-Ojero, Ana; Durrieu, Geneviève; Depiesse, Frédéric; Schmitt, Laurent; Riviere, Daniel; Montastruc, Jean-Louis


    Doping Preventing Medical Centres (Antennes Médicales de Prévention du Dopage) were established in France in 2000 in order to help sportsmen using illegal substances. These services are also information centres on illegal substances (drugs or others) used in sport. The aim of the study was to analyze the characteristics of sportsmen outpatient clinics in Antenne Médicale de Prevention du Dopage Midi-Pyrénées (AMPD-MP). We present the results of outpatient clinics in AMPD-MP from 2002 to 2008. A descriptive analysis of demographic data, substances used and sports practised were performed. During this 7 year-period, 35 outpatient clinics were performed [32 men, 3 women, mean age: 28 years (extreme values: 18-47; 10 patients ≥ 30 years)]. They were mainly involved in national (16), international (8) or regional (7) competitions. The main sports involved were rugby (9) followed by cycling (5), athletics (3) and body-building (3). The most frequently used illegal substances were cannabis (15) followed by glucocorticoïds (9), androgens (4), indirect sympathomimetics amphetaminics (4), beta 2 adrenergic agonists (2) and NSAIDs (2). Two veterinary substances (clenbuterol, boldone-veterinaire) were also found in body-builders. This study shows a clear under use of Doping Preventing Medical Centres by sportsmen and practitioners. It also indicates a relative high age for sportsmen referred to the centre. The main sports involved were rugby and cycling. Cannabis and glucocorticoïds were the drugs more often involved in doping behaviours.

  20. Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflex. (United States)

    Hysek, Cédric M; Liechti, Matthias E


    Pupillometry can be used to characterize autonomic drug effects. This study was conducted to determine the autonomic effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), administered alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin, on pupillary function. Infrared pupillometry was performed in five placebo-controlled randomized studies. Each study included 16 healthy subjects (eight men, eight women) who received placebo-MDMA (125 mg), placebo-placebo, pretreatment-placebo, or pretreatment-MDMA using a crossover design. MDMA produced mydriasis, prolonged the latency, reduced the response to light, and shortened the recovery time. The impaired reflex response was associated with subjective, cardiostimulant, and hyperthermic drug effects and returned to normal within 6 h after MDMA administration when plasma MDMA levels were still high. Mydriasis was associated with changes in plasma MDMA concentration over time and longer-lasting. Both reboxetine and duloxetine interacted with the effects of MDMA on pupillary function. Clonidine did not significantly reduce the mydriatic effects of MDMA, although it produced miosis when administered alone. Carvedilol and doxazosin did not alter the effects of MDMA on pupillary function. The MDMA-induced prolongation of the latency to and reduction of light-induced miosis indicate indirect central parasympathetic inhibition, and the faster recovery time reflects an increased sympathomimetic action. Both norepinephrine and serotonin mediate the effects of MDMA on pupillary function. Although mydriasis is lasting and mirrors the plasma concentration-time curve of MDMA, the impairment in the reaction to light is associated with the subjective and other autonomic effects of MDMA and exhibits acute tolerance.

  1. Some aspects concerning modifications of the List of Prohibited Substances and Methods in sport

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    A Pokrywka


    Full Text Available In 1967 the International Olympic Committee (IOC founded Medical Commission to organize and supervise fight against doping. At that time, the Commission published the first list of substances prohibited for use in sport to meet the need of anti-doping testing at the 1968 Olympic Games. The Prohibited List included stimulants, sympathomimetic amines, narcotics (narcotic analgesics, antidepressants and tranquilizers. For years the list was expanding and underwent modifications, mainly prior to successive Olympic Games. Starting from 1 January 2004, the World Anti-Doping Agency (WADA has assumed the role of the main coordinator in fight against doping. WADA significantly modified the list of prohibited substances and methods (the Prohibited List. These modifications initiated changes, whose effects can be observed in three main areas of sport and anti-doping i.e. in: athletes, doping control laboratories, and sport entourage. In Poland, the removal some substances from the List or the addition other compounds to the basic List caused an increase of usage of pseudoephedrine and caffeine by athletes and a decrease of number of positive doping cases with cannabinoids and glucocorticosteroids. The annual modification of the Prohibited List by WADA and subsequent introduction of new examples of prohibited substances strengthened the world anti-doping system. Considering the open character of the list a regular update would be expected, especially indicating prohibited or permitted status of new substances and drugs. It would be advisable to publish, on the WADA website, some additional information regarding those substances which cause the most interpretation problems.

  2. Power spectral analysis of heart rate variability in cynomolgus monkeys in safety pharmacology studies: comparative study with beagle dogs. (United States)

    Champeroux, Pascal; Martel, Eric; Jude, Sebastien; Laigot, Christine; Laveissière, Arnaud; Weyn-Marotte, Andrée-Anne; Fowler, John Sinclair Lawrence; Maurin, Anne; Richard, Serge; Babuty, Dominique


    Power spectral analysis of heart rate variability is a tool known to provide information of interest on the autonomic control of heart rate in human. However, its use and its conditions of application and interpretation for safety purposes are not well defined for cardiovascular safety pharmacology studies. Likewise, data of power spectral analysis of heart rate variability in cynomolgus monkeys, a species often appropriate for use as second non rodent species in preclinical safety programmes, are not available. This study was designed to evaluate the relevance of this biomarker in this non human primate species, and to compare results with those from beagle dogs under the conditions of safety evaluation studies. Power spectral analysis of heart rate variability was performed on data collected in both species by telemetry following a standard design for cardiovascular safety pharmacology studies. Various pharmacological agents were tested in order to compare the profile of responses in both species after modifying the autonomic nervous balance. Heart rate variability in cynomolgus monkeys is mainly driven by the parasympathetic nervous system as in beagle dogs although vagal tone is less than in dogs. Power spectral analysis of heart rate variability allows detection of interaction with the autonomic nervous system in both species in all investigated situations, i.e. sympatholytic/sympathomimetic and parasympatholytic/parasympathomimetic drug induced effects. However, due to species difference in the autonomic control of heart rate, cynomolgus monkeys are likely to be more sensitive than beagle dogs for assessment of sympatholytic properties. This study confirms that power spectral analysis of heart rate variability from data derived from ECG recordings in telemetry studies is applicable in cardiovascular safety pharmacology studies and may provide relevant information about possible interaction with the autonomic nervous system when new drug entities are evaluated

  3. Effects of mydriatic agents in cockatoos, African gray parrots, and Blue-fronted Amazon parrots. (United States)

    Ramer, J C; Paul-Murphy, J; Brunson, D; Murphy, C J


    To compare, in psittacines, the mydriatic effects of several topically applied curariform, sympathomimetic, and parasympatholytic drugs with and without the addition of surface-acting penetrating agents. Prospective, randomized controlled trial. 10 adult cockatoos (Cacatua sulphurea subspecies), 2 adult African gray parrots (Psittacus erithacus), and 3 adult Blue-fronted Amazon parrots (Amazona aestiva). Three curariform drugs (d-tubocurarine, pancuronium, and vecuronium bromide) and 2 autonomic drugs (atropine and phenylephrine hydrochloride) were evaluated. Drugs were tested with and without the addition of a surface-acting penetrating agent, either saponin or benzalkonium chloride. The agent that resulted in the most significant change in pupillary diameter with the fewest systemic side effects in the cockatoos then was evaluated for its effects in the African gray parrots and the Blue-fronted Amazon parrots. During each drug trial, 1 eye was randomly selected to receive the control drug (0.9% NaCl), and the opposite eye was selected to receive the test drug. Each pupil was videotaped 5 (cockatoos only), 15, 30, 45, 60, and 75 minutes after treatment. Pupil diameters were measured by use of a computerized image analysis system. Data for pupil size were analyzed by means of repeated measures ANOVA. Vecuronium without the addition of a surface-acting penetrating agent produced the most consistent and greatest pupillary dilatation in all 3 species with the fewest systemic side effects. Vecuronium is potentially a clinically useful, topical mydriatic agent for use in avian species. Documented differences in the prevalence of systemic side effects between species suggests that caution should be applied when applying this drug bilaterally.

  4. Dietary supplement adverse events: report of a one-year poison center surveillance project. (United States)

    Haller, Christine; Kearney, Tom; Bent, Stephen; Ko, Richard; Benowitz, Neal; Olson, Kent


    The safety and efficacy of dietary supplements is of growing concern to regulators, health-care providers and consumers. Few scientific data exist on clinical effects and potential toxicities of marketed products. Harmful supplements may not be identified for months or years with existing adverse event monitoring mechanisms. Retrospective review of poison center statistics to capture supplement-associated toxicity also has limitations. We collaborated with the FDA Center for Food Safety and Nutrition (CFSAN) to conduct a 1-year prospective surveillance study of dietary supplement-related poison control center calls in 2006. Prompt follow-up of symptomatic cases, laboratory analysis of implicated dietary supplements, and causality assessment by a case review expert panel were performed. Of 275 dietary supplements calls, 41% involved symptomatic exposures; and two-thirds were rated as probably or possibly related to supplement use. Eight adverse events required hospital admission. Sympathomimetic toxicity was most common, with caffeine products accounting for 47%, and yohimbe products accounting for 18% of supplement-related symptomatic cases. Suspected drug-herb interactions occurred in 6 cases, including yohimbe co-ingested with buproprion (1) and methamphetamine (3), and additive anticoagulant/antiplatelet effects of NSAIDs taken with fish oils (1) and ginkgo (1). Laboratory analysis identified a pharmacologically active substance in 4 cases; supplement toxicity was ruled unlikely when analytical testing was negative in 5 cases. Most supplement-related adverse events were minor. Clinically significant toxic effects were most frequently reported with caffeine and yohimbe-containing products. Active surveillance of poison control center reports of dietary supplement adverse events enables rapid detection of potentially harmful products, which may facilitate regulatory oversight.

  5. Adderall induced inverted-Takotsubo cardiomyopathy. (United States)

    Alsidawi, Said; Muth, James; Wilkin, James


    Takotsubo Cardiomyopathy (TTC), also known as stress-induced cardiomyopathy, was initially described in Japan in 1990. Both illicit and prescription drugs have added to the growing list of insulting stressors. We describe an interesting case of atypical TTC triggered by adderall overdose. A 19-year-old female was brought to the Emergency Department after ingesting 30 Adderall tablets. She was complaining of pressure like chest pain and shortness of breath. Her cardiac enzymes were elevated but the electrocardiogram was unremarkable. Echocardiography identified an ejection fraction (EF) of 25-30% with severe hypokinesis of the base and a preserved apex. Cardiac angiography demonstrated normal coronary arteries with an EF of 35%, hyperkinetic apex and akinetic base consistent with the diagnosis of inverted-TTC. Her symptoms resolved in 24 hrs. Repeat echocardiogram performed 3 days later showed an EF of 60% with no regional wall motion abnormalities. TTC can be identified as a rapid development of severe and reversible left ventricular dysfunction extending beyond the territory of a single epicardial coronary artery in the absence of coronary artery disease or pheochromocytoma. Clinical presentation can be challenging and very hard to distinguish from acute myocardial infarction. Medication induced-TTC has been reported. In our case, the patient overdosed on Adderall which is a sympathomimetic medication. Cardiac imaging identified wall motion abnormalities consistent with inverted type TTC. Restoration of left ventricular function within days confirms the diagnosis of TTC. In conclusion, this case offers an interesting insight into the pathophysiology of TTC. Copyright © 2011 Wiley Periodicals, Inc.

  6. Clenbuterol toxicity: a NSW poisons information centre experience. (United States)

    Brett, Jonathan; Dawson, Andrew H; Brown, Jared A


    To describe the epidemiology and toxicity of clenbuterol in exposures reported to the NSW Poisons Information Centre (NSWPIC). Retrospective observational study analysing data from all calls about clenbuterol exposure recorded in the NSWPIC database from 1 January 2004 to 31 December 2012. The NSWPIC coversthe Australian jurisdictions New South Wales, Tasmania and the Australian Capital Territory 24 hours a day and provides after-hours cover for the rest of Australia for 7 nights each fortnight. Total number of exposures, source of call (hospital, health care worker, member of the public), time from exposure to call, reasons for drug use, clinical features and advice given. Callers reported 63 exposures to clenbuterol, with a dramatic increase from three in 2008 to 27 in 2012. Of the 63 calls, 35 were from hospital, two from paramedics, one from general practice and 21 direct from the public. At least 53 patients (84%) required hospitalisation. The commonest reasons for use were bodybuilding and slimming. The most common features were tachycardia (24 patients), gastrointestinal disturbance (16) and tremor (11). Exposure was also associated with cardiotoxicity including one cardiac arrest in a 21-year-old man. Although a well recognised doping issue among elite athletes, clenbuterol use has spread out into the general public, especially during 2012, and should be considered in patients using bodybuilding or slimming products who present with protracted sympathomimetic features. The potential for misuse of this substance requires reconsideration of its current poison schedule registration and its availability.

  7. Clinical characteristics of mephedrone toxicity reported to the UK National Poisons Information Service (United States)

    James, D; Adams, R D; Spears, R; Cooper, G; Lupton, D J; Thompson, J P


    Objective To describe the patterns and clinical features of toxicity related to recreational use of mephedrone and other cathinones in the UK using data collected by the National Poisons Information Service (NPIS). Methods The number of accesses to TOXBASE, the NPIS online poisons information database, details of consecutive cases uploaded onto TOXBASE and the number and details of telephone enquiries made to the NPIS by health professionals in the UK were collected for the period March 2009 to February 2010. Results Over the year of study there were 2901 TOXBASE accesses and 188 telephone enquiries relating to cathinones, the majority relating to mephedrone (TOXBASE 1664, telephone 157), with a month-on-month increase in numbers. In 131 telephone enquiries concerning mephedrone, alone or in combination with alcohol, common clinical features reported included agitation or aggression (n=32, 24%, 95% CI 18% to 33%), tachycardia (n=29, 22%, 95% CI 16% to 30%), confusion or psychosis (n=18, 14%, 95% CI 9% to 21%), chest pain (n=17, 13%, 95% CI 8% to 20%), nausea (n=15, 11%, 95% CI 7% to 18%), palpitations (n=14, 11%, 95% CI 6% to 18%), peripheral vasoconstriction (n=10, 8%, 95% CI 4% to 14%) and headache (n=7, 5%, 95% CI 2% to 11%). Convulsions were reported in four cases (3%, 95% CI 1% to 8%). One exposed person died following cardiac arrest (1%, 95% CI 0% to 4%), although subsequent investigation suggested that mephedrone was not responsible. Conclusions Toxicity associated with recreational mephedrone use is increasingly common in the UK. Sympathomimetic adverse effects are common and severe effects are also reported. Structured data collected by the NPIS may be of use in identifying trends in poisoning and in establishing toxidromes for new drugs of abuse. PMID:20798084

  8. The costo-uterine muscle of the rat contains a homogeneous population of beta-adrenoceptors. (United States)

    Hartley, M. L.; Pennefather, J. N.


    The effects of two selective beta-adrenoceptor antagonists on the inhibitory responses to some sympathomimetic amines of electrically-stimulated preparations of costo-uterine muscle, taken from virgin rats, have been examined quantitatively. pA2 values for the antagonist, atenolol (beta 1-selective) and ICI 118,551 (beta 2-selective) were obtained using as agonists, fenoterol (beta 2-selective agonist) and noradrenaline (alpha- and beta-adrenoceptor agonist, beta 1-selective); and in addition, with ICI 118,551 only, isoprenaline (beta-agonist, non-selective) and adrenaline (alpha- and beta-adrenoceptor agonist, beta 2-selective). Catecholamine uptake mechanisms and alpha-adrenoceptors were not blocked in any of these experiments. Atenolol competitively antagonized the effects of fenoterol and noradrenaline to a similar extent, the pA2 values being 5.4 and 5.7, respectively. ICI 118,551 competitively antagonized the effects of fenoterol, isoprenaline, adrenaline and noradrenaline to a similar extent; pA2 values ranged from 8.7 with noradrenaline to 9.1 with isoprenaline. These results extend our previous observations which indicated that the adrenoceptors mediating inhibition of electrically-evoked contractions of costo-uterine muscle of the virgin rat are homogeneous and of the beta 2-subtype. The potency of the beta 1-selective agonist RO 363 in producing inhibition of electrically-evoked contractions of this tissue was also examined. RO 363 was 200 times less potent than isoprenaline but was a full agonist. This indicates that there is efficient coupling between beta 2-adrenoceptor activation and tissue response in this non-innervated preparation. PMID:2858239

  9. When good times go bad: managing ‘legal high’ complications in the emergency department

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    Caffrey CR


    Full Text Available Charles R Caffrey, Patrick M Lank Department of Emergency Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Abstract: Patients can use numerous drugs that exist outside of existing regulatory statutes in order to get “legal highs.” Legal psychoactive substances represent a challenge to the emergency medicine physician due to the sheer number of available agents, their multiple toxidromes and presentations, their escaping traditional methods of analysis, and the reluctance of patients to divulge their use of these agents. This paper endeavors to cover a wide variety of “legal highs,” or uncontrolled psychoactive substances that may have abuse potential and may result in serious toxicity. These agents include not only some novel psychoactive substances aka “designer drugs,” but also a wide variety of over-the-counter medications, herbal supplements, and even a household culinary spice. The care of patients in the emergency department who have used “legal high” substances is challenging. Patients may misunderstand the substance they have been exposed to, there are rarely any readily available laboratory confirmatory tests for these substances, and the exact substances being abused may change on a near-daily basis. This review will attempt to group legal agents into expected toxidromes and discuss associated common clinical manifestations and management. A focus on aggressive symptom-based supportive care as well as management of end-organ dysfunction is the mainstay of treatment for these patients in the emergency department. Keywords: legal highs, novel psychoactive substances, toxicology, opioid toxidrome, anticholinergic toxidrome, sympathomimetic toxidrome, hallucinogens, inhalants

  10. Pharmacokinetics and Concentration-Effect Relationship of Oral LSD in Humans. (United States)

    Dolder, Patrick C; Schmid, Yasmin; Haschke, Manuel; Rentsch, Katharina M; Liechti, Matthias E


    The pharmacokinetics of oral lysergic acid diethylamide are unknown despite its common recreational use and renewed interest in its use in psychiatric research and practice. We characterized the pharmacokinetic profile, pharmacokinetic-pharmacodynamic relationship, and urine recovery of lysergic acid diethylamide and its main metabolite after administration of a single oral dose of lysergic acid diethylamide (200 μg) in 8 male and 8 female healthy subjects. Plasma lysergic acid diethylamide concentrations were quantifiable (>0.1 ng/mL) in all the subjects up to 12 hours after administration. Maximal concentrations of lysergic acid diethylamide (mean±SD: 4.5±1.4 ng/mL) were reached (median, range) 1.5 (0.5-4) hours after administration. Concentrations then decreased following first-order kinetics with a half-life of 3.6±0.9 hours up to 12 hours and slower elimination thereafter with a terminal half-life of 8.9±5.9 hours. One percent of the orally administered lysergic acid diethylamide was eliminated in urine as lysergic acid diethylamide, and 13% was eliminated as 2-oxo-3-hydroxy-lysergic acid diethylamide within 24 hours. No sex differences were observed in the pharmacokinetic profiles of lysergic acid diethylamide. The acute subjective and sympathomimetic responses to lysergic acid diethylamide lasted up to 12 hours and were closely associated with the concentrations in plasma over time and exhibited no acute tolerance. These first data on the pharmacokinetics and concentration-effect relationship of oral lysergic acid diethylamide are relevant for further clinical studies and serve as a reference for the assessment of intoxication with lysergic acid diethylamide. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  11. Slimmer or fertile? Pharmacological mechanisms involved in reduced sperm quality and fertility in rats exposed to the anorexigen sibutramine.

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    Cibele S Borges

    Full Text Available Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin

  12. The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature (United States)

    Alawi, Khadija M.; Aubdool, Aisah A.; Liang, Lihuan; Wilde, Elena; Vepa, Abhinav; Psefteli, Maria-Paraskevi; Brain, Susan D.; Keeble, Julie E.


    Transient receptor potential vanilloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling. Recently, it has been discovered that TRPV1 receptors also regulate basal body temperature in multiple species from mice to humans. In the present study, we investigated whether TRPV1 modulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radiotelemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected intraperitoneally. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected subcutaneously. In WT mice, the TRPV1 antagonist, AMG9810, caused significant hyperthermia, associated with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the β-adrenoceptor antagonist propranolol, the mixed α-/β-adrenoceptor antagonist labetalol, and the α1-adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensation. d-Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence that TRPV1 controls thermoregulation upstream of the SNS, providing a potential therapeutic target for sympathetic hyperactivity thermoregulatory disorders.—Alawi, K. M., Aubdool, A. A., Liang, L., Wilde, E., Vepa, A., Psefteli, M.-P., Brain, S. D., Keeble, J. E. The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature. PMID:26136480

  13. Pediatrician’s cough and cold medication prescription for hypothetical cases – A cross-sectional multi-centric study

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    Sudha Chandelia


    Full Text Available Background: Concerns over inappropriate use of cough and cold medication (CCM in children have been raised. In addition to being ineffective, these are now considered toxic for young children. Despite this fact studies from some regions have shown high use of these medications by physicians. However data on pediatricians and from India are negligible. Aim: To study the burden and patterns of cough and cold medications use by pediatricians for hypothetical cases. Methods: In this cross-sectional study; 172 pediatricians of various hospitals of Delhi and Haryana were enrolled from February 15 to March 15, 2012. They were contacted personally by authors and asked to write their prescriptions for two hypothetical case scenarios [having cough and cold] of two different age groups; (1 less than 2 years and (2 2–5 years. We made two categories as recommendations exist for children less than 2 years while recommendations for the second category are underway. Results were summarized as percentages, counts and; presented in tables and figures. Chi square test was used to establish association between categorical variables of subgroups. Results: Response rate was 93%. The most used CCM was antihistaminics (82% and systemic sympathomimetics (48%. The use of CCM was significantly less in teaching hospitals as compared to non-teaching (77% vs. 95%; p-value – 0.025. However there was no statistical difference in the practice of post graduates and more senior pediatricians (p value-0.895. No difference in CCM use in two age groups {(82% (less than 2 years vs. 85% (2–5 years; p-value – 0.531} was observed. Conclusion: Overall use of CCM is still high irrespective of patient age, pediatrician’s seniority or hospital setting. Efforts should be made to create awareness among the pediatricians regarding cautious use of these medications.

  14. Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B (United States)

    Youdim, Moussa B H; Gross, Aviva; Finberg, John P M


    Rasagiline [N-propargyl-1R(+)-aminoindan], was examined for its monoamine oxidase (MAO) A and B inhibitor activities in rats together with its S(−)-enantiomer (TVP 1022) and the racemic compound (AGN-1135) and compared to selegiline (1-deprenyl). The tissues that were studied for MAO inhibition were the brain, liver and small intestine.While rasagiline and AGN1135 are highly potent selective irreversible inhibitors of MAO in vitro and in vivo, the S(−) enantiomer is relatively inactive in the tissues examined.The in vitro IC50 values for inhibition of rat brain MAO activity by rasagiline are 4.43±0.92 nM (type B), and 412±123 nM (type A). The ED50 values for ex vivo inhibition of MAO in the brain and liver by a single dose of rasagiline are 0.1±0.01, 0.042±0.0045 mg kg−1 respectively for MAO-B, and 6.48±0.81, 2.38±0.35 mg kg−1 respectively for MAO-A.Selective MAO-B inhibition in the liver and brain was maintained on chronic (21 days) oral dosage with ED50 values of 0.014±0.002 and 0.013±0.001 mg kg−1 respectively.The degree of selectivity of rasagiline for inhibition of MAO-B as opposed to MAO-A was similar to that of selegiline. Rasagiline was three to 15 times more potent than selegiline for inhibition of MAO-B in rat brain and liver in vivo on acute and chronic administration, but had similar potency in vitro.These data together with lack of tyramine sympathomimetic potentiation by rasagiline, at selective MAO-B inhibitory dosage, indicate that this inhibitor like selegiline may be a useful agent in the treatment of Parkinson's disease in either symptomatic or L-DOPA adjunct therapy, but lack of amphetamine-like metabolites could present a therapeutic advantage for rasagiline. PMID:11159700

  15. The concept of peripheral modulation of bladder sensation. (United States)

    Eastham, Jane E; Gillespie, James I


    It is recognized that, as the bladder fills, there is a corresponding increase in sensation. This awareness of the volume in the bladder is then used in a complex decision making process to determine if there is a need to void. It is also part of everyday experience that, when the bladder is full and sensations strong, these sensations can be suppressed and the desire to void postponed. The obvious explanation for such altered perceptions is that they occur centrally. However, this may not be the only mechanism. There are data to suggest that descending neural influences and local factors might regulate the sensitivity of the systems within the bladder wall generating afferent activity. Specifically, evidence is accumulating to suggest that the motor-sensory system within the bladder wall is influenced in this way. The motor-sensory system, first described over 100 years ago, appears to be a key component in the afferent outflow, the afferent "noise," generated within the bladder wall. However, the presence and possible importance of this complex system in the generation of bladder sensation has been overlooked in recent years. As the bladder fills the motor activity increases, driven by cholinergic inputs and modulated, possibly, by sympathetic inputs. In this way information on bladder volume can be transmitted to the CNS. It can be argued that the ability to alter the sensitivity of the mechanisms generating the motor component of this motor-sensory system represents a possible indirect way to influence afferent activity and so the perception of bladder volume centrally. Furthermore, it is emerging that the apparent modulation of sensation by drugs to alleviate the symptoms of overactive bladder (OAB), the anti-cholinergics and the new generation of drugs the β 3 sympathomimetics, may be the result of their ability to modulate the motor component of the motor sensory system. The possibility of controlling sensation, physiologically and pharmacologically, by

  16. Adverse Cardiovascular Effects of Nitrous Oxide: It is not all about Hyperhomocysteinaemia

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    Ata Mahmoodpoor


    Full Text Available Once admired for its supposed safety, nitrous oxide is presently blamed to increase adverse cardiovascular effects through augmenting plasma homocysteine concentrations (1, 2. Hemodynamic alterations following the administration of nitrous oxide are extremely complicated and sometimes contradictory. Enhanced venous return, arterial pressure, pulmonary and systemic vascular resistance, cardiac output, pupillary dilation and diaphoresis occur under nitrous oxide administration consistent with sympathomimetic properties of nitrous oxide (3. Conversely, reductions in arterial pressure are also probable, especially in patients with coronary artery disease. Nitrous oxide can also depress myocardial contractility due to decreased availability of Ca2+ for contractile activation; yet, myocardial relaxation kinetics remains intact (4. In the presence of a volatile anesthetic, nitrous oxide decreases MVO2 (Myocardial oxygen consumption and myocardial O2 extraction which may exacerbate myocardial ischemia during concomitant reductions in arterial pressure in patients with coronary artery disease. Consequently, it could be conjectured that probable adverse cardiovascular effects following nitrous oxide administration are variable and consequent of a multi-variable phenomenon rather than a single variable such as increased levels of homocysteine. Studied purely focusing on the effects of nitrous oxide are difficult to conduct due to the numerous confounding factors. In a study by Myles et al., hyperhomocysteinemia has been introduced as the source of the adverse cardiovascular effects of nitrous oxide. However, in this study, increased inspired oxygen concentrations were used to overcome arterial desaturation (1. Given the fact that a constant volume and flow rates are used throughout the anesthesia in a particular patient, increasing the concentrations of oxygen would be associated with decreased delivered nitrous oxide and volatile anesthetic concentrations

  17. Effect of herbal Ephedra sinica and Evodia rutaecarpa on body composition and resting metabolic rate: a randomized, double-blind clinical trial in Korean premenopausal women. (United States)

    Kim, Ho-Jun; Park, Jung-Mi; Kim, Jin-Ah; Ko, Byeong-Pyo


    As obesity is becoming an epidemic, diet programs, including low-calorie diets, are continuously being developed. It is generally believed that a low-calorie diet is commonly followed by a resting metabolic rate decrease and ultimate weight regain. Ephedra sinica and evodia rutaecarpa are known to have sympathomimetic and anti-obesity effects. This study was a prospective; double-blinded, randomized and placebo-controlled clinical trial to evaluate the effects of ephedra sinica and evodia rutaecarpa on resting metabolic rate (RMR), body composition and short-term safety in obese Korean premenopausal women on a low-calorie diet. One hundred and twenty-five otherwise healthy obese women (body mass index > or =25 kg/m(2)) were recruited and randomly assigned to three groups: ephedra group (n = 41), evodia group (n = 45) and placebo group (n = 39). Subjects were administered ephedra extract in capsules (pseudo-ephedrine 31.52 mg) or evodia extract in capsules (evodiamine 6.75 mg, rutaecarpine 0.66 mg) or placebo capsules as well as participating in a low-calorie diet for 8 weeks. Resting metabolic rate and body composition were measured at baseline, 4 and 8 weeks. Basic serum tests were performed to evaluate the short-term safety and lipid-lowering effects of the herbs. All three groups showed significant body mass index (BMI) decreases, probably due to the low-calorie diet. Among the groups, the most prominent BMI-reducing effect was seen in the ephedra group. In RMR, no significant change in any group or significant difference among the groups was found. No significant adverse effects were observed in serum tests or in the self-questionnaire. Ephedra combined with a low-calorie diet was effective in reducing BMI. RMR change was not compensated for by the herbal medicines tried. RMR change seemed to be affected by constitution and body composition rather than by medicine. Ephedra and evodia were proven to be safe for short-term use in the herbal form.

  18. Impact of mydriatic eye drops on neonatal cerebral blood flow

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    Atef Alshafei


    Full Text Available Retinopathy of prematurity (ROP screening is a common routine procedure carried out on preterm infants in neonatal intensive care units (NICUs. Mydriatic eye drops containing phenylephrine hydrochloride 2.5% (a sympathomimetic agent and tropicamide 0.5% (a cycloplegic medication are readily absorbed from the conjunctiva and produce systemic responses in various organs. To our knowledge, no studies have investigated the direct effects of these medications on cerebral blood flow velocities (CBFVs in preterm infants. To evaluate the systemic effects of locally instilled mydriatic eye drops (phenylephrine hydrochloride 2.5% and tropicamide 0.5% used for ROP screening, on cerebral blood flow velocity in preterm infants, a prospective observational study was conducted among preterm infants with gestational age (GA < 31 weeks admitted to the NICU at Dubai Hospital between February 20, 2017 and June 20, 2017. The infants (at a post-menstrual age of 31-34 weeks underwent duplex ultrasound evaluation of CBFV before and after mydriatic eye drops administration.Pulsed-wave Doppler ultrasound studies were performed 1 h before and 1 h after eye mydriasis. We measured peak systolic velocity (PSV and end diastolic velocity (EDV for both the anterior cerebral artery (ACA and middle cerebral artery (MCA and calculated the resistive index (RI, defined as PSV – EDV/PSV. Mean arterial blood pressure (MAP, heart rate, oxygen saturation and pain score were assessed before and 1 h after ROP examination.A paired t-test and McNemar’s test were used to assess the statistical significance of the difference between pairs of means and the qualitative variables measured twice for the same study group.Among the 42 eligible preterm infants, the mean (SD GA was 27 (2.68 weeks (range, 24-31 weeks. The mean (SD RI of ACA before and 1 h after eye drops administration was 0.84 (0.06 and 0.83 (0.07 respectively (p = 0.453. The mean (SD RIs of MCA before and then 1 h after

  19. Management of depression in the elderly. (United States)

    Williams, G O


    reached. Failure of a noradrenergic antidepressant after 4 to 5 weeks can be followed by a trial of a serotonergic drug. Drug serum level monitoring is useful for imipramine, desipramine, and nortriptyline. Monoamine oxidase inhibitors are effective in many elderly patients who are resistant to TCAs. Sympathomimetic drugs must be avoided with MAOIs. Elderly patients are at high risk of toxicity and drug interactions with lithium. Electroconvulsive therapy is useful for patients who do not respond to drug treatment, but medical complications, particularly cardiovascular, often occur in patients 75 or older. Many patients relapse after ECT. Psychotherapy together with pharmacotherapy may be the optimal treatment for elderly depressives. Older patients are more likely to become chronically depressed than younger patients. The risk of suicide in depressed elderly males is high, particularly in those with psychosocial problems, and depression rises with age.

  20. Uso de drogas antiobesidade entre estudantes universitários Use of anti-obesity drugs among college students

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    Maria do Carmo de Carvalho e Martins


    Full Text Available OBJETIVO: Avaliar o uso de drogas antiobesidade entre estudantes de uma universidade pública. MÉTODOS: Estudo transversal com amostra probabilística constituída por 664 universitários. Foram observadas variáveis socioeconômicas, antropométricas e uso das drogas. O índice de massa corpórea (IMC e circunferência da cintura (CC foram classificados segundo critérios da Organização Mundial de Saúde. RESULTADOS: Uso atual ou anterior de agentes antiobesidade foi referido por 6,8% dos estudantes. As anfetaminas e as aminas simpaticomiméticas (40,5% foram as drogas mais usadas. Entre aqueles que referiram uso de agentes antiobesidade, 62,2% eram do sexo feminino. Apenas 31,1% das prescrições foram indicadas por médicos. As médias de IMC e CC foram maiores entre estudantes que referiram uso de tais drogas, mas 47% deles foram classificados como eutróficos pelo IMC, e 76,5% apresentavam medida de CC normal. CONCLUSÃO: O uso de drogas antiobesidade se mostrou preocupante, principalmente pela elevada proporção de uso sem indicação ou prescrição médica.OBJECTIVE: To evaluate the use of anti-obesity drugs among students attending a public university. METHODS: This was a cross sectional random study of 664 college students. Drug use, socioeconomic, and anthropometric variables were observed. Body mass index (BMI and waist circumference (WC were classified according to World Health Organization criteria. RESULTS: Current or previous use of anti-obesity drugs was reported by 6.8% of students. Amphetamine and sympathomimetic amines (40.5% were the most commonly used drugs. Among those who reported use of anti-obesity agents, 62.2% were female. Only 31.1% of medications were prescribed by doctors. Mean BMI and WC were higher among students reporting the use of such drugs, but 47% of them were classified as eutrophic by BMI, and 76.5% had normal WC measure. CONCLUSION: The use of anti-obesity drugs among college students is of concern

  1. Pharmacology of AH 5158; a drug which blocks both α- and β-adrenoceptors (United States)

    Farmer, J. B.; Kennedy, I.; Levy, G. P.; Marshall, R. J.


    1. AH 5158 differs from conventional adrenoceptor blocking drugs in producing competitive blockade of both α- and β-adrenoceptors. 2. AH 5158 is 5-18 times less potent than propranolol in blocking β-adrenoceptors. It resembles propranolol in its non-selective blockade of β1-cardiac and β2-vascular and tracheal adrenoceptors and in its lack of intrinsic sympathomimetic activity. 3. AH 5158 is 2-7 times less potent than phentolamine in blocking α-adrenoceptors. AH 5158 itself is more active on β- than α-adrenoceptors. 4. Blockade of noradrenaline vasopressor responses by AH 5158 in anaesthetized dogs was dose-dependent up to 1 mg/kg but no further blockade was obtained with larger doses of AH 5158. `Self-limiting' blockade was not observed in dogs pretreated with cocaine, or in untreated dogs if the vasopressor agent was oxymetazoline instead of noradrenaline. A possible cause of `self-limiting' blockade is discussed. 5. In doses higher than those required for either α- or β-adrenoceptor blockade, AH 5158 produced effects on cardiac muscle that are attributable to membrane-stabilizing activity. This was manifested as a negative inotropic action in spinal dogs and in guinea-pig left atrial strips, as a negative chronotropic action in syrosingopine pre-treated dogs, and as an increase in the effective refractory period of guinea-pig left atrial strips. AH 5158 was 3-11 times less potent than propranolol in these tests. 6. In open chest dogs AH 5158 resembled propranolol in reducing cardiac output, rate and contractility, effects which are attributable to β-adrenoceptor blockade. The drug differed from propranolol in decreasing rather than increasing total peripheral resistance and in causing larger decreases in arterial blood pressure at equipotent β-adrenoceptor blocking doses. These differences are attributable to the α-adrenoceptor blocking actions of AH 5158. 7. In anaesthetized dogs, intravenously administered AH 5158 antagonized both catecholamine

  2. Studies on the antinociceptive action of α-agonist drugs and their interactions with opioid mechanisms (United States)

    Bentley, G.A.; Newton, S.H.; Starr, Jennifer


    1 A modified abdominal constriction test, whereby the drugs used are injected intraperitoneally when the writhing response is maximal, has been used to study the antinociceptive activity of various sympathomimetic drugs. Of those tested, clonidine was the most potent, with an ID50 value in the nanomolar range. (-)-Isoprenaline, (-)-adrenaline and (-)-noradrenaline were only a little less potent. Phenylephrine, the least potent, had only about one-sixtieth of the activity of clonidine. 2 The antinociceptive action appears to occur within the peritoneum, since it was apparent almost immediately after the drugs were injected and was produced by doses far smaller than were effective by the subcutaneous route. 3 α-Adrenoceptors appear to be involved in the reaction, since noradrenaline showed stereospecificity, and the α-adrenoceptor antagonists phentolamine and piperoxan both shifted the dose-response curves of the α-adrenoceptor agonist drugs to the right, usually parallel to the control curves. 4 The high antinociceptive potency of clonidine and oxymetazoline, indicate the importance of α2-adrenoceptors and this was supported by the finding that piperoxan was a more effective antagonist than phentolamine. The moderate potency of phenylephrine suggests that α1-adrenoceptors may also be involved, although the selective α1-antagonist, prazosin, did not antagonize noradrenaline and had antinociceptive activity of its own. 5 β-Adrenoceptors also appear to be involved in the antinociceptive response, since propranalol antagonized the effect of isoprenaline, but not that of clonidine. 6 Piperoxan was a very effective antagonist of morphine, while phentolamine had a weaker action. Naloxone had little action against the α-adrenoceptor agonists. 7 Mice pretreated with clonidine or oxymetazoline but not noradrenaline showed a very great cross-tolerance to morphine. Morphine pretreatment caused marked desensitization of itself, but little cross-tolerance to clonidine or

  3. Management of mydriasis and pain in cataract and intraocular lens surgery: review of current medications and future directions

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    Grob SR


    Full Text Available Seanna R Grob,1–3 Luis A Gonzalez-Gonzalez,1–3 Mary K Daly1,2,4 1Department of Ophthalmology, Veterans Administration Boston Healthcare System, Boston, MA, USA; 2Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; 3Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA; 4Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA Abstract: The maintenance of mydriasis and the control of postoperative pain and ­inflammation are critical to the safety and success of cataract and intraocular lens replacement surgery. Appropriate mydriasis is usually achieved by topical and/or intracameral administration of anticholinergic agents, sympathomimetic agents, or both, with the most commonly used being cyclopentolate, tropicamide, and phenylephrine. Ocular inflammation is common after cataract surgery. Topical steroids and nonsteroidal anti-inflammatory drugs are widely used because they have been proved effective to control postsurgical inflammation and decrease pain. Topical nonsteroidal anti-inflammatory drugs have also been shown to help maintain dilation. However, use of multiple preoperative drops for pupil dilation, inflammation, and pain control have been shown to be time consuming, resulting in delays to the operating room, and they cause dissatisfaction among perioperative personnel; their use can also be associated with systemic side effects. Therefore, ophthalmologists have been in search of new options to streamline this process. This article will review the current medications commonly used for intraoperative mydriasis, as well as pain and inflammation control. In addition, a new combination of ketorolac, an anti-inflammatory agent, and phenylephrine, a mydriatic agent has recently been designed to maintain intraoperative mydriasis and to reduce postoperative pain and irritation from intraocular lens replacement surgery. Two Phase III clinical trials evaluating this

  4. Upper Eyelid and Pupillary Effects of Topical Dilute Epinephrine. (United States)

    Garcia, Giancarlo A; Ngai, Philip; Vemuri, Swapna; Tao, Jeremiah P

    Adrenergic medications may elevate the upper eyelid and dilate the pupil. The effects of topical phenylephrine on Müller's muscle have been well described. Dilute epinephrine (DE) is a sympathomimetic agent commonly administered in blepharoptosis surgery, and has been shown to elevate the upper eyelid margin when injected subcutaneously. The effects of DE applied topically to the eye, whether intentional or inadvertent during surgery have not been characterized. The purpose of this investigation was to quantify and compare the effects of topical DE and phenylephrine on upper eyelid position and pupil size. Prospective, nonrandomized trial of 41 adults without (n = 25, 25 eyes) and with ptosis (n = 16, 16 eyes). Upper eyelid margin reflex distance (MRD1) and pupil diameter were primary measures and pupil reactivity to light was a secondary measure. MRD1 and pupil diameter were recorded at baseline and at 30-second intervals for 5 minutes after administration of topical 1% lidocaine with epinephrine 1:100,000 (DE). After a washout period of >24 hours, the same measurements were recorded after administration of topical phenylephrine 2.5%. No statistically significant difference was observed between mean baseline and postexposure MRD1 after application of topical DE (p = 0.181). In contrast, a mean increase in MRD1 of 0.51 ± 0.09 mm (effect size 0.33) was observed after exposure to phenylephrine 2.5% (p MRD1 was significantly greater for phenylephrine compared with DE (p < 0.001, analysis of covariance). Mean pupil diameter increased 0.29 ± 0.09 mm (effect size 0.48) in response to DE and 0.27 ± 0.11 mm (effect size 0.41) after application of phenylephrine (p = 0.004 and p = 0.001, respectively). All pupils maintained a constrictive response to light. Although DE is similar to topical phenylephrine in causing mydriasis, it did not have a similar effect on elevating the upper eyelid. These findings may have implications on intraoperative assessment

  5. Echocardiography and ultrasound dopplerography assessment of central and peripheral hemodynamics in children with septic shock

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    V.V. Yevtushenko


    Full Text Available Background. The severe course of sepsis is usually associated with the development of septic shock and multiple organ failure. For effective treatment, it is recommended to perform instrumental monitoring of preload, contractile capacity of the heart and tissue perfusion. We aimed to evaluate changes in central and peripheral hemodynamics by echocardiography and Doppler ultrasound in children with septic shock. Materials and methods. A retrospective study of cases of septic shock in children aged 0 to 18 years who underwent treatment in the intensive care unit was conducted. Patients were monitored for central and peripheral hemodynamics by echocardiography and Doppler ultrasound. The initial study of hemodynamic parameters was carried out over the first 3 hours after hospitalization. The second study was carried out in 24–36 hours after the hospitalization. The third study was conducted in the period of convalescence within 24–48 hours after the withdrawal of sympathomimetic drugs. Results. Thirty-four cases of sepsis associated with septic shock were investigated. In 24 (70.6 % patients, the etiological factor was meningococcus, in 1 (2.9 % staphylococcus, and in 9 (26.5 % no aetiology was established. In 6 children from the study group fatal outcome occurred. Values of mean blood pressure, ejection fraction, peripheral resistance were relatively lower in the acute shock period, and increased after stabilization of hemodynamics. Evaluation of peripheral blood circulation at admission showed decreased diastolic velocity in abdominal aorta and upper mesenteric artery and systolic velocity in posterior tibial artery. The results of initial investigation demonstrated that 44.1 % patients had increased cardiac output along with decreased systemic vascular resistance (‘warm shock’, and just 8.8 % had features of ‘cold shock’ (decreased cardiac output and increased vascular resistance. The fatal course of the disease was associated with

  6. Toxicity evaluation of α-pyrrolidinovalerophenone (α-PVP): results from intoxication cases within the STRIDA project. (United States)

    Beck, Olof; Franzén, Lisa; Bäckberg, Matilda; Signell, Patrick; Helander, Anders


    were tachycardia (80%), agitation (70%), hypertension (33%), hallucinations (20%), and delirium (18%). Classification of poisoning severity yielded 25 (60%) moderate (PSS 2), 7 (17%) severe (PSS 3), and 2 fatal cases (PSS 4). In analytically confirmed α-PVP intoxication cases involving no other stimulant drugs, the urine and serum concentrations showed high variability. The clinical features were consistent with a severe sympathomimetic toxidrome. The results further demonstrated that α-PVP prevailed as a drug of abuse after being classified as a narcotic substance, and despite a high incidence of severe poisonings and fatalities. However, the low prevalence of α-PVP cases registered at the PIC suggested that many were unaware of the actual substance they had taken.

  7. Fatores de risco para incontinência urinária na mulher Factores de riesgo para incontinencia urinaria en la mujer Risk factors for urinary incontinence in women

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    Rosângela Higa


    analyzed using the MEDLINE and LILACS databases as well as through research in libraries. There is evidence that the main risk factors are age, pelvic floor trauma, hereditary factors, race, menopausal status, obesity, chronic diseases, use of some sympathomimetics and parasympatholitics, constipation, smoking, coffee consumption and intense abdominal exercises. Nurses are able to identify these factors through anamnesis and determine interventions for the prevention and treatment of UI, thus contributing to improve incontinent women's quality of life.

  8. Clinical experience with and analytical confirmation of "bath salts" and "legal highs" (synthetic cathinones) in the United States. (United States)

    Spiller, Henry A; Ryan, Mark L; Weston, Robert G; Jansen, Joanne


    salts >20 h prior to presentation. Three of five patients had MDPV detected in urine (range 34-1386 ng/mL, mean 856 ng/mL). No mephedrone or methylone was detected in any sample. Quantitative analysis performed on postmortem samples detected MDPV in blood at 170 ng/mL and in urine at 1400 ng/mL. No other synthetic cathinones were detected. This is the first report of MDPV exposures with quantitative blood level confirmation. Clinical effects displayed a sympathomimetic syndrome, including psychotic episodes often requiring sedation, movement disorders, and tachycardia. Within 8 months of their appearance, 16 states had added synthetic cathinones to the controlled substances list as a Schedule I drug. We report the emergence of a new group of substances of abuse in the USA, known as bath salts, with quantitative results in 18 patients. State and federal authorities used timely information from poison centers on the bath salt outbreak during investigations to help track the extent of use and the effects occurring from these new drugs. Close collaboration between state authorities and poison centers enhanced a rapid response, including legislation.

  9. [Cathinones use in Paris]. (United States)

    Batisse, A; Grégoire, M; Marillier, M; Fortias, M; Djezzar, S


    The pattern of recreational drug use has changed over the last decade and now includes a multitude of substances sold as "research chemicals" or new psychoactive substances, "NPS". In France, synthetic cathinones emerged in 2008 (while first mentioned by the French police force in 2007 first alerts among users appeared in 2008) and have grown to be popular drugs of abuse. Under the Official Journal dated 11th June 2010, only mephedrone has been listed as narcotics but "designer drugs" have synthesized new substitute cathinones in order to avoid anti-drug laws. However, since July 2012, in France, all synthetic drugs from the cathinones family have been banned and listed as narcotics following the example of United Kingdom. Despite their recent classification and inclusion on narcotic list, they are readily available on Internet and used widely. Paris Addictovigilance Centre observed a signal of derivate cathinones abuse (21 cases over a two-year period). Paris Addictovigilance Centre and Marmottan Hospital wanted to describe the use of cathinones in the Paris area and alert the health care community about the abuse identification and risk assessment problems of these compounds. After a review of derivated cathinone's chemical structure, pharmacology and toxicology, this article seeks to provide patricians with a clinical description and treatment's modality. Most users of synthetic cathinones will experience euphoria, increased energy, talkativeness, openness and increased sexual arousal. Signs and symptoms of toxicity are consistent with a sympathomimetic toxidrome. The main reasons for care access are psychiatric (hallucinations, psychotic symptoms, agitation) and addiction disorders. Somatic complications were described with various patterns of symptoms such as headache, tachycardia, confusional states, rhabdomyolysis with renal failure or serotonin syndrome. The most important fact is the apparition of the "slam" phenomenon among men who have sex with men

  10. Estimating the Direct Costs of Outpatient Opioid Prescriptions: A Retrospective Analysis of Data from the Rhode Island Prescription Drug Monitoring Program. (United States)

    Aroke, Hilary; Buchanan, Ashley; Wen, Xuerong; Ragosta, Peter; Koziol, Jennifer; Kogut, Stephen


    sympathomimetic stimulant, respectively. Average total spending for prescription opioids per patient increased with the average daily dosage: from 3-fold for patients using 50-90 morphine milligrams equivalent (MME) daily to 22-fold for those receiving 90 or more MME daily compared with those receiving less than 50 MME daily. This study provides the first estimate of the statewide direct cost burden of prescription opioid use using PDMP data and standardized pricing benchmarks. Total annual cost increased with age up to 65 years, mean daily dose, and concurrent use of benzodiazepines or stimulants. Commercial insurance bore the majority of the cost of prescription opioid use, but cost per patient was highest among Medicare beneficiaries. In addition to reducing harms associated with opioid overuse and misuse, substantial cost savings could be realized by reducing unnecessary opioid use, especially among middle-aged adults. This study was funded by the Rhode Island Department of Health. Aroke and Kogut report grants from the Rhode Island Department of Health during this study. Kogut is partially supported by Institutional Development Award Number U54GM115677 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds Advance Clinical and Translational Research (Advance-CTR). Koziol reports grants from the Centers for Disease Control and Prevention during this study. The other authors have nothing to disclose. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Study concept and design were contributed by Koziol, Ragosta, and Kogut, along with Aroke. Koziol, Ragosta, Aroke, and Kogut collected the data, and data interpretation was performed by Aroke, Buchanan, Wen, and Kogut. The manuscript was primarily written by Aroke, along with Buchanan and Kogut, and revised by Aroke, Buchanan, Wen, and Kogut.

  11. Desarrollo tecnológico de una formulación de betaxolol 0,5 % para administración oftálmica Technological development of 0.5 % Betaxolol formulation for ophthalmological use

    Directory of Open Access Journals (Sweden)

    Ania González Cortezón


    blocker that does not play a significant role as membrane stabilizer (local anesthestic and lacks intrinsic sympathomimetic activity. It diminishes the production of aqueous humor in the eye, thus reducing the intraocular pressure to normal, either with or without glaucoma. This drug is indicated in the treatment of chronic open angle glaucoma affecting patients with ocular hypertension. Objective: to design a formulation of 0.5 % Betaxolol eye drops that meets the quality control parameters for this pharmaceutical form and that provides the desired therapeutic effect. Methods: four technological variants were performed by adequately modifying the excipient quantities and by keeping the active principle amount, for which the composition of the leading formulation was taken into account. The aim was to select the most stable variant after 3-month follow-up. The pH and the isotonicity of the formulation were adjusted for the requirements of an ophthalmologic preparation. The isotonicity was reached with sodium chloride. Results: the technological development of this formulation was satisfactory; the final product met all the specifications for the quality control of the product as described in USP 30. The physical, chemical and microbiological properties of the preparation remained unchanged for 24 months under storage conditions of 30.0 ± 2.0 °C. Conclusions: the formulation of a medical eye drops containing Betaxolol chlorhydrate as active principle, meets all the quality specifications for this pharmaceutical form to treat glaucoma, which may expand the therapeutic options in Cuba.