Sample records for diphenhydramine

  1. Diphenhydramine

    ... and to treat insomnia (difficulty falling asleep or staying asleep). Diphenhydramine is also used to control abnormal ... contain the same active ingredient(s) and taking them together could cause you to receive an overdose. This ...

  2. Diphenhydramine Injection

    ... not to use diphenhydramine injection if you are breastfeeding because of the risk of harm to infants.tell your doctor if you have or have ever had asthma or other types of lung disease; glaucoma (a ...

  3. Diphenhydramine and Pregnancy

    ... few reports of withdrawal symptoms in infants whose mothers took diphenhydramine daily throughout pregnancy. Is there anyone who should avoid taking diphenhydramine during pregnancy? A single human report and animal data have suggested that ...

  4. Diphenhydramine-induced acute dystonia.

    Etzel, J V


    A 45-year-old woman was administered oral and intravenous diphenhydramine 25 mg for the treatment of an allergic reaction. Within 2 minutes she rapidly developed trismus, dysarthria, tremors of the upper extremities, left-sided weakness, and diminished consciousness. She was treated with intravenous diazepam and benztropine with good response. After approximately 12 hours the patient's condition was completely resolved except for minor subjective weakness of her left extremities. Her hospital stay was uneventful, and she was discharged after 4 days after refusing rechallenge with the drug. Several cases of acute dystonic reactions secondary to antihistamines have been reported in the literature, four of which involved diphenhydramine. Such reactions may occur after short- or long-term therapy. Most patients experienced rapidly developing trismus, facial dystonia, dysarthria, and occasionally, decreases in consciousness, motor incoordination, and weakness. Because of the widespread availability of diphenhydramine and other antihistamines to the general public, awareness of this effect is of great importance.

  5. Spectrophotometric determination of diphenhydramine hydrochloride using dipicrylamine.

    Shamsa, F A; Maghssoudi, R H


    A spectrophotometric procedure for the determination of diphenhydramine hydrochloride based on the reaction with dipicrylamine was developed. A yellow complex forms and is easily extractable by chloroform at pH 5. The mole ratio of diphenydramine hydrochloride to dipicrylamine in the complex is 1:3. The absorbance of the complex obeys Beer's law over the concentration range of 3-10 mug of diphenhydramine hydrochloride per ml of chloroform. This procedure can be carried out in the presence of other compounds without interference.

  6. Acute intoxication with guaifenesin, diphenhydramine, and chlorpheniramine.

    Wogoman, H; Steinberg, M; Jenkins, A J


    Mixed drug reactions are frequently encountered in emergency department overdose cases and also in fatal intoxications. Assessment of the relative contribution of each drug in producing adverse effects is often compounded by lack of case history and the paucity of cases reported in the literature. This report describes a fatal intoxication with three common over-the-counter medications: guaifenesin, diphenhydramine, and chlorpheniramine. A 48-year-old woman was found dead in the attic bedroom of her residence. Specimens obtained at autopsy for toxicologic analysis included heart blood, urine, bile, gastric contents, vitreous humor, and cerebrospinal fluid. The over-the-counter drugs were identified and quantitated by acid/neutral or basic liquid-liquid extraction followed by gas chromatographic analysis with nitrogen phosphorus detection. Concentrations of guaifenesin, diphenhydramine, and chlorpheniramine detected in the heart blood were 27.4, 8.8, and 0.2 mg/L, respectively. The cause of death was determined to be acute intoxication by the combined effects of guaifenesin, diphenhydramine, and chlorpheniramine, and the manner of death was determined to be suicide. To our knowledge, the blood guaifenesin concentration in this case is the highest reported concentration to date associated with an acute intoxication.

  7. The antihistamine diphenhydramine is extremely persistent in agricultural soil

    Topp, Edward, E-mail:; Sumarah, Mark W.; Sabourin, Lyne


    The widely used antihistamine diphenhydramine is present in municipal biosolids, and is detected in runoff from agricultural land fertilized with biosolids. In the present study the kinetics and major pathways of diphenhydramine dissipation in a loam, sandy loam, and clay loam soil were determined in laboratory incubations. The time to dissipate 50% (DT{sub 50}) of {sup 14}C-diphenhydramine residues at 30 Degree-Sign C ranged from 88 {+-} 28 days in the clay loam to 335 {+-} 145 days in the loam soil. Mineralization of {sup 14}C was insignificant, and diphenhydramine-N-oxide was the only detected extractable transformation product elucidated by radioisotope and HPLC-MS methods. There were no significant effects of municipal biosolids on the kinetics or pathways of removal. Overall, diphenhydramine is quite persistent in soils, and formation of non-extractable soil-bound residues is the major mechanism of diphenhydramine dissipation. -- Highlights: Black-Right-Pointing-Pointer Diphenhydramine is a widely used antihistamine drug, is found in biosolids, and in runoff from biosolids-fertilized fields. Black-Right-Pointing-Pointer The persistence of {sup 14}C-diphenhydramine was evaluated in soils. Black-Right-Pointing-Pointer Half lives ranged from 88 to 335 days. Diphenhydramine-N-oxide was the only detected transformation product. Black-Right-Pointing-Pointer Soil-bound residues was a major sink.

  8. The effectiveness of diphenhydramine HCI in pediatric sleep disorders.

    Russo, R M; Gururaj, V J; Allen, J E


    Fifty children with a variety of sleep disorders were studied in a placebo-controlled, double-blind clinical trial of diphenydramine elixir given in a dosage of 1.0 mg/kg at bedtime. Sleep records measuring latency time, number of awakenings, and duration of sleep were compiled by the patient's parent. A global assessment as to the severity of sleep disturbance and the therapeutic effect of the medication and placebo was made on a weekly basis. Diphenhydramine was significantly better than placebo in reducing sleep latency time and the number of awakenings per night, while sleep duration was marginally increased. There were no essential differences between diphenhydramine and placebo in the other study parameters, i.e., restlessness, nightmares, and difficulty awakening. Diphenhydramine was judged to be more effective than placebo on the weekly global assessment. The results indicate that diphenhydramine is a safe, effective bedtime sleep aid for pediatric patients.

  9. Sorption and Transport of Diphenhydramine in Natural Soils

    Rutherford, C. J.; Vulava, V. M.


    Pharmaceutical and related chemicals have been detected in streams and ground water sources throughout the world, as a result of sewage overflows, runoff, or sewage treatment facilities unequipped to remove trace levels of pharmaceuticals. Diphenhydramine- an antihistamine that is used to treat allergy and common cold symptoms, induce sleep, suppress cough, and treat motion sickness- is prominent among them. Diphenhydramine has a complex, highly polar organic structure including two benzene rings and an amine functional group. It has a solubility of 3.06 g/L and a pKa of 8.98. Recent studies have shown that diphenhydramine in streams disrupts the ecology by affecting the algal and bacterial biofilms present on the streambed. In streams, photosynthesis has been found to decrease by up to 99% and plant respiration has been inhibited. Diphenhydramine has also altered the types and numbers of bacteria found in streams. Its presence in contaminated stream bodies can result in contact with soils and sediment in the stream floodplain. The objective of this study is to measure sorption and transport behavior of diphenhydramine in natural soils and determine reactivity of soil components. These studies were conducted in the laboratory using natural soil collected from the Francis Marion National Forrest. Soil samples from A and B horizons of several soil series were characterized for physical and chemical properties: organic matter content ranged between 0.6-7.6%, clay content between 6-20%, and soil pH between 3.7-4.9. The B-horizon soils contain a higher amount of clay than the organic-rich A-horizon soils. Equilibrium sorption isotherms and reaction kinetic rates were measured using batch reactor experiments and chromatographic column experiments were conducted to measure transport behavior. Kinetic experiments showed that diphenhydramine sorbed more strongly to the clay-rich soils and reached equilibrium after seven days, compared to ten days in organic-rich soils. The

  10. Diphenhydramine for Acute Extrapyramidal Symptoms After Propofol Administration.

    Sherer, James; Salazar, Tomas; Schesing, Kevin B; McPartland, Shannon; Kornitzer, Jeffrey


    Extrapyramidal symptoms are an uncommon but well-recognized side effect after the administration of general anesthesia in patients without a significant neurologic history. Several case reports implicate propofol as the likely causative agent producing these symptoms, which include ballismus, dystonia, choreoathetosis, and opisthotonus. Currently, there is no clear consensus on first-line treatment of these symptoms. In each of the published cases, anticholinergic medications and benzodiazepines were central to initial management, although the speed and extent of symptom resolution were variable. Here we present a case of a 17-year-old boy with ulcerative colitis who presented with ballismus, torticollis, tongue thrusting, and oculogyric movements after colonoscopy under general anesthesia with propofol. The patient responded promptly to treatment with diphenhydramine. This is the first reported case in which diphenhydramine was successfully used as the primary treatment of severe extrapyramidal symptoms in a pediatric patient after propofol administration. Copyright © 2017 by the American Academy of Pediatrics.

  11. Correction of organophosphate-induced neuromuscular blockade by diphenhydramine.

    Clemmons, R M; Meyer, D J; Sundlof, S F; Rappaport, J J; Fossler, M E; Hubbell, J; Dorsey-Lee, M R


    Dogs exposed to topical organophosphate (fenthion) developed decreased plasma and muscle cholinesterase activities. After 2 doses were applied (1 week between doses), plasma concentrations declined 80% and muscle cholinesterase activity was reduced by 56%. Decremental responses to repetitive nerve stimulation developed after fenthion administration. Diphenhydramine, but not placebo, corrected the electrical abnormalities caused by organophosphate application, but without altering plasma or muscle cholinesterase activity. Control dogs housed in the same kennel demonstrated a slight decrease (18%) of plasma cholinesterase, which indicates that there may be potential cross contamination. Diphenydramine may be effective in treating organophosphate-induced neuromuscular weakness which is refractory to other forms of therapy.

  12. Effects of the antihistamine diphenhydramine on selected aquatic organisms.

    Berninger, Jason P; Du, Bowen; Connors, Kristin A; Eytcheson, Stephanie A; Kolkmeier, Mark A; Prosser, Krista N; Valenti, Theodore W; Chambliss, C Kevin; Brooks, Bryan W


    In recent years pharmaceuticals have been detected in aquatic systems receiving discharges of municipal and industrial effluents. Although diphenhydramine (DPH) has been reported in water, sediment, and fish tissue, an understanding of its impacts on aquatic organisms is lacking. Diphenhydramine has multiple modes of action (MOA) targeting the histamine H1, acetylcholine (ACh), and 5-HT reuptake transporter receptors, and as such is used in hundreds of pharmaceutical formulations. The primary objective of this study was to develop a baseline aquatic toxicological understanding of DPH using standard acute and subchronic methodologies with common aquatic plant, invertebrate, and fish models. A secondary objective was to test the utility of leveraging mammalian pharmacology information to predict aquatic toxicity thresholds. The plant model, Lemna gibba, was not adversely affected at exposures as high as 10 mg/L. In the fish model, Pimephales promelas, pH affected acute toxicity thresholds and feeding behavior was more sensitive (no-observed-effect concentration = 2.8 µg/L) than standardized survival or growth endpoints. This response threshold was slightly underpredicted using a novel plasma partitioning approach and a mammalian pharmacological potency model. Interestingly, results from both acute mortality and subchronic reproduction studies indicated that the model aquatic invertebrate, Daphnia magna, was more sensitive to DPH than the fish model. These responses suggest that DPH may exert toxicity in Daphnia through ACh and histamine MOAs. The D. magna reproduction no-observed-effect concentration of 0.8 µg/L is environmentally relevant and suggests that additional studies of more potent antihistamines and antihistamine mixtures are warranted. Copyright © 2011 SETAC.

  13. Effects of Terfenadine and Diphenhydramine on Brain Activity and Performance in a UH-60 Flight Simulator


    inability to sleep . In some situations, sedation and other CNS depressant effects may be clinically useful. However, in many instances, these effects...pharmacokinetics data suggest a polyphasic elimination (Carruthers et al., 1978). Diphenhydramine is considered characteristic of the antihistamines with...previously. In one study (Carruthers et al., 1978), 50 mg of diphenhydramine produced sleep in approximately half of the subjects during the first hour

  14. Evaluation the protective effect of diphenhydramine against acute toxicity induced by levamisole in male mice

    M.Y. Matti


    Full Text Available The aim of this study was to evaluate the protective effect of different doses of diphenhydramine against acute toxicosis with Levamisole. The Mechanism of levamisole induced acute toxicity and that of protective effect of diphenhydramine against Levamisole toxicosis also examined on the level of cholinesterase (ChE activity. Subcutanous injection of 100mg/kg levamisole in male mice with induced cholinergic over stimulation and death in 100% of animals. The Toxicosis was not related to the significantly decreased in plasma, red blood cells and brain ChE activity. Injection low dose of diphenhydramin 2.5mg/kg S.C. 15 min before levamisole produced protective effect against acute toxicity with levamisole. Significantly decreased the severity of toxicosis and increased survival rates to 100%. Diphenhydramine at low dose alone or with acute dose of levamisole did not Produced Significantly inhibition in ChE activity.The data suggested that the toxic effect of Levamisole was not related to inhibition of ChE. The low dose of diphenhydramine protected mice from Levamisole toxicity. The antidoatal effect of diphenhydramine not at the level of protection from ChE inhibition. There was no adverse interaction between two drugs.

  15. Biodistribution of diphenhydramine in reproductive organs in an overdose case.

    Oritani, Shigeki; Michiue, Tomomi; Chen, Jian-Hua; Tani, Naoto; Ishikawa, Takaki


    Motion sickness medications such as Travelmin(®) prescribed in Japan include diphenhydramine (DPH), dyphylline, diphenidol, and/or caffeine. Herein, we report a patient who died due to rhabdomyolysis after ingesting a DPH containing motion sickness medication. A Japanese male in his 30 s reported missing after going out for a drive early in the morning was found dead in his car in the evening of the same day. An autopsy showed moderate edema, congestion, and several petechiae in both lungs. The brain was congested and edematous with no atherosclerosis of cerebral arteries. The prostate and both testes were slightly edematous. Gastric contents included approximately 15 mL of dark-brown fluid without tablets or food residue. Toxicological examination showed that blood DPH levels in all tissues were between 4.90 and 7.27 μg/mL, which represented toxic to lethal levels. DPH (μg/mL) levels were approximately 3-9 times higher in the prostate (73.42) and testes (left, 28.23; right, 30.09) than those in all regions of the brain (range 7.75-12.33). Blood dyphylline, diphenidol and caffeine levels in reproductive organs reached high, but not toxic levels. In conclusion, DPH, dyphylline, diphenidol, and caffeine levels were higher in reproductive organs such as the prostate and testes than in the central nervous system and heart. As we determined in this case, motion sickness medications might accumulate in reproductive organs. Thus, further examination of tissue biodistribution of DPH, dyphylline, diphenidol, and caffeine is necessary to assess their potential long-term effects in these sites.

  16. Geochemical Fate and Transport of Diphenhydramine and Cetirizine in Soil

    Wireman, R.; Rutherford, C. J.; Vulava, V. M.; Cory, W. C.


    Pharmaceuticals compounds presence in natural soils and water around the world has become a growing concern. These compounds are being discharged into the environment through treated wastewater or municipal sludge applications. The main goal of this study is determine their geochemical fate in natural soils. In this study we investigated sorption and transport behavior of diphenhydramine (DPH) and cetirizine (CTZ) in natural soils. These two commonly-used antihistamines are complex aromatic hydrocarbons with polar functional groups. Two clean acidic soils (pH~4.5) were used for these studies - an A-horizon soil that had higher organic matter content (OM, 7.6%) and a B-horizon soil that had lower OM (1.6%), but higher clay content (5.1%). Sorption isotherms were measured using batch reactor experiments. Data indicated that sorption was nonlinear and that it was stronger in clay-rich soils. The pKa's of DPH and CTZ are 8.98 and 8.27 respectively, i.e., these compounds are predominantly in cationic form at soil pH. In these forms, they preferentially sorb to negatively charged mineral surfaces (e.g., clay) present in the soils. Soil clay mineral characterization indicated that kaolinite was the dominant clay mineral present along with small amount of montmorillonite. The nonlinear sorption isotherms were fitted with Freundlich model. Transport behavior of both compounds was measured using glass chromatography columns. As expected both DPH and CTZ were strongly retained in the clay-rich soil as compared with OM-rich soil. The asymmetrical shape of the breakthrough curves indicated that there were likely two separate sorption sites in the soil, each with different reaction rates with each compound. A two-region advection-dispersion transport code was used to model the transport breakthrough curves. There was no evidence of transformation or degradation of the compounds during our sorption and transport studies.

  17. Efficacy of diphenhydramine in the prevention of vertigo and nausea at 7 T MRI

    Thormann, Markus, E-mail: [Klinik für Radiologie und Nuklearmedizin, Universitätsklinikum Magdeburg A.ö.R., Otto-von-Guericke Universität, Leipziger Str. 44, 39120 Magdeburg (Germany); Amthauer, Holger [Klinik für Radiologie und Nuklearmedizin, Universitätsklinikum Magdeburg A.ö.R., Otto-von-Guericke Universität, Leipziger Str. 44, 39120 Magdeburg (Germany); Adolf, Daniela [Institut für Biometrie und Medizinische Informatik, Universitätsklinikum Magdeburg A.ö.R., Otto-von-Guericke Universität, Leipziger Str. 44, 39120 Magdeburg (Germany); Wollrab, Astrid [Biomedizinische Magnetresonanz, Universitätsklinikum Magdeburg A.ö.R., Otto-von-Guericke Universität, Leipziger Str. 44, 39120 Magdeburg (Germany); Ricke, Jens [Klinik für Radiologie und Nuklearmedizin, Universitätsklinikum Magdeburg A.ö.R., Otto-von-Guericke Universität, Leipziger Str. 44, 39120 Magdeburg (Germany); Speck, Oliver [Biomedizinische Magnetresonanz, Universitätsklinikum Magdeburg A.ö.R., Otto-von-Guericke Universität, Leipziger Str. 44, 39120 Magdeburg (Germany)


    Purpose: In this study the potential of diphenhydramine in reducing respectively preventing vertigo and nausea induced by the ultra-high static magnetic field at 7 T was evaluated. Materials and methods: In a prospective, double blinded, placebo controlled, cross-over randomized study the sensations of 34 volunteers before, during and after exposure to the static magnetic field with and without drug respectively placebo administration were quantified. Fast table motion was applied to increase the incidence of otherwise sparse reports of field related sensations. Results: The strength of vertigo can be reduced by the application of diphenhydramine. Conclusion: Diphenhydramine, even at a low dose, reduces the strength of vertigo at ultra-high static magnetic fields, may be used preventively, and could pave the way to even higher field strength.

  18. Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients.

    Agostini, J V; Leo-Summers, L S; Inouye, S K


    Diphenhydramine hydrochloride is a commonly prescribed medicine in hospitalized patients, but its adverse effects on older patients remain unclear. We enrolled 426 hospitalized medical patients aged 70 years or older in a prospective cohort study in a university hospital. Measurements included baseline and daily assessments including Mini-Mental State Examination scores, Confusion Assessment Method ratings, direct observations for medical devices (urinary catheter or physical restraints), and blinded medical record extractions for diphenhydramine use. Of the 426 patients, 114 (27%) received diphenhydramine during hospitalization and shared similar baseline characteristics including age, sex, delirium risk, and Mini-Mental State Examination scores compared with nonexposed patients. The diphenhydramine-exposed group was at an increased risk for any delirium symptoms (relative risk [RR], 1.7; 95% confidence interval [CI], 1.3-2.3) and for individual delirium symptoms, including inattention (RR, 3.0; 95% CI, 1.5-5.9), disorganized speech (RR, 5.5; 95% CI, 1.0-29.8), and altered consciousness (RR, 3.1; 95% CI, 1.6-6.1). Exposed patients also had increased risk for urinary catheter placement (RR, 2.5; 95% CI, 1.0-6.0) and longer median length of stay (7 vs 6 days; P =.009). A dose-response relationship was demonstrated for most adverse outcomes. Overall, 24% of diphenhydramine doses were administered inappropriately. Diphenhydramine administration in older hospitalized patients is associated with an increased risk of cognitive decline and other adverse effects with a dose-response relationship. Careful review of its use is necessary in this vulnerable population.

  19. Efficacy and safety of Linkus, Aminophylline diphenhydramine and acefyllin piperazine for the treatment of cough in children.

    Rehman, Hina; Naveed, Safila; Usmanghani, Khan


    To evaluate the safety and efficacy of Linkus, Aminophylline with Diphenhydramine group and Acefyllin Piperazine with Diphenhydramine cough syrup on children having cough and sleep difficulty associated with cough. To determine the effects of Linkus polyherbal syrup (group A) and compared with other parallel allopathic groups (Group B and C) for cough on children and associated sleep quality and improvement. 360 children having cough inducted in 3 different groups randomly selected. Three parallel groups were the part of the study. The first study group was the herbal syrup Linkus, second group of children were taking a syrup of multinational pharmaceutical industry having Aminophylline plus Diphenhydramine however the third group received another famous brand having Acefyllin Piperazine with Diphenhydramine. Informed assent and informed consent have taken from the study subjects and their parents. Subjects with acute cough were included in the study however the subjects with chronic cough considered to be excluded. Every group of individual in the study was informed about the investigational drugs provided. Ethnic groups, frequency of cough and diseases illness (Cough impact on child and its sleep of three different syrups (every group) were assessed on day1 and day 14(pcough including side effects as compare to the other parallel groups B and C (Aminophylline with Diphenhydramine and Acefyllin Piperazine with Diphenhydramine). For nocturnal sleep Linkus providing better results in cough and associated problems. Pain were significantly reduce on day 14 with the herbal Linkus syrup group A (coughs and benefit lung functions and better sleep facilitation.

  20. Inhibitory effects of antihistamines, diphenhydramine and chlorpheniramine, on proton currents in BV2 microglial cells.

    Kim, Jiwon; Song, Jin-Ho


    Microglial NADPH oxidase is a major source of toxic reactive oxygen species produced during chronic neuroinflammation. Voltage-gated proton channel (HV1) functions to maintain the intense activity of NADPH oxidase, and channel inhibition alleviates the pathology of neurodegenerative diseases such as ischemic stroke and multiple sclerosis associated with oxidative neuroinflammation. Antagonists of histamine H1 receptors have beneficial effects against microglia-mediated oxidative stress and neurotoxicity. We examined the effects of the H1 antihistamines, diphenhydramine and chlorpheniramine, on proton currents in BV2 microglial cells recorded using the whole-cell patch clamp technique. Diphenhydramine and chlorpheniramine reduced the proton currents with almost the same potency, yielding IC50 values of 42 and 43μM, respectively. Histamine did not affect proton currents, excluding the involvement of histamine receptors in their action. Neither drug shifted the voltage-dependence of activation or the reversal potential of the proton currents, even though diphenhydramine slowed the activation and deactivation kinetics. The inhibitory effects of the two antihistamines on proton currents could be utilized to develop therapeutic agents for neurodegenerative diseases and other diseases associated with HV1 proton channel abnormalities. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Treatment of Diphenhydramine with diferent AOPs including photo-Fenton at circumneutral pH.

    López Vinent, Núria; Plaza, Sandra; Afkhami, Arsalan; Marco, Pilar; Giménez Farreras, Jaume; Esplugas Vidal, Santiago


    The degradation of diphenhydramine hydrochloride (DPH), via UV-vis/H2O2, Fenton, photo-Fenton and photocatalysis processes, was studied under different radiation sources. In addition, the Fenton and photo-Fenton processes at acid pH and circumneutral pH have been compared. The importance of the source of irradiation, UV-C (λ = 254 nm), black blue lamps (BLB, λ = 365 nm) and simulated solar radiation (SB, SolarBox), was investigated at lab-scale. Moreover, compound parabolic collectors (CPC), ...

  2. Observed and modeled effects of pH on bioconcentration of diphenhydramine, a weakly basic pharmaceutical, by fathead minnows

    Understanding the influence of pH on uptake and accumulation of ionizable pharmaceuticals by fish was recently identified as a major research need. In the present study, fathead minnows were exposed to diphenhydramine (DPH), a weakly basic pharmaceutical (pKa = 9.1). Fish were ...

  3. Development of a rapid derivative spectrophotometric method for simultaneous determination of acetaminophen, diphenhydramine and pseudoephedrine in tablets.

    Souri, Effat; Rahimi, Aghil; Shabani Ravari, Nazanin; Barazandeh Tehrani, Maliheh


    A mixture of acetaminophen, diphenhydramine hydrochloride and pseudoephedrine hydrochloride is used for the symptomatic treatment of common cold. In this study, a derivative spectrophotometric method based on zero-crossing technique was proposed for simultaneous determination of acetaminophen, diphenhydramine hydrochloride and pseudoephedrine hydrochloride. Determination of these drugs was performed using the (1)D value of acetaminophen at 281.5 nm, (2)D value of diphenhydramine hydrochloride at 226.0 nm and (4)D value of pseudoephedrine hydrochloride at 218.0 nm. The analysis method was linear over the range of 5-50, 0.25-4, and 0.5-5 µg/mL for acetaminophen, diphenhydramine hydrochloride and pseudoephedrine hydrochloride, respectively. The within-day and between-day CV and error values for all three compounds were within an acceptable range (CV<2.2% and error<3%). The developed method was used for simultaneous determination of these drugs in pharmaceutical dosage forms and no interference from excipients was observed.

  4. Observed and modeled effects of pH on bioconcentration of diphenhydramine, a weakly basic pharmaceutical, by fathead minnows

    Understanding the influence of pH on uptake and accumulation of ionizable pharmaceuticals by fish was recently identified as a major research need. In the present study, fathead minnows were exposed to diphenhydramine (DPH), a weakly basic pharmaceutical (pKa = 9.1). Fish were ...

  5. [Effectiveness of intravenous sedation with midazolam-diphenhydramine in patients who are going to perform an magnetic resonance].

    Álvarez-Bastidas, Lucía; Sabag-Ruiz, Enrique; Medina-Soto, Alfonso


    The requirement of the anesthesiologist for patient care outside the surgical area is constantly increasing. It is an activity that encompasses the different degrees of monitoring, sedation, and anesthesia. To compare the safety and efficacy of midazolam midazolam-diphenhydramine against magnetic resonance with level of sedation on the Ramsay scale. We performed a study in the Instituto Mexicano del Seguro Social Obregon, Sonora, of patients scheduled for cranial magnetic resonance imaging with sedation, during October and December 2013, comparing two groups: midazolam/diphenhydramine against midazolam groups. We included 68 patients, 34 in the experimental group (midazolam-diphenhydramine) versus 34 controls (midazolam). The Ramsay scale showed, in the experimental group, an increased sedation effect resulting in one Ramsay 1, at 10 minutes 2.8 2.8 20 minutes and 30 minutes 2.0. In the control group the basal Ramsay was 1, 2.1 to 10 minutes, 20 minutes and 2.1 to 2.0 at 30 minutes (p = 0.0001). The analysis of heart rate, respiratory, and baseline oxygen saturation, at 10, 20 and 30 minutes, was p = 0.0001 for both groups. The combination of diphenhydramine with intravenous midazolam is safe, with the degree of sedation being better compared with use of midazolam alone, resulting in less failure of sedation during magnetic resonance imaging.

  6. Study on the interaction between diphenhydramine and erythrosin by absorption, fluorescence and resonance Rayleigh scattering spectra

    TANG XiaoLing; LIU ZhongFang; LIU ShaoPu; HU XiaoLi


    In pH 4.5 Britton-Robinson (BR) buffer solution, erythrosin (ET) can react with diphenhydramine (DP) to form a 1:1 ion-association complex, which not only results in the change of the absorption spectra, but also results in the great enhancement of resonance Rayleigh scattering (RRS) and the quenching of fluorescence. Furthermore, a new RRS spectrum will appear, and the maximum RRS wavelength was located at about 580 nm.In this work, the spectral characteristics of the absorption, fluorescence and RRS, the optimum conditions of the reaction and the properties of an analytical chemistry were investigated. A sensitive, simple and new method for the determination of DP by using erythrosin as a probe has been developed. The detection limits for DP were 0.0020 μg/mL for RRS method, 0.088 μg/mL for absorption method and 0.094 μg/mL for fluorophotometry. There was a linear relationship between the absorbance, RRS and fluorescence intensities and the drug concentration in the range of 0.0067-2.0, 0.29-6.4 and 0.31-3.2 μg/mL, respectively. The effects of the interaction of diphenhydramine and erythrosin on the absorption, fluorescence and resonance Rayleigh scattering spectra were discussed. In light polarization experiment, the polarization of RRS at maximum wavelength was measured to be P = 0.9779, and it revealed that the RRS spectrum of DP-ET complex consists mostly of resonance scattering and few resonance fluorescence. In this study, enthalpy of formation and mean polarizability were calculated by AM1 quantum chemistry method. In addition, the reaction mechanism and the reasons for the enhancement of scattering spectra and the energy transfer between absorption, fluorescence and RRS were discussed.

  7. Therapeutic Effects of "Ibuprofen, Diphenhydramine and Aluminium MgS" on Recurrent Aphthous Stomatitis: A Randomized Controlled Trial.

    Katayoun Borhan-Mojabi


    Full Text Available Recurrent aphthous stomatitis (RAS is the most common and painful oral inflammatory lesion with an unknown etiology. This study aims to determine the therapeutic effects of ibuprofen, diphenhydramine and aluminum magnesium simethicone (AlMgS syrup on reducing oral aphthous ulcer pain.Thirty-one patients with RAS participated in this double-blind clinical trial. Subjects were randomly divided into two groups. The control group (n=14 received drug mixture as drug A (diphenhydramine and AlMgS and the case group (n=17 received drug B (ibuprofen, diphenhydramine and AlMgS. Drugs were topically applied on ulcers by the patients three times a day for 3 days. Patients were re-examined for the symptoms on the fourth day following their first visits using VAS (Visual Analogue Scale tool. Statistical analysis was performed using paired t-test, independent t-test and chi-square test.The mean of pain reduction was 3.17±2 (P<0.001 and 3.82±1.79 (P<0.001 in the case and control group, respectively. The difference in pain reduction between both groups was not statistically significant. In addition, no significant difference was detected between the two groups regarding the duration of pain or burning sensation (P=0.57.The results of this study demonstrate that in comparison with diphenhydramine and AlMgS syrup, the studied mixture did not effectively reduce the level of pain, duration and burning sensation.

  8. Therapeutic Effects of “Ibuprofen, Diphenhydramine and Aluminium MgS” on Recurrent Aphthous Stomatitis: A Randomized Controlled Trial

    Borhan-Mojabi, Katayoun; Mirmiran, Faezeh; Nassiri-Asl, Marjan; Nazeman, Pantea; Jahanihashemi, Hassan


    Objective: Recurrent aphthous stomatitis (RAS) is the most common and painful oral inflammatory lesion with an unknown etiology. This study aims to determine the therapeutic effects of ibuprofen, diphenhydramine and aluminum magnesium simethicone (AlMgS) syrup on reducing oral aphthous ulcer pain. Materials and Methods: Thirty-one patients with RAS participated in this double-blind clinical trial. Subjects were randomly divided into two groups. The control group (n=14) received drug mixture as drug A (diphenhydramine and AlMgS) and the case group (n=17) received drug B (ibuprofen, diphenhydramine and AlMgS). Drugs were topically applied on ulcers by the patients three times a day for 3 days. Patients were re-examined for the symptoms on the fourth day following their first visits using VAS (Visual Analogue Scale) tool. Statistical analysis was performed using paired t-test, independent t-test and chi-square test. Results: The mean of pain reduction was 3.17±2 (P<0.001) and 3.82±1.79 (P<0.001) in the case and control group, respectively. The difference in pain reduction between both groups was not statistically significant. In addition, no significant difference was detected between the two groups regarding the duration of pain or burning sensation (P=0.57). Conclusion: The results of this study demonstrate that in comparison with diphenhydramine and AlMgS syrup, the studied mixture did not effectively reduce the level of pain, duration and burning sensation. PMID:24910692

  9. Age matters: Developmental stage of Danio rerio larvae influences photomotor response thresholds to diazinion or diphenhydramine

    Kristofco, Lauren A. [Department of Environmental Science, Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, TX (United States); Cruz, Luis Colon [Department of Anatomy and Neurobiology, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan (Puerto Rico); Haddad, Samuel P. [Department of Environmental Science, Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, TX (United States); Behra, Martine L. [Department of Anatomy and Neurobiology, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan (Puerto Rico); Chambliss, C. Kevin [Department of Environmental Science, Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, TX (United States); Department of Chemistry, Baylor University, Waco, TX (United States); Brooks, Bryan W., E-mail: [Department of Environmental Science, Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, TX (United States)


    Highlights: • Fish behavior impairments by biological active contaminants are limited yet necessary. • Aquatic toxicology assays with 0–4 dpf larval zebrafish are increasingly important. • Larval zebrafish locomotion varied with age and daylight during typical workday hours. • Photomotor behavior to diazinion and diphenhydramine differed by larval zebrafish age. • Behavioral responses of 7–10 dpf zebrafish were markedly more sensitive than 0–4 dpf. - Abstract: Because basic toxicological data is unavailable for the majority of industrial compounds, High Throughput Screening (HTS) assays using the embryonic and larval zebrafish provide promising approaches to define bioactivity profiles and identify potential adverse outcome pathways for previously understudied chemicals. Unfortunately, standardized approaches, including HTS experimental designs, for examining fish behavioral responses to contaminants are rarely available. In the present study, we examined movement behavior of larval zebrafish over 7 days (4–10 days post fertilization or dpf) during typical daylight workday hours to determine whether intrinsic activity differed with age and time of day. We then employed an early life stage approach using the Fish Embryo Test (FET) at multiple developmental ages to evaluate whether photomotor response (PMR) behavior differed with zebrafish age following exposure to diazinon (DZN), a well-studied orthophosphate insecticide, and diphenhydramine (DPH), an antihistamine that also targets serotonin reuptake transporters and the acetylcholine receptor. 72 h studies were conducted at 1–4, 4–7 and 7–10 dpf, followed by behavioral observations using a ViewPoint system at 4, 7 and 10 dpf. Distance traveled and swimming speeds were quantified; nominal treatment levels were analytically verified by isotope-dilution LC–MSMS. Larval zebrafish locomotion displayed significantly different (p < 0.05) activity profiles over the course of typical daylight and

  10. Immunoassay screening of diphenhydramine (Benadryl®) in urine and blood using a newly developed assay.

    Rodrigues, Warren C; Castro, Catherine; Catbagan, Philip; Moore, Christine; Wang, Guohong


    Diphenhydramine (DPH) is a common over the counter antihistamine that produces drowsiness and has the potential to cause driving under the influence of drugs-related accidents. To date there are no commercially available immunoassay screening kits for its detection in biological fluids such as urine and/or blood. We describe a newly developed enzyme-linked immunosorbent assay (ELISA) screen and report on its utility in the analysis of authentic specimens taken from volunteers. The assay is specific for detection of DPH and does not detect closely related antihistamines like brompheniramine, chlorpheniramine, and doxylamine. There is a varying amount of cross-reactivity seen with certain tricyclic compounds, due to similarities in side chain structure with DPH. Intra- and interday precision of the assay were determined to be less than 10%. The assay is highly sensitive and has a working range from 1 to 500 ng/mL for urine and 1 to 250 ng/mL for blood. The assay was further validated with authentic urine and blood specimens obtained from volunteers and coroner's laboratories.

  11. Next-day residual sedative effect after nighttime administration of an over-the-counter antihistamine sleep aid, diphenhydramine, measured by positron emission tomography.

    Zhang, Dongying; Tashiro, Manabu; Shibuya, Katsuhiko; Okamura, Nobuyuki; Funaki, Yoshihito; Yoshikawa, Takeo; Kato, Masato; Yanai, Kazuhiko


    Antihistamines often are self-administered at night as over-the-counter (OTC) sleep aids, but their next-day residual sedative effect has never been evaluated using a reliable quantitative method such as positron emission tomography (PET). We performed a double-blind, placebo-controlled, crossover study in which we evaluated the residual effect the next day after nighttime administration of diphenhydramine, a commonly used OTC sleep aid, in terms of brain H₁ receptor occupancy (H₁RO) measured using ¹¹C-doxepin-PET. We also compared the results of diphenhydramine with those of bepotastine, a second-generation antihistamine. Eight healthy adult male subjects underwent PET measurement the morning (11:00) after random oral administration of diphenhydramine (50 mg), bepotastine (10 mg), or placebo the night before (23:00). Binding potential ratios and H₁ROs were calculated in different brain regions of interest such as the cingulate gyrus, frontotemporal cortex, and cerebellum. Subjective sleepiness and plasma drug concentration also were measured. Calculation of binding potential ratios revealed significantly lower values for diphenhydramine than for bepotastine or placebo in all regions of interest (P drug or the placebo. In conclusion, the next-day residual sedative effect after nighttime administration of the OTC sleep aid diphenhydramine was verified for the first time by direct PET measurement of H₁RO. Taking into account the possible hangover effect of OTC antihistamine sleep aids, care needs to be taken during their administration.

  12. Randomized Trial of Adding Parenteral Acetaminophen to Prochlorperazine and Diphenhydramine to Treat Headache in the Emergency Department.

    Meyering, Stefan H; Stringer, Ryan W; Hysell, Matthew K


    Headaches represent over three million emergency department (ED) visits per year, comprising 2.4% of all ED visits. There are many proposed methods and clinical guidelines of treating acute headache presentations. However, data on intravenous acetaminophen usage in these settings are lacking. In this study, we sought to determine the efficacy of intravenous (IV) acetaminophen as an adjunct to a standard therapy for the treatment of patients who present to the ED with a chief complaint of "headache." We conducted a single site, randomized, double-blind, placebo-controlled trial investigating the clinical efficacy of IV acetaminophen as an adjunct to a standard therapy with prochlorperazine and diphenhydramine for the treatment of patients who present to the ED with a chief complaint of "headache" or variants thereof. (See below for variants). The primary outcome measure of the efficacy of parenteral acetaminophen as an adjunct treatment for headache in addition to a standard therapy was a threshold two-point reduction in visual analog scale (VAS) pain scores on a 1-10 level at 90 minutes. Secondary outcomes measures included assessment of decreased requirement of "rescue" pain medicines, defined as any analgesic medications outside of diphenhydramine, prochlorperazine and acetaminophen, with particular interest to potential opioid-sparing effects with parenteral acetaminophen. Additional secondary outcome measure included time to disposition from arrival in the ED. For the acetaminophen group the initial mean pain score was 8.67, for the placebo group 8.61. At 90 minutes pain score was 2.23 for the acetaminophen group and 3.99 for placebo (pacetaminophen vs. 25/45 (55%) with placebo (p acetaminophen arm and 159 minutes for placebo). However, 17/45 (38%) of patients who received IV acetaminophen required rescue analgesia, opposed to 24/45 (53%) of patients in the placebo group (p=0.13) 95% CI [-5%-34%]. IV acetaminophen when used with prochlorperazine and

  13. Stability of Diphenhydramine Hydrochloride, Lorazepam, and Dexamethasone Sodium Phosphate in 0.9% Sodium Chloride Stored in Polypropylene Syringes.

    Anderson, Collin R; Halford, Zachery; MacKay, Mark


    Chemotherapy induced nausea and vomiting is problematic for many patients undergoing chemotherapy. Multiple-drug treatments have been developed to mitigate chemotherapy induced nausea and vomiting. A patient-controlled infusion of diphenhydramine hydrochloride, lorazepam, and dexamethasone sodium phosphate has been studied in patients who are refractory to first-line therapy. Unfortunately, the physical and chemical compatibility of this three-drug combination is not available in the published literature. Chemical compatibility was evaluated using high-performance liquid chromatography with ultraviolet detection. Visual observation was employed to detect change in color, clarity, or gas evolution. Turbidity and pH measurements were performed in conjunction with visual observation at hours 0, 24, and 48. Results showed that diphenhydramine hydrochloride 4 mg/mL, lorazepam 0.16 mg/mL, and dexamethasone sodium phosphate 0.27 mg/mL in 0.9% sodium chloride stored in polypropylene syringes were compatible, and components retained greater than 95% of their original concentration over 48 hours when stored at room temperature.

  14. Effect of Surfactants and Thickeners on the Stability of Menthol-Diphenhydramine Cream Identified by Magnetic Resonance Imaging.

    Onuki, Yoshinori; Yokokawa, Masamitsu; Utsumi, Shunichi; Obata, Yasuko; Machida, Yoshiaki; Seike, Chieko; Hayashi, Yoshihiro; Takayama, Kozo


    A menthol-diphenhydramine cream is prepared in hospital pharmacies and then prescribed to patients for the treatment of pruritus associated with chronic kidney disease. The purpose of this study is to design a stable formulation without any concern about phase separation during its clinical use on patients. As a preventive measure against phase separation, various surfactants and thickeners were incorporated into the creams. The test creams were stored at 40°C, and then their phase separation behaviors were monitored. The key technology was magnetic resonance imaging T2 mapping. From the T2 maps, some surfactants showed a certain stabilizing effect. In addition, the data analysis using Kohonen's self-organizing map revealed that hydrophilic-lipophilic balance of the surfactant is an important factor for the stabilizing effects of the surfactants. However, as a whole, the effect of surfactant was not sufficient to improve completely the low stability. By contrast, the creams were significantly stabilized by addition of thickeners. In particular, the stabilizing effect of carbomer Hiviswako105(®) (H105) was very high; no phase separation was observed from the cream containing H105 even after 30 d storage at 40°C. This study also verified the combination effect of surfactants and thickeners on the improvement of the emulsion stability. In conclusion, we successfully established a stable formulation of menthol-diphenhydramine cream.

  15. Visible Spectrophotometric determination of Chlorpheniramine maleate and Diphenhydramine hydrochloride in raw and dosage form using Potassium permanganate

    Mohammed Al Bratty


    Full Text Available Two simple, rapid and sensitive spectrophotometric methods developed for Chlorpheniramine Maleate (CPM and Diphenhydramine Hydrochloride (DPH determination in pure and pharmaceutical preparation using Potassium Permanganate. The solvent system used was potassium permanganate. The method developed by adding a known amount of permanganate to CPM and DPH in acid and alkaline medium, the unreacted permanganate was determined at 550 nm; method A and bluish green colour of Manganate at 610 nm; method B. In method A decrease in absorbance or method B increase in absorbance as concentrations of CPM and DPH was measured. Beer’s law was obeyed at a range of 2.5 to 20 μg / ml in both the methods A and B. The method was validated as per International Council for Harmonisation guideline. The proposed methods were effectively used for the determination of CPM and DPH in commercially available syrup. The average percentages of recoveries of CPM were 99.20 ± 1.29% (method A, 100.6% ± 1.43% (method B; DPH 98.50 ± 1.29% (method A and 100.20 ± 1.43% (method B. The methods were efficiently validated and used for quantitative determination of Chlorpheniramine maleate and Diphenhydramine Hydrochloride in pure and syrup preparations.

  16. Chronic toxicity of diphenhydramine hydrochloride and erythromycin thiocyanate to Daphnia, Daphnia magna, in a continuous exposure test system

    Meinertz, Jeffery R.; Schreier, Theresa M.; Bernardy, Jeffry A.; Franz, Jeanne L.


    Diphenhydramine hydrochloride (DH; Benadryl(TM), an over-the-counter antihistamine) and erythromycin thiocyanate (ET; a commonly used macrolide antibiotic) are pharmaceutical compounds whose chronic toxicity to Daphnia magna had not been characterized. Continuous exposure to DH concentrations about 5 times greater than the maximum reported environmental concentration of 0.023 μg/L for 21 days or to ET concentrations about 40 times the maximum reported environmental concentration of 6 μg/L for 21 days did not significantly impact D. magna survival and production. In this study the no observable effect concentration for DH was 0.12 μg/L and for ET was 248 μg/L.

  17. Study on the interaction between diphenhydramine and erythrosin by absorption,fluorescence and resonance Rayleigh scattering spectra


    In pH 4.5 Britton-Robinson(BR)buffer solution,erythrosin(ET)can react with diphenhydramine(DP)to form a 1:1 ion-association complex,which not only results in the change of the absorption spectra,but also results in the great enhancement of resonance Rayleigh scattering(RRS)and the quenching of fluorescence.Furthermore,a new RRS spectrum will appear,and the maximum RRS wavelength was located at about 580 nm.In this work,the spectral characteristics of the absorption,fluorescence and RRS,the optimum conditions of the reaction and the properties of an analytical chemistry were inves- tigated.A sensitive,simple and new method for the determination of DP by using erythrosin as a probe has been developed.The detection limits for DP were 0.0020μg/mL for RRS method,0.088μg/mL for absorption method and 0.094μg/mL for fluorophotometry.There was a linear relationship between the absorbance,RRS and fluorescence intensities and the drug concentration in the range of 0.0067-2.0, 0.29-6.4 and 0.31-3.2μg/mL,respectively.The effects of the interaction of diphenhydramine and erythrosin on the absorption,fluorescence and resonance Rayleigh scattering spectra were discussed. In light polarization experiment,the polarization of RRS at maximum wavelength was measured to be P =0.9779,and it revealed that the RRS spectrum of DP-ET complex consists mostly of resonance scat- tering and few resonance fluorescence.In this study,enthalpy of formation and mean polarizability were calculated by AM1 quantum chemistry method.In addition,the reaction mechanism and the rea- sons for the enhancement of scattering spectra and the energy transfer between absorption,fluores- cence and RRS were discussed.

  18. Potentiometric determination of antihistaminic diphenhydramine hydrochloride in pharmaceutical preparations and biological fluids using screen-printed electrode.

    Frag, Eman Y Z; Mohamed, Gehad G; El-Sayed, Wael G


    The performance characteristic of sensitive screen-printed (SPE) and carbon paste (CPE) electrodes was investigated for the determination of diphenhydramine hydrochloride (DPH) drug in pure, pharmaceutical preparations and biological fluids. Different experimental conditions namely types of materials used to prepare the working electrode (plasticizer), titrant, pH, temperature and life time were studied. Under these conditions, the SPE shows the best performance than CPE with respect to total potential change and potential break at the end point. The SPE and CPE exhibit suitable response to DPH in a concentration range of 1.0.10(-2) to 1.0.10(-6) mol/L with a limit of detection 9.70.10(-7) and 9.80.10(-7) mol/L, respectively. The slope of the system was 55.2±1.0 and 54.7±1.0 mV/decade over pH range 3.0-8.0 and 3-7 for SPE and CPE, respectively. Selectivity coefficients for DPH relative to a numbers of potential interfering substances were investigated. The SPE and CPE show a fast response time of 10 and 16s and were used over a period of 2 months with a good reproducibility. The sensors were applied successfully to determine DPH in pharmaceutical preparations and biological fluids. The results are compared with the official method.

  19. The effects of sucralfate suspension and diphenhydramine syrup plus kaolin-pectin on radiotherapy-induced mucositis

    Barker, G.; Loftus, L.; Cuddy, P.; Barker, B. (Univ. of Missouri, Kansas City (USA))


    A prospective, double-blind study compared the effectiveness of sucralfate suspension with diphenhydramine syrup plus kaolin-pectin in reducing severity and pain of radiation-induced oropharyngeal mucositis. Fourteen patients who received at least 4600 cGy to the oral cavity used one of the mouth rinses four times a day, beginning at 1600 cGy. Data were collected on daily perceived pain and helpfulness of mouth rinse, weekly mucositis grade, weight change, and interruption of therapy. Analysis of data revealed no statistically significant differences between the two groups in any parameter. A retrospective review of 15 patients who had received at least 4600 cGy radiation to the oropharynx but had not used a daily mouth-coating rinse, was compared with the study group. Comparison of the two groups suggested that consistent daily oral hygiene and use of a mouth-coating agent will result in less pain and may reduce weight loss and interruption of radiation because of severe mucositis.

  20. Maternal exposure to diphenhydramine during the fetal period in rats: effects on physical and neurobehavioral development and on neurochemical parameters.

    Moraes, A P; Schwarz, A; Spinosa, H S; Florio, J C; Bernardi, M M


    Previous research from our laboratory suggested that the administration of antihistaminics (H(1) receptor antagonists) to pregnant Wistar rats throughout pregnancy altered brain sexual differentiation and dopaminergic physiology of the offspring. In the present study, we assessed the effects of 20 mg/kg diphenhydramine (DPH) administration to pregnant rats during the fetal period of pregnancy [Gestation Days (GDs) 16-21], a critical period for brain sexual differentiation and central nervous system (CNS) maturation. Maternal body weight and water and food consumption were measured during pregnancy and offspring physical and behavioral development were evaluated during lactation. Offspring open-field behavior was assessed at 21 and 100 days of age. After the final open-field test, male and female sexual behavior, stereotypy following an apomorphine challenge, striatal content of dopamine (DA), the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA), serotonin (5-HT) and the serotonin metabolite 5-hydroxyindolacetic acid (5-HIAA) were assessed. There were no significant treatment-related changes in maternal reproductive parameters, but DPH treatment decreased maternal body weight gain during the treatment period. Offspring physical parameters were not altered in the treated group, and no significant treatment-related changes were found in female open-field measures, sexual behavior or in striatal neurochemical measurements. However, delayed testis descent and altered patterns of sexual behavior occurred in male offspring accompanied by increased striatal DA, decreased striatal DOPAC as well as reduced DOPAC/DA, HVA/DA and 5-HIAA/5-HT ratios. Taken together, these data suggest that exposure to DPH during the fetal period of rat development altered postnatal CNS maturation and sexual development of male offspring via changes in striatal bioamine systems.

  1. Diphenhydramine interferes with MTT reduction assay%苯海拉明等有机胺类约物干扰MTT还原法的应用

    沈耀; 张晨辉; 胡薇薇; 陈忠


    目的:探讨苯海拉明等有机胺类药物对MTT还原法测定细胞活性准确性的影响.方法:采用原代新生大鼠皮层星形胶质细胞模型,以不同浓度的苯海拉明等有机胺类药物分别作用于星形胶质细胞24 h,以形态学观察、Hoechst 33342和PI核荧光双染法对比MTT染色结果.分析苯海拉明等对MTT还原法应用的影响.结果:苯海拉明(10-4 mol/L)、吡拉明(10-4 mol/L)和卓兰替丁(10-3 mol/L)作用于星形胶质细胞能显著增加甲瓒的生成,而核荧光双染法显示,这时星形胶质细胞的增殖和凋亡以及坏死情况并没有发生显著性改变.通过显微镜形态学观察发现,苯海拉明(10-4 moL/L)能显著减少星形胶质细胞膜上的针状晶体--甲瓒.结论:苯海拉明等有机胺类药物通过抑制甲瓒外排而促进胞内MTT被大量还原,从而影响MTT还原法测定细胞活性的准确性.%Objective: To determine the effects of organic amine diphenhydramine on the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye (MTT) reduction assay. Methods: The primarily cultured cortical astrocytes were incubated with various concentrations of diphenhydramine for 24 h. To analyze the effects of diphenhydramine and other organic amines on the MTT assay, the data obtained from the MTT assay were compared with the results obtained from morphological observation and hoechst 33342 and propidium iodide (PI) nucleus double staining. Results: The MTT assay showed that diphendramine ( 10-4 mol/L), pyrilamine ( 10-4 mol/L) and zolatidine ( 10-5 mol/L) caused a significant increase in MTT reduction in astrocytes. However there was no proliferation, apoptosis or necrosis detected by hoechst and PI nucleus double staining. Light microscopy revealed that exocytosis of formazan granules was inhibited by diphendramine. Conclusion: Diphenhydramine and other organic amines may enhance MTT reduction by suppression of MTT formazan exocytosis in astrocytes, which may

  2. The effects of cocaine and diphenhydramine upon the reactivity of rat vas deferens to supramaximal doses of noradrenaline and of other agonists: the mode of action of cocaine.

    Pennefather, J N


    The effects of cocaine on responses to supramaximal concentrations of agonists have been studied in preparations of rat vas deferens. Cocaine 10 muM decreased the mean time to peak and increased the mean magnitude of responses to noradrenaline but not to supramaximal field stimulation of sympathetic fibres, to high potassium or to methoxamine. Diphenydramine 10 muM affected responses to noradrenaline similarly. It is proposed that the prejunctional action of cocaine and of diphenhydramine to reduce the rate of neuronal uptake of noradrenaline may provide a sufficient explanation for the enhanced reactivity of the vas deferens to noradrenaline, as this would allow an increased rate of rise of amine concentration at the receptors. Cocaine also enhanced the reactivity of the vas deferens to acetylcholine. The basis of this enhancement by cocaine of the reactivity of the vas deferens to acetylcholine remains to be established, but clearly is not mediated postjunctionally since responses to carbachol were not similarly affected.

  3. Simultaneous determination of potassium guaiacolsulfonate, guaifenesin, diphenhydramine HCl and carbetapentane citrate in syrups by using HPLC-DAD coupled with partial least squares multivariate calibration.

    Dönmez, Ozlem Aksu; Aşçi, Bürge; Bozdoğan, Abdürrezzak; Sungur, Sidika


    A simple and rapid analytical procedure was proposed for the determination of chromatographic peaks by means of partial least squares multivariate calibration (PLS) of high-performance liquid chromatography with diode array detection (HPLC-DAD). The method is exemplified with analysis of quaternary mixtures of potassium guaiacolsulfonate (PG), guaifenesin (GU), diphenhydramine HCI (DP) and carbetapentane citrate (CP) in syrup preparations. In this method, the area does not need to be directly measured and predictions are more accurate. Though the chromatographic and spectral peaks of the analytes were heavily overlapped and interferents coeluted with the compounds studied, good recoveries of analytes could be obtained with HPLC-DAD coupled with PLS calibration. This method was tested by analyzing the synthetic mixture of PG, GU, DP and CP. As a comparison method, a classsical HPLC method was used. The proposed methods were applied to syrups samples containing four drugs and the obtained results were statistically compared with each other. Finally, the main advantage of HPLC-PLS method over the classical HPLC method tried to emphasized as the using of simple mobile phase, shorter analysis time and no use of internal standard and gradient elution. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Efficacy and tolerability studies evaluating a sleep aid and analgesic combination of naproxen sodium and diphenhydramine in the dental impaction pain model in subjects with induced transient insomnia.

    Cooper, S; Laurora, I; Wang, Y; Venkataraman, P; An, R; Roth, T


    The aim of this study was to evaluate the efficacy and tolerability of novel combination naproxen sodium (NS) and diphenhydramine (DPH) in subjects with postoperative dental pain along with transient insomnia induced by 5 h sleep phase advance. The present studies aimed to demonstrate the added benefit and optimal dosages of the combination product over individual ingredients alone in improving sleep and pain. Each of the two studies was a two-centre, randomised, double-blind and double-dummy trial. In the first study, subjects were randomised into one of the following treatment arms: NS 440 mg/DPH 50 mg, NS 220 mg/DPH 50 mg, NS 440 mg or DPH 50 mg. In the second study, subjects received either NS 440 mg/DPH 25 mg, NS 440 mg or DPH 50 mg. The co-primary end-points in both studies were wake time after sleep onset (WASO) and sleep latency (SL) measured by actigraphy. Other secondary sleep and pain end-points were also assessed. The intent-to-treat population included 712 and 267 subjects from studies one and two, respectively. In the first study, only the NS 440 mg/DPH 50 mg combination showed significant improvements in both WASO vs. NS alone (-70.3 min p = 0.0002) and SL vs. DPH alone (25.50 and 41.50 min respectively, p sleep latency vs. DPH 50 mg and sleep maintenance (WASO) vs. NS 440 mg. There were no serious or unexpected adverse events reported in either study. NCT01280591 (study 1); NCT01495858 (study 2). © 2015 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

  5. Comparison of the Effect of Two Kinds of Iranian Honey and Diphenhydramine on Nocturnal Cough and the Sleep Quality in Coughing Children and Their Parents

    Ayazi, Parviz; Mahyar, Abolfazl; Yousef-Zanjani, Mahdieh; Allami, Abbas; Esmailzadehha, Neda; Beyhaghi, Taraneh


    Coughing in a child induced by upper respiratory tract infections (URTIs) can be a problem, both for the child and its parents. Current studies show a lack of proven efficacy for over-the counter (OTC) medications, but promising data support the use of honey for children. The aim of this study was to compare the effects of two kinds of Iranian honey with diphenhydramine (DPH) on nocturnal pediatric coughs and the sleep quality of children and their parents. This was a clinical trial (registered in IRCT; No.: 28.20.7932, 15 October 2013). The study consisted of 87 patients. All the parents completed a standard previously validated questionnaire. The children were randomly assigned to one of three treatment groups: Group 1, Honey type 1 (Kimia Company, Iran) (n = 42), Group 2, Honey type 2 (Shahde-Golha, Iran) (n = 25), and Group 3, DPH (n = 20). Each group received double doses of the respective treatments on two successive nights. A second survey was then administered via a telephone interview in which the parents were asked the same questions. The mean scores for all aspects of coughs were significantly decreased in each group before and after the treatment. All three treatments improved the cough and sleep scores. Honey type 1 was superior to DPH in improving all aspects of coughs, except the frequency, and Honey type 2 was more effective than DPH in improving all aspects of coughs, except the sleep quality of the child. There was no significant difference between Honey type 1 and 2 in any aspects of cough relief in the present study. The results suggest that honey may provide better cough relief than DPH in children and improve the sleep quality of children and their parents. PMID:28103276

  6. 薄荷脑和樟脑对复方苯海拉明乳膏透皮作用的影响%Effect of menthol and camphor on permeation of compound diphenhydramin cream in vitro

    刘海乐; 周彦彬; 孙银香; 盛小茜; 张杰; 郑志难; 丁劲松


    Objective To determine the effect of menthol and camphor on the permeation of diphenhydramine hydrochloride and benzocaine in compound diphenhydramin cream.Methods The permeation experiments were performed in a modified Franz diffusion cell through porcine skin.The permeability coefficients and the accumulation amounts of diphenhydramine hydrochloride and benzocaine in the receptor fluid and skin were calculated.Results There was no significant difference (P>0.05) in the permeation and accumulation of diphenhydramine hydrochloride between cream with and without menthol and camphor.Menthol and camphor markedly prevented (P<0.01 ) the permeation of benzocaine transporting across the skin and promoted the skin accumulation after 12 h (P<0.05).Conclusion Menthol and camphor not only have pharmacological activities but also act as penetration enhancers.Those compounds, which can inhibit the benzocaine permeation transdermally and locally, may be beneficial to the topical treatment of compound diphenhydramin cream in clinical practice.%目的 研究薄荷脑和樟脑对复方苯海拉明乳膏中盐酸苯海拉明和苯佐卡因透皮作用的影响.方法 采用改良Franz直立式扩散池,以离体乳猪皮肤为渗透屏障进行体外透皮扩散试验,以盐酸苯海拉明和苯佐卡因的累积渗透量、稳态流量及皮肤滞留量为指标,考察薄荷脑和樟脑在处方中的透皮调节作用.结果 薄荷脑和樟脑对盐酸苯海拉明的累积渗透量、稳态流量及皮肤滞留量均无显著影响(P>0.05);对苯佐卡因的累积渗透量、稳态流量有显著抑制作用(P<0.01),并能提高其12 h皮肤滞留量(P<0.05).结论 薄荷脑和樟脑在复方苯海拉明乳膏中除发挥其药理活性外,还能调节药物的透皮吸收,其对苯佐卡因经皮渗透的抑制及皮肤滞留量的增加可能更有利于复方苯海拉明乳膏发挥局部治疗作用.

  7. Simultaneous Determination of Ibuprofen and Diphenhydramine Hydrochloride Dissolved from their Soft Capsules by a RP-HPLC Method%复方布洛芬苯海拉明软胶囊溶出度测定方法

    相文杰; 毛如虎; 李明


    A RP-HPLC method was developed and validated for the simultaneous determination of ibuprofen and diphenhydramine hydrochloride in the dissolution medium. The chromatographic separation was achieved on a C18 column using acetonitrile-methanol- PBS at pH 3.5 (3:2:5, v/v) as the mobile phase with the flow rate at 1.0mL·min-1. The detective wavelength was 215 nm. The effects of the conditions such as rotation rate and dissolution medium on the dissolution curves of the drugs were investigated. The linear quantitation ranges of ibuprofen and diphenhydramine hydrochloride were 55.1~551 μg·mL-1 and 6.9~ 69 μg·mL-1, respectively. The mean recoveries were 100.8%±0.7% for ibuprofen and 101.4%±0.6% for diphenhydramine hydrochloride. The dissolution limitation was over 80% of the labeled amount within 30 min.%建立了同时测定布洛芬和苯海拉明的含量反相高效液相法,确定以C18柱,流动相为乙腈-磷酸盐缓冲盐-甲醇为3∶2∶5,流速为1.0mL·min-1,检测波长为210 nm的色谱条件;通过对溶出转速、介质和溶出曲线等条件考察,建立了本软胶囊溶出度的测定方法.结果:布洛芬在55.1~551μg· mL-1浓度范围内呈良好的线性关系,苯海拉明在6.9~69 μg· mL-1浓度范围内呈良好的线性关系,布洛芬和盐酸苯海拉明的平均回收率分别100.8%±0.7%和101.4%±0.6%,溶出度测定结果限度为30 min大于标示量的80%.

  8. Study of crystallization of endogenous surfactant in Eudragit NE30D-free films and its influence on drug-release properties of controlled-release diphenhydramine HCl pellets coated with Eudragit NE30D.

    Lin, A Y; Muhammad, N A; Pope, D; Augsburger, L L


    This study investigates the crystallization of the endogenous surfactant nonoxynol 100 in Eudragit NE30D-free films during storage and the influences of nonoxynol 100 on the dissolution of diphenhydramine hydrochloric acid (HCl) pellets coated with Eudragit NE30D before and after aging at ambient conditions. Polarizing light microscopy showed that when Eudragit NE30D-free films were stored at ambient conditions, off-white, flower-shaped crystals formed and increased in the polymer film as storage time increased. Also, x-ray diffraction showed polymer crystals in the aged free film. Thermogravimetric analysis showed no evidence of combined volatile molecules with the polymer molecules, and Fourier transformed infrared spectroscopy (FTIR) data suggested the same chemical composition of the polymer before and after phase separation. Further, from normal light microscopy, the appearance of the melting droplets in the polymer film indicated that the polymer molecules did not form the crystals. After the extraction of nonoxynol 100 by water, the free film formed by the water-extracted Eudragit NE30D was found free of the crystals after aging at the same conditions. The combination of the thermogravimetric analysis, FTIR, and microscopy showed that the origin of the crystals in dry Eudragit NE30D-free films came from nonoxynol 100, and not from the polymer molecules themselves. Monitoring by differential scanning calorimeter, it was found that the rates of crystallization of nonoxynol 100 were faster when the films were stored at 30 degrees C and 40 degrees C than when stored at ambient conditions and 45 degrees C. When stored at -5 degrees C, the crystallization rate was nearly zero. As the temperature got closer to melting temperature, the crystallization rate was very low because the system was in a thermodynamically disfavored state. The rate gradually increased and finally passed through a maximum as the crystallization temperature decreased. As the temperature kept

  9. 布洛芬盐酸苯海拉明分散片的制备及质量评价%Preparation of Ibuprofen and Diphenhydramine Hydrochloride Dispersible Tablets and Their Quality Evaluation

    张玉洁; 罗永煌; 戈振凯; 田翠翠; 张贺; 尼玛仓木拉


    Objective To prepare and evaluate ibuprofen and diphenhydramine hydrochloride dispersible tablets in order to provide data for state category Ⅲ new drug application. Methods The formulations were optimized with disintegration time, dispersion homogeneity, rigidity and taste as reference parameters by single-factor and orthog onal tests. HPLC was performed to determine the content and dissolution of the tablets. Results Disintegrating a gent-6% PVPP (with an internal and external ratio of 2: 1) filling agent -24% MCC adhesive agent -2% PVPk30 solution and correctant with an aspartame/steviosin ratio of 1 ~ 9. The dispersible tablets thus prepared were good in taste, with a disintegration time of 64.6±5.73 s. The cumulative dissolution per- centage was more than 80 % within 5 min. Drug content and dispersion homogeneity were within the speci fied scope. Conclusion The prescription of the dispersible tablet is reasonable; the preparation process is simple the quality indexes conform to the requirement of dispersible tablets.%目的:筛选布洛芬盐酸苯海拉明分散片的最优处方并对其质量进行评价,为申报三类新药提供核心数据.方法:以崩解时限、分散均匀性、硬度和口感为指标,单因素试验筛选崩解剂和矫味剂,正交试验优化处方,湿法制粒制备分散片,HPLC测定其片剂的含量和溶出度.结果:崩解剂为6%PVPP(内外加比例2:1),填充剂为24%MCC,粘合剂为2%的PVPk30溶液适量,矫味剂占2%且阿司帕坦/甜菊素为1:9,所制备的分散片口感良好,崩解时限为64.63±3.58S,5min分散片中布洛芬和盐酸苯海拉明的溶出度均达到了80%以上,含量和分散均匀性均在规定范围内.结论:该分散片处方合理,工艺简单,质量指标符合分散片要求.

  10. Simultaneous determination of pseudoephedrine and diphenhydramine in human plasma by liquid chromatography-tandem mass spectrometry%液相色谱-串联质谱法同时测定人血浆中伪麻黄碱和苯海拉明

    韩莹; 陈笑艳; 谢智勇; 钟大放


    @@ 伪麻黄碱(pseudoephedrine)为拟交感神经类药物,临床常用于治疗感冒、支气管炎等上呼吸道感染疾病.苯海拉明(diphenhydramine)为H1-受体拮抗剂,具抗组胺活性,同时还具镇静、止呕和抗副交感神经生理作用等特点.临床上常将二者复方用药,既能发挥伪麻黄碱消除上呼吸道粘膜充血的功能,又可利用苯海拉明促进睡眠、有助于机体自身免疫系统发挥作用等特点.

  11. LC-MS/MS法测定人血浆中苯海拉明血药浓度及其制剂的生物等效性研究%Determination of Diphenhydramine in Human Plasma by LC-MS/MS and Bioequivalence Study of Its Preparation

    刘世军; 曹若明; 崔晞; 孙克明; 刘宪勇; 张敏; 郑慧敏


    OBJECTIVE: To develop a method for the determination of diphenhydramine in human plasma, and to study bioequivalence of its preparation in healthy volunteers. METHODS: After blood sample processing, LC-MS/MS method was used. The determination was performed on Inertsil Hilic column (150 mm×3.0 mm,5 μm) with mobile phase consisted of acetonitrile-wa-ter (10 mmol/L ammonium acetate)-formic acid (40:60:1, V|V|V). ESI was applied and operated in positive ion mode: mlz 256→ 167 for diphenhydramine and mlz 344→215 for clemastine (IS) under multiple reaction monitoring (MRM) mode. RESULTS: The linear ranges of diphenhydramine were 0.5-125 ng/ml (r=0.996 5); RSDs of intra-day and inter-day were less than 8% , and method recoveries were 99.4%-103.4% and extraction recoveries were 71.9%-75.3%. Main pharmacokinetic parameters of test preparation and reference preparation after oral administration were as follows: t1/2were(9.892 ± 1.615) h and (10.745 ± 3.227)h; tmax were (2.00 ± 0.81) h and (1.78 ± 0.55)h; cmax were (90.4 ± 20.6)h and (103.0 ± 30.1) h; AUC0-36 h were (806.293 ± 211.453) h and (827.856 ± 223.996)h. CONCLUSIONS: The method is sensitive and accurate, which is suitable for the determination of plasma concentration and bioequiavailability study of diphenhydramine. Two preparations are bioequivalent.%目的:建立测定人血浆中苯海拉明血药浓度的方法,并进行其生物等效性研究.方法:血样经处理后,采用高效液相色谱串联质谱电喷雾(LC-MS/MS)法进样测定.色谱柱为Intersil Hilic(150 mm×3.0mm,5 μm),流动相为乙腈-水(10 mmol/L乙酸铵)-甲酸(40:60:1,V/V/V);电喷雾电离(ESI)离子源,正离子模式,多级反应监测(MRM)方式检测,离子对分别为m/z 256→167(苯海拉明)、m/z 344→215(氯马斯汀,内标).结果:苯海拉明血药浓度在0.5~125 ng/ml范围内线性关系良好(r=0.996 5);日内、日间RSD均<8%,方法回收率为99.4%~103.4%,提取回收率为71.9%~75

  12. Liver failure induced by overdose of paracetamol, pseudoephedrine hydrochloride and dextromethorphan hydrobromide tablets Ⅱ/paracetamol, pseudoephedrine hydrochloride,diphenhydramine hydrochloride and dextromethorphan hydrobromide tablets%氨酚伪麻美芬片Ⅱ/氨麻苯美片过量致肝衰竭

    王开利; 徐长江; 金晶; 高登莲; 邢汉前; 颜丽; 赵军


    A 22-year-old man developed nausea and vomiting following suicide attempt taking 120 paracetamol, pseudoephedrine hydrochloride and dextromethorphan hydrobromide tablets Ⅱ /paracetamol, pseudoephedrine hydrochloride, diphenhydramine hydrochloride and dextromethorphan hydrobromide tablets (total dose of paracetamol 39 g). He was hospitalized about 13 hours after ingesting the drug. Laboratory tests revealed following levels and values; ALT 7385 U/L, Tbil 26.5 μmol/L, Dbil 15.4 μmol/L, PTA 23. 1% , and lactate 3.9 mmol/L. Drug-induced acute liver failure were diagnosed. He received treatment with liver-protective drugs, molecular adsorbent recirculating system (MARS) , and plasma exchange. On day 13 after admission, the patient nearly recovered to normal condition. Repeat liver function tests showed the following levels; ALT 146 U/L, Tbil 16.7 μmol/L, and Dbil 8. 3 μmol/L; and then he was discharged.%1例22岁男性,因企图自杀口服氨酚伪麻美芬片Ⅱ/氨麻苯美片120片(对乙酰氨基酚总剂量39 g),出现恶心呕吐,服药后13 h入院。实验室检查:丙氨酸转氨酶(ALT)7385 U/L,总胆红素(TBil)26.5μmol/L,直接胆红素(DBi1)15.4 μmol/L,凝血酶原活动度23.1%;血乳酸3.9 mmol/L。诊断为药物性肝衰竭。给予保肝药物,分子吸附再循环和血浆置换治疗。入院第13天患者基本恢复正常,肝功能复查:ALT 145U/L,TBil 16.7 μmol/L,DBil 8.3μmol/L,遂出院。

  13. Comparison of Lorazepam, Diphenhydramine, Haloperidol Combined with Tropisetron and Dexamethasone Combined with Tropisetron Efficacy in Preventing Emesis Induced by Highly Emetogenic Chemotherapy%劳拉西泮、苯海拉明、氟哌啶醇联合托烷司琼对比地塞米松联合托烷司琼预防高致吐风险化疗呕吐的疗效

    郭秋云; 于世英


    目的 探讨劳拉西泮(Ativan)、苯海拉明(Benadryl)和氟哌啶醇(Haldol)的方案(以下简称ABH)联合托烷司琼和地塞米松联合托烷司琼用于高致吐风险化疗[参见2011版多国癌症支持治疗学会(MASCC)止吐指南]后的急性、延迟性呕吐的疗效.方法 104例应用高致吐风险药物单天化疗的患者随机分为ABH组和地塞米松组,两组均在化疗前半小时静脉滴注托烷司琼5 mg,ABH组于化疗头4天予以劳拉西泮0.34 mg、苯海拉明25 mg、氟哌啶醇1.5 mg口服,每天3次;地基米松组于化疗当天予以地塞米松20 mg口服,化疗后3天予以地塞米松8 mg口服,每天2次.使用MASCC止吐问卷及生活功能指数(呕吐)问卷,了解患者急性及延迟性呕心呕吐控制率及生活质量.结果 ABH组和地塞米松组各入组52名患者.两组恶心、呕吐的控制均良好,急性恶心的控制率ABH组和地塞米松组分别为62%和52%,延迟性恶心情况分别为23%和17%,急性呕吐分别为88%和87%;延迟性呕吐分别为77%和65%,ABH的疗效优于地塞米松,但两者差异无统计学意义,可能与样本量小相关.值得一提的是,在延迟性恶心程度控制方面ABH组优于地塞米松组(2.63vs.3.69),两组差异有统计学意义(P<0.05).两组患者的生活质量均受到中度影响,差异无统计学意义,且均未发生严重不良反应.结论 劳拉西泮、苯海拉明、氟哌啶醇(ABH)联合5HT-3受体拮抗剂预防高致吐风险化疗后的恶心呕吐有一定疗效,可用于化疗相关恶心呕吐的防治.%Objective To comparè the efficacy of lorazepam,diphenhydramine and haloperidol(abbreviation as ABH)combined with Tropisetron therapies in preventing emesis induced by highly emetogenic chemotherapy refer to 2011 edition of MASCC antiemetic guidelines.Methods One hundred and four patients treated with highly emetogenic single day chemotherapy were randomized into ABH and dexamethasone group.Both groups

  14. Drug: D03854 [KEGG MEDICUS

    Full Text Available Tract/Pulmonary Agents Antihistamines Diphenhydramine D03854 Diphenhydramine citrate (USP) Target-based cla...ANTIHISTAMINES, ANESTHETICS, ETC. D04A ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC. D04AA Antihi...stamines for topical use D04AA32 Diphenhydramine D03854 Diphenhydramine citrate (US...(USP) Antiparkinson Agents Anticholinergics Diphenhydramine D03854 Diphenhydramine citrate (USP) Respiratory

  15. Drug: D03360 [KEGG MEDICUS

    Full Text Available 26 Epidermides 264 Analgesics, anti-itchings, astringents, anti-inflammatory agents 2642 Antihistamine...ICS, ETC. D04A ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC. D04AA Antihistamine... Tract/Pulmonary Agents Antihistamines Diphenhydramine D03360 Diphenhydramine laurylsulfate (JAN) Target-bas...Antiparkinson Agents Anticholinergics Diphenhydramine D03360 Diphenhydramine laurylsulfate (JAN) Respiratory

  16. Study of Preparation Recipe Preference of Diphenhydramine Hydrochloride Soft Capsules%盐酸苯海拉明软胶囊的处方优选研究

    谭银合; 孙维广; 温新国


    目的 优选稳定的盐酸苯海拉明软胶囊处方.方法 首先检索国外同品种的有关资料,通过组合胶囊壳配方与内容物配方制备样品,进行初步稳定性考察评价,并对优化处方进行验证.结果 按照A4处方制备的样品质量稳定.结论 组合处方A4最佳.

  17. Drug: D02419 [KEGG MEDICUS

    Full Text Available , INCL. ANTIHISTAMINES, ANESTHETICS, ETC. D04AA Antihistamines for topical use D0... Diphenhydramine D02419 Diphenhydramine salicylate (JAN) Respiratory Tract/Pulmonary Agents Antihistamines D

  18. Drug: D03285 [KEGG MEDICUS

    Full Text Available ICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC. D04A ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC. D04AA Antihistamines for top...ical use D04AA32 Diphenhydramine D03285 Diphenhydramine tannate (JP16) R RESPIRATOR

  19. Drug: D04311 [KEGG MEDICUS

    Full Text Available D04311 Mixture, Drug dl-Methylephedrine hydrochloride - diphenhydramine mixt; Asdrin (TN) dl-Methylephedrine hydrochloride [DR:D02109], Diphenhydramine hydrochloride [DR:D00669] PubChem: 17398049 ...

  20. Dermatographia

    ... your doctor may recommend allergy medications such as cetirizine (Zyrtec) or diphenhydramine (Benadryl). Signs and symptoms of dermatographia ... medications such as diphenhydramine (Benadryl), fexofenadine (Allegra) or cetirizine (Zyrtec). To reduce discomfort and prevent the symptoms ...

  1. Drug: D04425 [KEGG MEDICUS

    Full Text Available D04425 Mixture, Drug Diphenhydramine salicylate - hydrocortisone acetate - benzalko...nium chloride - chlorhexidine hydrochloride mixt; Despa (TN) Diphenhydramine salicylate [DR:D02419], Hydrocortisone...ts affecting individual organs 23 Digestive organ agents 239 Miscellaneous 2399 Others D04425 Diphenhydramine salicylate - hydrocorti...sone acetate - benzalkonium chloride - chlorhexidine hydrochloride mixt PubChem: 17398102 ...

  2. Drug: D08732 [KEGG MEDICUS

    Full Text Available D08732 Mixture, Drug Diphenhydramine - dry distillation tar of defatting soybean mi...xt; Diphenhydramine - glyteer mixt; Glypas C (TN) Diphenhydramine [DR:D00300], Dry distillation tar of defatting soybean (Glyteer) [DR:D08734] PubChem: 96025415 ...

  3. Drug: D00669 [KEGG MEDICUS

    Full Text Available cellular function 44 Allergic agents 441 Antihistamines 4411 Diphenhydramines D00...TIHISTAMINES, ANESTHETICS, ETC. D04AA Antihistamines for topical use D04AA32 Diph...ticholinergics Diphenhydramine D00669 Diphenhydramine hydrochloride (JP16/USP) Respiratory Tract/Pulmonary Agents Antihistamine

  4. Drug: D08769 [KEGG MEDICUS

    Full Text Available D08769 Mixture, Drug Diphenhydramine hydrochloride - calcium bromide mixt; Rescalmi...n (TN) Diphenhydramine hydrochloride [DR:D00669], Calcium bromide [DR:D01723] Therapeutic category: 4419 The... Antihistamines 4419 Others D08769 Diphenhydramine hydrochloride - calcium bromide mixt PubChem: 96025452 ...

  5. 21 CFR 341.72 - Labeling of antihistamine drug products.


    ... citrate, diphenhydramine hydrochloride, or doxylamine succinate identified in § 341.12(f), (g), and (h... diphenhydramine citrate, diphenhydramine hydrochloride, or doxylamine succinate identified in § 341.12(f), (g... 6 years of age: consult a doctor. (8) For products containing doxylamine succinate identified...

  6. Pharmacokinetics and Bioequivalence of Paracetamol, Dextromethorphan Hydrochloride, Pseudoephedrine Hydrochloride and Diphenhydramine Hydrochloride Tablets in Healthy Volunteers%氨麻苯美片人体生物等效性研究

    胡玉钦; 张运好; 侯艳宁; 赵曦; 张彦玲; 杨汉煜


    目的 评价2种氨麻苯美片的人体生物等效性.方法 20名健康受试者按两制剂双周期交叉试验设计口服2种氨麻苯美片后,采用高效液相色谱-质谱法测定血浆中伪麻黄碱、O-去甲右美沙芬和苯海拉明的浓度,采用高效液相色谱-紫外法测定血浆中对乙酰氨基酚的浓度,使用DAS1.0软件计算各药动学参数并进行生物等效性统计分析.结果 参比制剂和受试制剂中对乙酰氨基酚的ρ_(max)分别为(6.16±1.24)和(6.04±1.03)mg·L~(-1),t_(max)分别为(1.31±0.69)和(1.50±0.70)h,AUC_(0-16h)分别为(29.17±6.67)和(28.76±6.29)mg·h·L~(-1);伪麻黄碱的ρ_(max)分别为(210.0±30.3)和(214.6±35.7)μg·L~(-1),t_(max)分别为(2.33±1.08)和(2.23±1.19)h,AUC_(0-24h)分别为(1 887.4±364.3)和(1 936.8±444.3)μg·h·L~(-1);苯海拉明的ρ_(max)分别为(84.4±24.6)和(92.2±29.2)μg·L~(-1),t_(max)分别为(2.75±1.11)和(2.98±1.06)h,AUC_(0-36 h)分别为(819.2±284.7)和(937.5±391.4)μg·h·L~(-1);O-去甲右美沙芬的ρ_(max)分别为(6.63±2.90)和(6.00±2.15)μg·L~(-1),t_(max)分别为(2.73±0.92)和(2.58±1.05)h,AUC_(0-24 h)分别为(42.79±13.02)和(40.24±11.92)μg·h·L~(-1).以AUC_(0-t)计算,受试制剂中对乙酰氨基酚、伪麻黄碱、苯海拉明和右美沙芬的相对生物利用度分别为(99.1±9.6)%,(102.7±13.5)%,(114.3±25.3)%和(95.6±17.3)%.结论 统计分析结果表明,2种氨麻苯美片具有生物等效性.

  7. Pharmacokinetics and Bioequivalence of Paracetamol, Pseudoephedrine Hydrochloride, Diphenhydramine Hydrochloride and Dextromethorphan Hydrobromide Tablets in Healthy Volunteers%氨麻苯美片在健康人体内药动学和生物等效性

    张运好; 胡玉钦; 张伟东; 侯艳宁


    20名健康志愿者按两个制剂双周期交叉试验设计口服2种氨麻苯美片,采用HPLC-MS/MS法测定血浆中的伪麻黄碱、苯海拉明和O-去甲右美沙芬,采用HPLC-UV法测定血浆中的对乙酞氨基酚,结果表明:受试制剂中对乙酞氨基酚、伪麻黄碱、苯海拉明和O-去甲右美沙芬的相对生物利用度分别为(104.2±10.4)%,(107.4±17.9) %,(106.0±23.1)%和(106.5±17.4)%,表明两种氨麻苯美片具有生物等效性.

  8. 复方氨酚苯海拉明片中对乙酰氨基酚和咖啡因的含量测定%Determination of Paracetamol and Cafeine in Compound Paracetamol and Diphenhydramine Hydrochloride Tablets

    郭瑞锋; 郄冰冰


    目的 建立高效液相色谱法(HPLC法)同时测定复方氨酚苯海拉明片中对乙酰氨基酚和伽啡因的含量.方法 色谱柱为C18柱,流动相为甲醇-2%冰醋酸(30:70),检测波长为275 nm,流速为1.0 mL/min,柱温为室温.结果 对乙酰氨基酚和咖啡因的线性范围分别为0.75~4.50 mg/mL(r=0.999 9)和0.075~0.45 mg/mL(r=0.999 9),平均回收率分别为99.2%(RSD=1.0%)和99.6%(RSD=0.8%);两种成分能够达到很好的分离且柱效较高,辅料对测定无干扰.结论 HPLC法简便快速,准确可靠,可作为该复方制剂中两种成分的质量控制方法.

  9. HPLC测定复方氨酚苯海拉明片中对乙酰氨基酚和咖啡因含量%Determination of acetaminophen and caffeine in Compound Paracetamol and Diphenhydramine Hydro chloride Tablets by HPLC

    郑琰; 李荣华; 王继玉


    目的 建立高效液相色谱法测定复方氨酚苯海拉明片中对乙酰氨基酚和咖啡因的含量.方法 采用KromasilC18色谱柱(4.5 mm×150 mm,5μm),流动相为甲醇-水(30:70),流速为1.0 mL·min-1,检测波长为280 nm,柱温为室温,进样体积为20μL.结果 对乙酰氨基酚和咖啡因的线性范围分别为80~320 mg·L-1(r=0.999 7,n=7)和10~30 mg·L-1(r=0.999 7,n=5);高中低3种浓度的平均回收率分别为100.7%(RSD=0.69%),101.3%(RSD=0.53%),n=9.结论 本方法 简便、准确、灵敏、回收率高.

  10. Drug: D04806 [KEGG MEDICUS

    Full Text Available D04806 Mixture, Drug Hydrocortisone acetate - diphenhydramine hydrochloride - fradi...omycin sulfate mixt; Strong restamin cortisone (TN) Hydrocortisone acetate [DR:D00165], Diphenhydramine hydr... Analgesics, anti-itchings, astringents, anti-inflammatory agents 2649 Others D04806 Hydrocortisone acetate

  11. Drug: D00300 [KEGG MEDICUS

    Full Text Available 26 Epidermides 264 Analgesics, anti-itchings, astringents, anti-inflammatory agents 2642 Antihistamine... D04A ANTIPRURITICS, INCL. ANTIHISTAMINES, ANESTHETICS, ETC. D04AA Antihistamines...s Diphenhydramine D00300 Diphenhydramine (JP16/INN) Respiratory Tract/Pulmonary Agents Antihistamines Diphen

  12. Drug: D04324 [KEGG MEDICUS

    Full Text Available D04324 Mixture, Drug Noscapine hydrochloride - dl-methylephedrine hydrochloride - d...iphenhydramine hydrochloride mixt; Sekiel (TN) Noscapine hydrochloridie [DR:D02172], dl-Methylephedrine hydr...ratory organ agents 222 Antitussives 2229 Others D04324 Noscapine hydrochloride - dl-methylephedrine hydrochloride - diphenhydramine hydrochloride mixt PubChem: 17398052 ...

  13. Drug: D04707 [KEGG MEDICUS

    Full Text Available D04707 Mixture, Drug Lithospermum root extract - ethyl aminobenzoate - dibucaine hydrochloride - diphenhydr...amine hydrochloride - cetrimide mixt; Borraginol N (TN) Lithospermum root extract [D...R:D04705], Ethyl aminobenzoate [DR:D00552], Dibucaine hydrochloride [DR:D02220], Diphenhydramine hydrochloride [DR:D00669], Cetrimide [DR:D02164] PubChem: 17398145 ...

  14. Drug: D08715 [KEGG MEDICUS

    Full Text Available D08715 Mixture, Drug dl-Camphor - dl-menthol - methyl salicylate - diphenhydramine ...mixt; Salymetick S (TN) dl-Camphor [DR:D00098], (dl-Menthol [DR:D04849] | l-Menthol [DR:D00064]), Methyl salicylate [DR:D01087], Diphenhydramine [DR:D00300] PubChem: 96025398 ...

  15. [Effect of new antihistaminic preparations on the body's immunologic reactivity].

    Mashkovskiĭ, M D; Veksler, I G; Kaminka, M E; Iakimenko, V A


    The effect of new antihistaminic drugs, phencarol and bicarphen, on immunologic reactivity of experimental animals was studied in comparison with diphenhydramine. Phencarol and bicarphen inhibited the delayed type allergic reactions to a greater degree than diphenydramine. Unlike diphenhydramine, phencarol and bicarphen injected simultaneously with test-antigen markedly decreased the number of rosette-forming lymphocytes in the immunocompetent organs (spleen, thymus, lymph nodes). Phencarol, bicarphen and diphenhydramine produced the same inhibitory effect on the content of antibody-producing cells in the spleen of mice.

  16. Drug: D08731 [KEGG MEDICUS

    Full Text Available D08731 Mixture, Drug Methyl salicylate - diphenhydramine mixt; Air salonpas (TN) Me...thyl salicylate [DR:D01087], Diphenhydramine [DR:D00300], Glycol salicylate [DR:D01557], l-Menthol [DR:D0006...4], d-Camphor [DR:D06392], Benzyl nicotinate [DR:D01419] Therapeutic category: 2649 Therapeutic category of dr...64 Analgesics, anti-itchings, astringents, anti-inflammatory agents 2649 Others D08731 Methyl salicylate - diphenhydramine mixt PubChem: 96025414 ...

  17. Severe erythema multiforme-type drug eruption induced by paracetamol, pseudoephedrine hydrochloride and dextromethorphan hydrobromide tablets Ⅱ/paracetamol, pseudoephedrine hydrochloride, diphenhydramine hydrochloride and dextromethorphan hydrobromide ta%氨酚伪麻美芬片Ⅱ/氨麻苯美片致重症多形性红斑型药疹

    张秀红; 陆一


    1例55岁女性患者,因上呼吸道感染每天先后服用氨酚伪麻美芬片Ⅱ(日用片)1片及氨麻苯美片(夜用片)1片.2周后,患者面部出现红疹,且逐渐增多,延及躯干和四肢.并有口腔黏膜糜烂;结膜充血,睑缘处糜烂;脚趾处密集水疱;大阴唇可见红斑,T 39.2℃.尿常规检查:WBC 182.2 个/μL,RBC 89.6 个/μL,酮体(+),白细胞酯酶(++),葡萄糖(++++),潜血(+++).给予抗过敏、预防感染、对症及支持治疗.4 d后病情好转,13 d皮疹基本消退.

  18. Pharmacokinetics and bioequivalence of paracetamol in compound tablets of paracetamol, pseudoephedrine and dextromethorphan or paracetamol,pseudoephedrine,diphenhydramine and dextromethorphan in healthy volunteers%氨酚伪麻美芬片Ⅱ/氨麻苯美片中对乙酰氨基酚的药动学和生物等效性

    邓鸣; 胡玉钦; 牛坤; 张运好; 侯艳宁


    目的:研究氨酚伪麻美芬片Ⅱ/氨麻苯美片中对乙酰氨基酚的人体药动学和生物等效性.方法:采用随机交叉试验设计,20名健康男性受试者分别单剂量口服氨酚伪麻美芬片Ⅱ/氨麻苯美片受试制剂和参比制剂2片,高效液相色谱法测定血浆中对乙酰氨基酚的浓度.结果:氨酚伪麻美芬片Ⅱ受试制剂和参比制剂中对乙酰氨基酚的Cmax分别为(7.6±s 2.1)和(6.6±1.2)mg·L-1,tmax分别为(0.9±0.6)和(1.1±0.6)h,A UC0~16分别为(29±4)和(28±5)mg·h·L-1,受试制剂中对乙酰氨基酚的相对生物利用度为(103±8)%.氨麻苯美片中Cmax分别为(6.0±1.0)和(6.2±1.2)mg·L-1,tmax分别为(1.5±0.7)和(1.3±O.7)h,AUC0~16分别为(29±6)和(29±7)mg·h·L-1,相对生物利用度为(99±10)%.结论:按对乙酰氨基酚测定,受试制剂与参比制剂具有生物等效性.

  19. Studies on Quantitative Determination of Ingredients in "Dextromethorphan Hydrobromide Diphenhydramine Hydrochloride Paracetamol Pseudoephedrine Hydrochloride Dispersed Tablets" by HPLC%高效液相色谱法测定美息伪麻拉明分散片中组分含量的研究

    罗虹; 王利杰; 王军


    目的:采用高效液相色谱法考察并建立了测定复方制剂美息伪麻拉明分散片中对乙酰氨基酚(Par)、氢溴酸右美沙芬(Dex)、盐酸苯海拉明(Dip)和盐酸伪麻黄碱(Pse)的含量.方法:色谱柱为Diamonsil-C18(200 mm×4.6 mm,5 μm),测定Par用乙腈-甲醇-0.05 mol·L-1磷酸二氢钾溶液(5∶1∶25)为流动相,检测波长为245 nm,测定Dex、Dip和Pse用pH 3.3甲酸钠缓冲液-乙腈-甲醇-十二烷基硫酸钠(32∶28∶5∶0.06=V∶V∶V∶W)为流动相,检测波长为256 nm.结果:Par、Dex、Pse、Dip浓度在2.06~20.60 μg·mL-1,0.11~1.06,0.20~2.02,0.10~1.01 mg·mL-1范围内与峰面积呈良好的线性关系,r分别为0.999 7,0.999 4,0.999 5,0.999 7.平均回收率依次为100.2%,99.28%,100.6%,100.7%.结论:本法精密度好,结果准确可靠.适用于该复方制剂的质量检验分析.

  20. Efeitos hemodinâmicos do atracúrio e do cisatracúrio e o uso de difenidramina e cimetidina Efectos hemodinámicos del atracurio y del cisatracurio y el uso de la difenidramina y la cimetidina Hemodynamic effects of atracurium and cisatracurium and the use of diphenhydramine and cimetidine

    Claudia Maria Nogueira Correa


    Full Text Available JUSTIFICATIVA E OBJETIVOS: Haja visto que atracúrio pode causar hipotensão arterial no homem, investigaram-se os efeitos hemodinâmicos promovidos pelo atracúrio e pelo cisatracúrio e a proteção hemodinâmica conferida pela difenidramina e cimetidina em ratos. MÉTODO: 1 Ratos Wistar anestesiados com pentobarbital sódico e preparados de acordo com Brown e col. para avaliar doses de atracúrio e cisatracúrio para redução de T4/T1 da sequência de quatro estímulos maior ou igual a 95%. 2 Avaliação das alterações hemodinâmicas de atracúrio e cisatracúrio por injeção venosa, medindo-se a pressão arterial sistêmica da artéria carótida e eletrocardiograma de ratos. 3 Observação de proteção hemodinâmica pelo tratamento prévio com difenidramina (2 e/ou cimetidina (4 por injeção venosa. Análise estatística: teste t de Student, ANOVA. RESULTADOS: O atracúrio e o cisatracúrio não modificaram a pressão arterial média (PAM nas doses de 1 e 0,25, respectivamente. Doses de 4 promoveram diminuição da PAM de 62,8 ± 4,5% do controle para o atracúrio, e de 82,5 ± 2,3% do controle para o cisatracúrio. Com difenidramina e cimetidina, a pressão sistólica diminuiu 95,4 ± 2,5% do controle. Com cimetidina, pressão diastólica diminuiu 82,7 ± 8,4% do controle. O efeito conjunto sobre as pressões sistólica e diastólica refletiu-se nos valores observados da PAM. CONCLUSÕES: A difenidramina e a cimetidina, isoladamente, não impediram a diminuição da pressão arterial média induzida pelo atracúrio. No entanto, associação destes dois fármacos foi eficaz na prevenção dos efeitos hemodinâmicos induzidos pelo atracúrio. O cisatracúrio nas doses do experimento não promoveu diminuição da pressão arterial que justificasse as medidas preventivas aplicadas nos grupos onde se utilizou o atracúrio.JUSTIFICATIVA Y OBJETIVOS: Habida cuenta de que el atracurio puede causar hipotensión arterial en el hombre, se investigaron los efectos hemodinámicos promovidos por el atracurio y por el cisatracurio, y la protección hemodinámica dada por la difenidramina y la cimetidina en ratones. MÉTODO: 1 Ratones Wistar anestesiados con pentobarbital sódico y preparados de acuerdo con Brown y col. para evaluar las dosis de atracurio y cisatracurio para la reducción de T4/T1 de la secuencia de cuatro estímulos mayor o igual al 95%. 2 Evaluación de las alteraciones hemodinámicas del atracurio y el cisatracurio por inyección venosa, midiendo la presión arterial sistémica de la arteria carótida y electrocardiograma de ratones. 3 Observación de la protección hemodinámica por el tratamiento previo con difenidramina (2 y/o cimetidina (4 por inyección venosa. Análisis estadístico: test t de Student, ANOVA. RESULTADOS: El atracurio y el cisatracurio no modificaron la presión arterial promedio (PAP en las dosis de 1 y 0,25, respectivamente. Las dosis de 4 disminuyeron la PAP de 62,8 ± 4,5% del control para el atracurio, y de 82,5 ± 2,3% del control para el cisatracurio. Con la difenidramina y la cimetidina, la presión sistólica se redujo a 95,4 ± 2,5% del control. Con la cimetidina, la presión diastólica disminuyó 82,7 ± 8,4% del control. El efecto con-junto sobre las presiones sistólica y diastólica se reflejó en los valores observados de la PAP. CONCLUSIONES: La difenidramina y la cimetidina, aisladamente, no impidieron la disminución de la presión arterial promedio inducida por el atracurio. Sin embargo, la asociación de esos de los fármacos fue eficaz en la prevención de los efectos hemodinámicos inducidos por el atracurio. El cisatracurio, en las dosis del experimento, no promovió una disminución de la presión arterial que justificase las medidas preventivas aplicadas en los grupos donde se utilizó el atracurio.BACKGROUND AND OBJECTIVES: Since atracurium can cause hypotension in humans, the hemodynamic effects of atracurium and cisatracurium as well as the hemodynamic prote

  1. [Administration of premedication with fexofenadine for paclitaxel-induced hypersensitive reactions in breast cancer patients complicated with closed-angle glaucoma].

    Komatsubara, Kazuo; Miyoshi, Kyoko; Kogure, Yuuki; Matsuhisa, Tetsuaki; Eguchi, Hisae


    Paclitaxel (PTX) is one of the most important breast cancer treatment drugs. However, severe hypersensitivity reactions such as decreases in blood pressure and impaired breathing occur with high frequency. For the prevention of such hypersensitivity reactions, administration of a premedication composed of three components, diphenhydramine, ranitidine (or famotidine), and dexamethasone, has been advised in package insert information of medicine. Administration of diphenhydramine is difficult in breast cancer patients complicated with closed-angle glaucoma, because diphenhydramine has a weak anticholinergic adverse effect which can induce mydriasis and glaucoma attack. We studied the prevention of severe hypersensitivity reactions and of glaucoma attack in 2 breast cancer patients complicated with closed angle glaucoma at our hospital from April 2007 to March 2008. We switched from diphenhydramine to fexofenadine as the medicine to prevent hypersensitivity reactions. Hypersensitivity reactions were not observed throughout all courses in both patients, and no glaucoma attack was observed.

  2. Epinephrine Injection

    ... itching, swelling, skin redness, fast heartbeat, weak pulse, anxiety, confusion, stomach pain, losing control of urine or ... such as chlorpheniramine (Chlor-Trimeton) and diphenhydramine (Benadryl); beta blockers such as propranolol (Hemangeol, Inderal LA, Innopran XL); ...

  3. The relation between antihistamine medication during early ...

    Rabah M. Shawky


    May 11, 2015 ... 288. 2.2. Second generation histamine H1 receptor antagonists: . .... ria, incoordination, anxiety, insomnia, tremors, nausea and vomiting, dryness of the mouth, ... gastroschisis [18,19]. Diphenhydramine has also an oxytocin.

  4. Impairment of fear memory consolidation and expression by antihistamines.

    Nonaka, Ayako; Masuda, Fumitaka; Nomura, Hiroshi; Matsuki, Norio


    Antihistamines are widely used to treat allergy symptoms. First-generation antihistamines have adverse effects on the central nervous system (CNS), such as hypnotic and amnesic effects, whereas second-generation antihistamines have poor brain penetration, and therefore, have fewer CNS-related adverse effects. Memory consists of several phases, including acquisition, consolidation, expression, and extinction. It remains unclear whether these phases are affected by antihistamines. We investigated the effects of diphenhydramine, a first-generation antihistamine, and levocetirizine and olopatadine, second-generation antihistamines, on memory phases. Mice were subjected to fear conditioning on day 1 and tested on day 2. Antihistamines were administered before conditioning, immediately after conditioning, or before the test session. Diphenhydramine (30mg/kg) decreased freezing time when administered immediately after conditioning or before the test session. These effects were not attributable to a change in locomotor activity. Levocetirizine (0.1, 1, 10mg/kg) and olopatadine (1, 10, 20mg/kg) had no effects on conditioned fear. We also examined the effect of diphenhydramine and levocetirizine on the expression of an activity-dependent gene associated with the test session. Diphenhydramine, but not levocetirizine, increased Arc transcription in the central nucleus of the amygdala. These data indicate that diphenhydramine, but not levocetirizine or olopatadine, impairs the consolidation and expression of conditioned fear.

  5. Drug: D08717 [KEGG MEDICUS

    Full Text Available D08717 Mixture, Drug dl-Camphor - l-menthol - glycol salicylate - methyl salicylate...inflammatory agents 2649 Others D08717 dl-Camphor - l-menthol - glycol salicylate - methyl salicylate - diphenhydramine - benzyl nicotinate mixt PubChem: 96025400 ...

  6. Drug: D08720 [KEGG MEDICUS

    Full Text Available D08720 Mixture, Drug dl-Camphor - l-menthol - methyl salicylate -; diphenhydramine ...sics, anti-itchings, astringents, anti-inflammatory agents 2649 Others D08720 dl-Camphor - l-menthol - methyl salicylate - PubChem: 96025403 ...

  7. 75 FR 38915 - Removal of Thresholds for the List I Chemicals Pseudoephedrine and Phenylpropanolamine


    ... combination with the active ingredient guaifenesin, which is an expectorant. As a prescription drug, ephedrine.../guaifenesin combination products warrant special treatment and should not be subject to the proposed..., diphenhydramine, guaifenesin or triprolidine. The number of guaifenesin exhibits accounted for approximately 5...

  8. Edgewood Chemical Biological Center In-House Laboratory Independent Research Program Annual Report FY11


    ascorbic acid , caffeine, diphenhydramine, doxylamine, folic acid , isoniazid, levothyroxine, penicillin G, retinol, saccharin, thiamine, DMSO). The...understanding the comprehensive threat to the warfighter and providing the scientific knowledge , technology, and materiel required to protect and...capability provides integrated science and technology solutions that address CB defense knowledge gaps and vulnerabilities. The Center’s R&T

  9. Non-Invasive Screening Techniques for Drugs of Abuse,


    documentation. The system is capable of identifying all common drugs of abuse except cannabinoids, lysergic acid diethylamide (LSD), and psilocybin ...combined with LSD, diphenhydramine (Benadryl), mari- huana or other drugs. Methods of detection: TLC, GLC, EMIT, RIA. Psilocybin (’magic mushrooms...but highly toxic in combination with alcohol or other depressants . Oxazepam (Serax) is a metabolic product of most benzodia- zepines. Flurazepam

  10. Drug: D08695 [KEGG MEDICUS

    Full Text Available D08695 Mixture, Drug dl-Methylephedrine hydrochloride - dihydrocodeine phosphate - ...diprophylline - diphenhydramine salicylate - acetaminophen - bromovalerylurea mixt; Coughcode N (TN) dl-Methylephedrine...2 Agents affecting individual organs 22 Respiratory organ agents 222 Antitussives 2229 Others D08695 dl-Methylephedrine...eine, combinations D08695 dl-Methylephedrine hydrochloride - dihydrocodeine phosp

  11. Drug: D04299 [KEGG MEDICUS

    Full Text Available D04299 Mixture, Drug Diprophylline - ephedrine hydrochloride - papaverine hydrochloride - noscapine...atory organ agents 222 Antitussives 2229 Others D04299 Diprophylline - ephedrine hydrochloride - papaverine hydrochloride - noscapine...ions D04299 Diprophylline - ephedrine hydrochloride - papaverine hydrochloride - noscapine - diphenhydramine hydrochloride mixt PubChem: 17398047 ...

  12. Epidemiology of Toxicological Factors in Civil Aviation Accident Pilot Fatalities, 1999-2003


    central nervous system (5−7). For example, fi rst-generation antihistaminics—brompheniramine, chlorpheniramine, diphenhydramine, and doxylamine— cause...1 3 5 Quinidine 0 0 1 1 Ranitidine 2 3 9 17 Sertraline /Desmethylsertraline 0 6 11 19 Sildenafil/Metabolite(s) 0 1 3 4 Theophylline 1 3 2 6

  13. Evaluation of the rat embryo culture system as a predictive test for human teratogens.

    Guest, I; Buttar, H S; Smith, S; Varma, D R


    Ingestion of the anticonvulsant drug valproic acid and of the angiotensin converting enzyme inhibitor captopril during pregnancy has been associated with abnormal fetal outcome in humans. In contrast, the use of the antiinflammatory drug ibuprofen and the antihistamine diphenhydramine has not been documented to be embryotoxic in humans. We evaluated the rat embryo culture system as a predictive model of teratogenesis, using these four drugs as test agents. Valproic acid, ibuprofen, and diphenhydramine were embryotoxic, inducing concentration-dependent decreases in growth and a significant increase in anomalies. Valproic acid caused an increase in neural tube defects, ibuprofen increased the incidence of abnormal maxillary processes, and diphenhydramine increased the number of embryos with distorted body morphology. These abnormalities were induced at concentrations of valproic acid and diphenhydramine that are used clinically, but ibuprofen only induced toxicity at concentrations greatly exceeding the therapeutic range. Captopril was not embryotoxic up to 5 mM, the highest concentration tested. These results suggest that the rat embryo culture system produces both false positive and false negative data on the teratogenic potential of drugs. Although such an in vitro assay may be suitable to determine the mechanism of teratogenesis, it is not a sensitive indicator of potential human teratogens on its own. These data support the view that in vitro systems can only supplement clinical and epidemiological observations in humans, possibly as a method to determine mechanisms of actions of teratogens.

  14. A prospective, randomized trial of intravenous prochlorperazine versus subcutaneous sumatriptan in acute migraine therapy in the emergency department.

    Kostic, Mark A; Gutierrez, Francisco J; Rieg, Thomas S; Moore, Tammy S; Gendron, Richard T


    Intravenous (IV) prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in the treatment of migraine patients presenting to the emergency department (ED). In this randomized, double-blind, placebo-controlled trial, after providing written informed consent, patients presenting to the ED with a chief complaint of migraine received a 500-mL bolus of IV saline solution and either 10 mg prochlorperazine with 12.5 mg diphenhydramine IV plus saline solution placebo subcutaneously or saline solution placebo IV plus 6 mg sumatriptan subcutaneously. Pain intensity was assessed with 100-mm visual analog scales (visual analog scale at baseline and every 20 minutes for 80 minutes). The primary outcome was change in pain intensity from baseline to 80 minutes or time of ED discharge if subjects remained in the ED for fewer than 80 minutes after treatment. Sedation and nausea were assessed every 20 minutes with visual analog scale scales, and subjects were contacted within 72 hours to assess headache recurrence. Sixty-eight subjects entered the trial, with complete data for 66 subjects. Baseline pain scores were similar for the prochlorperazine/diphenhydramine and sumatriptan groups (76 versus 71 mm). Mean reductions in pain intensity at 80 minutes or time of ED discharge were 73 mm for the prochlorperazine/diphenhydramine group and 50 mm for those receiving sumatriptan (mean difference 23 mm; 95% confidence interval 11 to 36 mm). Sedation, nausea, and headache recurrence rates were similar. IV prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in the treatment of migraine. Copyright 2009 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

  15. Pharmacological analysis of certain mechanisms of morphine addiction.

    Ovcharov, R; Bantoutova, I; Kobourova, K


    The effects of L-Dopa, Methysergid, Diphenhydramine hydrochloride and LSD on the development of morphine dependence and the abstience syndrome after its withdrawal, were tested in experiments on 200 male Wistar albino rats. L-Dopa had no efect on the development of physical morphine dependence, while Methysergid prevented its development. Applied in rats during the abstinence syndrome, LSD intensified their aggressivity with no influence on the analgesic effect of morphine. Diphenhydramine reduced the aggressiveness of the rats during the abstinence syndrome. Biochemical tests show that in morphine-tolerant rats there was an increase in the content of brain serotonin, less of dopamine and no changes in noradrenaline. The significance of the brain levels of serotonin, dopamine and noradrenaline for the development of physical morphine-dependence is discussed. It is pointed out that serotonin and dopamine play an important role both for the origin of the physical morphine dependence, and in the abstinence syndrome after its withdrawal.

  16. Discriminative power of an assay for automated in vitro screening of teratogens

    Walmod, Peter S; Gravemann, Ute; Nau, Heinz


    -trans-retinoic acid, pentyl-4-yn-valproic acid, saccharin, salicylic acid and valproic acid. All compounds, with the exception of dimethadione inhibited proliferation in a linear dose-dependent manner, and there were statistically significant compound class-dependent differences between the IC(50)-values...... to teratogenicity were: 5-bromo-2(')-deoxyuridine, 6-aminonicotinamide, acrylamide, boric acid, D-(+)-camphor, dimethadione, dimethyl phthalate, diphenhydramine, hydroxyurea, isobutyl-ethyl-valproic acid, lithium chloride, methyl mercury chloride, methotrexate, methoxyacetic acid, penicillin G, all...

  17. Spasmogenic activity of chemotactic N-formylated oligopeptides: identity of structure--function relationships for chemotactic and spasmogenic activities.

    Marasco, W. A.; Fantone, J. C.; Ward, P. A.


    The chemotactic N-formylated oligopeptides are potent spasmogenic agents for guinea pig ileum. Structure-activity studies with various N-formylated peptides suggest the presence of a specific receptor that resembles in specificity the formyl peptide receptor on leukocytes. A competitive antagonist of the formyl peptide receptor on leukocytes also inhibits formyl peptide-induced ileum contraction, whereas the antihistamine diphenhydramine is without effect. The contractile response caused by t...

  18. Over-the-Counter Agents for the Treatment of Occasional Disturbed Sleep or Transient Insomnia: A Systematic Review of Efficacy and Safety

    Culpepper, Larry; Wingertzahn, Mark A.


    Objective: To investigate the level of evidence supporting the use of common over-the-counter (OTC) agents (diphenhydramine, doxylamine, melatonin, and valerian) for occasional disturbed sleep or insomnia. Data sources: A systematic review of the literature was conducted on July 31, 2014, using MEDLINE (PubMed) and the search terms (insomnia OR sleep) AND (over*the*counter OR OTC OR non*prescription OR antihistamine OR doxylamine OR diphenhydramine OR melatonin OR valerian) with the filters English, human, and clinical trials. Study selection: Identified publications (from 2003 to July 31, 2014, following previous published literature reviews) that met the inclusion criteria were selected. The criteria included randomized placebo-controlled clinical studies that utilized overnight objective (polysomnography) or next-day participant-reported sleep-related endpoints and that were conducted in healthy participants with or without occasional disturbed sleep or diagnosed insomnia. Results: Measures of efficacy and tolerability were summarized for each study individually and grouped according to OTC agent: H1 antagonists or antihistamines (3 studies, diphenhydramine), melatonin (8), and valerian or valerian/hops (7). Of the 3 sleep agents, studies conducted with melatonin, especially prolonged-release formulations in older individuals with diagnosed insomnia, demonstrated the most consistent beneficial effects (vs placebo) on sleep measures, specifically sleep onset and sleep quality, with favorable tolerability. In contrast, the clinical trial data for diphenhydramine, immediate-release melatonin, and valerian suggested limited beneficial effects. Conclusions: A review of randomized controlled studies over the past 12 years suggests commonly used OTC sleep-aid agents, especially diphenhydamine and valerian, lack robust clinical evidence supporting efficacy and safety. PMID:27057416

  19. Effect(s) of Pharmacologic Intervention on Oxygenation, Lung Water and Protein Leak in the Pseudomonas ARDS Porcine Model


    We have previously established that treatment with cimetidine, or ranitidine in combination with diphenhydramine, H2 and H, blockers, respectively...extravascular lung water (EVLW). In this technique 10 ml of iced, green dye solution (2 mg indocyanine green dye in 10 ml 5% dextrose) were injected as a...capture pulmonary effluent was attached to the left atrial catheter. All solutions were prepared using aseptic technique. Reagents were obtained from

  20. Tyrosine Supplementation Attenuates Cognitive and Psychomotor Deficits in Cold Environments


    caused by low body temperature. J Appl Physiol 55: 27-31, 1983. 11. Fine BJ, Kobrick JL and Lieberman HR. Effects of caffeine or diphenhydramine on...Hale B and Lieberman HR. Caffeine effects on marksmanship during high- stress military training with 72 hour sleep deprivation. Aviat Space Environ Med...D, Hyde, DE, Schrot, J, and Thomas, JR. Thermal protection and diver performance in special operations forces combat swimmers (resting diver phase

  1. Hypersensitivity to Etoposide in Case of Metastatic Gestational Choriocarcinoma

    Biljana Lazović


    Full Text Available Etoposide is commonly used in the treatment of a variety of neoplasms. Hypersensitivity reactions to etoposide are infrequently reported and include hypotension, hypertension, flushing, diaphoresis, chest discomfort, dyspnea, bronchospasm and loss of consciousness. We report the case of a 39-year-old woman who experienced acute bronchospasm, tachycardia, hypoxia and hypotension. The symptoms resolved within an hour after administration of intravenous fluids, methylprednisolone, diphenhydramine and oxygen. Subsequently, the patient was given etoposide phosphate without incident.

  2. Effects of H1–receptor antagonists in antidepressant tests in rats

    Chitra C. Khanwelkar


    : Considering the vast data suggesting the role of brain histamine(HA) in behaviour,emotions,anxiety and depression;four H1-receptor antagonists; promethazine, diphenhydramine, cyclizine and pheniramine were subjected to antidepressant tests in rats. All H1 – antagonists behaved like antidepressants in animal tests. They antagonized reserpine induced catalepsy, potentiated methamphetamine induced stereotypy and reduced the period of immobility in Porsolt’s behavioural despair test. It is sug...

  3. A Proposed Formulary Based on the Identification of Medications Determined by Diagnoses/Problems in a Troop Medical Clinic During Calendar Year 1983


    Tablets Diphenhydramine HCI (BENADRYL) Capsules, 50mg Triprolidine and Pseudoephedrine HCl (ACTIFED) Tablebs 08:00 ANTI-INFECTIVES 08:04 AMEBACIDE...BENTYL) Tablets, 20mg 144 12:12 SYMPATHOMIMETIC (ADRENERGIC’ AGENTS Metaproterenol Sulfate (ALUPENT) Inhaler Pseudoephedrine (SUDAFED) Tablets, 3 0mg 12... Ibuprofen (MOTRIN) Tablets, 600mg Indomethacin (INDOCIN) Capsule, 25mq and 50mg Naproxen (NAPROSYN) Tablets, 250mg Salsalate (DISALCID) Tablets, 500mg

  4. Dissociable effects of histamine H1 antagonists on reaction-time performance in rats.

    Blokland, A; Scholtissen, B; Vermeeren, A; Ramaekers, J


    The most pronounced side effect of antiallergic histaminergic drugs (H1 antagonists) is sedation. These effects have been linked with the effects of histaminergic drugs on central H1 receptors. In the present study, we investigated the dose-response relationship of different antihistamines on the performance in a reaction-time task that has been developed for rats. The dose-response relationship of diphenhydramine, cetirizine and terfenadine were examined for the various behavioural measures in this task (i.e., reaction time, motor time, premature responses and number of trials completed). In addition, the effects of scopolamine were assessed to evaluate the cholinergic profile in this task. Diphenhydramine did not reliably affect the reaction time, but increased the motor time and the proportion of premature responses, and decreased the number of trials completed in a session. A low dose of cetirizine decreased the reaction time, whereas an increase in reaction time was found for the high dose. The motor time was increased after both doses of cetirizine. Terfenadine did not affect the responding of rats in the reaction-time task at the doses tested. The effects of scopolamine were very similar to those of diphenhydramine. The reaction-time task used in this study was able to dissociate different types of antihistamines on aspects of psychomotor function, which were likely to be related to central muscarinic or H1 antagonism. These findings suggest that the reaction-time task may be a sensitive tool for assessing effects of drugs on psychomotor function.

  5. Beyond-use dating of lidocaine alone and in two "magic mouthwash" preparations.

    Kirk, Loren Madden; Brown, Stacy D; Luu, Yao; Ogle, Amanda; Huffman, Jessica; Lewis, Paul O


    Beyond-use dating (BUD) of lidocaine alone and in two "magic mouthwash" preparations stored in amber oral syringes at room temperature was determined. Two formulations of mouthwash containing oral topical lidocaine 2% (viscous), diphenhydramine 2.5 mg/mL, and aluminum hydroxide-magnesium hydroxide-simethicone were prepared in 1:1:1 and 1:2.5:2.5 ratios, divided into 3-mL samples, and stored in unit-dose oral amber syringes. Unit-dose single-product lidocaine samples were also prepared to serve as controls and stored in oral amber syringes. The lidocaine concentrations in these samples were measured periodically for 90 days. A stability-indicating high-performance liquid chromatographic method was developed and validated for system suitability, accuracy, repeatability, intermediate precision, specificity, linearity, and robustness. Based on the calculated percentages versus the initial concentration and the results from an analysis of variance comparing the two formulations, a BUD of 21 days is deemed appropriate for both magic mouthwash formulations. Based on the stability data, published safety concerns, and lack of efficacy in combination, packaging and dispensing lidocaine separately from other ingredients are recommended when administering magic mouthwash mixtures. Utilizing a 90-day BUD, lidocaine can be packaged separately from other magic mouthwash ingredients in individual dosage units and applied to the oral cavity using the swish-and-spit method. The delivery of the diphenhydramine and aluminum hydroxide-magnesium hydroxide-simethicone could be separated, allowing for a swish-and-swallow method of administration. A BUD of 21 days is recommended for lidocaine prepared with diphenhydramine and aluminum hydroxide-magnesium hydroxide-simethicone in ratios of 1:1:1 and 1:2.5:2.5 and stored at room temperature in amber oral plastic syringes. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  6. Isobolographic analysis of the sedative interaction between six central nervous system depressant drugs and Valeriana edulis hydroalcoholic extract in mice.

    Ugalde, Martha; Reza, Victoria; González-Trujano, Ma Eva; Avula, Bharathi; Khan, Ikhlas A; Navarrete, Andrés


    It has been declared frequently that valerian may potentiate the effect of other central nervous system (CNS) depressant drugs, however there has been a lack of experimental data. We have evaluated the profile of the interactions between the ethanol extract of Valeriana edulis spp procera and six CNS depressant drugs using an exploratory model to test the sedative effect in mice. All the compounds tested showed a dose-dependent sedative effect with the following ED50 values: valerian 181.62, diazepam 1.21, ethanol 1938, pentobarbital 11.86, buspirone 1.04, haloperidol 0.41 and diphenhydramine 17.06 mg kg-1. An isobolographic analysis was used to evaluate the sedative interaction of the intraperitoneal co-administration of 1:1 fixed-ratio combination of equi-effective doses of valerian extract with each CNS depressant drug. The ED50 theoretical (Zadd) and experimental (Zexp) for each combination were: valerian+diazepam,Zadd=91.41 mg kg-1, Zexp=81.64 mg kg-1; valerian+ethanol, Zadd=1060.22 mg kg-1, Zexp=687.89 mg kg-1; valerian+pentobarbital, Zadd=96.74 mg kg-1, Zexp=151.83 mg kg-1; valerian+buspirone, Zadd=91.33 mg kg-1, Zexp=112.73 mg kg-1; valerian+haloperidol, Zadd=91.01 mg kg-1, Zexp=91.52 mg kg-1; valerian+diphenhydramine, Zadd=99.34 mg kg-1, Zexp=123.52 mg kg-1. Neither synergistic nor attenuate effects were found in any of the combinations evaluated. We concluded that the valerian extract did not potentiate the sedative effect of commonly prescribed CNS depressant drugs as was expected. The additive effect found through the isobolographic analysis suggested that the sedative effect of V. edulis resulted from the activation of common mechanisms of haloperidol, diazepam, buspirone, pentobarbital, diphenhydramine and ethanol.

  7. H1-antihistamines induce vacuolation in astrocytes through macroautophagy

    Hu, Wei-Wei; Yang, Ying; Wang, Zhe; Shen, Zhe; Zhang, Xiang-Nan [Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, School of Basic Medical Sciences, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058 (China); Wang, Guang-Hui [College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123 (China); Chen, Zhong, E-mail: [Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, School of Basic Medical Sciences, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058 (China)


    H1-antihistamines induce vacuolation in vascular smooth muscle cells, which may contribute to their cardiovascular toxicity. The CNS toxicity of H1-antihistamines may also be related to their non-receptor-mediated activity. The aim of this study was to investigate whether H1-antihistamines induce vacuolation in astrocytes and the mechanism involved. The H1-antihistamines induced large numbers of giant vacuoles in astrocytes. Such vacuoles were marked with both the lysosome marker Lysotracker Red and the alkalescent fluorescence dye monodansylcadaverine, which indicated that these vacuoles were lysosome-like acidic vesicles. Quantitative analysis of monodansylcadaverine fluorescence showed that the effect of H1-antihistamines on vacuolation in astrocytes was dose-dependent, and was alleviated by extracellular acidification, but aggravated by extracellular alkalization. The order of potency to induce vacuolation at high concentrations of H1-antihistamines (diphenhydramine > pyrilamine > astemizole > triprolidine) corresponded to their pKa ranking. Co-treatment with histamine and the histamine receptor-1 agonist trifluoromethyl toluidide did not inhibit the vacuolation. Bafilomycin A1, a vacuolar (V)-ATPase inhibitor, which inhibits intracellular vacuole or vesicle acidification, clearly reversed the vacuolation and intracellular accumulation of diphenhydramine. The macroautophagy inhibitor 3-methyladenine largely reversed the percentage of LC3-positive astrocytes induced by diphenhydramine, while only partly reversing the number of monodansylcadaverine-labeled vesicles. In Atg5{sup −/−} mouse embryonic fibroblasts, which cannot form autophagosomes, the number of vacuoles induced by diphenhydramine was less than that in wild-type cells. These results indicated that H1-antihistamines induce V-ATPase-dependent acidic vacuole formation in astrocytes, and this is partly mediated by macroautophagy. The pKa and alkalescent characteristic of H1-antihistamines may be the

  8. [Evaluation of short-time premedication with d-chlorpheniramine maleate injection for paclitaxel-induced hypersensitivity reaction].

    Harada, Tomohiko; Doi, Masakazu; Yamada, Yasuhiko; Akase, Tomohide


    Paclitaxel(referred to hereinafter as PTX )is used in ovarian cancer, non-small cell lung cancer, breast cancer, gastric cancer, and endometrial cancer with positive treatment result reports. However, severe allergic reactions such as decreases in blood pressure and impaired breathing occur with relatively high frequency. For the prevention of such allergic reactions, administration of a premedication composed of the three components, dexamethasone sodium phosphate injection, diphenhydramine hydrochloride tablet, and ranitidine hydrochloride injection solution(or injectable famodine), is advised in the appended documentation. Administration is difficult because, among these three components, only diphenhydramine hydrochloride is administered orally and thus must be provided through the internal medicine department. Particularly when this combined dosage is administered as outpatient chemotherapy, the doctor must prescribe diphenhydramine hydrochloride tablets, and the patient must not forget to bring them on the day in which chemotherapy is administered. Also, checks by the medical staff such as pharmacists and nurses are required, complicating the administration of this therapy further. Taking this situation into consideration, our hospital uses a short-time premedication method wherein d-Chlorpheniramine Maleate injections are substituted for diphenhydramine hydrochloride tablets, and the time required for premedication is reduced to 15 minutes. This study investigated the allergic reaction ratio to consider the safety and usefulness of the short-time premedication method used at our hospital. The chemotherapy regimens conducted for the subject patients were 9 cases of PTX+CBDCA, 6 cases of biweekly- PTX, and 5 cases of weekly-PTX. A total of 67 PTX injections were given, 15 of them being first-time administrations. The ratio of allergic/hypersensitivity reactions was 10.0%(2 cases in 20). The short-time premedication method using d-Chlorpheniramine Maleate

  9. Pharmacological and neurophysiological aspects of space/motion sickness

    Lucot, James B.; Crampton, George H.


    A motorized motion testing device modeled after a Ferris wheel was constructed to perform motion sickness tests on cats. Details of the testing are presented, and some of the topics covered include the following: xylazine-induced emesis; analysis of the constituents of the cerebrospinal fluid (CSF) during motion sickness; evaluation of serotonin-1A (5-HT sub 1A) agonists; other 5HT receptors; antimuscarinic mechanisms; and antihistaminergic mechanisms. The ability of the following drugs to reduce motion sickness in the cats was examined: amphetamines, adenosinergic drugs, opioid antagonists, peptides, cannabinoids, cognitive enhancers (nootropics), dextromethorphan/sigma ligands, scopolamine, and diphenhydramine.

  10. Suicide through doxylamine poisoning.

    Bockholdt, B; Klug, E; Schneider, V


    Doxylamine is an antihistamine of the ethanolamine class. It is used primarily as a sleep-inducing agent. Only a few reports can be found in the literature about lethal intoxications with doxylamine, but many with combined intoxications. Doxylamine is, aside from diphenhydramine, the only chemically defined active ingredient in some sleeping medications which is available without a prescription in the Federal Republic of Germany. Two cases of doxylamine poisoning are presented, in which high doxylamine concentrations were found in the blood and organs.

  11. The Air Force Global Reach Laydown (GRL): Using the Estimating Supplies Program to Validate Clinical Requirements


    ibuprofen , sulfamethoxazole, trimethoprim, and diphenhydramine also come in bottles of 500. Of these items, ibuprofen was called for most, with a...CHEWABLE SUGAR FREE I.S. 30/PG BT 1 0 0.11 0.024 $0.34 0 0 $0.00 C 6505014917541 BROMPHENIRAMINE MALEATE/ PSEUDOEPHEDRINE HCL EX-REL CAPS 100S BT 1 5...GUAIFENESIN & DEXTROMETHORPHAN HYDROBROMIDE EXT-REL TABLETS100 BT 2 0 0.281 0.007 $11.37 0 0 $0.00 A 6505013258790 GUAIFENESIN & PSEUDOEPHEDRINE EX

  12. Recommendations for the proper use of nonprescription cough suppressants and expectorants in solid-organ transplant recipients.

    Gabardi, Steven; Carter, Danielle; Martin, Spencer; Roberts, Keri


    To describe the pharmacology and safety of oral over-the-counter cough suppressants and expectorants and to present recommendations for the use of these agents in solid-organ transplant recipients based on the potential for adverse drug reactions or drug-disease interactions. Data from journal articles and other sources describing the pharmacology and safety of over-the-counter cough suppressants and expectorants, drug-drug interactions with immunosuppressive agents, and drug-disease state interactions are reviewed. Potential and documented drug-drug interactions between immunosuppressive agents and over-the-counter cough medications guaifenesin, dextromethorphan, diphenhydramine, and codeine were evaluated on the basis of pharmacokinetic and pharmacodynamic principles. Interactions between these cough medications and the physiological changes in the body following transplantation also were examined. Diphenhydramine requires additional monitoring when used to treat cough in transplant recipients owing to its anticholinergic properties and the potential for interactions with cyclosporine. Dextromethorphan can be used in most transplant recipients, although greater caution should be exercised if the patient has undergone liver transplant or has liver impairment. Guaifenesin can be used in transplant recipients but should be used with caution in patients receiving kidney or lung transplants and in patients with renal impairment. Codeine combined with guaifenesin is another option for cough and can be used in most transplant patients although those with reduced renal function should be monitored carefully for adverse events.

  13. Involvement of the histaminergic system in renal sympathetic and cardiovascular responses to leptin and ghrelin.

    Tanida, Mamoru; Kaneko, Hidekazu; Shen, Jiao; Nagai, Katsuya


    Previous studies have demonstrated that histamine affects blood pressure (BP) in anesthetized rats. Here, we examined the effects of lateral cerebral ventricular (LCV) injection of various doses of histamine on renal sympathetic nerve activity (RSNA) and BP in anesthetized rats. LCV injection of a low dose of histamine (0.0001nmol) suppressed RSNA and BP. Conversely, a high dose of histamine (100nmol) elevated both RSNA and BP. Moreover, inhibiting effects of a low dose of histamine were eliminated by LCV pre-injection of thioperamide, an antagonist of histaminergic H3-receptor, and accelerating effects of a high dose of histamine were abolished by LCV pre-injection of diphenhydramine, an antagonist of histaminergic H1-receptor. Thus, these evidences suggest that central histamine affects RSNA and BP via histaminergic receptors. In addition, we examined a role for histaminergic system in cardiovascular modulators such as leptin and ghrelin. The LCV pre-injection of thioperamide clearly blocked suppressing effects of ghrelin on RSNA and BP. The LCV pre-injection of diphenhydramine also blocked elevating effects of leptin. Therefore, these results suggest that leptin and ghrelin might affect RSNA and BP by mediating central histaminegic H1- and H3-receptors, respectively.

  14. Involvement of central histamine in amygdaloid kindled seizures in rats.

    Kamei, C


    The involvement of central histamine in amygdaloid kindled seizures in rats was investigated using histamine-related compounds. Histamine contents in the amygdala of electrical stimulation site was significantly decreased after development of amygdaloid kindling. Intracerebroventricular (i.c.v.) injection of histamine resulted in inhibition of amygdaloid kindled seizures. The H(1)-agonists 2-methylhistamine and 2-thiazolylethylamine also inhibited amygdaloid kindled seizures. In addition, intraperitoneal (i.p.) injection of histidine and metoprine inhibited amygdaloid kindled seizures at doses that caused increases in histamine contents of the brain. H(1)-antagonists (diphenhydramine and chlorpheniramine) attenuated histamine (i.c.v.)-induced inhibition of amygdaloid kindled seizures, however, no significant antagonism was observed with H(2)-antagonists (cimetidine, ranitidine or zolantidine). Intracerebroventricular injection of H(3)-antagonists (thioperamide and AQ 0145) resulted in a dose-related inhibition of amygdaloid kindled seizures. The same findings were observed when thioperamide and clobenpropit were injected i.p. The effects of thioperamide (i.p.) and AQ 0145 (i.p.) were inhibited by an H(3)-agonist [(R)-alpha-methylhistamine] and H(1)-antagonists (diphenhydramine and chlorpheniramine). On the other hand, H(2)-antagonists (cimetidine and ranitidine) showed no antagonistic effects. These findings suggested that a histaminergic mechanism plays an important role in suppressing amygdaloid kindled seizures through histamine H(1)-receptors.

  15. Computational Evaluation of 2-Phenyl-4H-chromen-4-one Analogues as Antihistamines: Potential Histamine N-Methyltransferase (HMT Inhibitors

    Shikha S. Dave


    Full Text Available Abnormal release of histamine, which is present in relatively high concentration in the lungs, causes serious allergic vasoconstriction and anaphylactic manifestation in human beings. In mammals, a major pathway of histamine metabolism in the lungs is mediated by histamine N-methyl transferase (HMT and diamine oxidase. The need to design a strategy of mechanistic computational evaluation of protein-ligand affinity i.e. HMT- 2-phenyl-4H-chromen-4-ones, protein complex binding energy has been established. A library of synthesized 2-phenyl-4H-chromen-4-ones was docked into the active site cavity of target protein, HMT (Pdb: 2aot. The high-resolution crystal structure of HMT complex with the competitive inhibitor N [2 (benzhydryloxyethyl] N N-Dimethylamine (Diphenhydramine revealed a protein with a highly confined binding region that could be targeted in the design of specific anti-histamines. The validation of docking programme by Potential Mean Force was compared with binding energy results of known ligands in the active sites of HMT, diphenhydramine / benadryl, promethazine, cyproheptadine, trimeton / avil etc. All the synthesized chromone derivatives showed comparable negative binding energies pointing towards the fact that these molecules could be potent antihistamines.

  16. Suffocation using plastic bags: a retrospective study of suicides in Ontario, Canada.

    Bullock, M J; Diniz, D


    One hundred and ten cases of suicidal suffocation using a plastic bag were identified in the files of the Office of the Chief Coroner of Ontario, Canada, between 1993 and 1997. The records were reviewed to determine the demographic characteristics of this group compared with all cases of suicide in Ontario, the scene information, autopsy findings and toxicology results. Most suicides occurred in people over 60 years of age, with older women making up a considerable proportion of cases as compared with other methods of suicide. In 40% of cases the deceased was suffering from a serious illness. Autopsy findings were usually minimal, with facial, conjunctival and visceral petechiae present in a minority of cases. One or more drugs were detected in the blood in 92.6% of cases where toxicologic testing was performed. Benzodiazepines, diphenhydramine and antidepressants were the most common drugs found, with diphenhydramine the most common drug present at an elevated concentration. Information at the scene from "right to die" societies was uncommon. One quarter of decedents took additional measures, besides the use of drugs or alcohol, to ensure the rapidity, certainty or comfort of their death. This study further elucidates the characteristics of this uncommon method of suicide. It emphasizes additional scene findings, such as the presence of dust masks, physical restraints and modification of the plastic bag that may be of use to death investigators in determining the correct manner of death.

  17. Psychopharmacological neuroprotection in neurodegenerative disease: assessing the preclinical data.

    Lauterbach, Edward C; Victoroff, Jeff; Coburn, Kerry L; Shillcutt, Samuel D; Doonan, Suzanne M; Mendez, Mario F


    This manuscript reviews the preclinical in vitro, ex vivo, and nonhuman in vivo effects of psychopharmacological agents in clinical use on cell physiology with a view toward identifying agents with neuroprotective properties in neurodegenerative disease. These agents are routinely used in the symptomatic treatment of neurodegenerative disease. Each agent is reviewed in terms of its effects on pathogenic proteins, proteasomal function, mitochondrial viability, mitochondrial function and metabolism, mitochondrial permeability transition pore development, cellular viability, and apoptosis. Effects on the metabolism of the neurodegenerative disease pathogenic proteins alpha-synuclein, beta-amyloid, and tau, including tau phosphorylation, are particularly addressed, with application to Alzheimer's and Parkinson's diseases. Limitations of the current data are detailed and predictive criteria for translational clinical neuroprotection are proposed and discussed. Drugs that warrant further study for neuroprotection in neurodegenerative disease include pramipexole, thioridazine, risperidone, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, fluoxetine, buspirone, clonazepam, diphenhydramine, and melatonin. Those with multiple neuroprotective mechanisms include pramipexole, thioridazine, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, clonazepam, and melatonin. Those best viewed circumspectly in neurodegenerative disease until clinical disease course outcomes data become available, include several antipsychotics, lithium, oxcarbazepine, valproate, several tricyclic antidepressants, certain SSRIs, diazepam, and possibly diphenhydramine. A search for clinical studies of neuroprotection revealed only a single study demonstrating putatively positive results for ropinirole. An agenda for research on potentially neuroprotective agent is provided.

  18. Discriminative power of an assay for automated in vitro screening of teratogens.

    Walmod, Peter S; Gravemann, Ute; Nau, Heinz; Berezin, Vladimir; Bock, Elisabeth


    Screening for potential teratogenicity of 20 test compounds was performed using a computerised microscope workstation for determination of cytotoxicity, proliferation and morphology of fibroblastoid murine L929-cells. The test compounds, which were divided into four classes according to teratogenicity were: 5-bromo-2(')-deoxyuridine, 6-aminonicotinamide, acrylamide, boric acid, D-(+)-camphor, dimethadione, dimethyl phthalate, diphenhydramine, hydroxyurea, isobutyl-ethyl-valproic acid, lithium chloride, methyl mercury chloride, methotrexate, methoxyacetic acid, penicillin G, all-trans-retinoic acid, pentyl-4-yn-valproic acid, saccharin, salicylic acid and valproic acid. All compounds, with the exception of dimethadione inhibited proliferation in a linear dose-dependent manner, and there were statistically significant compound class-dependent differences between the IC(50)-values for the compounds (pteratogens being the most potent. Furthermore, the average efficacies (maximum relative change) for 10 parameters describing cell morphology exhibited statistically significant compound class-dependent differences (pteratogenic potency of the compounds. However, the moderate teratogens dimethadione and lithium chloride only had minor effects on the morphology and proliferation of the cells whereas the non-teratogen diphenhydramine had effects on both proliferation and morphology comparable to the strong teratogens.

  19. Effect of histamine on regional cerebral blood flow of the parietal lobe in rats.

    Yang, Peng-Bo; Chen, Xin-Lin; Zhao, Jian-Jun; Zhang, Jian-Shui; Zhang, Jun-Feng; Tian, Yu-Mei; Liu, Yong


    Histamine is a powerful modulator that regulates blood vessels and blood flow. The effect of histamine on the extracortical vessels has been well described, while much less is known about the effect of histamine on intracortical vessels. In this study, we investigated the effect of histamine on regional cerebral blood flow in rat parietal lobe with laser Doppler flowmetry. The pharmacological characteristics of distinct ways (intracerebroventricular injection, intraperitoneal injection, and cranial window infusion) in applying histamine to the brain were also obtained and compared. Histamine applied in three ways all produced a decrease of rCBF in parietal lobe in a concentration-dependent manner. Cranial window infusion was the most effective way and intraperitoneal injection of L-histidine was the most ineffective, although it is a simple and applied way. To determine which type of receptor takes part in the vessel contraction induced by histamine, H1 receptor antagonist, diphenhydramine, and H2 receptor antagonist, cimetidine, were applied, respectively, before histamine administration. When the injection of cimetidine was conducted in advance, histamine still resulted in a decrease of infusion amount; while the injection of diphenhydramine was conducted in advance, the infusion of blood amount wasn't changed. These findings indicated that histamine could result in a reduction of rCBF in the rat parietal lobe and this effect of histamine may attribute partly to its combination with H1 receptor.

  20. Histamine increases cytosolic Ca2+ in HL-60 promyelocytes predominantly via H2 receptors with an unique agonist/antagonist profile and induces functional differentiation.

    Seifert, R; Höer, A; Schwaner, I; Buschauer, A


    Histamine H1 receptors mediate activation of phospholipase C, with subsequent increases in cytosolic Ca2+ concentration ([Ca2+]i), and H2 receptors mediate accumulation of cAMP. HL-60 promyelocytes possess H2 receptors, but it is not known whether these cells also possess H1 receptors. We studied the effects of histamine on [Ca2+]i and the functional importance of histamine receptors in HL-60 promyelocytes. In these cells, histamine and dimaprit increased [Ca2+]i with EC50 values of 15 microM and 30 microM, respectively. Diphenhydramine inhibited the effect of histamine (100 microM) on [Ca2+]i up to 40%, with an IC50 of 100 nM. Famotidine and cimetidine diminished the effect of histamine (100 microM) up to 75%, with IC50 values of 85 nM and 300 nM, respectively. Diphenhydramine plus famotidine abolished histamine-induced rises in [Ca2+]i. Impromidine, with an IC50 of 100 nM, abolished the effect of histamine (100 microM) on [Ca2+]i. Diphenhydramine, famotidine, cimetidine, and impromidine showed marked noncompetitive antagonism with histamine. Histamine-induced increases in [Ca2+]i were largely due to influx of Ca2+ from the extracellular space. Ca2+ influx was inhibited by 1-(beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl)-1H-imida zole hydrochloride (SK&F 96365). Histamine activated phospholipase C. Histamine induced expression of formyl peptide receptors, which effect was abolished by famotidine. In U-937 promonocytes and in the human erythroleukemia cell lines HEL and K-562, histamine did not induce rises in [Ca2+]i. Our data suggest the following. (i) In HL-60 promyelocytes, histamine increases [Ca2+]i predominantly via H2 receptors and to a lesser extent via H1 receptors. (ii) The agonist/antagonist profile of the H2 receptor-mediated increases in [Ca2+]i differs markedly from that for cAMP accumulation, suggesting the involvement of different H2 receptor subtypes. (iii) In HL-60 promyelocytes, histamine activates nonselective cation channels and

  1. Exercise-Induced Anaphylaxis: A Case Report and Review of the Diagnosis and Treatment of a Rare but Potentially Life-Threatening Syndrome

    Nathan T. Jaqua


    Full Text Available A 24-year-old male Marine with an uncomplicated medical history and a long history of strenuous, daily exercise presented to the emergency department after experiencing anaphylactic shock while running. Symptoms resolved following administration of intramuscular diphenhydramine, ranitidine, intravenous methylprednisolone, and intravenous fluids. On followup in the allergy clinic, a meticulous clinical history was obtained which elucidated a picture consistent with exercise-induced anaphylaxis. He had experienced diffuse pruritus and urticaria while exercising on multiple occasions over the last three years. His symptoms would usually increase as exercise continued. Prior to the first episode, he regularly exercised without symptoms. Exercise-induced anaphylaxis is a rare but potentially life-threatening syndrome that requires a careful clinical history and is a diagnosis of exclusion. Treatment is primarily exercise avoidance. Prophylactic mediations are inconsistently effective but are empirically used. Successful treatment with omalizumab was recently reported in a case of refractory exercise-induced anaphylaxis.

  2. Spasmogenic activity of chemotactic N-formylated oligopeptides: identity of structure--function relationships for chemotactic and spasmogenic activities.

    Marasco, W A; Fantone, J C; Ward, P A


    The chemotactic N-formylated oligopeptides are potent spasmogenic agents for guinea pig ileum. Structure-activity studies with various N-formylated peptides suggest the presence of a specific receptor that resembles in specificity the formyl peptide receptor on leukocytes. A competitive antagonist of the formyl peptide receptor on leukocytes also inhibits formyl peptide-induced ileum contraction, whereas the antihistamine diphenhydramine is without effect. The contractile response caused by the synthetic N-formylated peptides differs from those induced by acetylcholine, histamine, and substance P. In particular, a latent period after treatment with the N-formyl peptides is seen before the onset of the response, and a sustained contractile response is not maintained. In addition, tachyphylaxis does occur, but complete recovery of activity is seen after a 20- to 30-min rest period. These observations suggest broad biological roles of prokaryotic signal peptides from bacteria as acute inflammatory mediators.

  3. Vancomycin induced Red Man Syndrome

    Drisyamol K.A


    Full Text Available Vancomycin is a glycoprotein antibiotic that has been associated with an anaphylactoid reaction termed the Red-man syndrome. It usually consists of erythema, flushing and pruritis of the face and upper torso and occasionally progresses to include dyspnoea, chest pain and hypotension. Red man syndrome (RMS is also known as “red neck syndrome. Discontinuation of the vancomycin infusion and administration of diphenhydramine can abort most of the reactions. Slow intravenous administration of vancomycin should minimize the risk of infusion-related adverse effects. Antibiotics such as ciprofloxacin, amphotericin B, rifampcin and teicoplanin can potentially cause red man syndrome. The effects of red man syndrome can be relieved by antihistamines.

  4. Quantitation of antihistamines in pharmaceutical preparations by liquid chromatography with a micellar mobile phase of sodium dodecyl sulfate and pentanol.

    Gil-Agustí, M; Monferrer-Pons, L; Esteve-Romero, J; García-Alvarez-Coque, M C


    A reversed-phase liquid chromatographic procedure with a micellar mobile phase of sodium dodecyl sulfate (SDS), containing a small amount of pentanol, was developed for the control of 7 antihistamines of diverse action in pharmaceutical preparations (tablets, capsules, powders, solutions, and syrups): azatadine, carbinoxamine, cyclizine, cyproheptadine, diphenhydramine, doxylamine, and tripelennamine. The retention times of the drugs were <9 min with a mobile phase of 0.15M SDS-6% (v/v) pentanol. The recoveries with respect to the declared compositions were in the range of 93-110%, and the intra- and interday repeatabilities and interday reproducibility were <1.2%. The results were similar to those obtained with a conventional 60 + 40 (v/v) methanol-water mixture, with the advantage of reduced toxicity, flammability, environmental impact, and cost of the micellar-pentanol solutions. The lower risk of evaporation of the organic solvent dissolved in the micellar solutions also increased the stability of the mobile phase.

  5. Drug Distribution: A Guided-Inquiry Laboratory Experiment in Coupled Homogeneous and Heterogeneous Equilibria

    Hein, John; Jeannot, Michael


    A simple and inexpensive experiment for the study of simultaneous homogeneous and heterogeneous equilibria is described using a common antihistamine drug, diphenhydramine. This experiment gives students an opportunity to study the distribution of a drug in a two-phase system by measuring the concentrations of two chemical species and predicting the others by considering charge balance, mass balance, and equilibrium constant expressions. Furthermore, the acid-dissociation constant and aqueous-organic distribution coefficient can be calculated. The experiment is attractive to students because it represents a simplified model for something experienced in everyday life, namely, drug distribution in the human body. Students also gain experience with two very important analytical techniques, gas chromatography and pH measurement with a glass electrode.

  6. Analysis of pharmaceutical preparations containing antihistamine drugs by micellar liquid chromatography.

    Martínez-Algaba, C; Bermúdez-Saldaña, J M; Villanueva-Camañas, R M; Sagrado, S; Medina-Hernández, M J


    Rapid chromatographic procedures for analytical quality control of pharmaceutical preparations containing antihistamine drugs, alone or together with other kind of compounds are proposed. The method uses C18 stationary phases and micellar mobile phases of cetyltrimethylammonium bromide (CTAB) with either 1-propanol or 1-butanol as organic modifier. The proposed procedures allow the determination of the antihistamines: brompheniramine, chlorcyclizine, chlorpheniramine, diphenhydramine, doxylamine, flunarizine, hydroxyzine, promethazine, terfenadine, tripelennamine and triprolidine, in addition to caffeine, dextromethorphan, guaifenesin, paracetamol and pyridoxine in different pharmaceutical presentations (tablets, capsules, suppositories, syrups and ointments). The methods require minimum handling sample and are rapid (between 3 and 12 min at 1 mLmin(-1) flow rate) and reproducible (R.S.D. values<5%). Limits of detection are lower than 1 microgmL(-1) and the recoveries of the analytes in the pharmaceutical preparations are in the range 100+/-10%.

  7. Therapeutic options for acute cough due to upper respiratory infections in children.

    Paul, Ian M


    Cough due to upper respiratory tract infections (URIs) is one of the most frequent complaints encountered by pediatric health-care providers, and one of the most disruptive symptoms for children and families. Despite the frequency of URIs, there is limited evidence to support the few therapeutic agents currently available in the United States (US) to treat acute cough due to URI. Published, well-designed, contemporary research supporting the efficacy of narcotics (codeine, hydrocodone) and US Food and Drug Administration (FDA)-approved over-the-counter (OTC) oral antitussives and expectorants (dextromethorphan, diphenhydramine, chlophedianol, and guaifenesin) is absent for URI-associated pediatric cough. Alternatively, honey and topically applied vapor rubs may be effective antitussives.

  8. Possible role of the histaminergic system in autonomic and cardiovascular responses to neuropeptide Y.

    Tanida, Mamoru; Shen, Jiao; Nagai, Katsuya


    Previous studies have demonstrated that neuropeptide Y (NPY) affects blood pressure (BP) in anesthetized rats. Here, we examined the effects of the third cerebral ventricular (3CV) injection of various doses of NPY on renal sympathetic nerve activity (RSNA) and BP in anesthetized rats. 3CV injection of NPY suppressed RSNA and BP in a dose-dependent manner. Moreover, suppressing effects of NPY on RSNA and BP were eliminated by lateral cerebral ventricular (LCV) preinjection of thioperamide, an antagonist of histaminergic H3-receptor, not diphenhydramine, an antagonist of histaminergic H1-receptor. In addition, 3CV injection of NPY accelerated gastric vagal nerve activity (GVNA) and inhibited brown adipose tissue sympathetic nerve activity (BAT-SNA) of anesthetized rats, and lowered brown adipose tissue temperature (BAT-T) of conscious rats. Thus, these evidences suggest that central NPY affects autonomic nerves containing RSNA, GVNA or BAT-SNA, and BP by mediating central histaminergic H3-receptors.

  9. Long QT syndrome in a patient with allergic rhinoconjunctivitis and auto-immune diabetes: focus on the choice of anti-H1 drugs.

    Moneret-Vautrin, D A; de Chillou, C; Codreanu, A


    The long QT syndrome is a rare disease. The prevalence is estimated at 1/5 000 to 1/20,000. Numerous drugs are contra-indicated because they can lengthen the QT interval. A case of pollen allergy in an adolescent with LQTS is described. The possibility to prescribe anti-H1 drugs is reviewed since cases of torsades de pointe and even deaths have been reported for terfenadine and astemizole. Diphenhydramine, orphenadrine and hydroxyzine are contra-indicated. No accidents and no effects on the QT interval have been published for ebastine, fexofenadine, desloratadine and levocetirizine. These anti-H1 drugs could be used with great care, without any association with drugs resulting in low serum potassium level. Azelastine eye drops have been authorized and a routine protection by inhaled corticosteroids during the pollinic period has been advised in this adolescent treated by betablockers.

  10. Study of ionizable drugs transfer across the water/1,2-dichloroethane interface with phase volume ratio equal to unity using a three-electrode system


    The electrochemical behavior of ionizable drugs (Amitriptyline, Diphenhydramine and Trihexyphene- dyl) at the water/1,2-dichloroethane interface with the phase volume ratio (r = Vo/Vw) equal to 1 are investigated by cyclic voltammetry. The system is composed of an aqueous droplet supported at an Ag/AgCl disk electrode and it was covered with an organic solution. In this manner, a conventional three-electrode potentiostat can be used to study the ionizable drugs transfer process at a liquid/liquid interface. Physicochemical parameters such as the formal transfer potential, the Gibbs energy of transfer and the standard partition coefficients of the ionized forms of these drugs can be evaluated from cyclic voltammograms obtained. The obtained results have been summarized in ionic partition diagrams, which are a useful tool for predicting and interpreting the transfer mechanisms of ionizable drugs at the liquid/liquid interfaces and biological membranes.

  11. Effects of antidepressants and antihistaminics on catalepsy induced by intracerebroventricular administration of histamine in mice.

    Onodera, K


    The intracerebroventricular (icv) administration of histamine but not N-telemethylhistamine and 1-methyl-4-imidazole acetic acid induced catalepsy in mice. Histamine H1-receptor blockers such as cyproheptadine, mepyramine and diphenhydramine reduced histamine-induced catalepsy. However, astemizole which is known to be without central effects, did not reduce histamine-induced catalepsy. The icv pretreatment with histamine H2-receptor blockers, such as metiamide and cimetidine, also had no effect. Moreover, various antidepressants, both imipramine- and atypical-type drugs antagonized histamine-induced catalepsy to various degrees in this experiment. Thus, the induction of catalepsy by icv administration of histamine was mediated through histamine H1-receptors, and suggested that antidepressants reduced histamine-induced catalepsy via this mechanism. Histamine-induced catalepsy is a possible new animal model of depression which can also be used for evaluation of atypical antidepressants.

  12. Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature in mice.

    Chen, Z; Sugimoto, Y; Kamei, C


    Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature were studied in mice. Histamine (0.1-1.0 mu g) and histidine (500-1,000 mg/kg) caused a dose-related hypothermia. H1 agonist, 2-methylhistamine and 2-thiazolylethylamine also displayed a dose-dependent hypothermia. In addition, H2 agonists, 4-methylhistamine and dimaprit elicited a decrease in body temperature. Preinjection of not only H1-antagonists (diphenhydramine and chlorpheniramine) but also H2 antagonists (cimetidine and ranitidine) abolished histamine-induced hypothermia. Either intracerebroventricular or intraperitoneal injection of thioperamide, a histamine H3 antagonist, showed hypothermia. The hypothermic effect produced by intracerebroventricular injection of thioperamide was significantly blocked by (R)-alpha-methylhistamine, a selective H3 agonist. In addition, the effect induced by thioperamide was inhibited by H1 and H2 antagonists, indicating that the H3 receptor also participates in histamine-induced hypothermia.

  13. High-throughput analysis of drugs in biological fluids by desorption electrospray ionization mass spectrometry coupled with thin liquid membrane extraction

    Rosting, Cecilie; Pedersen-Bjergaard, Stig; Hansen, Steen Honore'


    into the method, methadone was detected in urine in full-scan mode with an LOD of 4 ng mL(-1), while amitriptyline, nortriptyline and pethidine showed LODs of 17 ng mL(-1). Quantification was possible for several basic drugs using one common internal standard, providing relative accuracies in the range of 10......-30%. A reliability test was performed on 20 samples with methadone, amitriptyline, nortriptyline and pethidine in urine, showing that none of the samples having concentrations above the LOD were missed and no false positives were found. Diphenhydramine and one of its metabolites were detected in authentic samples...... of urine and saliva, and methadone was detected from a whole-blood sample spiked to a concentration of 100 ng mL(-1). The method has several advantages, such as extremely low price in consumables, the possibility of fast analysis of very crude biofluids such as whole blood and the potential for a very high...

  14. A Literature Review of the Use of Sodium Bicarbonate for the Treatment of QRS Widening.

    Bruccoleri, Rebecca E; Burns, Michele M


    Sodium bicarbonate is a well-known antidote for tricyclic antidepressant (TCA) poisoning. It has been used for over half a century to treat toxin-induced sodium channel blockade as evidenced by QRS widening on the electrocardiogram (ECG). The purpose of this review is to describe the literature regarding electrophysiological mechanisms and clinical use of this antidote after poisoning by tricyclic antidepressants and other agents. This article will also address the literature supporting an increased serum sodium concentration, alkalemia, or the combination of both as the responsible mechanism(s) for sodium bicarbonate's antidotal properties. While sodium bicarbonate has been used as a treatment for cardiac sodium channel blockade for multiple other agents including citalopram, cocaine, flecainide, diphenhydramine, propoxyphene, and lamotrigine, it has uncertain efficacy with bupropion, propranolol, and taxine-containing plants.

  15. A categorical review on electroanalytical determination of non-narcotic over-the-counter abused antitussive drugs.

    Thapliyal, Neeta; Patel, Harun; Karpoormath, Rajshekhar; Goyal, Rajendra N; Patel, Rajkumar


    Dextromethorphan (DXM) and diphenhydramine (DPH) are two commonly used over-the-counter non-narcotic antitussive drugs. Recent reports reveal the widespread abuse of DXM and DPH due to their euphoric and alcohol-like effects. Due to their medicinal importance as well as the apparent increase in their use as abused drugs, it has become critical to determine them in samples of biological, clinical and pharmaceutical interest. The electrochemical techniques for drug analysis have gathered considerable attention due to their pronounced selectivity, sensitivity and simplicity. The given review presents a compilation of published voltammetric and potentiometric methods developed for determination of DXM and DPH. It critically highlights the analytical performances, revealing the recent trends and progress in the specified approach for their analysis. The review forms a basis for further progress in this field and development of improved electrochemical sensors to determine the drug.

  16. Unusual etiology of gastrointestinal symptoms: the case of jojoba butter

    Minckler MR


    Full Text Available Michael R Minckler,1 Joseph Fisher,2 Rachel Bowers,2 Richard Amini1 1Department of Emergency Medicine, University of Arizona, 2College of Medicine, University of Arizona, Tucson, AZ, USA Background: Jojoba butter is cyanogenic and has gained attention among herbal supplement consumers due to claims that it may aid in weight loss. Jojoba butter is extracted from the seeds of jojoba shrubs found in the Sonoran Desert. The seeds have long been recognized as inedible, however clinical symptoms following ingestion are not well documented. Case report: This report describes a patient who developed restlessness and gastrointestinal complaints following ingestion of homemade jojoba seed butter. The patient’s presentation following ingestion is discussed, as well as effective workup and treatment. In our case, the patient was monitored and received fluid resuscitation, lorazepam, and diphenhydramine for symptomatic therapy. Conclusion: This case describes the gastrointestinal sequela and effective management following ingestion of jojoba butter. Keywords: jojoba butter, simmondsin, cyanoglycoside, anorectic

  17. Possible cross-sensitivity between sertraline and paroxetine in a panic disorder patient

    Khairkar Praveen


    Full Text Available Cross-sensitivity due to paroxetine and sertraline, the SSRIs, is rarely reported in the literature. We report an adverse drug reaction to paroxetine and sertraline in a patient of panic disorder, who initially developed a maculopapular, erythematous, pruritic rash in the third week with sertraline 50 mg/day. The rash resolved within 2 days of its discontinuation and oral supplementation of diphenhydramine and betamethasone. 10 days following discontinuation of sertraline, the patient was shifted on sustain release paroxetine 12.5 mg/day when another skin reaction with the same appearance and distribution appeared on day 4 of it, suggesting a possibility of cross-sensitivity, a drug class effect. This case report intends to improve the awareness among clinicians to use caution when choosing an alternative SSRIs.

  18. Phencyclidine Induced Oculogyric Crisis Responding Well to Conventional Treatment

    Hassan Tahir


    Full Text Available Background. Oculogyric crisis is a form of acute dystonic reaction characterized by involuntary upward deviation of eye ball. Its causes are broad with antipsychotics and antiemetics as the most common causes. Case Presentation. A 25-year-old man with the past medical history of marijuana use presented to ED with involuntary upward deviation of eye 1 day after using phencyclidine (PCP for the first time. He did not have any other symptoms and was hemodynamically stable. All laboratory investigations were normal except urine drug screen which was positive for PCP. Patient was treated with IV diphenhydramine which improved his symptoms. Conclusion. Illicit drug abuse is a growing problem in our society with increasingly more patients presenting to ED with its complications. The differential diagnosis of acute dystonic reactions should be extended to include illicit drugs as the potential cause of reversible acute dystonias especially in high risk patients.

  19. [Control of vomiting induced by antineoplastic chemotherapy in childhood].

    Madero López, L; Pérez Jurado, L; Martín Ramos, N; Contra Gómez, T; Ruiz López, M J; Robles Cascallar, P


    Twenty four children aged 2 to 13 years who were to receive cancer chemotherapy were enrolled in a prospective study (before-after-trial) in order to evaluate the efficacy of systematic antiemetic prophylaxis. The regimen of three drugs (metilpednisolone 4 mg/Kg/dose/iv 2 doses; metodopamide 0.5 mg/Kg/dose/iv 4 doses; diphenydramine 1 mg/Kg/dose/iv 4 doses) was used. We found a significative reduction (P less than 0.001) in the incidence of vomiting and nauseousness duration when the antiemetic prophylaxis was used. There were very few and slight adverse effects secondary to antiemetic drugs: Sedation happened in 25% of chemotherapic cycles and hypotension without clinical repercussion in 15%. No patient had distonia. We conclude that systematical antiemetic protection should be used in children receiving chemotherapy. The association of metilpednisolone, metopramide and diphenhydramine is a safe and effective combination.

  20. Treatment of radiation- and chemotherapy-induced stomatitis

    Carnel, S.B.; Blakeslee, D.B.; Oswald, S.G.; Barnes, M. (Fitzsimons Army Medical Center, Aurora, CO (USA))


    Severe stomatitis is a common problem encountered during either radiation therapy or chemotherapy. Most therapeutic regimens are empirical, with no scientific basis. The purpose of this study is to determine the efficacy of various topical solutions in the treatment of radiation- or chemotherapy-induced stomatitis. Eighteen patients were entered into a prospective double-blinded study to test several topical solutions: (1) viscous lidocaine with 1% cocaine; (2) dyclonine hydrochloride 1.0% (Dyclone); (3) kaolin-pectin solution, diphenhydramine plus saline (KBS); and (4) a placebo solution. Degree of pain relief, duration of relief, side effects, and palatability were evaluated. The results showed that Dyclone provided the most pain relief. Dyclone and viscous lidocaine with 1% cocaine provided the longest pain relief, which averaged 50 minutes This study provides objective data and defines useful guidelines for treatment of stomatitis.

  1. Simultaneous determination of ten antihistamine drugs in human plasma using pipette tip solid-phase extraction and gas chromatography/mass spectrometry.

    Hasegawa, Chika; Kumazawa, Takeshi; Lee, Xiao-Pen; Fujishiro, Masaya; Kuriki, Ayako; Marumo, Akemi; Seno, Hiroshi; Sato, Keizo


    Ten antihistamine drugs, diphenhydramine, orphenadrine, chlorpheniramine, diphenylpyraline, triprolidine, promethazine, homochlorcyclizine, cyproheptadine, cloperastine and clemastine, have been found to be extractable from human plasma samples using MonoTip C18 tips, inside which C18- bonded monolithic silica gel was fixed. Human plasma (0.1 mL) containing the ten antihistamines was mixed with 0.4 mL of distilled water and 25 microL of a 1 M potassium phosphate buffer (pH 8.0). After centrifugation of the mixture, the supernatant fraction was extracted to the C18 phase of the tip by 25 repeated aspirating/dispensing cycles using a manual micropipettor. The analytes retained on the C18 phase were then eluted with methanol by five repeated aspirating/dispensing cycles. The eluate was injected into a gas chromatography (GC) injector without evaporation and reconstitution steps, and was detected by a mass spectrometer with selected ion monitoring in the positive-ion electron impact mode. The separation of the ten drugs from each other and from impurities was generally satisfactory using a DB-1MS column (30 m x 0.32 mm i.d., film thickness 0.25 microm). The recoveries of the ten antihistamines spiked into plasma were 73.8-105%. The regression equations for the ten antihistamines showed excellent linearity with detection limits of 0.02-5.0 ng/0.1 mL. The within-day and day-to-day coefficients of variation for plasma were not greater than 9.9%. The data obtained from determination of diphenhydramine and chlorpheniramine in human plasma after oral administration of the drugs are also presented.

  2. Prescription writing trends of antihistamines at the university health centre.

    Kumar, Anil; Beenta


    The aim of the present study was to establish antihistamines drug prescribing pattern in order to improve the rational prescribing of antihistamines by physicians at Panjab University Health Centre. The study was performed in between the months of November 2005 to April 2006. Five hundred out patients were monitored and data was collected on WHO-based prescription-auditing performa. Demographic analysis of this prospective study revealed that out of the 500 patients, 293 (58.6 %) were male and 207 (41.4 %) were female and maximum patients were in the age group of 21-40 (34.8 %). Chlorpheniramine maleate (235 prescriptions) was the highest prescribed among antihistamine prescriptions (36.89 %) followed by diphenhydramine hydrochloride (186 prescriptions, 29.19%), cetirizine (175 prescriptions, 27.47 %) and promethazine (41 prescriptions, 6.4%). In comparison to generic drugs (169 prescriptions, 26.54%), branded were more prescribed at PUHC. Majority of antihistamines were in form of tablets (414 prescriptions, 64.99%) followed by liquid formulations (195 prescriptions, 30.61%) and injections (28 prescriptions, 4.40%). The average cost of different antihistamine drugs prescribed was as follows: diphenhydramine hydrochloride Rs. 34.74 followed by promethzine Rs. 22.46, chlorpheniramine maleate Rs. 15.30, and cetirizine Rs. 13.50. Average numbers of drugs prescribed per prescription were 1.27. The average consulting and dispensing time was 4.82 and 3.56 min, respectively. Out of the 500 university patients, 258 (51.6%) had the knowledge regarding the medication prescribed and 242 (48.4%) were unaware of the medication prescribed.

  3. The effect of repeated intramuscular alfentanil injections on experimental pain and abuse liability indices in healthy males.

    Tompkins, David Andrew; Smith, Michael T; Bigelow, George E; Moaddel, Ruin; Venkata, Swarajya Lakshmi Vatem; Strain, Eric C


    Opioid-induced hyperalgesia (OIH), increased sensitivity to noxious stimuli after repeated opioid exposures, has been demonstrated in preclinical studies. However, there is no accepted, prospective model of OIH after repeated opioid exposures currently available in humans. This study assessed a potential prospective OIH model. Double-blind intramuscular injections of a short-acting opioid (alfentanil 15 mcg/kg; N=8) were compared to active placebo (diphenhydramine 25 mg; N=3) on cold and pressure pain testing and standard abuse liability measures in eight 10-hour sessions (1 injection/session) over 4 to 5 weeks in healthy, pain-free males. Decreases from session baseline pain threshold (PThr) and tolerance (PTol) were calculated to represent hyperalgesia, and were assessed both within and across sessions. Mean decreases in cold PTol were seen in the alfentanil group at 180 minutes (-3.8 s, ±26.5) and 480 minutes (-1.63 s, ±31.5) after drug administration. There was a trend for differences between conditions on cold PThr hyperalgesia but not for pressure PThr. Alfentanil participants had greater mean ratings on Liking and High visual analog scales at peak effects (30 min), but these scores did not change across sessions. Repeated alfentanil exposures over 4 to 5 weeks resulted in within session decreases in cold pain tolerance from baseline but these differences were not substantially different from diphenhydramine controls. The results did not support the phenomenon of OIH in this model, although definitive conclusions regarding the existence of OIH in humans likely requires a larger sample size or an alternative model.

  4. Prescription writing trends of antihistamines at the university health centre

    Kumar Anil


    Full Text Available The aim of the present study was to establish antihistamines drug prescribing pattern in order to improve the rational prescribing of antihistamines by physicians at Panjab University Health Centre. The study was performed in between the months of November 2005 to April 2006. Five hundred out patients were monitored and data was collected on WHO-based prescription-auditing performa. Demographic analysis of this prospective study revealed that out of the 500 patients, 293 (58.6 % were male and 207 (41.4 % were female and maximum patients were in the age group of 21-40 (34.8 %. Chlorpheniramine maleate (235 prescriptions was the highest prescribed among antihistamine prescriptions (36.89 % followed by diphenhydramine hydrochloride (186 prescriptions, 29.19%, cetirizine (175 prescriptions, 27.47 % and promethazine (41 prescriptions, 6.4%. In comparison to generic drugs (169 prescriptions, 26.54%, branded were more prescribed at PUHC. Majority of antihistamines were in form of tablets (414 prescriptions, 64.99% followed by liquid formulations (195 prescriptions, 30.61% and injections (28 prescriptions, 4.40%. The average cost of different antihistamine drugs prescribed was as follows: diphenhydramine hydrochloride Rs. 34.74 followed by promethzine Rs. 22.46, chlorpheniramine maleate Rs. 15.30, and cetirizine Rs. 13.50. Average numbers of drugs prescribed per prescription were 1.27. The average consulting and dispensing time was 4.82 and 3.56 min, respectively. Out of the 500 university patients, 258 (51.6% had the knowledge regarding the medication prescribed and 242 (48.4% were unaware of the medication prescribed.

  5. Biphasic effects of orexin-A on autonomic nerve activity and lipolysis.

    Shen, Jiao; Tanida, Mamoru; Yao, Jia-Fei; Niijima, Akira; Nagai, Katsuya


    Previously, we showed that orexin-A, a 33-aa peptide, influences renal sympathetic nerve activity. Because the autonomic nervous system plays an important role in the regulation of lipid metabolism, we investigated the in vivo effects of orexin-A on the sympathetic nerve activity innervating white adipose tissue (WAT-SNA) and lipolysis. We found that intracerebroventricular (icv) administration of orexin-A at doses of 1 microg/rat and 10 ng/rat elevated and suppressed WAT-SNA, respectively. The effect of the high dose of orexin-A (1 microg/rat) was eliminated by pretreatment with diphenhydramine hydrochloride, a histamine H(1) receptor antagonist. In contrast, the effect of the low dose of orexin-A (10 ng/rat) was suppressed by thioperamide maleate salt, a histamine H(3) receptor antagonist. Moreover, icv administration of 1 microg/rat and 10 ng/rat of orexin-A increased and decreased the levels of plasma free fatty acids (FFAs), respectively. The effect of 1 microg/rat of orexin-A on plasma FFA was eliminated by propranolol hydrochloride, a beta-adrenergic receptor blocker, and also by diphenhydramine. The effect of orexin-A at dose of 10 ng/rat disappeared by pretreatment with atropine sulfate, a muscarinic receptor blocker, and thioperamide maleate salt. Our results suggest that high doses of orexin-A may regulate the lipolytic processes in adipose tissue through facilitation of the sympathetic nervous system, which is driven by histamine neurons through the H(1) receptor, and that the beta(3)-receptor may be involved in this enhanced lipolytic response. Low doses of orexin-A, on the other hand, may lower lipolysis by suppressing sympathetic nerve activity via the H(3)-receptor, and the muscarinic receptor may be related to this response.

  6. Effects of first- and second-generation histamine-H1-receptor antagonists on the pentobarbital-induced loss of the righting reflex in streptozotocin-induced diabetic mice.

    Kamei, Junzo; Hirano, Shoko; Miyata, Shigeo; Saitoh, Akiyoshi; Onodera, Kenji


    The second-generation histamine-H(1)-receptor antagonists, such as epinastine and cetirizine, are used as non-sedating antihistamines for treating allergic symptoms due to their poor ability to penetrate blood-brain barrier. Because it has been reported that the blood-brain barrier system is disturbed in diabetes, it is possible that second-generation histamine-H(1)-receptor antagonists may easily penetrate the blood-brain barrier and cause potent sedation in diabetics. In the present study, we investigated the effects of first-generation (diphenhydramine) and second-generation (epinastine and cetirizine) histamine-H(1)-receptor antagonists on the duration of pentobarbital-induced loss of the righting reflex (LORR) in non-diabetic and diabetic mice. Systemic treatment with diphenhydramine (3 - 30 mg/kg, s.c.), and intracerebroventricular treatment with epinastine (0.03 - 0.3 microg/mouse) and cetirizine (0.03 - 0.3 microg/mouse) dose-dependently and significantly increased the duration of pentobarbital-induced LORR in both non-diabetic and diabetic mice. Although systemic treatment with epinastine (3 - 30 mg/kg, s.c.) and cetirizine (3 - 30 mg/kg, s.c.) did not affect the duration of pentobarbital-induced LORR in non-diabetic mice, these treatments significantly prolonged it in diabetic mice. Our results suggest that the systemic administration of second-generation histamine-H(1)-receptor antagonists may produce a central nervous system depressant effect in diabetes.

  7. Evaluation of the oxytocic activity of the ethanol extract of the roots of Alchornea cordifolia

    Zuleikha Nworgu


    Full Text Available Alchornea cordifolia has been used traditionally for the induction of labour as an abortifacient. This study is aimed at verifying the folkloric use of the plant by investigating the effect of ethanolic extract of the root bark on the isolated stilboestrol pretreated uteri of non-pregnant female rats. The extract (1, 10, 50 g/l, oxytocin (4Χ10−5 to 8Χ10−3 g/l, acetylcholine (4Χ10−6 to 8Χ10−4 g/l, atropine (4Χ10−3 g/l, phenoxybenzamine (4Χ10−3 g/l, diphenhydramine(2Χ10−1 g/l, and verapamil (12Χ10−2 g/l were used. Log concentration response curves were plotted and EC 50 and Emax were obtained. One-way analysis of variance (ANOVA with Dunnet corrections using Graph pad Instat version 2.05a was used for statistical analysis. The extract produced dose-dependent contraction of the uterus. Its potency was less than that of oxytocin and acetylcholine (P<0.05, but the Emax showed no significant difference (P>0.05. The Emax values of the extract in the presence of all antagonists were significantly reduced (P<0.01. The EC 50 in the presence of atropine showed no significant increase (P>0.05; however, in the presence of phenoxybenzamine, the increase was significant (P<0.05. The presence of diphenhydramine and verapamil produced an inhibition such that the EC 50 was unattainable. A. cordifolia stimulates the uterus possibly by binding to alpha-adrenergic or histaminergic receptors or both. This indicates the existence of active principles in the plant, which may be responsible for some of the applications in traditional medicines as an abortifacient and in the induction of labour.

  8. Qualitative Analysis of Iranian Crack to Determine the Active Ingredient in Committing Crime in order to Determine Criminal Punishment

    Ali Hassan Rahmani


    Full Text Available Crime (the basis of criminal law is the behavior that intentionallyleadsto violation of legal orders and one of the things that hinder the realization of criminal liability is the condition called insanity. People lacking the healthy will, or unaware of the essence of the consequences their acts if they commit crimes they are not addressed in the law and do not have criminal responsibility.In a cross sectional study in Khuzestan forensic toxicology lab after 61 TLCsamplesof crack street, drug recognition tests was doneby HPLC and GC / MS. Examination of data (V22 SPSS (p value <0.05:% 93/4of crack samples were containing morphine,% 83/6 with caffeine, noscapine or dextromethorphan,% 27/9 heroin and codeine,% 37/7 six mono-acetylphloroglucinol morphine,% 34/4 acetyl codeine,% 13/1 narceine and acetaminophen, % 16/4 diazepam and% 9/8 chloramphenicol and other components of methyl amphetamines, diphenhydramine, lidocaine, thebaine, amoxicillin, amitriptyline and nortriptyline % 6/6 of samples were a mixture of methyl amphetamine - diphenhydramine and acetaminophen, it was a special type of Iraniancrack, due to the existence of amphetamines play a major role in dementia and mental illness like schizophrenia.Iraniancrack is not only different from a real crack (cocaine, but differs in the types, number and amount of additives drug ,Opioid and diluent. Crack has different amount of effective substances on the central nervous system pharmacological and non-pharmacological and psychedelic properties.Different Clinical manifestations like dementia and lack of determinationthat leads to crime.As a result, the need to determine the ingredients in the crack used in the examination of crime and helpingthe criminal justice system in determining the penalty is definite.

  9. Quality analysis of Iranian crack referred to Forensic Department of Khuzestan to determine substances affecting dementia

    Ali Hassan Rahmani


    Full Text Available Pharmaceutical drug abuse refers to conscious consumption of drugs for non-medical purposes such as changing the mood, and fitness, etc. Iranian crack (street crock is one of the most abused drugs in Iran. This crack has different medicinal compounds, synthetic, adulterants that have pharmacological structure. Determining type and amount of compounds of Iranian crack and its impact on individuals’ performance, creation of dementia and abnormal behavior, and crime rate are considered as objectives of this study. In this cross-sectional study, 61 crock sampleswere analyzed in forensic toxicology laboratory of Khuzestan. Samples were evaluated usingthin layer chromatography (TLC. Verification tests and identification of pharmaceutical substances were performed qualitatively by HPLC and GC / MS methods. Statistical examination of data by SPSS (V22 (p value <0.05 indicated that 93. 4 % of crack samples contained morphine, 83,6% of them contained caffeine, noscapine and dextromethorphan, 27.9% of them contained heroin and codeine, 37.7 of them contained monoacetyl morphine, 34.4% of them contained acetyl codeine, and 13.1% of them contained narceine and acetaminophen. Other compounds included methyl amphetamines, diphenhydramine, lidocaine, thebaine, amoxicillin, amitriptyline, and nortriptyline. In addition, 6.6% of samples were combination of methyl amphetamine, diphenhydramine and acetaminophen, playing an important role in dementia and mental illness similar to schizophrenia due to presence of amphetamine. Iranian crack not only differs from real crack (cocaine, but also they differ in terms of variety and amount of adulterants, opioid, and diluent substances. In fact, crack has different amounts of substances affecting central nervous system, and other drugs and substances play important role with their pharmacological and non-pharmacological properties in this regard.

  10. Occurrence and loss over three years of 72 pharmaceuticals and personal care products from biosolids-soil mixtures in outdoor mesocosms

    Walters, Evelyn; McClellan, Kristin; Halden, Rolf U.


    Municipal biosolids are in widespread use as additives to agricultural soils in the United States. Although it is well known that digested sewage sludge is laden with organic wastewater contaminants, the fate and behavior of micropollutants in biosolids-amended agricultural soils remain unclear. An outdoor mesocosm study was conducted in Baltimore, Maryland, to explore the fate of 72 pharmaceuticals and personal care products (PPCPs) over the course of three years in biosolids/soil mixtures (1:2) that were placed in plastic containers made from polyvinylchloride and kept exposed to ambient outdoor conditions. Of the 72 PPCPs tested for using EPA Method 1694, 15 were initially detected in the soil/biosolids mixtures at concentrations ranging from low parts-per-billion to parts-per-million levels. The antimicrobials triclocarban and triclosan showed the highest initial concentrations at 2715 and 1265 μg kg−1, respectively. Compounds showing no discernable loss over three years of monitoring included diphenhydramine, fluoxetine, thiabendazole and triclocarban. The following half-life estimates were obtained for compounds showing first-order loss rates: azithromycin (408 – 990 d) carbamazepine (462 – 533 d), ciprofloxacin (1155 – 3466 d), doxycycline (533 – 578 d), 4-epitetracycline (630 d), gemfibrozil (224 – 231 d), norfloxacin (990 – 1386 d), tetracycline (578 d), and triclosan (182 – 193 d). Consistent with other outdoor degradation studies, chemical half-lives determined empirically exceeded those reported from laboratory studies or predicted from fate models. Study results suggest that PPCPs shown in the laboratory to be readily biotransformable can persist in soils for extended periods of time when applied in biosolids. This study provides the first experimental data on the persistence in biosolids-amended soils for ciprofloxacin, diphenhydramine, doxycycline, 4-epitetracycline, gemfibrozil, miconazole, norfloxacin, ofloxacin, and thiabendazole

  11. Pediatric Tape: Accuracy and Medication Delivery in the National Park Service

    Danielle D. Campagne


    Full Text Available Introduction: The objective is to evaluate the accuracy of medication dosing and the time to medication administration in the prehospital setting using a novel length-based pediatric emergency resuscitation tape. Methods: This study was a two-period, two-treatment crossover trial using simulated pediatric patients in the prehospital setting. Each participant was presented with two emergent scenarios; participants were randomized to which case they encountered first, and to which case used the National Park Service (NPS emergency medical services (EMS length-based pediatric emergency resuscitation tape. In the control (without tape case, providers used standard methods to determine medication dosing (e.g. asking parents to estimate the patient’s weight; in the intervention (with tape case, they used the NPS EMS length-based pediatric emergency resuscitation tape. Each scenario required dosing two medications (Case 1 [febrile seizure] required midazolam and acetaminophen; Case 2 [anaphylactic reaction] required epinephrine and diphenhydramine. Twenty NPS EMS providers, trained at the Parkmedic/Advanced Emergency Medical Technician level, served as study participants. Results: The only medication errors that occurred were in the control (no tape group (without tape: 5 vs. with tape: 0, p=0.024. Time to determination of medication dose was significantly shorter in the intervention (with tape group than the control (without tape group, for three of the four medications used. In case 1, time to both midazolam and acetaminophen was significantly faster in the intervention (with tape group (midazolam: 8.3 vs. 28.9 seconds, p=0.005; acetaminophen: 28.6 seconds vs. 50.6 seconds, p=0.036. In case 2, time to epinephrine did not differ (23.3 seconds vs. 22.9 seconds, p=0.96, while time to diphenhydramine was significantly shorter in the intervention (with tape group (13 seconds vs. 37.5 seconds, p<0.05. Conclusion: Use of a length-based pediatric emergency

  12. Structural Basis for Inhibition of Histamine N-Methyltransferase by Diverse Drugs

    Horton,J.; Sawada, K.; Nishibori, M.; Cheng, X.


    In mammals, histamine action is terminated through metabolic inactivation by histamine N-methyltransferase (HNMT) and diamine oxidase. In addition to three well-studied pharmacological functions, smooth muscle contraction, increased vascular permeability, and stimulation of gastric acid secretion, histamine plays important roles in neurotransmission, immunomodulation, and regulation of cell proliferation. The histamine receptor H1 antagonist diphenhydramine, the antimalarial drug amodiaquine, the antifolate drug metoprine, and the anticholinesterase drug tacrine (an early drug for Alzheimer's disease) are surprisingly all potent HNMT inhibitors, having inhibition constants in the range of 10-100 nM. We have determined the structural mode of interaction of these four inhibitors with HNMT. Despite their structural diversity, they all occupy the histamine-binding site, thus blocking access to the enzyme's active site. Near the N terminus of HNMT, several aromatic residues (Phe9, Tyr15, and Phe19) adopt different rotamer conformations or become disordered in the enzyme-inhibitor complexes, accommodating the diverse, rigid hydrophobic groups of the inhibitors. The maximized shape complementarity between the protein aromatic side-chains and aromatic ring(s) of the inhibitors are responsible for the tight binding of these varied inhibitors.

  13. Mitragynine 'Kratom' related fatality: a case report with postmortem concentrations.

    McIntyre, Iain M; Trochta, Amber; Stolberg, Susan; Campman, Steven C


    A 24-year-old man whose medical history was significant for alcohol abuse and depression was found unresponsive in bed. He had several prior suicide attempts with 'pills' and had also been hospitalized for an accidental overdose on a previous occasion. Autopsy findings were unremarkable apart from pulmonary edema and congestion, and urinary retention. Postmortem peripheral blood initially screened positive for mitragynine 'Kratom' (by routine alkaline drug screen by gas chromatography-mass spectrometry, GC-MS), which was subsequently confirmed by a specific GC-MS selective ion mode analysis following solid-phase extraction. Concentrations were determined in the peripheral blood (0.23 mg/L), central blood (0.19 mg/L), liver (0.43 mg/kg), vitreous (<0.05 mg/L), urine (0.37 mg/L) and was not detected in the gastric. Therapeutic concentrations of venlafaxine, diphenhydramine and mirtazapine were also detected together with a negligible ethanol of 0.02% (w/v). The results are discussed in relation to previous cases of toxicity, and the lack of potential for mitragynine postmortem redistribution.

  14. Low-dose propofol for the abortive treatment of pediatric migraine in the emergency department.

    Sheridan, David C; Spiro, David M; Nguyen, Thuan; Koch, Thomas K; Meckler, Garth D


    Limited progress has been made in the past decade for abortive treatment of migraine headache in the pediatric emergency department (PED). Propofol, a general anesthetic, has been reported to be effective in the treatment of refractory headaches in adults at subanesthetic doses but never in the pediatric population. The goal of this study was to review our institution's experience with subanesthetic doses of propofol for the abortive treatment of pediatric migraine and compare propofol with standard abortive therapy in the PED. Retrospective review of all patients discharged from the Oregon Health and Science University PED with a diagnosis of migraine headache from January 2010 to July 2011. Patients treated with subanesthetic doses of propofol were compared with matched controls who received standard abortive migraine therapy, defined as the combined use of a nonsteroidal anti-inflammatory medication, diphenhydramine, and prochlorperazine. Outcome variables of interest included reduction of pain as measured on a self-reported visual analog scale and length of stay after administration of initial abortive medication. Patients who received subanesthetic doses of propofol achieved significantly greater reduction in pain scores (80.1% vs 61.1%; P Propofol seems to be effective for the abortive treatment of pediatric migraine headache in the PED. Further prospective trials are warranted to either support or refute these initial findings.

  15. In vitro detection of cardiotoxins or neurotoxins affecting ion channels or pumps using beating cardiomyocytes as alternative for animal testing.

    Nicolas, Jonathan; Hendriksen, Peter J M; de Haan, Laura H J; Koning, Rosella; Rietjens, Ivonne M C M; Bovee, Toine F H


    The present study investigated if and to what extent murine stem cell-derived beating cardiomyocytes within embryoid bodies can be used as a broad screening in vitro assay for neurotoxicity testing, replacing for example in vivo tests for marine neurotoxins. Effect of nine model compounds, acting on either the Na(+), K(+), or Ca(2+) channels or the Na(+)/K(+) ATP-ase pump, on the beating was assessed. Diphenhydramine, veratridine, isradipine, verapamil and ouabain induced specific beating arrests that were reversible and none of the concentrations tested induced cytotoxicity. Three K(+) channel blockers, amiodarone, clofilium and sematilide, and the Na(+)/K(+) ATPase pump inhibitor digoxin had no specific effect on the beating. In addition, two marine neurotoxins i.e. saxitoxin and tetrodotoxin elicited specific beating arrests in cardiomyocytes. Comparison of the results obtained with cardiomyocytes to those obtained with the neuroblastoma neuro-2a assay revealed that the cardiomyocytes were generally somewhat more sensitive for the model compounds affecting Na(+) and Ca(2+) channels, but less sensitive for the compounds affecting K(+) channels. The stem cell-derived cardiomyocytes were not as sensitive as the neuroblastoma neuro-2a assay for saxitoxin and tetrodotoxin. It is concluded that the murine stem cell-derived beating cardiomyocytes provide a sensitive model for detection of specific neurotoxins and that the neuroblastoma neuro-2a assay may be a more promising cell-based assay for the screening of marine biotoxins. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. A novel HPLC-MS/MS method for the simultaneous determination of astemizole and its major metabolite in dog or monkey plasma and application to pharmacokinetics.

    Back, Hyun-moon; Lee, Jong-Hwa; Chae, Jung-woo; Song, Byungjeong; Seo, Joung-Wook; Yun, Hwi-yeol; Kwon, Kwang-il


    Astemizole (AST), a second-generation antihistamine, is metabolized to desmethyl astemizole (DEA), and although it has been removed from the market for inducing QT interval prolongation, it has reemerged as a potential anticancer and antimalarial agent. This report describes a novel high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneously determining the concentrations of AST and DEA in beagle dog and cynomolgus monkey plasma with simple preparation method and short retention time. Prior to HPLC analyses, the plasma samples were extracted with simple liquid-liquid extraction method. The isocratic mobile phase was 0.025% trifluoroacetic acid (TFA dissolved in acetonitrile) and 20 mM ammonium acetate (94:6) at a flow rate of 0.25 mL/min and diphenhydramine used as internal standard. In MS/MS analyses, precursor ions of the analytes were optimized as protonated molecular ions: [M+H](+). The lower limit of quantification of astemizole was 2.5 ng/mL in both species and desmethyl astemizole were 7.5 ng/mL and 10 ng/mL in dog and monkey plasma, respectively. The accuracy, precision, and stability of the method were in accordance with FDA guidelines for the validation of bioanalytical methods. Finally this validated method was successfully applied to a pharmacokinetic study in dogs and monkeys after oral administration of 10 mg/kg AST.

  17. Catalytic ozonation of selected pharmaceuticals over mesoporous alumina-supported manganese oxide.

    Yang, Li; Hu, Chun; Nie, Yulun; Qu, Jiuhui


    Catalytic ozonation of five pharmaceutical compounds (PhACs)-phenazone, ibuprofen, diphenhydramine, phenytoin, and diclofenac sodium in alumina-supported manganese oxide (MnOx) suspension was carried out with a semicontinuous laboratory reactor. MnOx supported by mesoporous alumina (MnOx/MA) was highly effective in mineralizing the PhACs in aqueous solution. Fourier transform infrared (FTIR) spectroscopy and in situ attenuated total reflection FTIR (ATR-FTIR) spectroscopy were used to examine the interaction of ozone with different catalysts undervarious conditions. The crucial active sites, surface oxide species at 1380 cm(-1), were formed by the interaction of ozone with Lewis acid sites on the alumina surface. New surface hydroxyl groups at 2915 and 2845 cm(-1) were produced by the interaction of the catalyst and ozone in aqueous suspension and became active sites in the presence of MnOx. The introduction of MnOx enhanced the formation and activation of surface hydroxyl groups, causing higher catalytic reactivity. On the basis of these findings, a reaction mechanism is proposed for the catalytic ozonation of PhACs in MnOx/MA suspension.

  18. The occurrence of illicit and therapeutic pharmaceuticals in wastewater effluent and surface waters in Nebraska

    Bartelt-Hunt, Shannon L. [Department of Civil Engineering, University of Nebraska-Lincoln, 203B Peter Kiewit Institute, Omaha, NE 68182-0178 (United States)], E-mail:; Snow, Daniel D.; Damon, Teyona [Water Sciences Laboratory, University of Nebraska-Lincoln, Lincoln, NE 68583-0844 (United States); Shockley, Johnette [Department of Civil Engineering, University of Nebraska-Lincoln, 203B Peter Kiewit Institute, Omaha, NE 68182-0178 (United States); Hoagland, Kyle [UNL Water Center, University of Nebraska-Lincoln, Lincoln, NE 68583-0995 (United States)


    The occurrence and estimated concentration of twenty illicit and therapeutic pharmaceuticals and metabolites in surface waters influenced by wastewater treatment plant (WWTP) discharge and in wastewater effluents in Nebraska were determined using Polar Organic Chemical Integrative Samplers (POCIS). Samplers were installed in rivers upstream and downstream of treated WWTP discharge at four sites and in a discharge canal at a fifth location. Based on differences in estimated concentrations determined from pharmaceuticals recovered from POCIS, WWTP effluent was found to be a significant source of pharmaceutical loading to the receiving waters. Effluents from WWTPs with trickling filters or trickling filters in parallel with activated sludge resulted in the highest observed in-stream pharmaceutical concentrations. Azithromycin, caffeine, 1,7-dimethylzanthine, carbamazepine, cotinine, DEET, diphenhydramine, and sulfamethazine were detected at all locations. Methamphetamine, an illicit pharmaceutical, was detected at all but one of the sampling locations, representing only the second report of methamphetamine detected in WWTP effluent and in streams impacted by WWTP effluent. - Passive samplers were used to develop semi-quantitative estimates of pharmaceutical concentrations in receiving waters influenced by wastewater effluent.

  19. Evaluation and treatment of poisonous snakebites.

    Forks, T P


    Snakebite victims should be transported immediately to the nearest emergency department. Incision and suction are contraindicated unless performed by experienced personnel within five minutes of the bite, or unless transport of the patient to definitive medical care will take more than 30 minutes. Cryotherapy is contraindicated. All bites should be graded for severity of envenomation. The wound should be cleaned and broad-spectrum antibiotics administered. Tetanus status should be determined and tetanus toxoid administered if necessary. Antivenin is indicated in certain mild cases and in all moderate and severe cases of envenomation. Patients with a mild case of envenomation may require up to five vials of antivenin; patients with moderate bites may require 10 to 15 vials, and patients with severe bites may require 15 to 20 vials. Antivenin is effective only when administered intravenously; skin testing to predict the possibility of anaphylactic reaction is mandatory before administration. Diphenhydramine and epinephrine should be readily available in case of anaphylaxis. Fasciotomy is only indicated in rare cases involving elevated intracompartment pressures.

  20. Single-step multiresidue determination of ten multiclass veterinary drugs in pork, milk, and eggs using liquid chromatography with tandem mass spectrometry.

    Park, Jin-A; Zhang, Dan; Kim, Dong-Soon; Kim, Seong-Kwan; Cho, Kyeong-Su; Jeong, Dana; Shim, Jae-Han; Kim, Jin-Suk; Abd El-Aty, A M; Shin, Ho-Chul


    A multiclass, multiresidue determination method is reported for the detection of ten veterinary drugs, including scopolamine, metoclopramide, acriflavine, berberine, tripelennamine, diphenhydramine, acrinol, triamcinolone, loperamide, and roxithromycin in pork, milk, and eggs. The method involves a simple extraction using 0.1% formic acid in acetonitrile, followed by defatting with n-hexane, centrifugation, and filtration prior to liquid chromatography with tandem mass spectrometric analysis. As ion suppression and enhancement effects are reported, matrix-matched calibrations are used for quantification, with determination coefficients ≥0.9765. For the majority of the tested analytes, the intra- and interday accuracy (expressed as recovery %) range from 70.6 to 94.6% and from 70.1 to 93.3%, respectively, and the precision (expressed as relative standard deviation) ranges from 0.5 to 19.8% and from 2.8 to 18.4% in all matrices. The limits of quantification range between 0.5 and 10 ng/g. The validated tandem mass spectrometry method is successfully applied to market samples; the target analytes are not detected in any of the tested samples. In terms of accuracy, no extract cleanup is deemed necessary. The developed method is feasible for the simultaneous detection of the tested analytes in pork, milk, and eggs.

  1. Identification of histamine receptors and reduction of squalene levels by an antihistamine in sebocytes.

    Pelle, Edward; McCarthy, James; Seltmann, Holger; Huang, Xi; Mammone, Thomas; Zouboulis, Christos C; Maes, Daniel


    Overproduction of sebum, especially during adolescence, is causally related to acne and inflammation. As a way to reduce sebum and its interference with the process of follicular keratinization in the pilosebaceous unit leading to inflammatory acne lesions, antihistamines were investigated for their effect on sebocytes, the major cell of the sebaceous gland responsible for producing sebum. Reverse transcriptase-PCR analysis and immunofluorescence of an immortalized sebocyte cell line (SZ95) revealed the presence of histamine-1 receptor (H-1 receptor), and thus indicated that histamines and, conversely, antihistamines could potentially modulate sebocyte function directly. When sebocytes were incubated with an H-1 receptor antagonist, diphenhydramine (DPH), at non-cytotoxic doses, a significant decrease in squalene levels, a biomarker for sebum, was observed. As determined by high-performance liquid chromatography, untreated sebocytes contained 6.27 (+/-0.73) nmol squalene per 10(6) cells, whereas for DPH-treated cells, the levels were 2.37 (+/-0.24) and 2.03 (+/-0.97) nmol squalene per 10(6) cells at 50 and 100 microM, respectively. These data were further substantiated by the identification of histamine receptors in human sebaceous glands. In conclusion, our data show the presence of histamine receptors on sebocytes, demonstrate how an antagonist to these receptors modulated cellular function, and may indicate a new paradigm for acne therapy involving an H-1 receptor-mediated pathway.

  2. Spectrophotometric determination of some histamine H1-antagonists drugs in their pharmaceutical preparations

    Hassan, Wafaa S.; El-Henawee, Magda M.; Gouda, Ayman A.


    Two rapid, simple and sensitive extractive specrophotometric methods has been developed for the determination of three histamine H1-antagonists drugs, e.g., chlorphenoxamine hydrochloride (CPX), diphenhydramine hydrochloride (DPH) and clemastine (CMT) in bulk and in their pharmaceutical formulations. The first method depend upon the reaction of molybdenum(V) thiocyanate ions (Method A) with the cited drugs to form stable ion-pair complexes which extractable with methylene chloride, the orange red color complex was determined colorimetrically at λmax 470 nm. The second method is based on the formation of an ion-association complex with alizarin red S as chromogenic reagents in acidic medium (Method B), which is extracted into chloroform. The complexes have a maximum absorbance at 425 and 426 nm for (DPH or CMT) and CPX, respectively. Regression analysis of Beer-Lambert plots showed a good correlation in the concentration ranges of 5.0-40 and 5-70 μg mL -1 for molybdenum(V) thiocyanate (Method A) and alizarin red S (Method B), respectively. For more accurate analysis, Ringbom optimum concentration ranges were calculated. The molar absorptivity, Sandell sensitivity, detection and quantification limits were calculated. Applications of the procedure to the analysis of various pharmaceutical preparations gave reproducible and accurate results. Further, the validity of the procedure was confirmed by applying the standard addition technique and the results obtained in good agreement well with those obtained by the official method.

  3. In vitro study of histamine and histamine receptor ligands influence on the adhesion of purified human eosinophils to endothelium.

    Grosicki, Marek; Wójcik, Tomasz; Chlopicki, Stefan; Kieć-Kononowicz, Katarzyna


    It is a well-known fact that histamine is involved in eosinophil-dependent inflammatory responses including cellular chemotaxis and migration. Nevertheless, the relative role of histamine receptors in the mechanisms of eosinophils adhesion to endothelial cells is not known. Therefore the aim of presented study was to examine the effect of selective histamine receptors ligands on eosinophils adhesion to endothelium. For that purpose the highly purified human eosinophils have been isolated from the peripheral blood. The viability and functional integrity of isolated eosinophils have been validated in several tests. Histamine as well as 4-methylhistamine (selective H4 agonist) in concentration-dependent manner significantly increased number of eosinophils that adhere to endothelium. Among the selective histamine receptors antagonist or H1 inverse agonist only JNJ7777120 (histamine H4 antagonist) and thioperamide (dual histamine H3/H4 antagonist) had direct effect on eosinophils adhesion to endothelial cells. Antagonists of H1 (diphenhydramine, mepyramine) H2 (ranitidine and famotidine) and H3 (pitolisant) histamine receptors were ineffective. To the best of our knowledge, this is the first study to demonstrate that histamine receptor H4 plays a dominant role in histamine-induced eosinophils adhesion to endothelium.

  4. Subcutaneous delivery of sumatriptan in the treatment of migraine and primary headache

    Moore JC


    Full Text Available Johanna C Moore, James R MinerDepartment of Emergency Medicine, Hennepin County Medical Center, Minneapolis, MN, USAAbstract: Subcutaneous sumatriptan is an effective treatment for pain from acute migraine headache, and can be used in patients with known migraine syndrome and in patients with primary headaches when secondary causes have been excluded. In limited comparative trials, subcutaneous sumatriptan performed in a manner comparable with oral eletriptan and intravenous metoclopramide, was superior to intravenous aspirin and intramuscular trimethobenzamide-diphenhydramine, and was inferior to intravenous prochlorperazine for pain relief. The most common side effects seen with subcutaneous sumatriptan are injection site reactions and triptan sensations. As with all triptans, there is a risk of rare cardiovascular events with subcutaneous sumatriptan and its use should be limited to those without known cerebrovascular disease and limited in those with known cardiovascular risk factors and unknown disease status. In studies of patient preference and tolerability, the subcutaneous formulation has a faster time of onset and high rate of efficacy when compared with the oral formulation, but the oral formulation appears to be better tolerated. It is important to consider the needs of the patient, their past medical history, and what aspects of migraine treatment are most important to the patient when considering treatment of acute migraine or primary headache. Subcutaneous sumatriptan is a good first-line agent for the treatment of pain from acute migraine headaches and primary headaches.Keywords: sumatriptan, subcutaneous, migraine headache, primary headache

  5. A fast and efficient determination of amines and preservatives in cough and cold liquid and suspension formulations using a single isocratic ion-pairing high performance [correction of power] liquid chromatography method.

    Paciolla, M D; Jansen, S A; Martellucci, S A; Osei, A A


    A single, highly selective ion-pairing reverse phase-high power liquid chromatography (RP-HPLC) method has been developed for the determination of amines and preservatives in a wide range of Tylenol((R)) liquid and suspension liquid products. As with many OTC products, the challenge is to quantitatively extract the analytes from difficult matrices and specifically analyze them in the presence of various excipients and flavors. Historically, separate analytical methods were used for each class of analytes (acids, bases and neutral compounds). In this method a mobile phase consisting of a buffered ion-pairing agent with acetonitrile, methanol and tetrahydrofuran was used to separate the charged amines from neutral and acidic compounds on a Phenomenex LUNA C8(2) 75 x 4.6 mm i.d. analytical column with a 3-microm particle size. The analytes include acids (benzoic acid), bases (pseudoephedrine, chlorpheniramine, dextromethorphan, doxylamine and diphenhydramine) and a neutral compound (butylparaben). The effects of pH, the chain length of the ion-pairing reagent, ionic strength and organic modifiers on the separation are discussed. The method is linear from 15 to 150% of the target amounts. The optimized method proves to be specific, robust and accurate for the analysis of the compounds.

  6. Ion mobility spectrometry for the rapid analysis of over-the-counter drugs and beverages

    Fernández-Maestre, Roberto


    In the pharmaceutical industry, there are increasing requirements for analytical methods in quality assessment for the production of drugs. In this investigation, ion mobility spectrometry (IMS) was used for the rapid qualitative separation and identification of active ingredients in generic over-the-counter drugs and food additives in beverages. The active ingredients determined in drugs were acetaminophen, aspartame, bisacodyl, caffeine, dextromethorphan, diphenhydramine, famotidine, glucosamine, guaifenesin, loratadine, niacin, phenylephrine, pyridoxine, thiamin, and tetrahydrozoline. Aspartame and caffeine were determined in beverages. Fourteen over-the-counter drugs and beverages were analyzed. Analysis times below 10 s were obtained for IMS, and reduced mobilities were reported for the first time for 12 compounds. A quadrupole mass spectrometer coupled to a mobility spectrometer was used to assure a correct peak assignation. The combination of fast analysis, low cost, and inexpensive maintenance of IMS instruments makes IMS an attractive technique for the qualitative determination of the active ingredients in over-the-counter drugs and food additives in manufacture quality control and cleaning verification for the drug and food industries. PMID:20835390

  7. Acute pregabalin withdrawal: a case report and review of the literature

    Barrett JA


    Full Text Available Objective: Pregabalin is a commonly prescribed GABA analog most commonly used for the treatment of neuralgia. Recently, case reports on pregabalin have been published describing episodes that may be associated with withdrawal-like symptoms after extended or aggressive therapy. This report describes a case in which long term exposure of high dose pregabalin may have resulted in acute withdrawal, and outlines the subsequent medical management of these symptoms. Case Summary: A 61-year-old male presenting with severe agitation presumed to be withdrawal from long term and high dose exposure to pregabalin. Medical management included the use of haloperidol, diphenhydramine, lorazepam and the addition of clonidine over the course of several days for the pharmacological management of withdrawal symptoms. Discussion: Although case reports are available to guide clinicians in the recognition of acute pregabalin withdrawal, definitive evidence on how best to treat these patients remains severely limited. With an increase in the prescribing practices of pregabalin, insight into the acute management by fellow clinicians is further needed. Conclusion: Caution must be practiced when prescribing and educating patients on the use of pregabalin to prevent associated withdrawal-like symptoms. In addition, documentation by the medical community on methods utilized to treat pregabalin withdrawal syndromes remains crucial for the advancement of patient care. Benzodiazepines and clonidine are the current therapies that have been documented as potentially effective treatment modalities at this time.

  8. Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds

    Mengxuan Gao


    Full Text Available Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as “seizure-inducing” drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs.

  9. Childhood serum sickness: a case report.

    Chao, Y K; Shyur, S D; Wu, C Y; Wang, C Y


    Childhood serum sickness is a rare allergic disease that follows the administration of a foreign antigenic material, most commonly caused by injecting a protein or haptenic drug. The disease is a type III hypersensitivity reaction mediated by deposits of circulating immune complexes in small vessels, which leads to complement activation and subsequent inflammation. The clinical features are fever, cutaneous eruptions, lymphadenopathy, arthralgias, albuminuria, and nephritis. Serum sickness is an acute self-limited disease. We report a 3-year-old child who presented with fever and a rash; an invasive bacterial infection was strongly suspected. He was therefore given penicillin and gentamicin and responded well. At day 4 after admission, he developed a serum sickness reaction and showed symptoms of arthralgias, generalized edema, purpura, and gross hematuria. The white blood cell count was 12 190/mm3 with 7% eosinophils. Urinalysis revealed red blood cell above 100 per high power field, white blood cell 10 to 15 per high power field, and proteinuria. The antibiotics were discontinued and hydrocortisone (20 mg/kg/d), diphenhydramine HCl (4 mg/kg/d), aspirin (66 mg/kg/d) was administered, plus 1 dose of epinephrine (0.01 mL/kg) administered intramuscularly. On day 7, the 3rd day after withholding antibiotics, his condition dramatically improved. The clinical symptoms resolved progressively and his urinalysis returned to normal.

  10. Effects of antihistamines on the function of human α7-nicotinic acetylcholine receptors.

    Sadek, Bassem; Khanian, Seyedeh Soha; Ashoor, Abrar; Prytkova, Tatiana; Ghattas, Mohammad A; Atatreh, Noor; Nurulain, Syed M; Yang, Keun-Hang Susan; Howarth, Frank Christopher; Oz, Murat


    Effects of the histamine H₁ receptor (H1R) antagonists (antihistamines), promethazine (PMZ), orphenadrine (ORP), chlorpheniramine (CLP), pyrilamine (PYR), diphenhydramine (DPH), citerizine (CTZ), and triprolidine (TRP) on the functional properties of the cloned α7 subunit of the human nicotinic acetylcholine receptor expressed in Xenopus oocytes were investigated. Antihistamines inhibited the α7-nicotinic acetylcholine receptor in the order PYR>CLP>TRP>PMZ>ORP≥DPH≥CTZ. Among the antihistamines, PYR showed the highest reversible inhibition of acetylcholine (100 µM)-induced responses with IC₅₀ of 6.2 µM. PYR-induced inhibition was independent of the membrane potential and could not be reversed by increasing the concentration of acetylcholine. Specific binding of [¹²⁵I] α-bungarotoxin, a selective antagonist for α7-nicotinic acetylcholine receptor, was not changed in the presence of PYR suggesting a non-competitive inhibition of nicotinic receptors. In line with functional experiments, docking studies indicated that PYR can potentially bind allosterically with the α7 transmembrane domain. Our results indicate that the H₂-H₄ receptor antagonists tested in this study (10 µM) showed negligible inhibition of α7-nicotinic acetylcholine receptors. On the other hand, H₁ receptor antagonists inhibited the function of human α7-nicotinic acetylcholine receptor, with varying potencies. These results emphasize the importance of α7-nicotinic acetylcholine receptor for future pharmacological/toxicological profiling.

  11. Using Potentiometric Free Drug Sensors to Determine the Free Concentration of Ionizable Drugs in Colloidal Systems.

    Tran, Thuy; Chakraborty, Anjan; Xi, Xi; Bohets, Hugo; Cornett, Claus; Tsinman, Konstantin; Rades, Thomas; Müllertz, Anette


    The present study investigates the use of free drug sensors (FDS) to measure free ionized drug concentrations in colloidal systems, including micellar solutions, emulsions, and lipid formulations during in vitro lipolysis. Diphenhydramine hydrochloride (DPH) and loperamide hydrochloride (LOP) were selected as model drugs. Self-diffusion nuclear magnetic resonance studies were performed and confirmed the entrapment of drugs in micelles in Brij 35 and sodium taurodeoxycholate (TDC)/phosphatidylcholine (PC) micellar solutions. The FDS measurements indicated that with a constant level of drug, the percentage of free DPH and LOP decreased from 84% to 57% and from 51% to 18%, respectively, as the concentration of Brij 35 was increased from 4.7 to 22 mM; and from 99% to 46% and from 100% to 21%, respectively, as the concentration of TDC/PC was increased from 0.49/0.04 to 8.85/0.78 mM. During the in vitro lipolysis of a lipid formulation, free drug concentration decreased with lipolysis time. The percentage of free DPH was higher than for LOP in the same colloidal system because DPH is less lipophilic than LOP. The study showed that FDS can be used to monitor the free drug concentration in colloidal systems with fast response, no sample treatment and simple data analysis. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  12. Proliferative Effects of Histamine on Primary Human Pterygium Fibroblasts

    Zhenwei Qin


    Full Text Available Purpose. It has been confirmed that inflammatory cytokines are involved in the progression of pterygium. Histamine can enhance proliferation and migration of many cells. Therefore, we intend to investigate the proliferative and migratory effects of histamine on primary culture of human pterygium fibroblasts (HPFs. Methods. Pterygium and conjunctiva samples were obtained from surgery, and toluidine blue staining was used to identify mast cells. 3-[4, 5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT was performed to evaluate the proliferative rate of HPFs and human conjunctival fibroblasts (HCFs; ki67 expression was also measured by immunofluorescence analysis. Histamine receptor-1 (H1R antagonist (Diphenhydramine Hydrochloride and histamine receptor-2 (H2R antagonist (Nizatidine were added to figure out which receptor was involved. Wound healing model was used to evaluate the migratory ability of HPFs. Results. The numbers of total mast cells and degranulated mast cells were both higher in pterygium than in conjunctiva. Histamine had a proliferative effect on both HPFs and HCFs, the effective concentration (10 μmol/L on HPFs was lower than on HCFs (100 μmol/L, and the effect could be blocked by H1R antagonist. Histamine showed no migratory effect on HPFs. Conclusion. Histamine may play an important role in the proliferation of HPFs and act through H1R.

  13. Evaluation of microbial and physico-chemical qualities of some cough syrups marketed in Sana’a city, Yemen.

    Ali G. Al−Kaf


    Full Text Available Context: Microbial contamination of cough syrups can bring clinical hazards to the users or patients as well as physical and chemical changes in the product. Aims: To evaluate the microbial and physicochemical characteristics of two hundred samples of four different types of cough syrups marketed in Sana’a city, Yemen. Methods: All collected samples were subjected to the following examinations: the total microbial count, type of isolated microorganisms, physical parameters, and concentration of active ingredients were identified and assessed by standard techniques described in US Pharmacopeia. Results: All the cough syrup samples used contained viable microbial load within acceptable limit according Pharmacopeia specifications. Bacillus subtilis, Micrococcus fulvum, and Staphylococcus epidermidis were the most commonly recovered bacteria. However, Aspergillus niger, Aspergillus fumigatus, Penicillium notatum, Mucor sp., and Aspergillus flavus were the most fungi isolated. The physical properties represented in the appearance, density, and pH of the analyzed samples complied with Pharmacopoeia standards. The concentrations of diphenhydramine HCl (92,51 – 108,78%, pseudoephedrine HCl (94,55 – 109,07%, and triprolidine HCl (98,20 – 104,19% were recorded. Conclusions: All cough syrups marketed in Sana’a City had good microbiological and physico-chemical qualities.

  14. The simultaneous determination of active ingredients in cough-cold mixtures by isocratic reversed-phase ion-pair high-performance liquid chromatography.

    Lau, O W; Chan, K; Lau, Y K; Wong, W C


    A simple, rapid and accurate method for the simultaneous determination of active ingredients in cough-cold mixtures using isocratic reversed-phase ion-pair high-performance liquid chromatography has been developed. It involves the use of an octadecylsilane column as the stationary phase with methanol, water, tetrahydrofuran, phosphoric acid mixtures as mobile phase including sodium dioctylsulphosuccinate as the ion-pair agent. The pH of the mobile phase was adjusted to 4.6 by means of phosphoric acid and ammonium hydroxide solutions. The proposed method involves the simple dilution of the samples with the mobile phase and the addition of metoclopramide hydrochloride as the internal standard. The active ingredients under investigation were chlorpheniramine, codeine, diphenhydramine, ephedrine, ethylmorphine, phenylephrine, phenylpropanolamine and pholcodine, which exist as various combinations in cough-cold mixtures. The optimum composition of the mobile phase and the optimum flow rate were determined and are reported. The method was applied to the determination of active ingredients in seven commercially available cough-cold mixtures.

  15. Identification of position isomers by energy-resolved mass spectrometry.

    Menachery, Sunil Paul M; Laprévote, Olivier; Nguyen, Thao P; Aravind, Usha K; Gopinathan, Pramod; Aravindakumar, Charuvila T


    This study reports an energy-resolved mass spectrometric (ERMS) strategy for the characterization of position isomers derived from the reaction of hydroxyl radicals ((●)OH) with diphenhydramine (DPH) that are usually hard to differentiate by other methods. The isomer analogues formed by (●)OH attack on the side chain of DPH are identified with the help of a specific fragment ion peak (m/z 88) in the collision-induced dissociation (CID) spectrum of the protonated molecule. In the negative ion mode, the breakdown curves of the deprotonated molecules show an order of stability (supported by density functional theory (DFT) calculations) ortho > meta > para of the positional isomers formed by the hydroxylation of the aromatic ring. The gas phase stability of the deprotonated molecules [M - H](-) towards the benzylic cleavage depends mainly on the formation of intramolecular hydrogen bonds and of the mesomeric effect of the phenol hydroxyl. The [M - H](-) molecules of ortho and meta isomers result a peak at m/z 183 with notably different intensities because of the presence/absence of an intramolecular hydrogen bonding between the OH group and C9 protons. The ERMS approach discussed in this report might be an effective replacement for the conventional methods that requires very costly and time-consuming separation/purification methods along with the use of multi-spectroscopic methods.

  16. Mast cells are critical for protection against peptic ulcers induced by the NSAID piroxicam.

    Daniel D Hampton

    Full Text Available Many commonly used non-steroidal anti-inflammatory drugs (NSAIDs also cause gastrointestinal toxicity, including the development of life-threatening peptic ulcers. We report that mast cell-deficient mice have an extremely high incidence of severe peptic ulceration when exposed to the NSAID piroxicam. This enhanced ulcer susceptibility can be reversed by reconstitution with mast cells. Furthermore, wild type mice treated with diphenhydramine hydrochloride, a commonly used antihistamine that blocks histamine H1 receptors, develop a similarly high incidence of peptic ulcers following piroxicam exposure. The protective effect of mast cells is independent of TNF, blockade of H2 receptors, or acid secretion. These data indicate a critical role for mast cells and the histamine that they produce in prevention and/or repair of piroxicam-induced gastric mucosal injury. Additional studies will be required to determine whether this represents a NSAID class effect that can be exploited to develop novel therapeutic strategies to limit the incidence of NSAID-induced side effects in humans.

  17. [Machanism of the stimulatory effect of intracerebroventricular administration of histamine on gastatric acid secretion induced by pentagastrin in rats].

    Zhang, J; Wang, Z L; Lu, G Q


    The present experiment was designed to study the mechanism underlying the stimulatory effect of histamine (HA, i.c.v.) on the gastric acid secretion in subdiaphragmatic vagotomized SD rats. Gastric acid was continuously washed out with 37 degrees C saline by a perfusion pump. Drugs were injected into the third ventricle or the vein to examine the effect on gastric acid secretion and the level of plasma corticosterone. The results are as follows: (1) HA (1.0 microgram, i.c.v.) potentiated gastric acid secretion induced by G-5, which could be abolished by preintramuscular injection of diphenhydramine hydrochloride (8.0 micrograms). (2) Corticotropin-releasing factor (CRF) (0.5 microgram, 1.0 microgram, i.c.v.) augmented gastric acid secretion in a dose dependent manner. (3) HA (1.0 microgram, i.c.v.) increased the plasma corticosterone level. (4) Intravenous injection of corticosterone 21-sulfale (15, 30 micrograms) augmented gastric acid secretion in a dose dependent manner. These results suggested that intracerebroventricular injection of HA could stimulate the release of CRF by specificably binding with H1 receptor in some areas of hypothalamus, which, in turn, increased gastric acid secretion induced by G-5 via increasing the level of plasma corticosterone.

  18. Effects of histamine and related compounds on regional cerebral blood flow in rats.

    Suzuki, G; Chen, Z; Sugimoto, Y; Fujii, Y; Kamei, C


    The effects of histamine and related compounds on regional cerebral blood flow (rCBF) in the hippocampus of conscious rats were studied. Intracerebroventricular injection of histamine caused a dose-dependent increase in rCBF in the hippocampus, and similar findings were observed with not only the H1 agonist, 2-thiazolylethylamine, but also the H2 agonist, dimaprit. Intraperitoneal injection of L-histidine also resulted in an increase in rCBF in the hippocampus, in parallel with elevation of histamine content in the brain. The increase in rCBF in the hippocampus induced by L-histidine was antagonized by both H1 and H2 antagonists (diphenhydramine, pyrilamine and zolantidine). In addition, when both antagonists were injected simultaneously, an additive effect was observed in antagonism of the L-histidine-induced increase in rCBF. L-Histidine caused no marked changes in blood pressure even at a dose of 1,500 mg/kg, which showed an increase in rCBF in the hippocampus. These results indicate that histamine elicited an increase in rCBF via both H1 and H2 receptors.

  19. Rodent antinociception following acute treatment with different histamine receptor agonists and antagonists.

    Farzin, Davood; Asghari, Ladan; Nowrouzi, Mahvash


    The effects of different histamine receptor agonists and antagonists on the nociceptive threshold were investigated in mice by two different kinds of noxious stimuli: thermal (hot plate) and chemical (acetic acid-induced abdominal writhing). Intracerebroventricular (icv) injection of the histamine H(1) receptor agonist, HTMT (6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide) (50 microg/mouse), produced a hypernociception in the hot plate and writhing tests. Conversely, intraperitoneal (ip) injection of dexchlorpheniramine (30 and 40 mg/kg) and diphenhydramine (20 and 40 mg/kg) increased the pain threshold in both tests. The histamine H(2) receptor agonist, dimaprit (50 and 100 microg/mouse icv), or antagonist, ranitidine (50 and 100 microg/mouse icv), raised the pain threshold in both hot plate and writhing tests. In the mouse hot plate test, the histamine H(3) receptor agonist, imetit (50 mg/kg ip), reduced the pain threshold, while the histamine H(3) receptor antagonist, thioperamide (10 and 20 mg/kg ip), produced an antinociception. The hypernociceptive effects of HTMT and imetit were antagonized by dexchlorpheniramine (20 mg/kg ip) and thioperamide (5 mg/kg ip), respectively. The results suggest that histaminergic mechanisms may be involved in the modulation of nociceptive stimuli.

  20. [Role of central histamine in amygdaloid kindled seizures].

    Kamei, C; Okuma, C


    The role of central histamine in amygdaloid kindled seizures in rats was studied. Histamine content in the amygdala was significantly decreased after development of amygdaloid kindling. Intracerebroventricular (i.c.v.) injection of histamine resulted in inhibition of amygdaloid kindled seizures. The H1-agonists 2-methylhistamine and 2-thiazolylethylamine also inhibited amygdaloid kindled seizures. In addition, intraperitoneal (i.p.) injection of histidine and metoprine inhibited amygdaloid kindled seizures at doses that caused increases in histamine contents of the brain. H1-antagonists (diphenhydramine and chlorpheniramine) attenuated histamine- or histidine-induced inhibition of amygdaloid kindled seizures. Both i.c.v. and i.p. injections of H3-antagonists (thioperamide, AQ0145 and clobenpropit) resulted in a dose-related inhibition of amygdaloid kindled seizures. The effects of thioperamide and AQ0145 were inhibited by an H3-agonist (R)-alpha-methylhistamine and H1-antagonists. On the other hand, H2-antagonists showed no antagonistic effect. GABAmimetic drugs, diazepam, sodium valproate and muscimol potentiated the effect of clobenpropit. Bicuculline caused significant antagonism of the inhibition of amygdaloid kindled seizures induced by clobenpropit. These findings suggested that a histaminergic mechanism plays an important role in suppressing amygdaloid kindled seizures through histamine H1-receptors. In addition, an inhibition of amygdaloid kindled seizures induced by histamine is closely related with the action of GABA.

  1. Pharmacology of Casimiroa edulis; II. Cardiovascular effects in the anesthesized dog.

    Vidrio, H; Magos, G A


    The cardiovascular effects of an aqueous extract of seeds of Casimiroa edulis were assessed in pentobarbital-anesthetized dogs. The extract produced marked hypotension which lasted more than two hours; it was accompanied by moderate and less persistent bradycardia. The histaminergic nature of these effects was investigated in animals pretreated with the specific antagonists diphenhydramine, cimetidine, or a combination of both agents. These experiments showed that both H1- and H2-receptors were involved in the hypotensive response, while the bradycardia was mediated solely through an H1-mechanism. In open-chest dogs instrumented for recording cardiac output (ascending aortic flow), left ventricular contractility (dp/dt), central venous pressure (superior vena cava), systemic blood pressure, heart rate, total peripheral resistance and stroke volume, the extract decreased blood pressure and peripheral resistance and increased cardiac output and stroke volume, without modifying the other parameters. It was concluded that the cardiovascular pattern of Casimiroa edulis in the dog is that of a peripheral arterial vasodilator and that it increases cardiac output by reducing left ventricular afterload.

  2. Local histamine release increases leukocyte rolling in the cerebral microcirculation of the mouse.

    Yong, T; Zheng, M Q; Linthicum, D S


    Histamine-mediated induction of leukocyte rolling and adhesion in the cerebral microcirculation was examined in two inbred strains of mice (SJL/J and BALB/c). A cranial window was surgically prepared for the visualization of the cerebral microcirculation using intra-vital microscopy. Leukocyte rolling and adhesion to pial venular walls were assessed during off-line video playback analyses. The surgical preparation of the cranial windows was found to trigger 'spontaneous' leukocyte rolling, and this was attributed to disruption of dural mast cells and localized release of vasoactive histamine. This spontaneous leukocyte rolling was observed only in the SJL/J strain of mice, and could be prevented by presurgical treatment with the mast cell stabilizer sodium cromoglycate. BALB/c mice did not show 'spontaneous' leukocyte rolling or adhesion; this strain is known to have low numbers of CNS-associated mast cells. Exogenous histamine, applied topically to the cerebral microcirculation via the cranial window in mice pretreated with sodium cromoglycate, produced significant dose-dependent increases in leukocyte rolling and adhesion to pial venules in SJL/J mice, but not in BALB/c mice. Diphenhydramine (H1 receptor antagonist), but not cimetidine (H2 receptor antagonist), abolished both 'spontaneous' and histamine-induced leukocyte rolling. Anti-P-selectin antibody was found efficiently to block both spontaneous and histamine-induced increases in leukocyte rolling, but not leukocyte adhesion.

  3. In vitro antibacterial activity of some antihistaminics belonging to different groups against multi-drug resistant clinical isolates

    Moustafa A El-Nakeeb


    Full Text Available Antihistaminics are widely used for various indications during microbial infection. Hence, this paper investigates the antimicrobial activities of 10 antihistaminics belonging to both old and new generations using multiresistant Gram-positive and Gram-negative clinical isolates. The bacteriostatic activity of antihistaminics was investigated by determining their MIC both by broth and agar dilution techniques against 29 bacterial strains. Azelastine, cyproheptadine, mequitazine and promethazine were the most active among the tested drugs. Diphenhydramine and cetirizine possessed weaker activity whereas doxylamine, fexofenadine and loratadine were inactive even at the highest tested concentration (1 mg/ml. The MIC of meclozine could not be determined as it precipitated with the used culture media. The MBC values of antihistaminics were almost identical to the corresponding MIC values. The bactericidal activity of antihistaminics was also studied by the viable count technique in sterile saline solution. Evident killing effects were exerted by mequitazine, meclozine, azelastine and cyproheptadine. Moreover, the dynamics of bactericidal activity of azelastine were studied by the viable count technique in nutrient broth. This activity was found to be concentration-dependant. This effect was reduced on increasing the inoculum size while it was increased on raising the pH. The post-antimicrobial effect of 100 fg/ml azelastine was also determined and reached up to 3.36 h.

  4. Chemometrics optimization of six antihistamines separations by capillary electrophoresis with electrochemiluminescence detection.

    Zhu, Derong; Li, Xia; Sun, Jinying; You, Tianyan


    This work expanded the knowledge of the use of chemometric experimental design in optimizing of six antihistamines separations by capillary electrophoresis with electrochemiluminescence detection. Specially, central composite design was employed for optimizing the three critical electrophoretic variables (Tris-H(3)PO(4) buffer concentration, buffer pH value and separation voltage) using the chromatography resolution statistic function (CRS function) as the response variable. The optimum conditions were established from empirical model: 24.2mM Tris-H(3)PO(4) buffer (pH 2.7) with separation voltage of 15.9 kV. Applying theses conditions, the six antihistamines (carbinoxamine, chlorpheniramine, cyproheptadine, doxylamine, diphenhydramine and ephedrine) could be simultaneous separated in less than 22 min. Our results indicate that the chemometrics optimization method can greatly simplify the optimization procedure for multi-component analysis. The proposed method was also validated for linearity, repeatability and sensitivity, and was successfully applied to determine these antihistamine drugs in urine.

  5. Cocktail-Dosing Microdialysis Study to Simultaneously Assess Delivery of Multiple Organic-Cationic Drugs to the Brain.

    Kitamura, Atsushi; Okura, Takashi; Higuchi, Kei; Deguchi, Yoshiharu


    Brain microdialysis is a powerful tool to estimate brain-to-plasma unbound concentration ratio at the steady state (Kp,uu) of compounds by direct measurement of the unbound concentration in brain interstitial fluid. Here, we evaluated a method to estimate Kp,uu values of multiple organic-cationic drugs simultaneously, by means of brain microdialysis combined with cocktail dosing. Five cationic drugs (diphenhydramine, memantine, oxycodone, pyrilamine, and tramadol), substrates of the proton-coupled organic cation antiport system, were selected as model drugs, and compared under single-dosing and cocktail-dosing conditions. We selected doses of the drugs at which no significant drug-drug interaction occurs at the proton-coupled organic cation antiport system in the blood-brain barrier (BBB). This was confirmed by uptake studies in hCMEC/D3 cells, an in vitro BBB model. The Kp,uu values after cocktail administration were in the range of 1.8-5.2, and were in good agreement with those after single administration. These results suggest that the microdialysis method with cocktail dosing is suitable to estimate Kp,uu values of several cationic drugs simultaneously, if there is no drug-drug interaction during BBB transport. The method could be useful for evaluating drug candidates with high Kp,uu values at an early stage in the development of central nervous system-acting drugs.

  6. Influence of neurotropic compounds on the calmodulin- and troponin C-dependent processes

    Baldenkov, G.N.; Men' shikov, M.Yu.; Feoktistov, I.A.; Tkachuk, V.A.


    An analysis was made of the effects of neurotropic compounds on the Ca-binding proteins - calmodulin and troponin C. It was shown that most of the neuroleptics of the phenothiazine group interact effectively both with calmodulin and with troponin C and also inhibit the calmodulin-dependent phosphodiesterase of cyclic nucleotides and calcium-activated actomyosin ATPase. Neuroleptics of the butyrophenone group, as well as imipramine and diphenhydramine, are capable of a low-efficiency interaction only with calmodulin. It was found that one of the phenothiazines - methophenazine, which is an effective inhibitor of calmodulin and calmodulin-dependent phosphodiesterase - does not affect troponin C and Ca-dependent actomyosin ATPase. As a result of this, methophenazine can serve as a convenient tool for studying processes regulated by these Ca-binding proteins. It was concluded that troponin C possesses Ca-dependent binding sites for drugs structurally similar to those of calmodulin but binding the drugs less effectively and exhibiting selectivity with respect to certain preparations. It was shown that despite the homology of the two Ca-binding proteins, calmodulin and troponin C, a selective action on the processes regulated by them is possible.

  7. Influence of cytisine on catecholamine release in isolated perfused rat adrenal glands.

    Lim, Dong-Yoon; Jang, Seok-Jeong; Kim, Kwang-Cheol


    The aim of the present study was to determine the characteristics of cytisine on the secretion of catecholamines (CA) in isolated perfused rat adrenal glands, and to clarify its mechanism of action. The release of CA evoked by the continuous infusion of cytisine (1.5 x 10(-5) M) was time-dependently reduced from 15 min following the initiation of cytisine infusion. Furthermore, upon the repeated injection of cytisine (5 x 10(-5) M), at 30 min intervals into an adrenal vein, the secretion of CA was rapidly decreased following the second injection. Tachyphylaxis to the release of CA was observed by the repeated administration of cytisine. The cytisine-induced secretion of CA was markedly inhibited by pretreatment with chlorisondamine, nicardipine, TMB-8, and the perfusion of Ca2+-free Krebs solution, while it was not affected by pirenzepine or diphenhydramine. Moreover, the secretion of CA evoked by ACh was time-dependently inhibited by the prior perfusion of cytisine (5 x 10(-6) M). Taken together, these experimental data suggest that cytisine causes secretion of catecholamines from the perfused rat adrenal glands in a calcium-dependent fashion through the activation of neuronal nicotinic ACh receptors located in adrenomedullary chromaffin cells. It also seems that the cytisine-evoked release of catecholamine is not relevant to the activation of cholinergic M1-muscarinic or histaminergic receptors.

  8. Organic micro-pollutants’ removal via anaerobic membrane bioreactor with ultrafiltration and nanofiltration

    Wei, Chun Hai


    The removal of 15 organic micro-pollutants (OMPs) in synthetic municipal wastewater was investigated in a laboratory-scale mesophilic anaerobic membrane bioreactor (AnMBR) using ultrafiltration and AnMBR followed by nanofiltration (NF), where powdered activated carbon (PAC) was added to enhance OMPs removal. No significant effects of OMPs spiking and NF connection on bulk organics removal and biogas production were observed. Amitriptyline, diphenhydramine, fluoxetine, sulfamethoxazole, TDCPP and trimethoprim showed readily biodegradable characteristics with consistent biological removal over 80%. Atrazine, carbamazepine, DEET, Dilantin, primidone and TCEP showed refractory characteristics with biological removal below 40%. Acetaminophen, atenolol and caffeine showed a prolonged adaption time of around 45 d, with initial biological removal below 40% and up to 50-80% after this period. Most readily biodegradable OMPs contained a strong electron donating group. Most refractory OMPs contained a strong electron withdrawing group or a halogen substitute. NF showed consistent high rejection of 80-92% with an average of 87% for all OMPs, which resulted in higher OMPs removal in AnMBR-NF than in AnMBR alone, especially for refractory OMPs. Limited sorption performance of PAC for OMPs removal was mainly due to low and batch dosage (100 mg/L) as well as the competitive sorption caused by bulk organics.

  9. Contaminants of emerging concern in tributaries to the Laurentian Great Lakes: I. Patterns of occurrence

    Elliott, Sarah M.; Brigham, Mark E.; Lee, Kathy E.; Banda, Jo A.; Choy, Steven J.; Gefell, Daniel J.; Minarik, Thomas A.; Moore, Jeremy N.; Jorgenson, Zachary G.


    Human activities introduce a variety of chemicals to the Laurentian Great Lakes including pesticides, pharmaceuticals, flame retardants, plasticizers, and solvents (collectively referred to as contaminants of emerging concern or CECs) potentially threatening the vitality of these valuable ecosystems. We conducted a basin-wide study to identify the presence of CECs and other chemicals of interest in 12 U.S. tributaries to the Laurentian Great Lakes during 2013 and 2014. A total of 292 surface-water and 80 sediment samples were collected and analyzed for approximately 200 chemicals. A total of 32 and 28 chemicals were detected in at least 30% of water and sediment samples, respectively. Concentrations ranged from 0.0284 (indole) to 72.2 (cholesterol) μg/L in water and 1.75 (diphenhydramine) to 20,800 μg/kg (fluoranthene) in sediment. Cluster analyses revealed chemicals that frequently co-occurred such as pharmaceuticals and flame retardants at sites receiving similar inputs such as wastewater treatment plant effluent. Comparison of environmental concentrations to water and sediment-quality benchmarks revealed that polycyclic aromatic hydrocarbon concentrations often exceeded benchmarks in both water and sediment. Additionally, bis(2-ethylhexyl) phthalate and dichlorvos concentrations exceeded water-quality benchmarks in several rivers. Results from this study can be used to understand organism exposure, prioritize river basins for future management efforts, and guide detailed assessments of factors influencing transport and fate of CECs in the Great Lakes Basin.

  10. A Comparative Study Between 1% and 0.1% Lidocain with Adrenaline in Skin Local Anesthesia

    A. Zamanian


    Full Text Available Lidocain solution 1-2% have used with or without adrenaline for skin local anesthesia. Also normal salin, diphenhydramine and bacteriostatic salin have been used. The purpose of this study was to compare the effectiveness of 1% lidocain with 0.1% lidocain in local skin anesthesia.This study was carried out by triple blind method on 140 patients that submitted to Hamedan Sina Hospital in 2000. These patients divided in two groups randomly, 70 cases received 1% lidocain and other 70 cases received 0.1% lidocain. The pain assessment score was between 0-10 that was asked from each patient and collected data analyzed by statistical methods.This study showed that 51.1% of patients that received 1% lidocain and 48.9% that received 0.1% lidocain did not have any pain during injection (P>0.05. Also 54.3% of patients that received 1% lidocain and 45.7% that received 0.1% lidocain solution did not have any pain throw the procedure (P>0.05.The effect of 0.1% lidocain solution had no much difference from 1% lidocain in skin local anesthesia and thus it is suggested to use it for wide anesthesia in skin surgeries.

  11. Proton-Coupled Organic Cation Antiporter Contributes to the Hepatic Uptake of Matrine.

    Wu, Chunyong; Sun, Xiaomin; Feng, Chao; Liu, Xiaoying; Wang, Hufang; Feng, Fang; Zhang, Junying


    Matrine is the major bioactive alkaloid found in certain Sophora plants and has been used for the treatment of liver diseases and protection of liver function. The aim of this study was to investigate the human liver uptake mechanism of matrine by using HepG2 cells as the in vitro model. Matrine was transported into HepG2 cells in a time- and temperature-dependent manner. The cellular uptake was saturable and was significantly reduced by the metabolic inhibitors, such as sodium azide and rotenone. Furthermore, the uptake of matrine was found to be regulated by a protonophore (carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone) and pH, indicating that this influx transporter may be a proton-coupled antiporter. The uptake of matrine was sensitive to inhibition by the cationic drugs including pyrilamine, quinidine, verapamil, amantadine, diphenhydramine, and cimetidine but insensitive to other typical substrates or inhibitors of well-known organic cation transport systems. The present study reveals that, for the first time, in HepG2 cells, the existence of a proton-coupled organic cation antiporter that contributes substantially to the hepatic uptake of matrine.

  12. Immunoassay screening of lysergic acid diethylamide (LSD) and its confirmation by HPLC and fluorescence detection following LSD ImmunElute extraction.

    Grobosch, T; Lemm-Ahlers, U


    In all, 3872 urine specimens were screened for lysergic acid diethylamide (LSD) using the CEDIA DAU LSD assay. Forty-eight samples, mainly from psychiatric patients or drug abusers, were found to be LSD positive, but only 13 (27%) of these could be confirmed by high-performance liquid chromatography with fluorescence detection (HPLC-FLD) following immunoaffinity extraction (IAE). Additional analysis for LSD using the DPC Coat-a-Count RIA was performed to compare the two immunoassay screening methods. Complete agreement between the DPC RIA assay and HPLC-FLD results was observed at concentrations below a cutoff concentration of 500 pg/mL. Samples that were LSD positive in the CEDIA DAU assay but not confirmed by HPLC-FLD were also investigated for interfering compounds using REMEDI HS drug-profiling system. REMEDI HS analysis identified 15 compounds (parent drugs and metabolites) that are believed to cross-react in the CEDIA DAU LSD assay: ambroxol, prilocaine, pipamperone, diphenhydramine, metoclopramide, amitriptyline, doxepine, atracurium, bupivacaine, doxylamine, lidocaine, mepivacaine, promethazine, ranitidine, and tramadole. The IAE/HPLC-FLD combination is rapid, easy to perform and reliable. It can reduce costs when standard, rather than more advanced, HPLC equipment is used, especially for labs that perform analyses for LSD infrequently. The chromatographic analysis of LSD, nor-LSD, and iso-LSD is not influenced by any of the tested cross-reacting compounds even at a concentration of 100 ng/mL.

  13. 静滴多烯磷脂酰胆碱注射液至急性过敏反应1例报道%Static Drops of Polyene Phosphatidylcholine Injection to Acute Allergic Reaction:A Case Report



    One case of female patients with chronic intravenous polyene phosphatidylcholine injection in the treatment of liver, muscle and joint pain for 6 consecutive days infusion polyene phosphatidylcholine injection appeared about 20 minutes later, severe pain consideration due to allergy, then stopping, following its adoption diphenhydramine 20mg intramuscular injection needle, about 10 minutes the pain disappeared, liver continue antiviral therapy two weeks after liver function returned to normal discharge.%1例慢性乙型肝炎女性患者静滴多烯磷脂酰胆碱注射液护肝治疗,连续6 d输注多烯磷脂酰胆碱注射液约20 min后出现全身肌肉关节疼痛,疼痛剧烈,考虑过敏所致,遂停药,予以苯海拉明针20 mg肌肉注射后,约10 min左右疼痛消失,继续护肝抗病毒治疗2w后肝功能恢复正常出院。

  14. October 2016 critical care case of the month

    Fountain S


    Full Text Available No abstract available. Article truncated after first 150 words. A 27-year-old Caucasian man with past medical history of opioid abuse (reportedly sober for 10 years on buprenorphine, post traumatic stress disorder, depression and anxiety presented to the emergency department complaining of dysarthria after taking diphenhydramine and meclizine in addition to his prescribed trazodone and buprenorphine to try to sleep. He was discharged to home after his symptoms appeared to improve with intravenous fluid. He returned to the emergency department the following afternoon with worsening dysarthria, dysphagia, and subjective weakness. The patient was non toxic appearing, afebrile, vital signs were stable and his strength was reported as 5/5. Computed tomography of his head did not show any evidence of acute intracranial abnormality. Given his ongoing complaints, he was admitted for observation to the general medicine wards. That night a rapid response was initiated when the nurse found the patient to be unresponsive, but spontaneously breathing. The patient’s clinical status did ...

  15. Acute Dystonia in a Child Receiving Metoclopramide: Case Report

    Alaaddin Yorulmaz


    Full Text Available Metoclopramide is a benzamide that is a dopamine receptor, often preferred as a prokinetic agent to accelerate gastrointestinal passage in the treatment of gastroesophageal reflux disease; itis also used as an antiemetic agent in many diseases that progress with nausea-vomiting. It is effective on the digestive system both centrally and peripherally. It easily overcomes the blood-brain barrier and may create side effects pertaining to the extrapyramidal system. Acute dystonic reaction is rare among these side effects; it is, however, a condition that needs to be treated urgently. This paper presents a 5-month-old infant patient who developed acute dystonic reaction secondary to the use of Metpamid at a high dose. The diagnosis in this case was made based onpatient history. The patient%u2019s symptoms rapidly disappeared thanks to treatment with diphenhydramine. It should be remembered that metoclopramide may cause side effects in patients presenting to the emergency service with acute dystonia, soa complete history of drugs should definitely be taken for such patients.

  16. Variability of bioavailability and intestinal absorption mechanisms of metoprolol.

    Fukao, Miki; Ishida, Kazuya; Horie, Asuka; Taguchi, Masato; Nozawa, Takashi; Inoue, Hiroshi; Hashimoto, Yukiya


    We previously reported that aging and/or cytochrome P450 2D6 polymorphism are responsible for the interindividual variability in the systemic clearance (CL) and bioavailability (F) of metoprolol. The aim of the present study was to evaluate the residual variability of F of metoprolol in routinely treated Japanese patients and to investigate the intestinal absorption mechanism of the drug using human intestinal epithelial LS180 cells. We first re-analyzed the blood concentration data for metoprolol in 34 Japanese patients using a nonlinear mixed effects model. The oral clearance (CL/F) of metoprolol was positively correlated with the apparent volume of distribution (V/F), suggesting the residual variability of F. The uptake of metoprolol into LS180 cells was significantly decreased by the acidification of extracellular medium pH, and was dependent on temperature and intracellular pH. Furthermore, the cellular uptake of metoprolol was saturable, and was significantly decreased in the presence of hydrophobic cationic drugs such as diphenhydramine, procainamide, bisoprolol, and quinidine. These findings indicate that residual variability of F is one of the causes of the interindividual pharmacokinetic variability of metoprolol, and that the interindividual variability of not only presystemic first-pass metabolism, but also intestinal absorption, may be responsible for the variable F of the drug.

  17. Psychogenic Itch Management.

    Szepietowski, Jacek C; Reszke, Radomir


    Pruritus is a bothersome and prevalent symptom reported by patients suffering from both cutaneous and extracutaneous diseases. Psychogenic pruritus, also referred to as functional itch disorder, is a distinct clinical entity. According to the definition proposed by the French Psychodermatology Group (FPDG) in 2007, the disorder is characterized by pruritus which is the chief complaint and psychologic factors that contribute to eliciting, worsening, and sustaining the symptoms. Specific diagnostic criteria were proposed, including 3 compulsory and 7 optional, of which 3 have to be met in order to establish the diagnosis. Psychogenic pruritus may require cooperation between dermatologists, psychiatrists, and psychologists. Psychotherapy and psychopharmacotherapy are mainstays of managing the disease. However, publications regarding psychogenic itch management are uncommon. Initially, general measures have to be taken, including avoiding irritating factors, preventing skin dryness, and frequent application of emollients. As in pruritus of other causes, several drugs are used, with more emphasis on substances that influence central nervous system: H1-antihistamines (hydroxyzine, chlorpheniramine, cyproheptadine, diphenhydramine, promethazine), tricyclic antidepressants (doxepin), tetracyclic antidepressants (mirtazapine), selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), antipsychotic drugs (pimozide), anticonvulsants (topiramate), and benzodiazepines (alprazolam), preferably depending on the coexisting symptoms.

  18. Vasoactive intestinal polypeptide provokes acetylcholine release from the myenteric plexus

    Kusunoki, M.; Tsai, L.H.; Taniyama, K.; Tanaka, C.


    Effects of vasoactive intestinal polypeptide (VIP) on the release of acetylcholine (ACh) from longitudinal muscle strips with myenteric plexus (LM) preparations were examined in the guinea pig small intestine. VIP (10 to 10 W M) induced a concentration-dependent contraction of LM preparation. The VIP-induced contractions seem to be related to three components, the scopolamine-sensitive, the scopolamine-insensitive, the tetrodotoxin-sensitive, and the tetrodotoxin-insensitive contractions. VIP (10 to 10 W M) induced a concentration-dependent increase in the release of (TH)ACh from LM preparations preloaded with (TH)choline. The VIP-evoked (TH)ACh release was inhibited by removal of CaS from the perfusion medium and by treatment with tetrodotoxin but not by scopolamine and hexamethonium. The spontaneous and VIP-evoked (TH)ACh release was not affected by phentolamine, propranolol, methysergide, diphenhydramine, cimetidine, bicuculline, or (D-ProS, D-Trp/sup 7,9/)substance P. The result demonstrates that VIP induces contractions of longitudinal smooth muscle directly and indirectly by the stimulation of both cholinergic neurons and noncholinergic excitatory neurons.

  19. Effect of subarachnoid hemorrhage on contractile responses and noradrenaline release evoked in cat cerebral arteries by histamine

    Lobato, R.D.; Marin, J.; Salaices, M.; Rico, M.L.; Sanchez, C.F.


    This study analyzes the changes induced by subarachnoid hemorrhage (SAH) on the contractile responses and the noradrenaline release evoked in cat cerebral arteries by histamine. The dose-dependent vasoconstriction induced by histamine on the cerebral arteries of normal cats was significantly reduced by diphenhydramine and phentolamine. When SAH was produced 3 and 7 days before the experiment, the histamine-induced vasoconstriction also decreased. Thereafter, a tendency to normalization in the contractile vascular responses was observed such that in 15 days after the hemorrhage it was not significantly different from that found in controls animals. The decrease in the contractile responses to histamine provoked by SAH was similar to that seen after pretreatment with intracisternal injections of 6-hydroxydopamine. The amount of radioactivity released by histamine following preincubation with /sup 3/H-noradrenaline from the cerebral arteries of cats exposed to SAH 3, 7, and 15 days before the experiment was significantly reduced when compared with controls. Moreover, the basal level of tritium release and the radioactivity retained at the end of the experiment were also decreased after SAH. Results indicate histamine releases noradrenaline from cat cerebral arteries, and SAH produce a transient denervation of the perivascular adrenergic nerve endings, which explained by the impairment of the indirect adrenergic mechanism involved in the overall contractile response elicited by this amine in cerebral arteries. Histamine does not seem to play a significant role in the production of the cerebral vasospasm occurring after SAH.

  20. Action on ileal smooth muscle of synthetic detergents and pardaxin.

    Primor, N


    Pardaxin (PX), a toxic and repellent substance isolated from the Red Sea flatfish, causes a sharp ball-like profile of drop of saline placed on a hydrophobic film to turn into a flattened one. This effect results with a decrease of the contact angle (theta) from 96 degrees to a maximum of 42 degrees at 10(-4) M of PX. The action of sodium dodecyl sulphate (SDS), a synthetic anionic detergent, benzalkonium chloride (BAC) cationic detergent and pardaxin (PX) a toxic protein with detergent properties, were studied in the ileal guinea-pig longitudinal smooth muscle preparation. SDS (4 X 10(-4) M) and PX (5 X 10(-6) M) diminished the muscle contractile response to field stimulation (0.1 Hz, 1 msec) and to acetylcholine (Ach) and to histamine and elicited a prolonged (4-6 min) TTX-insensitive muscle contraction. The dose dependence of muscle contraction to SDS and PX was found to be sigmoidal and occurred over a narrow range of concentrations. The SDS- but not PX-induced muscle contraction could be reduced by diphenhydramine (H1 antihistamine). BAC (10(-5)-10(-4) M) suppressed the muscle's contractile response to electrical stimulation (0.1 Hz, 1 msec), to Ach, histamine and 5-hydroxytryptamine but did not produce muscle contraction. PX at concentrations higher than 5 X 10(-6) M is a potent detergent and at this concentration shares several pharmacological similarities with SDS.

  1. Determination of alprostadil in rat plasma by ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry after intravenous administration.

    Lin, Xia; Zhang, Yu; Cui, Yue; Wang, Lin; Wang, Jing; Tang, Xing


    A rapid, highly selective ultra performance liquid chromatography-electrospray ionisation-tandem mass spectrometry method (UPLC-ESI-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of alprostadil in rat plasma. After a simple sample preparation procedure involving a one-step liquid-liquid extraction, alprostadil and the internal standard, diphenhydramine, were chromatographed on an ACQUITY UPLC BEH C(18) column with gradient elution using a mobile phase consisting of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.25 mL min(-1). The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode via an electrospray ionization (ESI) source. The calibration curve was linear (r(2)=0.99) over the concentration range 0.4-250.0 ng mL(-1), with a lower limit of quantification of 0.4 ng mL(-1) for alprostadil. The inter- and intra-day precision (%R.S.D.) was less than 8.5% and 2.4%, respectively, and the accuracy (RE%) was between 9.3% and 1.0% (n=6). Alprostadil in rat plasma was stable when stored at room temperature for 0.5h and at -20 degrees C for two weeks. The method was very rapid, simple and reliable, and was employed for the first time for the pharmacokinetic studies of alprostadil in rats after a single intravenous administration of 50 microg kg(-1).

  2. Participation of histamine in the step-through active avoidance response and its inhibition by H1-blockers.

    Kamei, C; Tasaka, K


    The effects of intravenous and intracerebroventricular administrations of certain H1-blockers on the active avoidance response in rats were studied. Among the classic H1-blockers used in this study: pyrilamine, diphenydramine, promethazine and chlorpheniramine, promethazine was the most effective and chlorpheniramine the least in inhibiting the active avoidance response; namely, a variation of prolongation in the response latency of the avoidance response. Meanwhile, ketotifen most potently inhibited the active avoidance response when the drugs were administered intracerebroventricularly. Mequitazine, astemizole and oxatomide were weak depressants when administered by either route. Azelastine was less effective than the classic H1-blockers by intravenous injection, while by intracerebroventricular injection, the inhibition was almost identical to those induced by the classic H1-blockers. Intracerebroventricular injection of histamine was antagonized the prolonged latency in the avoidance response induced by pyrilamine or diphenhydramine. A similar effect was also produced by 2-methylhistamine, but 4-methylhistamine had no effect. Intracerebroventricular injection of acetylcholine was restored the retarded avoidance response induced by pyrilamine, but a dose 20 times greater than that of histamine was required. From these findings, it can be concluded that inhibition of the active avoidance response induced by H1-blockers may be exerted through interaction with H1-receptors in the brain.

  3. The effects of sufentanil in the feline pulmonary vascular bed.

    Kaye, Alan D; Phelps, James; Baluch, Amir; Ibrahim, Ikhlass N; Hoover, Jason M; Baber, Syed R; Zhang, Cuihua; Armstrong, Christopher; Huffman, Shane; Fields, Aaron


    The purpose of this prospective vehicle controlled study was to test the hypothesis that sufentanil induces a depressor response in the pulmonary vascular bed of the cat and identify the receptors involved in the mediation or modulation of these effects. In separate experiments, the effects of diphenydramine (histamine receptor blocker), glibenclamide (ATP-sensitive K+ channel blocker), L-N5-(1-Iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), nimesulide (selective cyclooxygenase (COX)-2 inhibitor), and naloxone (opiate receptor antagonist) were investigated on pulmonary arterial responses to sufentanil and other agonists in the feline pulmonary vascular bed. The lobar arterial perfusion pressures were continuously monitored, electronically averaged, and recorded. In the feline pulmonary vascular bed of the isolated left lower lobe, sufentanil induced a dose-dependent vasodepressor response that was not significantly altered after administration of glibenclamide, L-NIO, and nimesulide. However, the responses to sufentanil were significantly attenuated following administration of diphenhydramine and naloxone. The results of the present study suggest that sufentanil has potent vasodepressor activity in the pulmonary vascular bed of the cat and that this response may be mediated or modulated by both histaminergic and opioid receptor sensitive pathways.

  4. The inhibitory effect of magnolol on cutaneous permeability in mice is probably mediated by a nonselective vascular hyporeactivity to mediators.

    Wang, J P; Raung, S L; Chen, C C; Kuo, J S; Teng, C M


    In the present study, we demonstrated the inhibitory effect of magnolol on the plasma leakage in passive cutaneous anaphylactic (PCA) reaction, neurogenic inflammation, dorsal skin and ear edema in mice. Hind-paw skin plasma extravasation caused by antidromic stimulation of the saphenous nerve was reduced in mice pretreated with magnolol, diphenydramine or methysergide, but not with indomethacin. Ear edema formation in the PCA reaction was reduced by magnolol in dose-dependent manner. In addition, histamine-, serotonin-, compound 48/80-, bradykinin- and substance P-induced ear edema in mice was also suppressed by magnolol. A dose- and time-dependency of the inhibitory effect of magnolol was demonstrated in histamine- and compound 48/80-induced dorsal skin edema. The maximal inhibitory effect produced by a single dose of magnolol (10 mg/kg) persisted for 1 h, and significant suppression lasted for at least 3 h. In compound 48/80-pretreated mice, the histamine content of the ear was greatly reduced. Bradykinin- and substance P-induced ear edema in compound 48/80-pretreated mice was less severe than that seen in normal mice, but was still significantly reduced by magnolol pretreatment. Moreover, the inhibitory effect of magnolol was more marked than that of diphenhydramine combined with methysergide. These results suggest that the inhibitory effect of magnolol on local edema formation probably occurs through a nonselective inhibition on vascular tissue to prevent the permeability change caused by various mediators.

  5. The response of a human bronchial epithelial cell line to histamine: Intracellular calcium changes and extracellular release of inflammatory mediators

    Noah, T.L.; Paradiso, A.M.; Madden, M.C.; McKinnon, K.P.; Devlin, R.B. (Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill (United States))


    Epithelial cells are likely to modulate inflammation and tissue repair in the airways, but the factors responsible for these processes remain unclear. Because human airway epithelia are infrequently available for in vitro studies, transformed epithelial cell lines are of interest as models. The authors therefore investigated the response of an SV-40/adenovirus-transformed human bronchial epithelial cell line (BEAS-2B) to histamine, a mediator with relevance for airway diseases. The intracellular calcium response to histamine (10(-4) M) was measured, using Fura-2 and microspectrofluorimetry. Histamine induced a transient increase in intracellular calcium that originated from intracellular sources; this effect was inhibited by the H1 receptor antagonist diphenhydramine, suggesting that BEAS cells retain functioning histamine receptors. BEAS cells were grown to confluence on microporous, collagen-coated filters, allowing measurement of vectorial release of soluble mediators. Monolayers exposed to histamine for 30 min released interleukin-6 and fibronectin in the apical direction, in a dose-dependent manner. Little eicosanoid production was induced by histamine, either in the apical or the basolateral direction, although BEAS cells constitutively produced small amounts of prostaglandin E2 and 15-HETE. However, these cells formed large amounts of eicosanoids in response to ozone exposure as a positive control. Comparison of their data with published reports for human airway epithelia in primary culture suggests that the BEAS cell line is, in a number of respects, a relevant model for the study of airway epithelial responses to a variety of stimuli.

  6. Concurrent quantification and comparative pharmacokinetic analysis of bioactive compounds in the Herba Ephedrae-Semen Armeniacae Amarum herb pair.

    Song, Shuai; Chen, Feilong; Xing, Xuefeng; Ren, Mengyue; Ma, Qinhai; Xie, Ying; Tang, Qingfa; Luo, Jiabo


    The Mahuang-Xingren herb-pair (MX), the combination of Herba Ephedrae (Mahuang in Chinese) and Semen Armeniacae Amarum (Xingren in Chinese), is a classical combination used in traditional Chinese Medicine to treat asthma and bronchitis. A simple and reliable ultra-performance liquid chromatography-tandem mass spectrometry method was developed to simultaneously quantify and compare the pharmacokinetics of 5 ephedra alkaloids and epimers of amygdalin and prunasin in rat plasma after oral administration of Mahuang, Xingren, and MX aqueous extracts. Samples were pretreated by a single-step protein precipitation with acetonitrile, and diphenhydramine hydrochloride and puerarin were used as internal standards. Pharmacokinetic parameters were investigated using DAS 3.2.2 (Mathematical Pharmacology Professional Committee of China, Shanghai, China). The validated method demonstrated adequate sensitivity, selectivity, and process efficiency for the bioanalysis of 8 compounds, including 3 pairs of epimers. MX administration improved the bioavailability of amygdalin and prunasin. Furthermore, MX facilitated intake of lower doses of ephedra alkaloids and increased elimination rates in comparison with Mahuang alone. These results illustrate the rationale behind the preferred use of the combination of Mahuang and Xingren. To our knowledge, this is the first report of stereo-selective metabolism of amygdalin. Further, the metabolic mechanism underlying this phenomenon merits future research attention. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Concentrations of Selected Pharmaceuticals and Antibiotics in South-Central Pennsylvania Waters, March through September 2006

    Loper, Connie A.; Crawford, J. Kent; Otto, Kim L.; Manning, Rhonda L.; Meyer, Michael T.; Furlong, Edward T.


    /L), and trimethoprim (0.256 ug/L). For streams receiving runoff from animal-feeding operations, the only pharmaceuticals detected were acetaminophen, caffeine, cotinine, diphenhydramine, and carbamazepine. The maximum concentration for pharmaceuticals was 0.053 ug/L. Three streams receiving runoff from animal-feeding operations had detections of one or more antibiotic compound--oxytetracycline, sulfadimethoxine, sulfamethoxazole, and tylosin. The maximum concentration for antibiotics was 0.157 ug/L. The average number of compounds (pharmaceuticals and antibiotics) detected in sites downstream from animal-feeding operations was three. The average number of compounds detected downstream from municipal-wastewater effluents was 13. For wells used to supply livestock, four compounds were detected--two pharmaceuticals (cotinine and diphenhydramine) and two antibiotics (tylosin and sulfamethoxazole). There were five detections in all the well samples. The maximum concentration detected in well water was for cotinine, estimated to be 0.024 ug/L. Seasonal occurrence of pharmaceutical and antibiotic compounds in stream water varied by compound and site type. At four stream sites, the same compounds were detected in all four seasonal samples. At other sites, pharmaceutical or antibiotic compounds were detected only one time in seasonal samples. Winter samples collected in streams receiving municipalwastewater effluent had the greatest number of compounds detected (21). Research analytical methods were used to determine concentrations for pharmaceuticals and antibiotics. To assist in evaluating the quality of the analyses, detailed information is presented on laboratory methodology and results from qualitycontrol samples. Quality-control data include results for nine blanks, nine duplicate environmental sample pairs, and three laboratory-spiked environmental samples as well as the recoveries of compounds in laboratory surrogates and laboratory reagent spikes.

  8. Modulatory effects of taurine on jejunal contractility

    Yao, Q.Y.; Chen, D.P.; Ye, D.M.; Diao, Y.P.; Lin, Y.


    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism. PMID:25387674

  9. Effects of histamine on spontaneous neuropathic pain induced by peripheral axotomy

    Jie Yu; Guo-Dong Lou; Jia-Xing Yue; Ying-Ying Tang; Wei-Wei Hou; Wen-Ting Shou; Hiroshi Ohtsu


    The present study was designed to investigate the effects of histamine on spontaneous neuropathic pain (NP) induced by peripheral axotomy.Rats and mice were subjected to complete transection of the left sciatic and saphenous nerves to induce spontaneous NP (the neuroma model).Rats were then treated with drugs once daily for 30 days (histidine and Ioratadine,i.p.) or 21 days (histamine,i.c.v.).Autotomy behavior was scored daily until day 50 post-operation (PO).On days 14 to 21 PO,some rats in the control group were subjected to single-fiber recording.Autotomy behavior was also monitored daily in histidine decarboxylase (the key enzyme for histamine synthesis) knockout (HDC~) and wild-type mice for 42 days.We found that both histidine (500 mg/kg) (a precursor of histamine that increases histamine levels in the tissues) and histamine (50 μg/5 μL) significantly suppressed autotomy behavior in rats.HDC-/-mice lacking endogenous histamine showed higher levels of autotomy than the wild-type.In addition,the analgesic effect of histidine was not antagonized by Ioratadine (a peripherally-acting H1 receptor antagonist),while Ioratadine alone significantly suppressed autotomy.Electrophysiological recording showed that ectopic spontaneous discharges from the neuroma were blocked by systemic diphenhydramine (an H1 receptor antagonist).Our results suggest that histamine plays an important role in spontaneous NP.It is likely that histamine in the central nervous system is analgesic,while in the periphery,via H1 receptors,it is algesic.This study justifies the avoidance of a histamine-rich diet and the use of peripherally-acting H1 receptor antagonists as well as agents that improve histamine action in the central nervous system in patients with spontaneous NP.

  10. [Prevention and Treatment of Common Acute Adverse Effects With Antipsychotic Use in Adults With Schizophrenia Diagnosis].

    Arenas Borrero, Álvaro Enrique; Gómez Restrepo, Carlos; Bohórquez Peñaranda, Adriana Patricia; Vélez Traslaviña, Ángela; Castro Díaz, Sergio Mario; Jaramillo González, Luis Eduardo; García Valencia, Jenny


    To determine the most adequate strategies for the prevention and treatment of the acute adverse effects of the use of antipsychotics. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. A systematic literature search was carried out. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. The non-pharmacological interventions such as nutritional counseling by a nutritionist, exercise and psychotherapy are effective in preventing weight gain with the use of antipsychotics. (Kg Weight reduction in DM of -3.05 (-4.16, -1.94)). The antipsychotic change from olanzapine to aripiprazole showed weight loss and decreased BMI (decreased weight in KG DM -3.21 (-9.03, -2.61). The use of beta blockers was ineffective in reducing akathisia induced by antipsychotic; using as outcome the 50% reduction of symptoms of akathisia comparing beta-blockers with placebo RR was 1.4 (0.59, 1.83). It is recommended to make psychotherapeutic accompaniment and nutrition management of overweight for patients with weight gain. If these alternatives are ineffective is suggested to change the antipsychotic or consider starting metformin. For the management of drug-induced akathisia it is recommended to decrease the dose of the drug and the addition of lorazepam. It is recommended using 5mg biperiden IM or trihexyphenidyl 5mg orally in case of secondary acute dystonia and for the treatment of antipsychotic-induced parkinsonism to decrease the dose of antipsychotic or consider using 2 - 4mg/day of biperiden or diphenhydramine 50mg once daily. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  11. On-line sensor monitoring for chemical contaminant attenuation during UV/H2O2 advanced oxidation process.

    Yu, Hye-Weon; Anumol, Tarun; Park, Minkyu; Pepper, Ian; Scheideler, Jens; Snyder, Shane A


    A combination of surrogate parameters and indicator compounds were measured to predict the removal efficiency of trace organic compounds (TOrCs) using low pressure (LP)-UV/H2O2 advanced oxidation process (AOP), engaged with online sensor-based monitoring system. Thirty-nine TOrCs were evaluated in two distinct secondary wastewater effluents in terms of estimated photochemical reactivity, as a function of the rate constants of UV direct photolysis (kUV) and hydroxyl radical (OH) oxidation (kOH). The selected eighteen TOrCs were classified into three groups that served as indicator compounds: Group 1 for photo-susceptible TOrCs but with minor degradation by OH oxidation (diclofenac, fluoxetine, iohexol, iopamidol, iopromide, simazine and sulfamethoxazole); Group 2 for TOrCs susceptible to both direct photolysis and OH oxidation (benzotriazole, diphenhydramine, ibuprofen, naproxen and sucralose); and Group 3 for photo-resistant TOrCs showing dominant degradation by OH oxidation (atenolol, carbamazepine, DEET, gemfibrozil, primidone and trimethoprim). The results indicate that TOC (optical-based measurement), UVA254 or UVT254 (UV absorbance or transmittance at 254 nm), and total fluorescence can all be used as suitable on-line organic surrogate parameters to predict the attenuation of TOrCs. Furthermore, the automated real-time monitoring via on-line surrogate sensors and equipped with the developed degradation profiles between sensor response and a group of TOrCs removal can provide a diagnostic tool for process control during advanced treatment of reclaimed waters.

  12. Regenerated cellulose capsules for controlled drug delivery: Part IV. In-vitro evaluation of novel self-pore forming regenerated cellulose capsules.

    Bhatt, Bhavik; Kumar, Vijay


    In the present work, the release mechanisms of active pharmaceutical ingredients (APIs) enclosed in self-pore forming regenerated cellulose (RC) two-piece hard shell capsules are described. The RC capsules were fabricated using a modified dip-coating approach, which yielded an assembled dosage form that was equivalent in size and shape to a conventional gelatin two-piece hard shell capsule. Drug release characteristics from RC capsules were evaluated using potassium chloride, diphenhydramine hydrochloride, tramadol hydrochloride, niacinamide, acetaminophen and ketoprofen as model APIs. The RC capsules act as a barrier coated reservoir device that releases the enclosed API at a zero order release rate. When comparing all the API's release behavior from RC capsules, a power-law relationship was observed between their zero-order release rates and their respective aqueous solubilities. Osmotic as well as diffusive mechanisms are involved in the release of the enclosed API. The osmotic mechanism's contribution to zero order release rate increases as the aqueous solubility of the tested APIs inside the capsule increases. The osmotic mediated flux and the apparent diffusivity of the APIs through the capsule wall is a competitive process and the osmotic mediated flux of the enclosed API begins to override its diffusivity through the capsule wall as the API solubility increases. This behavior is attributed to the wide range of pore sizes observed in RC membranes, from our prior analysis. The fluid permeability analysis shows that the RC capsules presented in this work may be better suited for osmotic drug delivery applications than conventional encapsulated systems described in the literature. Copyright © 2016. Published by Elsevier B.V.

  13. Postadulticide pulmonary hypertension of canine heartworm disease: successful treatment with oxygen and failure of antihistamines.

    Rawlings, C A; Tackett, R L


    Postadulticide pulmonary hypertension mechanisms and treatment with antihistamines and supplemental oxygen were studied in eight dogs with heartworm disease. To ensure severe postadulticide thromboembolism, additional heartworms (either 20 or 40 into 4 dogs each) were transplanted into naturally infected dogs before thiacetarsamide treatment. During pentobarbital anesthesia, 2 pulmonary hemodynamic studies were conducted on each dog with a sequence of baseline, hypoxia with FlO2 = 10%, hyperoxia with FlO2 = 100%, a second baseline, treatment with either diphenhydramine (D) or cimetidine (C), and another hypoxia. All dogs were pulmonary hypertensive, with each dog having a mean pulmonary arterial pressure (PPA) greater than 20 mm of Hg. Mean PPA increased from baseline conditions (25.0 +/- 4.5 SD for D and 24.3 +/- 4.4 for C) to hypoxia (28.5 +/- 4.7 for D and 28.4 +/- 3.7 for C), and decreased during hyperoxia (16.9 +/- 3.0 for D and 17.4 +/- 3.0 for C), respectively. Neither antihistamine reduced PPA at normoxia. The degree of pulmonary hypertension when breathing room air increased even more during hypoxia, and this increase was not attenuated by either antihistamine. Histamine did not appear to mediate pulmonary hypertension during postadulticide thromboembolism, nor to modify the hypoxia-mediated pulmonary hypertension at this disease stage. Because baseline PO2 was low (66.6 +/- 11.7 mm of Hg for D and 69.4 +/- 14.2 for C) and because PPA decreased during administration of oxygen, the pulmonary hypertension was mostly hypoxia-induced. In addition to the arterial lesions, much of the pulmonary hypertensive mechanism was an active and reversible vasoconstriction in response to hypoxia caused by the secondary lung disease.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. A national reconnaissance of trace organic compounds (TOCs) in United States lotic ecosystems.

    Bernot, Melody J; Becker, Jesse C; Doll, Jason; Lauer, Thomas E


    We collaborated with 26 groups from universities across the United States to sample 42 sites for 33 trace organic compounds (TOCs) in water and sediments of lotic ecosystems. Our goals were 1) to further develop a national database of TOC abundance in United States lotic ecosystems that can be a foundation for future research and management, and 2) to identify factors related to compound abundance. Trace organic compounds were found in 93% of water samples and 56% of sediment samples. Dissolved concentrations were 10-1000× higher relative to sediment concentrations. The ten most common compounds in water samples with detection frequency and maximum concentration were sucralose (87.5%, 12,000ng/L), caffeine (77.5%, 420ng/L), sulfamethoxazole (70%, 340ng/L), cotinine (65%, 130ng/L), venlafaxine (65%, 1800ng/L), carbamazepine (62.5%, 320ng/L), triclosan (55%, 6800ng/L), azithromycin (15%, 970ng/L), diphenylhydramine (40%, 350ng/L), and desvenlafaxine (35%, 4600ng/L). In sediment, the most common compounds were venlafaxine (32.5%, 19ng/g), diphenhydramine (25%, 41ng/g), azithromycin (15%, 11ng/g), fluoxetine (12.5%, 29ng/g) and sucralose (12.5%, 16ng/g). Refractory compounds such as sucralose may be good indicators of TOC contamination in lotic ecosystems, as there was a correlation between dissolved sucralose concentrations and with the total number of compounds detected in water. Discharge and human demographic (population size) characteristics were not good predictors of compound abundance in water samples. This study further confirms the ubiquity of TOCs in lotic ecosystems. Although concentrations measured rarely approached acute aquatic-life criteria, the chronic effects, bioaccumulative potential, or potential mixture effects of multiple compounds are relatively unknown.

  15. Five things physicians and patients should question in hospice and palliative medicine.

    Fischberg, Daniel; Bull, Janet; Casarett, David; Hanson, Laura C; Klein, Scott M; Rotella, Joseph; Smith, Thomas; Storey, C Porter; Teno, Joan M; Widera, Eric


    Overuse or misuse of tests and treatments exposes patients to potential harm. The American Board of Internal Medicine Foundation's Choosing Wisely® campaign is a multiyear effort to encourage physician leadership in reducing harmful or inappropriate resource utilization. Via the campaign, medical societies are asked to identify five tests or procedures commonly used in their field, the routine use of which in specific clinical scenarios should be questioned by both physicians and patients based on the evidence that the test or procedure is ineffective or even harmful. The American Academy of Hospice and Palliative Medicine (AAHPM) was invited, and it agreed to participate in the campaign. The AAHPM Choosing Wisely Task Force, with input from the AAHPM membership, developed the following five recommendations: 1) Don't recommend percutaneous feeding tubes in patients with advanced dementia; instead, offer oral-assisted feeding; 2) Don't delay palliative care for a patient with serious illness who has physical, psychological, social, or spiritual distress because they are pursuing disease-directed treatment; 3) Don't leave an implantable cardioverter-defibrillator activated when it is inconsistent with the patient/family goals of care; 4) Don't recommend more than a single fraction of palliative radiation for an uncomplicated painful bone metastasis; and 5) Don't use topical lorazepam (Ativan®), diphenhydramine (Benadryl®), and haloperidol (Haldol®) (ABH) gel for nausea. These recommendations and their supporting rationale should be considered by physicians, patients, and their caregivers as they collaborate in choosing those treatments that do the most good and avoid the most harm for those living with serious illness.

  16. Chiral separation of (d- and (l-enantiomers of doxylamine succinate in rat plasma

    Tadiboyina Sirisha


    Full Text Available A selective chiral ultra fast liquid chromatography (UFLC-DAD method was developed and validated to separate and quantify the (d- and (l-enantiomers of doxylamine in rat plasma. After extraction of the plasma samples with acetonitrile, the separation of doxylamine succinate enantiomers and internal standard (I.S., diphenhydramine hydrochloride was achieved on a cellulose Tris (4-chloro,3-methylphenylcarbamate column with a mobile phase of 20 mM ammonium bicarbonate buffer–acetonitrile (65:35 v/v with 0.15% diethylamine in the buffer at a flow rate of 1.0 mL/min. The diode array (DAD detection wavelength was set at 220 nm. The peaks obtained were identified as (d and (l by injecting the pure (d form into the liquid chromatography and comparing the chromatograms. The effect of column oven temperature on the retention of doxylamine and mobile phase variables which have an effect on the enantiomers separation like ionic strength, type and concentration of organic modifier was studied. Linear calibration curves were obtained over the range of 100–1400 ng/mL in plasma for both enantiomers (R2 > 0.995. The mean extraction recoveries were 94.5–104.7% of rat plasma. The mean relative standard deviation (RSD% of accuracy and intra-day and inter-day precision for both enantiomers were ⩽10%. The method can be further applied to determine the pharmacokinetics of (d- and (l-enantiomers in rat plasma.

  17. Graphene oxide based ultrafiltration membranes for photocatalytic degradation of organic pollutants in salty water.

    Pastrana-Martínez, Luisa M; Morales-Torres, Sergio; Figueiredo, José L; Faria, Joaquim L; Silva, Adrián M T


    Flat sheet ultrafiltration (UF) membranes with photocatalytic properties were prepared with lab-made TiO2 and graphene oxide-TiO2 (GOT), and also with a reference TiO2 photocatalyst from Evonik (P25). These membranes were tested in continuous operation mode for the degradation and mineralization of a pharmaceutical compound, diphenhydramine (DP), and an organic dye, methyl orange (MO), under both near-UV/Vis and visible light irradiation. The effect of NaCl was investigated considering simulated brackish water (NaCl 0.5 g L(-1)) and simulated seawater (NaCl 35 g L(-1)). The results indicated that the membranes prepared with the GOT composite (M-GOT) exhibited the highest photocatalytic activity, outperforming those prepared with bare TiO2 (M-TiO2) and P25 (M-P25), both inactive under visible light illumination. The best performance of M-GOT may be due to the lower band-gap energy (2.9 eV) of GOT. In general, the permeate flux was also higher for M-GOT probably due to a combined effect of its highest photocatalytic activity, highest hydrophilicity (contact angles of 11°, 17° and 18° for M-GOT, M-TiO2 and M-P25, respectively) and higher porosity (71%). The presence of NaCl had a detrimental effect on the efficiency of the membranes, since chloride anions can act as hole and hydroxyl radical scavengers, but it did not affect the catalytic stability of these membranes. A hierarchically ordered membrane was also prepared by intercalating a freestanding GO membrane in the structure of the M-GOT membrane (M-GO/GOT). The results showed considerably higher pollutant removal in darkness and good photocatalytic activity under near-UV/Vis and visible light irradiation in continuous mode experiments.

  18. Comparison of contaminants of emerging concern removal, discharge, and water quality hazards among centralized and on-site wastewater treatment system effluents receiving common wastewater influent.

    Du, Bowen; Price, Amy E; Scott, W Casan; Kristofco, Lauren A; Ramirez, Alejandro J; Chambliss, C Kevin; Yelderman, Joe C; Brooks, Bryan W


    A comparative understanding of effluent quality of decentralized on-site wastewater treatment systems, particularly for contaminants of emerging concern (CECs), remains less understood than effluent quality from centralized municipal wastewater treatment plants. Using a novel experimental facility with common influent wastewater, effluent water quality from a decentralized advanced aerobic treatment system (ATS) and a typical septic treatment system (STS) coupled to a subsurface flow constructed wetland (WET) were compared to effluent from a centralized municipal treatment plant (MTP). The STS did not include soil treatment, which may represent a system not functioning properly. Occurrence and discharge of a range of CECs were examined using isotope dilution liquid chromatography-tandem mass spectrometry during fall and winter seasons. Conventional parameters, including total suspended solids, carbonaceous biochemical oxygen demand and nutrients were also evaluated from each treatment system. Water quality of these effluents was further examined using a therapeutic hazard modeling approach. Of 19 CECs targeted for study, the benzodiazepine pharmaceutical diazepam was the only CEC not detected in all wastewater influent and effluent samples over two sampling seasons. Diphenhydramine, codeine, diltiazem, atenolol, and diclofenac exhibited significant (ptreatment systems was generally not influenced by season. However, significant differences (pwater quality indicators were observed among the various treatment technologies. For example, removal of most CECs by ATS was generally comparable to MTP. Lowest removal of most CECs was observed for STS; however, removal was improved when coupling the STS to a WET. Across the treatment systems examined, the majority of pharmaceuticals observed in on-site and municipal effluent discharges were predicted to potentially present therapeutic hazards to fish.

  19. Effects of oral premedication on cognitive status of elderly patients undergoing cardiac catheterization

    Javed M Ashraf; Marc Schweiger; Neelima Vallurupalli; Sandra Bellantonio; James R Cook


    Background Sedatives and analgesics are often administered to achieve conscious sedation for diagnostic and therapeutic procedures. Appropriate concerns have been raised regarding post procedure delirium related to peri-procedural medication in the elderly. The objective of this study was to investigate the effect of premedication on new onset delirium and procedural care in elderly patients. Methods Patients≥70 years old and scheduled for elective cardiac catheterization were randomly assigned to receive either oral diphenhydramine and diaze-pam (25 mg/5 mg) or no premedication. All patients underwent a mini mental state exam and delirium assessment using confusion assess-ment method prior to the procedure and repeated at 4 h after the procedure and prior to discharge. Patients’ cooperation during the procedure and ease of post-procedure were measured using Visual Analog Scale (VAS). The degree of alertness was assessed immediately on arrival to the floor, and twice hourly afterwards using Observer’s Assessment of Alertness/Sedation Scale (OAA/S). Results A total of 93 patients were enrolled. The mean age was 77 years, and 47 patients received premedication prior to the procedure. None of the patients in either group developed delirium. Patients’ cooperation and the ease of procedure was greater and pain medication requirement less both during and after the procedure in the pre-medicated group (P < 0.05 for both). Nurses reported an improvement with patient management in the pre-medicated group (P=0.08). Conclusions In conclusion, premedication did not cause delirium in elderly patients undergoing cardiac catheterization. The reduced pain medication requirement, perceived procedural ease and post procedure management favors premedication in elderly patients undergoing cardiac catheterization.

  20. Potentiation of the mutagenicity and recombinagenicity of bleomycin in yeast by unconventional intercalating agents.

    Hoffmann, George R; Laterza, Amanda M; Sylvia, Katelyn E; Tartaglione, Jason P


    Interactions between bleomycin (BLM) and conventional or unconventional intercalating agents were analyzed in an assay for mitotic gene conversion at the trp5 locus and reversion of the ilv1-92 allele in Saccharomyces cerevisiae strain D7. BLM is a potent recombinagen and mutagen in the assay. Various chemicals modulate the genetic activity of BLM, producing either antimutagenic effects or enhanced genotoxicity. Effects of cationic amino compounds include enhancement of BLM activity by aminoacridines and protection against BLM by aliphatic amines. The potentiation of BLM is similar to findings in a micronucleus-based BLM amplification assay in Chinese hamster V79 cells. In this study, the amplification of BLM activity was explored in yeast using known intercalators, compounds structurally related to known intercalators, and unconventional intercalators that were identified on the basis of computer modeling or results in the Chinese hamster BLM amplification assay. As shown in previous studies, the classical intercalator 9-aminoacridine (9AA) caused dose-dependent enhancement of BLM activity. Other compounds found to enhance the induction of mitotic recombination and point mutations in strain D7 were chlorpromazine, chloroquine, mefloquine, tamoxifen, diphenhydramine, benzophenone, and 3-hydroxybenzophenone. The increased activity was detectable by cotreatment of yeast with BLM and the modulator compound in growth medium or by separate interaction of the intercalator with DNA followed by BLM treatment of nongrowing cells in buffer. The data support the interpretation drawn from micronucleus assays in mammalian cells that BLM enhancement results from DNA intercalation and may be useful in detecting noncovalent interactions with DNA. Environ. Copyright © 2010 Wiley-Liss, Inc.

  1. Desensitization to ceftaroline in a patient with multiple medication hypersensitivity reactions.

    Jones, Justin M; Richter, Lisa M; Alonto, Augusto; Leedahl, David D


    The case of a patient with multiple medication hypersensitivity reactions and a methicillin-resistant Staphylococcus aureus (MRSA) infection who underwent desensitization to ceftaroline is reported. A 32-year-old Caucasian woman with asthma, gastroesophageal reflux disease, heart murmur, and major depression was admitted for MRSA cellulitis with a subcutaneous abscess along the left sternomanubrial joint and clavicular osteomyelitis secondary to port placement after gastric bypass surgery. The patient had an extensive history of hypersensitivity reactions. Pertinent documented allergies were as follows: penicillin (anaphylaxis), daptomycin (anaphylaxis), vancomycin (hives), linezolid (hives), ertapenem (rash), ciprofloxacin (rash), and tigecycline (rash). The patient also reported previous reactions to aztreonam (unknown) and gentamicin (hives). The pharmacy was consulted to develop a desensitization protocol for ceftaroline. The desensitization protocol used three serial dilutions of ceftaroline to make 14 sequential infusions with escalating doses. Intramuscular epinephrine, i.v. diphenhydramine, and i.v. methylprednisolone were ordered as needed for the development of immediate hypersensitivity reactions during or after administration of ceftaroline. The cumulative dose (574.94 mg) was administered intravenously over 225 minutes with no breakthrough symptoms reported during or after the desensitization protocol. Ceftaroline fosamil 600 mg i.v. every 12 hours was continued for six weeks. Desensitization to ceftaroline was conducted for a patient with extensive history of hypersensitivity reactions to other drugs, including penicillin-induced anaphylaxis. Desensitization and subsequent treatment with full doses of ceftaroline were accomplished without apparent adverse effects. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  2. Influence of different histamine receptor agonists and antagonists on apomorphine-induced licking behavior in rat.

    Farzin, D; Attarzadeh, M


    The effects of different histamine receptor agonists and antagonists on apomorphine-induced licking behavior in rats were investigated. Subcutaneous (s.c.) injection of various doses of apomorphine (0. 125-1.25 mg/kg) induced licking. The licking response was counted by direct observation and recorded for a 75-min period. Intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of the histamine H(1) or H(2) receptor agonist, HTMT (6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide) (50 and 100 microg per rat), or dimaprit (10 and 15 mg/kg, i.p.), respectively, potentiated apomorphine-induced licking, while the histamine H(3) receptor agonist, imetit (5 and 10 mg/kg, i.p.), reduced the licking response induced by apomorphine. Pretreatment with various histamine receptor antagonists, dexchlorpheniramine (30 and 40 mg/kg, i.p.), diphenhydramine (20, 30 and 40 mg/kg, i.p.), famotidine (30 and 40 mg/kg, s.c.) and ranitidine (20, 30 and 40 mg/kg), reduced apomorphine-induced licking, while thioperamide (5 and 10 mg/kg, i.p.) potentiated the apomorphine effect. The effects of HTMT and dimaprit were blocked by dexchlorpheniramine (20 mg/kg, i.p.) and famotidine (20 mg/kg, s.c.), respectively. The inhibitory effect elicited by imetit on apomorphine-induced licking behavior was also abolished in animals treated with thioperamide (2.5 mg/kg, i.p.). The results suggest that histaminergic mechanisms may be involved in the modulation of apomorphine-induced licking behavior.

  3. Mechanism of renal effects of intracerebroventricular histamine in rabbits.

    Kook, Y J; Kim, K K; Yang, D K; Ahn, D S; Choi, B K


    Histamine, when given intracerebroventricularly (i.c.v.), has been reported to produce antidiuresis in the rabbit. In this study it was attempted to elucidate the mechanism involved in the effect. Histamine (H), 100 micrograms/kg i.c.v., produced antidiuresis with decreases in renal plasma flow and glomerular filtration rate in urethane-anesthetized rabbits. With larger doses, a tendency towards increased electrolyte excretion was noted in spite of decreased filtration. In the denervated kidney, marked diuresis and natriuresis were observed following i.c.v. H, whereas the contralateral innervated kidney responded with typical antidiuresis. Reserpinized rabbits also responded with marked natriuresis to i.c.v. H. Diphenhydramine (D), 250 micrograms/kg i.c.v., increased urine flow rate, sodium and potassium excretion, along with increase in renal perfusion. With 750 micrograms/kg i.c.v., marked natriuresis was observed in spite of decreased filtration. When H was given after D (250 micrograms/kg) the antidiuresis was completely abolished, and diuresis became more prominent. Cimetidine, 250 micrograms/kg i.c.v., elicited antidiuresis with decreases in renal hemodynamics, the pretreatment with cimetidine did not influence the antidiuresis by H and no natriuresis was noted. The present study suggests that histamine, given i.c.v., influences renal function in dual ways, i.e., antidiuresis by increasing the sympathetic tone to the kidney and diuresis due to some humoral natriuretic factor, the latter becoming apparent only when the former influence has been removed, and further suggests that H1-receptors might be involved in the nerve-mediated antidiuresis, whereas H2-receptors might mediate the humorally induced natriuresis and diuresis.

  4. ACE-I Angioedema: Accurate Clinical Diagnosis May Prevent Epinephrine-Induced Harm

    R. Mason Curtis


    Full Text Available Introduction: Upper airway angioedema is a life-threatening emergency department (ED presentation with increasing incidence. Angiotensin-converting enzyme inhibitor induced angioedema (AAE is a non-mast cell mediated etiology of angioedema. Accurate diagnosis by clinical examination can optimize patient management and reduce morbidity from inappropriate treatment with epinephrine. The aim of this study is to describe the incidence of angioedema subtypes and the management of AAE. We evaluate the appropriateness of treatments and highlight preventable iatrogenic morbidity. Methods: We conducted a retrospective chart review of consecutive angioedema patients presenting to two tertiary care EDs between July 2007 and March 2012. Results: Of 1,702 medical records screened, 527 were included. The cause of angioedema was identified in 48.8% (n=257 of cases. The most common identifiable etiology was AAE (33.1%, n=85, with a 60.0% male predominance. The most common AAE management strategies included diphenhydramine (63.5%, n=54, corticosteroids (50.6%, n=43 and ranitidine (31.8%, n=27. Epinephrine was administered in 21.2% (n=18 of AAE patients, five of whom received repeated doses. Four AAE patients required admission (4.7% and one required endotracheal intubation. Epinephrine induced morbidity in two patients, causing myocardial ischemia or dysrhythmia shortly after administration. Conclusion: AAE is the most common identifiable etiology of angioedema and can be accurately diagnosed by physical examination. It is easily confused with anaphylaxis and mismanaged with antihistamines, corticosteroids and epinephrine. There is little physiologic rationale for epinephrine use in AAE and much risk. Improved clinical differentiation of mast cell and non-mast cell mediated angioedema can optimize patient management.

  5. Typical and Atypical Antipsychotic Drugs Increase Extracellular Histamine Levels in the Rat Medial Prefrontal Cortex: Contribution of Histamine H1 Receptor Blockade

    Kjell A Svensson


    Full Text Available Atypical antipsychotics such as clozapine and olanzapine have been shown to enhance histamine turnover and this effect has been hypothesized to contribute to their improved therapeutic profile compared to typical antipsychotics. In the present study, we examined the effects of antipsychotic drugs on histamine (HA efflux in the mPFC of the rat by means of in vivo microdialysis and sought to differentiate the receptor mechanisms which underlie such effects. Olanzapine and clozapine increased mPFC HA efflux in a dose related manner. Increased HA efflux was also observed after quetiapine, chlorpromazine and perphenazine treatment. We found no effect of the selective 5-HT2A antagonist MDL100907, 5-HT2c antagonist SB242084 or the 5-HT6 antagonist Ro 04-6790 on mPFC HA efflux. HA efflux was increased following treatment with selective H1 receptor antagonists pyrilamine, diphenhydramine and triprolidine, the H3 receptor antagonist ciproxifan and the mixed 5HT2A/H1 receptor antagonist ketanserin. The potential novel antipsychotic drug FMPD, which has a lower affinity at H1 receptors than olanzapine, did not affect HA efflux. Similarly, other antipsychotics with lower H1 receptor affinity (risperidone, aripiprazole and haloperidol were also without effect on HA efflux. Perfusion of clozapine and pyrilamine into the TMN, but not the mPFC, increased local HA efflux. Finally, HA efflux after antipsychotic treatment was significantly correlated with affinity at H1 receptors whereas 9 other receptors, including 5-HT2A, were not. These results demonstrate that both typical and atypical antipsychotics increase mPFC histamine efflux and this effect may be mediated via antagonism of histamine H1 receptors.

  6. Choline transport via choline transporter-like protein 1 in conditionally immortalized rat syncytiotrophoblast cell lines TR-TBT.

    Lee, N-Y; Choi, H-M; Kang, Y-S


    Choline is an essential nutrient for phospholipids and acetylcholine biosynthesis in normal development of fetus. In the present study, we investigated the functional characteristics of choline transport system and inhibitory effect of cationic drugs on choline transport in rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT). Choline transport was weakly Na(+) dependent and significantly influenced by extracellular pH and by membrane depolarization. The transport process of choline is saturable with Michaelis-Menten constants (K(m)) of 68microM and 130microM in TR-TBT 18d-1 and TR-TBT 18d-2 respectively. Choline uptake in the cells was inhibited by unlabeled choline and hemicholinium-3 as well as various organic cations including guanidine, amiloride and acetylcholine. However, the prototypical organic cation tetraethylammonium and cimetidine showed very little inhibitory effect of choline uptake in TR-TBT cells. RT-PCR revealed that choline transporter-like protein 1 (CTL1) and organic cation transporter 2 (OCT2) are expressed in TR-TBT cells. The transport properties of choline in TR-TBT cells were similar or identical to that of CTL1 but not OCT2. CTL1 was also detected in human placenta. In addition, several cationic drugs such as diphenhydramine and verapamil competitively inhibited choline uptake in TR-TBT 18d-1 with K(i) of 115microM and 55microM, respectively. Our results suggest that choline transport system, which has intermediate affinity and weakly Na(+) dependent, in TR-TBT seems to occur through a CTL1 and this system may have relevance with the uptake of pharmacologically important organic cation drugs.

  7. Can personality traits and gender predict the response to morphine? An experimental cold pain study.

    Pud, Dorit; Yarnitsky, David; Sprecher, Elliot; Rogowski, Zeev; Adler, Rivka; Eisenberg, Elon


    The aim of the present study was to examine the possible role of personality traits, in accordance with Cloninger's theory, and gender, in the variability of responsiveness to opioids. Specifically, it was intended to test whether or not the three personality dimensions - harm avoidance (HA), reward dependence (RD) and novelty seeking (NS) - as suggested by Cloninger, can predict inter-personal differences in responsiveness to morphine after exposure to experimental cold pain. Thirty-four healthy volunteers (15 females, 19 males) were given the cold pressor test (CPT). Pain threshold, tolerance, and magnitude (VAS) were measured before and after (six measures, 30 min apart) the administration of either 0.5 mg/kg oral morphine sulphate (n=21) or 0.33 mg/kg oral active placebo (diphenhydramine) (n=13) in a randomized, double blind design. Assessment of the three personality traits, according to Cloninger's Tridimensional Personality Questionnaire, was performed before the CPT. A high HA score (but not RD, NS, or baseline values of the three pain parameters) predicted a significantly larger pain relief following the administration of morphine sulphate (but not of the placebo). Women exhibited a larger response in response to both treatments, as indicated by a significantly increased threshold and tolerance following morphine sulphate as well as significantly increased tolerance and decreased magnitude following placebo administration. The present study confirms the existence of individual differences in response to analgesic treatment. It suggests that high HA personality trait is associated with better responsiveness to morphine treatment, and that females respond better than men to both morphine and placebo.

  8. Modulatory effects of taurine on jejunal contractility

    Q.Y. Yao


    Full Text Available Taurine (2-aminoethanesulfonic acid is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

  9. Pharmacological screening of Ageratum conyzoides L. (mentrasto

    Lucia A. Yamamoto


    Full Text Available The pharmacological activities of a water extract (WE of Ageratum conyzoides L, a plant populary known for its analgesic and anti-inflamatory properties, were studied in vivo and in vitro preparations. Oral administration (p.o. of the water extract (WE, 0.1 to 5 g/Kg to rats and mice induced quietness and reduced the spontaneous motility. the sleeping time induced by sodium pentobarbital (50 mg/Kg, i.p. in mice was not altered by previous treatment with We (2 g/Kg, p.o.. The same treatment did not influence the paw edema induced by carrageenan or dextran, nor did it reduce the chronic paw edema induced by complete Freund's adjuvant or formaldehyde in rats. The tail flick response in immersion test and writhings induced by 0.8%acetic acid in mice were not altered by WE either. In isolated guinea-pig ilea WE (0.4 to 4 mg/ml did not alter the EC50 values of histamine or acetylcholine, but reduced the maximal response to the agonists by 20 to 50%. We (0.01 to 10 mg/ml produced tonic contractions of the ileal smooth muscle proportional to the doses, reaching a maximum of 75% relatively to the maximum obtained with histamine. Those contractions were blocked by diphenhydramine (10 nM and reduced by 32% in presence of atropine (10 nM. The results indicated that oral treatment of rodents with A. conyzoides L neither reduced the inflammatory edema nor did it decrease the reaction to pain stimuli. In vitro the extract presented an unexpected histamine-like activity characteristic of a partial agonist. The results did not confirm the popular medicinal indications of the plant.

  10. Assessment of full-scale biological nutrient removal systems upgraded with physico-chemical processes for the removal of emerging pollutants present in wastewaters from Mexico.

    Estrada-Arriaga, Edson Baltazar; Cortés-Muñoz, Juana Enriqueta; González-Herrera, Arturo; Calderón-Mólgora, César Guillermo; de Lourdes Rivera-Huerta, Ma; Ramírez-Camperos, Esperanza; Montellano-Palacios, Leticia; Gelover-Santiago, Silvia Lucila; Pérez-Castrejón, Sara; Cardoso-Vigueros, Lina; Martín-Domínguez, Alejandra; García-Sánchez, Liliana


    Two full-scale biological nutrient removal systems upgraded with three physico-chemical processes (coagulation, chemical precipitation, and neutral Fenton) were evaluated in order to determine the removal of emerging pollutants (EPs) present in municipal wastewater from Mexico. Between 41 and 55 EPs were detected in the influents of two wastewater treatment plants (WWTPs), including personal care products (PPCPs), antibiotics, analgesics, antiepileptics, antilipidemics, antihypertensives, antiseptics, stimulants, and hormones. Emerging pollutants were detected at concentrations ranging from 0.69ng/L to 94,600ng/L. High concentrations of emerging pollutants were found during dry season. WWTP 1, integrated by oxidation ditches and UV light lamps, showed removal efficiencies of EPs between 20% and 22%. On the other hand, WWTP 2 consisted of anaerobic/anoxic/aerobic tanks coupled with two disinfection processes; chlorine dioxide and UV light lamps, for which the removal of EPs was significant (up to 80%). The concentrations of emerging pollutants in WWTP 1 effluent was found within a rangeremovals, compared to those of WWTP 1, due to a greater activity of the simultaneous nitrification-denitrification processes, hydraulic retention time, and solids retention time. The compounds that were more persistent with removals below 50% in both effluents were: carbamazepine, dehydronifedipine, meprobamate, sertraline, propranolol, propoxyphene, norverapamil, diazepam, alprazolam, sulfamethoxazole, metoprolol, ofloxacin, norfloxacin, fluoxetine, erythromycin-H2O, diphenhydramine, dehydronifedipine, clarithromycin, hydrochlorothiazide, and albuterol. The application of neutral Fenton reaction as post-treatment for the two effluents from the WWTPs is promising for the removal of emerging pollutants (up to 100%) and for assuring high quality of treated water. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Amoxycillin and clavulanic acid induced Stevens-Johnson syndrome: a case report

    Ravi Shankar Manchukonda


    Full Text Available Stevens-Johnson syndrome (SJS is an immune complex mediated hypersensitivity complex that typically involves the skin and the mucous membranes. Various etiologic factors (e.g., infection, drugs and malignancies have been implicated as causes of Stevens-Johnson syndrome. However, as many as half of the cases are idiopathic. Bastuji and Roujeau proposed that the denomination of Stevens-Johnson syndrome should be used for a syndrome characterized by mucous membrane erosions and widespread small blisters that arise on erythematous or purpuric maculae that are different from classic targets. In this case report, a 6 year old girl who was administered a cough syrup (containing bromhexine, guaiphenesin, diphenhydramine and phenylephrine and amoxycillin and clavulanic acid dispersible tablet for the treatment of cough developed pruritic skin eruptions all over the body along with painful erosions on the tongue, buccal mucosa, genital and anal mucosa. A diagnosis of Stevens-Johnson syndrome was made. Amoxycillin and clavulanic acid combination was identified as the culprit based on the temporal relationship between the drug administration and the appearance of the rashes and based on a number of SJS reports implicating amoxycillin and clavulanic acid having been published before. The cough syrup and amoxycillin and clavulanic acid combination tablets were immediately stopped. Symptomatic treatment was administered. The child improved and was later discharged. Causality assessment using Naranjo adverse drug reaction probability scale revealed that amoxycillin and clavulanic acid combination was a possible cause for the harmful cutaneous adverse reaction with a score of 4. [Int J Basic Clin Pharmacol 2016; 5(3.000: 1140-1144

  12. Quantification of pharmaceuticals, personal care products, and perfluoroalkyl substances in the marine sediments of Puget Sound, Washington, USA.

    Long, Edward R; Dutch, Margaret; Weakland, Sandra; Chandramouli, Bharat; Benskin, Jonathan P


    Concentrations of 119 pharmaceuticals and personal care products (PPCPs) and 13 perfluoroalkyl substances (PFASs) in marine sediments measured throughout Puget Sound (n = 10) and Bellingham Bay (n = 30), Washington, USA, are reported. These data are among the first measurements of PPCPs and PFASs in marine sediments from the Pacific Northwest and provide a comparison to previous measurements of these chemicals in influent, effluent, and biosolids from municipal wastewater treatment plants throughout the region. The concentrations of both PPCPs and PFASs in sediments from Puget Sound and Bellingham Bay ranged from very low to non-detectable for most compounds. Only 14 of the 119 PPCPs and 3 of 13 PFASs were quantifiable in sediments. Diphenhydramine (an antihistamine) was most frequently detected (87.5% of samples), with a maximum concentration of 4.81 ng/g dry weight and an estimated mean detected concentration of 1.68 ng/g. Triclocarban (an antibacterial) was detected in 35.0% of the samples, with a maximum concentration of 16.6 ng/g dry weight. Perfluoroalkyl substances were detected in 2.5% of analyses. Perfluorobutanoate, perfluorooctane sulfonate, and perfluorooctane sulfonamide were detected in 7, 5, and 1 sample(s) each, respectively, with the highest concentrations observed for perfluorooctane sulfonate (1.5 ng/g). Detected concentrations were often highest within the industrial harbor in Bellingham Bay and near the cities of Seattle and Bremerton. Environ Toxicol Chem 2013;32:1701-1710. © 2013 SETAC. Copyright © 2013 SETAC.

  13. Pharmaceuticals and personal care products (PPCPs) in Australia's largest inland sewage treatment plant, and its contribution to a major Australian river during high and low flow.

    Roberts, Jenna; Kumar, Anupama; Du, Jun; Hepplewhite, Christopher; Ellis, David J; Christy, Andrew G; Beavis, Sara G


    Reports of pharmaceuticals in STPs and aquatic systems in the northern hemisphere have surged over the last decade. However, the Australian evidence base is relatively limited, and information on the role of seasonal dilution in attenuation of micropollutants is also scarce. We investigated the removal of 11 PPCPs during sewage treatment in Australia's largest inland STP, and concentrations in the effluent-receiving environment under 2 dilution scenarios. Five treatment stages were sampled, as well as upstream and downstream of the effluent outfall in the Lower Molonglo/Upper Murrumbidgee Catchment, which is dominated by effluent flow during dry periods. Compounds of interest include carbamazepine (CBZ), venlafaxine (VEN), sertraline (SER), fluoxetine (FLX), atenolol (ATL), sotalol (SOT), metoprolol (MET) propranolol (PRL), chlorpheniramine (CHP), diphenhydramine (DPH), and triclosan (TCS). Removal of most pharmaceuticals in the STP was incomplete, although the degree of removal was highly variable for compounds in the same therapeutic class, and for the same compounds in different seasons. Removal efficiency was highest for TCS and lowest for VEN (effluent concentrations 5-7 times higher than influent). Influent mass loads and removal efficiencies of cardiovascular medicines varied considerably. Effluent loads were highest for CBZ, VEN and SOT in both seasons (up to 64 g/day). The dilution conditions were clearly reflected in the 'zone of impact' of PPCPs in the catchment. This study confirms that risk assessment models for PPCPs must account for seasonality of influent loads and removal efficiency of STPs, and site validation is critical for predictive capability. Seasonal dilution can play an important role in ameliorating potentially adverse effects related to mixtures of PPCPs in effluent-impacted systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Occurrence of pharmaceuticals and personal care products in fish: results of a national pilot study in the United States.

    Ramirez, Alejandro J; Brain, Richard A; Usenko, Sascha; Mottaleb, Mohammad A; O'Donnell, John G; Stahl, Leanne L; Wathen, John B; Snyder, Blaine D; Pitt, Jennifer L; Perez-Hurtado, Pilar; Dobbins, Laura L; Brooks, Bryan W; Chambliss, C Kevin


    Pharmaceuticals and personal care products are being increasingly reported in a variety of biological matrices, including fish tissue; however, screening studies have presently not encompassed broad geographical areas. A national pilot study was initiated in the United States to assess the accumulation of pharmaceuticals and personal care products in fish sampled from five effluent-dominated rivers that receive direct discharge from wastewater treatment facilities in Chicago, Illinois; Dallas, Texas; Orlando, Florida; Phoenix, Arizona; and West Chester, Pennsylvania, USA. Fish were also collected from the Gila River, New Mexico, USA, as a reference condition expected to be minimally impacted by anthropogenic influence. High performance liquid chromatography-tandem mass spectrometry analysis of pharmaceuticals revealed the presence of norfluoxetine, sertraline, diphenhydramine, diltiazem, and carbamazepine at nanogram-per-gram concentrations in fillet composites from effluent-dominated sampling locations; the additional presence of fluoxetine and gemfibrozil was confirmed in liver tissue. Sertraline was detected at concentrations as high as 19 and 545 ng/g in fillet and liver tissue, respectively. Gas chromatography-tandem mass spectrometry analysis of personal care products in fillet composites revealed the presence of galaxolide and tonalide at maximum concentrations of 2,100 and 290 ng/g, respectively, and trace levels of triclosan. In general, more pharmaceuticals were detected at higher concentrations and with greater frequency in liver than in fillet tissues. Higher lipid content in liver tissue could not account for this discrepancy as no significant positive correlations were found between accumulated pharmaceutical concentrations and lipid content for either tissue type from any sampling site. In contrast, accumulation of the personal care products galaxolide and tonalide was significantly related to lipid content. Results suggest that the detection of

  15. Simultaneous determination of polar pharmaceuticals and personal care products in biological organs and tissues.

    Tanoue, Rumi; Nomiyama, Kei; Nakamura, Haruna; Hayashi, Terutake; Kim, Joon-Woo; Isobe, Tomohiko; Shinohara, Ryota; Tanabe, Shinsuke


    In the present study, a sensitive and accurate isotope dilution method was developed for the simultaneous determination of 17 polar pharmaceutical and personal care product (PPCP) residues (logKow=1.40-5.74), including 14 pharmaceuticals and 3 personal care products, in biological organs and tissues. The proposed method involved enzymatic hydrolysis, followed by sequential clean-up using silica gel chromatography and gel permeation chromatography, and analysis via ultra-high-performance liquid chromatography with tandem mass spectrometry. This method yielded acceptable absolute recoveries (48-88%) and internal standard-corrected recoveries (90-130%) for 17 PPCPs. Method detection limits were between 0.0092 and 3.2ngg(-1) wet weight, and the limits of quantification were between 0.020 and 8.7ngg(-1) wet weight. The method can be used to readily detect the target compounds at trace levels while minimizing the required sample volume. The developed method was applied to the determination of 17 PPCPs in the liver and kidney of 17 birds collected from Japan and also in the plasma, liver, and brain of 7 cyprinoid fish from an effluent-dominated stream in Japan. Triclosan was detected in 5 of 11 fish-eating birds but not in non-fish-eating birds, suggesting the contamination of prey fish by the chemical. Non-steroidal anti-inflammatory drugs, antibacterial agents, and psychotropic agents were frequently detected in the fish tissues. In addition, 7 of the target compounds were found in fish brain. The median brain/plasma ratios of the psychotropic agents ranged from 1.6 (carbamazepine) to 12 (diphenhydramine), indicating high transportability to fish brain. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Human health risk assessment of pharmaceuticals and personal care products in plant tissue due to biosolids and manure amendments, and wastewater irrigation.

    Prosser, R S; Sibley, P K


    Amending soil with biosolids or livestock manure provides essential nutrients in agriculture. Irrigation with wastewater allows for agriculture in regions where water resources are limited. However, biosolids, manure and wastewater have all been shown to contain pharmaceuticals and personal care products (PPCPs). Studies have shown that PPCPs can accumulate in the tissues of plants but the risk that accumulated residues may pose to humans via consumption of edible portions is not well documented. This study reviewed the literature for studies that reported residues of PPCPs in the edible tissue of plants grown in biosolids- or manure-amended soils or irrigated with wastewater. These residues were used to determine the estimated daily intake of PPCPs for an adult and toddler. Estimated daily intake values were compared to acceptable daily intakes to determine whether PPCPs in plant tissue pose a hazard to human health. For all three amendment practices, the majority of reported residues resulted in hazard quotients <0.1. Amendment with biosolids or manure resulted in hazard quotients ≥0.1 for carbamazepine, diphenhydramine, salbutamol, triclosan, and sulfamethazine. Irrigation with wastewater resulted in hazard quotients of ≥0.1 for ambrettolid, carbamazepine, diclofenac, flunixin, lamotrigine, metoprolol, naproxen, sildenafil and tonalide. [corrected]. Many of the residues that resulted in hazard quotients ≥0.1 were due to exposing plants to concentrations of PPCPs that would not be considered relevant based on concentrations reported in biosolids and manure or unrealistic methods of exposure, which lead to artificially elevated plant residues. Our assessment indicates that the majority of individual PPCPs in the edible tissue of plants due to biosolids or manure amendment or wastewater irrigation represent a de minimis risk to human health. Assuming additivity, the mixture of PPCPs could potentially present a hazard. Further work needs to be done to assess

  17. General pharmacological properties of a new non-opiate antitussive: zipeprol (3024 CERM). I. Action on respiratory function and acute toxicity.

    Rispat, G; Burgi, H; Cosnier, D; Duchêne-Marullaz, P; Streichenberger, G


    1-(2-Methoxy-2-phenyl)-ethyl-4-(2-hydroxy-3-methoxy-3-phenyl)-propyl-iperazine-dihydrochloride (zipeprol, Respilene) is a substance of non-phenanthrenic chemical structure. In the cat, it antagonised cough induced by stimulation of the superior laryngeal nerve or by direct mechanical excitation of the sensitive tracheo-bronchial receptors. The efficacy of zipeprol after enteral administration made it possible both to establish good intestinal absorption and to rank it favourably in relation to several major antitussive reference products; codeine, codethyline, dextromethorphan, diphenhydramine and pentoxyverine. The activity of zipeprol was superior or equal to that of all these substances, excdept codeine. The antitussive properties appeared to be due to a central action. Other properties have been demonstrated which suggest at least a supplementary mechanism in the inhibition of cough, in addition to the central action. These consisted of slight antihistamine and anticholinergic properties, marked local-anesthetic potency and bronchospasmolytic activity. This latter property was demonstrated by the inhibition of histamine and serotonin induced bronchospasm in the guinea-pig. In vitro, using human sputum, zipeprol had a mucolytic action, shown by a decrease in sputum vis viscosity and lysis of DNA and AMPS fibrils. In the dog, at high doses, zipeprol unlike codeine, did not inhibit central stimulation of respiration by hypercapnia, in addition no modification of ventilatory dynamics or blood gases was seen. On the basis of these results, zipeprol can be considered as possessing no respiratory depressant effect even in the upper ranges of its antitussive doses.

  18. Development and validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of acrivastine and pseudoephedrine in human plasma and its application in pharmacokinetics.

    He, J-C; Feng, E-F; Liu, M; Li, H-L; Tian, M; Zhang, Q; Dong, L-C; Xu, G-L


    A specific, sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of acrivastine and pseudoephedrine in human plasma samples. Plasma samples were processed and analyzed on a Phenomenex Luna 3 μ CN 100A column (150 mm×2.0 mm) eluted with the mobile phase consisting of methanol and 0.01 mol/L ammonium acetate water solution containing 0.1% formic acid (45:55, v/v) at a flow rate of 0.2 mL/min. The analytes were detected by positive ion electrospray ionization in multiple reaction monitoring mode. The transitions of m/z 349→278, m/z 166→148 and m/z 256→167 were monitored for acrivastine, pseudoephedrine and diphenhydramine (IS), respectively. The method was specific and sensitive with a lower limit of quantitation (LLOQ) of 1.52 ng/mL for acrivastine and 8.13 ng/mL for pseudoephedrine. The method showed good linearity in the range of 1.52~606.0 0 ng/mL for acrivastine and 8.13~813.12 ng/mL for pseudoephedrine (r≥0.996). The mean recovery were ranged 91.82% ~ 98.46% for acrivastine and 90.77% ~ 92.05% for pseudoephedrine. Validation results, such as accuracy, precision and repeatability were within the required limits. The method was successfully applied in a pharmacokinetic study of the acrivastine and pseudoephedrine hydrochloride compound capsule in humans.

  19. Induction and antagonism of pica induced by teriparatide in rats.

    Yamamoto, Kouichi; Kato, Naoto; Isogai, Yukihiro; Kuroda, Tatsuhiko; Ishida, Takayuki; Yamatodani, Atsushi


    Intermittent subcutaneous injection of teriparatide, an active fragment of human parathyroid hormone, is clinically used for the treatment of osteoporosis. Patients suffer from nausea, which is one of the side effects teriparatide induces; however, the etiology of teriparatide-induced nausea remains unknown. We have reported pica, kaolin ingestion behavior, can be used as an assessment of nausea-related response in rats. In this study, we investigated the characteristics of teriparatide-induced pica and the abilities of anti-emetic drugs to inhibit teriparatide-induced pica. Male and female adolescent (4-week-old), young (8-week-old), and adult (30-week-old) naive rats, and ovariectomized (OVX: 17-week-old) and sham-operated (17-week-old) rats subcutaneously received teriparatide (0.4 mg/kg, n=4), and their kaolin and food intakes were monitored for 24 h after the injection. Among the tested rats, we found that OVX rats, rather than male, female, and sham-operated rats, showed marked teriparatide-induced pica (0 mg/kg: 0.17±0.07 g, 0.4 mg/kg: 6.18±0.91 g). Teriparatide-induced pica in OVX rats was inhibited by intraperitoneal pretreatment with serotonin 5-HT3 (granisetron 0.5 mg/kg), dopamine D2 (prochlorperazine 0.5 mg/kg), neurokinin NK1 (fosaprepitant 1 mg/kg), and histamine H1 (diphenhydramine 10 mg/kg) receptor antagonists to 70%, 11%, 19%, and 59% of that in vehicle-treated control, respectively. These results suggest that teriparatide-induced pica in OVX rats has the potential to reflect teriparatide-induced nausea; 5-HT3, D2, NK1, and H1 receptor activation is involved in the development of this behavior; antagonists of these receptors have the potential to be medical candidates used as treatments for teriparatide-induced nausea in human patients.

  20. A comprehensive and sensitive method for hair analysis in drug-facilitated crimes and incorporation of zolazepam and tiletamine into hair after a single exposure.

    Kim, Jihyun; Yum, Hyesun; Jang, Moonhee; Shin, Ilchung; Yang, Wonkyung; Baeck, Seungkyung; Suh, Joon Hyuk; Lee, Sooyeun; Han, Sang Beom


    Hair is a highly relevant specimen that is used to verify drug exposure in victims of drug-facilitated crime (DFC) cases. In the present study, a new analytical method involving ultrahigh-performance liquid chromatography-tandem mass spectrometry was developed for determining the presence of model drugs, including zolazepam and tiletamine and their metabolites in hair specimens from DFCs. The incorporation of zolazepam and tiletamine into hair after a single exposure was investigated in Long-Evans rats with the ratio of the hair concentration to the area under the curve. For rapid and simple sample preparation, methanol extraction and protein precipitation were performed for hair and plasma, respectively. No interference was observed in drug-free hair or plasma, except for hair-derived diphenhydramine in blank hair. The coefficients of variance of the matrix effects were below 12%, and the recoveries of the analytes exceeded 70% in all of the matrices. The precision and accuracy results were satisfactory. The limits of quantification ranged from 20 to 50 pg in 10 mg of hair. The drug incorporation rates were 0.03 ± 0.01% for zolazepam and 2.09 ± 0.51% for tiletamine in pigmented hair. We applied the present method to real hair samples in order to determine the drug that was used in seven cases. These results suggest that this comprehensive and sensitive hair analysis method can successfully verify a drug after a single exposure in crimes and can be applied in forensic and clinical toxicology laboratories.

  1. Orexin receptor antagonist-induced sleep does not impair the ability to wake in response to emotionally salient acoustic stimuli in dogs

    Pamela L. Tannenbaum


    Full Text Available The ability to awaken from sleep in response to important stimuli is a critical feature of normal sleep, as is maintaining sleep continuity in the presence of irrelevant background noise. Dual orexin receptor antagonists (DORAs effectively promote sleep across species by targeting the evolutionarily conserved wake-promoting orexin signaling pathway. This study in dogs investigated whether DORA-induced sleep preserved the ability to awaken appropriately to salient acoustic stimuli but remain asleep when exposed to irrelevant stimuli. Sleep and wake in response to DORAs, vehicle, GABA-A receptor modulators (diazepam, eszopiclone and zolpidem and antihistamine (diphenhydramine administration were evaluated in telemetry-implanted adult dogs with continuous electrocorticogram, electromyogram, electrooculogram, and activity recordings. DORAs induced sleep, but GABA-A modulators and antihistamine induced paradoxical hyperarousal. Thus, salience gating studies were conducted during DORA-22 (0.3, 1, and 5 mg/kg; day and night and vehicle nighttime sleep. The acoustic stimuli were either classically conditioned using food reward and positive attention (salient stimulus or presented randomly (neutral stimulus. Once conditioned, the tones were presented at sleep times corresponding to maximal DORA-22 exposure. In response to the salient stimuli, dogs woke completely from vehicle and orexin-antagonized sleep across all sleep stages but rarely awoke to neutral stimuli. Notably, acute pharmacological antagonism of orexin receptors paired with emotionally salient anticipation produced wake, not cataplexy, in a species where genetic (chronic loss of orexin receptor signaling leads to narcolepsy/cataplexy. DORA-induced sleep in this species thereby retains the desired capacity to awaken to emotionally salient acoustic stimuli while preserving uninterrupted sleep in response to irrelevant stimuli.

  2. Modulatory effects of taurine on jejunal contractility

    Yao, Q.Y.; Chen, D.P.; Ye, D.M.; Diao, Y.P.; Lin, Y. [Dalian Medical University, Dalian, Liaoning (China)


    Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca{sup 2+} dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

  3. Resolution of Allergic Rhinitis and Reactive Bronchospasm With Supplements and Food-specific Immunoglobulin G Elimination: A Case Report.

    Kwiatkowski, Laura; Mitchell, Jessica; Langland, Jeffrey


    Context • Allergies are a common affliction, whether they are respiratory, food related, or dermatological. People often resort to continuous use of over-the-counter medications, such as antihistamines, to manage their symptoms. Controversy still remains over testing serum immunoglobulin (Ig) G to diagnose food allergies. Objective • This study intended to examine the benefits of treatment of a pediatric patient with natural supplements and an elimination diet for IgG food allergies. Design • The research team reported a case study. Setting • The study was conducted at Southwest Naturopathic Medical Center (Tempe, AZ, USA). Participant • The participant was a 10-y-old Caucasian female who had diagnoses of allergic rhinitis and reactive bronchospasm, the second of which was exacerbated by allergens such as wheat, perfumes, and seasonal flora. Intervention • Following testing for IgE- and IgG-reactive foods, the patient was treated with natural supplements to reduce her allergic responses and was instructed to make dietary changes to eliminate the IgG-reactive foods. Outcome Measures • The patient's symptom severity was tracked starting 1 mo after her initial visit to Southwest Naturopathic Medical Center. The severity was based on the patient's subjective reports about her congestion to her mother and on her mother's observations of the effect of symptoms on her attention and school performance. The bronchospasm severity was based on the frequency of a sensation of wheezing and chest tightness, the frequency of inhaler use, and the occurrence of any exacerbation of symptoms with acute respiratory illness Results • After 1 mo, in which the patient used the natural supplements, she experienced a 90% improvement in coughing; a 70% improvement in nasal congestion; less chest tightness; and no need for use of loratadine, diphenhydramine, or albuterol. At the 8-mo follow-up visit, her nasal congestion was reported to be entirely gone. Conclusions • The

  4. Quantitation of N,N-dimethyltryptamine and harmala alkaloids in human plasma after oral dosing with ayahuasca.

    Callaway, J C; Raymon, L P; Hearn, W L; McKenna, D J; Grob, C S; Brito, G S; Mash, D C


    Harmine, harmaline, tetrahydroharmine (THH), and N,N-dimethyltryptamine (DMT) were quantitated in plasma from 15 healthy male volunteers after the ingestion of ayahuasca, a beverage that has been used for religious purposes in Brazil since pre-Columbian times. A growing awareness of the interest in this ancient shamanistic practice in modern urban cultures and the widespread popular dissemination of the inebriant effects and type and sources of the plant admixtures used to prepare the beverage have provided additional impetus for this study. The three harmala alkaloids were quantitated from protein-precipitated plasma by high-performance liquid chromatography using fluorescence detection. Recovery from blank human plasma was quantitative, and the limit of quantitation (LOQ) was below 2 ng/mL of plasma for each of the harmala alkaloids. Standard concentrations ranged from 10 to 250 ng/mL for harmine and THH and from 1.0 to 25.0 ng/mL for harmaline, respectively. Linearity was observed for harmine, harmaline, and THH within these respective ranges. The highest concentrations of harmala alkaloids in human plasma were found to be 222.3 ng/mL for harmine, 134.5 ng/mL for THH, and 9.4 ng/mL for harmaline. DMT was quantitated by gas chromatography using nitrogen-phosphorus detection after liquid-liquid extraction with diphenhydramine as an internal standard. DMT recovery was quantitative, and the limit of detection and LOQ were 0.5 and 5 ng/mL, respectively. Linearity for DMT was observed from 5 to 1000 ng/mL. The one-step extraction method for DMT and the protein precipitation method for the three harmala alkaloids afford rapid, sensitive, and quantitative analyses of these alkaloids with minimal analyte loss. The analytical methods also may be applicable to other matrices, including whole blood and urine samples and homogenized tissue specimens. These are the first reported observations of DMT and harmala alkaloids in plasma after ritual ingestion of ayahuasca.

  5. Toxicology findings in cases of hanging in the City and County of San Francisco over the 3-year period from 2011 to 2013.

    San Nicolas, A C; Lemos, N P


    In postmortem cases where the cause of death is hanging, toxicological analyses may be considered unnecessary by some medical examiners, toxicologists, and other persons involved in medico-legal investigations because the cause of death seems "obvious." To ascertain if toxicological analyses are necessary when the cause of death is hanging, all 102 hanging cases (25 females; 77 males) from 2011 to 2013 that came under the jurisdiction of the San Francisco Office of the Chief Medical Examiner were examined from a total of 3912 sudden, unexpected, or violent death cases in the same period. Suicide was the manner of death in 99 of these cases, with two accidental and one undetermined death. The average age of decedents was 43.9 years (median 41), the youngest was an 11-year old male and the oldest was an 86-year old female. Of the 102 cases, 33 had negative toxicology while 69 cases had at least one positive toxicology result. Females were equally likely to have negative or positive results (12 and 13 cases respectively), but males were 37.5% more likely to have positive toxicology (n=56) rather than negative toxicology (n=21). For females, alcohol, mirtazapine, venlafaxine, and trazodone were the top psychoactive substances in peripheral blood while THC, cocaine, hydrocodone, bupropion, olanzapine, doxylamine, quetiapine and dextromethorphan were also reported. For males, alcohol, THC, cocaine, amphetamine, methamphetamine, bupropion, and diphenhydramine were the top psychoactive substances in blood, but several other drugs were also found in individual cases. Our study of hanging cases over a 3-year period support the idea that complete postmortem toxicology investigation of hangings should be performed, even when the "obvious" cause of death is asphyxia due to hanging. Many of these cases involved psychoactive substances (most often alcohol and cannabis), and having such knowledge provides a better understanding of the circumstances surrounding the decedent's death

  6. Sleep complaints: Whenever possible, avoid the use of sleeping pills.


    (1) Most sleep complaints involve difficulties in getting to sleep or staying asleep, or not feeling refreshed on awakening. Misconceptions and worrying over the lack of sleep and its consequences can contribute to reinforcing these disorders; (2) How can patients who complain of poor-quality sleep be helped, without resorting to treatments that can have adverse effects? To answer this question, we conducted a systematic review of the literature based on the standard Prescrire procedure; (3) One effective approach is to explain the basic physiology of sleep, to discuss misconceptions, and to adopt a strategy of "stimulus control". This method has a similar efficacy to prescribing a benzodiazepine. and the effect is longer lasting; (4) Moderate, regular physical exercise, especially in the morning, seems to help some patients, but the evidence is weak; (5) Some clinical trials of phytotherapy have shown a positive risk-benefit balance of weak aqueous or hydroalcoholic valerian extracts. Efficacy is limited, however; (6) A meta-analysis of placebo-controlled trials showed that benzodiazepines and related drugs increase the duration of sleep and help patients to fall asleep sooner. However, none of these trials provides comparative data spanning periods of more than two weeks. Efficacy is uncertain in the longer term, as patients quickly develop a tolerance to the hypnotic effects of benzodiazepines; (7) The adverse effects of benzodiazepines include frequent memory disorders, daytime drowsiness, falls, fractures and road accidents, and a withdrawal syndrome after treatment cessation. Related drugs such as zolpidem and zopiclone provoke similar adverse effects; (8) Sedative antihistamines have not been as well-evaluated as benzodiazepines in this setting. Small comparative trials of doxylamine and diphenhydramine showed no major difference in efficacy versus benzodiazepines and related drugs. The main adverse effects of sedative antihistamines are daytime drowsiness

  7. Pharmaceutical compounds in Merrimack River water used for public supply, Lowell, Massachusetts, 2008-09

    Massey, Andrew J.; Waldron, Marcus C.


    This report presents results of a study conducted by the U.S. Geological Survey (USGS), in cooperation with the Massachusetts Department of Environmental Protection, to determine the occurrence of 14 commonly used human-health pharmaceutical compounds and fecal-indicator bacteria in Merrimack River water used as a drinking-water source by 135,000 residents in eastern Massachusetts. The study was designed to complement the USGS National Water-Quality Assessment Program's Source Water-Quality Assessment, which identifies patterns of occurrence of 280 primarily unregulated organic wastewater contaminants in source water used by community water systems and determines whether these patterns also occur in treated drinking water prior to distribution. The study involved periodic collection and analysis of raw Merrimack River water and treated drinking water over the course of 1 year. Water samples were collected periodically without regard to flow regime or antecedent weather conditions at the Lowell Regional Water Utility's Merrimack River intake upstream from Lowell, Mass. The same parcel of water was then sampled as finished water following treatment. Despite the presence of many potential sources of contamination in the drinking-water source area, only 2 of the 14 pharmaceutical analytes were detected at reportable concentrations in the source-water samples, and these occurred in only one set of periodic samples. Acetaminophen, a nonprescription analgesic, and caffeine were detected in the September source-water samples at concentrations of 0.084 and 0.068 micrograms per liter, respectively. Three other compounds-carbamazepine, an antiepileptic; cotinine, a metabolite of nicotine; and diphenhydramine, a nonprescription antihistamine-were detected in source-water samples, but at concentrations too low to be reliably quantified. None of the 14 pharmaceuticals was found in the finished water at a reportable concentration, defined as two times the long-term detection

  8. Review of Safety and Efficacy of Sleep Medicines in Older Adults.

    Schroeck, Jennifer L; Ford, James; Conway, Erin L; Kurtzhalts, Kari E; Gee, Megan E; Vollmer, Krista A; Mergenhagen, Kari A


    adverse effects. Gabapentin may be useful in patients with restless leg syndrome or chronic neuropathic pain and insomnia. Diphenhydramine should be avoided in the elderly. Valerian and melatonin are unregulated products that have a small impact on sleep latency and can produce residual sedation. An ideal treatment for insomnia should help to improve sleep latency and sleep duration with limited awakenings and be without significant adverse effects such as daytime somnolence or decreased alertness. Cognitive behavioral therapy should always be first line treatment. Clinical inertia regarding previous prominent use of benzodiazepines and non-BzRAs will be a significant challenge for patients accustomed to their issuance. The future direction of insomnia treatment should have an emphasis on nonpharmacologic interventions, treating comorbid conditions, and focusing therapy on using benzodiazepines and non-BzRAs as last resorts. Published by Elsevier Inc.

  9. [Clinical significance of the relationship between expression of survivin and effects of neoadjuvant chemotherapy in locally advanced breast cancer].

    Fuzhong, Tong; Nan, Lu; Jiajia, Guo; Miao, Liu; Deqi, Yang


    Explore the relationship between the expression intensity of survivin and the effectiveness of neoadjuvant chemotherapy in locally advanced breast cancer patients. Neoadjuvant chemotherapy with epirubicin plus paclitaxel was administered to 76 patients in locally advanced breast cancer (including 25 cases of stage IIa, 26 of stage IIb, 16 of stage IIIa, and 9 of stage IIIb), the mean age is 52.8(33-79)years old. All patients were female. They were treated with epirubicin 60 mg/m(2), on day 1, by i. v. followed paclitaxel 175 mg/m(2) by 3 hours continues infusion on day 2 and every 3 weeks repeatedly. Premedication of dexamethasone, ondansetron, diphenhydramine and cimetidine were administered to prevent gastroenteric and allergic reactions before chemotherapy. Four cycles were used. The expression of survivin in breast cancer tissue was detected with SDS-PAGE, western-immunoblotting and immunohistochemistry (IHC), and then that were immunological stained by anti survivin monoclonal antibody, and also the results were analyzed for the relationship between the expressed intensity of survivin and the effect of neoadjuvant chemotherapy in locally advanced breast cancer patients. Nineteen out of 76 patients had a clinical complete response, 36 had clinical partial response, and 21 had no change. The response rate was 72.37%(55/76). We found survivin could be differently expressed in 76 patients with SDS-PAGE, western-immunoblotting and IHC and then immune stain by anti survivin monoclonal antibody. Forty six patients were low expressed of survivin and 9 patients were high expressed in all response patients. Eight patients were low expressed, only 1 patient was high expressed of survivin in 9 patients had pCR. But no finding the relationship between the expression of survivin and TNM stage, ER, PgR, HER-2. The patients have high response rate of low expression of survivin after neoadjuvant chemotherapy with TE regimen in locally advanced breast cancer patients. This

  10. One case of serious anaphylaxis induced by fluconazole injection%氟康唑注射液致严重过敏反应1例

    邓牡红; 黄芳芳; 陈志杰; 李秀秀


    [ABSTRACT]One 45-year-old male patient diagnosed with lung cancer received chemotherapy and radiotherapy. Throat swab culture and stool culture conifrmed fungal infections and lfuconazole injection (100 mg, ivgtt) was given for antifungal therapy. Two minutes after the end of infusion, the patient complained of shiver, hyperpyrexia, suffocation and severe cough, which was considered as severe allergic reaction. Inhalation of oxygen (4 L·min-1), dexamethasone sodium phosphate injection (5 mg, iv), diphenhydramine hydrochloride injection (1 mL, im), diprophylline injection (0.25 g, ivgtt), methylprednisolone sodium succinate for injection(40 mg, iv) and lysine acetylsalicylate for injection (0.9 g, iv) were given. Then the patient recovered gradually and the above symptoms disappeared 3 h later.%1例45岁男性患者,因确诊肺癌入院,此次化疗同时行颅脑放疗。患者咽拭子及大便中检出真菌,给予氟康唑注射液(100 mg,ivgtt)抗真菌治疗。在输注结束2 min后,患者出现寒战、高热、喘憋、剧烈咳嗽等症状,考虑为严重过敏反应,立即给予持续吸氧(4 L·min-1),地塞米松磷酸钠注射液(5 mg,iv)、盐酸苯海拉明注射液(1 mL,im)、二羟丙茶碱注射液(0.25 g,ivgtt)、注射用甲泼尼龙琥珀酸钠(40 mg,iv)、注射用赖氨匹林(0.9 g,iv)等对症治疗。之后患者症状逐渐缓解,3 h后症状消失。

  11. 紫杉醇脂质体治疗肿瘤的护理体会%The nursing of paclitaxel liposome formula on tumour

    刘玉芳; 梁英梅; 李倩; 何会娜; 王红茜; 张晓静


    Objectives To investigate the side effects and the nursing of paclitaxel liposome (lipusu) formula on advanced lung cancer and breast cancer. Methods 100 cancer patients diagnosed by pathology were given paclitaxel liposome (lipusu) in the first day of chemotherapy 135 mg/m2 plus 5% GS 500 mL intravenous drip for 3 hours. Firstly 5% GS injection 10 mL was injected into paclitaxel liposome bottle, rocked for 10~20 minutes with a special oscillator, until dissolved completely, then injected into 5 % GS 500 mL for intravenous drip. 30 minutes prior to the administration of paclitaxel liposome pre-treatment was carried out with dexamethasone 5 ~ 10 mg intravenous injection, diphenhydramine 40 mg intramuscular injection, and cimetidine 400 mg in-travenous drip. Result Based on the observation of side effects to medicines and nursing of patients, none of serious life-threatening adverse reactions arose. Conclusion Through pre-treatment, in and after treatment observation and care, the occurrence rate and extent of adverse drug reactions can be reduced.%目的 研究应用紫杉醇脂质体(力朴素)治疗晚期肺癌和乳腺癌出现的不良反应和护理.方法 100例经病理学确诊的癌症患者,采用力朴素在化疗第1天用135 mg/m2加入5% 葡萄糖(GS) 500 mL静脉滴入3 h, 先用5% G.S 10 mL注入紫杉醇脂质体瓶内,用专用振荡器振摇10~20 min, 待完全溶解后注入5% GS 500 mL静脉滴注,用药前30 min行预处理,地塞米松5~10 mg静脉入壶,苯海拉明40 mg肌肉注射,西咪替丁400 mg静脉滴注.结果通过对药物不良反应的观察和护理,患者无1例发生严重不良反应而危及生命.结论 经过用药前、用药中及用药后的观察和护理,可减轻药物不良反应的发生程度和发生机率.

  12. Different effects of H1 and H2 blockers on the tone and the contractile activity of guinea pig stomach fundus.

    Milenov, K; Todorov, S; Vassileva, M; Zamfirova, R; Shahbazian, A


    The action of H1 and H2 blockers on the spontaneous and evoked contractile activity of gastric fundus smooth muscles as well as the effects of H2 antagonists on the release of acetylcholine (ACh) from gastric myenteric neurons were studied. The experiments were performed on smooth muscle strips (25 x 3 mm) cut out in circular direction from guinea pig fundus region. In concentrations of 1 x 10(-7) M to 1 x 10(-4) M, the H1 blockers diphenhydramine (DPH), mepyramine (MEP) and dimethpyrindene (DMPD), but not the H2 blockers ranitidine (RAN), cimetidine (CIM) and roxatidine (ROX), increased in a concentration-dependent manner the smooth muscle tone, the maximum contractions being about 50% of the contractile effects of 1 x 10(-5) M ACH and 5 x 10(-5) M histamine (HA). The concentration-dependent contractions of the stomach fundus strips in response to electrical field stimulation (EFS) were enhanced by RAN, CIM and ROX (but not by MEP and DPH), all in concentrations of 1 x 10(-7) M to 1 x 10(-4) M. EFS increased the resting [3H]-ACh release by 67.8%, the S2/S1 ratio being 0.85 +/- 0.04. ROX in a concentration of 1 x 10(-5) M significantly increased (by 16.1%) the EFS-induced release with a S2/S1 ratio of 1.22 +/- 0.04. The ROX effect on the [3H]-ACh release was reduced or even abolished by 1 x 10(-6) M tetrodotoxin (TTX) and 1 x 10(-6) M scopolamine or in Ca(2+)-free medium, while 1 x 10(-6) M hexamethonium did not change it. It might be concluded that H2 blockers have no direct myogenic effect and do not interfere with muscarinic receptors in guinea pig stomach fundus. The H2 antagonists enhance the EFS-evoked contractions of the gastric smooth muscle most probably by increasing the release of ACH.

  13. Attenuation of trace organic compounds (TOrCs) inbioelectrochemical systems

    Werner, Craig M.


    Microbial fuel cells (MFCs) and microbial electrolysis cells (MECs) are two types of microbial bioelectrochemical systems (BESs) that use microorganisms to convert chemical energy in wastewaters into useful energy products such as (bio)electricity (MFC) or hydrogen gas (MEC). These two systems were evaluated for their capacity to attenuate trace organic compounds (TOrCs), commonly found in municipal wastewater, under closed circuit (current generation) and open circuit (no current generation) conditions, using acetate as the carbon source. A biocide was used to evaluate attenuation in terms of biotransformation versus sorption. The difference in attenuation observed before and after addition of the biocide represented biotransformation, while attenuation after addition of a biocide primarily indicated sorption. Attenuation of TOrCs was similar in MFCs and MECs for eight different TOrCs, except for caffeine and trimethoprim where slightly higher attenuation was observed in MECs. Electric current generation did not enhance attenuation of the TOrCs except for caffeine, which showed slightly higher attenuation under closed circuit conditions in both MFCs and MECs. Substantial sorption of the TOrCs occurred to the biofilm-covered electrodes, but no consistent trend could be identified regarding the physico-chemical properties of the TOrCs tested and the extent of sorption. The octanol-water distribution coefficient at pH 7.4 (log DpH 7.4) appeared to be a reasonable predictor for sorption of some of the compounds (carbamazepine, atrazine, tris(2-chloroethyl) phosphate and diphenhydramine) but not for others (N,N-Diethyl-meta-toluamide). Atenolol also showed high levels of sorption despite being the most hydrophilic in the suite of compounds studied (log DpH 7.4=-1.99). Though BESs do not show any inherent advantages over conventional wastewater treatment, with respect to TOrC removal, overall removals in BESs are similar to that reported for conventional wastewater

  14. Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning().

    Gosselin, Sophie; Hoegberg, Lotte C G; Hoffman, Robert S; Graudins, Andis; Stork, Christine M; Thomas, Simon H L; Stellpflug, Samuel J; Hayes, Bryan D; Levine, Michael; Morris, Martin; Nesbitt-Miller, Andrea; Turgeon, Alexis F; Bailey, Benoit; Calello, Diane P; Chuang, Ryan; Bania, Theodore C; Mégarbane, Bruno; Bhalla, Ashish; Lavergne, Valéry


    Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning. Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method. For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid(®) 20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best

  15. 固相萃取/高效液相色谱法测定化妆品中5种抗组胺药物残留%Determination of Five Antihistamine Residues in Cosmetics by SPE/HPLC

    车文军; 张征; 徐春祥; 王莉; 卢剑; 王燕芹; 邹洁; 武中平


    建立了固相萃取/高效液相色谱( SPE/HPLC)测定化妆品中5种抗组胺药物(多西拉敏、曲吡那敏、溴苯那敏、苯海拉明、氯苯沙明)残留的分析方法.试样经三氯乙酸溶液超声提取,PCX柱净化后,以甲醇-磷酸盐缓冲溶液为流动相,经C18柱分离后进行HPLC检测.5种抗组胺药物在5.0~ 100 mg/L范围内均呈良好的线性关系,线性系数均大于0.999.在5.0、10.0、25.0 mg/kg 3个加标水平下的平均回收率为92%~ 108%,相对标准偏差(RSD,n=6)为2.1%~4.2%,检出限为0.5~1.0 mg/L.该方法灵敏度高、重现性好、定量准确.%A solid phase extraction coupled with high performance liquid chromatography ( SPE/ HPLC) was developed for the determination of five antihistamines, e. g. doxylamine, tripelen-namine, brompheniramine, diphenhydramine, chlorphenoxamine, in cosmetics. The samples were extracted with trichloroacetic acid solution under ultrasonication, and cleaned up with PCX solid phase extraction. The separation of five antihistamines was carried out on a C18 column using metha-nol - phosphate buffer as mobile phase. The calibration curves of five drugs were linear in the range of 5. 0 - 100 mg/L, with correlation coefficients more than 0. 999. The mean recoveries at spiked levels of 5.0, 10.0, 25. 0 mg/kg were in the range of 92% -108% with RSDs(n =6)of 2. 1% -4. 2% . The limits of detection were in the range of 0. 5 -1.0 mg/L. The method was sensitive, reproducible and accurate.

  16. Pro-arrhythmic potential of oral antihistamines (H1: combining adverse event reports with drug utilization data across Europe.

    Elisabetta Poluzzi

    Full Text Available There is appreciable utilisation of antihistamines (H1 in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine and astemizole underwent regulatory restrictions in '90 because of their cardiac toxicity, but only scarce clinical data are available on other antihistamines.To investigate the pro-arrhythmic potential of antihistamines by combining safety reports of the FDA Adverse Event Reporting System (FAERS with drug utilization data from 13 European Countries.We identified signals of antihistamine arrhythmogenic potential by analyzing FAERS database for all cases of Torsades de Pointes (TdP, QT abnormalities (QTabn, ventricular arrhythmia (VA and sudden cardiac death/cardiac arrest (SCD/CA. Number of cases ≥3 and disproportionality were used to define alert signals: TdP and QTabn identified stronger signals, whereas SCD/CA identified weaker signals. Drug utilization data from 2005 to 2010 were collected from administrative databases through health authorities and insurance.Antihistamines were reported in 109 cases of TdP/QT prolongation, 278 VA and 610 SCD/CA. Five agents resulted in stronger signals (cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine and 6 in weaker signals (alimemazine, carbinoxamine, cyclizine, cyproeptadine, dexchlorpheniramine and doxylamine. Exposure to antihistamines with stronger signal was markedly different across European countries and was at least 40% in each Country. Cetirizine was >29 Defined Daily Doses per 1000 inhabitants per day (DID in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia. Drugs with weaker signals accounted for no more than 10% (in Sweden and in most European countries their use was negligible.Some second-generation antihistamines are associated with signal of torsadogenicity and largely used in most European countries. Although confirmation by analytical studies is required, regulators

  17. Pro-Arrhythmic Potential of Oral Antihistamines (H1): Combining Adverse Event Reports with Drug Utilization Data across Europe

    Poluzzi, Elisabetta; Raschi, Emanuel; Godman, Brian; Koci, Ariola; Moretti, Ugo; Kalaba, Marija; Wettermark, Bjorn; Sturkenboom, Miriam; De Ponti, Fabrizio


    Background There is appreciable utilisation of antihistamines (H1) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine and astemizole underwent regulatory restrictions in ’90 because of their cardiac toxicity, but only scarce clinical data are available on other antihistamines. Aim To investigate the pro-arrhythmic potential of antihistamines by combining safety reports of the FDA Adverse Event Reporting System (FAERS) with drug utilization data from 13 European Countries. Methods We identified signals of antihistamine arrhythmogenic potential by analyzing FAERS database for all cases of Torsades de Pointes (TdP), QT abnormalities (QTabn), ventricular arrhythmia (VA) and sudden cardiac death/cardiac arrest (SCD/CA). Number of cases ≥3 and disproportionality were used to define alert signals: TdP and QTabn identified stronger signals, whereas SCD/CA identified weaker signals. Drug utilization data from 2005 to 2010 were collected from administrative databases through health authorities and insurance. Results Antihistamines were reported in 109 cases of TdP/QT prolongation, 278 VA and 610 SCD/CA. Five agents resulted in stronger signals (cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine) and 6 in weaker signals (alimemazine, carbinoxamine, cyclizine, cyproeptadine, dexchlorpheniramine and doxylamine). Exposure to antihistamines with stronger signal was markedly different across European countries and was at least 40% in each Country. Cetirizine was >29 Defined Daily Doses per 1000 inhabitants per day (DID) in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia. Drugs with weaker signals accounted for no more than 10% (in Sweden) and in most European countries their use was negligible. Conclusions Some second-generation antihistamines are associated with signal of torsadogenicity and largely used in most European countries. Although confirmation by

  18. A case of anaphylaxis to peppermint.

    Bayat, Roian; Borici-Mazi, Rozita


    Anaphylaxis, a form of IgE mediated hypersensitivity, arises when mast cells and possibly basophils are provoked to secrete mediators with potent vasoactive and smooth muscle contractile activities that evoke a systemic response. We report a case of IgE mediated anaphylaxis to peppermint (Mentha piperita) in a male shortly after sucking on a candy. A 69 year old male developed sudden onset of lip and tongue swelling, throat tightness and shortness of breath within five minutes of sucking on a peppermint candy. He denied lightheadedness, weakness, nausea, vomiting, or urticaria. He took 25 mg of diphenhydramine, but his symptoms progressed to onset of cough, wheeze and difficulty with talking and swallowing. He was rushed to the nearest emergency department, where he was treated with intramuscular epinephrine, antihistamines and steroids. On history, he reported recent onset of mouth itchiness and mild tongue and lip swelling after using Colgate peppermint toothpaste. He denied previous history of asthma, allergic rhinitis, food or drug allergies. His past medical history was remarkable for hypercholesterolemia, gastroesophageal reflux and gout. He was on simvastatin, omeprazole, aspirin, and was carrying a self-injectable epinephrine device. He moved to current residence three years ago and cultivated mint plants in his backyard. He admitted to develop nasal congestion, cough and wheeze when gardening. Physical examination was unremarkable apart from slightly swollen pale inferior turbinates. Skin prick test (SPT) was strongly positive to a slurry of peppermint candy and fresh peppermint leaf, with appropriate controls. Same tests performed on five healthy volunteers yielded negative results. Skin testing to common inhalants including molds and main allergenic foods was positive to dust mites. Strict avoidance of mint containing items was advised. Upon reassessment, he had removed mint plants from his garden which led to resolution of symptoms when gardening. Ig

  19. Rapid and simultaneous quantification of levetiracetam and its carboxylic metabolite in human plasma by liquid chromatography tandem mass spectrometry.

    Li-Ling Yeap

    Full Text Available A simple liquid chromatography tandem mass spectrometry method was developed and validated according to the guidelines of the US Food and Drug Administration and the European Medicines Agency for a simultaneous quantification of levetiracetam (LEV and its metabolite, UCB L057 in the plasma of patients. A 0.050 mL plasma sample was prepared by a simple and direct protein precipitation with 0.450 mL acetonitrile (ACN containing 1 µg/mL of internal standard (IS, diphenhydramine, then vortex mixed and centrifuged. A 0.100 mL of the clear supernatant was diluted with 0.400 mL water and well mixed. A 0.010 mL of the resultant solution was injected into an Agilent Zorbax SB-C18 (2.1 mm×100 mm, 3.5 µm column with an isocratic elution at 0.5 mL/min using a mixture of 0.1% formic acid in water and ACN (40:60 v/v. Detection was performed using an AB Sciex API 3000 triple quadrupole mass spectrometer, equipped with a Turbo Ion Spray source, operating in a positive mode: LEV at transition 171.1>154.1, UCB L057 at 172.5>126.1, and IS at 256.3>167.3; with an assay run time of 2 minutes. The lower limit of quantification (LLOQ for both LEV and UCB L057 was validated at 0.5 µg/mL, while their lower limit of detection (LOD was 0.25 µg/mL. The calibration curves were linear between 0.5 and 100 µg/mL for both analytes. The inaccuracy and imprecision of both intra-assay and inter-assay were less than 10%. Matrix effects were consistent between sources of plasma and the recoveries of all compounds were between 100% and 110%. Stability was established under various storage and processing conditions. The carryovers from both LEV and UCB L057 were less than 6% of the LLOQ and 0.13% of the IS. This assay method has been successfully applied to a population pharmacokinetic study of LEV in patients with epilepsy.

  20. Rapid and simultaneous quantification of levetiracetam and its carboxylic metabolite in human plasma by liquid chromatography tandem mass spectrometry.

    Yeap, Li-Ling; Lo, Yoke-Lin


    A simple liquid chromatography tandem mass spectrometry method was developed and validated according to the guidelines of the US Food and Drug Administration and the European Medicines Agency for a simultaneous quantification of levetiracetam (LEV) and its metabolite, UCB L057 in the plasma of patients. A 0.050 mL plasma sample was prepared by a simple and direct protein precipitation with 0.450 mL acetonitrile (ACN) containing 1 µg/mL of internal standard (IS, diphenhydramine), then vortex mixed and centrifuged. A 0.100 mL of the clear supernatant was diluted with 0.400 mL water and well mixed. A 0.010 mL of the resultant solution was injected into an Agilent Zorbax SB-C18 (2.1 mm×100 mm, 3.5 µm) column with an isocratic elution at 0.5 mL/min using a mixture of 0.1% formic acid in water and ACN (40:60 v/v). Detection was performed using an AB Sciex API 3000 triple quadrupole mass spectrometer, equipped with a Turbo Ion Spray source, operating in a positive mode: LEV at transition 171.1>154.1, UCB L057 at 172.5>126.1, and IS at 256.3>167.3; with an assay run time of 2 minutes. The lower limit of quantification (LLOQ) for both LEV and UCB L057 was validated at 0.5 µg/mL, while their lower limit of detection (LOD) was 0.25 µg/mL. The calibration curves were linear between 0.5 and 100 µg/mL for both analytes. The inaccuracy and imprecision of both intra-assay and inter-assay were less than 10%. Matrix effects were consistent between sources of plasma and the recoveries of all compounds were between 100% and 110%. Stability was established under various storage and processing conditions. The carryovers from both LEV and UCB L057 were less than 6% of the LLOQ and 0.13% of the IS. This assay method has been successfully applied to a population pharmacokinetic study of LEV in patients with epilepsy.

  1. Characteristics of Suicides Caused by Drug Overdose in the State of Maryland

    Ling Li


    Full Text Available Suicidal drug overdose is a major public health issue. In the United States, every year more than 33,000 people commit suicides. Our study focused on the characteristics of suicide victims in the state of Maryland. Material and methods: This study was a retrospective review of autopsy cases of all suicide deaths caused by drug (s or drug (s with alcohol intoxication investigated by the OCME in Maryland over a 7-year period from January 2004 to December 2011. All deaths investigated by the OCME that require autopsy examination are subject to comprehensive toxicology testing for drugs and alcohol. The screen tests were performed using gas chromatography (GC and radioimmunoassay techniques. All detected drugs and/or metabolites were confirmed using GC-mass spectrometry (GC-MS. Results: From 2004 to 2011, 434 deaths were certified as suicide. Of the 434 suicidal overdose deaths, 84% were white, 11% were African-American, and about 5% were either Hispanic or Asian. The male and female ratio was almost equal. Their ages ranged 15-82 years. Of the 434 suicidal drug overdose deaths, 277 victims (63.8% consumed a single drug type and 157 (36.2% consumed more than one type of drug. Of the 277 single-drug overdose cases, 71.1% suicides were due to prescription drugs, 23.5% due to over-the-counter drugs, and 5.4% due to street/recreational drugs. Among single-type prescription drugs, analgesic (N = 76, antidepressant (N = 45, and neuroleptic (N = 35 classes were the three leading type of drugs used in suicidal deaths. Oxycodone, morphine, quetiapine, and amitriptyline were the most common prescription drugs in suicidal overdose. Diphenhydramine was the leading over-the-counter drug. Of the 157 victims who consumed more than one drug, combined prescription drugs were present in 54.1%, mixed prescription and over-the-counter drugs in 29.3%, and prescription drugs/over-the-counter drugs and street drugs in 16.6% of cases. Of the multiple-drug overdose suicides

  2. Contribution of in utero drug exposure when interpreting hair results in young children.

    Kintz, P


    Hair specimen is necessary to complement blood and/or urine analyses as it permits differentiation of a single exposure from chronic use of a drug by segmentation of the hair for a stated growth period. Moreover, due to a frequent long delay between event and police declaration, hair can be the only solution for lack of corroborative evidence of a committed crime. With the exception of lower amount of biological material in children versus adults, there is no specific analytical problem when processing samples from children. The issue is the interpretation of the findings, with respect to the different pharmacological parameters. In some very young children, the interpretation can be complicated by potential in utero exposure. Twenty-four cases from daily practice have been reviewed. Children were less than 1 year old, hair was always longer than 4 cm and the corresponding mothers admitted having used drugs during pregnancy. Drugs involved include methadone, tramadol, diphenhydramine, diazepam, cannabis, heroin, amitriptyline and bromazepam. Analyses were achieved by hyphenated chromatographic validated procedures after hair decontamination and segmentation. The concentrations measured in the hair of children were lower than those observed in subjects using therapeutically (or illegally) these drugs. In that sense, the frequency of exposures appears as un-frequent (low level of exposure), with marked decrease in the more recent period. However, the parents denied any administration in all cases and there was no reason to suspect re-exposure after delivery and no clinical problem during the period between delivery and hair collection during regular visits to the physician was noticed. The pattern of drug distribution was similar in all these cases, low concentrations in the proximal segments and highest concentration in the distal segment (last segment). When considering the concentration in the distal segment as the 100% of the response (highest concentration

  3. Urticaria induced by ropivacaine mesylate%甲磺酸罗哌卡因致荨麻疹

    闫诺; 杨程; 高艺凡


    1例42岁女性患者行右侧甲状腺次全切除术,术前心率80次/min,血压130/80 mm Hg (1 mm Hg=0.133 kPa).采用利罗合剂(2%利多卡因10 ml+0.894%甲磺酸罗哌卡因10 ml)行双侧颈神经丛阻滞麻醉.10 min后患者胸部出现荨麻疹,心率110次/min,血压155/110 mm Hg,随后腹部与下肢均出现荨麻疹,心率125次/min,血压160/100 mm Hg.即刻给予吸氧,静脉注射地塞米松10 mg,5 min后荨麻疹有所减退.又肌内注射苯海拉明20 mg,5 min后心率95次/min,血压140/90 mm Hg,荨麻疹完全消失.%An 42-year-old woman underwent right subtotal thyroidectomy. Preoperatively, her heart rate ( HT ) was 80 beats/min and blood pressure ( BP ) was 130/80 mm Hg. Bilateral cervical plexus block was performed with mixture of lidocaine and ropivacaine ( 2% lidocaine 10 ml +0. 894% ropivacaine mesylate 10 ml ). Ten minutes later, the patient developed urticaria on her chest, her HR was 110 beats/min and BP 150/110 mm Hg. Subsequently, the urticaria was appeared in abdomen and legs. Her HR was 125 beats/min and BP 160/100 mm Hg. Oxygen and IV dexamethasone 10 mg were given immediately. Five minutes later, her urticaria receded gradually. And IM diphenhydramine 20 mg was given. Five minutes later, her HR was 95 beats/min, BP was 140/90 mm Hg, and the urticaria disappeared completely.

  4. Effect of Sophora Alopecuroides on Contraction of Isolated Cholecyst Smooth Muscle Strips inGuinea Pigs in Vitro%苦豆子总碱对豚鼠离体胆囊平滑肌条收缩功能的影响

    苏丽梅; 戴贵东; 丁娟; 聂黎虹; 周旭


    alopecuroides groups,verapamil + sophora alopecuroides groups, diphenhydramine + sophora alopecuroides groups, indomethacin + sophora alopecuroides groups, Hexamethonium + sophora alopecuroides groups, with 12 strips in each group.Musclar strips in the above groups were treated with atropine 10-6mmol · L-1, phenolaminel0-6mmol · L-1 ,verapamill0 -7 mmol· L- 1, diphenhydramine 10 -6 mmol · L- 1, indomethacinl0 -6 mmol · L-1, hexamethoniuml0 -5 mmol· L-1 respectively and Sophora alopecuroides at above concentration was added 2 minutes later.Signals were output with FI- 100 biological tension sensor; tension of samples,average amplitude of systolic wave and changes of systolic frequency were recorded with BL - 420E + biological function experimental system. Results The tension of gallbladder smooth muscle strips was significantly increased in sophora alopecuroide ( 1.10 × 10-4 and 1.10 × 10 -3 mmol· L-1 ) group(P <0.01 ); Verapamil( 10 -7 mmol · L-1 ) could significantly reduce the effect of contraction tention of the sophora alopecuroide ( 1.10 × 10-4 and 1.10 × 10-3 mmol · L-1) on cholecyst smooth muscle strips of guinea pig( P <0.01 ). Conclusion Sophora alopecuroides can increase the tension of gallbladder muscle strips. Effect and mechanism of sophora alopecuroides on the gallbladder muscle strips may be related to Ca2+ channel.

  5. Simultaneous determination of caffeine and chlorpheniramine in human plasma by LC-MS/MS%LC-MS/MS法同时测定人血浆中的咖啡因和氯苯那敏

    赵婷; 张丹; 杨漫; 张娅喃; 韩静; 肖雪; 刘会臣


    OBJECTIVE To develop a method for simultaneous determination of caffeine and chlorpheniramine in human plasma by LC - MS/MS. METHODS After liquid - liquid extraction, caffeine, chlorpheniramine and diphenhydramine ( IS) were separated on an Inertsil ODS - SP analytical column using the mobile phase of methanol - 5 mmol · L-1 ammonium acetate ( containing 0.5% formic acid) (55 : 45) at a flow rate of 0. 3 mL·min-1. Detection was carried out by electrospray positive ionization mass spectrometry in the multiple reaction monitoring(MRM) mode. The MRM transitions of m/z 195.3→110.2, m/z 275. 2→230.2, m/z 256.2→167.3 were used to quantify caffeine, chlorpheniramine and IS, respectively. RESULTS The method was linear ( r > 0. 999 ) in the concentration ranges of 4.0 - 1. 2 × 103,0. 05 - 15. 0 μg·L-1 for caffeine and chlorpheniramine,respectively. Intra - batch and inter- batch RSD were both less than 13% ,and the RE were within ±5% . The mean extract recoveries were 67. 6% ±1.3% ,69.1% ±3.4% for caffeine and chlorpheniramine, respectively. CONCLUSION The method is a rapid, sensitive, selective and reliable method for the determination of caffeine and chlorpheniramine in human plasma. It was successfully applied to a bioequivalence study of the two analyses in healthy Chinese volunteers after administration of pediatric paracetamol and amantadine hydrochloride effervescent tablets.%目的 采用LC-MS/MS法同时测定人血浆中咖啡因和氯苯那敏的浓度.方法 人血浆样本经液液萃取后,选用Inertsil ODS-SP色谱柱(75 mm×2.1 mm,3μm),流动相为甲醇-5 mmol·L-1乙酸铵(含0.5%甲酸)(55∶45),流速0.3 mL·min-1,选用API3200型三重四极杆串联质谱仪的多重反应监测(MRM)扫描方式进行监测,电喷雾离子化源,正离子方式,选择监测离子反应分别为m/z 195.3→110.2(咖啡因)、m/z 275.2→230.2(氯苯那敏)和m/z256.2→167.3(苯海拉明内标).结果 血浆中咖啡因和氯苯那

  6. Effect of Total Organic Acid of Thladiantha dubia on Active Capacity of Isolated Rat Uterine Smooth Muscle in vitro%赤雹果总有机酸对大鼠离体子宫平滑肌的作用及机制研究

    赵盼; 佟继铭; 刘玉玲; 宋素英


    Objective: To explore the effects of the total organic acid of Thladiantha dubia (FTDBP) on activity of isolated rat uterus smooth muscle in vitro. Method: The effect of the FTDBP on activity of the isolated rat uterus smooth muscle of non-pregnant rats eight weeks old was recorded by Maclab/4e four channels physiological recorder. Four antagonists, propranolol hydrochloride tablets (3.4 × 10-7 mol · L-1 ), diphenhydramine hydrochloride tablets (2 × 10 mol ·L-1 ) , ranitidine hydrochloride tablets (2 × 10 mol · L-1 ) and atropine sulfate tablets (2 × 10 mol·L-1 ) were used to study their mechanism respectively. Result: Compare with model group, the FTDBP markedly inhibited the tension, frequency and activity of uterus of rat in vitro. And the IC50 of FTDBP was 0. 100 24 g·L-1. Conclusion: The effect of FTDBP on activity of uterine smooth muscle in rats is mainly associated with M receptor but not H1 receptor, H2 receptor or β receptor.%目的:观察赤雹果总有机酸(FTDBP)对大鼠离体子宫平滑肌活力的影响.方法:选用8周龄Wistar雌性未孕大鼠,以子宫平滑肌的收缩频率、收缩幅度指标,计算子宫平滑肌活力及FTDBP的半数抑制浓度(IC50).以盐酸普萘洛尔、盐酸苯海拉明、盐酸雷尼替丁、硫酸阿托品为阻断剂,观察FTDBP对子宫平滑肌作用与β,H1,H2,M受体的关系,探讨FTDBP对子宫平滑肌的作用机制.结果:与模型组比较,FTDBP剂量组(0.032,0.064,0.128 g·L-1)和元胡止痛片组对缩宫素所致大鼠离体子宫平滑肌的收缩频率、收缩幅度和活力均有明显的抑制作用(P<0.05或P<0.01),IC50为0.100 24 g·L-1;与模型组比较,硫酸阿托品组大鼠子宫平滑肌的收缩频率、幅度和活力差异无统计学意义.结论:FTDBP对大鼠子宫平滑肌活力有明显的抑制作用,其作用是通过抑制M受体实现的,与H1,H2,β受体无关.

  7. 2013 Survey of Iowa groundwater and evaluation of public well vulnerability classifications for contaminants of emerging concern

    Hruby, Claire E.; Libra, Robert D.; Fields, Chad L.; Kolpin, Dana W.; Hubbard, Laura E.; Borchardt, Mark R.; Spencer, Susan K.; Wichman, Michael D.; Hall, Nancy; Schueller, Michael D.; Furlong, Edward T.; Weyer, Peter J.


    g/L. Pharmaceutical compounds were detected in 35% of 63 samples. Of the 14 pharmaceuticals detected, six had reported concentrations above the method reporting limit, with the maximum reported concentration of 826 ng/L for acetaminophen. Diphenhydramine was the only pharmaceutical to have two detections above the reporting limit, at 24.5 and 145 ng/L. Eight pharmaceuticals had confirmed detections at concentrations below the method reporting limit. Caffeine was the most frequently detected pharmaceutical compound (25%), followed by the caffeine metabolite, 1,7- dimethylxanthine (16%).  Microorganisms were detected in 21% of the wells using quantitative polymerase chain reaction methodologies. The most frequently detected microorganism was the pepper mild mottle virus (PMMV), a plant pathogen found in human waste. PMMV was detected in 17% of samples at concentrations ranging from 0.4 to 6.38 gene copies per liter. GII norovirus, human polyomavirus, bovine polyomavirus, and Campylobacter were also detected, while adenovirus, enterovirus, GI norovirus, swine hepatitis E, Salmonella, and enterohemmorhagic E. coli were not detected. No correlations were found between viruses or pathogenic bacteria and microbial indicators. Wells with less than 50 feet (15 meters) of confining material were shown to have greater incidence of surface-related contaminants; however, significant relationships (p<0.05) between confining layer thickness and contaminants were only found for nitrate and herbicides.

  8. One case of acute Alocasia macrorrhiza poisoning and management%急性海芋中毒救治1例

    谢立璟; 王英伟; 龙鑫; 孙承业


    A 44-year-old man took the tuber of Alocasia macronhiza by mistake. Several minutes after ingestion of the tuber, he presented with numbness of lip, sore throat, nausea, vomiting, salivation, dyspnea, and dysphonia. Twenty minutes after poisoning, he was hospitalized and diagnosed as having acute laryngeal edema. He received diphenhydramine 20 mg and dexamethasone 5 mg via IV push, followed by an IV infusion of dexaroethasone 10 mg. Meanwhile oxygen inhalation, liver protective treatment, and other symptomatic treatment were given. Five hours after poisoning, his symptoms gradually resolved and, 50 days later, he recovered. Alocasia macronhiza is a poisonous plant of Alocasia Sckott in the family Araceae, and it contains sapotoxin and calcium oxalate which can induce neurological and gastrointestinal disorder after ingestion of the plant. The latent period from exposure to onset of symptoms is 10 to 30 minutes and death might occur in patients with severe poisoning. Skin contact or eye contact with Alocasia macronhiza juice can cause pruritus, conjunctivitis, and even blindness. Inhalation of Alocasia macronhiza powder can lead to severe mucosal irritation in the eye, nasal cavity, and throat. Poisoning could be diagnosed by the history of contact with the plant and clinical manifestations. There is no specific antidote for Alocasia macronhiza poisoning and main management is symptomatic treatment.%1例44岁男性误食海芋块根,数分钟后出现口唇麻木、咽喉疼痛、恶心、呕吐、流涎、呼吸困难、发音困难等症状,中毒后20 min入院,诊断为急性喉头水肿.给予静脉推注苯海拉明20 mg、地塞米松5mg和静脉滴注地塞米松10 ng等处理,并行吸氧、保肝等对症治疗.中毒5h后症状逐渐好转,50 d后痊愈.海芋是天南星科海芋属有毒植物,含有皂素毒苷及草酸钙等.口服后可致神经和胃肠系统症状,潜伏期一般为10~30 min,严重者可致死亡;皮肤或者眼接触海芋汁

  9. Cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución Quantification of glibenclamide in cleaning samples of pharmaceutical equipment through high performance liquid chromatography

    Alen Nils Baeza Fonte


    ; with 0.037 mol/L concentration pH 5.25 and flow of 1.5 mL/min, in a Nucleosil 100 C8 column. Glibenclamide was injected with progesterone as internal standard and using an UV detector= 230 nm Results: the method was linear in the 0.4-150 mg/mL concentration interval having a detection and quantization limits of 10 and 40 ng/mL respectively. It was specific to analyte when placebo is present, to degradation products and to other active ingredients. Possible interferences with the proposed method was considered for captopril, chlortalidone, dexametasone, diphenhydramin HCl, digoxine, 8-chlortheophylline, diphenhydramina HCl, phenobarbital, haloperidol, hydrochlorothiazide, fumaric acid, ketotifen, metoclopramide HCl, piridoxine HCl, piroxicam, prednisone and nifedipine, On the other hand, ibuprofen, indometacin, trifluoperazine HCl, thioridazine HCl and imipramine were identified as interferences in the procedure at concentration figures close to 10 mg/mL. Conclusions: the present method is sensitive, quick and selective for the evaluation of residues of active pharmaceutical principle glibenclamide in tablet production equipment after a swap sampling and it could be potentially used in case of cross-contamination of glibenclamide and other drugs already described.

  10. Determination of Nine Anti-allergy Drugs Residue in Cosmetics by Solid Phase Extraction-Rapid Resolution Liquid Chromatography-Tandem Mass Spectrometry%固相萃取-超快速液相色谱-串联质谱法同时测定化妆品中9种抗过敏药物残留

    王燕芹; 车文军; 王莉; 徐春祥; 卢剑


    建立了固相萃取-超快速液相色谱-串联质谱法(SPE-RRLC-MS/MS)同时测定化妆品中9种抗过敏药物残留(多西拉敏、美沙吡林、曲吡那敏、溴苯那敏、苯海拉明、赛克利嗪、二苯拉林、羟嗪和氯苯沙明)的方法.试样经三氯乙酸溶液超声提取、离心、Plexa PCX柱净化后,以甲醇-0.1%甲酸溶液(含5 mmol/L甲酸铵)为流动相,用RRLC进行分离.在电喷雾正离子模式下,以选择反应监测(SRM)方式采集数据进行定性与定量分析.9种药物在1.0 ~ 50.0 μg/L范围内均呈良好的线性关系,相关系数均大于0.99;在2.0,5.0和20.0 μg/kg 3个浓度加标水平下的平均回收率为90.6%~103.5%;相对标准偏差(RSD,n=6)为2.5%~6.0%;检出限为0.3~0.6 μg/kg,定量限为1.0~2.0 μg/kg.%A solid phase extraction coupled with rapid resolution liquid chromatography-tandem mass spectrometry ( SPE-RRLC-MS/MS) method was developed for the determination of nine anti-allergy drugs, e.g. doxylamine, tripelennamine, brompheniramine, diphenhydramine, chlorphenoxamine, diphenylpyraline, methapyrilene, cyclizine, and hydroxyzine in cosmetics. The samples were extracted with trichloroacetic acid solution under ultrasonication, centrifuged and cleaned up with Plexa PCX solid phase extraction. The separation of nine anti-allergy drugs was carried out on RRLC using methanol-phosphate buffer as mobile phase. Electrospray ionization mass spectrometry was operated in the positive mode using selective reaction monitoring ( SRM) for the qualitative and quantitative analysis of nine anti-allergy drugs. For the nine drugs, the calibration curves were linear between 1.0 to 50.0 μg/L, and the correlation coefficient was more than 0. 99. The mean recoveries at spiked levels of 2. 0, 5.0, 20. 0 μg/kg were in the range of 90. 6% -103.5% , the RSDs were 2.5%-6.0% (n = 6). The limits of detection and quantification were 0. 3-0.6 μg/kg and 1.0-2.0 μg/kg, respectively.

  11. Rococo study: a real-world evaluation of an over-the-counter medicine in acute cough (a multicentre, randomised, controlled study)

    Birring, S S; Brew, J; Kilbourn, A; Edwards, V; Wilson, R; Morice, A H


    Objectives To investigate the efficacy and safety of CS1002, an over-the-counter cough treatment containing diphenhydramine, ammonium chloride and levomenthol in a cocoa-based demulcent. Design A multicentre, randomised, parallel group, controlled, single-blinded study in participants with acute upper respiratory tract infection-associated cough. Setting 4 general practitioner (GP) surgeries and 14 pharmacies in the UK. Participants Participants aged ≥18 years who self-referred to a GP or pharmacist with acute cough of <7 days' duration. Participant inclusion criterion was cough severity ≥60 mm on a 0–100 mm visual analogue scale (VAS). Exclusion criteria included current smokers or history of smoking within the past 12 months (including e-cigarettes). 163 participants were randomised to the study (mean participant age 38 years, 57% females). Interventions Participants were randomised to CS1002 (Unicough) or simple linctus (SL), a widely used cough treatment, and treatment duration was 7 days or until resolution of cough. Main outcome measures The primary analysis was intention-to-treat (157 participants) and comprised cough severity assessed using a VAS after 3 days' treatment (prespecified primary end point at day 4). Cough frequency, sleep disruption, health status (Leicester Cough Questionnaire (LCQ-acute)) and cough resolution were also assessed. Results At day 4 (primary end point), the adjusted mean difference (95% CI) in cough severity VAS between CS1002 and SL was −5.9 mm (−14.4 to 2.7), p=0.18. At the end of the study (day 7) the mean difference in cough severity VAS was −4.2 mm (−12.2 to 3.9), p=0.31. CS1002 was associated with a greater reduction in cough sleep disruption (mean difference −11.6 mm (−20.6 to 2.7), p=0.01) and cough frequency (mean difference −8.1 mm (−16.2 to 0.1), p=0.05) compared with SL. There was greater improvement in LCQ-acute quality of life scores with CS1002 compared with SL: mean

  12. 舒血宁注射液致过敏性休克和肝肾功能损伤%Anaphylactic shock,liver and kidney injury caused by Shuxuening injection(舒血宁注射液)

    朱建新; 马丽萍; 赵继红; 沈司京


    1例66岁男性冠状动脉粥样硬化性心脏病患者白内障术后给予舒血宁注射液18 ml加入0.9%氯化钠注射液250 ml,1次/ d 静脉滴注。第2次给药约30 min 时,患者突然出现寒战、全身疼痛、恶心和呕吐,体温40.2℃,心率110次/ min,血压95/56 mmHg(1 mmHg =0.133 kPa)。实验室检查:ALT 116 U/ L,AST 165 U/ L,TBil 17.8μmol/ L,DBil 9.6μmol/ L,BUN 7.6 mmol/ L,Scr 110μmol/ L。诊断:过敏性休克,肝损伤,肾损伤。立即停用舒血宁注射液,给予苯海拉明20 mg 肌内注射,地塞米松5 mg 静脉滴注,还原型谷胱甘肽1.2 g 静脉滴注、1次/ d,百令胶囊2 g 口服、3次/ d。2 d后,患者体温36.6℃,血压124/76 mmHg,心率69次/ min。次日复查 ALT 75 U/ L,AST 37 U/ L,TBil 8.4μmol/ L,DBil 3.0μmol/ L,BUN 4.8 mmol/ L,Scr 73μmol/ L。%A 66-year-old male patient with coronary atherosclerotic heart disease received an IV infusion of Shuxuening injection 18 ml + 0. 9% sodium chloride injection 250 ml once daily after cataract surgery. About 30 minutes after the second infusion start,the patient suddenly experienced chill,whole body pain,nausea and vomiting. His body temperature was 40. 2 ℃,heart rate was 110 beats/ min,blood pressure was 95 / 56 mmHg. Laboratory test revealed the following levels:alanine aminotransferase 116 U/ L, aspartate aminotransferase 165 U/ L,total bilirubin 17. 8 μmol/ L,direct bilirubin 9. 6 μmol/ L,urea nitrogen 7. 6 mmol/ L,and creatinine 110 μmol/ L. The patient was diagnosed as anaphylactic shock,liver and kidney injury. Shuxuening injection was stopped. He was treated with intramuscular injection of diphenhydramine 20 mg,IV infusions of dexamethasone 5 mg,IV infusion of glutathione 1. 2 g once daily, oral Bailing capsule(百令胶囊)2 g thrice daily. Two days later,his body temperature was 36. 6 ℃,the blood pressure was 124 / 76 mmHg,and the heart rate was 69 beats/ min. The following day

  13. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group.

    Peyrade, Frédéric; Bologna, Serge; Delwail, Vincent; Emile, Jean François; Pascal, Laurent; Fermé, Christophe; Schiano, Jean-Marc; Coiffier, Bertrand; Corront, Bernadette; Farhat, Hassan; Fruchart, Christophe; Ghesquieres, Herve; Macro, Margaret; Tilly, Hervé; Choufi, Bachra; Delarue, Richard; Fitoussi, Olivier; Gabarre, Jean; Haioun, Corinne; Jardin, Fabrice


    In 2011 we reported a rituximab plus miniCHOP (reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone) combination for patients older than 80 years with diffuse large B-cell lymphoma (DLBCL). The 2-year overall survival was 59% (95% CI 49-67) with an excess of early toxicity. To improve those results we tested the same chemotherapy protocol in combination with ofatumumab and a pre-phase treatment. For this open-label, multicentre, single-group, phase 2 trial, we recruited patients older than 80 years with untreated histologically-proven CD20-positive DLBCL, Ann Arbor stage I to IV, from 41 academic and hospital centres in France and Belgium. Patients received a pre-phase with oral vincristine (1 mg total dose 1 week before cycle 1 [day -7]) and oral prednisone (60 mg total dose starting 1 week before cycle 1, for 4 days [day -7 to day -4]) before the first cycle of the ofatumumab plus miniCHOP regimen. The regimen consisted of 1000 mg total dose of intravenous ofatumumab, 25 mg/m(2) of intravenous doxorubicin, 400 mg/m(2) of intravenous cyclophosphamide, and 1 mg of intravenous vincristine, on day 1 of each cycle; and 40 mg/m(2) of oral prednisone on days 1-5. Ofatumumab was administered with 1000 mg of paracetamol and 50 mg of diphenhydramine. The primary endpoint was overall survival in the intention-to-treat population. The statistical analysis has been done on an intention-to-treat principle. This study was registered with, number NCT01195714. Between June 2, 2010, and Nov 4, 2011, we enrolled 120 patients. Age-adjusted International Prognostic Index was 2-3 in 68 (57%) of them. The median follow-up time was 26·8 months (IQR 24·5-30·1). The 2-year overall survival was 64·7% (95% CI 55·3-72·7) and median overall survival was not reached (95% CI 30·2-not reached). 45 patients died during the treatment, of whom 28 (62%) died due to lymphoma. The most common side-effect was haematological toxicity. Among the 120 patients

  14. 野菊花水提液对豚鼠离体回肠收缩的影响及抑菌作用观察%Effects of Flos chrysanthemum indicum on the bacterial pathogens and the muscular tension of the isolated ileum of guinea pigs

    白银亮; 田新慧; 毕跃峰; 王盼; 张旗


    To investigate the antibacterial effects of water extract of Flos chrysanthemum indicum and its effects on muscular tension of the isolated ileum of guinea pigs. Methods: The isolated guinea pig ileum in the organ-bath was used to measure the contractive tension of smooth muscle before and after administration of drug. Double dilution method was used to observe the antibacterial effect of water extract of Flos chrysanthemum indicum. Results: Water extract of Flos chrysanthemum indicum inhibited dose-dependently the contraction of normal guinea pig ileum( F = 11. 088, P <0. 001 ) and that induced by acetyl choline and diphenhydramine( F = 13. 881 and 19. 305 ,P < 0. 001 ). It also had antibacterial effects on Escherichia coli ,Pseudomonas aeruginosa, Bacillus subtilis, and especially on Staphylococcus aureus with a lowest antibacterial dosage of 125 g/L. Conclusion: Water extract of Flos chrysanthemum indicum relaxes the smooth muscle of ileum of guinea pigs, and can effectively inhibit the growth of bacteria in vitro.%目的:观察野菊花水提液对豚鼠离体回肠收缩的影响及其抑菌作用.方法:将豚鼠离体回肠标本悬吊于麦氏浴槽中,测量并记录给药前后离体回肠张力,计算张力变化百分率.采用二倍体积连续稀释法考察野菊花水提液的抗菌效果.结果:野菊花水提液对豚鼠离体回肠收缩有明显的抑制作用(F=11.088,P<0.001),并剂量依赖性地抑制乙酰胆碱及组胺引起的豚鼠回肠收缩(F=13.881、19.305,P均<0.001).野菊花水提液对金黄色葡萄球菌、大肠杆菌、绿脓假单胞菌和枯草芽孢菌均具有相对较好的抑菌效果,其中对金黄色葡萄球菌的抑菌效果最好,最小抑菌质量浓度为125 g/L.结论:野菊花水提液对豚鼠离体回肠具有直接的舒张作用,能够拮抗乙酰胆碱及组胺引起的豚鼠回肠收缩,同时具有体外抑菌作用.

  15. Occurrence of pharmaceuticals, hormones, and organic wastewater compounds in Pennsylvania waters, 2006-09

    Reif, Andrew G.; Crawford, J. Kent; Loper, Connie A.; Proctor, Arianne; Manning, Rhonda; Titler, Robert


    , caffeine, carbamazepine, and the four antibiotics tylosin, sulfadimethoxine, sulfamethoxazole, and oxytetracycline were detected in streamwater samples collected in 2006 from six paired stream sampling sites located upstream and downstream from animal-feeding operations. The highest reported concentration of these seven compounds was for the antibiotic sulfamethoxazole (157 ng/L), in a sample from the downstream site on Snitz Creek in Lancaster County, Pa. Twenty-one pharmaceutical compounds were detected in streamwater samples collected in 2006 from five paired stream sampling sites located upstream or downstream from a municipal wastewater-effluent-discharge site. The most commonly detected compounds and maximum concentrations were the anticonvulsant carbamazepine, 276 ng/L; the antihistamine diphenhydramine, 135 ng/L; and the antibiotics ofloxacin, 329 ng/L; sulfamethoxazole, 1,340 ng/L; and trimethoprim, 256 ng/L. A total of 51 different contaminants of emerging concern were detected in streamwater samples collected from 2007 through 2009 at 13 stream sampling sites located downstream from a wastewater-effluent-discharge site. The concentrations and numbers of compounds detected were higher in stream sites downstream from a wastewater-effluent-discharge site than in stream sites upstream from a wastewater-effluent-discharge site. This finding indicates that wastewater-effluent discharges are a source of contaminants of emerging concern; these contaminants were present more frequently in the streambed-sediment samples than in streamwater samples. Antibiotic compounds were often present in both the streamwater and streambed-sediment samples, but many OWCs were present exclusively in the streambed-sediment samples. Compounds with endocrine disrupting potential including detergent metabolites, pesticides, and flame retardants, were present in the streamwater and streambed-sediment samples. Killinger Creek, a stream where wastewater-effluent discharges contribute a large

  16. 麻黄-杏仁药对有效成分在大鼠体内组织分布的定量分析%Quantitative Analysis of Tissue Distribution of Bioactive Compounds in Rats After Oral Administration of Ephedrae Herba-Amygdalus Communis Vas Extract

    宋帅; 梁德东; 任孟月; 侯玮婷; 罗佳波


    Objective:To develop a simple UPLC-MS/MS method for simultaneous determination of norephedrine,norpseudoephedrine,ephedrine,pseudoephedrine,methylephedrine,amygdalin and prunasin in rat tissues and to analysis tissue distribution of these compounds in rats after oral administration of Ephedrae HerbaAmygdalus Communis Vas extract.Method:The current method was validated according to the FDA guidelines for the validation of biological sample analysis method.Diphenhydramine hydrochloride and puerarin were selected for quantitative analysis of alkaloids in Ephedrae Herba,amygdalin and prunasin,respectively.Result:Nine active compounds,including 3 pairs of epimers,were separated and quantified within 18 min by a sensitive and reliable UPLC-MS/MS method.Alkaloids in Ephedrae Herba were widely distributed in major tissues.Poor tissue distribution of amygdalin was observed,and prunasin (metabolite of amygdalin) can be detected in tissues except the brain.Contrary to D-amygdalin in vivo,D-prunasin had lower concentration (its concentrations in heart,liver,spleen,lung,kidney were 170.5,112.8,98.4,152.3,381.7 ng·g-1) in tissues by comparing with L-prunasin (its concentrations in heart,liver,spleen,lung,kidney were 906.4,652.3,177.4,500.9,2 060.4 ng· g-1).Conclusion:The method is successfully applied to tissue distribution study in rats after intragastric administration of Ephedrae Herba-Amygdalus Communis Vas extract.Reduction of D-prunasin in tissues may be the reason of toxicity antagonism in vivo.High concentration of alkaloids in Ephedrae Herba,amygdalin and prunasin are found in lung,which may be correlated with its synergistic anti-asthmatic effects.%目的:建立并验证同时测定大鼠组织中去甲基麻黄碱、去甲基伪麻黄碱、麻黄碱、伪麻黄碱、甲基麻黄碱、苦杏仁苷和野樱苷的UPLC-MS/MS,分析大鼠口服麻黄-杏仁药对水提物后有效成分在主要脏器组织中的分布情况.方法:参照FDA生物样本分析方法的

  17. LC-MS/MS法测定氨氯地平血药浓度及其片剂的生物等效性研究%Determination of Amlodipine Concentration in Human Plasma by LC-MS/MS Method and Bioequivalence Study of Its Tablets

    张丽娜; 刘曼; 杨漫; 杜爱华; 张娅喃; 张丹; 韩静; 王晓琳; 刘会臣


    OBJECTIVE: To develop method for the determination of amlodipine in human plasma, and to evaluate bioequivalence of 2 kinds of Amlodipine besylate tables in healthy volunteers. METHODS: After liquid-liquid extraction, the samples were separated on Zorbax SB-C18 Narrow Bore column with mobile phase consisted of methanol-10 mmol/L ammonium acetate (90:10, V/V) at the flow rate of 0.3 ml/min. Detection was carried out by electrospray positive ionization mass spectrometry in type API3200 multiple reaction monitoring (MRM) mode. The MRM transitions of mlz 409.2→-m/z 238.2 and mlz 256.2→m/z 167.3 were used to quantify amlodipine and diphenhydramine (I.S.), respectively. The bioequivalence of test preparation and reference preparation of Amlodipine besylate tablets in 24 healthy volunteers after oral administration were investigated in a randomized, two-periods cross-over study. RESULTS: Amlodipine and I.S. were eluted at 2.79 min and 2.43 min, respectively. The linear range of amlodipine were 0.10-10.0 ng/ml (r=0.999 7) with the lowest quantitation limit of 0.10 ng/ml. Intra-day and inter-day RSDs were both less than 15% ; relative errors (RE) were within ± 15%. The mean extraction recovery was (84.7 ± 5.5)% , and the mean matrix effect factor was (76.5±8.4)%. The relative bioavailability of test preparation to reference preparation was (105.8±20.9)% according to AUC0-120 h. CONCLUSIONS: The method is rapid, sensitive, selective and reproducible, and it is suitable for the determination of amlodipine in human plasma and bioequivalence study of Amlodipine besylate tablets in healthy volunteers.Two preparations are bioequivalent.%目的:建立测定人血浆中氨氯地平血药浓度的方法,并评价2种苯磺酸氨氯地平片的生物等效性.方法:人血浆样本经液-液萃取后,选用Zorbax SB-C18Narrow Bore色谱柱,以甲醇-10 mmol/L乙酸铵(90:10,V/V)为流动相,流速为0.3 ml/min,选用API3200型三重四极杆串联质谱仪的多重反应监

  18. A LC-MS/MS method for determination of ropinirole in healthy volunteers and application to pharmacokinetics study of ropinirole and it combined with levodopa and benserazide tablets%LC-MS/MS法测定人血浆中罗匹尼罗及联合多巴丝肼片后的药动学

    丁莉坤; 杨林; 王茂湖; 贾艳艳; 冯智军; 宋薇; 杨静; 文爱东


    AIM To establish a LC -MS/ MS method for the determination of ropinirole in human plasma and to evaluate its pharmacokinetics after combining with levodopa and benserazide tablets in healthy volunteers.METHODS Twelve healthy male volunteers were divided into two groups in a randomized two-way crossover design with one week washout period. A 1 mg dose of ropinirole hydrochloride dispersible tablet or ropinirole hydrochloride dispersible tablet with levodopa and benserazide tablets (250 mg) was given to volunteers. The plasma concentration of the drug was assayed by LC -MS/MS. Chromatographic separation was carried on an Spursil C18 column (150 mm × 2.1 mm, 5 μm), with a mobile phase consisting of acetonitrile-10 mmol·L-1 ammonium acetate-formic acid (50 : 50 : 0.1, V/V/V). Detection and quantification were performed by mass spectrometry in the multiple reaction monitoring mode with positive electrospray ionization at m/z 261→m/z 160 for ropinirole, and m/z 256→ m/z 167 for diphenhydramine (internal standard) , respectively. The main pharmacokinetic parameters were evaluated by DAS2.0.1 software. RESULTS The LLOQ of the method for ropinirole in plasma was 10.0 pg·mL-1 and the calibration curve was linear over the range of 10.0 - 5 000 pg· mL-1. The intra-and inter-run standard deviation was less than 15%. The major pharmacokinetic parameters were as follows: tmax(1.40 ± 0.53) h and (1.23 ± 0.49) h,ρmax (1 559 ± 508) pg·mL-1 and (1 629 ± 494) pg· mL-1, t1/2 (6.67 ± 1.13) h and (6.57 ± 1.11) h, AUC0-36h (10.8 ± 3.1) ng·h·mL-1 and (12.6 ± 3.1) ng·h· mL-1, respectively. CONCLUSION The method is reliable for pharmacokinetic study of ropinirole in human. The tmax and ρmax of ropinirole have no significant difference, but AUC is increased by approximately 16.7% after combining with levodopa and benserazide tablets.%目的 建立人血浆中罗匹尼罗浓度的LC-MS/MS分析方法,并应用于罗匹尼罗及联合多巴丝肼