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

Science.gov (United States)

Fathead minnows were exposed to diphenhydramine (DPH), a weakly basic pharmaceutical (pKa = 9.1), to examine pH effects on uptake and accumulation. Fish were exposed to 10 ìg/L DPH in water for up to 96 h at three nominal pH levels: 6.7, 7.7, and 8.7. In each case, an appa...

Carboxylic acid functionalization of halloysite nanotubes for sustained release of diphenhydramine hydrochloride

Energy Technology Data Exchange (ETDEWEB)

Zargarian, S. Sh.; Haddadi-Asl, V., E-mail: haddadi@aut.ac.ir; Hematpour, H. [Amirkabir University of Technology, Department of Polymer Engineering and Color Technology (Iran, Islamic Republic of)

2015-05-15

Halloysite nanotubes (HNT) (cylindrical shape with external diameter and length in the range of 30–80 nm and 0.2–1 µm, respectively) were functionalized with 3-aminopropyltriethoxysilane (APTES) from hydroxyl groups by a coupling reaction. Subsequently, maleic anhydride was attached to the APTES moieties to yield carboxylic acid-functionalized HNT. Loading and subsequent release of a model drug molecule diphenhydramine hydrochloride (DPH) on modified and unmodified nanotubes were investigated. Morphology of HNT was studied by electron microscopy. Successful attachment of APTES and carboxylic acid groups to halloysite and drug loading were evaluated by Fourier transform infrared spectroscopy. The amount of surface modification and drug adsorption capacity were calculated via thermogravimetric analysis. The ordered crystal structure of loaded drug was evaluated by X-ray diffraction. UV–Visible spectrophotometer was used to study drug release from modified and unmodified samples. Carboxylated halloysite exhibits higher loading capacity and prolonged release of DPH as compared to that of the natural halloysite.

Carboxylic acid functionalization of halloysite nanotubes for sustained release of diphenhydramine hydrochloride

International Nuclear Information System (INIS)

Zargarian, S. Sh.; Haddadi-Asl, V.; Hematpour, H.

2015-01-01

Halloysite nanotubes (HNT) (cylindrical shape with external diameter and length in the range of 30–80 nm and 0.2–1 µm, respectively) were functionalized with 3-aminopropyltriethoxysilane (APTES) from hydroxyl groups by a coupling reaction. Subsequently, maleic anhydride was attached to the APTES moieties to yield carboxylic acid-functionalized HNT. Loading and subsequent release of a model drug molecule diphenhydramine hydrochloride (DPH) on modified and unmodified nanotubes were investigated. Morphology of HNT was studied by electron microscopy. Successful attachment of APTES and carboxylic acid groups to halloysite and drug loading were evaluated by Fourier transform infrared spectroscopy. The amount of surface modification and drug adsorption capacity were calculated via thermogravimetric analysis. The ordered crystal structure of loaded drug was evaluated by X-ray diffraction. UV–Visible spectrophotometer was used to study drug release from modified and unmodified samples. Carboxylated halloysite exhibits higher loading capacity and prolonged release of DPH as compared to that of the natural halloysite

Expedited Development of Diphenhydramine Orally Disintegrating Tablet through Integrated Crystal and Particle Engineering.

Science.gov (United States)

Wang, Chenguang; Hu, Shenye; Sun, Changquan Calvin

2017-10-02

A palatable direct compression (DC) orally disintegrating tablet (ODT) product of a bitter drug, diphenhydramine (DPH), was developed using an integrated crystal and particle engineering approach. A DPH salt with a sweetener, acesulfame (Acs), DPH-Acs, was synthesized and its solid state properties were comprehensively characterized. Tablet formulation composition and compaction parameters were optimized by employing material sparing techniques. In vivo disintegration time, bitterness, and grittiness of the final ODT product, were evaluated by a taste panel. Physical stability of the ODT tablets was assessed to identify appropriate storage conditions. Phase-pure DPH-Acs exhibited significantly better tabletability and palatability than DPH-HCl. A DC formulation was designed and optimized to obtain a new ODT product with good manufacturability and excellent product characteristics, including fast in vivo disintegration, and acceptable bitterness and grittiness. A new ODT product of DPH with excellent pharmaceutical properties was successfully developed using 15 g of DPH and in two months. This example shows that integrated crystal and particle engineering is an effective approach for developing high quality ODT products using the DC process.

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

International Nuclear Information System (INIS)

Barker, G.; Loftus, L.; Cuddy, P.; Barker, B.

1991-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1991-03-01

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.

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

International Nuclear Information System (INIS)

Kristofco, Lauren A.; Cruz, Luis Colon; Haddad, Samuel P.; Behra, Martine L.; Chambliss, C. Kevin; Brooks, Bryan W.

2016-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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: Bryan_Brooks@baylor.edu [Department of Environmental Science, Center for Reservoir and Aquatic Systems Research, Baylor University, Waco, TX (United States)

2016-01-15

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

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

Science.gov (United States)

Kristofco, Lauren A.; Cruz, Luis Colon; Haddad, Samuel P.; Behra, Martine L; Chambliss, C. Kevin; Brooks, Bryan W.

2016-01-01

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 environmentally realistic lowest observed effect concentration of 200 ng/L. Though ELS and FET studies with zebrafish typically focus on mortality or teratogenicity in 0–4 dpf organisms, behavioral responses of slightly older fish were several orders of magnitude more sensitive to DPH. Our observations highlight the importance of understanding the influence of time of day on intrinsic locomotor activity, and the age-specific hazards of aquatic contaminants to fish behavior. PMID:26431593

A High-Performance Thin Layer Chromatography (HPTLC) Method for Simultaneous Determination of Diphenhydramine Hydrochloride and Naproxen Sodium in Tablets.

Science.gov (United States)

Bhole, R P; Shinde, S S; Chitlange, S S; Wankhede, S B

2015-01-01

A rapid and simple high-performance thin layer chromatography (HPTLC) method with densitometry at 230 nm was developed and validated for simultaneous determination of diphenhydramine hydrochloride (DPH) and naproxen sodium (NPS) from pharmaceutical preparation. The separation was carried out on aluminum plates precoated with silica gel 60 F254 using mobile phase toluene:methanol:glacial acetic acid (7.5:1:0.2, v/v/v). The linearity range lies between 200 and 1200 ng/band for DPH and 1760 and 10,560 ng/band for NPS with correlation coefficients of 0.994 and 0.995, respectively. The R f value for DPH is 0.20 ± 0.05 and for NPS is 0.61 ± 0.06. % Recoveries of DPH and NPS was in the range of 99.70%-99.95% and 99.63%-99.95%, respectively. Limit of detection value for DPH was 13.21 ng/band and for NPS was 8.03 ng/band. Limit of quantitation value for DPH was 40.06 ng/band and for NPS was 24.34 ng/band. The developed method was validated as per ICH guidelines. In stability testing, DPH was found unstable to acid and alkaline hydrolysis, and DPH and NPS were found unstable to oxidation, whereas both the drugs were stable to neutral and photodegradation. The proposed method was successfully applied for the routine quantitative analysis of dosage form containing DPH and NPS.

Double-Track Electrochemical Green Approach for Simultaneous Dissolution Profiling of Naproxen Sodium and Diphenhydramine Hydrochloride.

Science.gov (United States)

Shehata, Mostafa A; Fawaz, Esraa M; El-Rahman, Mohamed K Abd; Abdel-Moety, Ezzat M

2017-11-30

Acquisition of the dissolution profiles of more than single active ingredient in a multi-analyte pharmaceutical formulation is a mandatory manufacturing practice that is dominated by utilization of the off-line separation-based chromatographic methods. This contribution adopts a new "Double-Track" approach with the ultimate goal of advancing the in-line potentiometric sensors to their most effective applicability for simultaneous acquisition of the dissolution profiles of two active ingredients in a binary pharmaceutical formulation. The unique abilities of these sensors for real-time measurements is the key driver for adoption of "green analytical chemistry" (GAC) principles aiming to expand the application of eco-friendly analytical methods With the aim of performing a side-by-side comparison, this work investigates the degree of adherence of ISEs to the 12 principles of GAC in multicomponent dissolution profiling with respect to the HPLC. For the proof of concept, a binary mixture of naproxen sodium (NAPR) and diphenhydramine hydrochloride (DIPH) marketed as Aleve pm ® tablets was selected as a model for which dissolution profiles were attained by two techniques. The first "Double-Track" in-line strategy depends on dipping two highly integrated membrane sensors for continuous monitoring of the dissolution of each active pharmaceutical ingredient (API) by tracing the e.m.f change over the time scale. For the determination of NAPR, sensor I was developed using tridodecyl methyl ammonium chloride as an anion exchanger, while sensor II was developed for the determination of DIPH using potassium tetrakis (4-chlorophenyl) borate as a cation exchanger. The second off-line strategy utilizes a separation-based HPLC method via off-line tracking the increase of peak area by UV detection at 220nm over time using a mobile phase of acetonitrile: water (90:10) pH 3. The advantages of the newly introduced "Double-Track" approach regarding GAC principles are highlighted, and

Diphenhydramine

Science.gov (United States)

... dose that matches the child's age on the chart. Ask the child's doctor if you don't ... same conditions.if you are having surgery, including dental surgery, tell the doctor or dentist that you ...

Application of DNA Profiling in Resolving Aviation Forensic Toxicology Issues

Science.gov (United States)

2009-10-01

muscle,.spleen,.and.vitreous.fluid Toxicological Findings Pilot: Carboxyhemoglobin .20% Cyanide.1 .80.µg/mL.in.blood Diphenhydramine.0 .030.µg/mL.in.blood...Diphenhydramine.present.in.liver Copilot: Carboxyhemoglobin .25% Cyanide.2 .07.µg/mL.in.blood Diphenhydramine.0 .036.µg/mL.in.blood

A pharmacokinetic evaluation of five H(1) antagonists after an oral and intravenous microdose to human subjects.

Science.gov (United States)

Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

2009-03-01

To evaluate the pharmacokinetics (PK) of five H(1) receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). Five H(1) receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. The median clearance (CL), apparent volume of distribution (V(d)) and apparent terminal elimination half-life (t(1/2)) of diphenhydramine after an i.v. microdose were 24.7 l h(-1), 302 l and 9.3 h, and the oral C(max) and AUC(0-infinity) were 0.195 ng ml(-1) and 1.52 ng h ml(-1), respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection.

A pharmacokinetic evaluation of five H1 antagonists after an oral and intravenous microdose to human subjects

Science.gov (United States)

Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

2009-01-01

AIMS To evaluate the pharmacokinetics (PK) of five H1 receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). METHODS Five H1 receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. RESULTS The median clearance (CL), apparent volume of distribution (Vd) and apparent terminal elimination half-life (t1/2) of diphenhydramine after an i.v. microdose were 24.7 l h−1, 302 l and 9.3 h, and the oral Cmax and AUC0–∞ were 0.195 ng ml−1 and 1.52 ng h ml−1, respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. CONCLUSIONS Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection. PMID:19523012

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.

Directory of Open Access Journals (Sweden)

Parviz Ayazi

Full Text Available 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.

Transfer of wastewater associated pharmaceuticals and personal care products to crop plants from biosolids treated soil.

Science.gov (United States)

Wu, Chenxi; Spongberg, Alison L; Witter, Jason D; Sridhar, B B Maruthi

2012-11-01

The plant uptake of emerging organic contaminants such as pharmaceuticals and personal care products (PPCPs) is receiving increased attention. Biosolids from municipal wastewater treatment have been previously identified as a major source for PPCPs. Thus, plant uptake of PPCPs from biosolids applied soils needs to be understood. In the present study, the uptake of carbamazepine, diphenhydramine, and triclocarban by five vegetable crop plants was examined in a field experiment. At the time of harvest, three compounds were detected in all plants grown in biosolids-treated soils. Calculated root concentration factor (RCF) and shoot concentration factor (SCF) are the highest for carbamazepine followed by triclocarban and diphenhydramine. Positive correlation between RCF and root lipid content was observed for carbamazepine but not for diphenhydramine and triclocarban. The results demonstrate the ability of crop plants to accumulate PPCPs from contaminated soils. The plant uptake processes of PPCPs are likely affected by their physico-chemical properties, and their interaction with soil. The difference uptake behavior between plant species could not solely be attributed to the root lipid content. Copyright © 2012 Elsevier Inc. All rights reserved.

Risk Factors, Clinical Presentation, and Outcomes in Overdose With Acetaminophen Alone or With Combination Products: Results From the Acute Liver Failure Study Group.

Science.gov (United States)

Serper, Marina; Wolf, Michael S; Parikh, Nikhil A; Tillman, Holly; Lee, William M; Ganger, Daniel R

2016-01-01

Acetaminophen (APAP) is the most common cause of acute liver failure (ALF) in the west. It is unknown if APAP overdose in combination with diphenhydramine or opioids confers a different clinical presentation or prognosis. Study objectives were to compare (1) baseline patient characteristics; (2) initial clinical presentation; and (3) clinical outcomes among patients with ALF due to APAP alone or in combination with diphenhydramine or opioids. We analyzed 666 cases of APAP-related liver failure using the Acute Liver Failure Study Group database from 1998 to 2012. The database contains detailed demographic, laboratory, and clinical outcome data, including hemodialysis, transplantation, and death and in-hospital complications such as arrhythmia and infection. The final sample included 666 patients with APAP liver injury. A total 30.3% of patients were overdosed with APAP alone, 14.1% with APAP/diphenhydramine, and 56.6% with APAP/opioids. Patients taking APAP with opioids were older, had more comorbidities, and were more likely to have unintentional overdose (all Ppresentation, 58% in the APAP/opioid group had advanced encephalopathy as compared with 43% with APAP alone (P=0.001) The APAP/diphenhydramine group presented with the highest serum aminotransferase levels, no differences in laboratory values were noted at 3 days postenrollment. No significant differences were observed in clinical outcomes among the groups. Most patients with APAP-induced ALF were taking APAP combination products. There were significant differences in patient characteristics and clinical presentation based on the type of product ingested, however, there were no differences noted in delayed hepatotoxicity or clinical outcomes.

Sedation and memory: studies with a histamine H-1 receptor antagonist.

Science.gov (United States)

Turner, Claire; Handford, Alison D F; Nicholson, Anthony N

2006-07-01

The influence of sedation on the effect of an H-1 receptor antagonist on various cognitive functions, including memory, were evaluated. Diphenhydramine (50, 75 and 100 mg) and lorazepam (0.5 and 1.5 mg) were given on single occasions to 12 healthy volunteers (six males, six females) aged 20-33 (mean 23.4) years. Subjective assessments of sedation, sleep latencies, digit symbol substitution, choice reaction time, sustained attention and memory recall were studied 1.0 h before and 0.5, 2.0 and 3.5 h after drug ingestion. The study was double blind, placebo controlled and with a crossover design. With all doses of diphenhydramine there was subjective sedation, reduced sleep latencies and impairments in performance on the digit symbol substitution, choice reaction time and sustained attention tasks. No effects were observed with 0.5 mg lorazepam. With 1.5 mg lorazepam there was subjective sedation, fewer digit symbol substitutions, slowed choice reaction time, impaired attention and memory, but no effect on sleep latencies. Contrast analysis of data measured at all time points showed that although there was no difference in the effect of diphenhydramine (100 mg) and lorazepam (1.5 mg) on those tasks without a memory component, response times were slower with lorazepam on those tasks with a memory component. However, both 100 mg diphenhydramine and 1.5 mg lorazepam impaired prompted recall measured at 2 h post-ingestion only. It is considered that impaired memory is not necessarily associated with sedation, and that impairment of memory with drugs that lead to sedation may be effected through neuronal systems independent of those that affect arousal.

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

DEFF Research Database (Denmark)

Tran, Thuy; Chakraborty, Anjan; Xi, Xi

2018-01-01

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) wer...

77 FR 16039 - Abbott Laboratories et al.; Withdrawal of Approval of 35 New Drug Applications and 64 Abbreviated...

Science.gov (United States)

2012-03-19

...] Abbott Laboratories et al.; Withdrawal of Approval of 35 New Drug Applications and 64 Abbreviated New... Tablets... Abbott Laboratories, PA77/Bldg. AP30-1E, 200 Abbott Park Rd., Abbott Park, IL 60064-6157. NDA... (diphenhydramine Healthcare. HCl)) Injection Preservative Free. NDA 010021 Placidyl Abbott Laboratories...

Functional expression of a proton-coupled organic cation (H+/OC antiporter in human brain capillary endothelial cell line hCMEC/D3, a human blood–brain barrier model

Directory of Open Access Journals (Sweden)

Shimomura Keita

2013-01-01

Full Text Available Abstract Background Knowledge of the molecular basis and transport function of the human blood–brain barrier (BBB is important for not only understanding human cerebral physiology, but also development of new central nervous system (CNS-acting drugs. However, few studies have been done using human brain capillary endothelial cells, because human brain materials are difficult to obtain. The purpose of this study is to clarify the functional expression of a proton-coupled organic cation (H+/OC antiporter in human brain capillary endothelial cell line hCMEC/D3, which has been recently developed as an in vitro human BBB model. Methods Diphenhydramine, [3H]pyrilamine and oxycodone were used as cationic drugs that proved to be H+/OC antiporter substrates. The in vitro uptake experiments by hCMEC/D3 cells were carried out under several conditions. Results Diphenhydramine and [3H]pyrilamine were both transported into hCMEC/D3 cells in a time- and concentration-dependent manner with Km values of 59 μM and 19 μM, respectively. Each inhibited uptake of the other in a competitive manner, suggesting that a common mechanism is involved in their transport. The diphenhydramine uptake was significantly inhibited by amantadine and quinidine, but not tetraethylammonium and 1-methyl-4-phenylpyridinium (substrates for well-known organic cation transporters. The uptake was inhibited by metabolic inhibitors, but was insensitive to extracellular sodium and membrane potential. Further, the uptake was increased by extracellular alkalization and intracellular acidification. These transport properties are completely consistent with those of previously characterized H+/OC antiporter in rat BBB. Conclusions The present results suggest that H+/OC antiporter is functionally expressed in hCMEC/D3 cells.

Metronidazole hypersensitivity.

Science.gov (United States)

Knowles, S; Choudhury, T; Shear, N H

1994-03-01

To report a case of a possible hypersensitivity reaction induced by metronidazole. An Asian woman with a history of recurrent vaginitis had previously developed localized erythema while on intravaginal metronidazole and nystatin. While receiving oral metronidazole for treatment of a current bacterial vaginosis, she developed chills, fever, generalized erythema, and a rash within 60 minutes of the first dose. Treatment with diphenhydramine was instituted. The following day while in the hospital, the patient's condition worsened; she experienced shortness of breath and increased edema of the extremities. Methylprednisolone was administered with diphenhydramine and her condition improved over the next 5 days. The patient's vaginitis was treated with gentian violet and she was discharged on a tapering dosage of prednisone. Metronidazole-induced cutaneous reactions and systemic hypersensitivity reactions are reviewed. Alternatives to metronidazole and other potential cross-reactive drugs are suggested for the treatment of recurrent vaginitis. Although the patient's initial reaction to metronidazole represented a rare event, written documentation and communication in the patient's native language may have prevented the subsequent severe hypersensitivity reaction.

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

DEFF Research Database (Denmark)

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

2004-01-01

-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...

Simulated Evaluation of Drug-Impaired Psychomotor Performance

OpenAIRE

Richmond R

2014-01-01

The purpose of this placebo-controlled, randomized-crossover study was to evaluate a computer-based divided-attention task as a method for measure impaired human psychomotor performance. The ability of the divided-attention task to detect and differentiate was evaluated using single oral doses of placebo, caffeine and diphenhydramine. Ten healthy men were the subjects of the study. Subject performance on divided-attention was compared with tests of short-term memory and a set of visual analog...

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

Science.gov (United States)

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

2011-03-01

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.

Uptake of pharmaceutical and personal care products by soybean plants from soils applied with biosolids and irrigated with contaminated water.

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Wu, Chenxi; Spongberg, Alison L; Witter, Jason D; Fang, Min; Czajkowski, Kevin P

2010-08-15

Many pharmaceuticals and personal care products (PPCPs) are commonly found in biosolids and effluents from wastewater treatment plants. Land application of these biosolids and the reclamation of treated wastewater can transfer those PPCPs into the terrestrial and aquatic environments, giving rise to potential accumulation in plants. In this work, a greenhouse experiment was used to study the uptake of three pharmaceuticals (carbamazepine, diphenhydramine, and fluoxetine) and two personal care products (triclosan and triclocarban) by an agriculturally important species, soybean (Glycine max (L.) Merr.). Two treatments simulating biosolids application and wastewater irrigation were investigated. After growing for 60 and 110 days, plant tissues and soils were analyzed for target compounds. Carbamazepine, triclosan, and triclocarban were found to be concentrated in root tissues and translocated into above ground parts including beans, whereas accumulation and translocation for diphenhydramine and fluoxetine was limited. The uptake of selected compounds differed by treatment, with biosolids application resulting in higher plant concentrations, likely due to higher loading. However, compounds introduced by irrigation appeared to be more available for uptake and translocation. Degradation is the main mechanism for the dissipation of selected compounds in biosolids applied soils, and the presence of soybean plants had no significant effect on sorption. Data from two different harvests suggest that the uptake from soil to root and translocation from root to leaf may be rate limited for triclosan and triclocarban and metabolism may occur within the plant for carbamazepine.

Modeling Uptake of Selected Pharmaceuticals and Personal Care Products into Food Crops from Biosolids-Amended Soil

DEFF Research Database (Denmark)

Prosser, Ryan S.; Trapp, Stefan; Sibley, Paul K.

2014-01-01

and comparing them to an acceptable daily intake value. The equilibrium partitioning (EqP) portion of BASL4 overpredicted the concentrations of triclosan, triclocarban, and miconazole in root and shoot tissue by two to three orders of magnitude, while the dynamic carrot root (DCR) portion overpredicted...... by a single order of magnitude. DPU predicted concentrations of triclosan, triclocarban, miconazole, carbamazepine, and diphenhydramine in plant tissues that were within an order of magnitude of concentrations reported in the literature. The study also found that more empirical data are needed on the uptake...

Infusion-related reactions to infliximab in patients with rheumatoid arthritis in a clinical practice setting: relationship to dose, antihistamine pretreatment, and infusion number.

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Wasserman, Michael J; Weber, Deborah A; Guthrie, Judith A; Bykerk, Vivian P; Lee, Peter; Keystone, Edward C

2004-10-01

We describe infusion-related reactions to infliximab (during infusion or within 1 hour postinfusion) in patients with active rheumatoid arthritis (RA) treated in a quaternary care center. We followed 113 patients for a mean of 60.6 +/- 28.9 weeks, obtaining 10.5 +/- 4.9 infusions per patient. We observed 1183 infusions resulting in 104 infusion reactions (8.8%). All reactions resolved within several hours following cessation of the infusion and none was serious enough to warrant hospitalization. Reactions included allergic reactions (pruritus, urticaria) in 4.2% of infusions, cardiopulmonary (hypotension, hypertension, tachycardia) in 3.0%, and miscellaneous reactions (headache, nausea, vomiting) in 2.0%. Reactions occurred in 8.0% of 3 mg/kg infusions and in 10.3% of 5 mg/kg infusions. Reactions occurred in 13.2% of infusions that involved antihistamine pretreatment compared to only 7.5% of infusions that involved no pretreatment. At both infliximab doses, there was a similar frequency of infusion reactions in patients pretreated due to a previous infusion (12.6%) compared to those pretreated strictly based on infusion number (14.7%). A number of the reactions involving antihistamine pretreatment may be explained by known side effects of diphenhydramine, including headache, dizziness, nausea, and palpitations. Infusion-related reactions to infliximab were infrequent, rarely severe, and easily manageable. The frequency of reactions was equivalent in patients treated with 3 mg/kg compared to 5 mg/kg. Reactions were significantly more frequent in infusions where patients were pretreated with the antihistamine diphenhydramine, compared to those not involving pretreatment.

Knowledge and Attitude Towards Pharmacological Management of Acute Agitation: A Survey of Psychiatrists, Psychiatry Residents, and Psychiatric Nurses.

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Tangu, KeumbÔh; Ifeanyi, Adaora; Velusamy, Mayurapriya; Dar, Sara; Shah, Nurun; Ezeobele, Ifeoma E; Okusaga, Olaoluwa O

2017-06-01

The authors compared the current knowledge and attitude of psychiatrists, psychiatry residents, and psychiatric nurses towards the pharmacological management of acute agitation. Questionnaires were electronically distributed to all attending psychiatrists, psychiatry residents, and psychiatric nurses who were either employed by the University Department of Psychiatry and Behavioral Sciences or were staff at a 250-bed affiliated Psychiatric Hospital. Where possible, Fisher's exact test was used to compare responses to questions based on designation. Of the 250 questionnaires distributed, 112 were returned (response rate of 44.8%), of which 64 (57.1%) were psychiatric nurses, 27 (24.1%) were attending psychiatrists, and 21 (18.8%) were psychiatry residents. A significantly higher percentage of attending psychiatrists and psychiatric nurses compared to psychiatry residents thought that newer second- generation antipsychotics (SGAs) are not as effective as older first-generation antipsychotics (FGAs) for managing acute agitation (55.6, 48.4, and 9.5% respectively, p = 0.008). The combination of intramuscular haloperidol, lorazepam, and diphenhydramine was the most preferred option chosen by all designations for the psychopharmacological management of severe agitation. Furthermore, a larger percentage of the psychiatric nurses, in comparison to attending psychiatrists, also chose the combination of intramuscular chlorpromazine, lorazepam, and diphenhydramine as an option for managing severe agitation; no psychiatry resident chose this option. Knowledge of evidence-based psychopharmacological management of agitation differs among attending psychiatrists, psychiatry residents and psychiatric nurses. Although the management of agitation should be individualized and context specific, monotherapy should be considered first where applicable.

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

DEFF Research Database (Denmark)

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

2013-01-01

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...

Pharmacological and neurophysiological aspects of space/motion sickness

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Lucot, James B.; Crampton, George H.

1991-01-01

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.

Bioaccumulation of pharmaceutically active compounds and endocrine disrupting chemicals in aquatic macrophytes: Results of hydroponic experiments with Echinodorus horemanii and Eichhornia crassipes.

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Pi, N; Ng, J Z; Kelly, B C

2017-12-01

Information regarding the bioaccumulation behaviour of pharmaceutically active compounds (PhACs) and endocrine disrupting chemicals (EDCs) in aquatic plants is limited. The present study involved controlled hydroponic experiments to assess uptake and elimination rate constants (k u , k e ), bioconcentration factors (BCFs) and translocation factors (TFs) of several PhACs and EDCs in two aquatic macrophyte species, including one submerged species (Echinodorus horemanii) and one free-floating species (Eichhornia crassipes). The results revealed that the studied compounds are readily taken up in these aquatic plants. While bioconcentration factors (BCFs) and translocation factors (TFs) of the test compounds varied substantially, no discernible relationship with physicochemical properties such as octanol-water distribution coefficient (D ow ), membrane-water distribution coefficient (D mw ) and organic carbon-water partition coefficient (K oc ). Diphenhydramine and triclosan exhibited the highest degree of uptake and bioaccumulation potential. For example, the whole-plant BCF of triclosan in E. horemanii was 4390L/kg, while the whole-plant BCF of diphenhydramine in E. crassipes was 6130L/kg. BCFs of 17β-estradiol (E2), 17α-ethinylestradiol (EE2), estrone (E1) and bisphenol A (BPA) were relatively low (2-150L/kg). BCFs were generally higher in free-floating aquatic macrophyte species compared to the submerged species. For the free-floating species, E. crassipes, the majority of PhACs and EDCs were more allocated in roots compared to leaves, with TFs1). The study findings may be useful for design and implementation of phytoremediation systems, as well as aid future modeling and risk assessment initiatives for these emerging organic contaminants. Copyright © 2017 Elsevier B.V. All rights reserved.

Severe cutaneous reaction to cetuximab with possible association with the use of over-the-counter skin care products in a patient with oropharyngeal cancer.

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Waris, Waris; Naik, Seeta; Idrees, Imran; Taha, Hesham; Camosino, Linda; Mehrishi, Anshu; Saif, Muhammad Wasif

2009-01-01

The management of locally advanced head and neck cancer remains a challenge to most oncologists and their patients. Treatment with epithelial growth factor receptor inhibitors (EGFRIs) is associated with a good response. Cetuximab, a chimeric monoclonal antibody directed against epithelial growth factor receptor (EGFR), in combination with radiation therapy is indicated for the treatment of locally advanced squamous cell carcinoma of the head and neck. Although a mild acneiform skin rash (Grade 1, 2) is very common in these patients, severe rash (Grade 3) is uncommon. A 61-year-old African American man with locally advanced oropharyngeal cancer was treated with cetuximab and radiation. He developed a sudden flare-up of a skin rash after the 5th cycle of cetuximab following use of over-the-counter (OTC) skin care remedies. The rash manifested with severe maculopapular eruption and erythematous rash, along with desquamation and exfoliation of the skin, mainly on the face and neck area. The patient denied any extraordinary sun exposure. Cetuximab and radiation therapy were held for 1 week and the rash was treated with doxycycline, diphenhydramine, and continued use of natural emollient (Vaseline petroleum jelly). After 1 week, a dramatic improvement of the facial rash was noticed. Our report describes a sudden flare-up of a skin rash (Grade 3) after the 5th cycle of cetuximab following use of OTC skin care remedies, which was unusual for this patient, suggesting a possible relation to the therapy. Skin crucially depends on EGFR for its normal function and becomes extremely sensitive during cetuximab therapy. Topical OTC acne and dry skin remedies can suddenly change the mild acneiform rash into severe skin toxicity associated with marked desquamation and exfoliation. Avoidance of further skin damage caused by topical applications and the use of doxycycline and diphenhydramine show a significant success in the management of skin toxicity.

Proton-coupled organic cation antiporter-mediated uptake of apomorphine enantiomers in human brain capillary endothelial cell line hCMEC/D3.

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

2014-01-01

R(-)-Apomorphine is a dopamine agonist used for rescue management of motor function impairment associated with levodopa therapy in Parkinson's disease patients. The aim of this study was to examine the role of proton-coupled organic cation antiporter in uptake of R(-)-apomorphine and its S-enantiomer in human brain, using human endothelial cell line hCMEC/D3 as a model. Uptake of R(-)- or S(+)-apomorphine into hCMEC/D3 cells was measured under various conditions to evaluate its time-, concentration-, energy- and ion-dependency. Inhibition by selected organic cations was also examined. Uptakes of both R(-)- and S(+)-apomorphine increased with time. The initial uptake velocities of R(-)- and S(+)-apomorphine were concentration-dependent, with similar Km and Vmax values. The cell-to-medium (C/M) ratio of R(-)-apomorphine was significantly reduced by pretreatment with sodium azide, but was not affected by replacement of extracellular sodium ion with N-methylglucamine or potassium. Intracellular alkalization markedly reduced the uptake, while intracellular acidification increased it, suggesting that the uptake is driven by an oppositely directed proton gradient. The C/M ratio was significantly decreased by amantadine, verapamil, pyrilamine and diphenhydramine (substrates or inhibitors of proton-coupled organic cation antiporter), while tetraethylammonium (substrate of organic cation transporters (OCTs)) and carnitine (substrate of carnitine/organic cation transporter 2; (OCTN2)) had no effect. R(-)-Apomorphine uptake was competitively inhibited by diphenhydramine. Our results indicate that R(-)-apomorphine transport in human blood-brain barrier (BBB) model cells is similar to S(+)-apomorphine uptake. The transport was dependent on an oppositely directed proton gradient, but was sodium- or membrane potential-independent. The transport characteristics were consistent with involvement of the previously reported proton-coupled organic cation antiporter.

Blood-brain barrier in vitro models as tools in drug discovery: assessment of the transport ranking of antihistaminic drugs.

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Neuhaus, W; Mandikova, J; Pawlowitsch, R; Linz, B; Bennani-Baiti, B; Lauer, R; Lachmann, B; Noe, C R

2012-05-01

In the course of our validation program testing blood-brain barrier (BBB) in vitro models for their usability as tools in drug discovery it was evaluated whether an established Transwell model based on porcine cell line PBMEC/C1-2 was able to differentiate between the transport properties of first and second generation antihistaminic drugs. First generation antihistamines can permeate the BBB and act in the central nervous system (CNS), whereas entry to the CNS of second generation antihistamines is restricted by efflux pumps such as P-glycoprotein (P-gP) located in brain endothelial cells. P-gP functionality of PBMEC/C1-2 cells grown on Transwell filter inserts was proven by transport studies with P-gP substrate rhodamine 123 and P-gP blocker verapamil. Subsequent drug transport studies with the first generation antihistamines promethazine, diphenhydramine and pheniramine and the second generation antihistamines astemizole, ceterizine, fexofenadine and loratadine were accomplished in single substance as well as in group studies. Results were normalised to diazepam, an internal standard for the transcellular transport route. Moreover, effects after addition of P-gP inhibitor verapamil were investigated. First generation antihistamine pheniramine permeated as fastest followed by diphenhydramine, diazepam, promethazine and second generation antihistaminic drugs ceterizine, fexofenadine, astemizole and loratadine reflecting the BBB in vivo permeability ranking well. Verapamil increased the transport rates of all second generation antihistamines, which suggested involvement of P-gP during their permeation across the BBB model. The ranking after addition of verapamil was significantly changed, only fexofenadine and ceterizine penetrated slower than internal standard diazepam in the presence of verapamil. In summary, permeability data showed that the BBB model based on porcine cell line PBMEC/C1-2 was able to reflect the BBB in vivo situation for the transport of

Prehospital chemical restraint of a noncommunicative autistic minor by law enforcement.

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Ho, Jeffrey D; Nystrom, Paul C; Calvo, Darryl V; Berris, Marc S; Norlin, Jeffrey F; Clinton, Joseph E

2012-01-01

When responders are dealing with an agitated patient in the field, safety for all involved may sometimes only be accomplished with physical or chemical restraints. While experiences using chemical restraint in the prehospital setting are found in the medical literature, the use of this by law enforcement as a first-response restraint has not previously been described. We report a case of successful law enforcement-administered sedation of a noncommunicative, autistic, and violent minor using intramuscular droperidol and diphenhydramine. Although this case has some unique characteristics that allowed chemical restraint to be given by the law enforcement agency, it calls attention to some specific prehospital issues that need to be addressed when dealing with autistic patients with extreme agitation.

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

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Minckler, Michael R; Fisher, Joseph; Bowers, Rachel; Amini, Richard

2017-01-01

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. 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. This case describes the gastrointestinal sequela and effective management following ingestion of jojoba butter.

Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period

DEFF Research Database (Denmark)

Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose

2018-01-01

analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology......Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug......-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid...

Self-reported drug use among secondary school students in two rapidly developing Nigerian towns.

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Nevadomsky, J

1982-01-01

A 32-item standardized multiple-choice and open-ended questionnaire was completed by nearly 500 male and female secondary school students in two rapidly developing Nigerian towns. About two thirds of the students reported some exposure to alcohol, and about one quarter reported some experience with tobacco. There was much less use of caffeine, methaqualone in combination with diphenhydramine, 2-ethylamino-3-phenylorcamphane in combination with vitamins, chlordiazepoxide, diazepam, cannabis and dexamphetamine. Many students fell into the "past use" category. Parents were extremely disapproving of the use of almost any drug. Many students supported stronger penalties for the use of cannabis. Non-users claimed that drugs were dangerous to health. In addition, religious beliefs were associated with abstinence from drugs.

Immediate x-radiation induced contractions of the isolated guinea pig terminal ileum: the localization of the effect by drugs

Energy Technology Data Exchange (ETDEWEB)

Spruegel, W; Schubert, E; Mitznegg, P; Heim, F [Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Pharmakologisches Inst.; Hasl, G; Pauly, H [Erlangen-Nuernberg Univ., Erlangen (Germany, F.R.). Inst. fuer Radiologie

1977-04-01

Tone and motility of the isolated guinea pig ileum were increased by irradiation with a dose of 10 krad. The maximal effect corresponds to that induced by 0.001 ..mu..g/ml acetylcholine or 0.3 ..mu..g/ml nicotine. The pharmacological analysis of this effect performed with acetylcholine and nicotine and several blocking agents including hexamethonium, atropine, tetrodotoxin, diphenhydramine, and verapamil suggests that radiation acts on the postganglionic parasympathetic neuron and the neuromuscular synapse. The mechanism of radiation is likely to consist of both an increased release of acetylcholine from the postganglionic neuron and a sensibilization of the cholinergic receptor site at the smooth muscle cell. The latter effect is thought to result from an increased contractile action induced by acetylcholine or nicotine in the irradiated ileal smooth muscle.

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

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Danielle D. Campagne

2015-10-01

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

A study of western pharmaceuticals contained within samples of Chinese herbal/patent medicines collected from New York City's Chinatown.

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Miller, Gretchen M; Stripp, Richard

2007-09-01

In America, recent growth in the popularity of Chinese herbal/patent medicines (CHM/CPM) has generated concerns as to the safety of these and other herbal remedies. Lack of strict federal regulations has lead to the possibility of improper labeling and even adulteration of these products with western drugs or other chemical contaminants. Our laboratory has conducted an analytical study to determine the presence of undeclared pharmaceuticals and therapeutic substances within CHM/CPM sold in New York City's Chinatown. Ninety representative samples randomly purchased in the form of pills, tablets, creams and teas were screened by appropriate analytical techniques including TLC, GC/MS and HPLC. Five samples contained nine different western pharmaceuticals. Two of these samples contained undeclared or mislabeled substances. One sample contained two pharmaceuticals contraindicated in people for whom the product was intended. Drugs identified include promethazine, chlormethiazole, chlorpheniramine, diclofenac, chlordiazepoxide, hydrochlorothiazide, triamterene, diphenhydramine and sildenafil citrate (Viagra).

Rapid screening of pharmaceutical drugs using thermal desorption – SALDI mass spectrometry

International Nuclear Information System (INIS)

Grechnikov, A A; Kubasov, A E; Borodkov, A S; Georgieva, V B; Nikiforov, S M; Simanovsky, Ya O; Alimpiev, S S

2012-01-01

A novel approach to the rapid screening of pharmaceutical drugs by surface assisted laser desorption-ionization (SALDI) mass spectrometry with the rotating ball interface coupled with temperature programmed thermal desorption has been developed. Analytes were thermally desorbed and deposited onto the surface of amorphous silicon substrate attached to the rotating ball. The ball was rotated and the deposited analytes were analyzed using SALDI. The effectiveness of coupling SALDI mass spectrometry with thermal desorption was evaluated by the direct and rapid analysis of tablets containing lidocaine, diphenhydramine and propranolol without any sample pretreatment. The overall duration of the screening procedure was 30÷40 sec. Real urine samples were studied for drug analysis. It is shown that with simple preparation steps, urine samples can be quantitatively analyzed using the proposed technique with the detection limits in the range of 0.2÷0.5 ng/ml.

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

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Nathan T. Jaqua

2013-01-01

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.

October 2016 critical care case of the month

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Fountain S

2016-09-01

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 ...

Interaction of active compounds from Aegle marmelos CORREA with histamine-1 receptor

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Nugroho, Agung Endro; Agistia, Dany Dwi; Tegar, Maulana; Purnomo, Hari

2013-01-01

The aim of this study is to determine the affinity of six active compounds of Aegle Marmelos Correa, they are (E, R)-Marmin, skimmianine, (S)-aegeline, aurapten, zeorin, and dustanin as antihistamines in histamine H1 receptor in comparison to cetirizin, diphenhydramine and chlorpheniramine as ligands comparison. Previously, in the in vitro study marmin obviously antagonized the histamine H1 receptor in a competitive manner. Methods: molecular docking to determine the interaction of ligand binding to its receptor. Lower docking score indicates more stable binding to that protein. Results: Marmin, skimmianine, aegeline, aurapten, zeorin, and dustanin were potential to develop as antihistamine agents, especially as histamine H1 receptor antagonists by interacting with amino acid residues, Asp107, Lys179, Lys191, Asn198, and Trp428 of histamine H1 receptor. Conclusions: Based on molecular docking, Amino acid residues involved in ligand protein interactions were Asp107, Lys179, Lys191, Asn198, and Trp428. PMID:23750086

Occurrence of contaminants of emerging concern along the California coast (2009-10) using passive sampling devices

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Alvarez, David A.; Maruya, Keith A.; Dodder, Nathan G.; Lao, Wenjian; Furlong, Edward T.; Smalling, Kelly L.

2014-01-01

Three passive sampling devices (PSDs), polar organic chemical integrative samplers (POCIS), polyethylene devices (PEDs), and solid-phase microextraction (SPME) samplers were used to sample a diverse set of chemicals in the coastal waters of San Francisco Bay and the Southern California Bight. Seventy one chemicals (including fragrances, phosphate flame retardants, pharmaceuticals, PAHs, PCBs, PBDEs, and pesticides) were measured in at least 50% of the sites. The chemical profile from the San Francisco Bay sites was distinct from profiles from the sites in the Southern California Bight. This distinction was not due to a single compound or class, but by the relative abundances/concentrations of the chemicals. Comparing the PSDs to mussel (Mytilus spp.) tissues, a positive correlation exists for the 25 and 26 chemicals in common for the PEDs and SPME, respectively. Diphenhydramine was the only common chemical out of 40 analyzed in both POCIS and tissues detected at a common site.

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

Directory of Open Access Journals (Sweden)

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.

Unusual etiology of gastrointestinal symptoms: the case of jojoba butter

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Minckler MR

2017-02-01

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

Mast Cells Are Critical for Protection against Peptic Ulcers Induced by the NSAID Piroxicam

Science.gov (United States)

Hampton, Daniel D.; Hale, Laura P.

2011-01-01

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. PMID:21858200

Anti-tuberculosis medication-induced oculogyric crisis and the importance of proper history taking

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Wong LH

2017-10-01

Full Text Available Lin Ho Wong,1 Endean Tan2 1University College Cork, Cork, Ireland; 2Tan Tock Seng Hospital, Singapore Abstract: Oculogyric crisis (OGC, frequently caused by medications such as antiemetics, antidepressants, and anti-epileptics, is an acute dystonic reaction of the ocular muscles. It consists of wide-staring gaze (lasting variably from seconds to minutes, seizures, and a widely-opened mouth. To date, there have been no reports of anti-tuberculosis medications such as rifampicin, isoniazid, pyrazinamide or ethambutol inducing OGC. It is of utmost importance to recognize this adverse reaction, which could be incorrectly diagnosed as an anaphylactic-like reaction. In this paper, we highlight a case of a 66-year-old Indian man who presented with OGC induced by anti-tuberculosis medications which was initially suspected to be an anaphylactic reaction and was subsequently halted with the administration of diphenhydramine. Keywords: oculogyric crisis, tuberculosis, rifampicin, isoniazid, ethambutol, adverse drug reaction 

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

Energy Technology Data Exchange (ETDEWEB)

Bartelt-Hunt, Shannon L. [Department of Civil Engineering, University of Nebraska-Lincoln, 203B Peter Kiewit Institute, Omaha, NE 68182-0178 (United States)], E-mail: sbartelt2@unl.edu; 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)

2009-03-15

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.

[How safe are dimenhydrinate suppositories?].

Science.gov (United States)

Bernhard, M K; Mütze, U; Syrbe, S

2013-10-01

A 13-month-old girl suffered from 3 generalized tonic-clonic seizures for several minutes within a total period of 9 hours. History revealed that the child received a total of 5 dimenhydrinate containing suppositories à 40 mg during the previous 2 days (i. e. 23 mg dimenhydrinate per kg body weight) due to enteritis with vomiting. The first seizure occurred 10 hours after the last administration. The plasma level of diphenhydramin was 230 µg/l approximately one hour after the first seizure. Electroencephalography showed no pathological signs, an MRI scan of the brain was normal except of several small gliotic spots and body temperature was regularly. Two stationary occurring seizures were stopped with 5 mg diazepam rectally. Continued surveillance and an EEG two days later showed age-appropriate normal findings. There were no further seizures in the next 4 years. Infants have the risk to develop dimenhydrinate intoxication, especially in cases where suppositories were given repeatedly because of intermittent defecation. © Georg Thieme Verlag KG Stuttgart · New York.

A contemporaneous finding of fenproporex in a polydrug suicide.

Science.gov (United States)

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

2001-10-01

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

Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period.

Science.gov (United States)

Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose; Linnet, Kristian

2018-04-01

Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology. A literature review on concentrations in the published DFC-related hair cases and on concentrations in hair of these substances after single and multiple doses is included. These cases demonstrate the value of segmental hair analysis in DFCs and facilitate future interpretations of results. Copyright © 2018 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

Bartelt-Hunt, Shannon L.; Snow, Daniel D.; Damon, Teyona; Shockley, Johnette; Hoagland, Kyle

2009-01-01

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

Acute Dystonia in a Child Receiving Metoclopramide: Case Report

Directory of Open Access Journals (Sweden)

Alaaddin Yorulmaz

2016-11-01

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.

Sucralfate for radiation mucositis: results of a double-blind randomized trial

International Nuclear Information System (INIS)

Meredith, Ruby; Salter, Merle; Kim, Robert; Spencer, Sharon; Weppelmann, Burkhard; Rodu, Brad; Smith, Judy; Lee, Jeanette

1997-01-01

Purpose: To determine if addition of the ulcer-coating polysaccharide sucralfate could improve symptomatic relief of radiation mucositis over a popular combination of antacid, diphenhydramine, and viscous lidocaine alone. Methods and Materials: A double-blind study was conducted in which nurses and pharmacists coded patient groups and distributed medication in a manner blinded to both the patients and physicians. Eligible patients receiving radiation to the head and neck and/or chest sites that included the esophagus were randomized to a standard combination of antacid, diphenhydramine, and viscous lidocaine vs. the same solution plus sucralfate. Eligible patients were those receiving >40 Gy at 1.8 Gy/fraction, one fraction/day, five fractions/week. Participating patients were stratified between chest, small field head and neck, and large field head and neck. The observations and smears for Candidiasis screening. Medication was prescribed when the patient became symptomatic and concomitant use of other locally effective nonstudy agents was not allowed. The ability to eat various consistency of foods was graded 0-5, with 5 indicating no compromise of ability to ingest a food compared to baseline. Statistical analysis included mean + SD for food and soreness scores, paired t-test, and two-way analyses of variance to evaluate effects of site and treatment group on the changes in scores. Results: Over 2 years, 111 patients were entered. Because some withdrew and others did not require medication, results are presented for evaluable patients in each category. Mild adverse effects from the medication solution (usually mouth discomfort) were reported by <10% of patients in each treatment group among 106 patients evaluable for toxicity. There was a comparable incidence of mild-moderate mucositis for the two treatment groups. Severe mucositis was noted in two patients of the standard medication group and none among patients receiving sucralfate. The groups were comparable

Fenspiride inhibits histamine-induced responses in a lung epithelial cell line.

Science.gov (United States)

Quartulli, F; Pinelli, E; Broué-Chabbert, A; Gossart, S; Girard, V; Pipy, B

1998-05-08

Using the human lung epithelial WI26VA4 cell line, we investigated the capacity of fenspiride, an anti-inflammatory drug with anti-bronchoconstrictor properties, to interfere with histamine-induced intracellular Ca2+ increase and eicosanoid formation. Histamine and a histamine H1 receptor agonist elicited a rapid and transient intracellular Ca2+ increase (0-60 s) in fluo 3-loaded WI26VA4 cells. This response was antagonized by the histamine H1 receptor antagonist, diphenhydramine, the histamine H2 receptor antagonist, cimetidine, having no effect. Fenspiride (10(-7)-10(-5) M) inhibited the histamine H1 receptor-induced Ca2+ increase. In addition, histamine induced a biphasic increase in arachidonic acid release. The initial rise (0-30 s), a rapid and transient arachidonic acid release, was responsible for the histamine-induced intracellular Ca2+ increase. In the second phase release (15-60 min), a sustained arachidonic acid release appeared to be associated with the formation of cyclooxygenase and lipoxygenase metabolites. Fenspiride (10(-5) M) abolished both phases of histamine-induced arachidonic acid release. These results suggest that anti-inflammatory and antibronchoconstrictor properties of fenspiride may result from the inhibition of these effects of histamine.

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

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Ali G. Al−Kaf

2015-08-01

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.

Racial differences in anticholinergic use among community-dwelling elders.

Science.gov (United States)

Felton, Maria; Hanlon, Joseph T; Perera, Subashan; Thorpe, Joshua M; Marcum, Zachary A

2015-04-01

Few studies have examined racial differences in potentially inappropriate medication use. The objective of this study was to examine racial disparities in using prescription and/or nonprescription anticholinergics, a type of potentially inappropriate medication, over time. Longitudinal. Data from the Health, Aging, and Body Composition Study (years 1, 5, and 10). Three thousand fifty-five community-dwelling older adults, both blacks and whites, at year 1. Highly anticholinergic medication use per the 2012 American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Blacks represented 41.4% of the participants at year 1. At year 1, 13.4% of blacks used an anticholinergic medication compared with 17.8% of whites, and this difference persisted over the ensuing 10-year period. Diphenhydramine was the most common anticholinergic medication reported at baseline and year 5, and meclizine at year 10, for both races. Controlling for demographics, health status, and access to care factors, blacks were 24% to 45% less likely to use any anticholinergics compared with whites over the years considered (all P blacks than whites over a 10-year period, and the difference was unexplained by demographics, health status, and access to care.

Flushing and pruritus secondary to prescription fish oil ingestion in a patient with allergy to fish.

Science.gov (United States)

Howard-Thompson, Amanda; Dutton, Anna; Hoover, Robert; Goodfred, Jennifer

2014-12-01

A brand of fish oil capsules contains omega-3 fatty acids obtained from several fish sources. Although the manufacturer calls for caution in patients with fish hypersensitivity, insufficient data is available to make a definitive recommendation regarding its use in this population. A patient with documented seafood allergy presented to the emergency department 4 days after the initiation of prescription brand name fish oil capsules complaining of chest tightness, shortness of breath, tingling of upper extremities, flushing, and pruritus that was minimally relieved by excessive nonprescription diphenhydramine administration. During subsequent follow-up, the patient reported that all symptoms had resolved within 5 days of discontinuing the medication and 3 days of disposing of her pillbox and all medications that had come in contact with the fish oil capsules. Due to the patient's allergic history, timing of onset/offset of the reaction, laboratory evidence, and the use of the Naranjo probability scale, prescription fish oil capsules were deemed the probable cause of this patient's pruritus and flushing of the face and trunk. Practitioners and patients should always ensure they have an updated list of allergies within the patient's medical record that includes medications as well as foods and food additives.

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

Directory of Open Access Journals (Sweden)

Mengxuan Gao

2017-02-01

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.

A novel chiral GC/MS method for the analysis of fluoxetine and norfluoxetine enantiomers in biological fluids

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Janet Mifsud

2012-01-01

Full Text Available Aims: A novel robust chiral gas chromatographic/mass spectrometric (GC/MS method for the separation and measurement of fluoxetine and norfluoxetine enantiomers in urine and plasma was developed. Materials and Methods: The drug was extracted from the samples by a liquid-liquid technique, using chloroform, and the enantiomers were separated and measured on a chiral gas chromatographic column (HYDRODEX β-6TBDM®, 0.25 μm × 0.25 mm × 50 m. GC/MS instrumentation was used for the acquisition of data in the electron impact selective-ion monitoring mode. Results: The ions chosen were of a mass-to-charge ratio (m/z exactly equal to 44 units, in order to measure fluoxetine enantiomers, 134 units in order to measure norfluoxetine enantiomers, and 58 units in order to measure diphenhydramine, the internal standard. The method was found to be linear and reproducible in the 50-500 ng/mL concentration range for both urine samples and plasma samples and for both fluoxetine and norfluoxetine, with correlation coefficients ranging between 0.994 and 0.997. Conclusions: This methodology has an enormous potential for application in pharmacokinetic studies of the enantiomers of fluoxetine

A Case Report of Rare Tracheal Mucormycosis in a Diabetic Patient

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M Parham

2012-05-01

Full Text Available

Background and Objectives: Mucormycosis is a systemic killer fungal disease in diabetes resulting in immune deficiency and malignancies that can lead to death if left untreated. Its treatment includes eliminating background diseases, performing surgery, and using anti- fungal drugs such as Amphotripcin B. The aim of this study was to report a Tracheal Mucormycosis which was treated with surgery and anti- fungal drug.

Case Report

The patient was a diabetic woman that had referred to the hospital complaining of dyspnea, nausea and vomiting. She had been suffering from fever, dyspnea, and vomiting for two weeks. She went to a public care center and was treated with Ceftriacxon, Dexamethasone and Diphenhydramin. Despite this treatment, her problem worsened, so she referred to the hospital again. On admission, she was suffering from fever, respiratory distress, tachycardia and tachypenea. Epiglottis was edematous and Erythematous. Diabetic ketoacidosis was diagnosed based on her laboratory tests. Because of worsening of the respiratory distress, tracheostomy was performed. Diagnostic Bronchoscopy and biopsy were on done on the patient on the second day of her admission and Mucormycosis was reported by the pathologist.

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

KAUST Repository

Wei, Chunhai

2015-12-15

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.

Simultaneous determination of telmisartan and amlodipine in dog plasma by LC-MS-MS.

Science.gov (United States)

Wang, Baolian; Sheng, Li; Li, Yan

2015-01-01

A simple, rapid and sensitive method was established for the simultaneous determination of telmisartan and amlodipine in dog plasma by a HPLC-MS-MS analysis. The plasma sample preparation was a simple deproteinization by the addition of three volumes of methanol/acetonitrile mixture followed by centrifugation. The analytes and internal standard diphenhydramine were separated on a Zorbax SB-C18 column with a mobile phase of acetonitrile : water (45 : 55, v/v) at a flow rate of 0.2 mL/min with an operating temperature of 25°C. Detection was carried out by electrospray ionization in positive-ion multiple reaction monitoring mode. The calibration plots in dog plasma were linear over the ranges of 0.5-2,000 ng/mL for telmisartan and 0.5-500 ng/mL for amlodipine. The lower limit of quantification was 0.5 ng/mL for two analytes. The intra- and interday precisions (RSD%) were within 9.0%. The average recoveries of analytes were >85.0%. The method was successfully applied to the pharmacokinetic study of the two compounds after oral administration of telmisartan-amlodipine combination preparation to dogs. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Accumulation of contaminants of emerging concern in food crops-part 1: Edible strawberries and lettuce grown in reclaimed water.

Science.gov (United States)

Hyland, Katherine C; Blaine, Andrea C; Dickenson, Eric R V; Higgins, Christopher P

2015-10-01

Contaminants of emerging concern present in domestic waste streams include a highly diverse group of potentially biologically active compounds that can be detected at trace levels in wastewater. Concerns about potential uptake into crops arise when reclaimed water is used in food crop production. The present study investigated how 9 contaminants of emerging concern in reclaimed water are taken up into edible portions of two food crops. Two flame retardant chemicals, tris(1-chloro-2-propyl) phosphate (TCPP) and tris(2-chloroethyl) phosphate (TCEP) and several polar pharmaceuticals (carbamazepine, diphenhydramine, sulfamethoxazole, and trimethoprim) accumulated in a linear, concentration-dependent manner in lettuce (Lactuca sativa) irrigated with reclaimed water, suggesting passive uptake of both neutral and ionizable chemical contaminants in lettuce. Furthermore, concentration-dependent accumulation of TCEP and TCPP from reclaimed water was also observed in strawberry fruits (Fragaria ananassa). Collectively, these data suggest that highly polar or charged contaminants can be taken up by crops from water bearing contaminants of emerging concern and can be accumulated in the edible portions. Using these data, however, estimates of human exposure to these contaminants from reclaimed water food crop accumulation suggest that exposure to the contaminants of emerging concern examined in the present study is likely substantially lower than current exposure guidelines. © 2015 SETAC.

A fast ultra high pressure liquid chromatographic method for qualification and quantification of pharmaceutical combination preparations containing paracetamol, acetyl salicylic acid and/or antihistaminics.

Science.gov (United States)

Deconinck, E; Sacré, P Y; Baudewyns, S; Courselle, P; De Beer, J

2011-09-10

A fully validated UHPLC method for the identification and quantification of pharmaceutical preparations, containing paracetamol and/or acetyl salicylic acid, combined with anti-histaminics (phenylephrine, pheniramine maleate, diphenhydramine, promethazine) and/or other additives as quinine sulphate, caffeine or codeine phosphate, was developed. The proposed method uses a Waters Acquity BEH C18 column (2 mm × 100 mm, 1.7 μm) with a gradient using an ammonium acetate buffer pH 4.0 as aqueous phase and methanol as organic modifier. The obtained method was fully validated based on its measurement uncertainty (accuracy profile) and robustness tests. Calibration lines for all components were linear within the studied ranges. The relative bias and the relative standard deviations for all components were respectively smaller than 1.5% and 2%, the β-expectation tolerance limits did not exceed the acceptance limits of 10% and the relative expanded uncertainties were smaller than 5% for all of the considered components. A UHPLC method was obtained for the identification and quantification of these kind of pharmaceutical preparations, which will significantly reduce analysis times and workload for the laboratories charged with the quality control of these preparations. Copyright © 2011 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2016-04-15

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. Copyright © 2016 Elsevier B.V. All rights reserved.

A Randomized Controlled Trial of Intravenous Haloperidol vs. Intravenous Metoclopramide for Acute Migraine Therapy in the Emergency Department.

Science.gov (United States)

Gaffigan, Matthew E; Bruner, David I; Wason, Courtney; Pritchard, Amy; Frumkin, Kenneth

2015-09-01

Emergency Department (ED) headache patients are commonly treated with neuroleptic antiemetics like metoclopramide. Haloperidol has been shown to be effective for migraine treatment. Our study compared the use of metoclopramide vs. haloperidol to treat ED migraine patients. A prospective, double-blinded, randomized control trial of 64 adults aged 18-50 years with migraine headache and no recognized risks for QT-prolongation. Haloperidol 5 mg or metoclopramide 10 mg was given intravenously after 25 mg diphenhydramine. Pain, nausea, restlessness (akathisia), and sedation were assessed with 100-mm visual analog scales (VAS) at baseline and every 20 min, to a maximum of 80 min. The need for rescue medications, side effects, and subject satisfaction were recorded. QTc intervals were measured prior to and after treatment. Follow-up calls after 48 h assessed satisfaction and recurrent or persistent symptoms. Thirty-one subjects received haloperidol, 33 metoclopramide. The groups were similar on all VAS measurements, side effects, and in their satisfaction with therapy. Pain relief averaged 53 mm VAS over both groups, with equal times to maximum improvement. Subjects receiving haloperidol required rescue medication significantly less often (3% vs. 24%, p haloperidol-treated subjects experiencing more restlessness (43% vs. 10%). Intravenous haloperidol is as safe and effective as metoclopramide for the ED treatment of migraine headaches, with less frequent need for rescue medications. Published by Elsevier Inc.

Chronic Spontaneous Urticaria: Pathogenesis and Treatment Considerations.

Science.gov (United States)

Kaplan, Allen P

2017-11-01

The treatment of chronic spontaneous urticaria begins with antihistamines; however, the dose required typically exceeds that recommended for allergic rhinitis. Second-generation, relatively non-sedating H₁-receptor blockers are typically employed up to 4 times a day. First-generation antihistamines, such as hydroxyzine or diphenhydramine (Atarax or Benadryl), were employed similarly in the past. Should high-dose antihistamines fail to control symptoms (at least 50%), omalizumab at 300 mg/month is the next step. This is effective in 70% of antihistamine-refractory patients. H₂-receptor blockers and leukotriene antagonists are no longer recommended; they add little and the literature does not support significant efficacy. For those patients who are unresponsive to both antihistamines and omalizumab, cyclosporine is recommended next. This is similarly effective in 65%-70% of patients; however, care is needed regarding possible side-effects on blood pressure and renal function. Corticosteroids should not be employed chronically due to cumulative toxicity that is dose and time dependent. Brief courses of steroid e.g., 3-10 days can be employed for severe exacerbations, but should be an infrequent occurrence. Finally, other agents, such as dapsone or sulfasalazine, can be tried for those patients unresponsive to antihistamines, omalizumab, and cyclosporine. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.

Antihistamines suppress upregulation of histidine decarboxylase gene expression with potencies different from their binding affinities for histamine H1 receptor in toluene 2,4-diisocyanate-sensitized rats

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Hiroyuki Mizuguchi

2016-04-01

Full Text Available Antihistamines inhibit histamine signaling by blocking histamine H1 receptor (H1R or suppressing H1R signaling as inverse agonists. The H1R gene is upregulated in patients with pollinosis, and its expression level is correlated with the severity of nasal symptoms. Here, we show that antihistamine suppressed upregulation of histidine decarboxylase (HDC mRNA expression in patients with pollinosis, and its expression level was correlated with that of H1R mRNA. Certain antihistamines, including mepyramine and diphenhydramine, suppress toluene-2,4-diisocyanate (TDI-induced upregulation of HDC gene expression and increase HDC activity in TDI-sensitized rats. However, d-chlorpheniramine did not demonstrate any effect. The potencies of antihistamine suppressive effects on HDC mRNA elevation were different from their H1R receptor binding affinities. In TDI-sensitized rats, the potencies of antihistamine inhibitory effects on sneezing in the early phase were related to H1R binding. In contrast, the potencies of their inhibitory effects on sneezing in the late phase were correlated with those of suppressive effects on HDC mRNA elevation. Data suggest that in addition to the antihistaminic and inverse agonistic activities, certain antihistamines possess additional properties unrelated to receptor binding and alleviate nasal symptoms in the late phase by inhibiting synthesis and release of histamine by suppressing HDC gene transcription.

Long-term and within-day variability of working memory performance and EEG in individuals.

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Gevins, Alan; McEvoy, Linda K; Smith, Michael E; Chan, Cynthia S; Sam-Vargas, Lita; Baum, Cliff; Ilan, Aaron B

2012-07-01

Assess individual-subject long-term and within-day variability of a combined behavioral and EEG test of working memory. EEGs were recorded from 16 adults performing n-back working memory tasks, with 10 tested in morning and afternoon sessions over several years. Participants were also tested after ingesting non-prescription medications or recreational substances. Performance and EEG measures were analyzed to derive an Overall score and three constituent sub-scores characterizing changes in performance, cortical activation, and alertness from each individual's baseline. Long-term and within-day variability were determined for each score; medication effects were assessed by reference to each individual's normal day-to-day variability. Over the several year period, the mean Overall score and sub-scores were approximately zero with standard deviations less than one. Overall scores were lower and their variability higher in afternoon relative to morning sessions. At the group level, alcohol, diphenhydramine and marijuana produced significant effects, but there were large individual differences. Objective working memory measures incorporating performance and EEG are stable over time and sensitive at the level of individual subjects to interventions that affect neurocognitive function. With further research these measures may be suitable for use in individualized medical care by providing a sensitive assessment of incipient illness and response to treatment. Published by Elsevier Ireland Ltd.

Assessment of intravenous pbi-shRNA PDX1 nanoparticle (OFHIRNA-PDX1) in yucatan swine.

Science.gov (United States)

Jay, C M; Ruoff, C; Kumar, P; Maass, H; Spanhel, B; Miller, M; Arrington, A; Montalvo, N; Gresham, V; Rao, D D; Evans, C; Wang, Z; Brunicardi, F C; Liu, S-H; Zhou, G; Senzer, N; Nemunaitis, J; King, L; Weeks, B; Clubb, F J; Fossum, T W; Maples, P B

2013-12-01

PDX1 (pancreatic and duodenal homeobox 1) is overexpressed in pancreatic cancer, and its reduction results in tumor regression. Bi-functional pbi-shRNA PDX1 nanoparticle (OFHIRNA-PDX1) utilizes the endogenous micro-RNA biogenesis pathway to effect cleavage- and non-cleavage-dependent degradation of PDX1 mRNA. We have shown that OFHIRNA-PDX1 reduces pancreatic tumor volume in xenograft models. Thus, we are now exploring biorelevant large animal safety of OFHIRNA-PDX1. Mini pigs were chosen as the biorelevant species based on the similarity of human and pig PDX1 target sequence. In the initial study, animals developed fever, lethargy, hyporexia and cutaneous hyperemia following administration of OFHIRNA-PDX1. Twenty-one days later, the same animals demonstrated less toxicity with a second OFHIRNA-PDX1 infusion in conjunction with a prophylactic regimen involving dexamethasone, diphenhydramine, Indocin and ranitidine. In a new group of animals, PDX1 protein (31 kDa) expression in the pancreas was significantly repressed at 48 and 72 h (85%, P=0.018 and 88%, P=0.013; respectively) following a single infusion of OFHIRNA-PDX1 but recovered to normal state within 7 days. In conclusion, a single intravenous infusion of OFHIRNA-PDX1 in conjunction with premedication in pigs was well tolerated and demonstrated significant PDX1 knockdown.

Acute hypersensitivity reaction to Crotalidae polyvalent immune Fab (CroFab) as initial presentation of galactose-α-1,3-galactose (α-gal) allergy.

Science.gov (United States)

Rizer, Justin; Brill, Kaitlin; Charlton, Nathan; King, Joshua

2017-08-01

Crotalidae polyvalent immune Fab antivenom (CroFab), commonly used for the treatment of clinically significant North American crotalinae envenomation, is generally well-tolerated. A novel form of anaphylaxis due to an IgE antibody response to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) has been established following red-meat consumption as well as IV administration of cetuximab, which contain the α-gal epitope. We present a case of α-gal allergy discovered after acute hypersensitivity reaction to FabAV. A 61-year-old healthy female was bitten on her left ankle by Agkistrodon contortrix. Given the patient's rapid progression of pain and swelling, she was given FabAV. During infusion of FabAV, she developed diffuse hives over her entire body and itching, but denied respiratory or gastrointestinal symptoms and her vital signs remained stable. The FabAV was immediately discontinued and she received intravenous diphenhydramine and famotidine with gradual resolution of symptoms. On further discussion, she denied a history of α-gal or papaya allergy but rarely ate red meat and endorsed sustaining frequent tick bites. Subsequent antibody testing was significant for an α-1,3-galactose IgE concentration of 45,000 U/L (normal allergy. To our knowledge, this is the first report of FabAV hypersensitivity associated with an underlying α-gal allergy.

Are exposure predictions, used for the prioritization of pharmaceuticals in the environment, fit for purpose?

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Burns, Emily E; Thomas-Oates, Jane; Kolpin, Dana W; Furlong, Edward T; Boxall, Alistair B A

2017-10-01

Prioritization methodologies are often used for identifying those pharmaceuticals that pose the greatest risk to the natural environment and to focus laboratory testing or environmental monitoring toward pharmaceuticals of greatest concern. Risk-based prioritization approaches, employing models to derive exposure concentrations, are commonly used, but the reliability of these models is unclear. The present study evaluated the accuracy of exposure models commonly used for pharmaceutical prioritization. Targeted monitoring was conducted for 95 pharmaceuticals in the Rivers Foss and Ouse in the City of York (UK). Predicted environmental concentration (PEC) ranges were estimated based on localized prescription, hydrological data, reported metabolism, and wastewater treatment plant (WWTP) removal rates, and were compared with measured environmental concentrations (MECs). For the River Foss, PECs, obtained using highest metabolism and lowest WWTP removal, were similar to MECs. In contrast, this trend was not observed for the River Ouse, possibly because of pharmaceutical inputs unaccounted for by our modeling. Pharmaceuticals were ranked by risk based on either MECs or PECs. With 2 exceptions (dextromethorphan and diphenhydramine), risk ranking based on both MECs and PECs produced similar results in the River Foss. Overall, these findings indicate that PECs may well be appropriate for prioritization of pharmaceuticals in the environment when robust and local data on the system of interest are available and reflective of most source inputs. Environ Toxicol Chem 2017;36:2823-2832. © 2017 SETAC. © 2017 SETAC.

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

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Barrett JA

2015-05-01

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.

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

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Grobosch, T; Lemm-Ahlers, U

2002-04-01

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.

Direct injection of tissue extracts in liquid chromatography/tandem mass spectrometry for the determination of pharmaceuticals and other contaminants of emerging concern in mollusks.

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Bayen, Stéphane; Estrada, Elvagris Segovia; Juhel, Guillaume; Kelly, Barry C

2015-07-01

In the present study, a straightforward approach was validated for the analysis of pharmaceutically active compounds and endocrine-disrupting chemicals in the mollusk tissues, with a focus on two species commonly consumed in Southeast Asia (green mussels: Perna viridis; lokan clams: Polymesoda expansa). This approach relied on a simple solvent extraction (shaker table) followed by direct injection in liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). This "cleanup-free" approach was made possible by the use of isotopically labeled surrogates (to correct for matrix effects) and a post-column switch on the LC-MS/MS system (to remove potential interfering material). Altogether, relative recoveries were satisfactory for 36 out of 44 compounds (26-163% range) and excellent for 27 out of 44 compounds (79-107% range). Method detection limits (MDLs) were usually expressed in the nanogram per gram wet weight (ww) range and below. The method was successfully applied to 16 batches of green mussel samples collected in Singapore coastal waters. Trace levels of six compounds were detected in mussel tissues: caffeine (0.22-1.55 ng g(-1) ww), carbamazepine (diphenhydramine (

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

Science.gov (United States)

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.

2017-01-01

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.

Acute intestinal injury induced by acetic acid and casein: prevention by intraluminal misoprostol

International Nuclear Information System (INIS)

Miller, M.J.; Zhang, x.J.; Gu, x.A.; Clark, D.A.

1991-01-01

Acute injury was established in anesthetized rabbits by intraluminal administration of acetic acid with and without bovine casein, into loops of distal small intestine. Damage was quantified after 45 minutes by the blood-to-lumen movement of 51 Cr-labeled ethylenediaminetetraacetic acid (EDTA) and fluorescein isothiocyanate-tagged bovine serum albumin as well as luminal fluid histamine levels. The amount of titratable acetic acid used to lower the pH of the treatment solutions to pH 4.0 was increased by the addition of calcium gluconate. Luminal acetic acid caused a 19-fold increase in 51 Cr-EDTA accumulation over saline controls; casein did not modify this effect. In saline controls, loop fluid histamine levels bordered on the limits of detection (1 ng/g) but were elevated 19-fold by acetic acid exposure and markedly increased (118-fold) by the combination of acid and casein. Intraluminal misoprostol (3 or 30 micrograms/mL), administered 30 minutes before acetic acid, significantly attenuated the increase in epithelial permeability (luminal 51 Cr-EDTA, fluorescein isothiocyanate-bovine serum albumin accumulation) and histamine release (P less than 0.05). Diphenhydramine, alone or in combination with cimetidine, and indomethacin (5 mg/kg IV) were not protective. It is concluded that exposure of the epithelium to acetic acid promotes the transepithelial movement of casein leading to enhanced mast cell activation and mucosal injury. Damage to the epithelial barrier can be prevented by misoprostol

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

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Tadiboyina Sirisha

2015-12-01

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.

Histamine delays gastric emptying of solid food in man through histamine, receptors

International Nuclear Information System (INIS)

Sridhar, K.; Lange, R.; McCallum, R.W.

1984-01-01

The authors have shown that histamine (H) contracts the cat pylorus and duodenum through H/sub 1/ receptor mechanisms. The authors investigated the effect of H infusion on gastric emptying (GE) and the role of H/sub 1/ and H/sub 2/ receptor blockade in healthy volunteers. Radionuclide GE studies were performed using chicken liver labeled in vivo with /sup 99m/Technetium-sulfur colloid as a marker of solid food. Study days were as follows: a baseline GE study (Day 1); H infused continuously IV at a rate of 40 μg/kg/hr during the GE study (Day 2); an IV bolus of 50 mg of diphenhydramine (Day 3), or 300 mg cimetidine (Day 4) given just prior to the continuous infusion of H; a final day when cimetidine was given alone (Day 5). GE was monitored for 2 hours on each day. The results of days 1, 2 and 3 are summarized below (+p<0.05 vs baseline or Day 1). Pretreatment with cimetidine (Day 4) augmented the delay in GE induced by H infusion, while cimetidine without H (Day 5) had no effect on GE. The authors conclude that: 1) H given at a dose which elicits maximal acid secretory response in man significantly delays GE; and 2) H/sub 1/ receptor blockade but not H/sub 2/ blockade prevented this effect. Histamine may play a modulatory role in human gastric emptying through an H/sub 1/ receptor mechanism

Accumulation of contaminants of emerging concern in food crops-part 2: Plant distribution.

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Hyland, Katherine C; Blaine, Andrea C; Higgins, Christopher P

2015-10-01

Arid agricultural regions often turn to using treated wastewater (reclaimed water) to irrigate food crops. Concerns arise, however, when considering the potential for persistent contaminants of emerging concern to accumulate into plants intended for human consumption. The present study examined the accumulation of a suite of 9 contaminants of emerging concern into 2 representative food crops, lettuce and strawberry, following uptake via the roots and subsequent distribution to other plant tissues. Calculating accumulation metrics (concentration factors) allowed for comparison of the compartmental affinity of each chemical for each plant tissue compartment. The root concentration factor was found to exhibit a positive linear correlation with the pH-adjusted octanol-water partition coefficient (DOW ) for the target contaminants of emerging concern. Coupled with the concentration-dependent accumulation observed in the roots, this result implies that accumulation of these contaminants of emerging concern into plant roots is driven by passive partitioning. Of the contaminants of emerging concern examined, nonionizable contaminants, such as triclocarban, carbamazepine, and organophosphate flame retardants displayed the greatest potential for translocation from the roots to above-ground plant compartments. In particular, the organophosphate flame retardants displayed increasing affinity for shoots and fruits with decreasing size/octanol-water partition coefficient (KOW ). Cationic diphenhydramine and anionic sulfamethoxazole, once transported to the shoots of the strawberry plant, demonstrated the greatest potential of the contaminants examined to be then carried to the edible fruit portion. © 2015 SETAC.

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.

Science.gov (United States)

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

2015-10-10

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Acute intestinal injury induced by acetic acid and casein: prevention by intraluminal misoprostol

Energy Technology Data Exchange (ETDEWEB)

Miller, M.J.; Zhang, x.J.; Gu, x.A.; Clark, D.A. (Department of Pediatrics, Louisiana State University School of Medicine, New Orleans (USA))

1991-07-01

Acute injury was established in anesthetized rabbits by intraluminal administration of acetic acid with and without bovine casein, into loops of distal small intestine. Damage was quantified after 45 minutes by the blood-to-lumen movement of {sup 51}Cr-labeled ethylenediaminetetraacetic acid (EDTA) and fluorescein isothiocyanate-tagged bovine serum albumin as well as luminal fluid histamine levels. The amount of titratable acetic acid used to lower the pH of the treatment solutions to pH 4.0 was increased by the addition of calcium gluconate. Luminal acetic acid caused a 19-fold increase in {sup 51}Cr-EDTA accumulation over saline controls; casein did not modify this effect. In saline controls, loop fluid histamine levels bordered on the limits of detection (1 ng/g) but were elevated 19-fold by acetic acid exposure and markedly increased (118-fold) by the combination of acid and casein. Intraluminal misoprostol (3 or 30 micrograms/mL), administered 30 minutes before acetic acid, significantly attenuated the increase in epithelial permeability (luminal {sup 51}Cr-EDTA, fluorescein isothiocyanate-bovine serum albumin accumulation) and histamine release (P less than 0.05). Diphenhydramine, alone or in combination with cimetidine, and indomethacin (5 mg/kg IV) were not protective. It is concluded that exposure of the epithelium to acetic acid promotes the transepithelial movement of casein leading to enhanced mast cell activation and mucosal injury. Damage to the epithelial barrier can be prevented by misoprostol.

Concentrations of selected pharmaceuticals and antibiotics in south-central Pennsylvania waters, March through September 2006

Science.gov (United States)

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

2007-01-01

�g/L), and trimethoprim (0.256 μg/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 μg/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 μg/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 μg/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.

Modulatory effects of taurine on jejunal contractility

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Q.Y. Yao

2014-12-01

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.

Modulatory effects of taurine on jejunal contractility

Energy Technology Data Exchange (ETDEWEB)

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

2014-10-14

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.

A Randomized Controlled Pilot Study Comparing the Impact of Aprepitant and Fosaprepitant on Chemotherapy Induced Nausea and Vomiting in Patients Treated for Gynecologic Cancer.

Science.gov (United States)

Micha, John P; Rettenmaier, Mark A; Brown, John V; Mendivil, Alberto; Abaid, Lisa N; Lopez, Katrina L; Goldstein, Bram H

2016-02-01

The purpose of this pilot study was to compare the response rates and daily living activities of patients with newly diagnosed gynecologic cancer treated with fosaprepitant or aprepitant in the management of chemotherapy-induced nausea and vomiting. Eligible participants were randomized to either intravenous fosaprepitant (150 mg, day 1) or oral aprepitant (125 mg on day 1 and 80 mg on days 2-3) before undergoing weekly paclitaxel (80 mg/2)(2) and monthly carboplatin (AUC 6)-based chemotherapy. In addition, standard premedications (eg, ranitidine, dexamethasone, and diphenhydramine) were administered intravenously on day 1. Response evaluation and impact on daily life were measured throughout the acute phase (0-24 hours), delayed period (days 2-4), and overall phase (0-120 hours) of the patients' initial chemotherapy cycle via the Functional Living Index-Emesis. In the current investigation, 20 gynecologic cancer subjects were treated with either fosaprepitant (n = 10) or aprepitant (n = 10) before their first chemotherapy cycle. We observed 7 overall complete responses (70%, no emetic episodes or rescue medications) in the aprepitant group and 6 (60%) in the fosaprepitant cohort (P = 0.660). In addition, both treatment groups reported similarly, favorable rates of daily living activities throughout the acute (P = 0.626) and delayed (P = 0.648) phases of cycle 1 chemotherapy. The findings from the current analysis suggest that intravenous fosaprepitant and oral aprepitant confer beneficial antiemetic prevention. Moreover, the 2 medications theoretically afford a favorable impact on daily living, thereby potentially facilitating the completion of a patient's clinically prescribed chemotherapy regimen.

Analysis of risperidone and 9-hydroxyrisperidone in human plasma, urine and saliva by MEPS-LC-UV.

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Mandrioli, Roberto; Mercolini, Laura; Lateana, Domenico; Boncompagni, Giancarlo; Raggi, Maria Augusta

2011-01-15

Risperidone is currently one of the most frequently prescribed atypical antipsychotic drugs; its main active metabolite 9-hydroxyrisperidone contributes significantly to the therapeutic effects observed. An original analytical method is presented for the simultaneous analysis of risperidone and the metabolite in plasma, urine and saliva by high-performance liquid chromatography coupled to an original sample pre-treatment procedure based on micro-extraction by packed sorbent (MEPS). The assays were carried out using a C8 reversed-phase column and a mobile phase composed of 73% (v/v) acidic phosphate buffer (30 mM, pH 3.0) containing 0.23% triethylamine and 27% (v/v) acetonitrile. The UV detector was set at 238 nm and diphenhydramine was used as the internal standard. The sample pre-treatment by MEPS was carried out on a C8 sorbent. The extraction yields values were higher than 92% for risperidone and 90% for 9-hydroxyrisperidone, with RSD for precision always lower than 7.9% for both analytes. Limit of quantification values in the different matrices were 4 ng/mL or lower for risperidone and 6 ng/mL or lower for the metabolite. The method was successfully applied to plasma, urine and saliva samples from psychotic patients undergoing therapy with risperidone, with satisfactory accuracy results (recovery>89%) and no interference from other drugs. Thus, the method seems to be suitable for the therapeutic drug monitoring of schizophrenic patients using the three different biological matrices plasma, urine and saliva. Copyright © 2010 Elsevier B.V. All rights reserved.

Modulatory effects of taurine on jejunal contractility

International Nuclear Information System (INIS)

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

2014-01-01

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 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

Modulatory effects of taurine on jejunal contractility

Science.gov (United States)

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

2014-01-01

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

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

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

2015-02-01

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.

Event-related potentials reflect impaired temporal interval learning following haloperidol administration.

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Forster, Sarah E; Zirnheld, Patrick; Shekhar, Anantha; Steinhauer, Stuart R; O'Donnell, Brian F; Hetrick, William P

2017-09-01

Signals carried by the mesencephalic dopamine system and conveyed to anterior cingulate cortex are critically implicated in probabilistic reward learning and performance monitoring. A common evaluative mechanism purportedly subserves both functions, giving rise to homologous medial frontal negativities in feedback- and response-locked event-related brain potentials (the feedback-related negativity (FRN) and the error-related negativity (ERN), respectively), reflecting dopamine-dependent prediction error signals to unexpectedly negative events. Consistent with this model, the dopamine receptor antagonist, haloperidol, attenuates the ERN, but effects on FRN have not yet been evaluated. ERN and FRN were recorded during a temporal interval learning task (TILT) following randomized, double-blind administration of haloperidol (3 mg; n = 18), diphenhydramine (an active control for haloperidol; 25 mg; n = 20), or placebo (n = 21) to healthy controls. Centroparietal positivities, the Pe and feedback-locked P300, were also measured and correlations between ERP measures and behavioral indices of learning, overall accuracy, and post-error compensatory behavior were evaluated. We hypothesized that haloperidol would reduce ERN and FRN, but that ERN would uniquely track automatic, error-related performance adjustments, while FRN would be associated with learning and overall accuracy. As predicted, ERN was reduced by haloperidol and in those exhibiting less adaptive post-error performance; however, these effects were limited to ERNs following fast timing errors. In contrast, the FRN was not affected by drug condition, although increased FRN amplitude was associated with improved accuracy. Significant drug effects on centroparietal positivities were also absent. Our results support a functional and neurobiological dissociation between the ERN and FRN.

Rupatadine inhibits inflammatory mediator release from human laboratory of allergic diseases 2 cultured mast cells stimulated by platelet-activating factor.

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Alevizos, Michail; Karagkouni, Anna; Vasiadi, Magdalini; Sismanopoulos, Nikolaos; Makris, Michael; Kalogeromitros, Dimitrios; Theoharides, Theoharis C

2013-12-01

Mast cells are involved in allergy and inflammation by the secretion of multiple mediators, including histamine, cytokines, and platelet-activating factor (PAF), in response to different triggers, including emotional stress. PAF has been associated with allergic inflammation, but there are no clinically available PAF inhibitors. To investigate whether PAF could stimulate human mast cell mediator release and whether rupatadine (RUP), a dual histamine-1 and PAF receptor antagonist, could inhibit the effect of PAF on human mast cells. Laboratory of allergic diseases 2 cultured mast cells were stimulated with PAF (0.001, 0.01, and 0.1 μmol/L) and substance P (1 μmol/L) with or without pretreatment with RUP (2.5 and 25 μmol/L), which was added 10 minutes before stimulation. Release of β-hexosaminidase was measured in supernatant fluid by spectrophotoscopy, and histamine, interleukin-8, and tumor necrosis factor were measured by enzyme-linked immunosorbent assay. PAF stimulated a statistically significant release of histamine, interleukin-8, and tumor necrosis factor (0.001-0.1 μmol/L) that was comparable to that stimulated by substance P. Pretreatment with RUP (25 μmol/L) for 10 minutes inhibited this effect. In contrast, pretreatment of laboratory of allergic diseases 2 cells with diphenhydramine (25 μmol/L) did not inhibit mediator release, suggesting that the effect of RUP was not due to its antihistaminic effect. PAF stimulates human mast cell release of proinflammatory mediators that is inhibited by RUP. This action endows RUP with additional properties in treating allergic inflammation. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

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

2009-04-01

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.

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

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Pamela L. Tannenbaum

2014-05-01

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.

An NMR investigation of the structure, function and role of the hERG channel selectivity filter in the long QT syndrome.

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Gravel, Andrée E; Arnold, Alexandre A; Dufourc, Erick J; Marcotte, Isabelle

2013-06-01

The human ether-a-go-go-related gene (hERG) voltage-gated K(+) channels are located in heart cell membranes and hold a unique selectivity filter (SF) amino acid sequence (SVGFG) as compared to other K(+) channels (TVGYG). The hERG provokes the acquired long QT syndrome (ALQTS) when blocked, as a side effect of drugs, leading to arrhythmia or heart failure. Its pore domain - including the SF - is believed to be a cardiotoxic drug target. In this study combining solution and solid-state NMR experiments we examine the structure and function of hERG's L(622)-K(638) segment which comprises the SF, as well as its role in the ALQTS using reported active drugs. We first show that the SF segment is unstructured in solution with and without K(+) ions in its surroundings, consistent with the expected flexibility required for the change between the different channel conductive states predicted by computational studies. We also show that the SF segment has the potential to perturb the membrane, but that the presence of K(+) ions cancels this interaction. The SF moiety appears to be a possible target for promethazine in the ALQTS mechanism, but not as much for bepridil, cetirizine, diphenhydramine and fluvoxamine. The membrane affinity of the SF is also affected by the presence of drugs which also perturb model DMPC-based membranes. These results thus suggest that the membrane could play a role in the ALQTS by promoting the access to transmembrane or intracellular targets on the hERG channel, or perturbing the lipid-protein synergy. Copyright © 2013 Elsevier B.V. All rights reserved.

Respiratory drugs prescribed off-label among children in the outpatient clinics of a hospital in Malaysia.

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Mohamad, Nurul Fadilah; Mhd Ali, Adliah; Mohamed Shah, Noraida

2015-02-01

Prescribing medicines in an unlicensed and off-label manner for children is a widespread practice around the world. To determine the extent and predictors of off-label respiratory drug prescriptions for children in the outpatient clinics of a hospital in Malaysia. Outpatient clinics at the Universiti Kebangsaan Malaysia Medical Centre, a tertiary teaching hospital in Malaysia. The pharmacy-based computer system and medical records of the patients were utilized to collect data from 220 pediatric patients who were prescribed at least one respiratory drug from July 2011 to December 2011. Characteristics of the off-label respiratory drug prescriptions were measured. A total of 134 children (60.9 %) received at least one respiratory drug prescribed in an off-label manner. The most common reasons for the off-label prescribing of drugs were off-label use by indication (31.5 %), followed by higher than the recommended dose (24.9 %) and lower than the recommended frequency (17.1 %). Diphenhydramine was the most common respiratory drug prescribed off-label. The number of medications prescribed was the only significant predictor of off-label prescription of respiratory drugs. Pediatric patients receiving 4-6 medications were 7.8 times more likely to receive at least one off-label respiratory drug compared to pediatric patients that received 1-3 medications (OR 7.8, 95 % CI 1.74-37.44). There was substantial prescribing of respiratory drugs for children in an off-label manner at the outpatient clinics at the Universiti Kebangsaan Malaysia Medical Centre. This highlights the need for more research to be carried out on respiratory drugs in the pediatric population.

Simultaneous determination of ten antiepileptic drugs in human plasma by liquid chromatography and tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in therapeutic drug monitoring.

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Yin, Lei; Wang, Tingting; Shi, Meiyun; Zhang, Ying; Zhao, Xiaojun; Yang, Yan; Gu, Jingkai

2016-03-01

A simple, rapid, and high-throughput liquid chromatography with tandem mass spectrometry method for the simultaneous quantitation of ten antiepileptic drugs in human plasma has been developed and validated. The method required only 10 μL of plasma. After simple protein precipitation using acetonitrile, the analytes and internal standard diphenhydramine were separated on a Zorbax SB-C18 column (50 × 4.6 mm, 2.7 μm) using acetonitrile/water as the mobile phase at a flow rate of 0.9 mL/min. The total run time was 6 min for each sample. The validation results of specificity, matrix effects, recovery, linearity, precision, and accuracy were satisfactory. The lower limit of quantification was 0.04 μg/mL for carbamazepine, 0.02 μg/mL for lamotrigine, 0.01 μg/mL for oxcarbazepine, 0.4 μg/mL for 10-hydroxycarbazepine, 0.1 μg/mL for carbamazepine-10,11-epoxide, 0.15 μg/mL for levetiracetam, 0.06 μg/mL for phenytoin, 0.3 μg/mL for valproic acid, 0.03 μg/mL for topiramate, and 0.15 μg/mL for phenobarbital. The intraday precision and interday precision were less than 7.6%, with the accuracy ranging between -8.1 and 7.9%. The method was successfully applied to therapeutic drug monitoring of 1237 patients with epilepsy after administration of standard antiepileptic drugs. The method has been proved to meet the high-throughput requirements in therapeutic drug monitoring. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nicotine transport in lung and non-lung epithelial cells.

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Takano, Mikihisa; Kamei, Hidetaka; Nagahiro, Machi; Kawami, Masashi; Yumoto, Ryoko

2017-11-01

Nicotine is rapidly absorbed from the lung alveoli into systemic circulation during cigarette smoking. However, mechanism underlying nicotine transport in alveolar epithelial cells is not well understood to date. In the present study, we characterized nicotine uptake in lung epithelial cell lines A549 and NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Characteristics of [ 3 H]nicotine uptake was studied using these cell lines. Nicotine uptake in A549 cells occurred in a time- and temperature-dependent manner and showed saturation kinetics, with a Km value of 0.31mM. Treatment with some organic cations such as diphenhydramine and pyrilamine inhibited nicotine uptake, whereas treatment with organic cations such as carnitine and tetraethylammonium did not affect nicotine uptake. Extracellular pH markedly affected nicotine uptake, with high nicotine uptake being observed at high pH up to 11.0. Modulation of intracellular pH with ammonium chloride also affected nicotine uptake. Treatment with valinomycin, a potassium ionophore, did not significantly affect nicotine uptake, indicating that nicotine uptake is an electroneutral process. For comparison, we assessed the characteristics of nicotine uptake in another lung epithelial cell line NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Interestingly, these cell lines showed similar characteristics of nicotine uptake with respect to pH dependency and inhibition by various organic cations. The present findings suggest that a similar or the same pH-dependent transport system is involved in nicotine uptake in these cell lines. A novel molecular mechanism of nicotine transport is proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

Predicted and observed therapeutic dose exceedances of ionizable pharmaceuticals in fish plasma from urban coastal systems.

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Scott, W Casan; Du, Bowen; Haddad, Samuel P; Breed, Christopher S; Saari, Gavin N; Kelly, Martin; Broach, Linda; Chambliss, C Kevin; Brooks, Bryan W

2016-04-01

Instream flows of the rapidly urbanizing watersheds and estuaries of the Gulf of Mexico in Texas (USA) are increasingly dominated by reclaimed waters. Though ionizable pharmaceuticals have received increasing attention in freshwaters, many research questions remain unanswered, particularly in tidally influenced urban coastal systems, which experience significant spatiotemporal variability in pH that influences bioavailability and bioaccumulation. The authors coupled fish plasma modeling of therapeutic hazard values with field monitoring of water chemistry variability and pharmaceutical occurrence to examine whether therapeutic hazards to fish existed within these urban coastal ecosystems and whether therapeutic hazards differed within and among coastal locations and seasons. Spatial and temporal fluctuations in pH within study sites altered the probability of encountering pharmaceutical hazards to fish. Significant water quality differences were consistently observed among traditional parameters and pharmaceuticals collected from surface and bottom waters, which are rarely sampled during routine surface water quality assessments. The authors then compared modeling predictions of fish plasma concentrations of pharmaceuticals to measured plasma levels from various field-collected fish species. Diphenhydramine and diltiazem were observed in plasma of multiple species, and diltiazem exceeded human therapeutic doses in largemouth bass, catfish, and mullet inhabiting these urban estuaries. Though the present study only examined a small number of target analytes, which represent a microcosm of the exposome of these fish, coastal systems are anticipated to be more strongly influenced by continued urbanization, altered instream flows, and population growth in the future. Unfortunately, aquatic toxicology information for diltiazem and many other pharmaceuticals is not available for marine and estuarine organisms, but such field observations suggest that potential adverse

Receptor-independent, vacuolar ATPase-mediated cellular uptake of histamine receptor-1 ligands: Possible origin of pharmacological distortions and side effects

International Nuclear Information System (INIS)

Morissette, Guillaume; Lodge, Robert; Bouthillier, Johanne; Marceau, Francois

2008-01-01

The aims of this study were to investigate whether several histamine receptor agonists and antagonists are subjected to receptor-independent ion trapping into acidic organelles, and whether this sequestration influences their pharmacological or toxicological properties. Vacuolar (V)-ATPase-dependent intracellular sequestration of agonists was recognized as morphological alterations (large fluid-filled vacuoles for betahistine and 1-methylhistamine, granular uptake for fluorescent BODIPY FL histamine) prevented by the specific V-ATPase inhibitor bafilomycin A1 in rabbit vascular smooth muscle cells. Lipophilicity was the major determinant of these cellular effects (order of potency: BODIPY FL histamine > betahistine > 1-methylhistamine > histamine) that occurred at high concentrations. This ranking was dissociable from the potency order for H 1 receptor-mediated contraction of the rabbit aorta, a response uninfluenced by bafilomycin. Antihistamines are inherently more lipophilic and caused vacuolization of a proportion of cells at 5-500 μM. Agonist or antagonist-induced vacuoles were of macroautophagic nature (labeled with GFP-conjugated LC3, Rab7 and CD63; detection of LC3 II). Further, the 2 most lipophilic antihistamines tested, astemizole and terfenadine, were potentiated by V-ATPase blockade in the aortic contractility assay (13- and 3.6-fold more potent, respectively, pA 2 scale), suggesting that V-ATPase-mediated cation trapping sequesters these antagonists from the vicinity of H 1 receptors in the therapeutic concentration range. This potentiation did not apply to less lipophilic antagonists (pyrilamine, diphenhydramine). While some agonists and all tested antagonists of the histamine H 1 receptors induce the V-ATPase-dependent vacuolar and autophagic cytopathology, sequestration affects the pharmacology of only the most lipophilic antagonists, the ones prone to off-target arrhythmogenic side effects

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

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Kjell A Svensson

2012-05-01

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.

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

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R. Mason Curtis

2016-06-01

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.

Pharmacological screening of Ageratum conyzoides L. (mentrasto

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Lucia A. Yamamoto

1991-01-01

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.

Intranasal desmopressin versus blood transfusion in cirrhotic patients with coagulopathy undergoing dental extraction: a randomized controlled trial.

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Stanca, Carmen M; Montazem, Andre H; Lawal, Adeyemi; Zhang, Jin X; Schiano, Thomas D

2010-01-01

Cirrhotic patients waiting for liver transplantation who need dental extractions are given fresh frozen plasma and/or platelets to correct coagulopathy. This is costly and may be associated with transfusion reactions and fluid overload. We evaluated the efficacy of intranasal desmopressin as an alternative to transfusion to correct the coagulopathy of cirrhotic patients undergoing dental extraction. Cirrhotic patients with platelet counts of 30,000 to 50,000/microL and/or international normalized ratio (INR) 2.0 to 3.0 were enrolled in a prospective, controlled, randomized clinical trial. Blood transfusion (fresh frozen plasma 10 mL/kg and/or 1 unit of single donor platelets, respectively) or intranasal desmopressin (300 microg) were given before dental extraction. A standard oral and maxillofacial surgical treatment protocol was performed by the same surgeon. Patients were followed for postextraction bleeding and side-effects over the next 24 to 48 hours. No significant differences were noted between the 2 groups in gender, age, INR, platelet count, creatinine, total bilirubin, ALT, albumin, MELD score, or number of teeth removed (median 3 vs 4). The number of teeth removed ranged between 1 and 31 in the desmopressin group and 1 and 22 in the transfusion group. No patients in desmopressin group required rescue blood transfusion after extraction. One patient in the transfusion group had bleeding after the procedure and required an additional transfusion. Another patient experienced an allergic reaction at the end of transfusion, which was effectively treated with diphenhydramine. Treatment associated average costs were lower for desmopressin ($700/patient) compared with transfusion ($1,173/patient). Intranasal desmopressin was as effective as blood transfusion in achieving hemostasis in cirrhotic patients with moderate coagulopathy undergoing dental extraction. Intranasal desmopressin was much more convenient, less expensive, and well tolerated.

Clozapine-associated extrapyramidal reaction.

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Elliott, E S; Marken, P A; Ruehter, V L

2000-05-01

To report a case of extrapyramidal reaction associated with a dosage increase of clozapine. A 44-year-old white man with a 20-year history of chronic paranoid schizophrenia was admitted to an inpatient psychiatric facility. His prior medications restarted on admission were clozapine 650 mg at bedtime, haloperidol 10 mg at bedtime, clonazepam 2 mg/d, and aspirin 325 mg/d. Two days after admission (hospital day 3), clozapine and clonazepam were discontinued, and he was prescribed haloperidol 5 mg every morning and 10 mg every evening. Stabilization occurred over the following 24 days, with progressively lower dosages of haloperidol and increasing dosages of clozapine. Haloperidol was discontinued on day 24. On day 47, the patient was agitated and making bizarre statements; thus, the morning dose of clozapine was increased by 50 mg (total 450 mg/d). On day 48 at 2200, a dystonic reaction was diagnosed; he received intramuscular diphenhydramine 50 mg, which caused the reaction to subside. At the time of the adverse reaction, he was prescribed clozapine 450 mg/d, vitamin E 400 IU three times daily, aspirin 325 mg/d, and acetaminophen, milk of magnesia, and Maalox as needed. Although the risk of extrapyramidal symptoms (EPS) is significantly lower with clozapine than with conventional agents, elevated clozapine blood concentrations have been reported to cause EPS; other reports have cited severe dystonias and dyskinesias on abrupt clozapine withdrawal. Considering the medications prescribed at the time and the discontinuation of haloperidol 24 days before the event, clozapine was the most likely cause of the extrapyramidal reaction. Regardless of anticipated safety associated with novel antipsychotics such as clozapine, reports of dystonic reactions must be taken into account and patients monitored appropriately.

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

Science.gov (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

2009-12-01

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

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

Science.gov (United States)

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

2016-11-15

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 rangeemerging pollutants in the effluent were below 210ng/L. WWTP 2 showed high emerging pollutant removals, 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

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

Science.gov (United States)

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

2014-01-01

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.

Analysis of Gastric Lavage Reported to a Statewide Poison Control System.

Science.gov (United States)

Donkor, Jimmy; Armenian, Patil; Hartman, Isaac N; Vohra, Rais

2016-10-01

As decontamination trends have evolved, gastric lavage (GL) has become a rare procedure. The current information regarding use, outcomes, and complications of GL could help refine indications for this invasive procedure. We sought to determine case type, location, and complications of GL cases reported to a statewide poison control system. This is a retrospective review of the California Poison Control System (CPCS) records from 2009 to 2012. Specific substances ingested, results and complications of GL, referring hospital ZIP codes, and outcomes were examined. Nine hundred twenty-three patients who underwent GL were included in the final analysis, ranging in age from 9 months to 88 years. There were 381 single and 540 multiple substance ingestions, with pill fragment return in 27%. Five hundred thirty-six GLs were performed with CPCS recommendation, while 387 were performed without. Complications were reported for 20 cases. There were 5 deaths, all after multiple ingestions. Among survivors, 37% were released from the emergency department, 13% were admitted to hospital wards, and 48% were admitted to intensive care units. The most commonly ingested substances were nontricyclic antidepressant psychotropics (n = 313), benzodiazepines (n = 233), acetaminophen (n = 191), nonsteroidal anti-inflammatory drugs (n = 107), diphenhydramine (n = 70), tricyclic antidepressants (n = 45), aspirin (n = 45), lithium (n = 36), and antifreeze (n = 10). The geographic distribution was clustered near regions of high population density, with a few exceptions. Toxic agents for which GL was performed reflected a broad spectrum of potential hazards, some of which are not life-threatening or have effective treatments. Continuing emergency physician and poison center staff education is required to assist in patient selection. Copyright © 2016 Elsevier Inc. All rights reserved.

Systemic delivery of atropine sulfate by the MicroDose Dry-Powder Inhaler.

Science.gov (United States)

Corcoran, T E; Venkataramanan, R; Hoffman, R M; George, M P; Petrov, A; Richards, T; Zhang, S; Choi, J; Gao, Y Y; Oakum, C D; Cook, R O; Donahoe, M

2013-02-01

Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses × 0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine.

A model for self-treatment of four sub-types of symptomatic 'depression' using non-prescription agents: neuroticism (anxiety and emotional instability); malaise (fatigue and painful symptoms); demotivation (anhedonia) and seasonal affective disorder 'SAD'.

Science.gov (United States)

Charlton, Bruce G

2009-01-01

This article will present a model for how 'depression' (i.e. depressive symptoms) can be divided into four self-diagnosed sub-types or causes which might then be self-treated using agents available without prescription. (Another, much rarer, cause of depressed symptoms is the classical illness of 'melancholia', which when severe cannot be self-treated and typically requires hospitalization.) A self-management option and alternative is now needed due to the an inappropriate emphasis of modern psychiatry on treatment of imprecise syndromal 'disorders' which may entail treating 'depression' at the cost of making the patient feel and function worse. By contrast, the basic theoretical stance of self-management is that depressed mood should be seen as a result of unpleasant symptoms - and it is the symptoms that require treatment, not the mood itself. Furthermore, drugs (or other interventions) need to be classified in terms of their potential therapeutic effects on these symptoms that may cause depressed mood. The four common causes of depressed mood considered here are the personality trait of Neuroticism; the state of malaise (fatigue, aching etc) which accompanies an illness with an activated immune system; demotivation due to lack of positive emotions (anhedonia); and the syndrome of seasonal affective disorder (SAD). Each of the four sub-types is then 'matched' with a first-line non-prescription agent. The 'stabilizing' agents such as St John's Wort and the antihistamines chlorpheniramine and diphenhydramine are used for treatment of Neuroticism; analgesics/pain killers such as aspirin, ibuprofen, paracetamol/acetaminophen and the opiates are used to treat malaise; energizing agents such as caffeine and nicotine are used for the treatment of demotivation; and bright light used in the early morning to treat SAD. Self-treatments are intended to be used after research and experimentally, on a trial-and-error basis; with self-monitoring of beneficial and harmful

Profile of diseases prevalent in a tribal locality in Jharkhand, India: A family medicine practitioner′s perspective

Directory of Open Access Journals (Sweden)

Sumit Kumar

2015-01-01

Full Text Available Background: Majority of Indian population is dependent on general practitioners (GPs for medical services at primary care level in India. They are most preferred and considered to be first contact person for medical services at primary care level. But advances in medical science has put more emphasis on specialist culture and average Bachelor of Medicine and Bachelor of Surgery (MBBS graduates who are working as general physician are gradually feeling themselves less competent because they are less exposed to latest advances in treatment of diseases. Amidst such scenario, Christian Medical College (CMC has come up with an idea: "The refer less and resolve more initiative". It has started a decentralized 2-year family medicine distance diploma course (Postgraduate Diploma in Family Medicine (PGDFM now accredited by Dr. MGR Medical University, Chennai, Tamil Nadu, that trains the GPs to become family medicine specialist. Materials and Methods: As component of PGDFM course, this study was conducted to provide better understanding of prevalent ailments and common treatment provided by the GPs in the community at present giving key insight of current practice in rural area by a registered family medicine practitioner. Results: As part of study, among 500 patients evaluated, three most common diagnosis were upper respiratory infections (URIs; 18%, acute gastroenteritis including water-borne diseases (15.8%, and anemia (10.4%. Treatment given to these patients comprised of mostly of antipyretic, analgesic, and antimicrobial agents. Most common drug prescribed was paracetamol for fever. Other common drugs prescribed were amoxicillin/clavulanic acid, chloroquine, artemisin derivative, doxycycline, co-trimoxazole, miltefosine, cephalexin, ceftriaxone sodium, cefixime, oral rehydration salts, ranitidine, omeprazole, pantoprazole, metronidazole, albendazole, ondansetron, diclofenac sodium, piroxicam, ibuprofen, diphenhydramine, codeine-sulfate, amlodipine

Peroxynitrite-induced relaxation in isolated rat aortic rings and mechanisms of action

International Nuclear Information System (INIS)

Li Jianfeng; Li Wenyan; Altura, Bella T.; Altura, Burton M.

2005-01-01

The present study was designed to evaluate the effects of peroxynitrite (ONOO - ), the product of superoxide and nitric oxide, on isolated segments of rat aorta. In the absence of any vasoactive agent, ONOO - (from 10 -8 to 10 -4 M) failed to alter the basal tension. In phenylephrine (PE; 5 x 10 -7 M)-precontracted rat aortic rings (RAR), ONOO - elicited concentration-dependent relaxation at concentrations of from 10 -8 to 10 -4 M. The effective concentrations producing approximately 50% of maximal relaxation (ED 5 ) to ONOO - were 1.84 x 10 -5 M and 1.96 x 10 -5 M in intact and denuded RAR, respectively (P > 0.05). No significant differences in the relaxation responses were found between RAR with or without endothelium (P > 0.05). The presence of either 5 μM methylene blue (MB) or 5 μM 1H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one (ODQ) significantly inhibited the relaxations induced by ONOO - . Sildenafil (10 -7 M), on the other hand, significantly potentiated the ONOO - -induced relaxations. Tetraethylammonium chloride (T-2265) significantly decreased the ONOO - -induced relaxations in a concentration-dependent manner. However, ONOO - had no effect on RAR precontracted by high KCL (40 mM, n = 6, P > 0.05). Addition of calyculin A also significantly decreased the ONOO - -induced relaxation in a dose-dependent manner. Furthermore, ONOO - significantly inhibited calcium-induced contractions of K + -depolarized aortic rings in a concentration-related manner. Lastly, a variety of other pharmacological agents and antagonists including L-NMMA, L-arginine, indomethacin, atropine, naloxone, diphenhydramine, cimetine, glibenclamide, haloperidol, superoxide dismutase (SOD), and catalase did not influence the relaxant effects of ONOO - on RAR. Our new results suggest that ONOO - -triggered relaxation on rat aortic rings is mediated by elevation of cGMP levels, membrane hyperpolarization via K + -channel activation, activation of myosin phosphatase activity, and

Attenuation of trace organic compounds (TOrCs) inbioelectrochemical systems

KAUST Repository

Werner, Craig M.

2015-04-01

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

Medicine use practices in management of symptoms of acute upper respiratory tract infections in children (≤12 years) in Kampala city, Uganda.

Science.gov (United States)

Ocan, Moses; Aono, Mary; Bukirwa, Clare; Luyinda, Emmanuel; Ochwo, Cathy; Nsambu, Elastus; Namugonza, Stella; Makoba, Joseph; Kandaruku, Enock; Muyende, Hannington; Nakawunde, Aida

2017-09-21

Medicines are commonly accessed and used for management of illness in children without a prescription. This potentially increases the risk of unwanted treatment outcomes. We investigated medicine use practices in management of symptoms of acute upper respiratory tract infections among children (≤12 years) in households in Nakawa division, Kampala city. This was a cross-sectional study conducted among 390 randomly selected children. Data on use of medicines in children (≤12 years) during recent episode of acute upper respiratory tract infection was collected from their care takers using an interviewer administered questionnaire. A recall period of two weeks (14 days) was used in during data collection. The prevalence of giving children non-prescription antimicrobial medicines was 44.8% (38.3-52.2). The most common disease symptoms that the children reportedly had included flu, 84.9% (331/390), cough, 83.1% (324/390), and undefined fever, 69.7% (272/390). Medicines commonly given to children included, paracetamol 53.1% (207/390), Coartem 29.7% (116/390), cough linctus 20.8% (81/390), amoxicillin 18.9% (74/390), Co-trimoxazole 18.5% (72/390), and diphenhydramine 15.4% (60/390). The major sources of medicines given to the children was hospital/clinic, 57.26% (223/390). Most of the children, 81% were given more than one medicine at a time. The majority, 62.3% (243/390) of the care takers who gave the children medicine during the recent illness were not aware of any medicine (s) that should not be given to children. The predictors of non-prescription use of antimicrobial medicines in managing symptoms of acute upper respiratory tract infections in children included, medicines obtained from drug shop (PR: 1.45, CI: 1.14-1.85), medicines at home (PR: 1.8, CI: 0.83-1.198) and type of medicine (antimalarial) (PR: 2.8, CI: 1.17-6.68). Children are commonly given multiple medicines during episodes of acute upper respiratory tract infections with most antimicrobial

Magnetic nanoparticles based dispersive micro-solid-phase extraction as a novel technique for coextraction of acidic and basic drugs from biological fluids and waste water.

Science.gov (United States)

Asgharinezhad, Ali Akbar; Mollazadeh, Narges; Ebrahimzadeh, Homeira; Mirbabaei, Fatemeh; Shekari, Nafiseh

2014-04-18

The coextraction of acidic and basic drugs from different samples is a considerable and disputable concept in sample preparation strategies. In this study, for the first time, simultaneous extraction of acidic and basic drugs with magnetic nanoparticles based dispersive micro-solid phase extraction followed by high performance liquid chromatography-ultraviolet detection was introduced. Cetyltrimethyl ammonium bromide-coated Fe3O4@decanoic acid as an efficient sorbent was successfully applied to adsorb diclofenac (DIC) as an acidic and diphenhydramine (DPH) as a basic model compound. First, appropriate amount of synthetic Fe3O4@decanoic acid nanoparticles was added to aqueous solution of drugs. After adjusting the pH of the solution, cetyltrimethyl ammonium bromide (CTAB) was added to the mixture being stirred at a constant rate. After the adsorption of drugs and decantation of supernatant with a magnetic field, the sorbent was eluted with methanol by fierce vortex. The parameters affecting the extraction efficiency were optimized and obtained as: pH of the sample=9, concentration of CTAB=0.2mmolL(-1), amount of sorbent=10mg, extraction time=5min, no salt addition to sample, type and volume of the eluent=50μL methanol, and desorption time=1min. Under the optimum conditions detection limits and linear dynamic ranges were achieved in the range of 1.8-3.0, 5-1500μgL(-1) for DPH and 1.5-3.5, 5-1500μgL(-1) for DIC, respectively. The percent of extraction recovery and relative standard deviations (n=5) were in the range of 47.3-60, 5.2-9.0 for DPH and 64-76.7, 5.1-5.8 for DIC, respectively. Ultimately, the applicability of the method was successfully confirmed by the extraction and determination of DIC and DPH in human urine, plasma and waste water samples in the range of microgram per liter and satisfactory results were obtained. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

San Nicolas, A C; Lemos, N P

2015-10-01

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

Opioid-Induced "Likeability" and "Feeling Good" Are Not Associated With Return Visits to an ED Among Migraine Patients Administered IV Hydromorphone.

Science.gov (United States)

Friedman, Benjamin W; Latev, Alexander; Campbell, Caron; White, Deborah

2018-05-01

Parenteral opioids are used in more than 50% of emergency department (ED) visits for migraine. Use of opioids for migraine has been associated with subsequent ED visits, perhaps because of opioid-induced euphoria. In this study, we quantify the extent to which nontherapeutic effects of opioids influence migraine outcomes. We hypothesized that "feeling good" and medication likeability would in fact be associated with receipt of opioids (rather than relief of migraine pain) and that receipt of opioids (rather than relief of migraine pain) would be associated with return visits to the ED. During an ED-based clinical trial, migraine patients were randomized to receive hydromorphone 1 mg or prochlorperazine 10 mg + diphenhydramine 25 mg IV. Thirty minutes after medication administration, we asked, (1) How much did you like the medication you received? and (2) How good did the medication make you feel? Participants were asked to provide answers on a 0-10 scale. We also determined 0-10 pain scores at baseline and 1 hour and number of return visits for headache during the subsequent month. Sixty-three patients received prochlorperazine and 64 hydromorphone. Prochlorperazine pain scores improved by 6.8 (SD: 2.6), hydromorphone by 4.7 (SD: 3.3) (95%CI for difference of 2.1: 1.0, 3.2). On the 0-10 likeability scale, prochlorperazine patients reported a mean of 7.2 (SD: 2.8), hydromorphone 6.9 (SD: 2.9) (95% CI for difference of 0.3: -0.7, 1.3). On the 0-10 feeling good scale, prochlorperazine patients reported a mean of 7.5 (SD: 2.3), hydromorphone 6.8 (SD: 2.8) (95%CI: for difference of 0.7: -0.2, 1.6). In the hydromorphone group, 8/57 (14%, 95%CI: 7, 26%) returned to the ED vs 5/63 (8%, 95%CI: 3,18%) in the prochlorperazine group. In regression modeling, feeling good was independently associated with pain relief (P relief (P relief was associated with medication likeability and feeling good. © 2018 American Headache Society.

Peroxynitrite-induced relaxation in isolated canine cerebral arteries and mechanisms of action

International Nuclear Information System (INIS)

Li Jianfeng; Li Wenyan; Altura, Bella T.; Altura, Burton M.

2004-01-01

The present study was undertaken to determine the vascular actions of peroxynitrite (ONOO - ), the product of superoxide and nitric oxide (NO), in isolated canine cerebral arteries and to gain insight into its potential mechanisms of action. In the absence of any vasoactive agent, ONOO - (from 10 -7 to 10 -6 M) was able to reduce the basal tension. In prostaglandin F2α-precontracted canine basilar arterial rings, ONOO - elicited concentration-dependent relaxation at concentrations from 10 -8 to 10 -5 M. The effective concentrations producing approximately 50% maximal relaxation (EC 50 ) to ONOO - were 4.06 x 10 -6 and 4.12 x 10 -6 M in intact and denuded rings, respectively (P > 0.05). No significant differences in relaxation responses were found in ring preparations with or without endothelium (P > 0.05). The presence of either 5 μM methylene blue (MB) or 5 μM 1H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one (ODQ) significantly inhibited the relaxations induced by ONOO - . Tetraethylammonium chloride (T-2265) significantly decreased the ONOO - -induced relaxations in a concentration-dependent manner. However, ONOO - had no effect on rings precontracted by high KCL (P > 0.05). Addition of low concentrations of calyculin A (50 nM) was able to abolish the ONOO - -induced relaxation. Furthermore, ONOO - significantly inhibited calcium-induced contractions of K + -depolarized canine cerebral rings in a concentration-related manner. Lastly, a variety of pharmacological agents and antagonists including L-NMMA, L-arginine, indomethacin, atropine, naloxone, diphenhydramine, cimetine, glibenclamide, haloperidol, etc., did not influence the relaxant effects of ONOO - on the rings. Our new results suggest that ONOO - -triggered relaxation, on canine cerebral arteries, is mediated by elevation of cyclic guanosine monophosphate (cGMP) levels, membrane hyperpolarization via K+ channel activation, activation of myosin light chain phosphatase activity, and interference with

Medicine use practices in management of symptoms of acute upper respiratory tract infections in children (≤12 years in Kampala city, Uganda

Directory of Open Access Journals (Sweden)

Moses Ocan

2017-09-01

Full Text Available Abstract Background Medicines are commonly accessed and used for management of illness in children without a prescription. This potentially increases the risk of unwanted treatment outcomes. We investigated medicine use practices in management of symptoms of acute upper respiratory tract infections among children (≤12 years in households in Nakawa division, Kampala city. Methods This was a cross-sectional study conducted among 390 randomly selected children. Data on use of medicines in children (≤12 years during recent episode of acute upper respiratory tract infection was collected from their care takers using an interviewer administered questionnaire. A recall period of two weeks (14 days was used in during data collection. Results The prevalence of giving children non-prescription antimicrobial medicines was 44.8% (38.3-52.2. The most common disease symptoms that the children reportedly had included flu, 84.9% (331/390, cough, 83.1% (324/390, and undefined fever, 69.7% (272/390. Medicines commonly given to children included, paracetamol 53.1% (207/390, Coartem 29.7% (116/390, cough linctus 20.8% (81/390, amoxicillin 18.9% (74/390, Co-trimoxazole 18.5% (72/390, and diphenhydramine 15.4% (60/390. The major sources of medicines given to the children was hospital/clinic, 57.26% (223/390. Most of the children, 81% were given more than one medicine at a time. The majority, 62.3% (243/390 of the care takers who gave the children medicine during the recent illness were not aware of any medicine (s that should not be given to children. The predictors of non-prescription use of antimicrobial medicines in managing symptoms of acute upper respiratory tract infections in children included, medicines obtained from drug shop (PR: 1.45, CI: 1.14-1.85, medicines at home (PR: 1.8, CI: 0.83-1.198 and type of medicine (antimalarial (PR: 2.8, CI: 1.17-6.68. Conclusion Children are commonly given multiple medicines during episodes of acute upper respiratory

Docetaxel as neoadjuvant chemotherapy in patients with advanced cervical carcinoma.

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Vallejo, Carlos T; Machiavelli, Mario R; Pérez, Juan E; Romero, Alberto O; Bologna, Fabrina; Vicente, Hernán; Lacava, Juan A; Ortiz, Eduardo H; Cubero, Alberto; Focaccia, Guillermo; Suttora, Guillermo; Scenna, Mirna; Boughen, José M; Leone, Bernardo A

2003-10-01

The purpose of this study was to evaluate the efficacy and toxicity of docetaxel as single-agent neoadjuvant chemotherapy in locoregionally advanced cervical carcinoma. Between April 1998 and August 2000, 38 untreated patients with International Federation of Gynecology and Obstetrics stages IIB to IVA were entered onto this study. The median age was 44 years (range: 25-66 years). Stages: IIB 22 patients, IIIB 15 patients, and IVA 1 pt. Treatment consisted of docetaxel 100 mg/m2 IV infusion during 1 hour. Standard premedication with dexamethasone, diphenhydramine, and ranitidine was used. Cycles were repeated every 3 weeks for three courses, followed by radical surgery when it was judged appropriate, or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. 106 cycles of therapy were administered; all patients were evaluable for TX, whereas 35 were evaluable for response (3 patients refused further treatment after the first cycle of therapy). Complete response (CR): 1 patient (3%); partial response: 11 patients (31%), for an overall objective response rate of 34% (95% CI: 15-53%); no change (NC): 16 patients (46%); and progressive disease: 7 patients (20%). Six patients (17%) underwent surgery and a pathologic CR was confirmed in 1 of them. The median time to treatment failure and the median survival have not been reached yet. The limiting toxicity was leukopenia in 25 patients (69%) (G1-G2: 14 patients, G3: 10 patients, and G4: 1 patient). Neutropenia: 28 patients (78%) (G1-G2: 10 patients, G3: 8 and G4: 10). Myalgias: 17 patients (47%) (G1-G2: 15 patients and G3: 2 patients). Emesis: 21 patients (55%) (G1-G2: 19 patients and G3: 2 patients). Alopecia G3: 13 patients (36%); rash cutaneous 26 patients (68%) (G1-G2: 22 patients and G3: 4 patients). There were no hypersensitivity reactions or fluid-retention syndrome. The received dose intensity was 91% of that projected. Docetaxel is an active drug against advanced

[Research on antiemetics: an Italian model of success].

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Roila, F

1998-01-01

At the beginning of the 80's the Italian Group for Clinical Research (G.O.I.R.C.) identified chemotherapy-induced nausea and vomiting as one of the most distressing adverse events, and decided to plan and execute clinical trials on antiemetics in order to reduce this negative impact on patients. Therefore, some consecutive double-blind randomized trials were conducted on cisplatin-treated patients. The first was a dose-finding study on four different high-doses of domperidone, followed by a study comparing two different high-doses of metoclopramide, and a study comparing the addition of a corticosteroid to high-dose metoclopramide with respect to metoclopramide alone. Finally, a study demonstrating that a combination of a higher dose of metoclopramide (3 mg/kg x 2) plus dexamethasone and diphenhydramine was significantly superior with respect to a lower dose of metoclopramide (1 mg/kg x 4) combined with methylprednisolone was carried out. With the introduction of the 5-HT3 receptor antagonists the interest for antiemetic therapy increased and other Italian gynecological and medical oncology centres became involved in the antiemetic research. The Italian Group for Antiemetic Research was formed in 90's and its first study demonstrated the superiority of a combination of a 5-HT3 receptor antagonist plus dexamethasone with respect to the standard three drug combination of high doses of metoclopramide in the prevention of cisplatin-induced acute emesis. In the following years, the Group contributed to the identification of the best antiemetic prophylaxis for acute emesis induced by moderately emetogenic chemotherapy, and for delayed emesis induced by cisplatin. Also a drug utilization review on antiemetics in clinical practice has recently been carried out. Today, the interest of the Group is concentrated in studying the optimal antiemetic prophylaxis for delayed emesis induced by moderately emetogenic chemotherapy. The rules always followed by the Italian Group for

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

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Ling Li

2015-01-01

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

Parenteral treatment of episodic tension-type headache: a systematic review.

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Weinman, Danielle; Nicastro, Olivia; Akala, Olabiyi; Friedman, Benjamin W

2014-02-01

continuous outcomes otherwise. Our search returned 640 results. One hundred eighty-seven abstracts were reviewed, and 8 studies involving 486 patients were included in our analysis. The most common reasons for exclusion of abstracts were no assessment of acute pain relief, use of nonparenteral medications only, and no differentiation of headache type. Risk of bias ranged from low to high. The following medications were more effective than placebo for acute pain (NNT, 95%CI): metamizole (4, 2-26), chlorpromazine (4, 2-26), and metoclopramide (2, 1-3). The combination of metoclopramide + diphenhydramine was superior to ketorolac (4, 2-8) The following medications were not more effective than placebo: mepivacaine, meperidine + promethazine, and sumatriptan. Various parenteral medications other than salicylates or nonsteroidals provide acute relief of tension-type headache. Comparative efficacy studies are needed. © 2014 American Headache Society.

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

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Massey, Andrew J.; Waldron, Marcus C.

2011-01-01

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

Contribution of positron emission tomography for the study of response variability to opioid drugs

International Nuclear Information System (INIS)

Auvity, Sylvain

2017-01-01

investigate the neuro-pharmacokinetic component of opioid pharmacology. "1"1C-diphenhydramine was developed in rats as a specific probe to estimate the H"+/antiporter function at the blood-brain barrier. This newly identified carrier transport System was shown to control the brain exposure of many CNS drugs, including oxycodone. Then, we used "1"1C-buprenorphine PET imaging and validated a co-injection strategy to quantify the parameters that describe the brain kinetics of buprenorphine in nonhuman primates. Throughout this project, several methods have been evaluated or developed in order to address original hypothesis regarding the pharmacology of opioid drugs. The choice for noninvasive and quantitative methods such as PET imaging allows for clinical translation. These tools may thus be useful to investigate the neuro-immune and neuro-pharmacokinetic component of the variability of response to opioid drugs in humans. (author) [fr

Propafenone Overdose-induced Arrhythmia and Subsequent Correction After Administration of Sodium Bicarbonate

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Patrick Bruss, MD

2018-04-01

and a terminal R wave in AVR (an R wave greater than the S wave or an R wave greater than 3 mm. Similar ECG findings can be seen with cocaine,1 diphenhydramine,1 antipsychotics, and antidepressants toxicity. Sodium bicarbonate has proven to be a useful “antidote” for these and other sodium channel blocker overdoses. It is thought that sodium bicarbonate acts either to stabilize the myocardium or inactivate the drug itself.1 We believe this case further illustrates the value in administering sodium bicarbonate early in the course of suspected propafenone, and for that matter, all sodium channel blocker overdoses. One ampule of sodium bicarbonate is very safe and any downside to its use in the setting described above is most definitely outweighed by the almost immediate potential benefit seen after it is administered. Topics: Propafenone, sodium bicarbonate, overdose, ECG, sodium channel blocker

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

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

2017-01-16

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. A multicentre, randomised, parallel group, controlled, single-blinded study in participants with acute upper respiratory tract infection-associated cough. 4 general practitioner (GP) surgeries and 14 pharmacies in the UK. 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). 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. 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. 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 difference (95% CI) 1.2 (0.05 to 2.36), p=0.04 after 5 days' treatment. More participants prematurely

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

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Alen Nils Baeza Fonte

2012-03-01

; 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.

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

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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.

2015-01-01

�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.

Haloperidol for the treatment of nausea and vomiting in palliative care patients.

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Murray-Brown, Fay; Dorman, Saskie

2015-11-02

assessment of studies. We considered 27 studies from the 2007 search. In this update we considered a further 38 studies from the 2013 search, and two in the 2014 search. We identified one RCT of moderate quality with low risk of bias overall which met the inclusion criteria for this update, comparing ABH (Ativan®, Benadryl®, Haldol®) gel, applied to the wrist, with placebo for the relief of nausea in 22 participants. ABH gel includes haloperidol as well as diphenhydramine and lorazepam. The gel was not significantly better than placebo in this small study; however haloperidol is reported not to be absorbed significantly when applied topically, therefore the trial does not address the issue of whether haloperidol is effective or well-tolerated when administered by other routes (e.g. by mouth, subcutaneously or intravenously). We identified one ongoing trial of haloperidol for the management of nausea and vomiting in patients with cancer, with initial results published in a conference abstract suggesting that haloperidol is effective for 65% of patients. The trial had not been fully published at the time of our review. A further trial has opened, comparing oral haloperidol with oral methotrimeprazine (levomepromazine) for patients with cancer and nausea unrelated to their treatment, which we aim to include in the next review update. Since the last version of this review, we found one new study for inclusion but the conclusion remains unchanged. There is incomplete evidence from published RCTs to determine the effectiveness of haloperidol for nausea and vomiting in palliative care. Other than the trial of ABH gel vs placebo, we did not identify any fully published RCTs exploring the effectiveness of haloperidol for nausea and vomiting in palliative care patients for this update, but two trials are underway.

Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline.

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Sateia, Michael J; Buysse, Daniel J; Krystal, Andrew D; Neubauer, David N; Heald, Jonathan L

2017-02-15

the quality of evidence for these treatments is predictable in GRADE, due to the funding source for most pharmacological clinical trials and the attendant risk of publication bias; the relatively small number of eligible trials for each individual agent; and the observed heterogeneity in the data. The ultimate judgment regarding propriety of any specific care must be made by the clinician in light of the individual circumstances presented by the patient, available diagnostic tools, accessible treatment options, and resources. We suggest that clinicians use suvorexant as a treatment for sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use eszopiclone as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use zaleplon as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use zolpidem as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use triazolam as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use temazepam as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use ramelteon as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use doxepin as a treatment for sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use trazodone as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use tiagabine as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use diphenhydramine as a treatment for sleep onset and sleep maintenance insomnia (versus no

Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline

Science.gov (United States)

Sateia, Michael J.; Buysse, Daniel J.; Krystal, Andrew D.; Neubauer, David N.; Heald, Jonathan L.

2017-01-01

evidence in published data. Downgrading the quality of evidence for these treatments is predictable in GRADE, due to the funding source for most pharmacological clinical trials and the attendant risk of publication bias; the relatively small number of eligible trials for each individual agent; and the observed heterogeneity in the data. The ultimate judgment regarding propriety of any specific care must be made by the clinician in light of the individual circumstances presented by the patient, available diagnostic tools, accessible treatment options, and resources. We suggest that clinicians use suvorexant as a treatment for sleep maintenance insomnia (versus no treatment) in adults. (WEAK) We suggest that clinicians use eszopiclone as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK) We suggest that clinicians use zaleplon as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK) We suggest that clinicians use zolpidem as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK) We suggest that clinicians use triazolam as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK) We suggest that clinicians use temazepam as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK) We suggest that clinicians use ramelteon as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK) We suggest that clinicians use doxepin as a treatment for sleep maintenance insomnia (versus no treatment) in adults. (WEAK) We suggest that clinicians not use trazodone as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK) We suggest that clinicians not use tiagabine as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK) We suggest that clinicians not use diphenhydramine as a treatment for sleep onset and sleep

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

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

2012-01-01

, 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

The general public's perceptions and use of antimicrobials in Trinidad and Tobago Las percepciones del público general y el uso de antimicrobianos en Trinidad y Tabago

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Neeta Parimi

2002-07-01

Full Text Available Objective. To determine the general public's perceptions and use of antibiotics in Trinidad and Tobago, a two-island republic in the Caribbean. Methods. This prospective study surveyed 824 randomly selected households listed in the telephone directory, from November 1998 to January 1999. Through telephone interviews we determined knowledge about antibiotics and beliefs concerning their safety and efficacy. We studied the influence of age, gender, education, and having private health insurance on knowledge, self-medication, storing medication at home for emergency use ("hoarding", and asking a private doctor to prescribe antibiotics ("demand prescribing". Results. For the 824 telephone calls that the interviewers completed, 753 of the households agreed to participate (91.4% response rate. Of those 753 participants, 699 of them (93% knew the term "antibiotic," 29% (206/699 said it was a drug for bacterial infections, and 25% (170/690 had asked a doctor for an antibiotic prescription. Penicillin was correctly identified as an antibiotic across age, gender, and education categories, but 36% of respondents incorrectly said Benadryl (diphenhydramine, a common over-the-counter cough and cold formulation, was an antibiotic. Gender was not significantly associated with knowledge of antibiotic safety, with self-medication, or with hoarding antibiotics. On the other hand, completion of tertiary (university education was significantly associated with correct knowledge of the safety of antibiotics and whether or not they could cure all infections. Of the various antimicrobials, beta-lactams were the ones that survey respondents had used most frequently in the preceding year, and 20% of antibiotics users had used multiple antibiotics in that period. In comparison to persons with private health insurance, more individuals without private health insurance said that antibiotics are safe and do not have side effects, and more of them also incorrectly called