To see the other types of publications on this topic, follow the link: Antihistamine.
Dissertations / Theses on the topic 'Antihistamine'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Antihistamine.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Rice, Valerie J. Berg. "Complex cognitive performance and antihistamine use." Diss., This resource online, 1990. http://scholar.lib.vt.edu/theses/available/etd-02052007-081232/.
Full text
2
Delargy, Paula M. C. "Quantifying adverse reactions to antihistamine compounds." Thesis, Queen's University Belfast, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359062.
Full text
3
Baxter, R. I. "Voltammetric studies of some important antihistamine drugs." Thesis, Queen's University Belfast, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374204.
Full text
4
Whitehouse, Gail Lynn. "The effects of antihistamine use on visual search tasks." Thesis, Virginia Tech, 1990. http://hdl.handle.net/10919/41500.
Full textAbstract:
Previous research has shown that most antihistamines have sedative effects and can lead to deterioration of psychomotor performance. The objective of this research was to determine if two antihistamines (diphenhydramine and astemizole) administered at a therapeutic dose level will affect a subject's visual search capabilities. The results of this research indicate that astemizole did not significantly decrement a subject’s ability to visually search as compared to the performance of that same subject after ingesting a placebo. Diphenhydramine produced significantly poorer visual search results than did astemizole.Master of Science
5
Treherne, Jonathan Mark. "A quarternary radioligand for histamine Hâ†1-receptor." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328973.
Full text
6
Donado, Budiño Esther Guillermina. "Evaluation of caridotoxicity of rupatadine, and antihistamine, as recommendeded by ICH E14." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/370122.
Full textAbstract:
OBJETIVOS:
Para evaluar los efectos de las dosis terapéuticas y supraterapéuticas de
rupatadina en la repolarización cardiaca mediante un 'thorough QT/QTc study',
realizado de acuerdo con la Conferencia Internacional sobre las directrices de
armonización.
MÉTODOS:
Ensayo clínico, de grupos paralelos (balanceado por género), aleatorio, que
incluyó 160 voluntarios sanos. Tanto rupatadina, 10 y 100 mg od, como
placebo, se administraron durante 5 días en simple ciego, mientras que
moxifloxacino 400 mg/día, se administró los días 1 y 5 en abierto. Los
registros ECG se recogieron durante un período de 23 h mediante Holter en el
día basal del estudio y durante el tratamiento en los días 1 y 5. Se
descargaron tres muestras de 10-s ECG a intervalos regulares y se analizaron
de forma independiente. El análisis primario de QTc se basó en QT corregido
de forma individual (QTcI). Los efectos del tratamiento sobre QTcI se
evaluaron utilizando la mayor diferencia de medias vez emparejados entre el
medicamento y el placebo (baseline-subtracted) para el intervalo QTcI. Un
"thorough QT/QTc study" negativo es aquel en el que la variable principal es
de alrededor de < o = 5 ms, con un intervalo de confianza unilateral del 95%
que excluye un efecto > 10 ms.
RESULTADOS:
La validez de la prueba fue confirmada por el hecho de que el grupo de
control positivo-moxifloxacino- produjo el cambio esperado en la duración
QTci (alrededor de 5 ms). Los datos del ECG con rupatadina a dosis 10 y 100
mg no mostraron efectos relevantes en el ECG, ni después de la
administración única ni tras administración repetida. Además, no se observó
ninguna relación farmacocinética / farmacodinámica, efectos de género o
cambios clínicamente relevantes en los valores extremos o de morfología en
el ECG. No se reportaron muertes ni eventos adversos graves o inesperadas.
CONCLUSIONES:
Este "'thorough QT/QTc study' 'confirmó la experiencia previa con rupatadina y
demostró que no presenta potencial proarrítmico y no planteó preocupaciones
con respecto a su seguridad cardíaca.AIMS: To evaluate the effects of therapeutic and supratherapeutic doses of rupatadine on cardiac repolarization in line with a 'thorough QT/QTc study' protocol performed according to International Conference on Harmonization guidelines. METHODS: This was a randomized (gender-balanced), parallel-group study involving 160 healthy volunteers. Rupatadine, 10 and 100 mg od, and placebo were administered single-blind for 5 days, whilst moxifloxacin 400 mg/day was given on days 1 and 5 in open-label fashion. ECGs were recorded over a 23-h period by continuous Holter monitoring at baseline and on treatment days 1 and 5. Three 10-s ECG samples were downloaded at regular intervals and were analysed independently. The primary analysis of QTc was based on individually corrected QT (QTcI). Treatment effects on QTcI were assessed using the largest time-matched mean difference between the drug and placebo (baseline-subtracted) for the QTcI interval. A negative 'thorough QT/QTc study' is one where the main variable is around < or =5 ms, with a one-sided 95% confidence interval that excludes an effect >10 ms. RESULTS: The validity of the trial was confirmed by the fact that the moxifloxacinpositive control group produced the expected change in QTcI duration (around 5 ms). The ECG data for rupatadine at both 10 and 100 mg showed no signal effects on the ECG, after neither single nor repeated administration. Furthermore, no pharmacokinetic/pharmacodynamic relationship, gender effects or clinically relevant changes in ECG waveform outliers were observed. No deaths or serious or unexpected adverse events were reported. CONCLUSIONS: This 'thorough QT/QTc study' confirmed previous experience with rupatadine and demonstrated that it had no proarrhythmic potential and raised no concerns regarding its cardiac safety.
7
Lindmark, Elin. "Dykare i Difenhydramin : Förändrar antihistaminet difenhydramin beteendet hos dykarlarver, Dytiscidae?" Thesis, Umeå universitet, Institutionen för ekologi, miljö och geovetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-159825.
Full textAbstract:
A diverse cocktail of pharmaceuticals is spreading via water treatment plants’ effluent to surface water with known and unknown consequences of individual organisms and the ecosystem. In prior research on what consequences the pharmaceutical discharge can have, the antihistamine diphenhydramine has been found in surface waters and has been linked to alteration in organisms’ behaviours. In this study, Dytiscidae larvae were filmed before and after being exposed to diphenhydramin with a concentration of 1 µg/l. The exposure was done using four different treatments: no diphenhydramine, diphenhydramine in water, in their food or in both water and food. This was done to observe whether the behaviour, specifically activity and boldness, of Dytiscidae larvae would change with the exposure of the antihistamine and therefore potentially be a problem in aquatic ecosystems exposed to effluent. The experiment showed a significant difference (P = 0.015) between larvae in the control group and larvae only exposed to diphenhydramine through water, where exposed larvae were less active than the control group. Also, a trend pointed to a potential difference in exploration between the same groups, where the group exposed to diphenhydramine explored more than the control group. No behavioural change was found when larvae was exposed via food or food and water. The changed behaviour found here could influence fitness of the larvae and potentially also other parts of the ecosystem through cascading effects. Further research is required to confirm the dangers and consequences of diphenhydramine in surface waters, but my results suggest that it can alter the organism’s behaviour in aquatic ecosystems.
8
Koch, Katja [Verfasser]. "Antihistamine updosing reduces disease activity in difficult-to-treat cholinergic urticaria patients / Katja Koch." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2017. http://d-nb.info/1127579959/34.
Full text
9
Schooley, Elizabeth K. "The effects of an antiseritonergic drug and antihistamine in an experimental model of feline asthma." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/5033.
Full textAbstract:
Thesis (M.S.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "May 2007" Includes bibliographical references.
10
Verner, Jennifer Joan. "Formulation and dissolution assessment of a novel repeat action tablet containing a decongestant and an antihistamine." Thesis, Rhodes University, 2001. http://hdl.handle.net/10962/d1003276.
Full textAbstract:
Controlled and sustained release dosage forms are the focus of worldwide research. These dosage forms facilitate patient compliance by simplifying the dosage regimen, and decrease the risk of adverse effects by reducing large fluctuations in the plasma concentration of the drug. The objective of this study was to formulate a repeat-action tablet to provide a sustained release dose of pseudoephedrine sulfate (PSS), and an immediate release dose of both PSS and loratadine. The release profile was compared to that of a commercially available preparation, Clarityne-D®. This formulation developed presents a novel mechanism of sustaining the release of PSS. The prototype tablet consisted of a sustained release core coated with an ethylcellulose dispersion to introduce a lag phase into the release profile and a second outer film coat incorporating PSS and loratadine. The core comprised an ethylcellulose granulation of PSS compressed into a hydroxypropyl methylcellulose matrix. The release of PSS from prototypes was assessed using USP Apparatus 3, as this apparatus was more representative of in vivo conditions and discriminated more effectively between the different tablet compositions produced during development. All dissolution samples were analysed for PSS and loratadine using validated highperformance liquid chromatographic methods. The prototype sustained release cores were found to be more resistant than the reference product to elevated temperature and humidity (40°C/87% RH) with fewer observed changes to the release profiles following storage for up to six months. This study was a feasibility study to obtain proof of concept. The release profile obtained from the prototype tablets was similar (f₂ = 50.0) to that of the reference product. Further development and optimisation of this dosage form is necessary, including evaluation of the choice of hydrophobic polymer, the effect of compression force and tablet geometry and characterisation of the release mechanism from the coated matrix. Assessment of these factors is necessary in order to optimise the formulation with respect to the desired therapeutic objectives.
11
Alharbi, S. A. "Effect of antihistamine compounds on Gram-negative bacteria and their ability to release or neutralize bacterial endotoxin." Thesis, University of Sheffield, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.496303.
Full text
12
Bomark, Ellinor. "The antihistamine hydroxyzine and Odonata : Bioaccumulation and effects on predator-prey interactions between dragonfly and damselfly larvae." Thesis, Umeå universitet, Institutionen för ekologi, miljö och geovetenskap, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-86388.
Full textAbstract:
Through wastewater entering aquatic environments, aquatic insects are continuously exposed to pharmaceuticals including neurologically active antihistamines. The antihistamine hydroxyzine has previously been found to lower activity in damselflies and to reach 2000 times the concentration of surrounding water in damselfly tissue. The purpose of this short-term exposure study was to investigate if hydroxyzine also bioaccumulates in dragonflies and if dilute hydroxyzine (362 ± 50, mean ng/l ± SD) have effects on predator-prey interactions between dragonfly Aeshna grandis and damselfly Coenagrion hastulatum larvae, i.e. number of attacks and predation success. Predators and prey were captured and exposed during one, three or five days (with controls) before taking part in predation experiments; Dragonflies were put in separate containers with six damselflies, they were video recorded and attacks and predated damselflies noted during four hours. Tissue concentrations of hydroxyzine were analyzed from all dragonflies and a subsample of the damselflies showing a mean bioconcentration factor (BCF) of 27 and 7 respectively, surprisingly much lower than previous research. There was no difference in attack rate or predation efficiency between controls and exposed dragonflies. However, dragonflies exposed for five days were found to attack more and capture more prey than dragonflies exposed for one day, a change that was not seen in the controls. This confounding factor motivates further studies to clarify if hydroxyzine after a period of exposure can have a sublethal effect altering foraging and/or predator avoidance traits with the net result of increased predation success for dragonflies in the predator-prey interaction between dragonflies and damselflies.
13
Costa, Edson Barbosa da. "Aplicação da química quântica ao estudo de um grupo de moléculas antihistamínicas H3." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/75/75131/tde-23042010-093424/.
Full textAbstract:
Nesta tese foi estudado um grupo de 28 compostos não-imidazólicos antagonistas do receptor H3 através de cálculos de orbitais moleculares utilizando os métodos de química quântica Austin Model 1, Hartree-Fock-Roothaan e Teoria do Funcional da Densidade com o objetivo de investigar possíveis relações entre descritores eletrônicos teóricos e as afinidades ligantes experimentais desses compostos (pKi). Observou-se nos resultados obtidos que as energias dos orbitais FERMOs (Frontier Effective-for-Reaction Molecular Orbitals) apresentam melhor correlação com os valores de pKi do que as energias dos orbitais de fronteira HOMO (Highest Occupied Molecular Orbital) e LUMO (Lowest Unoccupied Molecular Orbital). Além disso, verificou-se pelas análises de métodos multivariados PCA (Principal Componente Analysis) e HCA (Hierarchical Cluster Analysis) que um conjunto de quatro descritores foi capaz de separar os compostos em dois grupos distintos, o primeiro que apresenta valores de afinidades ligantes maiores e o segundo com menores valores de pKi. Esta separação foi possível com o uso dos seguintes descritores teóricos: energia do FERMO (εFERMO), carga derivada do potencial eletrostático no átomo de nitrogênio N1, índice de densidade eletrônica no átomo N1 (Σ(FERMO) ci2) e eletrofilicidade (ω\'). Estes descritores foram utilizados, posteriormente, para a construção de três equações de regressão pelo método PLS (Partial Least Squares). O melhor modelo de regressão gerou os seguintes parâmetros estatísticos Q2 = 0,88 e R2 = 0,927, obtidos com um conjunto treino e de validação externa de 23 e 5 moléculas, respectivamente. Logo após a avaliação da equação de regressão, juntamente com os valores dos descritores selecionados e outros não selecionados, foi sugerido que altos valores de energias dos FERMOs e de Σ(FERMO) ci2 em conjunto com baixos valores de eletrofilicidades e cargas extremamente negativas no átomo N1 são parâmetros relevantes para potencializar as afinidades ligantes de outros compostos a serem sintetizados, que apresentem estruturas químicas semelhantes às moléculas estudadas neste trabalho. Além disso, esses compostos podem ser considerados como doadores de elétrons e, logo, há uma grande probabilidade que tais moléculas interajam com o receptor histamínico H3 a partir de um processo de transferência de carga.In this thesis, molecular orbital calculations were carried out on a set of 28 non-imidazole H3 antihistamine compounds using Austin Moldel 1, Hartree-Fock-Roothaan, and Density Functional Theory methods in order to investigate the possible relationships between electronic descriptors and binding affinity for H3 receptors (pKi). It was observed that the frontier effective-for-reaction molecular orbital (FERMO) energies were better correlated with pKi values than HOMO (Highest Occupied Molecular Orbital) and LUMO (Lowest Unoccupied Molecular Orbital) energy values. Exploratory data analysis through hierarchical cluster (HCA) and principal component analysis (PCA) showed a separation of the compounds into two sets by using four descriptors, one grouping the molecules with high pKi values, the other gathering low pKi value compounds. This separation was obtained with the use of the following descriptors: FERMO energies (εFERMO), charges derived from the electrostatic potential on the nitrogen atom (N1), electronic density indexes for FERMO on the N1 atom (Σ(FERMO) ci2), and electrophilicity (ω\'). These electronic descriptors were used to construct three quantitative structure-activity relationship (QSAR) models through the Partial Least Squares Method (PLS). The best model generated Q2 = 0.88 and R2 = 0.927 values obtained from a training set and external validation of 23 and 5 molecules, respectively. After the analysis of the PLS regression equation, the values for the selected electronic descriptors and other descriptors, it is suggested that high values of FERMO energies and of Σ(FERMO) ci2, together with low values of electrophilicity and pronounced negative charges on N1 appear as desirable properties for the conception of new molecules which might have high binding affinity. Moreover, these molecules can be classified as electron donating compounds and have a great probability of interacting through a charge transfer process with the biological receptor H3.
14
Rombaut, Niekol Elvire Irma. "Antihistamines and sedation : methods and measures." Thesis, University of Surrey, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308643.
Full text
15
Bildsten, Meriem. "Val av antihistaminer på specialistmottagning i allergologi." Thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-267438.
Full text
16
Badenhorst, Hester Elizabeth. "Antihistamines as neuroprotective agents / Hester Elizabeth Badenhorst." Thesis, North-West University, 2004. http://hdl.handle.net/10394/95.
Full textAbstract:
Biomolecules are continuously exposed to potentially harmful oxidative stress as a consequence
of free radical formation. Increased free radical generation has been associated with aging as
well as neurodegenerative disorders. Antioxidants affect processes associated with oxidative
stress by quenching free radicals and acting as oxygen scavengers. Parkinson's disease results
from a deficiency in the neurotransmitter, dopamine and it is also evident that damage caused by
free radicals play an important role in the progression of this neurodegenerative disorder. The
histamine HI antagonist, diphenhydramine is used to treat mild cases of Parkinson's disease and
cimetidine can scavenge hydroxyl radicals. The histamine H3 antagonists are known to promote
the release of dopamine. Together with a free radical scavenging activity, these compounds
might have a dual therapeutic effect in the reduction of the progression of Parkinson's disease.
The aim of this study was thus to determine whether histamine antagonists could act as free
radical scavengers and to compare the results with aspirin, a known free radical scavenger.
Ibuprofen was included to compare the free radical scavenging activities of aspirin to another
non-steroidal anti-inflammatory drug.
The free radical scavenging activities of the following compounds were determined and
compared: diphenhydramine; cimetidine; roxatidine; clobenpropit; impentarnine; thioperamide;
aspirin and ibuprofen. The ORAC assay was used to determine whether the test compounds
were able to scavenge peroxyl radicals and the FRAP assay was used to determine the reducing
abilities of the compounds. No meaningll results were obtained from these two assays,
suggesting that the compounds were not able to act as direct antioxidants or as peroxyl radical
scavengers. The comet assay was used to determine whether the compounds were able to reduce
oxidative damage after MPTP administration. No damage was however obtained after a single
dose of MPTP and it is suggested that one year old mice and chronic rather than acute treatment
is used. Using a cyanide model to induce neurotoxic effects in rat brain homogenates, the
neuroprotective properties of the histamine antagonists were examined and compared to aspirin.
Superoxide anion levels and malondialdehyde concentrations were assessed using the nitrobluetetrazolium
and lipid peroxidation assays. Clobenpropit and thioperamide significantly reduced
superoxide anion generation and lipid peroxidation. At a concentration of lmM, these two
histamine Hj antagonists reduced lipid peroxidation to values lower than that of the control.
Impentamine reduced lipid peroxidation at all concentrations used and superoxide anion
generation at a concentration of 1mM. Diphenhydramine (0.25 and 0.5mM) significantly
reduced both variables at lower concentrations. Cimetidine (1mM) was able to reduce
superoxide anion generation and significantly reduced lipid peroxidation at all concentrations
Abstract
used. Roxatidine (0.5mM and 1mM) significantly reduced the rise in superoxide anion
generation and significantly reduced malondialdehyde concentration in a dose dependent
manner. Ibuprofen significantly decreased superoxide anions in a dose dependant manner and
lipid peroxidation at a concentration of 1mM. In the lipid peroxidation assay, all the drugs
compared favourably to aspirin. The in vivo free radical scavenging effects of the selected
compounds were also examined with the nitroblue tetrazoliurn and lipid peroxidation assays.
MPP' was used to induce a Parkinsonian like condition. Diphenhydramine, ibuprofen,
thioperamide and clobenpropit significantly reduced free radical generation in both assays.
Thioperamide and clobenpropit were able to reduce lipid peroxidation and superoxide anion
generation to values lower than that of the control, suggesting that these two compounds could
be able to attenuate normal free radical processes in the brain. Cimetidine did not have the
expected in vivo scavenging effects and it is suggested that blood-brain barrier permeability
might play a role. All the compounds, except diphenhydramine had significantly lower in vivo
values than aspirin.
The superoxide anion plays an important role in the formation of further free radicals. It leads to
the formation of peroxyl radicals during the inititation step of lipid peroxidation and also leads to
the generation of hydroxyl radicals, where transition metals like iron, is a key factor.
Diphenhydramine at lower concentrations, and the newly discovered histamine Hj antagonists,
clobenpropit and thioperamide significantly reduced superoxide anion generation and lipid
peroxidation. Although the compounds did not have meaningful effects in the FRAY and ORAC
assay, their significant ability to reduce lipid peroxidation and superoxide levels make them
promising tools to attenuate oxidative damage.
This study demonstrates the potential of these agents to be neuroprotective with a dual therpeutic
effect by exerting a scavenging effect on superoxide anions and increasing dopamine levels.Thesis (M.Sc. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2005.
17
Ramos, Luiz Antonio. "Investigação do comportamento térmico e de polimorfismo do anti-histamínico loratadina." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/75/75132/tde-04082011-143805/.
Full textAbstract:
O comportamento térmico, a obtenção e caracterização de formas cristalinas do anti-histamínico loratadina foram investigado. A escolha do anti-histamínico loratadina como objeto de estudo resulta do seu interesse farmacológico. A loratadina é a Denominação Comum Internacional (DCI) dada ao etil 4-(8-cloro-5,6-dihidro-11H-benzo[5,6]cicloheptano[1,2-b]piridino-11-ilideno)-1-piperidinocarboxilato, que é um potente antialérgico e anti-histamínicos tricíclico, não-sedativo de ação prolongada. Formas cristalinas foram preparadas e estudadas com vista à identificação de formas polimórficas. Os solventes utilizados na preparação das soluções foram: álcool etílico, acetonitrila, álcool isopropílico, acetona, álcool metílico, éter isopropílico, éter metil terc-butílico, tolueno, clorofórmio. A cristalização foi realizada por evaporação do solvente em diferentes temperaturas. A calorimetria exploratória diferencial (DSC), termogravimetria e termogravimetria derivada (TG/DTG), análise térmica diferencial (DTA), difração de raios X (DRX) e a ressonância magnética nuclear (RMN) foram às técnicas utilizadas na caracterização das formas polimórficas. A maioria das amostras obtidas pelas técnicas de cristalização consistiam de misturas de formas cristalinas, contendo, por vezes, formas metaestáveis e formas amorfas. Identificaram-se duas formas cristalinas como polimorfos da loratadina, cujas curvas DSC mostrou interconversão entre ambas.The preparation, characterization and thermal behavior of the crystalline forms of the antihistamine loratadine has been developed. The selection of loratadine as an object of study results from its pharmacological interest. Loratadine is the International Common Denomination (ICD) given to ethyl 4-(8-chloro-5,6-dihydro-11H-benzo [5,6] cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate, a potent anti-allergic and anti-histamincs, tricyclic, non-sedating long acting. Crystalline forms were prepared and studied for the identification of polymorphic forms. The solvents used in preparing the solutions were: ethanol, acetonitrile, isopropyl alcohol, acetone, methyl alcohol, isopropyl ether, methyl tert-butyl ether, toluene, chloroform. The crystallization was performed by evaporating the solvent at different temperatures. The differential scanning calorimetry (DSC), thermogravimetry and derivative thermogravimetry (TG/DTG), differential thermal analysis (DTA), X-ray diffraction (XRD) and nuclear magnetic resonance (NMR) techniques were used to characterize the polymorphic forms. Most of the samples obtained by the crystallization were mixtures of crystalline forms, containing sometimes forms metastable and amorphous forms. It was identified as two crystalline polymorphic forms of loratadine, whose DSC curves demonstrated that they are interconvertable.
18
Vermeeren, Annemiek. "Hypnotics and antihistamines effects on cognitive functions and driving performance /." Maastricht : Maastricht : Neuropsych Publishers ; University Library, Maastricht University [Host], 2003. http://arno.unimaas.nl/show.cgi?fid=5504.
Full text
19
Shamsi, Ziba. "Measurement of drug action in man : psychometric aspects of antihistamines." Thesis, University of Surrey, 1999. http://epubs.surrey.ac.uk/843065/.
Full textAbstract:
The use of antihistamines (AHs) has until recently been associated with a number of undesirable side effects, the most troublesome of which is sedation. There are two aspects to sedation. The first, an objectively determined measure based on the results of psychometric tests from controlled trials, and the second, the subject's response to the administration of a drug. Since AHs are largely used in ambulant patients, a complete evaluation of sedation should be performed through standardised objective tests, shown to be sensitive to the central effects of AHs and reliable ratings of subjective experiences. A critical review of the literature on the experimental studies with AHs revealed that the traditional AHs had a greater propensity to produce adverse central nervous system (CNS) effects, whereas the so called second generation AHs were generally less impairing when administered within their recommended 'dose window'. A similar review of the clinical literature surveying subjective reports of sedation following the administration of AHs showed that the traditional AHs were perceived as more sedative than the second generation AHs. On the basis of these findings, a series of controlled experiments in non-atopic volunteers investigated the effects of a number of second generation AHs on various aspects of cognitive functioning and psychomotor performance. It is concluded that the second generation AHs have a lesser effect with respect to objective indices of sedation when compared to their predecessors, and that fexofenadine, has a claim to be the first truly non-sedating antihistamine as there is no objective evidence of CNS effects. The identification of an antihistamine, devoid of adverse CNS activity regardless of the administered dose, highlights the need for the introduction of a 'third generation' of AHs.
20
Waggoner, Charlotte M. "Dual task performance and antihistimane use." Thesis, This resource online, 1990. http://scholar.lib.vt.edu/theses/available/etd-03032009-040655/.
Full text
21
Moret, Illana M. Merce. "Study of the effects of methapyrilene on fresh and cryopreserved rat hepatocytes." Thesis, University of Surrey, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318660.
Full text
22
Ndlebe, Vuyelwa Jacqueline. "Thermal and photostability studies of triprolidine hydrochloride and its mixtures with cyclodextrin and glucose." Thesis, Rhodes University, 2004. http://hdl.handle.net/10962/d1005052.
Full textAbstract:
Triprolidine hydrochloride (C₁₉H₂₂N₂.HCl.H₂O) (TPH) is a well-known antihistamine drug. It melts between 118°C and 122°C and the amount of water present is 4.5 mass percent. TPH is reported as being photosensitive and must be stored in sealed, light-tight containers. The thermal stabilities of TPH and of 1:1 molar and 1:1 mass ratio physical mixtures of TPH with beta-cyclodextrin (BCD) and with glucose have been examined using DSC, TG and TG-FTIR, complemented by X-ray powder diffraction (XRD) and infrared spectroscopic (IR) studies. Thermal studies of the solid TPH/BCD mixtures indicated that interaction between the components occurs and it is possible that the TPH molecule may be least partially accommodated in the cavity of the BCD host molecule. XRD results support this indication of inclusion. The results for mixtures of TPH/glucose also suggest that there is interaction between the two components. The results of molecular modelling suggest that TPH is most likely to be accommodated in the BCD cavity as a neutral triprolidine molecule with the toluene portion of the molecule entering first. There is also an indication that the Z-isomer should be accommodated slightly more readily than the E-isomer. Photostability studies were done by irradiating thin layers of solid samples of TPH and its mixtures for various times at 40°C using an Atlas Sun test CPS lamp operating at 550 W h m⁻². An analytical method using HPLC was developed and validated to determine the amounts of any photodegradants. DSC, TG, FTIR, XRD and IR were also used examine the irradiated samples. XRD results showed that changes in the TPH crystal structure occurred during irradiation and that these changes increased with the time of irradiation. Irradiation for 20 hours with UV or exposure to sunlight showed the presence of degradants. The results obtained illustrate the general stability of TPH, especially in the solid state. Although the potential for isomerization to the pharmaceutically inactive Z-isomer exists, this transformation would require extreme light conditions. The study has also shown TPH to be compatible with both glucose and BCD, which are potential excipients both in solid and liquid dosage forms. The presents of these excipients in dosage forms will thus not adversely affect the stability and the therapeutic efficacy of TPH. . An analytical method using HPLC was developed and validated to determine the amounts of any photodegradants. DSC, TG, FTIR, XRD and IR were also used examine the irradiated samples. XRD results showed that changes in the TPH crystal structure occurred during irradiation and that these changes increased with the time of irradiation. Irradiation for 20 hours with UV or exposure to sunlight showed the presence of degradants.
23
Reardon, Gregory. "Contingent valuation and utility models for economic evaluation of pharmaceuticals : a study of antihistamines /." The Ohio State University, 1987. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487325740719789.
Full text
24
Mousa, Aisha H. "Characterization of a novel histamine G protein-coupled receptor from Schistosoma mansoni (SmGPCR)." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=79055.
Full textAbstract:
A G protein-coupled receptor with structural characteristics of a biogenic amine GPCR was cloned from Schistosoma mansoni (SmGPCR). SmGPCR was codon-optimized and double-tagged with FLAG and His epitopes at the N- and C-terminal ends, respectively. Immunofluorescence experiments targeting these epitopes revealed that the expression of codon-optimized SmGPCR was highly increased compared to wild-type in mammalian cells. These studies also demonstrated that SmGPCR has a typical GPCR topology, the N-terminus being extracellular and C-terminus intracellular. Functional assays revealed that codon-optimized SmGPCR was responsive only to histamine, which caused a dose-dependent increase in intracellular Ca2+ (EC50 = 0.54 +/- 0.05 muM), but not cAMP, consistent with a Gq pathway of signal transduction. In vitro behavioral studies showed that treatment of S. mansoni cercaria with exogenous histamine caused a dose-dependent increase in the motility of the parasite.
25
Zdanytė, Birutė. "Antihistamininių vaistų (klemastino fumarato, loratadino, desloratadino) mišinio išskyrimas iš kraujo plazmos ir identifikavimas efektyviosios skysčių chromatografijos metodu." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2014~D_20140630_135949-87726.
Full textAbstract:
Darbo tikslas: optimizuoti metodiką, kuria būtų galima atlikti antihistamininių vaistų mišinio, sudaryto iš klemastino fumarato, loratadino ir desloratadino, ekstrakciją iš kraujo plazmos ir kokybinį nustatymą efektyviosios skysčių chromatografijos metodu.
Darbo uždaviniai: Atlikti mokslinės literatūros analizę siekiant įvertinti antihistamininių vaistų savybes ir pasirinktų junginių ekstrakcijos iš kraujo plazmos ir tapatybės nusatymo metodikas. Optimizuoti ir validuoti ESC metodiką kokybiniam pasirinktų preparatų mišinio nustatymui iš kraujo plazmos. Parinkti klemastino fumarato, loratadino ir desloratadino skysčių – skysčių ekstrakcijos iš kraujo plazmos sąlygas. Apibendrinti gautus ekstrakcijos ir ESC rezultatus.
Metodai: skysčių – skysčių ekstrakcija ir ESC.
Tyrimo objektas: kraujo plazma, į kurią įterpti antihistamininiai vaistai klemastino fumaratas, loratadinas, desloratadinas ir jų mišinys.
Rezultatai: tiriamųjų medžiagų sulaikymo laikai: desloratatadino apie – 5,9 min, loratadino – apie 11,4 min, klemastino fumarato – apie 13,2 min. Validuota ESC atlikimo metodika. Atliekant ekstrakciją su trichlormetanu neišsiekstrahavo nei vienas tiriamasis junginys, su dichlormetanu – loratadinas, su dietileteriu ir cikloheksanu – visi trys tiriamieji junginiai.
Išvados: 1. Atlikta mokslinės literatūros analizė, apžvelgiant antihistamininių vaistų savybes, ekstrakcijos iš kraujo plazmos būdus bei identifikavimo metodus, didžiausią dėmesį skiriant efektyviajai skysčių... [toliau žr. visą tekstą]Aim: to optimise a method, by which mixture of antihistamines containing clemastine fumarate, loratadine and desloratadine could be extracted from human plasma and qualitative determination using high performance liquid chromatogrophy could be made. Tasks: to carry out analysis of scientific literature and evaluate characteristics of antihistamines and methods of chosen compounds extraction from human plasma and identity determination. Optimise and validate HPLC method for qualitative determination of chosen medicines. Select conditions suitable for chosen antihistamines liquid – liquid extraction from human plasma. Carry out qualitative determination of clemastine fumarate, loratadine and desloratadine in human plasma using validated HPLC method. Summarize results of extraction and HPLC. Methods: liquid – liquid extraction and HPLC. Object: human plasma with embedded antihistamines: clemastine fumarate, loratadine, deloratadine and their mixture. Results: retention times of test substances: desloratadine – 5,9 min, loratadine – 11,4 min, clemastine fumarate – 13,2 min. HPLC method was validated. None of the compounds were extracted using trichlormethan. Only loratadine was extracted using dichlormethan. All three compounds were extracted using diethyl ether and cyclohexane. Conclusions: 1. Analysis of scientific literature was caried out, characteristics of antihistamines, methods of extraction from human plasma and identity determination of chosen compounds were overviewed... [to full text]
26
Fernandes, João Paulo dos Santos. "Planejamento e sintese de compostos potencialmente ligantes dos receptores 5-HT2C e H4." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/9/9138/tde-18022013-135502/.
Full textAbstract:
A serotonina e a histamina são duas das mais importantes aminas biogênicas do organismo. Regulam série de funções fisiológicas, como fluxo sanguíneo, temperatura corpórea, sono, fome, liberação de hormônios, comportamento afetivo e humor, entre outras. Assim, há grande interesse no planejamento e desenvolvimento de fármacos que interferem na transmissão serotoninérgica e histaminérgica, para futura aplicação como antidepressivos, antipsicóticos, ansiolíticos e anorexígenos, além de perifericamente, apresentarem possíveis ações antiinflamatórias. O objetivo deste trabalho é apresentar a síntese de compostos contendo os núcleos pirrolquinolínico, benzoindólico e benzodiidrofurânico com potencial atividade ligante nos receptores 5-HT2C e H4, assim como avaliar a seletividade desses compostos em comparação aos receptores 5-HT2A/B e H3. Sintetizou-se série de compostos utilizando reações de alilação, adição à carbonila, termociclização, rearranjo de Claisen, iodociclização e substituição nucleofílica para a obtenção dos compostos finais. Estudos de otimização de síntese por metodologia de superfície de resposta também são apresentados, assim como estudos de relações quantitativas entre estrutura química e atividade biológica de compostos ligantes dos receptores 5-HT2C e H4.Serotonin and histamine are two major biogenic amines in the body. They regulate several physiological functions such as blood flow, body temperature, sleep, hunger, hormone release, emotional behavior and mood, among others. Thus, there is great interest in the design and development of drugs that interfere with serotoninergic and histaminergic transmission, for future use as antidepressants, antipsychotics, anxiolytics and anorectic, and peripherally, possible anti-inflammatory actions. The aim of this work is to present the synthesis of compounds containing the pyrroloquinoline, benzoindole and benzodihydrofurane nucleus with potential binding activity to 5-HT2C and H4 receptors, as well as to evaluate the selectivity of these compounds in comparison to 5-HT2A/B and H3. Series of compounds were synthesized using allylation, carbonyl addition, thermal cyclization, Claisen rearrangement, iodocyclization and nucleophilic substitution reactions. Optimization studies for the synthesis using response surface methodology are also presented, as well as quantitative structure-activity relationships studies of ligands of 5-HT2C and H4 receptors.
27
Cornet, Masana Josep Maria. "Reposicionament d’antihistamínics lisosomòtrops per a neoplàsies hematològiques." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/664131.
Full textAbstract:
Els antihistamínics són un conjunt de fàrmacs antagonistes del receptor d’histamina 1 (HRH1) àmpliament emprats per al tractament de l’al·lèrgia. Els darrers anys s’ha investigat la importància de HRH1 en càncer, i s’han descrit efectes antitumorals d’alguns antihistamínics. Al present treball s’ha ampliat aquesta recerca a les neoplàsies hematològiques, amb especial interès en leucèmia mieloide aguda (LMA), una malaltia amb recaigudes freqüents i mal pronòstic, i on existeix la necessitat de tractaments innovadors. Aquí, es descriu l’expressió en superfície de HRH1 en neoplàsies hematològiques, però descartant-ne un efecte clau en la leucemogènesi. Es descriuen, així mateix, els efectes antileucèmics selectius d’ebastina, terfenadina, loratadina i rupatadina al rang micromolar baix, validats en experiments en línies cel·lulars i amb mostres primàries de pacients en experiments ex vivo i in vivo. Aquest grup de fàrmacs, que hem anomenat antihistamínics antineoplàsics (ANHA), mostren efectes sinèrgics amb quimioteràpia convencional i posseeixen capacitat d’eliminar cèl·lules mare leucèmiques de LMA, considerades responsables de les recaigudes, preservant majoritàriament l’hematopoesi normal. El mecanisme pel qual els ANHA exerceixen els seus efectes antileucèmics és independent de HRH1, i es produeix mitjançant acumulació a lisosomes i mitocondris. Aquest tropisme dual inicia un procés de mort cel·lular caracteritzat per un augment de superòxid mitocondrial, una permeabilització de la membrana lisosomal i una activació de caspases. En línia amb aquestes observacions, els ANHA es caracteritzen per ser fàrmacs hidrofòbics amb estructura catiònica i amfifílica, característiques que s’han relacionat prèviament amb l’acumulació a aquests orgànuls. A partir d’aquestes observacions, es proposa l’ús de fàrmacs lisosomo- i mitocondriòtrops com a estratègia terapèutica per a la LMA i la resta de neoplàsies hematològiques, en la qual s’està treballant mitjançant química mèdica.Antihistamines constitute a drug family comprising antagonists of histamine receptor 1 (HRH1), extensively used for the relief of allergic symptoms. Over the last years, the importance of HRH1 in cancer has been investigated, and antitumoral effects of some antihistamines have been reported. The present work has expanded this research to hematological neoplasias, with special interest in acute myeloid leukemia (AML), a disease characterized by frequent relapse and bad prognosis for which novel treatments are desperately needed. Herein, we report surface expression of HRH1 in hematological neoplasias, while ruling out a key role in leukemogenesis. Likewise, we report selective antileukemic effects induced by ebastine, terfenadine, loratadine and rupatadine at the low micromolar range, as assessed in cell lines and in patient samples in ex vivo and in vivo experiments. This group of drugs, hereafter referred to as antineoplasic antihistamines (ANHA), display synergic effects when combined with conventional chemotherapy and are active against the AML leukemic stem cell compartment, considered responsible for the relapses, while mostly sparing healthy hematopoesis. ANHA-mediated antileukemic effects are HRH1-independent, and rely instead on lysosomal and mitochondrial accumulation. This dual tropism triggers a cell death process characterized by an increase in mitochondrial superoxide species, a lysosomal membrane permeabilization and caspase activation. In line with these findings, ANHAs possess a cationic amphiphilic structure with overall hydrophobicity, features previously related to accumulation in those organelles. Considering these observations, the use of lysosomo- and mitochondriotropic drugs is proposed as a therapeutic strategy in AML and other hematological neoplasias. Drug optimization to reach clinics is being currently pursued by medicinal chemistry.
28
Pinto, Ana Leonor Neto. "Anti-histamínicos H3: uma nova classe terapêutica." Master's thesis, [s.n.], 2012. http://hdl.handle.net/10284/3739.
Full textAbstract:
Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências FarmacêuticasA histamina é um importante mediador de vários processos do organismo humano. Além de estar envolvida em processos bioquímicos de respostas imunológicas, esta amina exerce também funções a nível do sistema gastrointestinal e actua como neurotransmissor. A descoberta dos receptores da histamina permitiu o desenvolvimento de vários compostos usados como agentes terapêuticos no tratamento de diversas doenças como reacções alérgicas (anti-histamínicos H1) e úlcera gástrica (anti-histamínicos H2). Actualmente são conhecidos quatro receptores da histamina: H1, H2, H3 e H4. Os receptores H3, devido à sua localização e acções que exercem no sistema nervoso central, como auto e hétero-receptores, têm despertado um interesse especial para o desenvolvimento de compostos que actuem nestes receptores. Os anti-histamínicos H3 apresentam-se então como uma nova classe terapêutica para o tratamento de patologias como a doença de Alzheimer, esquizofrenia, obesidade e narcolepsia. Histamine is an important mediator of various processes in the human body. Besides being involved in the biochemical processes of immune responses, this amine is also active in the gastrointestinal system and acts as a neurotransmitter. The discovery of histamine receptors permitted the development of various compounds used as therapeutic agents in the treatment of various diseases such as allergic reactions (H1 antihistamines) and gastric ulcer (H2 antihistamines). There are presently four known histamine receptors: H1, H2, H3 and H4. H3 receptors, due to its location and performs actions on the central nervous system, such as auto and hetero-receptors, have aroused a particular interest for the development of compounds that act on these receptors. Antihistamines H3 are then presented as a new class of therapeutics for treating pathologies such as Alzheimer's, schizophrenia, obesity and narcolepsy.
29
Mothé, Cintia Maria Alves. "Desenvolvimento de métodos analíticos por cromatografia líquida de alta eficiência e eletroforese capilar para medicamentos anti-histamínicos." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/9/9139/tde-15012014-150324/.
Full textAbstract:
Loratadina, desloratadina, rupatadina e ebastina são anti-histamínicos H1 de segunda geração, pertencentes ao grupo piperidínico, utilizados em casos clínicos de afecções alérgicas devido a sua ação sobre a histamina, que é o principal mediador da alergia e, também, pela sua ação anti-inflamatória ocorrida pelo bloqueio do fator de ativação plaquetária (PAF). Esses fármacos são denominados agonistas inversos dos receptores H1 não-sedativos. No presente estudo, foram desenvolvidos e validados métodos para a quantificação de loratadina, desloratadina, rupatadina e da ebastina em produtos farmacêuticos utilizando as técnicas de cromatografia líquida de alta eficiência (CLAE) e eletroforese capilar (CE). As análises por CLAE foram realizadas utilizando coluna LiChroCART® 100 RP- CN, 5 µm, (125 x 4 mm), fase móvel constituída MEOH:Tampão Fosfato de Sódio 20 mmol/L pH 3,0, (65:35 v/v), vazão de 1,0 mL/min; volume de injeção 20 µL, temperatura de 25°C ± 1ºC, detecção CLAE-UV λmáx: 254 nm. Paralelamente, foram desenvolvidos e validados métodos por CE, utilizando modo de separação por CZE com capilar de sílica fundida de 40,5 cm efetivos e 50 cm totais, 75 µm de diâmetro interno e 375 µm de diâmetro externo, eletrólito: ácido bórico 35 mmol/L, pH 2,5, tensão aplicada de 20 kV para, loratadina, desloratadina e rupatadina, e de 24 kV para ebastina, injeção hidrodinâmica de 0,5 psi por 3 segundos, temperatura de 25ºC ± 1ºC. Detecção CE-UV λmáx:205 nm. Os procedimentos foram validados, avaliando-se os parâmetros de especificidade, linearidade, precisão, exatidão, limite de detecção e quantificação e robustez, cujos resultados cumpriram os requisitos preconizados pela RE nº 899 da ANVISA. Os métodos propostos foram aplicados na análise de produtos farmacêuticos. Deste modo, os procedimentos estabelecidos podem ser aplicados para o aprimoramento do controle de qualidade de medicamentos, bem como garantir a segurança e a eficácia do uso terapêutico.Loratadine, desloratadine, rupatadine and ebastine are second generation H1 antihistamines belonging to the group piperidine. They are often used in the clinical cases of allergic diseases due to their action on histamine, which is the main mediator of allergy and also by their anti-inflammatory action mediated through platelet activating factor (PAF) blocking activity. These drugs are called inverse agonists of non-sedating H1 receptor. In present study a high performance liquid chromatographic (HPLC) and capillary electrophoresis (CE) methods were developed and validated for quantitative determination of loratadine, desloratadine, ebastine rupatadine in pharmaceutical drug products. The HPLC method was developed using LiChroCART ® RP-100 CN 5 microns (125 x 4 mm) column, mobile phase composed of MeOH: sodium phosphate buffer 20 mmol/L, pH 3.0 (65:35 v/v ) at a flow rate 1.0 mL/min, injection volume 20µL. The temperature was maintained at 25 ± 1 °C and UV detection was made at 254 nm. In parallel, a CE method was developed and validated using CZE mode using a fused silica capillary of 40.5 cm effective length and 50 cm total length with inner and outer diameter of 75 µm and 375µm, respectively. The background electrolyte was composed of 35 mmol/L boric acid, pH 2.5, applied voltage of 20 kV for loratadine, desloratadine and rupatadine and 24 kV for ebastine, hydrodynamic injection at 0.5 psi for 3 seconds. All analyses were made at 25 ± 1 °C and UV detection was made at 205 nm. The CE method was validated and following parameters were evaluated; specificity, linearity, precision, accuracy, limit of detection and quantification and robustness. The results met the requirements recommended by RE No. 899 of ANVISA. The proposed methods were applied in the analysis of referred pharmaceuticals. Thus, the proposed methods can be applied to improve the quality control of pharmaceuticals and consequently ensure the safety and efficacy of these products in therapeutic use.
30
Ciurlizza, Celis Claudia Paola. "Aportación al estudio de permeación transdérmica de cetirizina." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/457668.
Full textAbstract:
Actualmente los antihistamínicos son muy utilizados en el tratamiento de patologías relacionadas con procesos alérgicos, tanto aplicados directamente sobre la piel para obtener un efecto local, como administrados por vía oral. Sin embargo, en el transcurso de los últimos años, se ha puesto de manifiesto que puede utilizarse la piel como vía de administración de fármacos, formulados de tal forma que el principio activo desarrolle una acción sistémica. Así pues, el empleo de la vía dérmica y de la transdérmica como alternativa a la vía oral, ha dado lugar a un avance en cuanto al conocimiento de la estructura de la piel y en cuanto a los mecanismos de transporte de sustancias a través de ella. Cabe considerar que una de las líneas de investigación aplicada en el campo de la industria farmacéutica es el diseño de nuevos sistemas de liberación de fármacos sobre la piel (parches transdérmicos, liposomas, microemulsiones, nanoemulsiones, etc), que contienen excipientes novedosos y promotores de la permeación cutánea que permitan alcanzar el objetivo deseado: liberación local, regional o transdérmica del fármaco.
Por lo tanto, resulta interesante estudiar las características de permeación cutánea de la cetirizina en piel humana, vehiculizada en sistemas de liberación nanoestructurados destinados al tratamiento de alteraciones patológicas locales que cursen con procesos alérgicos.
Así pues, el objetivo principal del presente proyecto de tesis consiste, en la obtención de formulaciones nanoestructuradas de cetirizina (hidrogel y nanoemulsión) con el fin de obtener un efecto antihistamínico local, por un lado, y un efecto sistémico por el otro.
Para llevar a cabo este objetivo, se realiza un estudio “ex vivo” de la absorción transdérmica de cetirizina con distintos promotores, así, también se optimizan las formulaciones por medio de redes neuronales con el fin de obtener concentraciones plasmáticas predichas dentro del intervalo terapéutico, por último, se desarrolla y evalúa una formulación nanoestructurada de cetirizina para la obtención de un efecto local tópico sobre la piel.
El estudio de permeación transdérmica del hidrogel y de la nanoemulsión al 5% de cetirizina, demostró que sólo la nanoemulsión penetró a través de la piel después de 19h de la aplicación tópica, a pesar de esto, el flujo, el tiempo de latencia y el coeficiente de permeabilidad resultaron ser bajos. Pequeñas cantidades de la dosis tópica aplicada son absorbidas y las concentraciones séricas están significativamente por debajo del rango terapéutico (0,257-0,384 μg/ml). Parece que la aplicación tópica de cetirizina es óptima sólo para un efecto de aplicación local.
La velocidad de liberación de cetirizina para las nanoemulsiones fueron estadísticamente más bajas cuando se compararon con los hidrogeles. Ambos vehículos proporcionaron una liberación sostenida de cetirizina, siendo los hidrogeles los más adecuados, ya que se alcanzó un 75% de fármaco liberado en 6 horas.
En el estudio de la actividad antihistamínica del hidrogel y de la nanoemulsión de cetirizina en conejos, estadísticamente no se observaron diferencias, pero se pudo observar que el hidrogel demostró el efecto máximo en 30 min. El antihistamínico comercial, la dexclorfeniramina, exhibió levemente mayor reducción de la pápula que el hidrogel de cetirizina (14,12 y 12,60%), seguida por el dimetindeno maleato (9,02%) y finalmente la nanemulsión (8,32%).
En la búsqueda y selección de formulaciones transdérmicas de cetirizina con ayuda de redes neuronales artificiales, se construyó un test de 89 vectores de entrada, “xi pertenece a R18”, donde cada xi representa la composición de una formulación propuesta en términos de 18 constituyentes (agua, propilenglicol, transcutol, isostearato, etc.), como en el conjunto de entrenamiento. Las veintiuna redes entrenadas se aplicaron a las entradas de test para predecir los valores de las cuatro características (J (μg/h), Tl (h), Kp (cm/h) y Cee (μg/mL)) para cada nueva formulación. A partir de estas predicciones, se seleccionaron siete formulaciones candidatas para las que al menos el 50% de las redes (incluyendo la lineal) predijeron resultados satisfactorios, y en dos de ellas (las más prometedoras) al menos el 75% de las redes coincidieron.
Actualmente no existe en el mercado farmacéutico antihistamínicos de segunda generación disponibles para ser administrados por vía tópica, por lo que se puede concluir de acuerdo con los estudios realizados en este proyecto de tesis, que la nanoemulsión de cetirizina diclorhidrato es un sistema prometedor para el tratamiento de alergias producidas en la piel.
31
Kossuth-Cabrejos, Stefano, Arquímedes M. Gavino-Gutiérrez, and Wilmer Silva-Caso. "Factors associated with the severity of pruritus in patients with terminal chronic kidney disease undergoing hemodialysis in Lima, Peru." Page Press Publications, 2020. http://hdl.handle.net/10757/655593.
Full textAbstract:
The objective of the study is to analyze the factors associated with the severity of pruritus in patients with terminal chronic kidney disease undergoing hemodialysis. The methodology used is based on a cross-sectional study in patients receiving hemodialysis at the Centro Nacional de Salud Renal. Severe pruritus was defined as a score on the visual analogue scale greater than or equal to 7, and the strength of association with the possible risk factors was assessed by calculating prevalence ratios. Regarding the results, 264 patients were included, 59.9% were male, with a mean time on hemodialysis of 10.26 ± 7.14 years. 75% experienced pruritus, of this group, 1 in 3 presented severe pruritus. Hyperphosphatemia and the use of antihistamines were associated with a higher prevalence of severe pruritus (RP 1.71, 95% CI 1.09-267 and RP 2.39, 95% CI 1.51-3.75, respectively). The positive serology for Hepatitis C Virus was described as a protective factor for presenting severe pruritus (RP 0.55, 95% CI 0.33 - 0.89). In conclusion, severe uremic pruritus is a frequent problem in patients with chronic terminal kidney disease who have hyperphosphatemia and treatment with antihistamines independently of the time they have been on hemodialysis.Revisión por pares
32
García-Gea, Consuelo. "Evaluación de la seguridad conductual de un nuevo antihistamínico: relación dosis-respuesta e interacción con compuestos depresores (alcohol y benzodiacepinas)." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/368573.
Full textAbstract:
Las agencias reguladoras recomiendan la realización de estudios de interacción entre fármacos que suelen ser administrados de forma concomitante. Los antihistamínicos, las benzodiazepinas y el alcohol están entre los fármacos/sustancias mayoritariamente utilizadas en el mundo y, con frecuencia, de forma concomitante. Bilastina es un nuevo antihistamínico de segunda generación que ha mostrado ser clínicamente eficaz en pacientes con rinitis/rinoconjutivitis estacional/crónica o con urticaria idiopática crónica, mostrando un excelente perfil de seguridad en términos de efectos a nivel de SNC. En ensayos clínicos Fase I previos, bilastina mostró ausencia de efectos sedantes en estudios realizados en condiciones de laboratorio y en estudios de conducción real, cuando se administró a dosis terapéutica (20 mg) o al doble de dosis recomendada (40 mg). Sin embargo, bilastina 80 mg indujo deterioro psicomotor en jóvenes sanos. Incluso cuando el potencial para producir sedación es mínimo, éste podría ser incrementado por la administración concomitante de otras sustancias con un efecto depresor sobre el SNC.
Con el objetivo de completar el desarrollo clínico de bilastina, se diseñaron dos ensayos clínicos Fase I para investigar la posible interacción farmacodinámica entre bilastina y alcohol o entre bilastina y lorazepam. Ambos estudios se realizaron en condiciones de laboratorio y según un diseño cruzado, aleatorizado, a doble-ciego y controlado con placebo. Los efectos sobre el SNC se evaluaron mediante una batería de tests objetivos de rendimiento psicomotor y cuestionarios de evaluación subjetiva. Las evaluaciones se realizaron a nivel basal y a diferentes tiempos postmedicación. Los resultados se analizaron mediante una aproximación paramétrica (ANOVAs de medidas repetidas) y mediante una aproximación multivariante no paramétrica.
En el estudio de “interacción con alcohol”, participaron 24 jóvenes sanos de ambos sexos, y separados por 1 semana de blanqueo, se evaluaron 6 condiciones de tratamiento (administración única): placebo (PLA), alcohol 0.8 g/Kg (ALC), ALC más bilastina 20 mg (B20+A), ALC más bilastina 80 mg (B80+A), ALC más cetirizina 10 mg (CET+A), ALC más hidroxizina 25 mg (HYD+A). Todos los tratamientos activos indujeron un significativo deterioro a nivel objetivo de rendimiento psicomotor. El deterioro de mayor magnitud y duración se evidenció con HYD+A, seguido por B80+A y CET+A. En contraste, B20+A y ALC indujeron un deterioro de magnitud inferior sin diferencias significativas entre ambos tratamientos. En todas las condiciones en las que se administró alcohol, se evidenció un efecto sedante a nivel subjetivo.
En el estudio de “interacción con lorazepam”, 17 jóvenes sanos de ambos sexos completaron su participación en el estudio. Se evaluaron 3 condiciones de tratamiento: placebo, lorazepam 3 mg, bilastina 20 mg más lorazepam 3 mg. La medicación de estudio se administró como dosis únicas diarias durante 8 días consecutivos. Los resultados obtenidos evidenciaron un significativo deterioro a nivel de SNC (objetivo y subjetivo) tras la administración de lorazepam, solo o en combinación con bilastina, sin diferencias significativas entre ambas condiciones de tratamiento activo y con un menor efecto tras la administración repetida (día 8) en comparación al efecto evidenciado tras la administración de la primera dosis (día 1).
En conclusión, la administración concomitante de bilastina, a dosis terapéutica (20 mg), junto con alcohol o lorazepam no produjo un deterioro a nivel de SNC diferente al inducido por la ingesta de alcohol o lorazepam solos.Pharmacodynamic drug-drug interactions studies are recommended by regulatory agencies for drugs which are likely to be used concomitantly. Antihistamines and benzodiazepines or alcohol are among the most widely used drugs in the world and often they are consumed concomitantlLy. Bilastineis a new second-generation antihistamine compound which has been shown to be clinically effective in patients with seasonal/perennial allergic rhinitis/rhinoconjunctivitis or chronic idiopathic urticaria, with an excellent safety profile in terms of CNS effects. In previous controlled phase I clinical studies, bilastine showed lack of sedative effects under laboratory conditions or on actual driving ability when it was administered at therapeutic dose (20 mg) or twice the recommendeddose (40 mg). In contrast,bilastine80 mg induced psychomotor impairment in healthy subjects. Even if a drug has only a minimal potential to induce sedation, this effect could, potentially, be exacerbated by the concomitant use of other CNS depressant drugs. In order to complete the clinical development of bilastine, two clinical trials Fase I were designed for to investigate the potential pharmacodymic interaction between bilastine and alcohol and between bilastine and lorazepam. Both trials were carried out in laboratory conditions following a crossover, randomized, double-blind and placebo-controlled design. CNS effects were evaluated using a battery of psychomotor performance tests and subjective evaluation tools. Evaluations were performed at baseline and several times post-medication. Results were analyzed by mean a parametric approach (ANOVAs for repeated measures) and a multivariate non-parametric approach. In the “alcohol-interactionstudy”, twenty-four healthy young volunteers of both sexes were randomized and, at 1-week interval,6 treatments conditions (single administration) were evaluated: placebo (PLA), alcohol 0.8 g/Kg (ALC), ALC plus bilastine 20 mg (B20+A), ALC plus bilastine 80 mg (B80+A), ALC plus cetirizine 10 mg (CET+A), ALC plus hydroxyzine 25 mg (HYD+A). All active treatments induced a significant objective psychomotor impairment. The greatest and most lasting impairment was observed with HYD+A followed by B80+A and CET+A. In contrast, objective measures showed less impairment with B20+A and ALC, both with a similar magnitude. Self-reports showed a subjective perception of performance impairment in all active treatments. In the “lorazepam-interaction study”, 17 healthy young male and female volunteers completed their participation in the study. Three treatment conditions were evaluated: placebo,lorazepam 3 mg, bilastine 20 mg plus lorazepam 3 mg. The study medication was administered for 8 consecutive days as a single daily dose in each of the treatment periods. Results demonstrated significant detrimental CNS effects (objective and subjective) when lorazepam was administered alone or in combination with bilastine, without significant differences between both and with a lower effect after repeated administration (day 8) versus the first administration (day 1). In conclusión, concomitant administration of bilastine, at therapeutic dose (20 mg) with alcohol or lorazepam does not produce greater central nervous system depressant effects than alcohol or lorazepam administered alone.
33
Wasicky, André. "Estudo farmacognóstico comparativo de Passiflora alata Curtis e Passiflora nítida Kunth (Passifloraceae). Avaliação das atividades antiúlcera e antioxidante dos seus extratos." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/9/9138/tde-25102017-165240/.
Full textAbstract:
Passiflora alata Curtis e P. nitida Kunth, espécies brasileiras, foram submetidas ao estudo farmacognóstico comparativo. P. alata tem sido utilizada há tempos na medicina tradicional e em preparações farmacêuticas. No estudo farmacobotânico, as folhas das duas espécies apresentaram semelhança na forma, no tamanho e na ausência de indumento. Diferem quanto ao número de glândulas peciolares. P. alata apresenta geralmente dois pares de glândulas e P. nitida, um par. Anatomicamente, as duas espécies mostraram características comuns ao gênero Passiflora: mesofilo dorsiventral; drusas no mesofilo, na nervura mediana, na região cortical, medular e floemática do caule; feixes vasculares colaterais. Embora as duas espécies apresentem nervura mediana biconvexa, a de P. alata evidencia as carenas pronunciadamente salientes, principalmente na face abaxial. Outro aspecto diferencial observa-se na forma do caule: em P. alata é quadrangular e, em P. nitida, arredondada. A seqüência de tecidos assemelha-se, com exceção do maior desenvolvimento de colênquima nas arestas de P. alata. A triagem fitoquímica evidenciou a presença de flavonóides nas duas espécies e a ausência de alcalóides em ambas, tanto na droga vegetal quanto nos extratos. Formação de espuma persistente foi observada com a droga vegetal preparada com P. alata. A hemólise foi observada com a droga e o extrato desta espécie. Os flavonóides foram quantificados como 0,42% ± 0,01 em P. alata e 0,10% ± 0,01 em P. nitida. No ensaio da atividade antioxidante, a EC50 de P. alata foi de 1061,2 ± 8,5 µg/mL e a de nitida 128,0 ± 0,9 µg/mL, no ensaio do DPPH, e de 1076 ± 85 µµmol de Trolox/g de extrato e de 1985 ± 104 µmol de Trolox/g de extrato no ensaio de ORAC, respectivamente. No ensaio de atividade antiúlcera aguda P. alata exibiu, na área total de lesão (ATL), proteção contra as lesões gástricas de 100%, P. nitida de 84% e lansoprazol, o controle positivo, de 76%. Quanto à área relativa de lesão (ARL), alata exibiu proteção contra as lesões de 99,45%; P. nitida, de 82,27% lansoprazol, de 81,44%, no ensaio de lesão gástrica induzida por etanol/HCI com 300 mmol/L de HCI e extratos na dose de 400 mg/kg. As doses de 100,200 e 400 mg/kg dos extratos foram testadas nas mesmas condições com 150 mmol/L de HCI. P. alata apresentou, na ATL, 100% de proteção contra as lesões gástricas nas três concentrações e lansoprazol, de 75%. Na ARL, P. alata exibiu 100% de proteção lansoprazol, de 76,92%. P. nitida apresentou, na ATL, proteção contra as lesões gástricas de 25%, 74% e 94% nas três concentrações, respectivamente e, lansoprazol, de 80%. Na ARL, P. nitida exibiu 27,40%, 74,00% e 91,78% de proteção, respectivamente e lansoprazol, de 78,08%. Baseando-se neste estudo possível distinguir as duas espécies através de características morfoanatômicas das folhas e dos caules e, através do perfil cromatográfico. Ambas as espécies apresentaram atividade antiúlcera promissora.Passiflora alata Curtis and P. nitida Kunth, Brazilian species, were selected for the comparative pharmacognostic study. P. alata has been used for a long time folk medicine and pharmaceutical preparations. In the pharmacobotanic study, leaves from both species showed similarities in shape, size and in the absence indumenta. They differ by the number of petiolar glands. P. alata presents generally two pairs of glands and P. nitida, one pair. Anatomically, both species showed common characteristics to the Passiflora genera: dorsiventral mesophyll; druses the mesophyll, midrib, cortex, medulla and phloem; collateral vascular bundles. Both species\' midrib presented a biconvex shape, but P. alata\'s was prominently shaped, notably in the abaxial surface. Another differential aspect was observed the stem shape: P. alata was quadrangular and P. nitida was rounded. The tissues sequence presented similarity, with exception to larger collenchyma development in P. alata\'s edges. The phytochemical screening showed presence of flavonoids and absence of alkaloids in both species, in the crude drug and extracts. Formation persistent foam was observed with the crude drug of P. alata. Hemolisis was observed with the crude drug and extract of this species. Flavonoids were quantified as 0.42% ± 0.01 in P. alata and 0.10% ± 0.01 in P. nitida. In the antioxidant activity assay, the EC50 of P. alata was 1061.2 ± 8.5 µg/mL and of P. nitida , 128.0 ± 0.9 µg/mL, in the DPPH assay, and 1076 ± 85 µmol Trolox/g extract and 1985 ± 104 µmol Trolox/g extract in the ORAC assay, respectively. In the antiulcer activity assay P. alata showed, in total lesion area (TLA), protection against gastric lesions 100%, P. nitida 84% and lansoprazole, the positive control, 76%. In relative lesion area (RLA), P. alata showed protection against lesions of 99.45%, P. nitida82.27% and lansoprazole 81.44%, in the HCl/ethanol-induced gastric lesion assay, with HCI 300 mmol/L and extracts at doses of 400 mg/kg. Doses of 100, 200 e 400 mg/kg extracts were tested in the same conditions with HCl 150 mmol/L. P. alata showed, TLA, protection against gastric lesions of 100% in the three concentrations and lansoprazole 75%. In RLA, P. alata showed 100% of protection and lansoprazole 76.92%. P. nitida showed, in TLA, protection against gastric lesions of 25%,74% and 94% in the three concentrations, respectively and lansoprazole 80%. In RLA, nitida showed 27.40%, 74.00% and 91.78% of protection, respectively and lansoprazole 78.08%. Based upon this study it is possible to distinguish both species by leaf and stem morphoanatomic characters and by chromatographic profile. Both species presented promising antiulcer activity.
34
Ishikawa, Tati. "Estudo fitoquímico e biológico do cambucá Plinia edulis (Vell.) Sobral - Myrtaceae." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/9/9138/tde-09112016-112132/.
Full textAbstract:
Plinia edulis (Myrtaceae), espécie arbórea popularmente conhecida como cambucá, é nativa da Mata Atlântica brasileira. Apesar do emprego na medicina tradicional em diversas moléstias, incluindo distúrbios gástricos, não existem estudos relacionando as atividades biológicas e os constituintes químicos da espécie. Esta tese relata a avaliação da gastroproteção, da atividade antioxidante, da citotoxicidade e da mutagenicidade do extrato etanol/água de folhas de P. edulis e das frações. Com o objetivo de correlacionar os metabólitos secundários com a eficácia da droga vegetal na medicina tradicional, o extrato foi submetido à partição e posterior fracionamento cromatográfico. O extrato apresentou atividade gastroprotetora significativa em modelo de indução de úlceras por etanol acidificado em ratos em doses de 100, 200 e 400 mg/kg via oral, sendo mais ativo que o fármaco de referência lansoprazol. Entre as frações, a hexânica (100 mg/kg p.o.) foi a mais eficaz, mas apresentou menor atividade do que o extrato bruto. A gastroproteção do ácido ursólico também foi avaliada, mas embora outros triterpenos sejam conhecidos como gastroprotetores, o ácido ursólico (50 mg/kg p.o.) reduziu a área lesionada, mas não apresentou atividade significativa no modelo empregado. O extrato não evidenciou mutagenicidade na concentração de 20 mg/placa no Ensaio de Ames e apresentou atividade antioxidante pronunciada, com CE50 de 5,75 µg/mL no ensaio com DPPH e valor de ORAC de 3.948 µmol de Trolox/g de extrato. O extrato e as frações foram avaliados quanto à citotoxicidade em linhagens de células tumorais humanas de UACC62 (melanoma), MCF-7 (mama), NCI 460 (pulmão), OVCAR03 (ovário), PC-03 (próstata), HT-29 (cólon), 786-0 (rins), NCI-ADR (mama com fenótipo de resistência a múltiplos fármacos) e linhagem de células normais de ovário de hamster chinês (CHO) in vitro. O extrato e as frações apresentaram citotoxicidade seletiva dose-dependente em células cancerígenas e atividade proliferativa em células normais. A partir das frações de hexano e acetato de etila foram identificados β-amirina, lupeol, β-sitosterol, ácido oleanólico, ácido ursólico, ácido maslínico, ácido corosólico, galato de etila, ácido gálico, quercitrina, miricitrina e quercetina por meio de análises espectrométricas. Estes resultados dão suporte à utilização popular desta espécie e estão provavelmente associados à presença dos flavonóides e triterpenos identificados no extrato.Plinia edulis (Myrtaceae), an arboreous species popularly known as cambucá, is native in Brazilian Atlantic Rain Forest. Despite its traditional uses in many diseases, which include gastric disorders, no reports are available on the relationship between the biological activities of its extract and its chemical constituents. This thesis reports the evaluations of the the aqueous ethanol extract of leaves of P. edulis and its fractions on gastroprotective effect, antioxidant capacity, cytotoxicity and mutagenicity of. In order to correlate the secondary metabolites and the efficacy of the crude drug in traditional medicine, the extract was submitted to solvent partition followed by chromatographic fractionation. The extract exhibited significant gastroprotective effect on HCl/ethanol-induced ulcers in rats at doses of 100, 200 and 400 mg/kg p.o., even more active than the reference drug lansoprazole. Among the fractions, the hexane fraction (100 mg/kg p.o.) was the most effective, but showed lower activity than the crude extract. In addition, the gastroprotective effect of ursolic acid was evaluated. Although others triterpenes are well known as gastroprotective agents, ursolic acid (50 mg/kg p.o.) reduced the lesion area, but did not show significant activity on this model. The extract did not show mutagenicity at the concentration of 20 mg/plate in the Ames test and exhibited high antioxidant activity, with EC50 of 5.75 µg/mL on the DPPH assay and ORAC value of 3948 µmol Trolox/g of extract. The extract and its fractions were evaluated for cytotoxic activity against human tumour cell lines as UACC62 (melanoma), MCF-7 (breast), NCI 460 (lung, non-small cells), OVCAR03 (ovarian), PC-03 (prostate), HT-29 (colon), 786-0 (renal), NCI-ADR (breast expressing phenotype multiple drugs resistance) and CHO (Chinese Hamster Ovary) normal cell line in vitro. The extract and its fractions showed selectively dose-dependent cytotoxicity against cancer cells and proliferative activity in normal cells. The hexane and ethyl acetate fractions yielded β-amyrin, lupeol, β-sitosterol, oleanolic acid, ursolic acid, maslinic acid, corosolic acid, ethyl gallate, gallic acid, quercitrin, myricitrin and quercetin, which were identified based on spectrometric analyses. These results provide scientific support to the traditional use of this species, which are probably associated with the flavonoids and triterpenoids identified in the extract.
35
Pasquale, Raquel Donatini De. "Atividades antiúlcera e antioxidante de Syzygium jambos (L.) Alston." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/9/9138/tde-04112016-160627/.
Full textAbstract:
O jambeiro (Syzygium jambos (L.) Alston) constitui uma das diversas espécies frutíferas e medicinais pertencentes à família Myrtaceae. O extrato hidroetanólico a 70% liofilizado de folhas de S. jambos apresentou atividade dose-dependente em modelo de úlcera gástrica induzida por etanol acidificado, sendo que a dose de 400 mg/kg reduziu significativamente a Área Total de Lesão (81,64%) e a Área Relativa de Lesão (65,11 %), em comparação ao grupo controle. Nesta dose, o extrato apresentou-se mais eficaz que o fármaco empregado como referência (lansoprazol 30 mg/kg). No modelo de indução de úlcera gástrica por ácido acético, o extrato (400 mg/kg) não apresentou resultados significativos na cura das lesões. A atividade antioxidante do mesmo extrato e de quatro frações foi avaliada através da medida da capacidade seqüestrante de radicais 1,1-difenil-2-picrilidrazila. O extrato hidroetanólico a 70% liofilizado apresentou CE50 de 5,36 ± 0,06 µg/mL, valor comparável ao do Trolox (CE50 =4,98 ± 0,04 µg/mL) , substância antioxidante de referência. As frações clorofórmica, acetato de etila, etanólica e hidroetanólica a 50% apresentaram CEso de, respectivamente, 64,06 ± 0,68 µg/mL, 19,02 ± 0,22 µg/mL, 6,89 ± 0,12 µg/mL e 8,47 ± 0,05 µg/mL. Da fração clorofórmica do extrato foi isolado o triterpeno ácido ursólico. Na avaliação da toxicidade subcrônica através da administração oral a ratos Wistar, durante 30 dias, de três diferentes doses do extrato (400, 1000 e 2500 mg/kg), não foram observados sinais clínicos de toxicidade. As análises macroscópica e microscópica dos órgãos não mostraram alterações dignas de nota para nenhuma das doses empregadas. Não houve diferenças estatisticamente significativas nos resultados das análises bioquímicas do sangue dos animais. Os resultados revelam o potencial do extrato no tratamento de úlceras gástricas, sendo necessários estudos mais aprofundados do mecanismo de ação desta atividade, bem como de toxicidade crônica.Syzygium jambos (L.) Alston is one of the species of Myrtaceae with medicinal properties. The dried 70% hydroethanolic extract of the leaves showed a doseresponse effect in ethanol/HCI-induced ulcers, significantly decreasing the total lesion area (81,64%) and relative lesion area (65,11 %) compared to control group. At this dose the extract was more effective than lansoprazol (30 mg/kg), used as reference drug. The same extract at 400 mg/kg was not effective on healing acetic acid-induced ulcers. Antioxidant activity of S. jambos extract and four fractions was measured using 1,1-diphenyl-2-picryl-hydrazyl radical scavenging ability. The EC50 value for the extract was 5,36 ± 0,06 µg/mL, while Trolox, antioxidant substance of reference, showed EC50 of 4,98 ± 0,04 µg/mL. The tested fractions (chloroform, ethyl acetate, ethanol and 50% ethanol) showed EC50 of 64,06 ± 0,68 µg/mL, 19,02 ± 0,22 µg/mL, 6,89 ± 0,12 µg/mL e 8,47 ± 0,05 µg/mL, respectively. Ursolic acid was identified in the chloroformic fraction of the extract. Subchronic toxicity studies were performed by oral administration of the leaf extract to rats, during 30 days, at three different doses (400, 1000 and 2500 mg/kg). The extract did not show any clinicai sign of toxicity. Macroscopic and microscopic analysis of the organs demonstrated no alterations for the three doses tested. There were no statistically differences between results of biochemical analysis of blood. These results show the potential of the extract in treatment of gastric ulcer, although more studies of mechanism of action and chronic toxicity are necessary.
36
Kuo, Kun-Fu, and 郭崑福. "Development of optimum formulation for an antihistamine using experimental design." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/3ntwa8.
Full textAbstract:
碩士嘉南藥理科技大學
藥物科技研究所
97
Experimental design can be used to reduce experiment frequency and cost as well as, discover influence factor and level in the experiment. Experimental design may probe several factors into experimental variables, which use the least experimental frequency to procure experimental purpose. Therefore, it can reduce time and the cost. In this study, desloratadine is used as a model drug to explore the effects of formulation variables on drug dissolution from tablets. The experimental design is Taguchi method for three factors by three levels (L9(34)) of Taguchi orthogonal array. The aims of this study are to identity formulation factors on drug release from desloratadine tablets, to develop of an experimental design method and to optimize formulation utilizing experimental design method . The tablet sample were prepared by direct compression. The dissolution test were performed using the USP apparatus Ⅱ(paddle) method under 37±0.5℃ and 50 rpm in medium for 2 hours. HPLC analysis method was used by using RP-C18 column. Statistical analysis were performed on percent released at certain time point (% Ptime) and similarity factor (f2). Response surface methodology was used to simulate to obtain the possible optimum formulation.
37
Mathir, Zohra Mohamed. "Pharmaceutical availability on newly formulated oral sustained release pellets containing the antihistamine, chlorpheniramine maleate." Thesis, 1991. http://hdl.handle.net/10413/8017.
Full textAbstract:
The main objective of the present study was to determine the feasibility of obtaining aqueous polymer-coated pellet formulations using EudragitR NE 30 D dispersion and chlorpheniramine maleate as the model drug. Many factors influence the rate of drug release from coated beads including, the substrate, the coating formulation and the coating process. A drug release profile that was comparable to that of the reference standard, DykatussR Capsules was obtained with a formulation employing 8.3% EudragitR NE 30 D, 0.5% talc and 1% polyethylene glycol. In vitro dissolution tests on this formulation showed drug release to be predictable, reproducible and independent of the
dissolution methods or media. Short term storage confirmed the stability at room temperature (20°C) and low temperature (5C). Scanning electron micrographs of pellets stored at elevated temperatures i.e. 37°C with 80% relative humidity and 40°C illustrated the phenomenon of 'further gradual coalescence' which corresponded to the decrease in release of drug from the pellets.Thesis (M.Sc.)-University of Natal, Durban, Westville, 1991.
38
Wu, Jia-Syuan, and 吳佳璇. "Analyzing the Allergic Reactions Induced by the Chemotherapy Regimens Including Oxaliplatin and Evaluating the Effectiveness of Receiving Preventive Antihistamine Drugs." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/66498648402200227481.
Full textAbstract:
碩士高雄醫學大學
藥學研究所碩士在職專班
102
【Background】 According to the latest 2011 cancer registration report announced by Taiwan Health Promotion Administration, Ministry of Health and Welfare, the incidence of gastric cancer is ranked No. 6 in males and No. 8 in females, while the incidence of colorectal cancer ranked No. 1 in males and ranked No. 2 in females. Oxaliplatin is currently one of the main drugs of chemotherapy for colorectal cancer and end-stage gastric cancer. Oxaliplatin is a third- generation platinum compound, which is approved by the National Health Insurance Bureau for treatment of stage III colon-rectal cancer, metastatic colorectal cancer and partially end-stage or metastatic gastric cancer. According to many studies, about 90% of the patients who have received oxaliplatin treatments are accompanied by peripheral neuropathy, whose grade is related to the dosage of oxaliplatin. Most of these adverse events can recover during the chemotherapy cycles. The clinical medical staff can provide patients with instructions to against these adverse drug reactions. However, registered allergic reactions as another adverse drug reaction of oxaliplatin, besides neuropathy, are increasing in recent years, severe allergic reactions even interrupted ongoing oxaliplatin treatments because some of the patients came to the end of endurance. Objective : During the clinical treatment, patients are given antihistamine drugs to alleviate allergic reactions induced by oxaliplatin, and it is successful in most of them. Due to the effect, some clinical doctors give the patients antihistamine drugs in advance to prevent allergic reactions before the patients receive oxaliplatin infusions. However, on the one side, antihistamine drugs often cause dizziness, nausea, or conscious disturbance. On the other side, the antihistamine drugs cannot prevent some patients effectively from oxaliplatin-induced allergic reactions by clinical observation. Because there is no relevant guideline for the prevention from oxaliplatin-induced allergic reactions, this study aims to evaluate the effectiveness of the prevention of antihistamine drugs against oxaliplatin-induced allergic reactions in order to provide information on clinical treatment and post-treatment care. 【Methods】 This is a retrospective case-control study with subjects composed of patients who have allergic reactions after receiving oxaliplatin infusions from January 2008 to May 2013 in a medical center in southern Taiwan. The subjects are divided into two groups: the study group consisted of patients without taking antihistamine drugs before the oxaliplatin infusion; the control group consisted of patients taking antihistamine drugs before the oxaliplatin infusions. By means of case review and combining with the adverse drug reaction registration system in the hospital, we analyze the incidence of oxaliplatin-induced allergic reactions and the grade of allergic reactions. The data are processed and analyzed by SPSS 19.0 for Windows and explained with descriptive statistics of percentage, mean value, median value and standard deviation, as well as inferential statistics of Chi-Square test and 95% confidence interval analysis. 【Results】 There were 545 patients receiving oxaliplatin infusions from January 2008 to May 2013. Finally 535 patients are included for analysis, including 85 patients (15.6%) reported with allergic reactions, which occurred after a median of the eighth infusion of oxaliplatin. 61 patients of them received oxaliplatin re-challenge; 46 of these 61 patients (75.4%) led to further reactions, and 24 patients (28.2%) stopped their oxaliplatin treatment owing to intolerance to oxaliplatin-induced allergic reactions. The symptoms of oxaliplatin-induced allergic reactions are primarily skin rashes (76.5%), secondly shortness of breath and chest tightness (32.3%), sweating, vomiting and so on. These 535 patients receiving oxaliplatin infusions were divided into two groups, 164 patients without receiving antihistamine drugs before the oxaliplatin infusion in the study group, and 371 patients receiving antihistamine drugs before the oxaliplatin infusion in the control group. 27 patients (16.46%) in the study group had allergic reactions, while allergic reactions happened to 58 patients (15.22%) in the control group. The rates of oxaliplatin-induced allergic reactions show no statistically significant difference (P> 0.05) between the two groups, revealing that receiving antihistamine drugs before the oxaliplatin infusion cannot effectively prevent allergic reactions. 【Conclusion】 This study reveals that the effectiveness of giving patients in the study group antihistamine drugs to prevent allergic reactions caused by oxaliplatin had no statistically significant difference from that in the control group. It was also found that giving antihistamine drugs in advance not only increases side effects such as dizziness, nausea and conscious disturbance but also could not effectively prevent allergic reactions caused by oxaliplatin. The findings provide information for clinical treatments that giving antihistamine drugs after allergic reactions occur due to oxaliplatin instead of giving it in advance for prevention not only reduces the complexity of the clinical implementation and adverse reactions caused by antihistamine drugs but also helps increase cost-effectiveness in all the aspects of medical treatment. Clinically, patient instructions about patient’s awareness of allergic reactions and self-care abilities, besides the often seen gastrointestinal side effects and neuropathy, should be enhanced, especially for the patients who have had allergic symptoms due to oxaliplatin and to more than 70% of whom it happens again after oxaliplatin re-challenge. Other preventive methods such as extending the time of oxaliplatin infusions or decreasing oxaliplatin dosage to reduce allergic reactions need more researches to verify their effectiveness.
39
Lee, Wan-Hua, and 李宛樺. "Prescribing Patterns and Pharmacovigilance of Antihistamines in Children." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/45595112824996736294.
Full textAbstract:
碩士國立臺灣大學
臨床藥學研究所
97
Background Although H1-antihistamines, one of the common drugs used in children, have been introduced to clinical use for more than 60 years, many of them were deficient of appropriate clinical trial evaluations. Additionally, based on ethic and practical factors, it’s difficult to promote a clinical trial to children, which makes it insufficient information to prove efficacy and safety of antihistamines and makes pediatric drug are prescribed ”off-label” excessively which may increase potential risk of adverse drug reactions in children. Therefore, it is worth to analyze current status of antihistamine usage in children. Objective We focus the study on analyzing the prescribing patterns of antihistamines by clinicians for children, and investigate the risk of adverse drug reactions including neurological-, psychological-, and cardiac-related events related to antihistamines. Methods The study used the National Health Insurance Research Database (NHIRD) in 2007 and extracted data of patients aged below 18, focusing on prescriptions containing antihistamines to analyze prescribing patterns in Taiwan. Antihistamine prescriptions were quantified as person-time to analyze the prescription pattens associated with different settings of hospital and prescribers. Bseides, we make use of a retrospective study to analyze antihistamine-related adverse events, including insomnia, movement disorders, psychosis, seizures, consciousness changes and arrhythmia. The analyses were done by using sampling data (one tenth of original data) from patients aged below 18 in 2007 with exclusion of data from those with underlying disorders of neurologic, psychotic, and cardiovascular system in 2006. We constructed time-dependent Cox’s proportional hazard models for each variable. Results Among a total of 205841 out-patients aged under 18 from the NHIRD in 2007, 86.6% of children received at least one antihistamine during visits and 61.1% prescriptions contained some antihistamines. Children aged between 2 to 12 (76.77%) were the major age group receiving antihistamines and 87.3% of antihistamine usages were 1st-generation antihistamines. The top 10 frequently used antihistamines were chlorpheniramine, cyproheptadine, dexchlorpheniramine, carbinoxamine, triprolidine, mequitazine, cetirizine, loratadine, buclizine and brompheniramine. Oral solid form (83.4%) was the major dose form of antihistamine, and multi form was 37.0%. Most antihistamines were used for acute respiractory infection, and a high percentage of 2nd-generation antihistamines were used in chronic respiractory disease and dermatitis. Pediatric and E.N.T. departments were the major medical utilizations of antihistamines. More than one antihistamine were used in 31.1% of prescriptions, especially for pediatricians (48.68%) and private clinics (66.13%). We sampled one tenth of original data to get 19000 patients whose ages was 10.7 ± 5.0 years in average for analysis of drug-associated adverse events. Patients exposed to 1st-generation antihistamines are more likely to experience insomnia than those who did not (HR = 3.72, 95% CI=1.21-11.44, p = 0.022), and 1st -generation antihistamines in multi liquid form were more likely to be associated with insomnia (HR = 4.17, 95% CI = 1.09-16.00, p = 0.0377). Patients exposed to 1st -generation antihistamines were more likely to have movement disorders than those who didn’t (HR = 9.56, 95% CI = 4.72-19.38, p < 0.0001). Patients used 1st -generation antihistamines were more likely to have consciousness changes than those who didn’t (HR = 1.45, 95% CI = 1.10-1.92, p = 0.0089). The occurrence of seizures and arrhythmia did not significantly related to any variables in the analysis. Conclusions Children aged between 2 to 12 were the major age group receiving antihistamines. Antihistamines were used in 6 out of every 10 prescriptions. Most antihsitamines were 1st -generation antihistamines, and the major dose forms were oral solid form. Chlorpheniramine, cyproheptadine, dexchlorpheniramine, carbinoxamine were most commonly used. More than one antihistamine were used in 31.1% of prescriptions. Insomnia, movement disorders, and consciousness changes were releated to the use of 1st -generation antihistamine, but not 2nd-generation antihistamines. Otherwise, using the multi liquid form of 1st -antihistamines has a higher hazard ratio to induce insomnia. Events of seizures and arrythmeia were not related to the use of antihistamines in our study. Further studies may use different strategies to delineate the drug safety of antihistamine use in children, including correlating different categories of antihistamine’s structures and adverse events, using questionnaires to obtain direct information from patients, and prolonging the duration of study to increase the sample size.
40
Ling-Lan, Chen, and 陳怜蘭. "Electropharmacological effects of antihistamines in Guinea pig ventricular myocytes." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/44740815840350512346.
Full textAbstract:
碩士國防醫學院
藥理學研究所
86
First Abstract : ATP-sensitive potassium channels (KATP) can be activated during hypoxia and contribute to shortening of the action potentials. Histamine is one of the modulators during ischaemia/reperfusion arrhythmias. The aim of the present study was, therefore, to examine the possible actions of histamine and antihistamines on KATP channels.Isolated papillary muscles were dissected from right ventricle of guinea pigs and superfused with normal Tyrode solution at 37 ℃. Action potentials were recorded using conventional glass microelectrode technique. Stimulation frequency was 1 Hz.Cromakalim 0.1-100 uM), a KATP opener, shortened the action potentials in a dose-dependent manner. This action was reversed by 10 uM glibenclamide. First generation H1-antihistamines (diphenhydramine, chlorpheniramine ; 100 uM) significantly antagonized the shortening actions of cromakalim, but not by second generation H1-antihistamines (terfenadine, astemizole ; 100 uM) and H2-antihistamine (cimetidine ; 100 uM). Histamine (10 uM), but not forskolin (10 uM) or IBMX (100 uM), also antagonized the actions of cromakalim. In conclusion, both H1-antihistamines and histamine can antagonize the actions of potassium channel opener cromakalim. Direct blocking actions on KATP channels are plausible mechanism and PKA modulation is not involved.Key words : ATP-sensitive potassium channels, protein kinase A, crom akalim, histamine, antihistamines. Second Abstract : Terfenadine (TFN) and a stemizole (AST) are widely prescribed nonsedating H1-antihistamines that have been associated with QT-interval prolongation and ventricular arrhythmias (e.g., torsade de pointes). Since potassium channels are intrinsically involved in repolarization, many studies have evaluated the inhibitory effect of the nonsedating H1-antihistamines on potassium channels. In contrast, the first generation H1-antihistamines only have weekly inhibition on potassium channels. The aim of the present study was, therefore, to examine the possible actions of antihistamines on L-type calcium channels (ICa(L)).The whole-cell patch-clamp technique was use to study ICa(L) in emzymatically isolated guinea pig ventricular myocytes. The ICa(L) was elicited by a single 300-ms voltage pulses to +10mV from a holding potential of -40 mV once every 10 s.First generation H1-antihistamines (diphenhydramine : DPH, chlorpheniramine : CPN ; 100 uM) and second generation H1-antihistamines (TFN : 10 uM ; AST : 50 uM) significantly inhibited the ICa(L) in a dose-dependent manner. Cimetidine (CTM, 100 uM) did not affect the basal ICa(L). First generation H1-antihistamines (DPH, CPN ; 100 uM) and second generation H1-antihistamines (TFN : 10 uM；AST : 50 uM) inhibited the ICa(L) in a use-dependent manner. First generation H1-antihistamines (DPH,CPN ; 100 uM) inhibited the ICa(L) in a resting-block manner, but not by second generation H1-antihistamines (TFN : 10 uM；AST : 50 uM).In conclusion, the 1st and 2nd generations of H1-antihistamines show a differential blocking acti ons on cardiac ICa(L).Key words : L-type calcium channels; use-dependent block; resting-block; antihistamine.
41
Tang, Yi-fen, and 湯怡芬. "Quantitative Chiral Analysis of Ethanolamine-Based Antihistamines by Capillary Zone Electrophoresis." Thesis, 2000. http://ndltd.ncl.edu.tw/handle/58080424740501020861.
Full textAbstract:
碩士高雄醫學大學
藥學研究所
88
A simple capillary zone electrophoresis method is described for the simultaneous separation and quantitation of chiral carbinoxamine maleate, doxylamine succinate and orphenadrine citrate using achiral diphenhydramine·HCl as an internal standard. The chiral analysis of these drugs was performed in a Tris buffer with sulfated -CD as a chiral selector. Several parameters affecting the separation were studied, including the pH of the buffer and the concentrations of buffer and chiral selector. Quantitation of the individual enantiomer from related racemate is attainable at 25 ~ 125 M for carbinoxamine maleate, doxylamine succinate or orphenadrine citrate, and the detection limits are about 4 M for carbinoxamine and orphenadrine salts, and 8M for doxylamine succinate. The migration order of the separated enantiomers is compared to that of structurally related dexchlorpheniramine and dexbrompheniramine.
42
Liu, Shao-Cheng, and 劉紹正. "Effects of glucocorticoids and H1-antihistamines on tracheal and nasal mucosa." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/ckfxwg.
Full textAbstract:
博士臺北醫學大學
臨床醫學研究所
105
Objective: Both glucocorticoids and H1-antihistamines are widely used on patients with chronic airway diseases. H1-antihistamines are well known for their short-term effect, by rapidly inhibiting allergic symptoms. Glucocorticoids work primarily through their anti-inflammatory properties. However, their genomic and non-genomic effects against airway remodeling have not been fully explored. On the other hand, exposure to cold air is a major environmental factor exacerbating chronic inflammatory airway diseases, but the distribution and physiological role of the cold receptor in the nose is not clear. Therefore, the aim of this study is to explore the genomic and non-genomic effects of glucocorticoids and H1-antihistamines and its implications for airway remodeling. Meanwhile, we hypothesize the cold receptor, transient receptor potential channel melastatin 8 (TRPM8), exists in nasal airway epithelial cells. When TRPM8 is activated, the tone of the airway and the secretion productions corresponding to stimulants will be changed. Methods: Using isometric contraction ex-vivo studies, we tested the genomic effects of glucocorticoids (Kidsolone) and H1-antihistamines (Xyzal) on isolated rat trachea. Changes in contractility in response to the application of parasympathetic mimetic agents were measured. We also tested the effectiveness of the TRPM8 agonist, menthol, on nasal mucosa. The human nasal epithelial cells (HNEpC) primary cultures were established and immunohistology was used to examine the expression of TRPM8, as well as in the nasal mucosa strips. Then, HNEpC were cultivated with/without glucocorticoids (budesonide) and H1-antihistamines (azelastine). The histamine1-receptor (H1R), muscarinic1-receptor (M1R) and M3R were measured using immunocytochemistry and western blotting after 7-days treatment. We used histamine and methacholine to stimulate the mucus secretion from HNEpC and observed the MUC5AC expression in culture supernatants. Meanwhile, we also explored the physiological role of TRPM8 for mucus production in the nose, with/without its agonist and antagonist. Results: Sole use of Kidsolone or Xyzal elicited no significant effect or only a minor relaxation response on tracheal tension following methacholine treatment. However, a significant synergetic spasmolytic effect was observed following co-administration of Kidsolone and Xyzal. As for the genomic effects of those two drugs, concentration-dependent treatment induced-inhibition of the HNEpC growth rate was observed. Cells incubated with azelastine proliferated significantly slower than that with budesonide and the combined use of those drugs significantly inhibited HNEpC proliferations. Western-blotting revealed budesonide could significantly up-regulate the H1R, M1R and M3R level while azelastine had the opposite effects. Histamine and methacholine stimulated MUC5AC secretion was greater in cells treated with budesonide but less in those treated with azelastine, as compared to controls. On the other hand, for the first time we demonstrated TRPM8 was expressed by the nasal mucosa epithelium and glandular tissue. Both menthol and cold at 24oC induced a statistically significant increased level of mucins production by HNEpC. The TRPM8 antogonist had a statistically significant inhibitory effect in mucins production induced by menthol and cold. Menthol had a negligible effect on the basal tension of the nasal mucosa, but higher doses of menthol had a significant spasmolytic effect on nasal mucosa precontracted with methoxamine. Conclusions: We confirmed both glucocorticoids and H1-antihistamines exert their effects via both genomic and non-genomic mechanisms, which are beneficial in reducing airway remodeling. Glucocorticoids could be synergized with H1-antihistamines to dramatically relax the trachea smooth muscle. H1-antihistamines offer benefit in reducing airway hyper-reactivity symptoms and reducing mucus productions, by regulating the H1R, M1R and M3R levels, and might offset the side effects resulting from glucocorticoids. Therefore, combined use of glucocorticoids and H1-antihistamines in patients with chronic inflammatory airway diseases is recommended. We also for the first time demonstrated the TRPM8 immunoreactivity and its physiologic role in the human nose. The subjective clear feeling after menthol inhalation might be an illusion because menthol has no direct effect on the basal tension of nasal mucosa. Meanwhile, the prolonged exposure to cold will lead to the activation of TRPM8, mucin hypersecretion, and increase in airway resistance, which is thought to increase the risk of acute exacerbation of nasal allergy and asthma. Therefore, TRPM8 antagonists deserve consideration for treatment of chronic inflammatory airway diseases.
43
Aneesa, Shaik. "Evaluation of antihistamines for in vitro antimalarial activity against Plasmodium falciparum." Thesis, 2010. http://hdl.handle.net/11394/3489.
Full textAbstract:
Magister Pharmaceuticae - MPharmThe declining efficacy of antimalarial drugs against resistant Plasmodium falciparum strains in several endemic regions has amplified the world’s burden of neglected diseases. This has highlighted the need for alternate strategies for chemotherapy and chemoprophylaxis. Since malaria is prevalent primarily in third world countries, it is critical for novel therapies to be affordable. Previous research has found that some antihistamines possess inherent antimalarial activity and cause a marked reversal of chloroquine resistance in vitro and in vivo. Promising results have been demonstrated when chlorpheniramine was combined with chloroquine to reverse chloroquine resistance in two African studies (Sowunmi et al, 1997; Abok., 1997).Recently, astemizole and its principle human metabolite desmethylastemizole were identified as potent inhibitors of Plasmodium falciparum at sub-micromolar concentrations in both chloroquine sensitive and chloroquine resistant parasites, showing efficacy in vitro and in two mouse models. The promising results observed with these studies warrant a more comprehensive understanding of how antihistamines interact with the malaria parasite. Additionally, analysing the different structural and mechanistic characteristics of antihistamines may lead to the design and development of effective and affordable antimalarial agents or chloroquine resistance modulators.This thesis describes the antimalarial activity of mainly off-patent (generic) antihistamines by comparing the efficacy of a total of 24 antihistamines, representing histamine1, histamine2, and histamine3 receptor antagonists, against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Cyproheptadine, ketotifen, loratadine, desloratadine, 3-(1HImidazol-4-yl) propyldi (p-fluorophenyl) methyl ether hydrochloride and ciproxifan display IC50 values less than 4μg/ml. There was no significant difference in the sensitivity to antihistamines among the chloroquine sensitive and resistant parasites tested. A tricyclic nucleus appears to be an important structural scaffold for antihistamines which exhibit low IC50 values. Synergistic studies indicate that enhancement of the antimalarial effect of chloroquine on P.falciparum was observed with the ethanolamines against the chloroquine sensitive parasites.Cyproheptadine, ketotifen and desloratadine exerted a marked synergistic action with chloroquine against chloroquine sensitive and resistant parasites. Chlorpheniramine exhibited synergism with chloroquine against resistant parasites only.Microscopic studies illustrate the effect of antihistamines on parasite morphology when compared to control. Using immunofluorescence microscopy, it was seen that ketotifen decreases haemoglobin localization while cyproheptadine increases haemoglobin localization in the parasite’s food vacuole. Western blots have confirmed these results, in addition to indicating that chlorpheniramine decreases the haemoglobin content in the parasite. The results confirm that certain antihistamines do indeed cause a reduction in the growth of malaria parasites. Furthermore, the histamine1 and histamine3 receptor antagonists are most active while histamine2 receptor antagonists have no antimalarial activity. Microscopic studies suggest that antihistamines do not exert their antimalarial effect via a single mechanism of action.I wish to express my sincere appreciation to the following people and institutions whose supervision and assistance made the presentation of this thesis possible:My supervisor, Prof. Henry Leng. Thank for always believing in me. Your encouragement, kindness and calm temperament has given me the strength to complete this thesis even when times were tough. Your wisdom and understanding will always be remembered.My co-supervisor, Prof. Pete Smith. I sincerely thank you for allowing me the opportunity to work in your laboratory and for welcoming me into the department. Your kindness and welcoming attitude will forever be appreciated. Thank you for always being patient and understanding.Dr. Uschi Wiehart. Thank you for all the help in the laboratory and always being there for me. I truly value and appreciate your contribution to this thesis. Your friendship has added so much positive energy to my life. Thank you for your wisdom, inspirational advice and unfaltering encouragement Sumaya and Ntokosi, your help, advice and company in tissue culture, are truly appreciated.The UCT, Pharmacology students. Thank for all your assistance.My dearest Pharmaceutical Chemistry colleagues, Jaques Joubert, for your friendship and support and for always listening and Prof. Peter Eagles, your kindness, support and wise advice has given me strength when I needed it most. To my other School of Pharmacy colleagues. Prof. Sarel Malan and team, for your support and motivation.To my family for all your support and wisdom and to my baby brothers; Omar and Uzair for all the joy that you bring to my life.And finally to my dearest husband, Zaheer for all your love and support throughout my studies and for taking me to UCT to culture parasites every weekend
44
Wu, Shao-Ying, and 吳紹瑩. "The Association between Antihistamines and Acute Urinary Retention Among Elderly Patients." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/08055903502944655060.
Full textAbstract:
碩士國立成功大學
臨床藥學研究所
97
Background Acute urinary retention (AUR) is a common clinical emergent condition. The incidence of AUR increases with ages. Drugs with potent anticholinergic properties are not inappropriate for elderly patients according to Beers’ criteria. These drugs include first-generation antihistamines, tricyclic antidepressant agents, antispasmodics, and muscle relaxants. However, these medicines are still widely used among elderly patients. Therefore, the aim of this study is to evaluate the association between antihistamines and AUR in elderly patients. Method The data source is from non-sampled National Health Insurance in 2003~2004. The case group was defined as elderly patients with the first AUR event between 1 Jan 2004 and 31 Dec 2004. The control group is defined as elderly patients without AUR during 2004. Control subjects were matched to cases for age (±3years), gender, area, hospital level, the date of case included, and benign prostatic hyperplasia. After matching, we analyzed the risk of AUR in elderly patients who took antihistamines. The use of antihistamines is defined as current use (antihistamines within 7 days), past use (within 8~30 days) and no use (did not use antihistamines within 30 days). Result We identified 5,164 case patients and 36,894 control patients after matching. More patients have covariant factors of cardiac disease (27.35%), diabetes mellitus (18.55%), and NSAID (17.88%). Current antihistamine use was associated with an increased risk of AUR (adjusted OR, 2.220 [95% CI, 1.981~2.488]). Both first-generation (adjusted OR, 2.746 [95% CI, 2.408~3.132]) and second-generation (adjusted OR, 1.385 [95% CI, 1.108~1.731]) antihistamine use increased the risk of AUR significantly. Compare to first-generation antihistamines, second-generation antihistamines had lower risk of AUR (adjusted OR, 0.384 [95% CI, 0.197~0.748]). Conclusion Both first-generation and second-generation antihistamine therapy in the elderly patients within 7 days were associated with an increased risk of AUR. In addition, second-generation antihistamines had lower risk of AUR compared with first-generation antihistamines.
45
Charan, V. S. "New physico-chemical methods for the assay of some antihistamines and antiallergics." Thesis, 2003. http://hdl.handle.net/2009/3151.
Full text
46
Huang, Wen-Ping, and 黃玟萍. "Studies of Migration Behavior and Enantioseparation of Antihistamines in Capillary Zone Electrophoresis." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/44948680975911277080.
Full textAbstract:
碩士國立臺灣大學
化學研究所
92
Capillary zone electrophoresis has proven to be a powerful technique for enantioseparation. In this study, five chiral antihistamines were investigated using cyclodextrins as chiral selectors. The results of this thesis are presented in two parts: In the first part, we focus on the binding constants of antihistamines with addition of neutral cyclodextrins (HP-β-CD, β-CD, DM-β-CD). In this work, the interaction of chiral analytes with chiral selectors was studied through the variation of mobility as a function of neutral cyclodextrins concentration. Binding constants of antihistamines to HP-β-CD, β-CD and DM-β-CD were evaluated through curve-fitting. The results indicate that the interaction of antihistamines with neutral cyclodextrins, which are also affected by antihistamines structures, play a major role in the determination of enantioseparation. In the second part , we focus on the enantioseparation of antihistamines with addition of randomly sulfate-substituted β-CD (MI-S-β-CD) and single-isomer heptakis (2,3-dihydroxy-6-O-sulfo )-β-cyclodextrin (SI-S-β-CD) and the optimization of separation. Moreover, by mixing MI-S-β-CD with SI-S-β-CD, the enantioseparation efficiency is considerably enhanced. In comparison with the use of SI-S-β-CD alone, the enantiomers of three antihistamines could be baseline separated when mixed cyclodextrins were used.
47
Mandíková, Jana. "Transportní studie antihistaminik a vliv verapamilu na in vitro model hematoencefalické bariéry." Master's thesis, 2008. http://www.nusl.cz/ntk/nusl-292474.
Full textAbstract:
Studies of drug permeation across the blood-brain barrier (BBB) are an indispensable part of the drug development strategy. Recent in vitro studies have suggested that P-gP and passive membrane permeability may influence the brain concentrations of non-sedating (second generation) H1-antagonists. The purpose of this thesis was to determine the importance of P-gP mediated efflux of the first and the second generation of H1-antagonists in an in vitro BBB model and the influence of P-gP inhibitor verapamil. CNS adverse effects of the first generation of H1-antagonists are linked with their ability to penetrate the BBB and cause sedation and drowsiness. The second and the third generation of H1-antagonists are relatively free of sedation and their limited brain penetration has been suggested to arise from P-gP mediated effux (Obradovic, Dobson et al. 2006). In our in vitro PBMEC/C1-2 model, three H1-antagonists (promethazine, fexofenadine and cetirizine) and a known P-gP substrate rhodamine 123 were tested for their permeation properties. Firstly, P-gP experiments in PBMEC/C1-2 was proven by western blotting. The functional activity of P-gP was assessed by the permeation experiments with an established Transwell in vitro model. The resulting drug quantificantion were evaluated by RP-HPLC and fluorescence...
48
Badri, Roopram. "An investigation into the effects and possible mechanisms of action of cimetidine and ranitidine on the sexual behaviour of male rats." Thesis, 1985. http://hdl.handle.net/10413/9574.
Full textAbstract:
The development of a new class of antihistamines, the
H2-receptor antagonists, introduced a new era in the
treatment of peptic ulcer diseases. Cimetidine, the first
clinically effective H2-blocker, was introduced in 1976.
Recently ranitidine, a second member approved for clinical
use, has been found to be as effective as cimetidine in
the management of peptic ulcer diseases. Soon after the
introduction of cimetidine several reports of loss of
libido, impotence and gynaecomastia were described in male
patients who were on normal or high therapeutic doses of
cimetidine. A few unsubstantiated reports of loss of
libido and gynaecomastia attributed to ranitidine therapy
have also appeared in literature.
This study was undertaken to examine in detail the effects
of acute and subchronic treatment with cimetidine and
ranitidine on mating behaviour in sexually active male
rats. Motor activity counts were recorded immediately
before sexual behaviour observations. The animals were
tested on every third day and observations were terminated
after the first intromission of the next series of
copulations. In the single dose study, mating behaviour
tests were commenced 2 hours after treatment; mating tests
during the subchronic dose studies were done 4 to 7 hours
after the 6hOO dose. The following measures were used in
the analysis of data: mount latency, intromission latency,
mount frequency, intromission frequency, ejaculation
latency, and the postejaculatory intromission latency. At
the termination of the subchronic dose studies blood
samples were collected by cardiac puncture and the animals
were subsequently autopsied. Cauda epididymal sperm counts
and motility were determined, testes and accessory sex
organs were weighed, and one testis was processed for
histological examination.
Cimetidine in the low dose, 128.6 mg/kg, significantly
shortened the ejaculatory latency and to a lesser extent
the postejaculatory intromission latency. At the higher
dose, 257.1 mg/kg, cimetidine markedly prolonged the
postejaculatory intromission latency and to a lesser
extent increased the ejaculation latency. The inhibitory
effect of cimetidine on copulatory behaviour at the higher
dose level was accompanied by significant depression in
motor activity.
At the conclusion of the subchronic dose studies marked
reductions in serum testosterone levels and decreased
testes and accessory organ weights were observed in the
cimetidine group. No significant changes in sperm counts
were observed, although the sperm counts in the cimetidine
group were lower than the control values. Histological
examination of testes showed apparently normal
spermatogenesis in all three treatment groups.
However, in spite of the reduced testosterone levels and
decreased testes and accessory sex organ weights in the
cimetidine group, no impairment in mating behaviour was
observed.
In both the acute and the subchronic dose studies, similar
to placebo, treatment with ranitidine showed no effect on
mating behaviour.
On final analysis of the results it is concluded that
cimetidine, and not ranitidine, disrupts sexual behaviour
in male rats. Furthermore, it is concluded that the effect
of cimetidine on sexual behaviour is not related to
H2-receptor blockade as equipotent doses of ranitidine did
not produce similar effects. The mechanism of
cimetidine-induced impairment of sexual performance in the
male rat may possibly be attributed to some non-specific,
direct or indirect action of cimetidine on some
neurotransmitter system responsible for the control of
sexual behaviour. It is further suggested that the effect
may possibly be mediated by a blockade of central dopamine
receptors. However, it must be stressed that further
experimentation is necessary to elucidate the mechanism of
action of cimetidine on sexual behaviour.Thesis (M.Sc.)-University of Durban-Westville, 1985.
49
Elzainy, Abeer. "Topical liposome formulations of hydroxyzine and cetirizine : evaluation of the physicochemical characteristics and stability, and the peripheral H1-antihistaminic activity and systemic absorption in a rabbit model." 2005. http://hdl.handle.net/1993/20136.
Full text
50
Palhau, Diana Raquel Abrantes. "Manifestações orais das doenças infantis no paciente pediátrico." Master's thesis, 2017. http://hdl.handle.net/10284/6491.
Full textAbstract:
Objetivo: Evidenciar as manifestações orais das principais doenças que acometem os
pacientes infantis, assim como, as manifestações orais decorrentes da terapêutica
medicamentosa implementada para o seu tratamento.
Metodologia: A pesquisa bibliográfica realizou-se nas bases de dados eletrónicas: PubMed e
Scielo entre maio e julho de 2017 com as palavras-chave: infância, doenças virais, exantemas,
paciente pediátrico, antibióticos, antivirais, anti-histamínicos e manifestações orais. Foram
estipulados critérios de inclusão e de exclusão para a seleção dos artigos e no total foram
considerados 84 artigos para análise.
Tópico abordado: As doenças da infância apresentam manifestações orais específicas e, por
vezes, o Médico Dentista é o primeiro profissional de saúde a contactar com as crianças nesta
fase da doença. É necessário, sobretudo o Odontopediatra estar familiarizado com os sinais e
sintomas destas condições patológicas, assim como as terapêuticas a implementar para o seu
controlo e tratamento.Objective: To demonstrate the oral manifestations of the main diseases that affect children, as well as the oral manifestations resulting from the drug therapy implemented for their treatment. Methodology: The bibliographic research was carried out in the electronic databases: PubMed and Scielo between May and July 2017 with the following keywords: childhood, viral diseases, exanthems, pediatric patients, antibiotics, antivirals, antihistamines and oral manifestations. Inclusion and exclusion criteria were stipulated for the selection of articles and in total, 84 articles were considered for analysis. Topic: Childhood diseases present specific oral manifestations and sometimes the Dentist is the first health professional to contact children at this stage of the disease. It is necessary, above all, that Pediatric Dentists should be familiar with the signs and symptoms of these pathological conditions, as well as the therapeutics to be implemented for their control and treatment.