Cardiorespiratory assessment of decongestant-antihistamine effects of altitude, +Gz, and fatigue tolerances.

DOT National Transportation Integrated Search

1978-04-01

Decongestants and antihistamines are known to produce effects capable of adversely modifying physiological function and psychomotor task performance. Because of relevance to safe pilot performance, the effects of single doses of two decongestant-anti...

Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from a bird's eye view.

PubMed

Sharma, A; Hamelin, B A

2003-04-01

The so-called "classic" histamine H(1) receptor antagonists are highly lipophilic compounds associated with significant biotransformation and tissue distribution. They are categorized according to their chemical structure into ethanolamines, alkylamines, ethylenediamines, piperazines, phenothiazines and piperidines, all of which have characteristic metabolic fates. The former four categories undergo primarily cytochrome P450-mediated oxidative N-desalkylations and deamination whereas the aromatic rings of the latter two undergo P450-mediated oxidative hydroxylation and/or epoxide formation. The common tertiary amino group is susceptible to oxidative metabolism by flavin containing monooxygenases forming N-oxides, and the alicyclic tertiary amines produce small amounts (up to 7%) of N-glucuronides in humans. Species, sex and racial differences in the metabolism and pharmacokinetics of antihistamines are known. Specific P450-isozymes implicated in the metabolism were identified in a few cases, such as CYP2D6 that contributes to the metabolism of promethazine, diphenhydramine and chlorpheniramine. Low circulating plasma concentrations of antihistamines are in part explained by significant first-pass effect and tissue distribution. Antihistaminic effects last up to 6 hours though some compounds exhibit a longer duration of action due to circulating active metabolites. Importantly, diphenhydramine inhibited CYP2D6 leading to a clinically significant drug-drug interaction with metoprolol. Other classic antihistamines were shown to be potent in vitro inhibitors of CYP2D6 and CYP3A4. The prescription-free access to most classic antihistamines can easily lead to their co-administration with other drugs metabolized by the same enzyme system thereby leading to drug accumulation and adverse effects. In depth knowledge of the metabolic pathways of classic antihistamines and the enzymes involved is crucial to prevent the high incidence of drug interactions in humans, which are predictable based on pre-clinical data but unexpected when such data is unavailable.

Cardiovascular safety of antihistamines

PubMed Central

Olasiński, Jerzy; Grajek, Stefan

2014-01-01

Histamine is a mediator, which increases the permeability of capillaries during the early phase of allergic reaction, causes smooth muscle contraction of bronchi and stimulates mucous glands in the nasal cavity. Antihistamines are the basis of symptomatic treatment in the majority of allergic diseases, especially allergic rhinitis, allergic conjunctivitis, urticaria and anaphylaxis. The cardiotoxic effects of the two withdrawn drugs, terfenadine and astemizole, were manifested by prolonged QT intervals and triggering torsades de pointes (TdP) caused by blockade of the ‘rapid’ IKr potassium channels. These phenomena, however, are not a class effect. This review deals with a new generation of antihistamine drugs in the context of QT interval prolongation risk. PMID:25097491

An overview of the novel H1-antihistamine bilastine in allergic rhinitis and urticaria.

PubMed

Jáuregui, Ignacio; García-Lirio, Eduardo; Soriano, Ana María; Gamboa, Pedro M; Antépara, Ignacio

2012-01-01

Currently available second-generation H1-antihistamines include a wide group of drugs with a better therapeutic index (or risk-benefit ratio) than the classic antihistamines, although their properties and safety profiles may differ. Bilastine is a newly registered H1-antihistamine for the oral treatment of allergic rhinitis and urticaria, with established antihistaminic and antiallergic properties. Clinical studies in allergic rhinitis and chronic urticaria show that once-daily treatment with bilastine 20 mg is effective in managing symptoms and improving patient's quality of life, with at least comparable efficacy to other nonsedative H1-antihistamines. As far as studies in healthy volunteers, clinical assays and clinical experience can establish, bilastine's safety profile is satisfactory, since it lacks anticholinergic effects, does not impair psychomotor performance or actual driving, and appears to be entirely free from cardiovascular effects.

Effect of bilastine upon nasal obstruction.

PubMed

Dávila, I; Sastre, J; Mullol, J; Montoro, J; Jáuregui, I; Ferrer, M; del Cuvillo, A; Bartra, J; Valero, A

2011-01-01

H1 antihistamines constitute one of the main references for the treatment of allergic rhinitis. Classically, these drugs have been considered effective in controlling sneezing, rhinorrhea and itching, though they have not been regarded as particularly effective in application to nasal obstruction. The most recent studies, involving second-generation H1 antihistamines (desloratadine, fexofenadine, levocetirizine, rupatadine), have shown these drugs to offer effects upon nasal obstruction significantly superior to those of placebo. The present review examines the effect of bilastine, a new, potent and highly specific H1 antihistamine without sedative effects or cardiac toxicity, upon nasal obstruction. The analysis of the data from the different clinical trials indicates that in patients with allergic rhinitis, the effect of bilastine upon nasal obstruction is superior to that of placebo and similar to that of other second-generation H1 antihistamines, manifesting within 24 hours after the start of treatment.

Risk of ventricular arrhythmias associated with nonsedating antihistamine drugs

PubMed Central

José de Abajo, Francisco; Rodríguez, Luis Alberto García

1999-01-01

Aims To quantify and compare the incidence of ventricular arrhythmias associated with the use of five nonsedating antihistamines: acrivastine, astemizole, cetirizine, loratadine and terfenadine. The effects of age, sex, dose, duration of treatment, and the interaction with P450 inhibitor drugs were also examined. Methods We carried out a cohort study with a nested case-control analysis using the UK-based General Practice Research Database (GPRD). The study cohort included persons aged less than 80 years old who received their first prescription for any of the five study drugs between January 1, 1992 and September 30, 1996. We estimated relative risks and 95% confidence intervals of idiopathic ventricular arrhythmias with current use of antihistamines as compared with non use. Results The study cohort included 197 425 persons who received 513 012 prescriptions. Over the study period 18 valid cases of idiopathic ventricular arrhythmias were detected. Nine occurred during the current use of any antihistamine, resulting in a crude incidence of 1.9 per 10 000 person-years (95%CI: 1.0–3.6) and a relative risk of 4.2 (95%CI: 1.5–11.8) as compared with non use. Astemizole presented the highest relative risk (RR = 19.0; 95%CI: 4.8–76.0) of all study drugs, while terfenadine (RR = 2.1; 95%CI:0.5–8.5) was in the range of other nonsedating antihistamines. Older age was associated with a greater risk of ventricular arrhythmias (RR = 7.4; 95%CI: 2.6–21.4) and seemed to increase the effect of antihistamines (RR = 6.4; 95%CI: 1.7–24.8). The proportions of high dose terfenadine and the concomitant use with P450 inhibitors among current users of terfenadine were 2.7% and 3.4%, respectively over the study period with no single case of ventricular arrhythmias occurring in the presence of these two risk factors. Conclusions The use of nonsedating antihistamines increases the risk of ventricular arrhythmias by a factor of four in the general population. Yet, the absolute effect is quite low requiring 57 000 prescriptions, or 5300 person-years of use for one case to occur. The risk associated with terfenadine was no different from that with other nonsedating antihistamines. PMID:10215756

The Target Residence Time of Antihistamines Determines Their Antagonism of the G Protein-Coupled Histamine H1 Receptor

PubMed Central

Bosma, Reggie; Witt, Gesa; Vaas, Lea A. I.; Josimovic, Ivana; Gribbon, Philip; Vischer, Henry F.; Gul, Sheraz; Leurs, Rob

2017-01-01

The pharmacodynamics of drug-candidates is often optimized by metrics that describe target binding (Kd or Ki value) or target modulation (IC50). However, these metrics are determined at equilibrium conditions, and consequently information regarding the onset and offset of target engagement and modulation is lost. Drug-target residence time is a measure for the lifetime of the drug-target complex, which has recently been receiving considerable interest, as target residence time is shown to have prognostic value for the in vivo efficacy of several drugs. In this study, we have investigated the relation between the increased residence time of antihistamines at the histamine H1 receptor (H1R) and the duration of effective target-inhibition by these antagonists. Hela cells, endogenously expressing low levels of the H1R, were incubated with a series of antihistamines and dissociation was initiated by washing away the unbound antihistamines. Using a calcium-sensitive fluorescent dye and a label free, dynamic mass redistribution based assay, functional recovery of the H1R responsiveness was measured by stimulating the cells with histamine over time, and the recovery was quantified as the receptor recovery time. Using these assays, we determined that the receptor recovery time for a set of antihistamines differed more than 40-fold and was highly correlated to their H1R residence times, as determined with competitive radioligand binding experiments to the H1R in a cell homogenate. Thus, the receptor recovery time is proposed as a cell-based and physiologically relevant metric for the lead optimization of G protein-coupled receptor antagonists, like the H1R antagonists. Both, label-free or real-time, classical signaling assays allow an efficient and physiologically relevant determination of kinetic properties of drug molecules. PMID:29033838

[Antihistaminic and antiserotonin properties of new complex tropine esters].

PubMed

Mashkovskiĭ, M D; Shvarts, G Ia

1979-01-01

The antihistaminic and antiserotonin properties of 16 new tropine esters, analogues of atropine, tropacin and tropaphen, were studied. All of them were found to lessen the spasmogenic effects of histamine and serotonin. The intensity of the antihistaminic and antiserotonin action of the drugs varied depending upon the structure of the radical at the alpha-carbon atom in the acidic part of the molecule. Both types of the activity are most marked in the desoxymethyl propyl and butyl analogues of atropine. The absence of the oxymethyl group at alpha-carbon in the series of atropine analogues is shown to facilitate the manifestation of the antihistaminic activity.

Can Twitter Be a Source of Information on Allergy? Correlation of Pollen Counts with Tweets Reporting Symptoms of Allergic Rhinoconjunctivitis and Names of Antihistamine Drugs.

PubMed

Gesualdo, Francesco; Stilo, Giovanni; D'Ambrosio, Angelo; Carloni, Emanuela; Pandolfi, Elisabetta; Velardi, Paola; Fiocchi, Alessandro; Tozzi, Alberto E

2015-01-01

Pollen forecasts are in use everywhere to inform therapeutic decisions for patients with allergic rhinoconjunctivitis (ARC). We exploited data derived from Twitter in order to identify tweets reporting a combination of symptoms consistent with a case definition of ARC and those reporting the name of an antihistamine drug. In order to increase the sensitivity of the system, we applied an algorithm aimed at automatically identifying jargon expressions related to medical terms. We compared weekly Twitter trends with National Allergy Bureau weekly pollen counts derived from US stations, and found a high correlation of the sum of the total pollen counts from each stations with tweets reporting ARC symptoms (Pearson's correlation coefficient: 0.95) and with tweets reporting antihistamine drug names (Pearson's correlation coefficient: 0.93). Longitude and latitude of the pollen stations affected the strength of the correlation. Twitter and other social networks may play a role in allergic disease surveillance and in signaling drug consumptions trends.

Advertisements impact the physiological efficacy of a branded drug

PubMed Central

Kamenica, Emir; Naclerio, Robert; Malani, Anup

2013-01-01

We conducted randomized clinical trials to examine the impact of direct-to-consumer advertisements on the efficacy of a branded drug. We compared the objectively measured, physiological effect of Claritin (Merck & Co.), a leading antihistamine medication, across subjects randomized to watch a movie spliced with advertisements for Claritin or advertisements for Zyrtec (McNeil), a competitor antihistamine. Among subjects who test negative for common allergies, exposure to Claritin advertisements rather than Zyrtec advertisements increases the efficacy of Claritin. We conclude that branded drugs can interact with exposure to television advertisements. PMID:23878212

Advertisements impact the physiological efficacy of a branded drug.

PubMed

Kamenica, Emir; Naclerio, Robert; Malani, Anup

2013-08-06

We conducted randomized clinical trials to examine the impact of direct-to-consumer advertisements on the efficacy of a branded drug. We compared the objectively measured, physiological effect of Claritin (Merck & Co.), a leading antihistamine medication, across subjects randomized to watch a movie spliced with advertisements for Claritin or advertisements for Zyrtec (McNeil), a competitor antihistamine. Among subjects who test negative for common allergies, exposure to Claritin advertisements rather than Zyrtec advertisements increases the efficacy of Claritin. We conclude that branded drugs can interact with exposure to television advertisements.

Pyrilamine-induced prolonged QT interval in adolescent with drug overdose.

PubMed

Paudel, Govinda; Syed, Muhammad; Kalantre, Sarika; Sharma, Jayendra

2011-10-01

The widespread availability of antihistamines in many over-the-counter preparations can lead to significant hazard to the public because of their possible link to potential ventricular arrhythmias secondary to prolongation of QT interval. The effect can be further compounded by the use of other commonly used medications such as macrolides, antifungal agents, antipsychotics, and other antihistamine-containing preparations. The effect of antihistamines on QT interval is not a class effect but is unique to certain medications. Pyrilamine, a first-generation antihistaminic agent, is considered safe as there are no reports regarding its cardiac toxicity available in literature. We report a case of an adolescent with prolonged QT interval after an overdose of pyrilamine.

Bilastine and the central nervous system.

PubMed

Montoro, J; Mullol, J; Dávila, I; Ferrer, M; Sastre, J; Bartra, J; Jáuregui, I; del Cuvillo, A; Valero, A

2011-01-01

Antihistamines have been classifed as first or second generation drugs, according to their pharmacokinetic properties, chemical structure and adverse effects. The adverse effects of antihistamines upon the central nervous system (CNS) depend upon their capacity to cross the blood-brain barrier (BBB) and bind to the central H1 receptors (RH1). This in turn depends on the lipophilicity of the drug molecule, its molecular weight (MW), and affinity for P-glycoprotein (P-gp) (CNS xenobiotic substances extractor protein). First generation antihistamines show scant affinity for P-gp, unlike the second generation molecules which are regarded as P-gp substrates. Histamine in the brain is implicated in many functions (waking-sleep cycle, attention, memory and learning, and the regulation of appetite), with numerous and complex interactions with different types of receptors in different brain areas. Bilastine is a new H1 antihistamine that proves to be effective in treating allergic rhinoconjunctivitis (seasonal and perennial) and urticaria. The imaging studies made, as well as the objective psychomotor tests and subjective assessment of drowsiness, indicate the absence of bilastine action upon the CNS. This fact, and the lack of interaction with benzodiazepines and alcohol, define bilastine as a clinically promising drug with a good safety profile as regards adverse effects upon the CNS.

Pharmacology of Antihistamines

PubMed Central

Church, Martin K; Church, Diana S

2013-01-01

H1-antihistamines, the mainstay of treatment for urticaria, were developed from anticholinergic drugs more than 70 years ago. They act as inverse agonists rather than antagonists of histamine H1-receptors which are members of the G-protein family. The older first generation H1-antihistamines penetrate readily into the brain to cause sedation, drowsiness, fatigue and impaired concentration and memory causing detrimental effects on learning and examination performance in children and on impairment of the ability of adults to work and drive. Their use should be discouraged. The newer second-generation H1-antihistamines are safer, cause less sedation and are more efficacious. Three drugs widely used for symptomatic relief in urticaria, desloratadine, levocetirizine and fexofenadine are highlighted in this review. Of these levocetirizine and fexofenadine are the most potent in humans in vivo. However, levocetirizine may cause somnolence in susceptible individuals, whereas fexofenadine has a relatively short duration of action and may be required to be given twice daily for all round daily protection. Although desloratadine is less potent, it has the advantages of rarely causing somnolence and having a long duration of action. PMID:23723474

Effect of bilastine upon the ocular symptoms of allergic rhinoconjunctivitis.

PubMed

Bartra, J; Mullol, J; Montoro, J; Jáuregui, I; del Cuvillos, A; Dávila, I; Ferrer, M; Sastre, J; Valero, A

2011-01-01

Ocular symptoms often accompany allergic rhinitis and can be as or even more bothersome for the patient than the actual nasal symptoms. Ocular manifestations of allergic rhinoconjunctivitis may result from both direct allergen-mediated mast cell stimulation on the surface of the eye and naso-ocular reflexes--histamine being one of the mediators of symptoms onset. An H1 antihistamine would be the first line treatment for allergic conjunctivitis. Since allergic conjunctivitis is always (or almost always) accompanied by nasal symptoms, a second-generation H1 antihistamine administered via oral route is the drug of choice for jointly managing both the nasal and the ocular symptoms--minimizing the impact of the effects inherent to first-generation H, antihistamine, including particularly drowsiness. Bilastine is a new H1 antihistamine with an excellent safety profile, developed for the treatment of allergic rhinoconjunctivitis and urticaria, with potency similar to that of cetirizine and desloratadine, and superior to that of fexofenadine. This new drug has been shown to be effective in controlling the ocular symptoms of allergic rhinoconjunctivitis.

The changing face of antihistamines and cardiac adverse drug reactions: a clinical perspective.

PubMed

Shaikh, W A

2000-07-01

Recent times have witnessed a qualitative shift in the recognition and management of adverse drug effects. Many of them occur in organs that are unconnected to the primary target of pharmacological action. Out of these, cardiac side-effects have drawn particular attention because of their potential to cause death. Starting with the early observations on antibiotics such as macrolides, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever increasing levels of environmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban the use of this drug. Alerted by these developments, studies on a new member, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever incresing levels of envrionmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban use of this drug. Alerted by these developments, studies on a new member of non-sedating antihistamine class viz, fexofenadine, have been reviewed especially because of the structural similarity between terfenadine and fexofenadine. It is now clear that despite the closeness of its chemical structure to terfenadine fexofenadine behaves in a different manner and does not affect the electrophysiology of the heart muscle tissue, as proved by data from extensive clinical trials as well as membrane models in vitro. Interestingly, the solitary false alarm that was sounded on the drug by a group of workers in the Netherlands was later rectified by the same group. Clinically speaking, the cardiovascular safety of fexofenadine has been convincingly demonstrated at various dose levels and various time intervals, alone and together with other drugs of potential toxigenicity. All things put together, it appears reasonable to conclude that fexofenadine is free from cardiovascular ADRs of clinical significance. It could also be concluded that cardiac side-effects of antihistamines is not a class effect.

Antiemetics With Concomitant Sedative Use in Civil Aviation Pilot Fatalities: From 2000 to 2006

DTIC Science & Technology

2007-10-01

Unclassified Unclassified 13 Form DOT F 1700.7 (8-72) Reproduction of completed page authorized iii CONTENTS INTRODUCTION...sedative hypnotics , and ethanol. Antiemetics and drugs with antiemetic properties such as metoclopramide, diphenhydramine (a sedating...antihistamines, ethanol, barbiturates, serotonin modulators, and/or sedative- hypnotics . Antihistamines such as diphenhydramine are commonly used. The

Selecting optimal second-generation antihistamines for allergic rhinitis and urticaria in Asia.

PubMed

Recto, Marysia Tiongco; Gabriel, Ma Teresita; Kulthanan, Kanokvalai; Tantilipikorn, Pongsakorn; Aw, Derrick Chen-Wee; Lee, Tak Hong; Chwen, Ch'ng Chin; Mutusamy, Somasundran; Hao, Nguyen Trong; Quang, Vo Thanh; Canonica, Giorgio Walter

2017-01-01

Allergic diseases are on the rise in many parts of the world, including the Asia-Pacific (APAC) region. Second-generation antihistamines are the first-line treatment option in the management of allergic rhinitis and urticaria. International guidelines describe the management of these conditions; however, clinicians perceive the additional need to tailor treatment according to patient profiles. This study serves as a consensus of experts from several countries in APAC (Hong Kong, Malaysia, the Philippines, Singapore, Thailand, Vietnam), which aims to describe the unmet needs, practical considerations, challenges, and key decision factors when determining optimal second-generation antihistamines for patients with allergic rhinitis and/or urticaria. Specialists from allergology, dermatology, and otorhinolaryngology were surveyed on practical considerations and key decision points when treating patients with allergic rhinitis and/or urticaria. Clinicians felt the need for additional tools for diagnosis of these diseases and a single drug with all preferred features of an antihistamine. Challenges in treatment include lack of clinician and patient awareness and compliance, financial constraints, and treatment for special patient populations such as those with concomitant disease. Selection of optimal second-generation antihistamines depends on many factors, particularly drug safety and efficacy, impact on psychomotor abilities, and sedation. Country-specific considerations include drug availability and cost-effectiveness. Survey results reveal bilastine as a preferred choice due to its high efficacy and safety, suitability for special patient populations, and the lack of sedative effects. Compliance to the international guidelines is present among allergists, dermatologists and otorhinolaryngologists; however, this is lower amongst general practitioners (GPs). To increase awareness, allergy education programs targeted at GPs and patients may be beneficial. Updates to the existing international guidelines are suggested in APAC to reflect appropriate management for different patient profiles and varying symptoms of allergic rhinitis and urticaria.

Ranitidine-Associated Sleep Disturbance: Case Report and Review of H2 Antihistamine-Related Central Nervous System Adverse Effects.

PubMed

Werbel, Tyler; Cohen, Philip R

2018-04-03

Ranitidine is an H2 antihistamine used as an off-label therapy for recalcitrant verruca vulgaris. We describe a man who developed a sleep disturbance after initiating therapy with ranitidine and review similar adverse effects associated with other drugs in this class. The patient was a 40-year-old man with an eight-year history of a wart on his right plantar foot that was recalcitrant to several topical therapies. Adjunctive treatment with ranitidine 150 mg twice daily was initiated. He developed sleep disturbance with bizarre dreams and gastrointestinal symptoms. All symptoms resolved after discontinuation of the medication and recurred when he restarted the drug. PubMed was searched for the following terms: disturbance, dream, ranitidine, verruca, wart, and Zantac. The papers containing these terms and their references were reviewed. Sleep disturbance caused by ranitidine is an uncommon adverse event in patients receiving the drug. However, similar reactions have been observed with other H2 antihistamines such as cimetidine and famotidine. Clinicians should be aware that sleep disturbance secondary to ranitidine is a potential side effect of this medication.

[Management of side effects of targeted therapies in renal cancer: iatrogenic side effects].

PubMed

Massard, Christophe; Patard, Jean-Jacques; Hermine, Olivier; Ravaud, Alain

2011-01-01

Since premedication of patients with an H1 antihistamine is recommended before the start of the intravenous infusion of temsirolimus, temsirolimus is to be used with caution in cases where there is a history of hypersensitivity to this class of antihistamines, or medical contra-indication for treatment with antihistamines. Comorbidities and co-medications must be taken into account in the prescription of targeted therapies. For sunitinib, sorafenib, and pazopanib: potential drug interactions are possible with inducers/inhibitors of CYP3A4, anti-hypertensive drugs, antidiabetic drugs, thyroid hormones, and anticoagulant treatments. The combination of bevacizumab and sunitinib is very toxic (microangiopathic haemolytic anaemia), and is contra-indicated unless part of a clinical trial. Screening, equilibration or treatment of hypothyroidism, anaemia, undernutrition, hypophosphatemia, hypomagnesaemia, sleep disorders, depression or other comorbidities, which may contribute to asthenia is recommended. In patients treated with sunitinib or pazopanib, a thyroid function test is recommended at the treatment centre as well as regular TSH assays. Copyright © 2011 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Can human allergy drug fexofenadine, an antagonist of histamine (H1) receptor, be used to treat dog and cat? Homology modeling, docking and molecular dynamic Simulation of three H1 receptors in complex with fexofenadine.

PubMed

Sader, Safaa; Cai, Jun; Muller, Anna C G; Wu, Chun

2017-08-01

Fexofenadine, a potent antagonist to human histamine 1 (H 1 ) receptor, is a non-sedative third generation antihistamine that is widely used to treat various human allergic conditions such as allergic rhinitis, conjunctivitis and atopic dermatitis. Encouragingly, it's been successfully used to treat canine atopic dermatitis, this supports the notion that it might have a great potential for treating other canine allergic conditions and other mammal pets such as dog. Regrettably, while there is a myriad of studies conducted on the interactions of antihistamines with human H 1 receptor, the similar studies on non-human pet H 1 are considerably scarce. The published studies using the first and second generation antihistamines drugs have shown that the antihistamine response is varied and unpredictable. Thus, to probe its efficacy on pet, the homology models of dog and cat H 1 receptors were built based on the crystal structure of human H 1 receptor bound to antagonist doxepin (PDB 3RZE) and fexofenadine was subsequently docked to human, dog and cat H 1 receptors. The docked complexes are then subjected to 1000ns molecular dynamics (MD) simulations with explicit membrane. Our calculated MM/GBSA binding energies indicated that fexofenadine binds comparably to the three receptors; and our MD data also showed the binding poses, structural and dynamic features among three receptors are very similar. Therefore, our data supported the application of fexofenadine to the H 1 related allergic conditions of dog and cat. Nonetheless, subtle systemic differences among human, dog and cat H 1 receptors were also identified. Clearly, there is still a space to develop a more selective, potent and safe antihistamine alternatives such as Fexofenadine for dog or cat based on these differences. Our computation approach might provide a fast and economic way to predict if human antihistamine drugs can also be safely and efficaciously administered to animals. Copyright © 2017 Elsevier Inc. All rights reserved.

Allergy Medications During Pregnancy.

PubMed

Gonzalez-Estrada, Alexei; Geraci, Stephen A

2016-09-01

Allergic diseases are common in women of childbearing age. Both asthma and atopic conditions may worsen, improve or remain the same during pregnancy. Primary care physicians commonly encounter women receiving multiple medications for pre-existing atopic conditions, who then become pregnant and require medication changes to avoid potential fetal injury or congenital malformations. Each medication should be evaluated; intranasal and inhaled steroids are relatively safe to continue during pregnancy (budesonide is the drug of choice), second-generation antihistamines of choice are cetirizine and loratadine, leukotriene receptor antagonists are safe, sparing use of oral decongestants during the first trimester and omalizumab may be used for both uncontrolled asthma and for antihistamine-resistant urticaria. Medications to avoid during pregnancy include intranasal antihistamines, first-generation antihistamines, mycophenolate mofetil, methotrexate, cyclosporine, azathioprine and zilueton. Common allergic diseases may develop de novo during pregnancy, such as anaphylaxis. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Considerations in pharmaceutical conversion: focus on antihistamines.

PubMed

Garbus, S B; Moulton, B W; Meltzer, E O; Reich, P R; Weinreb, L F; Friedman, J A; Orland, B I

1997-04-01

The practice of pharmaceutical conversion, which encompasses three types of drug interchange (generic, brand, and therapeutic substitution), is increasing in managed care settings. Pharmaceutical conversion has numerous implications for managed care organizations, their healthcare providers, and their customers. Although drug cost may be a driving consideration in pharmaceutical conversion, a number of other considerations are of equal or greater importance in the decision-making process may affect the overall cost of patient care. Among these considerations are clinical, psychosocial, and safety issues; patient adherence; patient satisfaction; and legal implications of pharmaceutical conversion. Patient-centered care must always remain central to decisions about pharmaceutical conversion. This article discusses the issues related to, and implications of, pharmaceutical conversion utilizing the antihistamines class of drugs as the case situation.

Bitterness prediction of H1-antihistamines and prediction of masking effects of artificial sweeteners using an electronic tongue.

PubMed

Ito, Masanori; Ikehama, Kiyoharu; Yoshida, Koichi; Haraguchi, Tamami; Yoshida, Miyako; Wada, Koichi; Uchida, Takahiro

2013-01-30

The study objective was to quantitatively predict a drug's bitterness and estimate bitterness masking efficiency using an electronic tongue (e-Tongue). To verify the predicted bitterness by e-Tongue, actual bitterness scores were determined by human sensory testing. In the first study, bitterness intensities of eight H(1)-antihistamines were assessed by comparing the Euclidean distances between the drug and water. The distances seemed not to represent the drug's bitterness, but to be greatly affected by acidic taste. Two sensors were ultimately selected as best suited to bitterness evaluation, and the data obtained from the two sensors depicted the actual taste map of the eight drugs. A bitterness prediction model was established with actual bitterness scores from human sensory testing. Concerning basic bitter substances, such as H(1)-antihistamines, the predictability of bitterness intensity using e-Tongue was considered to be sufficiently promising. In another study, the bitterness masking efficiency when adding an artificial sweetener was estimated using e-Tongue. Epinastine hydrochloride aqueous solutions containing different levels of acesulfame potassium and aspartame were well discriminated by e-Tongue. The bitterness masking efficiency of epinastine hydrochloride with acesulfame potassium was successfully predicted using e-Tongue by several prediction models employed in the study. Copyright © 2012 Elsevier B.V. All rights reserved.

21 CFR 522.2063 - Pyrilamine maleate injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522... treating horses in conditions in which antihistaminic therapy may be expected to lead to alleviation of...

Lack of efficacy of a decongestant-antihistamine combination for otitis media with effusion ("secretory" otitis media) in children. Results of a double-blind, randomized trial.

PubMed

Cantekin, E I; Mandel, E M; Bluestone, C D; Rockette, H E; Paradise, J L; Stool, S E; Fria, T J; Rogers, K D

1983-02-10

In a double-blind, randomized trial of 553 infants and children who had otitis media with effusion ("secretory" otitis media), we compared the efficacy of a four-week course of an oral decongestant-antihistamine combination (pseudoephedrine hydrochloride, 4 mg per kilogram of body weight per day, and chlorpheniramine maleate, 0.35 mg per kilogram per day) with that of placebo. Among patients with initially unilateral disease, resolution of middle-ear effusion occurred at four weeks in 38 per cent of those treated with placebo and 34 per cent of those treated with drug (P = 0.74). Among patients with initially bilateral disease the corresponding proportions were 19 and 21 per cent, respectively (P = 0.67). Side effects were reported more often among drug-treated than placebo-treated patients. Decongestant-antihistamine combinations do not appear to be indicated for the treatment of otitis media with effusion in infants and children.

Evidence-based guidelines for anti-allergic drug withdrawal times before allergen-specific intradermal and IgE serological tests in dogs.

PubMed

Olivry, Thierry; Saridomichelakis, Manolis

2013-04-01

Anti-allergic drugs (e.g. antihistamines, glucocorticoids and ciclosporin) are often administered to dogs with atopic dermatitis to relieve pruritus and skin lesions. Allergen-specific intradermal tests (IDT) and allergen-specific IgE serological (ASIS) tests are used to characterize the allergens to which dogs are hypersensitive. Anti-allergic drugs have the potential to influence the results or interpretation of these tests. To provide evidence-based recommendations for anti-allergic drug withdrawal times before IDT and ASIS tests. Three citation databases and abstracts from international meetings were searched for relevant studies. Studies were grouped based on similar interventions and types of tests. Withdrawal times for each type of drug and test were then extrapolated from the study results. Before the assessment of immediate reactions to IDT, proposed optimal withdrawal times for antihistamines, oral glucocorticoids, topical/otic glucocorticoids and ciclosporin are 7, 14, 14 and 0 days, respectively. Studies have provided no evidence for drug withdrawal prior to ASIS tests for oral ciclosporin or prednisone/prednisolone. Owing to a lack of studies, recommendations for withdrawal times before ASIS tests cannot be made for topical glucocorticoids and antihistamines. These proposed withdrawal times are based on the existing evidence at the end of 2011. Care must be taken before extrapolating the suggested withdrawal times to other species, higher dosages, different formulations and/or durations of administration of tested drugs, as well as to other medications from the same category. © 2013 The Authors. Veterinary Dermatology © 2013 ESVD and ACVD.

Antihistamine medication may alleviate negative effects of prenatal exposure to polycyclic aromatic hydrocarbons (PAH) on lung function in children. Birth cohort prospective study.

PubMed

Jedrychowski, Wieslaw A; Perera, Frederica P; Maugeri, Umberto; Majewska, Renata; Spengler, Jack; Mroz, Elzbieta; Flak, Elzbieta; Klimaszewska-Rembiasz, Maria; Camman, David

2015-05-01

The main purpose of the present study was to test the hypothesis that the depressed lung growth attributable to prenatal exposure to polycyclic aromatic hydrocarbons (PAH) may be modified by the intake of antihistamine medications. Individual prenatal PAH exposure was assessed by personal air monitoring in 176 children who were followed over nine years, in the course of which outdoor residential air monitoring, allergic skin tests for indoor allergens, lung function tests (FVC, FEV(1), FEV(05), and FEF(25-75)) were performed. The analysis with the General Estimated Equation (GEE) showed no association between prenatal PAH exposure and lung function in the group of children who were reported to be antihistamine users. However, in the group of antihistamine non-users all lung function tests except for FEF(25-75) were significantly and inversely associated with prenatal airborne PAH exposure. The results of the study suggest that the intake of antihistamine medications in early childhood may inhibit the negative effect of fetal PAH exposure on lung growth and provides additional indirect evidence for the hypothesis that lung alterations in young children resulting from PAH exposure may be caused by the allergic inflammation within lung. © 2014 Wiley Periodicals, Inc.

The effect on social welfare of a switch of second-generation antihistamines from prescription to over-the-counter status: a microeconomic analysis.

PubMed

Shih, Ya-Chen Tina; Prasad, Manishi; Luce, Bryan R

2002-04-01

The US Food and Drug Administration (FDA) recently held a meeting to determine whether the status of second-generation antihistamines (SGAs) should be switched from prescription (Rx) to over-the-counter (OTC) status. This article provides a conceptual microeconomic framework for addressing issues regarding the impact of such a switch on social welfare. A review of the economic literature on Rx-to-OTC switches was conducted. Relevant articles published in English between 1990 and 2001 were identified through searches of ABI Info, EconLit, PsychInfo, MEDLINE, CANCERLIT, AIDSLINE, and HealthStar, as well as a general Internet search for statements in the press or on the FDA Web site. The search terms used were Rx, prescription, OTC, over-the-counter, second-generation antihistamines, nonsedating antihistamines, first-generation antihistamines, and sedating antihistamines. Microeconomic models focusing on consumer surplus were employed to determine the potential price response and social-welfare implications of a switch of SGAs to OTC status. Unlike the agents involved in previous Rx-to-OTC switches, SGAs are still under patent protection. Economic theory suggests that a firm that is protected by a patent will price aggressively. The market for OTC SGAs is likely to be more elastic due to a lack of insurance coverage for OTC products; hence, drug manufacturers would be likely to charge a lower price if SGAs were sold OTC. However, a lower price does not necessarily guarantee an improvement in social welfare; the net impact is determined by whether the increase in consumer surplus outweighs the deadweight loss (losses of consumer and producer surplus not transferred to other parties). Additionally, the assumption of a price reduction would be called into question if there were inequalities in marginal costs between the Rx and OTC markets. In this situation, the postswitch price might increase or not be reduced significantly. It is uncertain whether granting OTC status to SGAs would be cost saving to society, particularly as these drugs are patent protected. The social-welfare implications of such a switch would depend heavily on pricing strategies and consumer behavior. Further analyses are needed to determine how both factors influence social welfare; only then can the costs and benefits of a switch be understood completely.

Development of modified-release dosage forms containing loratadine and pseudoephedrine sulfate.

PubMed

Sznitowska, Małgorzata; Cal, Krzysztof; Kupiec, Katarzyna

2004-12-01

Pseudoephedrine sulfate (PES) is a short-acting sympathomimetic amine and decongestant. Loratadine (L) is a long-acting antihistamine, H1 blocker. These drugs administered together provide relief from a whole range of rhinitis (hay fever) symptoms. Combination of both drugs is available in the form of sugar-coated modified-release tablets Clarinase (Schering-Plough). In this product, 5 mg of L and 60 mg of PES is present in the sugar-coating layer ready for an immediate release, and the rest of PES (60 mg) is incorporated in the extended-release core of the tablet. This enables fast as well as prolonged release of PES over 6-8 h. Because the sugar coating technologies are troublesome and rarely used nowadays, the aim of this study was to develop alternative oral dosage forms containing L (5 mg) and PES (120 mg). It was assumed that, similarly to the original product, the total dose of L and the half dose of PES should be released during 1 h and the remaining dose of PES ought to be gradually released for up to 8 h.

Evidence for the hERG Liability of Antihistamines, Antipsychotics, and Anti-Infective Agents: A Systematic Literature Review From the ARITMO Project.

PubMed

Hazell, Lorna; Raschi, Emanuel; De Ponti, Fabrizio; Thomas, Simon H L; Salvo, Francesco; Ahlberg Helgee, Ernst; Boyer, Scott; Sturkenboom, Miriam; Shakir, Saad

2017-05-01

A systematic review was performed to categorize the hERG (human ether-a-go-go-related gene) liability of antihistamines, antipsychotics, and anti-infectives and to compare it with current clinical risk of torsade de pointes (TdP). Eligible studies were hERG assays reporting half-minimal inhibitory concentrations (IC50). A "hERG safety margin" was calculated from the IC50 divided by the peak human plasma concentration (free C max ). A margin below 30 defined hERG liability. Each drug was assigned an "uncertainty score" based on volume, consistency, precision, and internal and external validity of evidence. The hERG liability was compared to existing knowledge on TdP risk (www.credibledrugs.org). Of 1828 studies, 82 were eligible, allowing calculation of safety margins for 61 drugs. Thirty-one drugs (51%) had evidence of hERG liability including 6 with no previous mention of TdP risk (eg, desloratadine, lopinavir). Conversely, 16 drugs (26%) had no evidence of hERG liability including 6 with known, or at least conditional or possible, TdP risk (eg, chlorpromazine, sulpiride). The main sources of uncertainty were the validity of the experimental conditions used (antihistamines and antipsychotics) and nonuse of reference compounds (anti-infectives). In summary, hERG liability was categorized for 3 widely used drug classes, incorporating a qualitative assessment of the strength of available evidence. Some concordance with TdP risk was observed, although several drugs had hERG liability without evidence of clinical risk and vice versa. This may be due to gaps in clinical evidence, limitations of hERG/C max data, or other patient/drug-specific factors that contribute to real-life TdP risk. © 2016, The American College of Clinical Pharmacology.

Physiological recording from pilots operating an aircraft simulator.

DOT National Transportation Integrated Search

1964-09-01

The questions to be answered were reduced to the following : (1) to determine whether or not theraputic doses of two common drugs, a tranquilizer and an antihistamine, cause decrements in the operating proficiency of pilots, and (2) do those drugs wh...

Utility of NBD-Cl for the spectrophotometric determination of some skeletal muscle relaxant and antihistaminic drugs

NASA Astrophysics Data System (ADS)

Saleh, Hanaa M.; EL-Henawee, Magda M.; Ragab, Gamal H.; El-Hay, Soad S. Abd

2007-08-01

A simple, accurate, precise and sensitive colorimetric method for the determination of some skeletal muscle relaxant drugs, namely orphenadrine citrate ( I), baclofen ( II), antihistaminic drugs as acrivastine ( III) and fexofenadine hydrochloride ( IV) is described. This method is based on the formation of charge transfer complex with 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) in non-aqueous medium. The orange color products were measured at 472, 465, 475 and 469 nm for drugs I, II, III and IV, respectively. The optimization of various experimental conditions was described. Beer's Law was obeyed in the range (2.5-17.5), (5-70), (2.5-25) and (10-50) μg/ml for drugs I, II, III and IV, respectively. The molar absorptivity ( ɛ), sandell sensitivity, detection (LOD) and quantitation limits (LOQ) are calculated. The procedure was favorably applied for determination of certain pharmaceutical dosage forms containing the studied drugs. The obtained results were compared with the official and reported methods. There were no significant differences between proposed, reported and the official methods.

Misuse and dependence on non-prescription codeine analgesics or sedative H1 antihistamines by adults: a cross-sectional investigation in France.

PubMed

Roussin, Anne; Bouyssi, Annabelle; Pouché, Lucie; Pourcel, Laure; Lapeyre-Mestre, Maryse

2013-01-01

Given the growing worldwide market of non-prescription drugs, monitoring their misuse in the context of self-medication represents a particular challenge in Public Health. The aim of this study was to investigate the prevalence of misuse, abuse, and dependence on non-prescription psychoactive drugs. During one month, in randomly solicited community pharmacies, an anonymous questionnaire was offered to adults requesting paracetamol (control group), codeine combined with paracetamol in analgesics, or sedative H1 antihistamines. Responses about misuse (drug use not in agreement with the Patient Information Leaflet) abuse (excessive drug use having detrimental consequences), and dependence (established according to questions adapted from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria) on psychoactive drugs were compared to those of the paracetamol control group. 295 patients (mean age 48.5 years, 68.5% of women) having used one of the studied drugs during the previous month were included. Misuse and dependence to codeine analgesics concerned 6.8% and 17.8% of the patients exposed to these drugs, respectively, (n = 118), which was significantly higher than for paracetamol. 19.5% had used codeine analgesics daily for more than six months. Headache was the most frequent reason for persistent daily use. A high prevalence of persistent daily users of sedative H1 antihistamines was also observed. Whereas these drugs are recommended only for short treatment courses of occasional insomnia, 72.2% of the participants having taken doxylamine (n = 36) were daily users, predominantly for more than six months. Results on misuse and dependence on non-prescription codeine analgesics suggest that chronic pain, in particular chronic cephalalgia, requires better medical care. In addition, as for hypnotics on prescription, persistent use of doxylamine for self-medication is not justified until an acceptable benefit-risk ratio for chronic sleep disturbance is shown by clinical data.

An overview of bilastine metabolism during preclinical investigations.

PubMed

Lucero, María Luisa; Gonzalo, Ana; Mumford, Rory; Betanzos, Mónica; Alejandro, Ana

2012-06-01

Knowledge of the biotransformation of oral H₁ antihistamines is clinically important because it can define their pharmacokinetic profile through possible effects on absorption (i.e., first-pass metabolism) and elimination. Further, clinically significant interactions with inhibitors of cytochrome P450 (CYP) have previously been reported for drugs of this therapeutic group, such as terfenadine and astemizole, indicating the possibility of drug-drug interactions involving agents that share the same metabolic pathway. The aim of this article was to review the preclinical testing of a new antihistamine (i.e., bilastine) in terms of its biotransformation in various animal species, including humans, and to evaluate its potential for possible drug-drug interactions involving the CYP system. A wide array of preclinical experiments were reviewed, all of which demonstrated that bilastine undergoes minimal metabolism in all species tested to date, including humans. Further, bilastine did not interact significantly, either as an inhibitor or inducer, with the CYP enzyme system, suggesting a low propensity for involvement in drug-drug interactions. These characteristics demonstrate the potential for bilastine to be a good choice for allergic patients receiving treatment for other concomitant diseases, including those with renal or hepatic dysfunction.

29 CFR Appendix A to Subpart T to... - Examples of Conditions Which May Restrict or Limit Exposure to Hyperbaric Conditions

Code of Federal Regulations, 2012 CFR

2012-07-01

... duration of isolation. History of seizure disorder other than early febrile convulsions. Malignancies... or drug use. Conditions requiring continuous medication for control (e.g., antihistamines, steroids, barbiturates, moodaltering drugs, or insulin). Meniere's disease. Hemoglobinopathies. Obstructive or...

29 CFR Appendix A to Subpart T of... - Examples of Conditions Which May Restrict or Limit Exposure to Hyperbaric Conditions

Code of Federal Regulations, 2013 CFR

2013-07-01

... duration of isolation. History of seizure disorder other than early febrile convulsions. Malignancies... or drug use. Conditions requiring continuous medication for control (e.g., antihistamines, steroids, barbiturates, moodaltering drugs, or insulin). Meniere's disease. Hemoglobinopathies. Obstructive or...

29 CFR Appendix A to Subpart T to... - Examples of Conditions Which May Restrict or Limit Exposure to Hyperbaric Conditions

Code of Federal Regulations, 2011 CFR

2011-07-01

... duration of isolation. History of seizure disorder other than early febrile convulsions. Malignancies... or drug use. Conditions requiring continuous medication for control (e.g., antihistamines, steroids, barbiturates, moodaltering drugs, or insulin). Meniere's disease. Hemoglobinopathies. Obstructive or...

29 CFR Appendix A to Subpart T of... - Examples of Conditions Which May Restrict or Limit Exposure to Hyperbaric Conditions

Code of Federal Regulations, 2014 CFR

2014-07-01

... duration of isolation. History of seizure disorder other than early febrile convulsions. Malignancies... or drug use. Conditions requiring continuous medication for control (e.g., antihistamines, steroids, barbiturates, moodaltering drugs, or insulin). Meniere's disease. Hemoglobinopathies. Obstructive or...

29 CFR Appendix A to Subpart T to... - Examples of Conditions Which May Restrict or Limit Exposure to Hyperbaric Conditions

Code of Federal Regulations, 2010 CFR

2010-07-01

... duration of isolation. History of seizure disorder other than early febrile convulsions. Malignancies... or drug use. Conditions requiring continuous medication for control (e.g., antihistamines, steroids, barbiturates, moodaltering drugs, or insulin). Meniere's disease. Hemoglobinopathies. Obstructive or...

A dose-ranging study of the effects of mequitazine on actual driving, memory and psychomotor performance as compared to dexchlorpheniramine, cetirizine and placebo.

PubMed

Theunissen, E L; Vermeeren, A; van Oers, A C M; van Maris, I; Ramaekers, J G

2004-02-01

Mequitazine is a so-called 'non-sedative' second-generation antihistamine even though it has never been firmly established that this drug's sedative potential actually differs from that of the 'sedative' first-generation antihistamines. The present study compares the sedative effects of three doses of mequitazine on actual driving, psychomotor performance and memory with those of a first- and a second-generation antihistamine. Eighteen healthy volunteers received on separate days a single dose of 5, 10 and 15 mg mequitazine, 10 mg cetirizine, 6 mg dexchlorpheniramine and placebo. Drug effects were assessed using two actual driving tests (highway-driving test and car-following test), cognitive and psychometric tests (tracking, divided attention, memory, reasoning and critical flicker fusion), pupil size and questionnaires. Highway-driving data revealed an overall effect of Treatment on the standard deviation of lateral position (SDLP). Dexchlorpheniramine impaired driving performance as indicated by a significant rise in SDLP. Mequitazine significantly increased SDLP in a dose-related manner, but the separate dose effects failed to reach statistical significance. Divided attention performance was also affected by Treatment. Reaction time (RT) during mequitazine treatments increased in a dose-related manner and significantly differed from placebo at the highest dose. Subjects reported to be less alert after treatment with dexchlorpheniramine. Cetirizine did not affect performance in any of the tasks. It was concluded that mequitazine is mildly sedating. The effects of mequitazine are comparable to those of other second-generation antihistamines, in that it causes mild driving impairment, particularly at higher doses.

Treatment of allergic rhinitis and urticaria: a review of the newest antihistamine drug bilastine.

PubMed

Wang, Xue Yan; Lim-Jurado, Margaret; Prepageran, Narayanan; Tantilipikorn, Pongsakorn; Wang, De Yun

2016-01-01

Allergic rhinitis and urticaria are common allergic diseases that may have a major negative impact on patients' quality of life. Bilastine, a novel new-generation antihistamine that is highly selective for the H1 histamine receptor, has a rapid onset and prolonged duration of action. This agent does not interact with the cytochrome P450 system and does not undergo significant metabolism in humans, suggesting that it has very low potential for drug-drug interactions, and does not require dose adjustment in renal impairment. As bilastine is not metabolized and is excreted largely unchanged, hepatic impairment is not expected to increase systemic exposure above the drug's safety margin. Bilastine has demonstrated similar efficacy to cetirizine and desloratadine in patients with seasonal allergic rhinitis and, in a Vienna Chamber study, a potentially longer duration of action than fexofenadine in patients with asymptomatic seasonal allergic rhinitis. It has also shown significant efficacy (similar to that of cetirizine) and safety in the long-term treatment of perennial allergic rhinitis. Bilastine showed similar efficacy to levocetirizine in patients with chronic spontaneous urticaria and can be safely used at doses of up to fourfold higher than standard dosage (80 mg once daily). The fourfold higher than standard dose is specified as an acceptable second-line treatment option for urticaria in international guidelines. Bilastine is generally well tolerated, both at standard and at supratherapeutic doses, appears to have less sedative potential than other second-generation antihistamines, and has no cardiotoxicity. Based on its pharmacokinetic properties, efficacy, and tolerability profile, bilastine will be valuable in the management of allergic rhinitis and urticaria.

High-dose anti-histamine use and risk factors in children with urticaria.

PubMed

Uysal, Pınar; Avcil, Sibelnur; Erge, Duygu

2016-12-01

The drugs of choice in the treatment of urticaria in children are H1-antihistamines. The aim of the study was to evaluate children with urticaria and define risk factors for requirement of high-dose H1-antihistamines in children with urticaria. The medical data of children who were diagnosed as having urticaria admitted to our outpatient clinic between January 2014 and January 2016 were searched. The medical histories, concomitant atopic diseases, parental atopy histories, medications, treatment responses, blood eosinophil and basophil counts, and serum total IgE levels were recorded. In addition, the urticaria activity score for seven days, autoimmune antibody tests, and skin prick test results were evaluated in children with chronic urticaria. The numbers of the children with acute and chronic urticaria were 138 and 92, respectively. The age of the children with chronic urticaria was higher than that of those with acute urticaria (p<0.0001). There was no difference between the two groups in terms of blood eosinophil and basophil counts, and serum total IgE levels (p>0.05). There was a negative correlation between blood eosinophil count and the UAS7 score in children with chronic urticaria (r=-0.276, p=0.011). Chronic urticaria and requirement of high dose H1-antihistamines were significant in children aged ≥10 years (p<0.001, p=0.015). High UAS7 score (OR: 1.09; CI 95%: [1.03-1.15]) and basopenia (OR: 6.77; CI 95%: [2.01-22.75]) were associated with the requirement of high-dose H1-AH in children with chronic urticaria. The requirement of high-dose H1-antihistamines was higher with children's increasing age. Disease severity and basopenia were risk factors for the requirement of high-dose H1-antihistamines.

Lack of effects of astemizole on vestibular ocular reflex, motion sickness, and cognitive performance in man

NASA Technical Reports Server (NTRS)

Kohl, Randall L.; Homick, Jerry L.; Cintron, Nitza; Calkins, Dick S.

1987-01-01

Astemizole was orally administered to 20 subjects in a randomized, double-blind design to assess the efficacy of this peripherally active antihistamine as an antimotion sickness drug possessing no central side-effects. Measures of vestibular ocular reflex (VOR) were made to evaluate the agent as a selective vestibular depressant. Following one week of orally administered astemizole (30 mg daily), a Staircase Profile Test, a VOR test, and a variety of tests of cognitive performance were administered. These tests revealed no statistically significant effects of astemizole. This leads to the conclusion that, although the drug probably reaches the peripheral vestibular apparatus in man by crossing the blood-vestibular barrier, a selective peripheral antihistamine (H1) action is inadequate to control motion sickness induced through cross-coupled accelerative semicircular canal stimulation in a rotating chair.

Desloratadine and pseudoephedrine combination therapy as a comprehensive treatment for allergic rhinitis and nasal congestion.

PubMed

Anolik, Robert

2009-06-01

Allergic rhinitis (AR) is rapidly increasing in global prevalence. Symptoms of AR, particularly nasal congestion, can cause quality of life (QoL) impairment. Second-generation antihistamines are a recommended first-line therapy for AR but are not viewed as very effective for the treatment of congestion. Therefore, an antihistamine plus a decongestant, such as the combination of desloratadine and pseudoephedrine, is a convenient and efficacious treatment. To review the clinical evidence on the efficacy and safety of combination desloratadine/pseudoephedrine for the treatment of AR symptoms, particularly nasal congestion. Four large studies found that improvement in nasal congestion is enhanced when patients are treated with combination desloratadine/pseudoephedrine. The combination drug significantly improved mean reflective nasal congestion scores in these studies compared with either component as monotherapy (p

Impact of fexofenadine, osthole and histamine on peripheral blood mononuclear cell proliferation and cytokine secretion.

PubMed

Karolina Kordulewska, Natalia; Kostyra, Elżbieta; Matysiewicz, Michał; Cieślińska, Anna; Jarmołowska, Beata

2015-08-15

This paper compares results of peripheral blood mononuclear cell (PBMC) incubation with fexofenadine (FXF) and osthole. FXF is a third-generation antihistamine drug and osthole is assumed a natural antihistamine alternative. To our best knowledge, this is the first comparative study on FXF, osthole and histamine cytokine secretion and cytotoxicity in PBMC in vitro cultures using cell proliferation ELISA BrdU. The cultures were treated 12, 42, 48 and 72h with FXF and osthole at 150, 300 and 450ng/ml concentrations and histamine at 50, 100 and 200ng/ml. Our study results confirm that FXF, osthole and histamine exert no cytotoxic effect on PBMCs and that IL-6, IL-10 and TNF-α cytokine secretion following osthole cell stimulation was similar to that by FXF stimulation.This confirms our hypothesis that osthole is a natural histamine antagonist, and can therefore be beneficially applied in antihistamine treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

In vivo pharmacological characterisation of bilastine, a potent and selective histamine H1 receptor antagonist.

PubMed

Corcóstegui, Reyes; Labeaga, Luis; Innerárity, Ana; Berisa, Agustín; Orjales, Aurelio

2006-01-01

We set out to establish the in vivo histamine H(1) receptor antagonistic (antihistaminic) and antiallergic properties of bilastine. In vivo antihistaminic activity experiments consisted of measurement of: inhibition of increase in capillary permeability and reduction in microvascular extravasation and bronchospasm in rats and guinea pigs induced by histamine and other inflammatory mediators; and protection against lethality induced by histamine and other inflammatory mediators in rats. In vivo antiallergic activity experiments consisted of measurement of passive and active cutaneous anaphylactic reactions as well as type III and type IV allergic reactions in sensitised rodents. In the in vivo antihistaminic activity experiments, bilastine was shown to have a positive effect, similar to that of cetirizine and more potent than that of fexofenadine. The results of the in vivo antiallergic activity experiments showed that the properties of bilastine in this setting are similar to those observed for cetirizine and superior to fexofenadine in the model of passive cutaneous anaphylactic reaction. When active cutaneous anaphylactic reaction experiments were conducted, bilastine showed significant activity, less potent than that observed with cetirizine but superior to that of fexofenadine. Evaluation of the type III allergic reaction showed that of the antihistamines only bilastine was able to inhibit oedema in sensitised mice, although its effect in this respect was much less potent than that observed with dexamethasone. In terms of the type IV allergic reaction, neither bilastine, cetirizine nor fexofenadine significantly modified the effect caused by oxazolone. The results of our in vivo preclinical studies corroborate those obtained from previously conducted in vitro experiments of bilastine, and provide evidence that bilastine possesses antihistaminic as well as antiallergic properties, with similar potency to cetirizine and superior potency to fexofenadine.

Use of cough and cold preparations during breastfeeding.

PubMed

Mitchell, J L

1999-12-01

Adverse reactions in infants from maternal drug ingestion depend largely on the amount of milk consumed by the infant, timing of breastfeeding in relation to dosing, dose of the medication, dosing interval, and duration of therapy. When taking medications, breastfeeding mothers should be instructed to take their medication after breastfeeding, at the lowest effective dose and for the shortest duration. Overall, there are few data from human studies on the use of antihistamines, decongestants, and cough products during breastfeeding. Studies of pseudoephedrine, triprolidine, and loratadine in humans conclude that low levels of each drug would reach a breastfed infant. Since triprolidine and pseudoephedrine are also considered compatible with breastfeeding by the AAP, these 2 drugs should be the first-line choices. Codeine is considered compatible with breastfeeding by the AAP, and would be an acceptable choice for short-term use as a cough suppressant. It is important to note that many of the liquid cough and cold products contain alcohol. In addition, many of the combination products are a mixture of an antihistamine and a decongestant and may also contain aspirin, acetaminophen, ibuprofen, or caffeine. It is preferable for nursing mothers to only take medications that are necessary and to avoid such combination products. The AAP considers alcohol, acetaminophen, ibuprofen, and caffeine compatible with breastfeeding. Aspirin has been associated with significant negative effects on some nursing infants, and the AAP recommends giving aspirin to nursing mothers with caution. Mothers taking cough and cold products should watch for adverse events in their breastfed infants. Infants may experience paradoxical central nervous stimulation from antihistamines and irritability and insomnia from decongestants.

High-dose anti-histamine use and risk factors in children with urticaria

PubMed Central

Uysal, Pınar; Avcil, Sibelnur; Erge, Duygu

2016-01-01

Aim The drugs of choice in the treatment of urticaria in children are H1-antihistamines. The aim of the study was to evaluate children with urticaria and define risk factors for requirement of high-dose H1-antihistamines in children with urticaria. Material and Methods The medical data of children who were diagnosed as having urticaria admitted to our outpatient clinic between January 2014 and January 2016 were searched. The medical histories, concomitant atopic diseases, parental atopy histories, medications, treatment responses, blood eosinophil and basophil counts, and serum total IgE levels were recorded. In addition, the urticaria activity score for seven days, autoimmune antibody tests, and skin prick test results were evaluated in children with chronic urticaria. Results The numbers of the children with acute and chronic urticaria were 138 and 92, respectively. The age of the children with chronic urticaria was higher than that of those with acute urticaria (p<0.0001). There was no difference between the two groups in terms of blood eosinophil and basophil counts, and serum total IgE levels (p>0.05). There was a negative correlation between blood eosinophil count and the UAS7 score in children with chronic urticaria (r=−0.276, p=0.011). Chronic urticaria and requirement of high dose H1-antihistamines were significant in children aged ≥10 years (p<0.001, p=0.015). High UAS7 score (OR: 1.09; CI 95%: [1.03–1.15]) and basopenia (OR: 6.77; CI 95%: [2.01–22.75]) were associated with the requirement of high-dose H1-AH in children with chronic urticaria. Conclusion The requirement of high-dose H1-antihistamines was higher with children’s increasing age. Disease severity and basopenia were risk factors for the requirement of high-dose H1-antihistamines. PMID:28123332

Proarrhythmic potential of halofantrine, terfenadine and clofilium in a modified in vivo model of torsade de pointes

PubMed Central

Batey, Andrew J; Coker, Susan J

2002-01-01

This study was designed to compare the proarrhythmic activity of the antimalarial drug, halofantrine and the antihistamine, terfenadine, with that of clofilium a K+ channel blocking drug that can induce torsade de pointes. Experiments were performed in pentobarbitone-anaesthetized, open-chest rabbits. Each rabbit received intermittent, rising dose i.v. infusions of the α-adrenoceptor agonist phenylephrine. During these infusions rabbits also received increasing i.v. doses of clofilium (20, 60 and 200 nmol kg−1 min−1), terfenadine (75, 250 and 750 nmol kg−1 min−1), halofantrine (6, 20 and 60 μmol kg−1) or vehicle. Clofilium and halofantrine caused dose-dependent increases in the rate-corrected QT interval (QTc), whereas terfenadine prolonged PR and QRS intervals rather than prolonging cardiac repolarization. Progressive bradycardia occurred in all groups. After administration of the highest dose of each drug halofantrine caused a modest decrease in blood pressure, but terfenadine had profound hypotensive effects resulting in death of most rabbits. The total number of ventricular premature beats was highest in the clofilium group. Torsade de pointes occurred in 6 out of 8 clofilium-treated rabbits and 4 out of 6 of those which received halofantrine, but was not seen in any of the seven terfenadine-treated rabbits. These results show that, like clofilium, halofantrine can cause torsade de pointes in a modified anaesthetized rabbit model whereas the primary adverse effect of terfenadine was cardiac contractile failure. PMID:11861329

The action of 5-hydroxytryptamine and some of its antagonists on the umbilical vessels of the human placenta

PubMed Central

Åström, A.; Samelius, U.

1957-01-01

The vasoconstrictor action of 5-hydroxytryptamine (5-HT) in the human placental preparation is about 10 times stronger than that of adrenaline and is antagonized by anti-adrenaline compounds like phentolamine. Both 5-HT and adrenaline are antagonized by yohimbine and chlorpromazine. Specific and strong anti-5-HT action is demonstrated for lysergic acid diethylamide (LSD) and tryptamine. Both LSD and tryptamine in larger doses have a vasoconstrictor action. Mescaline has no certain modifying effect on the action of 5-HT, but itself causes vasoconstriction in large doses. The antihistamine drug phenbenzamine in histamine blocking doses abolishes the action of 5-HT in half the preparations tested. The ganglionic blocking agent trimetaphan in large doses antagonizes the action of 5-HT added subsequently, and also, to a lesser degree, the effect of adrenaline. Hexamethonium and tetraethylammonium bromides are ineffective in this preparation. No certain modifying action of reserpine on subsequently added 5-HT could be demonstrated, and the same was true for heparin even in very high concentrations. PMID:13489166

Chapter 5: Allergic rhinitis.

PubMed

Uzzaman, Ashraf; Story, Rachel

2012-01-01

Rhinitis is a symptomatic inflammatory disorder of the nose with different causes such as allergic, nonallergic, infectious, hormonal, drug induced, and occupational and from conditions such as sarcoidosis and necrotizing antineutrophil cytoplasmic antibodies positive (Wegener's) granulomatosis. Allergic rhinitis affects up to 40% of the population and results in nasal (ocular, soft palate, and inner ear) itching, congestion, sneezing, and clear rhinorrhea. Allergic rhinitis causes extranasal untoward effects including decreased quality of life, decreased sleep quality, obstructive sleep apnea, absenteeism from work and school, and impaired performance at work and school termed "presenteeism." The nasal mucosa is extremely vascular and changes in blood supply can lead to obstruction. Parasympathetic stimulation promotes an increase in nasal cavity resistance and nasal gland secretion. Sympathetic stimulation leads to vasoconstriction and consequent decrease in nasal cavity resistance. The nasal mucosa also contains noradrenergic noncholinergic system, but the contribution to clinical symptoms of neuropeptides such as substance P remains unclear. Management of allergic rhinitis combines allergen avoidance measures with pharmacotherapy, allergen immunotherapy, and education. Medications used for the treatment of allergic rhinitis can be administered intranasally or orally and include oral and intranasal H(1)-receptor antagonists (antihistamines), intranasal and systemic corticosteroids, intranasal anticholinergic agents, and leukotriene receptor antagonists. For intermittent mild allergic rhinitis, an oral or intranasal antihistamine is recommended. In individuals with persistent moderate/severe allergic rhinitis, an intranasal corticosteroid is preferred. When used in combination, an intranasal H(1)-receptor antagonist and a nasal steroid provide greater symptomatic relief than monotherapy. Allergen immunotherapy is the only disease-modifying intervention available.

Seasonal changes in antibiotics, antidepressants/psychiatric drugs, antihistamines and lipid regulators in a wastewater treatment plant.

PubMed

Golovko, Oksana; Kumar, Vimal; Fedorova, Ganna; Randak, Tomas; Grabic, Roman

2014-09-01

Seasonal changes in the concentration of 21 pharmaceuticals in a wastewater treatment plant (WWTP) in České Budějovice were investigated over 12months. The target compounds were 10 antibiotics, 4 antidepressants, 3 psychiatric drugs, 2 antihistamines and 2 lipid regulators. 272 Wastewater samples (136 influents and 136 effluents) were collected from March 2011 to February 2012 and analyzed using two-dimensional liquid chromatography coupled with tandem mass spectrometry. All studied pharmaceuticals were frequently detected in both the influent and the effluent wastewater samples, except for meclozine, which was only found in the influent. The mean concentration of pharmaceuticals varied from 0.006μgL(-1) to 1.48μgL(-1) in the influent and from 0.003μgL(-1) to 0.93μgL(-1) in the effluent. The concentration of most pharmaceuticals was higher during winter. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Nanoporous Alumina Membrane Based Electrochemical Biosensor for Histamine Determination with Biofunctionalized Magnetic Nanoparticles Concentration and Signal Amplification

PubMed Central

Ye, Weiwei; Xu, Yifan; Zheng, Lihao; Zhang, Yu; Yang, Mo; Sun, Peilong

2016-01-01

Histamine is an indicator of food quality and indispensable in the efficient functioning of various physiological systems. Rapid and sensitive determination of histamine is urgently needed in food analysis and clinical diagnostics. Traditional histamine detection methods require qualified personnel, need complex operation processes, and are time-consuming. In this study, a biofunctionalized nanoporous alumina membrane based electrochemical biosensor with magnetic nanoparticles (MNPs) concentration and signal amplification was developed for histamine determination. Nanoporous alumina membranes were modified by anti-histamine antibody and integrated into polydimethylsiloxane (PDMS) chambers. The specific antibody modified MNPs were used to concentrate histamine from samples and transferred to the antibody modified nanoporous membrane. The MNPs conjugated to histamine were captured in the nanopores via specific reaction between histamine and anti-histamine antibody, resulting in a blocking effect that was amplified by MNPs in the nanopores. The blockage signals could be measured by electrochemical impedance spectroscopy across the nanoporous alumina membrane. The sensing platform had great sensitivity and the limit of detection (LOD) reached as low as 3 nM. This biosensor could be successfully applied for histamine determination in saury that was stored in frozen conditions for different hours, presenting a potentially novel, sensitive, and specific sensing system for food quality assessment and safety support. PMID:27782087

Role of bilastine in the management of allergic rhinitis and urticaria: an Asia-Pacific consensus statement

PubMed Central

Lee, Dennis Lip Yen; Abong, Jovilia; Siasoco, Bella; Chow, Steven KW; Leong, Jern-Lin; Singh, Harvinder; Kuljit, S; Campomanes, Benjamin

2016-01-01

The prevalence of allergic diseases is increasing globally, most particularly in middle- to low-income countries. This article examines the burden of allergic rhinitis and chronic urticaria in the Asia-Pacific region, unmet clinical needs, and the potential role of bilastine in the management of these conditions. An International Advisory Group meeting was convened in association with the Asian Pacific Society of Respirology Annual Congress in November 2014, followed by a literature review, and consensus-based outcomes from the meeting and literature review are described. Regional estimates of the prevalence of allergic rhinitis range from 10% to 50%, while little is known regarding the burden of urticaria in the Asia-Pacific region. A survey of allergy patients in the region identified fast, complete, and long-lasting symptom relief as the medication attributes most important to patients. International treatment guidelines for allergic rhinitis and urticaria advocate the first-line use of second-generation, no-sedating H1-antihistamines, such as bilastine, over their first-generation counterparts and a range of these agents are available to Asia-Pacific patients. The newer agents possess many of the properties of an "ideal" antihistamine (once daily administration, rapid and complete symptom relief, limited potential for drug-drug interactions, minimal side effects). The burgeoning prevalence of allergic diseases in the Asia-Pacific region and the uncontrolled symptoms that these patients experience demand a new antihistamine that offers the highest number of positive features according to the international guidelines. PMID:26844221

Role of bilastine in the management of allergic rhinitis and urticaria: an Asia-Pacific consensus statement.

PubMed

Mösges, Ralph; Lee, Dennis Lip Yen; Abong, Jovilia; Siasoco, Bella; Chow, Steven Kw; Leong, Jern-Lin; Singh, Harvinder; Kuljit, S; Campomanes, Benjamin

2016-01-01

The prevalence of allergic diseases is increasing globally, most particularly in middle- to low-income countries. This article examines the burden of allergic rhinitis and chronic urticaria in the Asia-Pacific region, unmet clinical needs, and the potential role of bilastine in the management of these conditions. An International Advisory Group meeting was convened in association with the Asian Pacific Society of Respirology Annual Congress in November 2014, followed by a literature review, and consensus-based outcomes from the meeting and literature review are described. Regional estimates of the prevalence of allergic rhinitis range from 10% to 50%, while little is known regarding the burden of urticaria in the Asia-Pacific region. A survey of allergy patients in the region identified fast, complete, and long-lasting symptom relief as the medication attributes most important to patients. International treatment guidelines for allergic rhinitis and urticaria advocate the first-line use of second-generation, no-sedating H1-antihistamines, such as bilastine, over their first-generation counterparts and a range of these agents are available to Asia-Pacific patients. The newer agents possess many of the properties of an "ideal" antihistamine (once daily administration, rapid and complete symptom relief, limited potential for drug-drug interactions, minimal side effects). The burgeoning prevalence of allergic diseases in the Asia-Pacific region and the uncontrolled symptoms that these patients experience demand a new antihistamine that offers the highest number of positive features according to the international guidelines.

Establishing the place in therapy of bilastine in the treatment of allergic rhinitis according to ARIA: evidence review.

PubMed

Bousquet, Jean; Ansótegui, Ignacio; Canonica, G Walter; Zuberbier, Torsten; Baena-Cagnani, Carlos E; Bachert, Claus; Cruz, Alvaro A; González, Sandra N; Kuna, Piotr; Morais-Almeida, Mario; Mullol, Joaquim; Ryan, Dermot P; Sánchez-Borges, Mario; Valiente, Román; Church, Martin K

2012-01-01

The ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines development group examined the properties of oral H(1)-antihistamines and made proposals about an 'optimal' drug. Several criteria should be met by oral H(1)-antihistamines in terms of their pharmacological, and clinical efficacy and safety profiles. Bilastine, a new H(1)-antihistamine, has been approved in 28 European countries for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria in adults and children older than 12 years. To determine its potential place in therapy in the treatment of allergic rhinitis, this manuscript examines whether bilastine meets the criteria defined in the European Academy of Allergy and Clinical Immunology (EAACI)/ARIA proposals for oral H(1)-antihistamines. The optimal properties of oral H(1)-antihistamines and current ARIA recommendations for their use in allergic rhinitis are presented, as well as relevant pharmacological and clinical data for bilastine obtained from the published literature that specifically address the defined criteria. Bilastine is a potent inhibitor of the histamine H(1) receptor. Data from preclinical studies have confirmed its selectivity for the histamine H(1) receptor over other receptors, and demonstrated antihistaminic properties in vitro and in vivo. Bilastine does not interfere with the cytochrome P450 system and is devoid of cardiac side effects. Studies in healthy volunteers and patients have shown that bilastine does not affect driving ability, cardiac conduction or alertness. In large pivotal randomized, placebo-controlled trials (RCTs), bilastine had a favourable safety profile. Bilastine 20 mg once daily improved all nasal and ocular symptoms of allergic rhinitis with greater efficacy than placebo and comparable to that of cetirizine and desloratadine. Moreover, bilastine was shown to improve quality of life, an important outcome of RCTs in allergic diseases. There were no significant changes in laboratory tests, electrocardiograms or vital signs. A potential limitation of this assessment of bilastine is that it is a literature-based review and the findings are dependent upon the quality of the published evidence. Bilastine meets current EAACI/ARIA criteria for medications used in the treatment of allergic rhinitis.

The Use of a Poisson Regression to Evaluate Antihistamines and Fatal Aircraft Mishaps in Instrument Meteorological Conditions.

PubMed

Gildea, Kevin M; Hileman, Christy R; Rogers, Paul; Salazar, Guillermo J; Paskoff, Lawrence N

2018-04-01

Research indicates that first-generation antihistamine usage may impair pilot performance by increasing the likelihood of vestibular illusions, spatial disorientation, and/or cognitive impairment. Second- and third-generation antihistamines generally have fewer impairing side effects and are approved for pilot use. We hypothesized that toxicological findings positive for second- and third-generation antihistamines are less likely to be associated with pilots involved in fatal mishaps than first-generation antihistamines. The evaluated population consisted of 1475 U.S. civil pilots fatally injured between September 30, 2008, and October 1, 2014. Mishap factors evaluated included year, weather conditions, airman rating, recent airman flight time, quarter of year, and time of day. Due to the low prevalence of positive antihistamine findings, a count-based model was selected, which can account for rare outcomes. The means and variances were close for both regression models supporting the assumption that the data follow a Poisson distribution; first-generation antihistamine mishap airmen (N = 582, M = 0.17, S2 = 0.17) with second- and third-generation antihistamine mishap airmen (N = 116, M = 0.20, S2 = 0.18). The data indicate fewer airmen with second- and third-generation antihistamines than first-generation antihistamines in their system are fatally injured while flying in IMC conditions. Whether the lower incidence is a factor of greater usage of first-generation antihistamines versus second- and third-generation antihistamines by the pilot population or fewer deleterious side effects with second- and third-generation antihistamines is unclear. These results engender cautious optimism, but additional research is necessary to determine why these differences exist.Gildea KM, Hileman CR, Rogers P, Salazar GJ, Paskoff LN. The use of a Poisson regression to evaluate antihistamines and fatal aircraft mishaps in instrument meteorological conditions. Aerosp Med Hum Perform. 2018; 89(4):389-395.

The Effectiveness of Automatic Recommending System for Premedication in Reducing Recurrent Radiocontrast Media Hypersensitivity Reactions

PubMed Central

Bae, Yun-Jeong; Hwang, Ye Won; Yoon, Sun-young; Kim, Sujeong; Lee, Taehoon; Lee, Yoon Su; Kwon, Hyouk-Soo; Cho, You Sook; Shin, Myung Jin; Moon, Hee-Bom; Kim, Tae-Bum

2013-01-01

Background Non-ionic radiocontrast media (RCM) is rarely associated with hypersensitivity reactions. Premedication of patients who reacted previously to RCM with systemic corticosteroids and/or antihistamines can help reduce recurrent hypersensitivity reactions. However, premedication is still not prescribed in many cases for various reasons. This study aimed to determine the effectiveness of our novel RCM hypersensitivity surveillance and automatic recommending system for premedication. Methods and Results Hospitalized patients with a history of RCM hypersensitivity were identified in an electronic medical record system that included a mandatory reporting system for past adverse drug reactions. In 2009, a novel automatic prescription system was added that classified index RCM reactions by severity and dispensed appropriate corticosteroid and/or antihistamine pretreatment prior to new RCM exposures. The data from 12 months under the previous system and 12 months under the current system were compared. The two systems had similar overall premedication rates (91% and 95%) but the current system was associated with a significantly higher corticosteroid premedication rate (65% vs. 14%), which significantly reduced the breakthrough reaction rate (6.7% vs. 15.2%). The current system was also associated with increased corticosteroid and antihistamine premedication of patients with a mild index reaction (61% vs. 7%) and a reduction in their breakthrough reaction rate (6% vs. 15%). Conclusions Premedication with corticosteroid and/or antihistamine, which was increased by our novel automatic prescription system, significantly reduced breakthrough reactions in patients with a history of RCM hypersensitivity. PMID:23840391

Novel levocetirizine HCl tablets with enhanced palatability: synergistic effect of combining taste modifiers and effervescence technique

PubMed Central

Labib, Gihan S

2015-01-01

Objectives Levocetirizine HCl, a second-generation piperazine derivative and H1-selective antihistaminic agent, possesses few side effects. The first objective of the study was to compare and evaluate the taste-masking effect of different ratios of 2-hydroxypropyl-β-cyclodextrin and mannitol on levocetirizine HCl using an inclusion complex and solid dispersion, respectively. The second objective was to study the possibility of preparing and evaluating effervescent tablets from the best-chosen taste-masked blends for the purpose of their use either as orodispersible tablets or as water-soluble effervescent tablets, according to patients’ will. Materials and methods Prepared taste-masked blends were prepared and subjected to palatability, Fourier-transform infrared spectroscopy, and differential scanning calorimetry studies. Tablets containing different percentages of effervescent mixtures were prepared by direct compression on the selected taste-modified blends. Evaluation tests were conducted, including flowability and compressibility on the precompressed blends and hardness, friability, wetting time, effervescent time, in vitro, in vivo disintegration time, and in vitro dissolution study on the compressed tablets. Formulated tablets were evaluated and compared to marketed orodispersible tablets for mouth feel and palatability. Results All prepared tablets showed convenient physical and palatability properties compared to the selected brand. The in vitro drug-release study revealed fast release of levocetirizine HCl within 5 minutes from all prepared tablets. Conclusion Levocetirizine HCl effervescent tablets are likely to increase patient compliance with drug administration. Moreover, the use of these effervescent tablets in an orodispersible dosage form can improve oral drug bioavailability and act as an attractive pediatric dosage form. PMID:26379426

Histamine and H1-antihistamines: celebrating a century of progress.

PubMed

Simons, F Estelle R; Simons, Keith J

2011-12-01

In this review we celebrate a century of progress since the initial description of the physiologic and pathologic roles of histamine and 70 years of progress since the introduction of H(1)-antihistamines for clinical use. We discuss histamine and clinically relevant information about the molecular mechanisms of action of H(1)-antihistamines as inverse agonists (not antagonists or blockers) with immunoregulatory effects. Unlike first (old)-generation H(1)-antihistamines introduced from 1942 to the mid-1980s, most of the second (new)-generation H(1)-antihistamines introduced subsequently have been investigated extensively with regard to clinical pharmacology, efficacy, and safety; moreover, they are relatively free from adverse effects and not causally linked with fatalities after overdose. Important advances include improved nasal and ophthalmic H(1)-antihistamines with rapid onset of action (in minutes) for allergic rhinitis and allergic conjunctivitis treatment, respectively, and effective and safe use of high (up to 4-fold) doses of oral second-generation H(1)-antihistamines for chronic urticaria treatment. New H(1)-antihistamines introduced for clinical use include oral formulations (bilastine and rupatadine), and ophthalmic formulations (alcaftadine and bepotastine). Clinical studies of H(3)-antihistamines with enhanced decongestant effects have been conducted in patients with allergic rhinitis. Additional novel compounds being studied include H(4)-antihistamines with anti-inflammatory effects in allergic rhinitis, atopic dermatitis, and other diseases. Antihistamines have a storied past and a promising future. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Bilastine for the treatment of urticaria.

PubMed

Jáuregui, Ignacio; Ferrer, Marta; Bartra, Joan; del Cuvillo, Alfonso; Dávila, Ignacio; Montoro, Javier; Mullol, Joaquim; Sastre, Joaquín; Valero, Antonio

2013-08-01

Urticaria is a highly prevalent disease among people. First-choice treatment continues to be centred on the second-generation H1 antihistamines, including a wide group of drugs with a better therapeutic index (or risk:benefit ratio) than the classic ones, even in the high, off-label dosage occasionally required in chronic urticaria. Bilastine is a newly registered H1-antihistamine for treatment of allergic rhinoconjunctivitis and urticaria. With established antihistaminic and antiallergic properties, it is widely reviewed in the medical literature; however, to our knowledge, a specific review of bilastine's role in the treatment of urticaria was lacking. This article reviews the medical literature on the effectiveness and safety of bilastine in urticarial syndromes, either spontaneous or inducible, by means of a Medline search from 1990 to present, completed with some nonpublished data provided by the manufacturer. Once-daily treatment with bilastine 20 mg is effective in managing symptoms and improving patient's quality of life in chronic urticaria, with at least comparable efficacy to levocetirizine. As far as studies in healthy volunteers, clinical assays, and recent clinical experience can establish, bilastine's safety profile is adequate, appearing to be entirely free from cardiovascular effects, and not impairing psychomotor performance or actual driving, even at twice the therapeutic dose.

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

PubMed

Kim, Jiwon; Song, Jin-Ho

2017-03-05

Microglial NADPH oxidase is a major source of toxic reactive oxygen species produced during chronic neuroinflammation. Voltage-gated proton channel (H V 1) functions to maintain the intense activity of NADPH oxidase, and channel inhibition alleviates the pathology of neurodegenerative diseases such as ischemic stroke and multiple sclerosis associated with oxidative neuroinflammation. Antagonists of histamine H 1 receptors have beneficial effects against microglia-mediated oxidative stress and neurotoxicity. We examined the effects of the H 1 antihistamines, diphenhydramine and chlorpheniramine, on proton currents in BV2 microglial cells recorded using the whole-cell patch clamp technique. Diphenhydramine and chlorpheniramine reduced the proton currents with almost the same potency, yielding IC 50 values of 42 and 43μM, respectively. Histamine did not affect proton currents, excluding the involvement of histamine receptors in their action. Neither drug shifted the voltage-dependence of activation or the reversal potential of the proton currents, even though diphenhydramine slowed the activation and deactivation kinetics. The inhibitory effects of the two antihistamines on proton currents could be utilized to develop therapeutic agents for neurodegenerative diseases and other diseases associated with H V 1 proton channel abnormalities. Copyright © 2017 Elsevier B.V. All rights reserved.

Diagnosis, pathogenesis, and treatment of chronic spontaneous urticaria.

PubMed

Kaplan, Allen P

2018-05-01

Chronic Spontaneous Urticaria (CSU) is an endogenous disorder that is strongly associated with autoimmunity, particularly with immunoglobulin G (IgG) antibody to the alpha subunit of the IgE receptor seen in 35-40% of patients. Basophils and cutaneous mast cells can be activated and lead to a late-phase-like perivascular infiltration about small venules and hive formation. Review of current literature. Antibody to thyroid antigens are seen in 25% of patients; a small fraction of these may be clinically hypothyroid (Hashimoto's Thyroiditis). Forty percent of patients have angioedema, but not laryngeal edema. Therapy typically begins with second-generation antihistamines (H1 receptor blockers) up to four times a day. The failure rate is substantial, and estimates vary from 25% to 50%. The drug of choice for antihistamine resistant cases is omalizumab, at 300 mg/month, which is effective in 70% of patients. H-2-antagonists and leucotriene antagonists are no longer recommended because the literature does not support additional efficacy beyond blockage of H-1 receptors. For patients unresponsive to antihistamines and omalizumab, cyclosporine is recommended next. This is similarly effective in 65-70% of patients; however, assessment of blood pressure and renal function need to be followed every 4-6 weeks. Corticosteroid should not be employed chronically; however, a brief course of 3-10 days can be used acutely for severe exacerbations. Other agents, such as dapsone, sulfasalazine, or hydroxychloroquin, can be tried when the aforementioned medications fail, but the results are unpredictable because they have not been shown to have efficacy beyond the placebo effect (25-30%), and have not been studied in patients for whom the aforementioned approach i.e. antihistamines, omalizumab, and cyclosporine has failed. High dose antihistamines, omalizumab and cyclosporine (in that order) are effective and recommended for therapy of CUS, an inflammatory skin disorder associated with autoimmunity in 45% of patients.

Allergic reactions to antithyroid drugs are associated with autoimmunity a retrospective case-control study.

PubMed

Chivu, R D; Chivu, Laura Ioana; Ion, Daniela Adriana; Barbu, Carmen; Fica, Simona

2006-01-01

Thiamazole is the most used antithyroid drug for thyrotoxicosis in Basedow-Graves' (BG) (autoimmune) disease and in toxic multinodular goitre (TMG) (non-autoimmune). This study aims to find whether allergic reactions to thiamazole occur more frequently during the treatment of BG than of TMG. Retrospective study, of 128 patients newly diagnosed and treated for thyrotoxicosis in the first 6 months of 2006, in the Endocrinology Department of "Elias" Hospital, Bucharest. Cases were all patients treated with thiamazole who developed allergic reactions. Controls were all patients treated with thiamazole without allergic reactions. Risk factor was considered to be the presence of BG. Cases group consisted of 6 patients. All 6 started treatment with thiamazole for BG, and developed allergic reactions after 2-4 weeks of treatment. When thiamazole was withdrawn, allergic symptoms ceased under antihistamines and steroids. In order to control the thyrotoxicosis, antihistamines and oral steroids was administered, together with thiamazole in slow increasing doses. After about 4 weeks under this combination, a tolerance to thiamazole seems to appear. Control group consisted of 122 patients who started thiamazole: 66 for BG and 56 for TMG (without allergic reactions). Allergy to thiamazole was significantly associated with the autoimmune BG, and not with TMG (p = 0.03, OR = 11.04). None of the patients with TMG developed allergic reactions to the drug. Tolerance to this drug may occur.

The role and choice criteria of antihistamines in allergy management – expert opinion

PubMed Central

Jurkiewicz, Dariusz; Czarnecka-Operacz, Magdalena M.; Pawliczak, Rafał; Woroń, Jarosław; Moniuszko, Marcin; Emeryk, Andrzej

2016-01-01

Allergic diseases are the most common chronic conditions lasting throughout the patient’s life. They not only cause significant deterioration in the quality of life of patients but also lead to significant absenteeism and reduced productivity, resulting in very high costs for society. Effective and safe treatment of allergic diseases is therefore one of the main challenges for public health and should be carried out by all the specialists in family medicine, internists and paediatricians in collaboration with allergists, otorhinolaryngologists and dermatologists. Antihistamines are most commonly used in the treatment of allergies. Several dozen drugs are available on the pharmaceutical market, and their generic forms are advertised widely as very effective drugs for the treatment of allergic diseases. What is the truth? What are the data from clinical trials and observational studies? Are all drugs equally effective and safe for the patient? According to a panel of experts representing various fields of medicine, inappropriate treatment of allergies can be very risky for patients, and seemingly equally acting medications may differ greatly. Therefore, a panel of experts gathered the latest data from the entire scientific literature and analysed the latest standards and recommendations prepared by scientific societies. This paper provides a summary of these studies and highlights the importance for the patient of the proper choice of drug to treat his allergies. PMID:28035215

The role and choice criteria of antihistamines in allergy management - expert opinion.

PubMed

Kuna, Piotr; Jurkiewicz, Dariusz; Czarnecka-Operacz, Magdalena M; Pawliczak, Rafał; Woroń, Jarosław; Moniuszko, Marcin; Emeryk, Andrzej

2016-12-01

Allergic diseases are the most common chronic conditions lasting throughout the patient's life. They not only cause significant deterioration in the quality of life of patients but also lead to significant absenteeism and reduced productivity, resulting in very high costs for society. Effective and safe treatment of allergic diseases is therefore one of the main challenges for public health and should be carried out by all the specialists in family medicine, internists and paediatricians in collaboration with allergists, otorhinolaryngologists and dermatologists. Antihistamines are most commonly used in the treatment of allergies. Several dozen drugs are available on the pharmaceutical market, and their generic forms are advertised widely as very effective drugs for the treatment of allergic diseases. What is the truth? What are the data from clinical trials and observational studies? Are all drugs equally effective and safe for the patient? According to a panel of experts representing various fields of medicine, inappropriate treatment of allergies can be very risky for patients, and seemingly equally acting medications may differ greatly. Therefore, a panel of experts gathered the latest data from the entire scientific literature and analysed the latest standards and recommendations prepared by scientific societies. This paper provides a summary of these studies and highlights the importance for the patient of the proper choice of drug to treat his allergies.

Treatment of canine atopic dermatitis with cetirizine, a second generation antihistamine: A single-blinded, placebo-controlled study

PubMed Central

2004-01-01

Abstract Cetirizine and placebo were administered orally as individual agents to 23 dogs with atopic dermatitis. The pruritus was satisfactorily reduced in 4/22 (18%) dogs that completed the trial with cetirizine. Two dogs vomited after administration of the active drug. PMID:15206590

[ENT inflammation and importance of fenspiride].

PubMed

Jankowski, R

2002-09-01

PERSISTENT INFLAMMATION: Inflammation may persist despite the eviction of the aggressive agent because of the disruption of the regulator mechanisms. In such patients, drugs such as fenspiride can be effective at several levels, from onset of inflammation, in an attempt to control its progression. INHIBITION OF NEUROPHIL MIGRATION: Could be a very interesting propriety for controlling inflammation of the human respiratory mucosa. CONTROL OF FREE RADICALS: In certain cases, clearance of free oxygen radicals by cells implicated in the inflammatory process may be overrun. Fenespiride can limit the production of free radicals, probably at the level of the producing cells. ACTION ON THE ARACHIDONIC ACID CASCADE: The mechanism and site of action of fenspiride remains to be clarified. It does not act like conventional antiinflammatory drugs by inhibiting cyclo-oxygenase. ANTIHISTAMINE ACTIVITY: Fenspiride has a certain antihistamine activity, basically by blocking H1 receptors. This action should be tested in subjects with nonspecific nasal hyperreactivity. OTHER PROPERTIES: Fenspiride also has an alpha-1-adrenolytic activity and an inhibitor effect on cyclic AMP, two properties which could have an impact on inflammatory diseases of the upper airways.

Histamine H1 receptor antagonist cetirizine impairs working memory processing speed, but not episodic memory.

PubMed

van Ruitenbeek, P; Vermeeren, A; Riedel, W J

2010-09-01

The histaminergic neurotransmitter system is currently under investigation as a target for drug treatment of cognitive deficits in clinical disorders. The therapeutic potential of new drugs may initially be screened using a model of histaminergic dysfunction, for example, as associated with the use of centrally active antihistamines. Of the selective second generation antihistamines, cetirizine has been found to have central nervous system effects. The aim of the present study was to determine whether cetirizine can be used as a tool to model cognitive deficits associated with histaminergic hypofunction. The study was conducted according to a three-way, double-blind, cross-over design. Treatments were single oral doses of cetirizine 10 and 20 mg and placebo. Effects on cognition were assessed using tests of word learning, memory scanning, vigilance, divided attention, tracking and visual information processing speed. Cetirizine 10 mg impaired tracking performance and both doses impaired memory scanning speed. None of the other measures indicated impaired performance. Cetirizine affects information processing speed, but these effects were not sufficient to serve as a model for cognitive deficits in clinical disorders.

Potential negative effects of anti-histamines on male reproductive function.

PubMed

Mondillo, Carolina; Varela, María Luisa; Abiuso, Adriana María Belén; Vázquez, Ramiro

2018-05-01

Histamine (HA) is a pleiotropic biogenic amine synthesized exclusively by histidine decarboxylase (HDC) in most mammalian tissues. The literature on the role of HA within the male gonad has expanded over the last years, attracting attention to potential unexpected side-effects of anti-histamines on testicular function. In this regard, HA receptors (HRH1, HRH2 and HRH4) have been described in Leydig cells of different species, including human. Via these receptors, HA has been reported to trigger positive or negative interactions with the LH/hCG signaling pathway depending upon its concentration, thereby contributing to the local control of testicular androgen levels. It should then be considered that anti-histamines may affect testicular homeostasis by increasing or decreasing steroid production. Additionally, HRH1 and HRH2 receptors are present in peritubular and germ cells, and HRH2 antagonists have been found to negatively affect peritubular cells and reduce sperm viability. The potential negative impact of anti-histamines on male reproduction becomes even more dramatic if we consider that HA has also been associated with human sexual behavior and penile erection. What is more, although testicular mast cells are the major source of locally produced HA, recent studies have described HDC expression in macrophages, Leydig cells and germ cells, revealing the existence of multiple sources of HA within the testis. Undoubtedly, the more we learn about the testicular histaminergic system, the more opportunities there will be for rational design of drugs aimed at treating HA-related pathologies, with minimum or nule negative impact on fertility. © 2018 Society for Reproduction and Fertility.

[Pharmacotherapy of urticaria--an analysis of the discrepancies between guidelines of expert bodies, registration documents and evidence for the effectiveness of drugs].

PubMed

Plichta, Danuta; Spiewak, Radosław

2013-01-01

The year 2012 has seen relevant changes in Polish pharmaceutical legislation and drug reimbursement, among others limiting the reimbursement solely to indications stated in the Summaries of Product Characteristics (SPCs). A discrepancy with expert recommendations became apparent. The aim of this study was to analyze discordances between up-to-date expert recommendations, the SPCs in force, and the evidence for the effectiveness of recommended drugs in urticaria. Guidelines for the treatment of urticaria issued by Polish and international expert bodies were analyzed, along with the SPCs. A systematic review of clinical trials of recommended drugs was carried out. Of drugs recommended by the experts, 203 were authorized in Poland for urticaria treatment, including 167 oral preparations of second-generation antihistamines (SGAH, 8 active substances), 29 oral preparations of first-generation antihistamines (6 substances), 4 preparations of systemic glucocorticosteroids (2), 2 topical glucocorticosteroid preparations (2) and one combined preparation of human immunoglobulin with histamine. Among products both recommended by experts and licensed for the treatment of urticaria in Poland, high or moderate-level of evidence of effectiveness was available for 7 active substances (bilastine, cetirizine, desloratadine, fexofenadine, loratadine, levocetirizine, rupatadine). Nevertheless, 39% of SGAH available in Poland (66 preparations of cetirizine, emedastine, levocetirizine, loratadine or fexofenadine) were registered exclusively for "chronic idiopathic urticaria" - a diagnosis inconsistent with the current state of medical knowledge. We conclude that there exist considerable discrepancies between expert recommendations for the pharmacotherapy of urticaria, the licensed use of drugs as defined in Summaries of Product Characteristics and scientific evidence for their effectiveness.

The drug-use patterns of helping-profession students in Brisbane, Australia.

PubMed

Engs, R C

1980-10-01

A survey of 1691 first-and final-year students in the helping professions (medicine, law, nursing, pharmacy, police science, seminary, social work/ psychology, and teaching) as to their use of drugs was carried out during February to April, 1980, in Brisbane, Australia. The results indicated that about 86% drank coffee or tea, 85% drank alcohol, 85% used non-prescription analgesics, 31% used tobacco, 25% antihistamines, 9% marijuana, 9% sedatives, 6% tranquilizers, 2% hallucinogens, 2% stimulants, 1% cocaine and 1% used opiates at least once a year. Of these students, females used analgesics and antihistamines significantly more frequently than males and consumed more caffeine, tobacco and analgesics than males, while males drank significantly more alcohol than females. Final-year students used more alcohol, coffee or tea and tobacco, and used marijuana, coffee and tea and tobacco significantly more frequently than first-year students. Individuals who did not consider religion important used more alcohol and tobacco and used marijuana, tobacco and hallucinogens more frequently compared to individuals who considered religion to be important. There was also a significant difference in drug usage between the different courses of study for most of the substances, with law students using the majority of substances the most frequently and seminarians the least frequently.

Treatment of allergic rhinitis and urticaria: a review of the newest antihistamine drug bilastine

PubMed Central

Wang, Xue Yan; Lim-Jurado, Margaret; Prepageran, Narayanan; Tantilipikorn, Pongsakorn; Wang, De Yun

2016-01-01

Allergic rhinitis and urticaria are common allergic diseases that may have a major negative impact on patients’ quality of life. Bilastine, a novel new-generation antihistamine that is highly selective for the H1 histamine receptor, has a rapid onset and prolonged duration of action. This agent does not interact with the cytochrome P450 system and does not undergo significant metabolism in humans, suggesting that it has very low potential for drug–drug interactions, and does not require dose adjustment in renal impairment. As bilastine is not metabolized and is excreted largely unchanged, hepatic impairment is not expected to increase systemic exposure above the drug’s safety margin. Bilastine has demonstrated similar efficacy to cetirizine and desloratadine in patients with seasonal allergic rhinitis and, in a Vienna Chamber study, a potentially longer duration of action than fexofenadine in patients with asymptomatic seasonal allergic rhinitis. It has also shown significant efficacy (similar to that of cetirizine) and safety in the long-term treatment of perennial allergic rhinitis. Bilastine showed similar efficacy to levocetirizine in patients with chronic spontaneous urticaria and can be safely used at doses of up to fourfold higher than standard dosage (80 mg once daily). The fourfold higher than standard dose is specified as an acceptable second-line treatment option for urticaria in international guidelines. Bilastine is generally well tolerated, both at standard and at supratherapeutic doses, appears to have less sedative potential than other second-generation antihistamines, and has no cardiotoxicity. Based on its pharmacokinetic properties, efficacy, and tolerability profile, bilastine will be valuable in the management of allergic rhinitis and urticaria. PMID:27110120

Allergic rhinitis: continuous or on demand antihistamine therapy?

PubMed

Montoro, J; Sastre, J; Jáuregui, I; Bartra, J; Dávila, I; del Cuvillo, A; Ferrer, M; Mullol, J; Valero, A

2007-01-01

Allergic rhinitis is an inflammatory disease of the nasal mucosa, caused by an IgE-mediated reaction after exposure to the allergen to which the patient is sensitized. Histamine is the most important preformed mediator released in the early stage of the allergic reaction, and also contributes to the late phase of the latter, exhibiting proinflammatory effects. Minimal persistent inflammation is a physiopathological phenomenon induced by the presence of an inflammatory cell infiltrate, together with ICAM-1 expression in the epithelial cells of the mucosa exposed to the allergen to which they are sensitized, in the absence of clinical symptoms. This molecule is considered to be an allergic inflammatory marker. The priming effect first described by Connell in 1968 consists of the reduction in the allergen concentration required to elicit a nasal hyper-response when performing a daily nasal exposure test. This implies that with natural exposure to inhaled allergens, small amounts of environmental allergen will maintain the patient symptoms, and thus of course minimal persistent inflammation. Considering the above, it is questionable whether antihistamines should be administered on a continuous basis or upon demand. The antihistamines, and fundamentally the second-generation drugs, have been shown to exert an antiinflammatory effect, and this effect is greater when the drug is administered continuously than when administered upon demand. Likewise, a reduction in treatment cost and an improvement in quality of life among patients treated on a continuous basis has been documented. However, no studies have been specifically designed to clarify the indication of treatment on a continuous basis or upon demand, as occurs in the GINA. As a result, the individualization of treatment according to the concrete characteristics of each patient seems to be the best approach, at least for the time being.

FT-IR and FT-Raman spectra, molecular structure and first-order molecular hyperpolarizabilities of a potential antihistaminic drug, cyproheptadine HCl

NASA Astrophysics Data System (ADS)

Sagdinc, Seda G.; Erdas, Dilek; Gunduz, Ilknur; Sahinturk, Ayse Erbay

2015-01-01

Cyproheptadine hydrochloride (CYP HCl) {4-(5H-dibenzo[a,d]-cyclohepten-5-ylidene)-1-methylpiperidine hydrochloride} is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local-anesthetic properties. The geometry optimization, Mulliken atomic charges and wavenumber and intensity of the vibrational bands of all of the possible modes of CYP HCl have been calculated using ab initio Hartree-Fock (HF) and density functional theory (DFT) employing the B3LYP functional with the 6-311G(d,p) basis set. We have compared the calculated IR and Raman wavenumbers with experimental data. Quantum-chemical calculations of the geometrical structure, energies, and molecular electrostatic potential and NBO analysis of CYP HCl have been performed using the B3LYP/6-311G(d,p) method. The electric dipole moment (μ), static polarizability (α) and the first hyperpolarizability (β) values of the title compound have been computed using HF and DFT methods. The study reveals that the antihistaminic pharmacological property of CYP HCl has a large β value and, hence, may in general have potential applications in the development of non-linear optical materials. The experimental and calculated results for CYP HCl have also been compared with those for mianserin HCl.

Aeroallergens, allergic rhinitis, and sedating antihistamines: risk factors for traumatic occupational injury and economic impact.

PubMed

Hanrahan, L P; Paramore, L C

2003-10-01

The U.S. workplace injury burden is significant. Our objective was to assess the particular impact of aeroallergen, allergic rhinitis, and antihistamine exposures and side effects on the risk of traumatic work-related injuries, and the associated economic impact. This is an observational case-control study with 1,223 acute traumatic injury cases that are compared to 1,202 chronic back injury controls. Structured telephone interviews were conducted in 1998 and 1999 on Workers' Compensation applicants injured in 1997. Antihistamine use and pollen levels were measured 2 weeks prior to the injury date. Sedating antihistamine exposures elevated acute injury risk (main effect OR: 2.93). A significant increase in traumatic injury risk was observed for combined sedating antihistamine and high pollen exposures among subjects with physician and self-diagnosed allergic rhinitis (OR: 2.41). Direct medical costs associated with this increased risk were estimated at $143 million in 2001. Workers with physician-diagnosed allergic rhinitis have as high a reliance on sedating antihistamines as do self-diagnosed and self-medicating nasal allergy sufferers. High pollen exposures along with sedating antihistamine use may confer significant additional injury risks among allergic rhinitis sufferers. Medical management "best practices" of diagnosed allergic rhinitis should include avoidance of sedating antihistamines to minimize acute, traumatic injury risks. Copyright 2003 Wiley-Liss, Inc.

Grapefruit juice reduces the oral bioavailability of fexofenadine but not desloratadine.

PubMed

Banfield, Christopher; Gupta, Samir; Marino, Mark; Lim, Josephine; Affrime, Melton

2002-01-01

Certain foods, such as grapefruit juice, are known to substantially alter the bioavailability of some drugs. These effects may be mediated by interactions with enzyme systems, such as cytochrome P450, or with active transporter systems, such as P-glycoprotein and organic anion transporting polypeptides. To assess the effect of consumption of grapefruit juice on the oral bioavailability of two nonsedating antihistamines, fexofenadine and desloratadine. Non-blinded, randomised, single-dose, four-way crossover study. Twenty-four healthy adult volunteers. Single oral doses of desloratadine 5mg and fexofenadine 60mg taken without and with grapefruit juice (pretreatment with 240ml of double-strength juice three times daily for 2 days prior to administration of study drug, plus the same amount simultaneously with, and 2 hours after, the drug dose). Each treatment was separated by at least 10 days. Log-transformed pharmacokinetic parameters [peak plasma concentration (C(max)) and area under the curve (AUC)], time to maximum concentration, elimination half-life and electrocardiographic (ECG) parameters. Comparing the ratio of the pharmacokinetic parameter means (C(max) and AUC) with and without grapefruit juice (expressed as a percentage), the rate (C(max)) and extent (AUC) of absorption of fexofenadine were reduced by 30% by consumption of grapefruit juice. In contrast, the bioavailability of desloratadine was unaffected by grapefruit juice. No clinically significant changes in ECG parameters were observed following coadministration of grapefruit juice with desloratadine or fexofenadine compared with either antihistamine given alone. The bioavailability of drugs that do not undergo significant intestinal or hepatic metabolism, such as fexofenadine, may be altered when administered with agents that influence drug transport mechanisms.

Histamine H1-receptor antagonists against Leishmania (L.) infantum: an in vitro and in vivo evaluation using phosphatidylserine-liposomes.

PubMed

Pinto, Erika G; da Costa-Silva, Thais A; Tempone, Andre Gustavo

2014-09-01

Considering the limited and toxic therapeutic arsenal available for visceral leishmaniasis (VL), the drug repositioning approach could represent a promising tool to the introduction of alternative therapies. Histamine H1-receptor antagonists are drugs belonging to different therapeutic classes, including antiallergics and anxyolitics. In this work, we described for the first time the activity of H1-antagonists against L. (L.) infantum and their potential effectiveness in an experimental hamster model. The evaluation against promastigotes demonstrated that chlorpheniramine, cinnarizine, hydroxyzine, ketotifen, loratadine, quetiapine and risperidone exerted a leishmanicidal effect against promastigotes, with IC50 values in the range of 13-84μM. The antihistaminic drug cinnarizine demonstrated effectiveness against the intracellular amastigotes, with an IC50 value of 21μM. The mammalian cytotoxicity was investigated in NCTC cells, resulting in IC50 values in the range of 57-229μM. Cinnarizine was in vivo studied as a free formulation and entrapped into phosphatidylserine-liposomes. The free drug was administered for eight consecutive days at 50mg/kg by intraperitoneal route (i.p.) and at 100mg/kg by oral route to L. infantum-infected hamsters, but showed lack of effectiveness in both regimens, as detected by real time PCR. The liposomal formulation was administered by i.p. route at 3mg/kg for eight days and reduced the parasite burden to 54% in liver when compared to untreated group; no improvement was observed in the spleen of infected hamsters. Cinnarizine is the first antihistaminic drug with antileishmanial activity and could be used as scaffold for drug design studies for VL. Copyright © 2014 Elsevier B.V. All rights reserved.

Antihistamines for the common cold.

PubMed

De Sutter, An I M; Saraswat, Avadhesh; van Driel, Mieke L

2015-11-29

The common cold is an upper respiratory tract infection, most commonly caused by a rhinovirus. It affects people of all age groups and although in most cases it is self limiting, the common cold still causes significant morbidity. Antihistamines are commonly offered over the counter to relieve symptoms for patients affected by the common cold, however there is not much evidence of their efficacy. To assess the effects of antihistamines on the common cold. We searched CENTRAL (2015, Issue 6), MEDLINE (1948 to July week 4, 2015), EMBASE (2010 to August 2015), CINAHL (1981 to August 2015), LILACS (1982 to August 2015) and Biosis Previews (1985 to August 2015). We selected randomised controlled trials (RCTs) using antihistamines as monotherapy for the common cold. We excluded any studies with combination therapy or using antihistamines in patients with an allergic component in their illness. Two authors independently assessed trial quality and extracted data. We collected adverse effects information from the included trials. We included 18 RCTs, which were reported in 17 publications (one publication reports on two trials) with 4342 participants (of which 212 were children) suffering from the common cold, both naturally occurring and experimentally induced. The interventions consisted of an antihistamine as monotherapy compared with placebo. In adults there was a short-term beneficial effect of antihistamines on severity of overall symptoms: on day one or two of treatment 45% had a beneficial effect with antihistamines versus 38% with placebo (odds ratio (OR) 0.74, 95% confidence interval (CI) 0.60 to 0.92). However, there was no difference between antihistamines and placebo in the mid term (three to four days) to long term (six to 10 days). When evaluating individual symptoms such as nasal congestion, rhinorrhoea and sneezing, there was some beneficial effect of the sedating antihistamines compared to placebo (e.g. rhinorrhoea on day three: mean difference (MD) -0.23, 95% CI -0.39 to -0.06 on a four- or five-point severity scale; sneezing on day three: MD -0.35, 95% CI -0.49 to -0.20 on a four-point severity scale), but this effect is clinically non-significant. Adverse events such as sedation were more commonly reported with sedating antihistamines although the differences were not statistically significant. Only two trials included children and the results were conflicting. The majority of the trials had a low risk of bias although some lacked sufficient trial quality information. Antihistamines have a limited short-term (days one and two of treatment) beneficial effect on severity of overall symptoms but not in the mid to long term. There is no clinically significant effect on nasal obstruction, rhinorrhoea or sneezing. Although side effects are more common with sedating antihistamines, the difference is not statistically significant. There is no evidence of effectiveness of antihistamines in children.

21 CFR 341.72 - Labeling of antihistamine drug products.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of the following: “relieves,” “alleviates,” “decreases,” “reduces,” or “dries”) “runny nose and... the nose or throat, and itchy, watery eyes due to hay fever” (which may be followed by one or both of... temporary relief of runny nose, sneezing, itching of the nose or throat, and itchy, watery eyes due to hay...

21 CFR 341.72 - Labeling of antihistamine drug products.

Code of Federal Regulations, 2011 CFR

2011-04-01

... of the following: “relieves,” “alleviates,” “decreases,” “reduces,” or “dries”) “runny nose and... the nose or throat, and itchy, watery eyes due to hay fever” (which may be followed by one or both of... temporary relief of runny nose, sneezing, itching of the nose or throat, and itchy, watery eyes due to hay...

21 CFR 341.72 - Labeling of antihistamine drug products.

Code of Federal Regulations, 2013 CFR

2013-04-01

... of the following: “relieves,” “alleviates,” “decreases,” “reduces,” or “dries”) “runny nose and... the nose or throat, and itchy, watery eyes due to hay fever” (which may be followed by one or both of... temporary relief of runny nose, sneezing, itching of the nose or throat, and itchy, watery eyes due to hay...

21 CFR 341.72 - Labeling of antihistamine drug products.

Code of Federal Regulations, 2012 CFR

2012-04-01

... of the following: “relieves,” “alleviates,” “decreases,” “reduces,” or “dries”) “runny nose and... the nose or throat, and itchy, watery eyes due to hay fever” (which may be followed by one or both of... temporary relief of runny nose, sneezing, itching of the nose or throat, and itchy, watery eyes due to hay...

21 CFR 341.72 - Labeling of antihistamine drug products.

Code of Federal Regulations, 2014 CFR

2014-04-01

... of the following: “relieves,” “alleviates,” “decreases,” “reduces,” or “dries”) “runny nose and... the nose or throat, and itchy, watery eyes due to hay fever” (which may be followed by one or both of... temporary relief of runny nose, sneezing, itching of the nose or throat, and itchy, watery eyes due to hay...

Allergy to dexchlorpheniramine. Study of a case.

PubMed

Cáceres Calle, O; Fernández-Benítez, M

2004-01-01

Dexchlorpheniramine (DH) is a classical or first generation antihistamine belonging to the ethanolamine group. Adverse effects related to these antihistamines are frequent, but the hypersensitivity reactions described in the literature since 1940 are exceptional. We report the case of a 32-year-old woman who experienced two episodes of akathisia secondary to intravenous (i.v.) dexchlorpheniramine administration for a possible hypersensitivity reaction to local anesthetics. Allergological study consisted of the following tests: skin prick tests with routine allergens, with a negative result; skin prick and intradermal tests with local anesthetics and DH, with a positive result to DH in the intradermal skin test (+ +); serum specific IgE, which was within normal levels; histamine release test with DH with a negative result, and the basophil activation test (BAT) with local anesthetics and DH, which was positive for DH and weakly positive to Lidocaine. BAT is proving to be a highly useful tool in the field of drug allergy, with a higher sensitivity and specificity than other in vitro tests. Because it avoids the need for provocation tests, this is especially important in drug-induced allergic reactions in which in vivo tests are repeatedly negative despite a clear clinical history.

Prediction of the Efficacy of Antihistamines in Chronic Spontaneous Urticaria Based on Initial Suppression of the Histamine- Induced Wheal.

PubMed

Sánchez, J; Zakzuk, J; Cardona, R

2016-01-01

Antihistamines are the first line of treatment for chronic spontaneous urticaria. However, there is no effective method to predict whether an antihistamine will have a beneficial clinical effect or not. To assess whether the change in histamine-induced wheal and flare measurements 24 hours after administration of antihistamine can predict the efficacy of treatment. We performed a multicenter, triple-blind, randomized study. Patients received a daily oral dose of cetirizine, fexofenadine, bilastine, desloratadine, or ebastine over 8 weeks. After 4 weeks, a higher dose of antihistamine was administered to patients who did not experience a clinical response. A histamine skin prick test was carried out at baseline and 24 hours after the first dose of antihistamine. Disease severity (Urticaria Activity Score [UAS]), response to the histamine skin prick test, and impact on the patient's quality of life (Dermatology Life Quality Index [DLQI]) were determined every 2 weeks. The study population comprised 150 patients (30 per group) and 30 controls. Twenty-four hours after administration of antihistamine, inhibition of the histamine wheal by >75% was significantly associated with better UAS and DLQI scores. The safety and efficacy of the 5 antihistamines were similar. After updosing, rates of disease control (DLQI score <5) increased from 58.7% to 76.7%. Measurement of the histamine-induced wheal can predict which patients will have a strong clinical response to antihistamines but has limited utility for identifying nonresponders. The clinical significance of these data could be relevant in the search for new urticaria treatment regimens.

[Pseudoallergies].

PubMed

Bernardini, R; Novembre, E; Lombardi, E; Monaco, M G; Monte, M T; Pucci, N; Rossi, M E; Vierucci, A

2001-01-01

Pseudo-allergic-reactions (PAR) are clinical manifestations including urticaria, angioedema, conjunctivitis, rhinitis, asthma, and anaphylaxis. The prevalence of PAR ranges from 0.1% to 75% according to various studies. The pathogenetic mechanism of these diseases is not immunologically mediated. Food, additives, and drugs are the main responsibilities for PAR. The diagnosis of PAR is characterized by the absence of specific IgE for the suspected products. The absence of immunological mechanisms is confirmed by in vitro and in vivo tests. The treatment of PAR is similar to that of allergic diseases (antihistamine drugs, steroids, B2 agonists, epinephrine).

Use of Antihistamine Medications During Early Pregnancy and Isolated Major Malformations

PubMed Central

Gilboa, Suzanne M.; Strickland, Matthew J.; Olshan, Andrew F.; Werler, Martha M.; Correa, Adolfo

2013-01-01

BACKGROUND Antihistamines are commonly used during pregnancy. There is little evidence that they have teratogenic effects, but there are knowledge gaps with respect to newer products, as well as the relationship between specific antihistamines and specific birth defects. METHODS Using the National Birth Defects Prevention Study (1997-2003), the authors examined associations between maternal use of 14 antihistamines during early pregnancy and 26 isolated major birth defects. A Bayesian analysis incorporating prior knowledge about the relationships between the antihistamines, birth defects, and measured covariates was conducted. RESULTS Of the 364 associations investigated, 24 had 95% posterior intervals excluding 1.0. All 24 associations were positive; 23 associations were of weak to moderate magnitude (posterior odds ratio [OR] < 3.0) and one was strong (OR > 6.0) but very imprecise. Of the 24 associations, 20 were with non-cardiac defects. Eight associations involved the antihistamine diphenhydramine. CONCLUSIONS The results of this study generally were consistent with no association between birth defects and antihistamine use during early pregnancy. Several of the findings might warrant further investigation, although the observed elevated associations should be interpreted in the context of the number of associations investigated and the analysis of retrospective, self-reported data. PMID:19161158

Brain-penetrating 2-aminobenzimidazole H(1)-antihistamines for the treatment of insomnia.

PubMed

Coon, Timothy; Moree, Wilna J; Li, Binfeng; Yu, Jinghua; Zamani-Kord, Said; Malany, Siobhan; Santos, Mark A; Hernandez, Lisa M; Petroski, Robert E; Sun, Aixia; Wen, Jenny; Sullivan, Sue; Haelewyn, Jason; Hedrick, Michael; Hoare, Samuel J; Bradbury, Margaret J; Crowe, Paul D; Beaton, Graham

2009-08-01

The benzimidazole core of the selective non-brain-penetrating H(1)-antihistamine mizolastine was used to identify a series of brain-penetrating H(1)-antihistamines for the potential treatment of insomnia. Using cassette PK studies, brain-penetrating H(1)-antihistamines were identified and in vivo efficacy was demonstrated in a rat EEG/EMG model. Further optimization focused on strategies to attenuate an identified hERG liability, leading to the discovery of 4i with a promising in vitro profile.

[Efficacy of intranasal antihistamine in the treatment of allergic rhinitis: a meta-analysis].

PubMed

Feng, Shaoyan; Deng, Chuntao; Li, Lei; Liao, Wei; Fan, Yunping; Xu, Geng; Li, Huabin

2014-10-01

To systematically evaluate the efficacy of intranasal antihistamine in the treatment of allergic rhinitis. The randomized controlled trials (RCT) about intranasal antihistamines for the treatment of allergic rhinitis between January 1985 and January 2014 were searched in OVID, PubMed, EMBASE, CNKI, WanFang Data and Cochrane Library. Two reviewers independently screened the literatures, extracted the data, and evaluated the methodological quality, then meta-analysis was performed by using RevMan 5.1 software. A total of thirteen RCTs were included. The results of meta-analysis showed that the efficacy of intranasal antihistamine group was superior to the placebo group in total nasal symptom scores (TNSS), the difference was significant[WMD = -1.96, 95%CI (-2.06;-1.85), P < 0.01], and individual nasal symptom scores (blocked nose, rhinorrhea, and sneezing) [WMD = -0.18, 95%CI (-0.28;-0.08); WMD = -0.45, 95%CI (-0.52;-0.38); WMD = -0.41, 95%CI (-0.58;-0.24), all P < 0.01], with significant differences. There was no significant difference between the intranasal antihistamine group and the corticosteroid group in TNSS [WMD = -1.51, 95%CI (-3.51;0.49), P = 0.14], but the intranasal antihistamines group was superior to the corticosteroid group in individual nasal symptom scores (blocked nose, rhinorrhea, and sneezing) [WMD = -0.23, 95%CI (-0.40;-0.06); WMD = -0.35, 95%CI (-0.65;-0.05); WMD = -0.25, 95%CI (-0.42;-0.08), all P < 0.05], with significant differences. The intranasal antihistamine group was superior to the oral antihistamines group in TNSS [WMD = -0.88, 95%CI (-1.51;-0.25), P < 0.01]. Intranasal antihistamine is effective in the control of nasal symptoms in AR patients.

Characterization of anti-inflammatory properties and evidence for no sedation liability for the novel antihistamine SUN-1334H.

PubMed

Mandhane, Sanjay N; Shah, Jigar H; Bahekar, Prashant C; Mehetre, Sameer V; Pawar, Chandrashekhar A; Bagad, Ashish S; Chidrewar, Gajanan U; Rao, Chitturi Trinadha; Rajamannar, Thennati

2010-01-01

The anti-inflammatory potential of antihistamines has significant clinical utility. Long-term pharmacotherapy of so-called 'safe' antihistamines may be hampered by side effects in the central nervous system. In the present study, the new potential antihistamine SUN-1334H was compared with different antihistamines for anti-inflammatory effects, sedation potential and interaction with alcohol. Nasal and skin allergy were induced in guinea pig and mice by ovalbumin sensitization and challenge. Neurogenic nasal inflammation was induced by capsaicin. Sedation potential and interaction with alcohol were assessed by i.v. and intracerebroventricular pentobarbital-induced sedation and alcohol-induced ataxia models. Ovalbumin sensitization and challenge caused rhinitis pathology including inflammatory cell infiltration, IL-4, and protein leakage in the nasal lavage fluid (NLF) and presence of inflammatory cells in nasal epithelium. A 5-day treatment of antihistamines reduced these markers of inflammation. SUN-1334H, cetirizine and hydroxyzine caused comparable inhibition of NLF leukocytes, IL-4 and total protein concentrations. Fexofenadine and desloratadine showed moderate inhibition of NLF leukocytes and had no significant effect on IL-4 concentration. While fexofenadine had no effect on total protein concentration, the effect of desloratadine was comparable with the other antihistamines. In neurogenic nasal inflammation induced by capsaicin, SUN-1334H and fexofenadine caused better inhibition at lower and middle dose levels than the other antihistamines. In skin allergy models, SUN-1334H showed potent reduction of passive and active cutaneous anaphylactic reactions. In central nervous system side effects models, SUN-1334H, desloratadine and fexofenadine were devoid of any significant effects. The results are suggestive of a high anti-inflammatory to sedation index of SUN-1334H among leading antihistamines.

Early pregnancy exposure to antihistamines and risk of congenital heart defects: results of two case-control studies.

PubMed

Smedts, Huberdina P M; de Jonge, Linda; Bandola, Sarah J G; Baardman, Marlies E; Bakker, Marian K; Stricker, Bruno H C; Steegers-Theunissen, Régine P M

2014-09-01

We aimed to study the association between use of antihistamines in early pregnancy and congenital heart defects (CHD) in the offspring. Two case-control studies. HAVEN study, Erasmus MC, University Medical Centre, Rotterdam, and Eurocat Northern Netherlands (NNL), University Medical Center Groningen, Groningen, the Netherlands. We studied 361 children with CHD and 410 controls without congenital malformations from the HAVEN study and replicated the analyses in 445 children with CHD and 530 controls from the Eurocat NNL registry. Information about antihistamine use in early pregnancy and potential confounders was obtained from questionnaires postpartum. We calculated the association between antihistamines and CHD risk by multivariable logistic regression analysis. Odds ratios (OR) with 95% confidence intervals (CI). In the HAVEN study, 25 of 771 mothers used antihistamines that were associated with an increased CHD risk (OR 3.0, 95% CI 1.2-7.3), particularly atrioventricular septal defects (AVSD) (OR 5.1, 95 % CI 1.3-20.5) and perimembranous ventricular septal defects (pVSD) (OR 5.1, 95% CI 1.8-14.4). Mothers with severe nausea who did not use antihistamines had a reduced risk (OR 0.7, 95% CI 0.5-0.98), whereas nauseous mothers using antihistamines showed an almost fivefold increased risk of pVSD (OR 4.8, 95% CI 1.1-21.8). The association between antihistamines and AVSD was confirmed in the Eurocat cohort (OR 3.5, 95% CI 1.4-8.7), but we could not replicate the association with overall CHD risk. We found a positive association between antihistamine use in early pregnancy and CHD risk, particularly AVSD, which seemed to be independent of nausea/vomiting.

Antagonism of the effects of tremorine by tropine derivatives.

PubMed

FARQUHARSON, M E; JOHNSTON, R G

1959-12-01

Methods of testing new drugs for anti-Parkinson activity are briefly reviewed. The production in animals of Parkinson-like effects by Tremorine (1,4-dipyrrolidin-1'-ylbut-2-yne), and the inhibition of these effects in mice by a number of tropine derivatives, are described. No correlation was found between the activity against tremor and the anticholinergic, antihistaminic or local anaesthetic properties of the compounds.

Cytokine production by PBMC and serum from allergic and non-allergic subjects following in vitro histamine stimulation to test fexofenadine and osthole anti-allergic properties.

PubMed

Kordulewska, Natalia Karolina; Kostyra, Elżbieta; Cieślińska, Anna; Fiedorowicz, Ewa; Jarmołowska, Beata

2016-11-15

FXF is a third-generation antihistamine drug and osthole is assumed a natural antihistamine alternative. This paper compares peripheral blood mononuclear cell (PBMC) incubation with FXF and osthole, by studying FXF, osthole and histamine cytokine secretion in PBMC in vitro cultures. Mabtech kits determined the interleukins IL-1β, IL-4, IL-10, IL-13 and TNF-α. The influence of the above active substances on cytokine secretion in PBMC's and serum was assessed: cytokines were IL-1β, IL-4, IL-10, IL-13 and TNF-α; and cytokine levels secreted by untreated PBMCs in pure culture medium formed the absolute control (ctrl). We determined that osthole affects PBMC cytokine secretion to almost precisely the same extent as FXF (IL-1β, IL-4, IL-10 and TNF). In addition osthole had greater IL-13 blocking ability than FXF. Moreover, we observed significantly decreased IL-4 level in histamine/osthole theatment compared to histamine alone. Meanwhile, FXF not significantly decrease the level of IL-4 increased by histamine. This data indicates osthole's strong role in allergic inflamation. All results confirm our hypothesis that osthole is a natural histamine antagonist and therefore can be beneficially used in antihistamine treatment of conditions such as allergies. Copyright © 2016 Elsevier B.V. All rights reserved.

Prescription medicine use by pedestrians and the risk of injurious road traffic crashes: A case-crossover study.

PubMed

Née, Mélanie; Avalos, Marta; Luxcey, Audrey; Contrand, Benjamin; Salmi, Louis-Rachid; Fourrier-Réglat, Annie; Gadegbeku, Blandine; Lagarde, Emmanuel; Orriols, Ludivine

2017-07-01

While some medicinal drugs have been found to affect driving ability, no study has investigated whether a relationship exists between these medicines and crashes involving pedestrians. The aim of this study was to explore the association between the use of medicinal drugs and the risk of being involved in a road traffic crash as a pedestrian. Data from 3 French nationwide databases were matched. We used the case-crossover design to control for time-invariant factors by using each case as its own control. To perform multivariable analysis and limit false-positive results, we implemented a bootstrap version of Lasso. To avoid the effect of unmeasured time-varying factors, we varied the length of the washout period from 30 to 119 days before the crash. The matching procedure led to the inclusion of 16,458 pedestrians involved in an injurious road traffic crash from 1 July 2005 to 31 December 2011. We found 48 medicine classes with a positive association with the risk of crash, with median odds ratios ranging from 1.12 to 2.98. Among these, benzodiazepines and benzodiazepine-related drugs, antihistamines, and anti-inflammatory and antirheumatic drugs were among the 10 medicines most consumed by the 16,458 pedestrians. Study limitations included slight overrepresentation of pedestrians injured in more severe crashes, lack of information about self-medication and the use of over-the-counter drugs, and lack of data on amount of walking. Therapeutic classes already identified as impacting the ability to drive, such as benzodiazepines and antihistamines, are also associated with an increased risk of pedestrians being involved in a road traffic crash. This study on pedestrians highlights the necessity of improving awareness of the effect of these medicines on this category of road user.

Complex Cognitive Performance and Antihistamine Use

DTIC Science & Technology

1990-04-01

22 Antihistamine Use and Sedation ...........................................24 Antihistamine Use and Physiological Measures...Reactivity and Sedation in Healthy Volunteers after Administration of Hismanal, Alone or in Combination with Central Nervous System Depressants...cross the blood-brain barrier easily, resulting in central nervous system effects such as sedation , drowsiness, and altered psychomotor performance

Antihistamines and birth defects: a systematic review of the literature.

PubMed

Gilboa, Suzanne M; Ailes, Elizabeth C; Rai, Ramona P; Anderson, Jaynia A; Honein, Margaret A

2014-12-01

Approximately 10 - 15% of women reportedly take an antihistamine during pregnancy for the relief of nausea and vomiting, allergy and asthma symptoms, or indigestion. Antihistamines include histamine H1-receptor and H2-receptor antagonists. This is a systematic evaluation of the peer-reviewed epidemiologic literature published through February 2014 on the association between prenatal exposure to antihistamines and birth defects. Papers addressing histamine H1- or H2-receptor antagonists are included. Papers addressing pyridoxine plus doxylamine (Bendectin in the United States, Debendox in the United Kingdom, Diclectin in Canada, Lenotan and Merbental in other countries) prior to the year 2001 were excluded post hoc because of several previously published meta-analyses and commentaries on this medication. The literature on the safety of antihistamine use during pregnancy with respect to birth defects is generally reassuring though the positive findings from a few large studies warrant corroboration in other populations. The findings in the literature are considered in light of three critical methodological issues: i) selection of appropriate study population; ii) ascertainment of antihistamine exposures; and iii) ascertainment of birth defect outcomes. Selected antihistamines have been very well studied (e.g., loratadine); others, especially H2-receptor antagonists, require additional study before an assessment of safety with respect to birth defect risk could be made.

No high level evidence to support the use of oral H1 antihistamines as monotherapy for eczema: a summary of a Cochrane systematic review

PubMed Central

2014-01-01

Background The most important symptom as well as one of the major diagnostic criteria for eczema is itch. Although oral antihistamines continue to be prescribed for people with eczema, it is unclear if they are effective and safe in relieving itch and skin lesions. We sought to evaluate the available evidence on effectiveness of oral antihistamines (H1 antagonists) as monotherapy in children and adults with eczema. Methods Searches included 10 databases and trial registers as well as conference proceedings (January 2014). Randomised controlled trials that assessed the effects of oral H1 antihistamines as monotherapy in children and adults with eczema were included. Results Our searches retrieved 757 references, but no randomised controlled trial met our inclusion criteria. Most studies allowed concomitant treatments, making the assessment of the individual effects of oral H1 antihistamines impossible. Conclusions There is currently no high-level evidence to support or refute the efficacy or safety of oral H1 antihistamines used as monotherapy for eczema. A further review of studies that assesses the effects of oral H1 antihistamines as ‘add-on’ therapy together with concomitant treatments is warranted to determine the beneficial effects of this group of medications in the treatment of eczema. PMID:24625301

Not in My Navy. A Legal Guide to Drug Abuse.

DTIC Science & Technology

1984-06-01

opiates produces drowsiness, sleep, and a reduction in physical activity. Side effects can include nausea and vomiting, constipation, itching, flushing...diarrhea, pallor, and dilation of the pupils. Such effects are generally seen only with high doses or as occasional side effects with therapeutic doses...that will produce low-level side effects . or, a person might be drowsy from ingesting a nonprescription product - such as an antihistamine. A clue to

Antagonism of the effects of tremorine by tropine derivatives

PubMed Central

Farquharson, Muriel E.; Johnston, R. G.

1959-01-01

Methods of testing new drugs for anti-Parkinson activity are briefly reviewed. The production in animals of Parkinson-like effects by Tremorine (1,4-dipyrrolidin-1'-ylbut-2-yne), and the inhibition of these effects in mice by a number of tropine derivatives, are described. No correlation was found between the activity against tremor and the anticholinergic, antihistaminic or local anaesthetic properties of the compounds. PMID:13821613

Critical appraisal of bilastine for the treatment of allergic rhinoconjunctivitis and urticaria.

PubMed

Sadaba, Belen; Azanza, Jose Ramon; Gomez-Guiu, Almundena; Rodil, Raquel

2013-01-01

Bilastine is a second generation antihistamine indicated for the treatment of seasonal or perennial allergic rhinoconjunctivitis and chronic urticaria with a daily dose of 20 mg, in adults and children over 12 years of age. The efficacy of bilastine has been shown to be similar to that of the comparator drugs for the control of the nasal and nonnasal symptoms of allergic rhinoconjunctivitis, while also showing a subjective improvement in the quality of life and in overall clinical impression. For chronic urticaria the symptoms (itching and the development of papules) lessens from the second day of treatment onwards, in a similar way to other antihistamines used as comparators. Bilastine should not be administered at meal times to avoid interference with the absorption process. It is not distributed to the central nervous system, is scarcely metabolized, and elimination is through the kidneys and feces, with a 14-hour elimination half-life. It has no effect on cytochrome P450. During clinical development, bilastine was shown to be a drug that is adequately tolerated, with a similar effect to placebo with regard to drowsiness and changes in heart rate. In relation to its use, headaches were the most frequent adverse effect to be reported. No cardiotoxic effects have been observed, and the therapeutic dose does not alter the state of alertness.

Antihistamines and Birth Defects: A Systematic Review of the Literature

PubMed Central

Gilboa, Suzanne M.; Ailes, Elizabeth C.; Rai, Ramona P.; Anderson, Jaynia A.; Honein, Margaret A.

2015-01-01

Introduction Approximately 10-15% of women reportedly take an antihistamine during pregnancy for the relief of nausea and vomiting, allergy and asthma symptoms, or indigestion. Antihistamines include histamine H1-receptor and H2-receptor antagonists. Areas covered This is a systematic evaluation of the peer-reviewed epidemiologic literature published through February 2014 on the association between prenatal exposure to antihistamines and birth defects. Papers addressing histamine H1- or H2-receptor antagonists are included. Papers addressing pyridoxine plus doxylamine (Bendectin in the United States, Debendox in the United Kingdom, Diclectin in Canada, Lenotan and Merbental in other countries) prior to the year 2001 were excluded post-hoc because of several previously published meta-analyses and commentaries on this medication. Expert opinion The literature on the safety of antihistamine use during pregnancy with respect to birth defects is generally reassuring though the positive findings from a few large studies warrant corroboration in other populations. The findings in the literature are considered in light of three critical methodological issues: (1) selection of appropriate study population; (2) ascertainment of antihistamine exposures; and (3) ascertainment of birth defects outcomes. Selected antihistamines have been very well-studied (e.g. loratadine); others, especially H2- receptor antagonists, require additional study before an assessment of safety with respect to birth defects risk could be made. PMID:25307228

Antinauseants in Pregnancy: Teratogens or Not?

PubMed Central

Biringer, Anne

1984-01-01

Nausea and/or vomiting affect 50% of all pregnant women. For most women, this is a self-limited problem which responds well to conservative management. However, there are some situations where the risk to the mother and fetus posed by the illness are greater than the possible risks of teratogenicity of antinauseant drugs. Antihistamines have had the widest testing, and to date, there has been no evidence linking doxylamine, dimenhydrinate or promethazine to congenital malformations. Since no available drugs have official approval for use in nausea and vomiting of pregnancy the physician is left alone to make this difficult decision. PMID:21279128

Antihistamines and driving safety.

PubMed

O'Hanlon, J F

1988-10-27

The results of two placebo-controlled driving performance studies confirm laboratory data showing that the nonsedating antihistamine terfenadine does not influence the driving performance of users. The amplitude of vehicle weaving calculated for drivers who received this agent did not differ from control values. Neither terfenadine nor loratadine, another nonsedating antihistamine, potentiated the adverse effects of alcohol on driving performance.

Evaluating approved medications to treat allergic rhinitis in the United States: an evidence-based review of efficacy for nasal symptoms by class.

PubMed

Benninger, Michael; Farrar, Judith R; Blaiss, Michael; Chipps, Bradley; Ferguson, Berrylin; Krouse, John; Marple, Bradley; Storms, William; Kaliner, Michael

2010-01-01

To evaluate how well the medications currently approved in the United States for allergic rhinitis (AR) treat nasal symptoms when examined according to Food and Drug Administration-indicated uses and dosages. MEDLINE (1966 onward), EMBASE (1974 onward), and the Cochrane Library (2007) were systematically searched according to the following criteria defined at a roundtable meeting of the authors: randomized controlled trial, at least a 2-week duration, and approved indication and dosage in the United States. Data from studies that met the inclusion criteria were extracted into evidence tables, which were reviewed twice by the full panel of authors. Individual panel members also were asked to comment on abstracts, articles, and summary tables based on their known expertise. The entire faculty approved the selection of studies included in this review. Fifty-four randomized, placebo-controlled studies involving more than 14,000 adults and 1,580 children with AR met the criteria for review: 38 studies of seasonal allergic rhinitis (SAR; n = 11,980 adults and 946 children) and 12 studies of perennial allergic rhinitis (PAR; n = 3,800 adults and 366 children). The median percentage changes from baseline for total nasal symptom score for SAR were as follows: nasal antihistamines, -22.2%; oral antihistamines, -23.5%; intranasal steroids (INSs), -40.7%; and placebo, -15.0%. For PAR, the changes were as follows: oral antihistamines, -51.4%; INSs, -37.3%; and placebo, -24.8%. Data for mediator antagonists were limited. The data, although limited, confirm that INSs produce the greatest improvements in nasal symptoms in patients with SAR. In addition, INSs are effective for PAR, but the data were of variable quality, and oral antihistamines may be equally effective for some patients. The reporting of published data should be standardized to permit better comparisons in future studies.

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

PubMed

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

2001-01-01

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

Interactions of bilastine, a new oral H₁ antihistamine, with human transporter systems.

PubMed

Lucero, Maria Luisa; Gonzalo, Ana; Ganza, Alvaro; Leal, Nerea; Soengas, Itziar; Ioja, Eniko; Gedey, Szilvia; Jahic, Mirza; Bednarczyk, Dallas

2012-06-01

Membrane transporters play a significant role in facilitating transmembrane drug movement. For new pharmacological agents, it is important to evaluate potential interactions (e.g., substrate specificity and/or inhibition) with human transporters that may affect their pharmacokinetics, efficacy, or toxicity. Bilastine is a new nonsedating H₁ antihistamine indicated for the treatment of allergic rhinoconjunctivitis and urticaria. The in vitro inhibitory effects of bilastine were assessed on 12 human transporters: four efflux [multidrug resistance protein 1 (MDR1) or P-glycoprotein, breast cancer resistance protein (BCRP), multidrug resistance associated protein 2 (MRP2), and bile salt export pump) and eight uptake transporters (sodium taurocholate cotransporting polypeptide, organic cation transporter (OCT)1, organic anion transporter (OAT)1, OAT3, OCT2, OATP2B1, OATP1B1, and OATP1B3). Only mild inhibition was found for MDR1-, OCT1-, and OATP2B1-mediated transport of probe substrates at the highest bilastine concentration assayed (300 μM; half-maximal inhibitory concentration: ≥300 μM). Bilastine transport by MDR1, BCRP, OAT1, OAT3, and OCT2 was also investigated in vitro. Only MDR1 active transport of bilastine was relevant, whereas it did not appear to be a substrate of OCT2, OAT1, or OAT3, nor was it transported substantially by BCRP. Drug-drug interactions resulting from bilastine inhibition of drug transporters that would be generally regarded as clinically relevant are unlikely. Additionally, bilastine did not appear to be a substrate of human BCRP, OAT1, OAT3, or OCT2 and thus is not a potential victim of inhibitors of these transporters. On the other hand, based on in vitro evaluation, clinically relevant interactions with MDR1 inhibitors are anticipated.

The efficacy of cetirizine hydrochloride on the pruritus of cats with atopic dermatitis: a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Wildermuth, Kerstin; Zabel, Sonja; Rosychuk, Rod A W

2013-12-01

Various antihistamines have been used in the management of feline atopic dermatitis, with variable reported benefit. To date, there have been no randomized, double-blind, placebo-controlled, crossover clinical trials on the use of this drug class in cats. To evaluate the clinical efficacy of cetirizine hydrochloride for the control of pruritus and dermatitis in cats diagnosed with atopic dermatitis. In this randomized, double-blind, placebo-controlled crossover clinical trial, 21 client-owned cats diagnosed with mild to moderate nonseasonal atopic dermatitis were randomly assigned to two groups. Cats in each group received either 1 mg/kg cetirizine hydrochloride or placebo once daily per os for 28 days followed by a 14 day wash-out period. Treatments were then crossed over, and cats received placebo or cetirizine hydrochloride for another 28 days. Owners marked a pruritus severity scale before inclusion in the study and weekly throughout the entire study period. Lesions were scored by the clinician using a Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03 modified for the cat before enrolment and at day 28 of each treatment. Nineteen cats completed the study. There were no statistically significant differences between treatment with cetirizine hydrochloride and placebo for modified CADESI-03 or pruritus scores. This study suggests that cetirizine hydrochloride cannot be recommended for the management of feline atopic dermatitis. © 2013 ESVD and ACVD.

[Socio-economic impact of allergic rhinitis and perspectives of appropriate therapy].

PubMed

May, Uwe

2014-07-24

Allergic rhinitis is a very common disease that causes high economic costs. Furthermore inadequate treatment can lead to bronchial asthma. Against this background, drugs for the treatment of allergic rhinitis should be evaluated from a comprehensive medical-economic perspective. The new combination of an antihistamine and a corticosteroid, introduced in the market in 2013, emerges as useful pharmaceutical alternative, both with regard to the medical outcome parameters as well as cost-effectiveness.

First-Generation H1 Antihistamines Found in Pilot Fatalities of Civil Aviation Accidents, 1990-2005

DTIC Science & Technology

2007-05-01

ephedrine, paroxetine, phenylpropanolamine, pseudoephedrine , quinine, and/or tetrahydrocannabinol carboxylic acid—were also present in the fatalities...antihistamine (Table II). Chlorpheniramine, ephedrine, phenylpropanolamine, and pseudoephedrine were also detected in one case and pheniramine and...detected in both cases and pseudoephedrine in 1. Blood was not available in either case. Pheniramine: This antihistamine was found in just 1 fatality

Antihistamine Pretreatment to Reduce Incidence of Withdrawal Movement After Rocuronium Injection

PubMed Central

Lee, Ho Jun; Han, Sung Jin; Kim, Heezoo; Lee, Il Ok; Kong, Myoung Hoon; Kim, Nan Suk; Lim, Sang Ho

2009-01-01

The purpose of this study was to determine the effectiveness of antihistamine therapy for withdrawal movements caused by rocuronium injection. One hundred seventy one ASA I-II adults undergoing elective surgery were randomly assigned to one of two groups. Patients in the control group (Group C) were premedicated with 2 mL normal saline, and those in the antihistamine group (Group A) were pre-medicated with 2 mL (45.5 mg) pheniramine maleate. After the administration of thiopental sodium 5 mg/kg, rocuronium 0.6 mg/kg was injected. Withdrawal movements were assessed using a four-grade scale. The administration of antihistamine reveals lower grade of withdrawal movement after rocuronium injection. PMID:19794987

Updosing of Nonsedating Anti-histamines in Recalcitrant Chronic Urticaria

PubMed Central

Godse, Kiran; Bhattar, Prachi; Patil, Sharmila; Nadkarni, Nitin; Gautam, Manjyot

2016-01-01

Chronic urticaria (CU) is a persistent, debiliating condition that causes severe impairment on the quality of life (QoL) of patient by interrupting work productivity. Current guidelines recommend second-generation (nonsedating) anti-histamines for the treatment for all forms of urticaria. In patients who do not respond adequately to conventional doses of anti-histamines, it is recommended to increase the dose to up to four times to obtain control. But there are only few controlled studies that have assessed the efficacy and safety of nonsedating anti-histamines. Though sedating histamines are frequently used as an add-on therapy in severe cases, they have a negative impact on QoL by compromising sleep and performance. The use of other suggested therapeutic options (omalizumab, cyclosporine A, montelukast and dapsone) is also limited by paucity of data on their efficacy and adverse effect profile. Second-generation anti-histamines which are relatively safer require more proven data to support their judicious use to improve disease in patients with CU. PMID:27293247

Chronic Spontaneous Urticaria: Pathogenesis and Treatment Considerations.

PubMed

Kaplan, Allen P

2017-11-01

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

Critical appraisal of bilastine for the treatment of allergic rhinoconjunctivitis and urticaria

PubMed Central

Sadaba, Belen; Azanza, Jose Ramon; Gomez-Guiu, Almundena; Rodil, Raquel

2013-01-01

Bilastine is a second generation antihistamine indicated for the treatment of seasonal or perennial allergic rhinoconjunctivitis and chronic urticaria with a daily dose of 20 mg, in adults and children over 12 years of age. The efficacy of bilastine has been shown to be similar to that of the comparator drugs for the control of the nasal and nonnasal symptoms of allergic rhinoconjunctivitis, while also showing a subjective improvement in the quality of life and in overall clinical impression. For chronic urticaria the symptoms (itching and the development of papules) lessens from the second day of treatment onwards, in a similar way to other antihistamines used as comparators. Bilastine should not be administered at meal times to avoid interference with the absorption process. It is not distributed to the central nervous system, is scarcely metabolized, and elimination is through the kidneys and feces, with a 14-hour elimination half-life. It has no effect on cytochrome P450. During clinical development, bilastine was shown to be a drug that is adequately tolerated, with a similar effect to placebo with regard to drowsiness and changes in heart rate. In relation to its use, headaches were the most frequent adverse effect to be reported. No cardiotoxic effects have been observed, and the therapeutic dose does not alter the state of alertness. PMID:23667312

Systemic Contact Dermatitis.

PubMed

Aquino, Marcella; Rosner, Greg

2018-05-15

Systemic contact dermatitis (SCD) traditionally refers to a skin condition where an individual who is cutaneously sensitized to an allergen will subsequently react to that same allergen or a cross reacting allergen via a different route. It occurs to allergens including metals, medications, and foods. The exact pathophysiology underlying this disease remains unknown, although it appears to be mediated by type 4 hypersensitivity reactions and possibly type 3 hypersensitivity reactions. The p-I concept (pharmacologic interaction with immunoreceptors) hypothesized that drugs are able to bind directly to a T cell receptor without first being presented by MHC (major histocompatibility complex) molecules and without prior metabolism, which would help explain why SCD can be seen on first exposure to medications. Nomenclature remains a challenge as SCD can be subcategorized using terms such as ACDS (allergic contact dermatitis syndrome) and its four clinical stages, Baboon syndrome, and SDRIFE (symmetrical drug-related intertriginous and flexural exanthema), which share many overlapping features. Food allergens may be responsible for uncontrolled or persistent symptoms in patients with contact dermatitis who do not respond to topical avoidance. With medications, symptoms may be induced by topical application versus systemic administration. Patch testing (PT) may be beneficial in diagnosing SCD caused by metals and many topical medications including corticosteroids, antimicrobials (ampicillin, bacitracin, erythromycin, neomycin, nystatin), NSAIDs (diclofenac, ibuprofen), anesthetics, and antihistamines (chlorphenamine, piperazine). Current treatment options include topical steroids and oral antihistamines for symptom relief and dietary avoidance to causative foods or metals.

Over-the-counter medicines

MedlinePlus

... throat lozenges can be soothing. Be careful in young children because of the choking risk. ALLERGIES Antihistamine pills and liquids work well for treating allergy symptoms . Antihistamines that may ...

[Analysis of the Cochrane Review: Antihistamines for the Common Cold. Cochrane Database Syst Rev. 2015;11:CD009345].

PubMed

Sterrantino, Carmel; Duarte, Gonçalo; Costa, João; Vaz-Carneiro, António

2016-03-01

The common cold is an acute, self-limiting inflammation of the mucosa of the upper airways, which may involve one or all the sinuses, nasopharynx, oropharynx and larynx. It is common to have at least one episode per year. Common cold symptoms, which may include sore throat, sneezing, nasal congestion, runny nose, headache, malaise and mild fever usually disappear within a few days without treatment. The causative agent of most colds is rhinovirus. Although not associated with mortality, common cold is associated with significant morbidity. There is no vaccine or cure for common cold and, therefore, their treatment is centered on relieving the symptoms. This Cochrane review aimed to synthesize the existing evidence about the clinical benefit of antihistamines, used as monotherapy, compared with placebo or no treatment in children and adult patients with common cold. A total of 18 randomized clinical trials with 4342 participants were included. Main results were: 1) Antihistamines have a small (days one and two) beneficial effect in the short term on the severity of overall symptoms in adult patients, although this effect is not present in the medium to long term; 2) antihistamines were not associated with a clinically significant beneficial effect on the individual symptoms (nasal congestion, rhinorrhea, and sneezing); 3) Antihistamines are not associated with an increased risk of adverse effects; 4) No conclusion can be made about the effectiveness of antihistamines in pediatric populations. Our interpretation of the results is that the available evidence is insufficient to support the prescription or buying OTC antihistamines to relieve the symptoms of common cold without allergic component.

Antihistamine Use in Early Pregnancy and Risk of Birth Defects

PubMed Central

Li, Qian; Mitchell, Allen A.; Werler, Martha M.; Yau, Wai-Ping; Hernández-Díaz, Sonia

2014-01-01

Background Several studies have reported an association between use of specific antihistamines in early pregnancy and certain specific birth defects. Objective To test 16 previously-hypothesized associations between specific antihistamines and specific birth defects, and identify possible new associations. Methods We used 1998-2010 data from the Slone Epidemiology Center Birth Defects Study, a multicenter case-control surveillance program of birth defects in North America. Mothers were interviewed within six months of delivery about demographic, reproductive, medical, and behavioral factors, and details on use of prescription and non-prescription medications. We compared 1st trimester exposure to specific antihistamines between 13,213 infants with specific malformations and 6,982 non-malformed controls, using conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders, including indication for use. Results Overall, 13.7% of controls were exposed to antihistamines during the 1st trimester. The most commonly-used medications were diphenhydramine (4.2%), loratadine (3.1%), doxylamine (1.9%), and chlorpheniramine (1.7%). Where estimates were stable, none supported the previously-hypothesized associations. Among over 100 exploratory comparisons of other specific antihistamine/defect pairs, 14 had ORs ≥1.5 of which 6 had 95% CI bounds excluding 1.0 before but not after adjustment for multiple comparisons. Conclusion Our findings do not provide meaningful support for previously-posited associations between antihistamines and major congenital anomalies; at the same time, we identified associations that had not been previously suggested. We suspect that previous associations may be chance findings in the context of multiple comparisons, a situation which may also apply to our new findings. PMID:24565715

Efficacy and safety of desloratadine/pseudoephedrine combination vs its components in seasonal allergic rhinitis.

PubMed

Grubbe, R E; Lumry, W R; Anolik, R

2009-01-01

Antihistamines are first-line therapy for the treatment of seasonal allergic rhinitis (AR); however, an oral decongestant is often added to improve control of nasal congestion. To examine whether a tablet combining the nonsedating antihistamine desloratadine and the decongestant pseudoephedrine was more effective than either drug administered alone in reducing the symptoms of seasonal AR, including nasal congestion. In this multicenter, double-blind study, participants (N = 598) with symptomatic seasonal AR were administered either a combination tablet of desloratadine 2.5 mg/pseudoephedrine 120 mg (DL/PSE) bid, a desloratadine 5.0 mg qd and a placebo tablet, or pseudoephedrine 120 mg bid. Participants assessed their symptom severity twice daily over the 2-week treatment period. The primary variable to assess the effects of the antihistamine component--mean change from baseline in average AM/PM reflective total symptom score (TSS), excluding nasal congestion--was significantly greater (-6.54) for DL/PSE than for desloratadine (-5.09) or pseudoephedrine (-5.07) monotherapy (P < .001 for both). The primary variable to assess the effects of the decongestant component--mean change from baseline in average AM/PM reflective nasal congestion score--was also significantly greater (-0.93) for DL/PSE than for desloratadine (-0.66) or pseudoephedrine (-0.75) (P < .001 vs desloratadine; P = .006 vs pseudoephedrine). This study demonstrated that DL/PSE therapy was more effective in reducing symptoms of seasonal AR, including nasal congestion, than the individual components when administered alone, thus supporting use of this combination in participants with symptomatic seasonal AR and prominent nasal congestion.

Separation of pharmacologically active nitrogen-containing compounds on silica gels modified with 6,10-ionene, dextran sulfate, and gold nanoparticles

NASA Astrophysics Data System (ADS)

Ioutsi, A. N.; Shapovalova, E. N.; Ioutsi, V. A.; Mazhuga, A. G.; Shpigun, O. A.

2017-12-01

New stationary phases for HPLC are obtained via layer-by-layer deposition of polyelectrolytes and studied: (1) silica gel modified layer-by-layer with 6,10-ionene and dextran sulfate (Sorbent 1); (2) silica gel twice subjected to the above modification (Sorbent 2); and (3) silica gel modified with 6,10-ionene, gold nanoparticles, and dextran sulfate (Sorbent 3). The effect the content of the organic solvent in the mobile phase and the concentration and pH of the buffer solution have on the chromatographic behavior of several pharmacologically active nitrogen-containing compounds is studied. The sorbents are stable during the process and allow the effective separation of beta-blockers, calcium channel blockers, alpha-agonists, and antihistamines. A mixture of caffeine, nadolol, tetrahydrozoline, pindolol, orphenadrine, doxylamine, carbinoxamine, and chlorphenamine is separated in 6.5 min on the silica gel modified with 6,10-ionene, gold nanoparticles, and dextran sulfate.

Mechanisms of Radiation-Induced Conditioned Taste Aversion Learning

DTIC Science & Technology

1986-01-01

to Walter A. Hunt. 86 4 21 144 . J Jr -.W U *’ = 7 . 7 .: M: W. ,WLW;i , .-, -’ .’P. %k T .- - ’ .: ’W ; .a --,.-" -. t .:-. , 56 RABIN AND HUNT can...8217. 7m. U RADIATION-INDUCED TASTE AVERSIONS 57 induced CTA 11021. Alternatively, when the antihistamine is [ 21 . A radiation-induced CTA can be...in rats. Pharmmad psychioactive drugs. J (omp Phvsiod Pvchld .;’: 21 -26. 1972. Biochem Behav 17: 305-311. 1982. 4. Berger. B. D.. C. D. Wise and L

Antihistamines for allergies

MedlinePlus

... care provider what type of antihistamine and what exact dosage is right for you or your child. ... must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get ...

Evolving paradigm in the management of allergic rhinitis-associated ocular symptoms: role of intranasal corticosteroids.

PubMed

Blaiss, Michael S

2008-03-01

Along with nasal symptoms, ocular symptoms such as itching, tearing, and redness are common, bothersome components of the allergic rhinitis (AR) profile. Treatment of the patient with ocular allergy symptoms should take into account a variety of factors, including severity of symptoms, convenience/compliance issues, and patient preferences. To review from the primary care perspective the epidemiology, pathophysiology, and management of ocular symptoms associated with AR, and to evaluate the emerging role of intranasal corticosteroids (INSs). A search of the PubMed database identified clinical trials that assessed efficacy of agents in reducing ocular allergy symptoms. Internet searches identified further information including data on over-the-counter agents for treatment of ocular symptoms. Searches were conducted using search terms such as pathophysiology, epidemiology, ocular allergy, quality of life, drug class, and drug names. Primary care physicians are often the first point of contact for patients with seasonal AR (SAR) or perennial AR (PAR) symptoms. Ocular allergy associated with SAR and PAR (seasonal and perennial allergic conjunctivitis, respectively) is characterized by both early- and late-phase reactions, with symptoms often persisting long after allergen exposure. Non-pharmacologic measures such as allergen avoidance, use of artificial tears, and cool compresses are pertinent for all ocular allergy sufferers, but may not afford adequate symptom control. Pharmacotherapy options have traditionally included topical ophthalmic products for cases of isolated ocular symptoms, and oral antihistamines for patients with both nasal and ocular symptoms. However, this paradigm is changing with new evidence regarding the efficacy of INSs in reducing ocular symptoms. A number of meta-analyses and individual studies, most of which studied ocular symptoms as secondary variables, have demonstrated the ocular effects of INSs versus topical and oral antihistamines. Additional prospective studies on this topic are encouraged to provide further evidence for these findings. In light of their well-established efficacy in reducing nasal allergy symptoms, INSs offer a comprehensive treatment option in patients with nasal and ocular symptoms. Oral antihistamines and/or topical eye drops may also be necessary depending on symptom control.

Investigational new drugs for allergic rhinitis.

PubMed

Ricketti, Peter A; Alandijani, Sultan; Lin, Chen Hsing; Casale, Thomas B

2017-03-01

Allergic rhinitis (AR) is a multifactorial disease characterized by paroxysmal symptoms of sneezing, rhinorrhea, postnasal drip and nasal congestion. For over a century, subcutaneous allergen immunotherapy (SCIT) has been recognized as the most effective therapy to date that may modify the underlying disease course and provide long-term benefits for individuals refractory to pharmacotherapy. However, over the past 25 years, there has been substantial growth in developing alternative therapies to traditional SCIT. Areas covered: This article will review the most current literature focusing on advancements of AR therapies. Novel AR therapies that are currently under investigation include: the addition of omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody (mAb), to SCIT; altering the method of delivery of allergen immunotherapy (AIT) including sublingual (SLIT), epicutaneous (EIT), intralymphatic (ILIT), intranasal (INIT) and oral mucosal immunotherapy (OMIT); use of capsaicin spray; novel H3 and H4 antihistamines; activation of the innate immune system through Toll-like receptor agonists; and the use of chemically altered allergens, allergoids, recombinant allergens and relevant T-cell epitope peptides to improve the efficacy and safety of AIT. Expert opinion: These promising novel therapies may offer more effective and/or safer treatment options for AR patients, and in some instances, induce immunologic tolerance.

Hydroxychloroquine-induced erythroderma.

PubMed

Pai, Sunil B; Sudershan, Bhuvaneshwari; Kuruvilla, Maria; Kamath, Ashwin; Suresh, Pooja K

2017-01-01

Erythroderma is characterized by diffuse erythema and scaling of the skin involving more than 90% of the total body skin surface area. Drug-induced erythroderma has rarely been reported with hydroxychloroquine. We report a case of a 50-year-old female patient, with systemic lupus erythematosus, who developed itchy lesions all over the body 1 month after starting treatment with hydroxychloroquine. Drug-induced erythroderma was suspected. Hydroxychloroquine was withdrawn and the patient was treated with emollients, mid-potency corticosteroids, and oral antihistamines. A biopsy was done which confirmed the diagnosis of erythroderma. She recovered with treatment and was discharged. A careful history and clinical examination to search for potential causative factors will help prevent disabling sequelae in erythroderma.

Hydroxychloroquine-induced erythroderma

PubMed Central

Pai, Sunil B.; Sudershan, Bhuvaneshwari; Kuruvilla, Maria; Kamath, Ashwin; Suresh, Pooja K.

2017-01-01

Erythroderma is characterized by diffuse erythema and scaling of the skin involving more than 90% of the total body skin surface area. Drug-induced erythroderma has rarely been reported with hydroxychloroquine. We report a case of a 50-year-old female patient, with systemic lupus erythematosus, who developed itchy lesions all over the body 1 month after starting treatment with hydroxychloroquine. Drug-induced erythroderma was suspected. Hydroxychloroquine was withdrawn and the patient was treated with emollients, mid-potency corticosteroids, and oral antihistamines. A biopsy was done which confirmed the diagnosis of erythroderma. She recovered with treatment and was discharged. A careful history and clinical examination to search for potential causative factors will help prevent disabling sequelae in erythroderma. PMID:28458440

Survey of colourings and preservatives in drugs.

PubMed Central

Pollock, I.; Young, E.; Stoneham, M.; Slater, N.; Wilkinson, J. D.; Warner, J. O.

1989-01-01

OBJECTIVE--To assess the prevalence of colourings and preservatives in drug formulations in the United Kingdom. DESIGN--Postal survey. PARTICIPANTS--All pharmaceutical manufacturers in the United Kingdom were requested to supply data on drug formulations with particular regard to the content of colourings and preservatives. MAIN OUTCOME MEASURE--Prevalence in proprietary drugs of colourings or preservatives, or both, that have been implicated in adverse reactions. Computation of a list of formulations of bronchodilators, antihistamines, and antibiotics that are free of such additives. RESULTS--A total of 118 out of 120 pharmaceutical companies supplied the data requested. In all, 2204 drug formulations were analysed and found to contain 419 different additives, of which 52 were colourings and preservatives that have been implicated in adverse reactions; 930 formulations contained such an additive. Tartrazine was the fourth most commonly occurring colouring, being present in 124 drug formulations. CONCLUSION--Many drugs contain additives that help to identify them and prolong their shelf life but are implicated in adverse reactions in some people. Some form of labelling of drug additives would enable these people to avoid drugs containing such additives. PMID:2508849

Bilastine as a potential treatment in allergic rhinitis.

PubMed

Kowal, Krzysztof; DuBuske, Lawrence

2014-01-01

Allergic rhinitis is a very frequent disease. H1 antihistamines have been used for treatment of allergic rhinitis for more than 5 decades. They differ in chemical structure, pharmacokinetics, pharmacodynamics, clinical efficacy and adverse effects. We performed a detailed analysis of all available publications concerning the new H1-antihistamine bilasitine. Bilastine, a piperidine derivative, is a novel potent H1 antihistamine. It is at least as potent as cetirizine or fexofenadine in in vitro studies. In animal studies it demonstrates dose-dependent antihistaminic and antiallergic effects. In humans its metabolism is not affected by age, gender or renal function but may be affected by coadministration of P glycoprotein inhibitors. Efficacy of bilastine in therapy of allergic rhinitis patients has been documented in several large controlled clinical trials showing bilastine being at least as effective as cetirizine or desloratadine. No significant suppressive effect on central nervous system could be demonstrated when bilastine was used in the recommended doses. Bilastine is a novel H1 antihistamine with anti-allergic properties which is highly effective in the treatment of symptoms of allergic rhinitis. It has a favorable pharmacokinetic and pharmacodynamic profile and is generally well tolerated.

Transitioning the second-generation antihistamines to over-the-counter status: a cost-effectiveness analysis.

PubMed

Sullivan, Patrick W; Follin, Sheryl L; Nichol, Michael B

2003-12-01

A U.S. Food and Drug Administration advisory committee deemed the second-generation antihistamines (SGA) safe for over-the-counter use against the preliminary opposition of the manufacturers. As a result, loratadine is now available over-the-counter. First-generation antihistamines (FGA) are associated with an increased risk of unintentional injuries, fatalities, and reduced productivity. Access to SGA over-the-counter could result in decreased use of FGA, thereby reducing deleterious outcomes. The societal impact of transitioning this class of medications from prescription to over-the-counter status has important policy implications. To examine the cost-effectiveness of transitioning SGA to over-the-counter status from a societal perspective. A simulation model of the decision to transition SGA to over-the-counter status was compared with retaining prescription-only status for a hypothetical cohort of individuals with allergic rhinitis in the United States. Estimates of costs and effectiveness were obtained from the medical literature and national surveys. Sensitivity analysis was performed using a second-order Monte Carlo simulation. Discounted, quality-adjusted life-years saved as a result of amelioration of allergic rhinitis symptoms and avoidance of motor vehicle, occupational, public and home injuries and fatalities; discounted direct and indirect costs. Availability of SGA over-the-counter was associated with annual savings of 4 billion dollars (2.4-5.3 billion dollars) or 100 dollars (64-137 dollars) per allergic rhinitis sufferer and 135,061 time-discounted quality-adjusted life years (84,913-191,802). The sensitivity analysis provides evidence in support of these results. Making SGA available over-the-counter is both cost-saving and more effective for society, largely as a result of reduced adverse outcomes associated with FGA-induced sedation. Further study is needed to determine the differential impact on specific vulnerable populations.

Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis

PubMed Central

Schapowal, Andreas

2002-01-01

Objectives To compare the efficacy and tolerability of butterbur (Petasites hybridus) with cetirizine in patients with seasonal allergic rhinitis (hay fever). Design Randomised, double blind, parallel group comparison. Setting Four outpatient general medicine and allergy clinics in Switzerland and Germany. Participants 131 patients were screened for seasonal allergic rhinitis and 125 patients were randomised (butterbur 61; cetirizine 64). Interventions Butterbur (carbon dioxide extract tablets, ZE 339) one tablet, four times daily, or cetirizine, one tablet in the evening, both given for two consecutive weeks. Main outcome measures Scores on SF-36 questionnaire and clinical global impression scale. Results Improvement in SF-36 score was similar in the two treatment groups for all items tested hierarchically. Butterbur and cetirizine were also similarly effective with regard to global improvement scores on the clinical global impression scale (median score 3 in both groups). Both treatments were well tolerated. In the cetirizine group, two thirds (8/12) of reported adverse events were associated with sedative effects (drowsiness and fatigue) despite the drug being considered a non-sedating antihistamine. Conclusions The effects of butterbur are similar to those of cetirizine in patients with seasonal allergic rhinitis when evaluated blindly by patients and doctors. Butterbur should be considered for treating seasonal allergic rhinitis when the sedative effects of antihistamines need to be avoided. What is already known on this topicSeasonal allergic rhinitis (hay fever) is common in countries with temperate climates.Most patients have their symptoms treated for short periods, particularly during peaks in atmospheric pollen countWhat this study addsAfter two weeks, the effects of butterbur and cetirizine were comparable in patients with hay feverButterbur produced fewer sedating effects than cetirizineButterbur should be considered when the sedating effects of antihistamines must be avoided PMID:11799030

Effects of antihistamine on up-regulation of histamine H1 receptor mRNA in the nasal mucosa of patients with pollinosis induced by controlled cedar pollen challenge in an environmental exposure unit.

PubMed

Kitamura, Yoshiaki; Nakagawa, Hideyuki; Fujii, Tatsuya; Sakoda, Takema; Enomoto, Tadao; Mizuguchi, Hiroyuki; Fukui, Hiroyuki; Takeda, Noriaki

2015-11-01

In the present study, we examined the effects of antihistamine on the up-regulation of H1R mRNA in the nasal mucosa of patients with pollinosis induced by controlled exposure to pollen using an environmental exposure unit. Out of 20 patients, we designated 14 responders, whose levels of H1R mRNA in the nasal mucosa were increased after the first pollen exposure and excluded 6 non-responders. Accordingly, the first exposure to pollen without treatment significantly induced both nasal symptoms and the up-regulation of H1R mRNA in the nasal mucosa of the responders. Subsequently, prophylactic administration of antihistamine prior to the second pollen exposure significantly inhibited both of the above effects in the responders. Moreover, the nasal expression of H1R mRNA before the second pollen exposure in the responders pretreated with antihistamine was significantly decreased, as compared with that before the first pollen exposure without treatment. These findings suggest that antihistamines suppressed histamine-induced transcriptional activation of H1R gene in the nasal mucosa, in addition to their blocking effect against histamine on H1R, resulting in a decrease of nasal symptoms. These findings further suggest that by their inverse agonistic activity, antihistamines suppress the basal transcription of nasal H1R in the absence of histamine in responders. Copyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

Chronic urticaria in adults: state-of-the-art in the new millennium*

PubMed Central

Criado, Paulo Ricardo; Criado, Roberta Facchini Jardim; Maruta, Celina Wakisaka; dos Reis, Vitor Manoel Silva

2015-01-01

Chronic urticaria has been explored in several investigative aspects in the new millennium, either as to its pathogenesis, its stand as an autoimmune or auto-reactive disease, the correlation with HLA-linked genetic factors, especially with class II or its interrelation with the coagulation and fibrinolysis systems. New second-generation antihistamines, which act as good symptomatic drugs, emerged and were commercialized over the last decade. Old and new drugs that may interfere with the pathophysiology of the disease, such as cyclosporine and omalizumab have been developed and used as treatments. The purpose of this article is to describe the current state of knowledge on aspects of chronic urticaria such as, pathophysiology, diagnosis and the current therapeutic approach proposed in the literature. PMID:25672302

Urticarial Reactions: Vascular Erythema, Urticaria, Vasculitis

PubMed Central

Sibbald, R. Gary

1987-01-01

Vascular erythemas, including urticaria and vasculitis, represent diagnostic and therapeutic challenges. A careful systemic approach to history and physical examination should be followed by appropriate investigations to rule out systemic disease. Chronic urticaria patients should be physically tested to identify cholinergic, dermagraphic, and cold-induced responses. Food diaries and careful drug history may be important to identify exacerbating factors in chronic urticaria. A skin biopsy is necessary to diagnose vasculitis. Therapy of any underlying cause is supplemented with H1 antihistamines in urticaria patients, while vasculitis requires a different anti-inflammatory approach. PMID:21263956

Antihistamines and driving-related behavior : a review of the evidence for impairment

DOT National Transportation Integrated Search

2004-05-01

A review of the scientific literature concerning the effects of antihistamines on driving-related skills was conducted. After reviewing all pertinent publications from 1998 and earlier, a total of 130 publications were found to meet criteria for incl...

Efficacy of dimetinden and hydroxyzine/chlorpheniramine in atopic dogs: a randomised, controlled, double-blinded trial

PubMed Central

Eichenseer, M.; Johansen, C.; Mueller, R. S.

2013-01-01

Antihistaminic drugs are commonly used as symptomatic therapy of atopic dermatitis in dogs. Unfortunately, their clinical benefit is largely unsubstantiated. In a double-blinded, placebo-controlled, cross-over trial, the influence of dimetinden and of a combination of chlorpheniramine and hydroxyzine on pruritus and lesions was evaluated in 19 dogs. They were treated with either product or a placebo orally for 14 days, each time followed by a 14-day washout period. Before and after each period, the dogs were examined and the Canine Atopic Dermatitis Extent and Severity Index (CADESI) determined by a clinician, and the pruritus and general condition by the owner. Dimetinden improved the pruritus significantly (P=0.014) but not the CADESI (P=0.087), the combination of hydroxyzine and chlorpheniramine improved the CADESI (P=0.049) and pruritus (P=0.05) significantly. Ten of 17 dogs improved by more than 25 per cent in pruritus with the combination of hydroxyzine and chlorpheniramine, 12 of 18 with dimetindenmaleate and only 2 of 19 with placebo. Antihistamines can help to reduce pruritus in atopic dogs, but in most cases, the improvement is limited and additional treatment may be needed. PMID:24114734

[Allergic transfusion reactions in a patient with multiple food allergies].

PubMed

Strobel, E; Schöniger, M; Münz, M; Hiefinger-Schindlbeck, R

2012-07-01

A 13-year-old girl with an osteosarcoma was treated by surgery and chemotherapy. During three transfusions of apheresis platelet concentrates allergic reactions occurred, partly in spite of premedication with an antihistamine and a corticoid. As the patient declared to be allergic to some foods, in-vitro tests for allergen-specific IgE antibodies were performed and showed markedly positive results for specific IgE to carrot and celery, less so to hazelnut, peanut and a lot of other food antigens. The donor of one of the unsuitable platelet concentrates remembered when questioned, that he had eaten carrots and chocolate with hazelnuts during the evening before platelet donation. Two washed platelet concentrates were transfused without any problem. Furthermore, transfusions of nine red blood cell concentrates and one unit of virus-inactivated frozen pooled plasma were well tolerated. Patients should be asked for allergies previous to transfusions to be alert to allergic reactions in patients with a positive history of food or drug allergies. If premedication with antihistamines does not prevent severe allergic transfusion reactions, transfusion of washed platelet concentrates and of virus-inactivated frozen pooled plasma can be considered. © Georg Thieme Verlag KG Stuttgart · New York.

Antihistamines in drivers, aircrew and occupations of risk.

PubMed

Jáuregui, I; Ferrer, M; Montoro, J; Dávila, I; Bartra, J; del Cuvillo, A; Mullol, J; Sastre, J; Valero, A

2013-01-01

The most commonly occurring allergic diseases can involve a daytime drowsiness associated with the condition itself. The antihistamines used in their treatment can also have central effects and affect certain occupations concerned with risk, road safety and maritime and air navigation. Cognitive tests, experimental studies and epidemiological data recommend avoiding 1st generation antihistamines for people who must drive regularly and/or professions concerned with safety. Although there are no comparative studies on real driving between 1st and 2nd generation antihistamines, in this type of patients there should be a preference for prescribing those with least possible central effect, especially those which are a good substrate for transmembrane transporter pumps such as P-glycoprotein and therefore have a low capacity for crossing the hematoencephalic barrier, thus allowing a broader window for therapy. In this sense, bilastine is a good P-glycoprotein substrate and shows good tolerance at CNS level, in both psychometric trials and real driving test protocols, even at double the dose recommended in the technical file.

Separation of drug stereoisomers by the formation of. beta. -cyclodextrin inclusion complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Armstrong, D.W.; Ward, T.J.; Armstrong, R.D.

For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized ..beta..-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as ..beta..-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of ..beta..-cyclodextrin complexes ofmore » propanol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of ..beta..-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiometric drugs. 27 references, 3 figures, 2 tables.« less

Antiallergic effect of ZCR-2060: antihistaminic action.

PubMed

Abe, T; Omata, T; Yoshida, K; Matsumura, T; Ikeda, Y; Segawa, Y; Matsuda, K; Nagai, H

1994-09-01

The antihistaminic effect of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate (ZCR-2060), a newly synthesized antiallergic agent, was investigated in both in vitro and in vivo studies. ZCR-2060 clearly antagonized histamine-induced contraction of isolated guinea pig ileum and trachea. In contrast, carbachol-, BaCl2- and 5-hydroxytryptamine-induced contractions of isolated guinea pig ileum were slightly inhibited by higher concentrations of ZCR-2060. 3H-Mepyramine specific binding to membranes from guinea pig lung and brain were markedly inhibited by ZCR-2060 in a concentration-dependent fashion. In the in vitro studies, the antihistaminic effect of ZCR-2060 was greater than those of cetirizine and terfenadine, but was less than that of ketotifen. In the in vivo studies, ZCR-2060 significantly inhibited the histamine-induced cutaneous reaction in rats, when administered orally 1 hr before the histamine injection. Moreover, ZCR-2060 has a long-lasting antihistaminic effect. In the in vivo studies, the antihistaminic effect of ZCR-2060 was found to be greater than that of cetirizine and terfenadine, and it was the same as that of ketotifen. Thiopental-induced sleep and spontaneous ambulatory activity in mice, however, were unaffected by ZCR-2060 at higher doses. These results indicate that ZCR-2060 has a potent, selective and long acting histamine H1-receptor antagonistic action without causing any unwanted CNS side effect.

Safety and efficacy of bilastine: a new H(1)-antihistamine for the treatment of allergic rhinoconjunctivitis and urticaria.

PubMed

Church, Martin K

2011-09-01

New H(1)-antihistamines should be effective in relieving the symptoms of allergic disease, should have a rapid onset and long duration of action and should neither cause sedation nor interact with cytochrome P450. A review of bilastine was undertaken to determine whether this newer H(1)-antihistamine meets these requirements. A Medline search was conducted to identify preclinical and clinical studies of bilastine. This was supplemented with additional articles or abstracts cited in reference lists and/or obtained from online sources and internal reports supplied by Faes Farma. Review of these data indicated that bilastine has high selectivity for H(1)-receptors, is rapidly and effectively absorbed, undergoes negligible metabolism and is a substrate for P-glycoprotein, which limits its passage across the blood-brain barrier. At the recommended dose of 20 mg, bilastine is non-sedative, does not enhance the effects of alcohol or CNS sedatives, does not impair actual driving tests, shows no cardiotoxicity and has a similar efficacy to other second-generation H(1)-antihistamines in the treatment of allergic rhinoconjunctivitis and urticaria. In view of its favorable pharmacological and clinical characteristics, bilastine is likely to have particular benefit in urticaria for which guidelines recommend increasing the dosage of H(1)-antihistamines up to fourfold if standard dosing is ineffective.

Validated spectroscopic methods for determination of anti-histaminic drug azelastine in pure form: Analytical application for quality control of its pharmaceutical preparations.

PubMed

El-Masry, Amal A; Hammouda, Mohammed E A; El-Wasseef, Dalia R; El-Ashry, Saadia M

2018-02-15

Two simple, sensitive, rapid, validated and cost effective spectroscopic methods were established for quantification of antihistaminic drug azelastine (AZL) in bulk powder as well as in pharmaceutical dosage forms. In the first method (A) the absorbance difference between acidic and basic solutions was measured at 228nm, whereas in the second investigated method (B) the binary complex formed between AZL and Eosin Y in acetate buffer solution (pH3) was measured at 550nm. Different criteria that have critical influence on the intensity of absorption were deeply studied and optimized so as to achieve the highest absorption. The proposed methods obeyed Beer ' s low in the concentration range of (2.0-20.0μg·mL -1 ) and (0.5-15.0μg·mL -1 ) with % recovery±S.D. of (99.84±0.87), (100.02±0.78) for methods (A) and (B), respectively. Furthermore, the proposed methods were easily applied for quality control of pharmaceutical preparations without any conflict with its co-formulated additives, and the analytical results were compatible with those obtained by the comparison one with no significant difference as insured by student's t-test and the variance ratio F-test. Validation of the proposed methods was performed according the ICH guidelines in terms of linearity, limit of quantification, limit of detection, accuracy, precision and specificity, where the analytical results were persuasive. Copyright © 2017 Elsevier B.V. All rights reserved.

The safety issues and hardware-related complications of deep brain stimulation therapy: a single-center retrospective analysis of 478 patients with Parkinson’s disease

PubMed Central

Zhang, Jing; Wang, Tao; Zhang, Chen-cheng; Zeljic, Kristina; Zhan, Shikun; Sun, Bo-min; Li, Dian-you

2017-01-01

Introduction Deep brain stimulation (DBS) is a well-established therapy for the treatment of advanced Parkinson’s disease (PD) in patients experiencing motor fluctuations and medication-refractory tremor. Despite the relative tolerability and safety of this procedure, associated complications and unnatural deaths are still unavoidable. Methods In this study, hardware-related complications and the causes of unnatural death were retrospectively analyzed in 478 patients with PD who were treated with DBS. Results The results showed a 3-year survival rate of 98.6% and a 5-year survival rate of 96.4% for patients with PD who underwent DBS treatment at the study center. Pneumonia was the cause of death with the highest frequency. Prophylactic antibiotics and steroids or antihistamine drugs were adopted to reduce the risk of infection. Twenty-two patients (4.6%) experienced hardware-related complications. Conclusion Deaths of PD patients who receive DBS are typically unrelated to the disease itself or complications associated with the surgery. Pneumonia, malignant tumors, asphyxia, and multiple-organ failure are the common causes of death. Swallowing-related problems may be the most important clinical symptom in late-stage PD, as they cannot be stabilized or improved by DBS alone, and are potentially lethal. Although prophylactic antibiotics and steroids or antihistamine drugs may reduce the risk of infection, it is imperative to identify high-risk patients for whom a therapeutic approach not requiring an implantable device is more suitable, for example, pallidotomy and potentially transcranial ultrasound. PMID:28652714

If 'atypical' neuroleptics did not exist, it wouldn't be necessary to invent them: perverse incentives in drug development, research, marketing and clinical practice.

PubMed

Charlton, Bruce G

2005-01-01

Perverse incentives in drug development, research, marketing and clinical usage can be illustrated by considering the example of the so-called 'atypical' neuroleptics which have grown to become a standard - indeed expanding - part of psychiatric practice despite their probable inferiority to older sedative agents. There is now ample evidence to suggest that neuroleptics (aka. anti-psychotics and major tranquillizers) are dangerous drugs, and patients' exposure to them should be minimized wherever possible. This clinical imperative applies whether neuroleptics are of the traditional type or atypical variety, albeit for different reasons since the traditional agents are neurotoxic, while atypicals are mainly metabolic poisons. Usage of traditional neuroleptics seems indeed to be declining progressively, but the opposite seems to be happening for 'atypicals', and new indications for these drugs are being promoted. Yet the atypical neuroleptics are a category of pharmaceuticals which are close to being un-necessary since there are safer, cheaper and pleasanter substitutes, such as benzodiazepines and the sedative antihistamines (e.g. promethazine). If 'atypical' neuroleptics did not exist, it would not be necessary to invent them. Analysis of how such expensive, dangerous and inferior drugs as the 'atypicals' have nevertheless come to dominate clinical practice casts light on the perverse incentives which now motivate the pharmaceutical industry in an era of massive state regulation. The lack of positive incentives to deploy off-patent drugs is longstanding, but there is a new disincentive in the widespread but erroneous belief that only randomized controlled trials (RCTs) can provide valid 'evidence' of effectiveness. Consequently, those who control RCTs now control clinical practice. It sometimes makes commercial sense to develop and market new drugs that are inferior to existing agents, since new drugs are patent-protected and can be promoted on the back of a mass of new RCTs funded and 'owned' by the pharmaceutical corporations. The current regulatory and patenting situation, therefore, requires major reform if drug efficacy and patient safety are to become higher priorities. Given that psychiatric practice is apparently 'locked-in' to prescribing atypicals, and if (as seems likely) most informed individuals would wish to avoid neuroleptics for themselves and their loved-ones except as a last resort; then in the short-term it may be wise for patients and their families to explore the possibilities of increased self-management of psychiatric problems using over-the-counter drugs, such as the sedative antihistamines. In the long-term, there need to be legal reforms to change the regulatory and commercial framework of incentives relating to drug development. These might include new forms of short-term re-patenting of old drugs.

Synthesis of Structurally Diverse 2,3-Fused Indoles via Microwave-Assisted AgSbF6-Catalysed Intramolecular Difunctionalization of o-Alkynylanilines

PubMed Central

Huang, Yuanqiong; Yang, Yan; Song, Hongjian; Liu, Yuxiu; Wang, Qingmin

2015-01-01

2,3-Fused indoles are found in numerous natural products and drug molecules. Although several elegant methods for the synthesis of this structural motif have been reported, long reaction times and harsh conditions are sometimes required, and the yields tend to be low. Herein, we report a microwave method for straightforward access to various types of 2,3-fused indoles via AgSbF6-catalysed intramolecular difunctionalization of o-alkynylanilines. AgSbF6 played a role in both the hydroamination step and the imine-formation step. This method, which exhibited excellent chemoselectivity (no ring-fused 1,2-dihydroquinolines were formed), was used for formal syntheses of the natural products conolidine and ervaticine and the antihistamine drug latrepirdine. PMID:26310858

Clinical practice

PubMed Central

Mulder, W. M. C.

2010-01-01

Immediate type allergic reactions to medication are potentially life threatening and can hamper drug therapy of several medical conditions. Exact incidence and prevalence data for these reactions in children are lacking. If no alternative drug treatment is available, a desensitization procedure may secure the continuation of necessary therapy. Desensitization is only appropriate in case of a strong suspicion of an IgE-mediated allergic reaction. It should be performed by trained clinicians (allergy specialists) in a hospital setting where treatment of a potential anaphylactic reaction can be done without any delay. In this article, literature describing desensitization procedures for several antibiotics, antineoplastic agents, and vaccines in children is reviewed. In general, desensitization schemes for children differ only in final dose from schemes for adults. Contradictory data were found regarding the protective effects of premedication with antihistamines and glucocorticoids. PMID:20571825

Loss of work productivity due to illness and medical treatment.

PubMed

Cockburn, I M; Bailit, H L; Berndt, E R; Finkelstein, S N

1999-11-01

We examined the effects on work productivity of treatment with antihistamines in a retrospective study using linked health claims data and daily work output records for a sample of nearly 6000 claims processors at a large insurance company, between 1993 and 1995. We explained the variation in work output depending on the subjects' demographic characteristics, their jobs, and whether they were treated with "sedating" versus "nonsedating" antihistamines for nasal allergies. Differences of up to 13% in productivity were found after the subjects took sedating or nonsedating antihistamines. The observed effect suggests substantial indirect economic costs, which up to now have been largely overlooked because work productivity has proved difficult to measure objectively.

H1 antihistamines and driving.

PubMed

Popescu, Florin Dan

2008-01-01

Driving performances depend on cognitive, psychomotor and perception functions. The CNS adverse effects of some H1 antihistamines can alter the patient ability to drive. Data from studies using standardized objective cognitive and psychomotor tests (Choice Reaction Time, Critical Flicker Fusion. Digital Symbol Substitution Test), functional brain imaging (Positron Emission Tomography, functional Magnetic Resonance Imaging), neurophysiological studies (Multiple Sleep Latency Test, auditory and visual evoked potentials), experimental simulated driving (driving simulators) and real driving studies (the Highway Driving Test, with the evaluation of the Standard Deviation Lateral Position, and the Car Following Test, with the measurement of the Brake Reaction Time) must be discussed in order to classify a H1 antihistamine as a true non-sedating one.

Is there a role for nonsedating antihistamines in motion sickness? Fallout from space research may soon benefit your patients

NASA Technical Reports Server (NTRS)

Kohl, R. L.

1991-01-01

The rotating chair test, a novel research technique for simulating motion sickness, is used to study the effect of nonsedating oral antihistamines in preventing or forestalling motion sickness. After receiving terfenadine, astemizole, doxepin, or placebo, four groups of male volunteers were rotated at accelerating speed, and they made head movements out of the axis of rotation until they perceived that vomiting would occur if additional head movements were made. Those pretreated with doxepin or terfenadine experienced a statistically significant prophylactic effect, as measured by increased tolerance to Coriolis stimulation. This suggests that selective peripheral H1 antihistamine action may protect against motion sickness.

H1 antihistamines and driving

PubMed Central

Florin-Dan, Popescu

2008-01-01

Driving performances depend on cognitive, psychomotor and perception functions. The CNS adverse effects of some H1 antihistamines can alter the patient ability to drive. Data from studies using standardized objective cognitive and psychomotor tests (Choice Reaction Time, Critical Flicker Fusion, Digital Symbol Substitution Test), functional brain imaging (Positron Emission Tomography, functional Magnetic Resonance Imaging), neurophysiological studies (Multiple Sleep Latency Test, auditory and visual evoked potentials), experimental simulated driving (driving simulators) and real driving studies (the Highway Driving Test, with the evaluation of the Standard Deviation Lateral Position, and the Car Following Test, with the measurement of the Brake Reaction Time) must be discussed in order to classify a H1 antihistamine as a true non-sedating one. PMID:20108503

Bilastine: a new H1 -antihistamine with an optimal profile for updosing in urticaria.

PubMed

Church, M K; Labeaga, L

2017-09-01

This review set out to examine published papers detailing the efficacy of bilastine in skin models and urticaria to assess whether it meets the optimal profile for updosing in urticaria, that is, strong clinical efficacy and freedom from unwanted side effects, particularly sedation. Bilastine is a highly effective H 1 -antihistamine even when used at the basic dose of 20 mg daily. Its facilitated uptake after oral dosage gives it a rapid onset and long duration of action. In both wheal and flare studies and in urticaria updosing fourfold showed increased effectiveness. With respect to somnolence, bilastine is a substrate for P-glycoprotein, a membrane pump which prevents it crossing the blood-brain barrier. Consequently, bilastine is a practically 'non-sedating' H 1 -antihistamine. In conclusion, the excellent profile of bilastine in both efficacy and safety make it the ideal H 1 -antihistamine for updosing the daily dose fourfold in difficult-to-treat urticaria as recommended by the EAACI/GA 2 LEN/EDF/WAO guideline for the management of urticaria. © 2017 European Academy of Dermatology and Venereology.

Bilastine: new insight into antihistamine treatment.

PubMed

Ridolo, Erminia; Montagni, Marcello; Bonzano, Laura; Incorvaia, Cristoforo; Canonica, Giorgio Walter

2015-01-01

Bilastine is a new second generation H1-antihistamine recently approved for the symptomatic treatment of allergic rhinitis (AR) and chronic urticaria (CU). Bilastine epitomizes the evolution of research on antihistamines concerning both efficacy and safety. In AR treatment, a number of large controlled clinical trials documented its efficacy, as assessed by improvement of all nasal and ocular symptoms and quality of life. These outcomes show that bilastine meets current EAACI/ARIA criteria for medications used in the treatment of AR. Also in CU, the review of the literature indicates that once-daily treatment with bilastine 20 mg was effective in managing symptoms and improving patient's quality of life. Concerning safety and tolerability, the profile of bilastine is very similar to placebo and in particular the adverse effects on central nervous system are insignificant. The balance of efficacy and safety of bilastine is particularly helpful when dosages higher than standard are needed to control the symptoms, as frequently occurs in patients with urticaria, in whom antihistamines doses up to four times the standard dose may be administered.

Computational fluid dynamics: a suitable assessment tool for demonstrating the antiobstructive effect of drugs in the therapy of allergic rhinitis.

PubMed

Achilles, N; Pasch, N; Lintermann, A; Schröder, W; Mösges, R

2013-02-01

This systematic review aims first to summarize the previous areas of application of computational fluid dynamics (CFD) and then to demonstrate that CFD is also a suitable instrument for generating three-dimensional images that depict drug effects on nasal mucosa. Special emphasis is placed on the three-dimensional visualization of the antiobstructive effect of nasal steroids and antihistamines in the treatment of allergic rhinitis. In the beginning, CFD technology was only used to demonstrate physiological and pathophysiological airflow conditions in the nose and to aid in preoperative planning and postoperative monitoring of surgical outcome in the field of rhinosurgery. The first studies using CFD examined nasal respiratory physiology, important functions of the nose, such as conditioning and warming of inspired air, and the influence of pathophysiological changes on nasal breathing. Also, postoperative outcome of surgical procedures could be "predicted" using the nasal airflow model. Later studies focused on the three-dimensional visualization of the effect of nasal sprays in healthy subjects and postoperative patients. A completely new approach, however, was the use of CFD in the area of allergic rhinitis and the treatment of its cardinal symptom of nasal obstruction. In two clinical trials, a suitable patient with a positive history of allergic rhinitis was enrolled during a symptom-free period after the pollen season. The patient developed typical allergic rhinitis symptoms after provocation with birch pollen. The 3-D visualization showed that the antiallergic treatment successfully counteracted the effects of nasal allergen provocation on nasal airflow. These observations were attributed to the antiobstructive effect of a nasal steroid (mometasone furoate) and a systemic antihistamine (levocetirizine), respectively. CFD therefore constitutes a non-invasive, precise, reliable and objective examination procedure for generating three-dimensional images that depict the effects of drugs used in the treatment of allergic rhinitis.

Actual therapeutic management of allergic and hyperreactive nasal disorders

PubMed Central

Rudack, Claudia

2004-01-01

Allergic rhinitis (AR) and hyperractive disorders of the upper airways, depending upon the type of releasing stimuli, are defined as nasal hyperreactivity, for example in the case of AR, or as non-specific nasal hyperreactivity and as idiopathic rhinitis (IR) (synonyms frequently used in the past: non-specific nasal hyperreactivity; vasomotor rhinitis) in the case of non-characterised stimuli. An early and professional therapy of allergic disorders of the upper airways is of immense importance as allergic rhinitis is detected in comorbidities such as asthma and rhino sinusitis. The therapeutic concept is influenced by new and further developments in pharmacological substance classes such as antihistamines and glucocorticosteroids. Specific immune therapy, the only causal therapy for AR, has been reviewed over the past few years in respect of the type and pattern of application. However, to date no firm recommendations on oral, sublingual and /or nasal immune therapy have yet been drawn up based on investigations of these modifications. Therapeutic management of IR is aimed at a symptom-oriented therapy of nasal hyperactivity as etiological factors relating to this form of rhinitis are not yet sufficiently known. Drug groups such as mast cell stabilizers, systemic and topic antihistamines, topic and systemic glucocorticosteroids, ipatroium bromide and alpha symphatomimetics belong to the spectrum of the therapeutics employed. PMID:22073046

H1-antihistamines in pregnancy and lactation.

PubMed

Schatz, Michael

2002-01-01

Antihistamines may be used for the treatment of allergic rhinitis, upper respiratory infections, urticaria/angioedema, atopic dermatitis, and, rarely, as adjunctive treatment for anaphylaxis, during pregnancy. Because these illnesses may affect maternal comfort and safety as well as threaten the fetus directly (anaphylaxis) or indirectly, they often require therapy during pregnancy. Based on the information available to date, in this chapter we have attempted to provide rational guidelines for the gestational use of H1-receptor antagonists in a manner that will lead to the optimal well-being of both the mother and her infant. As more information becomes available, the recommendations herein may require modification. Although this chapter has dealt specifically with gestational management, a case can be made for considering this information when making therapeutic decisions in all women of childbearing potential. First, most pregnancies are unplanned, and the peak period of fetal vulnerability to drug-induced teratogenesis begins the day a woman's period is due. Second, during gestation, substantial alterations in a previously successful but not optimal-for-pregnancy chronic therapeutic regimen may be psychologically threatening to the patient and may lead to either uncontrolled disease or unanticipated side effects. Thus, pregnancy-appropriate regimens should ideally be discussed with all women of childbearing age as part of the informed therapeutic decision-making process.

Global scanning of antihistamines in the environment: Analysis of occurrence and hazards in aquatic systems.

PubMed

Kristofco, Lauren A; Brooks, Bryan W

2017-08-15

Concentration of the global population is increasingly occurring in megacities and other developing regions, where access to medicines is increasing more rapidly than waste management systems are implemented. Because freshwater and coastal systems are influenced by wastewater effluent discharges of differential quality, exposures in aquatic systems must be considered. Here, we performed a global scanning assessment of antihistamines (AHs), a common class of medicines, in surface waters and effluents. Antihistamines were identified, literature occurrence and ecotoxicology data on AHs collated, therapeutic hazard values (THVs) calculated, and environmental exposure distributions (EEDs) of AHs compared to ecotoxicity thresholds and drug specific THVs to estimate hazards in surface waters and effluents. Literature searches of 62 different AHs in environmental matrices identified 111 unique occurrence publications of 24 specific AHs, largely from Asia-Pacific, Europe, and North America. However, the majority of surface water (63%) and effluent (85%) observations were from Europe and North America, which highlights relatively limited information from many regions, including developing countries and rapidly urbanizing areas in Africa, Latin America and Asia. Less than 10% of all observations were for estuarine or marine systems, though the majority of human populations reside close to coastal habitats. EED 5 th and 95 th centiles for all AHs were 2 and 212ng/L in surface water, 5 and 1308ng/L in effluent and 6 and 4287ng/L in influent, respectively. Unfortunately, global hazards and risks of AHs to non-target species remain poorly understood. However, loratadine observations in surface waters exceeded a THV without an uncertainty factor 40% of the time, indicating future research is needed to understand aquatic toxicology, hazards and risks associated with this AH. This unique global scanning study further illustrates the utility of global assessments of pharmaceuticals and other contaminants to identify chemicals requiring toxicology study and regions where environmental monitoring, assessment and management efforts appear limited and necessary. Copyright © 2017. Published by Elsevier B.V.

Suicide due to cyclizine overdose.

PubMed

Arnestad, Marianne; Eldor, Kari Beate Boye; Stray-Pedersen, Arne; Bachs, Liliana; Karinen, Ritva

2014-03-01

Cyclizine is an antihistamine with sedative effect used to treat motion sickness. A few studies have reported on cyclizine abuse among teenagers, and cyclizine abuse has been reported among opioid dependants receiving methadone, with the combination having been reported to produce strong psychoactive effects. Few reports exist on the possible toxic effects of cyclizine, and it is regarded as a safe drug most often sold as a non-prescription/over-the-counter drug. Very few cases of fatalities resulting from cyclizine overdose can be found in the literature. We present a case where a 22-year-old female was found unconscious and intoxication with drugs and alcohol was suspected. Whole blood from the femoral vein, urine and stomach content were collected during autopsy and screened for drugs of abuse and medicinal drugs. GC-MS screening of the stomach contents revealed presence of cyclizine and meclozine. Cyclizine and meclozine concentrations in blood were determined using a UPLC-MS-MS method. Quantification of femoral blood revealed a high concentration of cyclizine (16 mg/L), a low concentration of meclozine (0.2 mg/L) and ethanol 0.16 g/dL. No other medicinal drugs or drugs of abuse were detected. We report on a case of suicide where cyclizine was found to be the principal drug and question the safety of this drug.

PubMed Central

ACHILLES, N.; PASCH, N.; LINTERMANN, A.; SCHRÖDER, W.; MÖSGES, R.

2013-01-01

SUMMARY This systematic review aims first to summarize the previous areas of application of computational fluid dynamics (CFD) and then to demonstrate that CFD is also a suitable instrument for generating three-dimensional images that depict drug effects on nasal mucosa. Special emphasis is placed on the three-dimensional visualization of the antiobstructive effect of nasal steroids and antihistamines in the treatment of allergic rhinitis. In the beginning, CFD technology was only used to demonstrate physiological and pathophysiological airflow conditions in the nose and to aid in preoperative planning and postoperative monitoring of surgical outcome in the field of rhinosurgery. The first studies using CFD examined nasal respiratory physiology, important functions of the nose, such as conditioning and warming of inspired air, and the influence of pathophysiological changes on nasal breathing. Also, postoperative outcome of surgical procedures could be "predicted" using the nasal airflow model. Later studies focused on the three-dimensional visualization of the effect of nasal sprays in healthy subjects and postoperative patients. A completely new approach, however, was the use of CFD in the area of allergic rhinitis and the treatment of its cardinal symptom of nasal obstruction. In two clinical trials, a suitable patient with a positive history of allergic rhinitis was enrolled during a symptom-free period after the pollen season. The patient developed typical allergic rhinitis symptoms after provocation with birch pollen. The 3-D visualization showed that the antiallergic treatment successfully counteracted the effects of nasal allergen provocation on nasal airflow. These observations were attributed to the antiobstructive effect of a nasal steroid (mometasone furoate) and a systemic antihistamine (levocetirizine), respectively. CFD therefore constitutes a non-invasive, precise, reliable and objective examination procedure for generating three-dimensional images that depict the effects of drugs used in the treatment of allergic rhinitis. PMID:23620638

Drugs in breast milk.

PubMed

Hervada, A R; Feit, E; Sagraves, R

1978-09-01

The amount of drug excreted into breast milk is dependent upon the lipid solubility of the medication, the mechanism of transport, the degree of ionization, and change in plasma pH. The higher the lipid solubility, the greater the concentration in human milk. The majority of drugs are transported into mammary blood capillaries by passive diffusion. The rest are transported by reverse pinocytosis. Once the drug has entered the epithelial cells of breast tissue, the drug molecules are excreted into the human milk by active transport, passive diffusion, or apocrine secretion. The amount of free (active) drug available for transport depends on the degree of protein binding the plasma pH. Another factor affecting excretion of drugs is the time when breast feeding occurs. In the 1st few days of life, when colostrum is present, water-soluble drugs pass through the breast more easily than afterwards when milk is produced. Then lipid-soluble drugs cross in higher concentrations. The effect on nursing infants is dependent on the amount excreted into the milk, the total amount absorbed by the infant, and the toxicity of the drug. The use of the following drugs in breast feeding mothers is reviewed: anticoagulants, antihypertensives and diuretics, antimicrobials, drugs affecting the central nervous system (alcohol, chloral hydrate, meprobamate, lithium, and aspirin), marijuana, other drugs (antihistamines, atropine, ergot alkaloids, laxatives, nicotine, iodides, propylthiouracil, theophylline), hormones (insulin, thyroxine, and oral contraceptives), and radiopharmaceuticals.

Psychiatric co-morbidity associated with pheniramine abuse and dependence

PubMed Central

Pal, Hemraj; Kumar, Rajesh; Bhushan, Shashi; Berry, Neeraj

2005-01-01

The abuse of cough syrups containing antihistamines and codeine is being increasingly noted. The abuse of antihistamines alone has also been reported. The use of antihistamines alone or in combination with other substances of abuse may predispose individuals to develop psychiatric symptoms or syndromes as a part of intoxication, withdrawal or as co-morbid conditions. We present two case reports to highlight the occurrence of co-morbid psychopathology in association with antihistamine abuse and dependence. Case I used high doses of pheniramine for about 2 years and became suspicious of his wife; he even doubted the paternity of his yet-to-be-born child. The associated behavioural abnormalities suggested that he was acting out on the delusion. He also had seizures associated with the intake of a high dose of pheniramine. Case II had multiple substance use, and dependence on alcohol and pheniramine. He demonstrated abnormal behaviour suggestive of psychosis and organic brain syndrome that persisted for a few days and remitted on discontinuation of the substances. These two cases demonstrate the occurrence of psychotic syndromes associated with heavy pheniramine use. The psychopathology can vary from an independent psychotic syndrome to an organic brain syndrome-like disorder.

Bilastine: A New Nonsedating Oral H1 Antihistamine for Treatment of Allergic Rhinoconjunctivitis and Urticaria

PubMed Central

2013-01-01

Bilastine is a new, well-tolerated, nonsedating H1 receptor antihistamine. In the fasting state bilastine is quickly absorbed, but the absorption is slowed when it is taken with food or fruit juice. Therefore, it is recommended that bilastine is taken at least one hour before and no sooner than two hours after a meal. Clinical studies sponsored by the manufacturer have shown that bilastine 20 mg once daily is as efficacious as other nonsedating antihistamines in allergic rhinoconjunctivitis and chronic urticaria in individuals from 12 and 18 years of age, respectively. Bilastine is efficacious in all nasal symptoms including obstruction and in eye symptoms. The observations indicate that non-sedating antihistamines, as opposed to what has been thought previously, may be helpful in patients with allergic rhinitis in whom nasal obstruction is a major concern. Current international guidelines need to be revised in the light of the recent evidence. Research into aspects of pharmacokinetics and efficacy and adverse effect profiles of bilastine in children under 12 years of age is needed as are dose-response assessments and studies planned rigorously with the aim of assessing quality of life effects. PMID:23956994

Bilastine: a new nonsedating oral H1 antihistamine for treatment of allergic rhinoconjunctivitis and urticaria.

PubMed

Wolthers, Ole D

2013-01-01

Bilastine is a new, well-tolerated, nonsedating H1 receptor antihistamine. In the fasting state bilastine is quickly absorbed, but the absorption is slowed when it is taken with food or fruit juice. Therefore, it is recommended that bilastine is taken at least one hour before and no sooner than two hours after a meal. Clinical studies sponsored by the manufacturer have shown that bilastine 20 mg once daily is as efficacious as other nonsedating antihistamines in allergic rhinoconjunctivitis and chronic urticaria in individuals from 12 and 18 years of age, respectively. Bilastine is efficacious in all nasal symptoms including obstruction and in eye symptoms. The observations indicate that non-sedating antihistamines, as opposed to what has been thought previously, may be helpful in patients with allergic rhinitis in whom nasal obstruction is a major concern. Current international guidelines need to be revised in the light of the recent evidence. Research into aspects of pharmacokinetics and efficacy and adverse effect profiles of bilastine in children under 12 years of age is needed as are dose-response assessments and studies planned rigorously with the aim of assessing quality of life effects.

Antihistamine effect on synaptosomal uptake of serotonin, norepinephrine and dopamine

NASA Technical Reports Server (NTRS)

Brown, P. A.; Vernikos, J.

1980-01-01

A study on the effects of five H1 and H2 antihistamines on the synaptosomal uptake of serotonin (5HT), norepinephrine (NE), and dopamine (DA) is presented. Brain homogenates from female rats were incubated in Krebs-Ringer phosphate buffer solution in the presence of one of three radioactive neurotransmitters, and one of the five antihistamines. Low concentrations of pyrilamine competitively inhibited 5HT uptake, had little effect on NE uptake, and no effect on DA uptake. Promethazine, diphenhydramine, metiamide, and cimetidine had no effect on 5HT or DA uptake at the same concentration. Diphenhydramine had a small inhibitory effect on NE uptake. It is concluded that pyrilamine is a selective and potent competitive inhibitor of 5HT uptake at concentrations between .05 and .5 micromolars.

[Drug rash with eosinophilia and systemic symptoms syndrome induced by carbamazepine: Case report].

PubMed

Marín, Jorge Alonso; Ortega, Mayra Alexandra; Sánchez, Isaura Pilar; Pacheco, José Armando

2017-06-01

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a hypersensitivity reaction associated with a variety of drugs, mainly anticonvulsants, which is characterized by systemic symptoms and erythematous lesions, common to other toxicodermas. It is an uncommon clinical entity that requires a high suspicion by clinical staff given its varied initial presentation, and the fact that symptoms can overlap with those of other adverse cutaneous reactions to drugs. Without early diagnosis and appropriate treatment, mortality increases.We report the case of a 22-year-old patient with impaired neurodevelopment who received treatment with carbamazepine. Two months later he presented with general symptoms and skin erythematous lesions that began on his trunk. The patient received outpatient care with antihistamines and antipyretics without an appropriate response. His case progressed with increased skin lesions and systemic symptoms that met the diagnostic criteria for DRESS syndrome. He was hospitalized and received medical treatment according to recommended guidelines. The patient's condition improved as his symptoms and associated complications resolved. He was discharged with gradual clearing of the steroid therapy.

Phytochemicals to prevent inflammation and allergy.

PubMed

Bellik, Yuva; Hammoudi, Si M; Abdellah, Fatiha; Iguer-Ouada, Mokrane; Boukraâ, Laïd

2012-05-01

Recently, much interest has been generated for a wide range of phyto-constituents with reports demonstrating their role in the modulation of inflammatory responses, including phenolics, alkaloids, and terpenoids. Natural products have long been, over the years, contributed to the development of modern therapeutic drugs. At present, steroids, antihistaminic drugs, suppressants or inhibitors of the release of mediators and the like have been used as anti-allergic agents. However, some of them lack immediate effectiveness or have central side effects. Drug discovery from plants involves a multidisciplinary approach combining botanical, ethno-botanical, phytochemical and biological techniques. Several natural product drugs of plant origin are in clinical use and some are undergoing Phase II and Phase III clinical trials. A major effort was directed toward discovery of novel anti-inflammatory and anti-allergic agents, which resulted in the invention of several patented formulations. These formulations concern a variety of pharmaceutical preparations which can be used as solid or liquid dosage forms or encapsulated as a soft or hard gelatin capsule. The present article is a short review of recent patents on the role of phytochemicals in preventing inflammation and allergy.

A Study on Drug Safety Monitoring Program in India

PubMed Central

Ahmad, A.; Patel, Isha; Sanyal, Sudeepa; Balkrishnan, R.; Mohanta, G. P.

2014-01-01

Pharmacovigilance is useful in assuring the safety of medicines and protecting the consumers from their harmful effects. A number of single drugs as well as fixed dose combinations have been banned from manufacturing, marketing and distribution in India. An important issue about the availability of banned drugs over the counter in India is that sufficient adverse drug reactions data about these drugs have not been reported. The most common categories of drugs withdrawn in the last decade were nonsteroidal antiinflammatory drugs (28%), antidiabetics (14.28%), antiobesity (14.28%), antihistamines (14.28%), gastroprokinetic drugs (7.14%), breast cancer and infertility drugs (7.14%), irritable bowel syndrome and constipation drugs (7.14%) and antibiotics (7.14%). Drug withdrawals from market were made mainly due to safety issues involving cardiovascular events (57.14%) and liver damage (14.28%). Majority of drugs have been banned since 3-5 years in other countries but are still available for sale in India. The present study compares the drug safety monitoring systems in the developed countries such as the USA and UK and provides implications for developing a system that can ensure the safety and efficacy of drugs in India. Absence of a gold standard for a drug safety surveillance system, variations in culture and clinical practice across countries makes it difficult for India to completely adopt another country's practices. There should be a multidisciplinary approach towards drug safety that should be implemented throughout the entire duration spanning from drug discovery to usage by consumers. PMID:25425751

A study on drug safety monitoring program in India.

PubMed

Ahmad, A; Patel, Isha; Sanyal, Sudeepa; Balkrishnan, R; Mohanta, G P

2014-09-01

Pharmacovigilance is useful in assuring the safety of medicines and protecting the consumers from their harmful effects. A number of single drugs as well as fixed dose combinations have been banned from manufacturing, marketing and distribution in India. An important issue about the availability of banned drugs over the counter in India is that sufficient adverse drug reactions data about these drugs have not been reported. The most common categories of drugs withdrawn in the last decade were nonsteroidal antiinflammatory drugs (28%), antidiabetics (14.28%), antiobesity (14.28%), antihistamines (14.28%), gastroprokinetic drugs (7.14%), breast cancer and infertility drugs (7.14%), irritable bowel syndrome and constipation drugs (7.14%) and antibiotics (7.14%). Drug withdrawals from market were made mainly due to safety issues involving cardiovascular events (57.14%) and liver damage (14.28%). Majority of drugs have been banned since 3-5 years in other countries but are still available for sale in India. The present study compares the drug safety monitoring systems in the developed countries such as the USA and UK and provides implications for developing a system that can ensure the safety and efficacy of drugs in India. Absence of a gold standard for a drug safety surveillance system, variations in culture and clinical practice across countries makes it difficult for India to completely adopt another country's practices. There should be a multidisciplinary approach towards drug safety that should be implemented throughout the entire duration spanning from drug discovery to usage by consumers.

Management for the children with otitis media with effusion in the tertiary hospital.

PubMed

Choung, Yun-Hoon; Shin, You Ree; Choi, Seong Jun; Park, Keehyun; Park, Hun Yi; Lee, Jong Bin; Han, Dong Hee; Kahng, Hison

2008-12-01

Recently, new evidence-based recommendations have been introduced for diagnosing and managing otitis media with effusion (OME) in children. However, there are some difficulties to follow the general guidelines in the tertiary hospitals. The purpose is to evaluate the efficiency of antibiotics or antihistamines for treatment of children with OME in the tertiary hospital with a randomized prospective clinical study. Eighty-four children with OME who had been diagnosed in the tertiary hospital were randomized to receive 5 different medications for 2 weeks. We prescribed antibiotics (amoxicillin-clavulanate syrup) in Group I (n=16), antibiotics/steroids (prednisolone) in Group II (n=18), antibiotics/antihistamines (ebastine) in Group III (n=15), antibiotics/steroids/antihistamines in Group IV (n=17), and mucolytics (ivy leaf extract) in Group V (n=17) for control. We followed-up children every 2 weeks and evaluated the state of OME at 3 months. Thirty six (42.9%) of 84 children were resolved within average 6.9 weeks after the treatments. Thirty-six (42.9%) were treated with ventilation tube insertion and 12 patients (14.3%) were observed. There was no difference in the resolution rates of OME among the five different protocols (P>0.05). There was no difference in the resolution rates among groups who used steroids, antihistamines, steroids and antihistamines, or other medications to manage 42 children with allergies (P>0.05). In the tertiary hospital, the cure rate of children with OME was not as high as well-known, and antibiotics or anti-allergic medications were not more effective than control. We may, therefore, need any other guidelines which are different from the previous evidence-based recommendations, including early operation in the tertiary hospitals.

Night-time sedating H1-antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial

PubMed Central

Staevska, M; Gugutkova, M; Lazarova, C; Kralimarkova, T; Dimitrov, V; Zuberbier, T; Church, MK; Popov, TA

2014-01-01

Background Many physicians believe that the most effective way to treat chronic urticaria is to take a nonsedating second-generation H1-antihistamine in the morning and a sedating first-generation H1-antihistamine, usually hydroxyzine, at night to enhance sleep. But is this belief well founded? Objectives To test this belief by comparing the effectiveness and prevalence of unwanted sedative effects when treating patients with chronic spontaneous urticaria (CSU) with levocetirizine 15 mg daily plus hydroxyzine 50 mg at night (levocetirizine plus hydroxyzine) vs. levocetirizine 20 mg daily (levocetirizine monotherapy). Methods In this randomized, double-blind, cross-over study, 24 patients with difficult-to-treat CSU took levocetirizine plus hydroxyzine or levocetirizine monotherapy for periods of 5 days each. At the end of each treatment period, assessments were made of quality of life (Chronic Urticaria Quality of Life Questionnaire, CU-Q2oL), severity of urticaria symptoms (Urticaria Activity Score, UAS), sleep disturbance during the night and daytime somnolence. Results Both treatments significantly decreased UAS, night-time sleep disturbances and CU-Q2oL scores (P < 0·001) without significant differences between the two. Compared with baseline, daytime somnolence was significantly reduced by levocetirizine monotherapy (P = 0·006) but not by levocetirizine plus hydroxyzine (P = 0·218). Direct comparison of the two treatment modalities in terms of daytime somnolence favoured levocetirizine monotherapy (P = 0·026). Conclusions The widespread belief that sleep is aided by the addition of a sedating first-generation H1-antihistamine, usually hydroxyzine, at night is not supported. These results are in line with the urticaria guidelines, which state that first-line treatment for urticaria should be new-generation, nonsedating H1-antihistamines only. PMID:24472058

Preclinical pharmacology of bilastine, a new selective histamine H1 receptor antagonist: receptor selectivity and in vitro antihistaminic activity.

PubMed

Corcóstegui, Reyes; Labeaga, Luis; Innerárity, Ana; Berisa, Agustin; Orjales, Aurelio

2005-01-01

This study aimed to establish the receptor selectivity and antihistaminic activity of bilastine, a new selective antihistamine receptor antagonist. In vitro experiments were conducted using a receptor binding screening panel and guinea-pig and rat tissues. Antihistaminic activity was determined using H1 receptor binding studies and in vitro H1 antagonism studies conducted in guinea-pig tissues and human cell lines. Receptor selectivity was established using a receptor binding screening panel and a receptor antagonism screening conducted in guinea-pig, rat and rabbit tissues. Inhibition of inflammatory mediators was determined through the Schultz-Dale reaction in sensitised guinea-pig ileum. Bilastine binds to histamine H1-receptors as indicated by its displacement of [3H]-pyrilamine from H1-receptors expressed in guinea-pig cerebellum and human embryonic kidney (HEK) cell lines. The studies conducted on guinea-pig smooth muscle demonstrated the capability of bilastine to antagonise H1-receptors. Bilastine is selective for histamine H1-receptors as shown in receptor-binding screening conducted to determine the binding capacity of bilastine to 30 different receptors. The specificity of its H1-receptor antagonistic activity was also demonstrated in a series of in vitro experiments conducted on guinea-pig and rat tissues. The results of these studies confirmed the lack of significant antagonism against serotonin, bradykinin, leukotriene D4, calcium, muscarinic M3-receptors, alpha1-adrenoceptors, beta2-adrenoceptors, and H2- and H3-receptors. The results of the in vitro Schultz-Dale reaction demonstrated that bilastine also has anti-inflammatory activity. These preclinical studies provide evidence that bilastine has H1- antihistamine activity, with high specificity for H1-receptors, and poor or no affinity for other receptors. Bilastine has also been shown to have anti-inflammatory properties.

Antihistamines and other prognostic factors for adverse outcome in hyperemesis gravidarum

PubMed Central

Fejzo, Marlena S.; Magtira, Aromalyn; Schoenberg, Frederic Paik; MacGibbon, Kimber; Mullin, Patrick; Romero, Roberto; Tabsh, Khalil

2014-01-01

Objective The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors. Study design This is a case-control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test. Results Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p < 0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p < 0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p < 0.0089). Poor outcomes were associated with early start of symptoms (p < 0.019), and treatment with methylprednisolone (p < 0.0217), promethazine (p < 0.0386), and other antihistamines [diphenhy- dramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p < 0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome. Conclusion Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy. PMID:23751910

Hypersensitivity reactions to etoposide.

PubMed

Hoetelmans, R M; Schornagel, J H; ten Bokkel Huinink, W W; Beijnen, J H

1996-04-01

To report a hypersensitivity reaction to etoposide occurring in a patient after 2 months of drug therapy. A 20-year-old man with a diagnosis of testicular carcinoma was treated with bleomycin, etoposide, and cisplatin (BEP regimen). After dose 20 of etoposide, an exanthema was noted, which was attributed to etoposide. The patient had received 19 doses of etoposide during the previous 2 months without any sign of an allergic reaction. Rechallenging the patient with etoposide from another batch resulted in recurrence of the exanthema. Both etoposide and its excipient (polysorbate 80) are suspected of causing hypersensitivity reactions. Although the exact mechanism of the hypersensitivity reaction is not known, it is believed to be of nonimmunogenic origin. With a lower rate of infusion of etoposide and/or by premedication with antihistamines and/or corticosteroids, hypersensitivity reactions to etoposide might be prevented in patients with a history of hypersensitivity to this drug.

[Acute asthma in children--anaphylaxis].

PubMed

Carlsen, K H

1993-05-30

Acute asthma is a manifestation of chronic inflammation of airways, and may be due to inadequate control. Assessment of acute asthma is based upon respiratory rate and pattern, thoracic respiratory recessions, auscultatory rales and rhonchi, skin colour (cyanosis/pallor) and heart rate. Acute asthma in children is best treated with inhaled nebulised drugs, especially beta 2-agonists and adrenaline. Acute severe asthma should be treated with systemic steroids (by injection or orally), and it is important that this treatment is not started too late. Symptomatic treatment with intravenous theophyllamine may also be relevant. Anaphylactic shock occurs most often after injection of drugs or after bites by a wasp or a bee. Food allergy may be the cause in some patients. Speed is necessary in the treatment of anaphylactic shock, and intramuscular injection of adrenaline is the treatment of choice. Systemic steroids or antihistaminics may be used to stabilize the state of the patient.

Trends in prescription drug expenditures by Medicaid enrollees.

PubMed

Banthin, Jessica S; Miller, G Edward

2006-05-01

As prescription drug expenditures consume an increasingly larger portion of Medicaid budgets, states are anxious to control drug costs without endangering enrollees' health. In this report, we analyzed recent trends in Medicaid prescription drug expenditures by therapeutic classes and subclasses. Identifying the fastest growing categories of drugs, where drugs are grouped into clinically relevant classes and subclasses, can help policymakers decide where to focus their cost containment efforts. We used data from the Medical Expenditure Panel Survey linked to a prescription drug therapeutic classification system, to examine trends between 1996/1997 and 2001/2002 in utilization and expenditures for the noninstitutionalized Medicaid population. We separated aggregate trends into changes in population with use and changes in expenditures per user, and percent generic. We also highlighted differences within the Medicaid population, including children, adults, disabled, and elderly. We found rapid growth in expenditures for antidepressants, antipsychotics, antihyperlipidemics, antidiabetic agents, antihistamines, COX-2 inhibitors, and proton pump inhibitors and found evidence supporting the rapid take-up of new drugs. In some cases these increases are the result of increased expenditures per user and in other cases the overall growth also comes from an increase in the population with use. Medicaid programs may want to reassess their cost-containment policies in light of the rapid take-up of new drugs. Our analysis also identifies areas in which more information is needed on the comparative effectiveness of new versus existing treatments.

Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century.

PubMed

Castells Guitart, M C

2014-01-01

The frequency of hypersensitivity reactions (HSR) to drugs has risen in the last 10 years owing to increased exposure to better and more allergenic medications including monoclonal antibodies. HSRs prevent patients from using their first-line therapy, leading to decreased quality of life and life expectancy. Although premedication with antihistamines, leukotriene blockers, and corticosteroids can protect against mild-to-moderate HSR, none of these medications has provided protection against anaphylaxis. Rapid drug desensitization is a treatment option for patients with HSR to their first-line medication that protects against anaphylaxis.Although the mechanisms of drug desensitization are not completely understood, in vitro mast cell models of IgE antigen desensitization have led to the design of safe and effective in vivo protocols aimed at protecting highly sensitized patients from hypersensitivity reactions and anaphylaxis. This review provides an insight into the mechanisms of IgE/mast cell desensitization, the principles and practice of drug desensitization, and an overview of the different desensitization protocols and their safety and efficacy profiles. Drug desensitization should only be performed by allergists, trained nurses, and experienced pharmacists, since this high-risk procedure involves reintroducing allergenic medication to highly sensitized patients, with the consequent potential for severe or fatal HSRs.

The involvement of prescribed drugs in road trauma.

PubMed

Drummer, Olaf H; Yap, Suwan

2016-08-01

Coroners files and toxicological records of fatally-injured drivers in Victoria from 2000 to 2006 and from 2007 to 2013 were reviewed in separate studies to establish the role of prescribed drugs on crash risk. 2638 driver fatalities were included in the study, which represented over 97% of all driver fatalities in this period. The detection limits of the drugs were at the low end of those seen with common illicit drugs or prescribed drugs. Drugs of any type were found in 34.4% of the study group, medicinal drugs 21.2%, and alcohol (≥0.05 gram/100mL) was found in 24.8%. The prevalence of the most common drugs detected that are legally available by prescription were anti-depressants (7.9%), benzodiazepines (7.0%), opiates/opioids (6.6%), and sedating anti-histamines (1.1%). Each driver was assessed for responsibility using a previously published and validated method. The crash risk of drivers taking opioids, benzodiazepines, or anti-depressants (primarily the serotonin reuptake inhibitors), were not significantly over-represented compared to the drug-free control group, although there was a suggestion of increased crash risk for benzodiazepines. Crash risk was elevated for drivers using cannabis (by presence of THC in blood at>2ng/mL) and amphetamines. These data show that drivers using medicinal drugs alone are unlikely to show significant crash risk even if drugs are potentially impairing. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prolonged anticholinergic delirium following antihistamine overdose.

PubMed

Scott, James; Pache, David; Keane, Greg; Buckle, Helen; O'Brien, Natalie

2007-06-01

A case of anticholinergic delirium in a female adolescent is described, exploring the pharmacokinetic reasons for the prolonged time course and reviewing the management provided. A 14 year old female hospitalised for depression ingested large quantities of promethazine and cyproheptadine. A severe anticholinergic delirium ensued which resolved after six days, much longer than the expected duration. The likely cause of the prolonged delirium was the interaction of promethazine and fluvoxamine through the inhibition of the CYP2D6 enzyme. The patient's young age, the severity of the poisoning and the use of drugs with anticholinergic properties to manage the delirium may also have contributed. The delirium may have been reversed had a cholinesterase inhibitor been provided soon after the overdose.

Nonprescription medications for respiratory symptoms: Facts and marketing fictions.

PubMed

Weinberger, Miles; Hendeles, Leslie

2018-05-01

There are many nonprescription (over-the-counter [OTC]) medications available on pharmacy shelves marketed for relief of respiratory symptoms. The number of such medications has been increasing. This review provides an evidence-based examination of OTC products used for respiratory symptoms. Antihistamines, decongestants, mucolytics, antitussives, and intranasal steroids were selected as the most common OTC medications taken by adults and children for various respiratory symptoms. Controlled clinical trials of efficacy were identified by searching a medical literature data base. Those trials and key publications related to the pharmacokinetics and pharmacodynamics of the products were reviewed. Comparisons of the various OTC antihistamines' ability to suppress the effects of histamine were related to their clinical benefit. Intranasal corticosteroids are the preferred agents for maintenance therapy of persistent nasal congestion and are highly effective for symptoms of inhalant allergy other than allergic conjunctivitis. The disconnect between marketing claims and evidence was demonstrated for antihistamines and oral alpha-1 adrenergic agonist decongestants. Data for OTC mucolytics and antitussives were insufficient to justify their use based on the evidence. There was little relationship between marketing claims and evidence regarding OTC medications used for respiratory symptoms. Analysis of data supported cetirizine, levocetirizine, and fexofenadine as the most effective of the OTC antihistamines. There were no data that supported the use of oral phenylephrine as a decongestant. Neither OTC mucolytics or antitussives provided sufficient evidence to justify their use.

Night-time sedating H1 -antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial.

PubMed

Staevska, M; Gugutkova, M; Lazarova, C; Kralimarkova, T; Dimitrov, V; Zuberbier, T; Church, M K; Popov, T A

2014-07-01

Many physicians believe that the most effective way to treat chronic urticaria is to take a nonsedating second-generation H1 -antihistamine in the morning and a sedating first-generation H1 -antihistamine, usually hydroxyzine, at night to enhance sleep. But is this belief well founded? To test this belief by comparing the effectiveness and prevalence of unwanted sedative effects when treating patients with chronic spontaneous urticaria (CSU) with levocetirizine 15 mg daily plus hydroxyzine 50 mg at night (levocetirizine plus hydroxyzine) vs. levocetirizine 20 mg daily (levocetirizine monotherapy). In this randomized, double-blind, cross-over study, 24 patients with difficult-to-treat CSU took levocetirizine plus hydroxyzine or levocetirizine monotherapy for periods of 5 days each. At the end of each treatment period, assessments were made of quality of life (Chronic Urticaria Quality of Life Questionnaire, CU-Q2 oL), severity of urticaria symptoms (Urticaria Activity Score, UAS), sleep disturbance during the night and daytime somnolence. Both treatments significantly decreased UAS, night-time sleep disturbances and CU-Q2 oL scores (P < 0·001) without significant differences between the two. Compared with baseline, daytime somnolence was significantly reduced by levocetirizine monotherapy (P = 0·006) but not by levocetirizine plus hydroxyzine (P = 0·218). Direct comparison of the two treatment modalities in terms of daytime somnolence favoured levocetirizine monotherapy (P = 0·026). The widespread belief that sleep is aided by the addition of a sedating first-generation H1 -antihistamine, usually hydroxyzine, at night is not supported. These results are in line with the urticaria guidelines, which state that first-line treatment for urticaria should be new-generation, nonsedating H1 -antihistamines only. © 2014 The Authors. British Association of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Treatment of nausea and vomiting in terminally ill cancer patients.

PubMed

Glare, Paul A; Dunwoodie, David; Clark, Katherine; Ward, Alicia; Yates, Patsy; Ryan, Sharon; Hardy, Janet R

2008-01-01

Nausea and vomiting is a common and distressing symptom complex in patients with far-advanced cancer, affecting up to 60% of individuals at some stage of their illness. The current approach to the palliative care of patients with nausea and vomiting is based on identifying the cause, understanding its pathophysiology and knowing the pharmacology of the drugs available for its amelioration. The following six main syndromes are identified: gastric stasis, biochemical, raised intracranial pressure, vestibular, mechanical bowel obstruction and ileus. A careful history, focused physical examination and appropriate investigations are needed to elucidate the syndrome and its cause, so that therapy is rational. Drugs are the mainstay of treatment in terminal cancer, and the main classes of antiemetic agents are prokinetics, dopamine antagonists, antihistamines, anticholinergics and serotonin antagonists. Dexamethasone and octreotide are also used, especially in bowel obstruction. Non-drug measures are important in relieving the associated distress. Patients should be able to die comfortably, without tubes. Despite decades of practice affirming this approach, the evidence base is weak and well designed studies are urgently needed.

Therapeutic Targeting of Eosinophil Adhesion and Accumulation in Allergic Conjunctivitis

PubMed Central

Baiula, Monica; Bedini, Andrea; Carbonari, Gioia; Dattoli, Samantha Deianira; Spampinato, Santi

2012-01-01

Considerable evidence indicates that eosinophils are important effectors of ocular allergy. Increased worldwide prevalence of allergic eye pathologies has stimulated the identification of novel drug targets, including eosinophils and adhesion molecules. Accumulation of eosinophils in the eye is a key event in the onset and maintenance of allergic inflammation and is mediated by different adhesion molecules. Antihistamines with multiple mechanisms of action can be effective during the early and late phases of allergic conjunctivitis by blocking the interaction between β1 integrins and vascular cell adhesion molecule (VCAM)-1. Small molecule antagonists that target key elements in the process of eosinophil recruitment have been identified and reinforce the validity of α4β1 integrin as a therapeutic target. Glucocorticoids are among the most effective drugs for ocular allergy, but their use is limited by adverse effects. Novel dissociated glucocorticoids can prevent eosinophil accumulation and induce apoptosis of eosinophils, making them promising candidates for ophthalmic drugs. This article reviews recent understanding of the role of adhesion molecules in eosinophil recruitment in the inflamed conjunctiva along with effective treatments for allergic conjunctivitis. PMID:23271999

Emerging drugs for allergic conjunctivitis.

PubMed

Ridolo, Erminia; Montagni, Marcello; Caminati, Marco; Senna, Gianenrico; Incorvaia, Cristoforo; Canonica, Giorgio Walter

2014-06-01

Allergic conjunctivitis (AC) is a very common disease, especially in association with allergic rhinitis but may also occur in isolated presentation. The treatment of AC has long been based on antihistamines, cromones and topical corticosteroids, but none of these drugs completely abolishes the clinical expression of AC. The development of new drugs for AC is analyzed highlighting the recent insights into the pathophysiological mechanisms of the disease. The major aim of development of drugs for AC is to have agents able to prevent the inflammatory effects of the interaction between the allergen and the specific IgE antibodies on mast cell surface. This may be obtained by blocking the effects of histamine (the main mediator of early allergic response) by H1-receptor antagonists, inhibiting the release of soluble factors able to recruit inflammatory cells (that sustain prolonged inflammation) by mast-cell stabilizers, inhibiting the effects of single mediators, inducing tolerance to the allergen by specific immunotherapy or even acting on factors related to activation and differentiation of T lymphocytes such as the toll-like receptors. AC is an underestimated disease for which there is a search of more effective treatments. The availability of the drugs under current evaluation will allow more refined therapeutic strategies to apply according to the characteristics and the clinical severity of AC.

Validation of LC–TOF-MS Screening for Drugs, Metabolites, and Collateral Compounds in Forensic Toxicology Specimens

PubMed Central

Guale, Fessessework; Shahreza, Shahriar; Walterscheid, Jeffrey P.; Chen, Hsin-Hung; Arndt, Crystal; Kelly, Anna T.; Mozayani, Ashraf

2013-01-01

Liquid chromatography time-of-flight mass spectrometry (LC–TOF-MS) analysis provides an expansive technique for identifying many known and unknown analytes. This study developed a screening method that utilizes automated solid-phase extraction to purify a wide array of analytes involving stimulants, benzodiazepines, opiates, muscle relaxants, hypnotics, antihistamines, antidepressants and newer synthetic “Spice/K2” cannabinoids and cathinone “bath salt” designer drugs. The extract was applied to LC–TOF-MS analysis, implementing a 13 min chromatography gradient with mobile phases of ammonium formate and methanol using positive mode electrospray. Several common drugs and metabolites can share the same mass and chemical formula among unrelated compounds, but they are structurally different. In this method, the LC–TOF-MS was able to resolve many isobaric compounds by accurate mass correlation within 15 ppm mass units and a narrow retention time interval of less than 10 s of separation. Drug recovery yields varied among spiked compounds, but resulted in overall robust area counts to deliver an average match score of 86 when compared to the retention time and mass of authentic standards. In summary, this method represents a rapid, enhanced screen for blood and urine specimens in postmortem, driving under the influence, and drug facilitated sexual assault forensic toxicology casework. PMID:23118149

Validation of LC-TOF-MS screening for drugs, metabolites, and collateral compounds in forensic toxicology specimens.

PubMed

Guale, Fessessework; Shahreza, Shahriar; Walterscheid, Jeffrey P; Chen, Hsin-Hung; Arndt, Crystal; Kelly, Anna T; Mozayani, Ashraf

2013-01-01

Liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) analysis provides an expansive technique for identifying many known and unknown analytes. This study developed a screening method that utilizes automated solid-phase extraction to purify a wide array of analytes involving stimulants, benzodiazepines, opiates, muscle relaxants, hypnotics, antihistamines, antidepressants and newer synthetic "Spice/K2" cannabinoids and cathinone "bath salt" designer drugs. The extract was applied to LC-TOF-MS analysis, implementing a 13 min chromatography gradient with mobile phases of ammonium formate and methanol using positive mode electrospray. Several common drugs and metabolites can share the same mass and chemical formula among unrelated compounds, but they are structurally different. In this method, the LC-TOF-MS was able to resolve many isobaric compounds by accurate mass correlation within 15 ppm mass units and a narrow retention time interval of less than 10 s of separation. Drug recovery yields varied among spiked compounds, but resulted in overall robust area counts to deliver an average match score of 86 when compared to the retention time and mass of authentic standards. In summary, this method represents a rapid, enhanced screen for blood and urine specimens in postmortem, driving under the influence, and drug facilitated sexual assault forensic toxicology casework.

Validated spectroscopic methods for determination of anti-histaminic drug azelastine in pure form: Analytical application for quality control of its pharmaceutical preparations

NASA Astrophysics Data System (ADS)

El-Masry, Amal A.; Hammouda, Mohammed E. A.; El-Wasseef, Dalia R.; El-Ashry, Saadia M.

2018-02-01

Two simple, sensitive, rapid, validated and cost effective spectroscopic methods were established for quantification of antihistaminic drug azelastine (AZL) in bulk powder as well as in pharmaceutical dosage forms. In the first method (A) the absorbance difference between acidic and basic solutions was measured at 228 nm, whereas in the second investigated method (B) the binary complex formed between AZL and Eosin Y in acetate buffer solution (pH 3) was measured at 550 nm. Different criteria that have critical influence on the intensity of absorption were deeply studied and optimized so as to achieve the highest absorption. The proposed methods obeyed Beer's low in the concentration range of (2.0-20.0 μg·mL- 1) and (0.5-15.0 μg·mL- 1) with % recovery ± S.D. of (99.84 ± 0.87), (100.02 ± 0.78) for methods (A) and (B), respectively. Furthermore, the proposed methods were easily applied for quality control of pharmaceutical preparations without any conflict with its co-formulated additives, and the analytical results were compatible with those obtained by the comparison one with no significant difference as insured by student's t-test and the variance ratio F-test. Validation of the proposed methods was performed according the ICH guidelines in terms of linearity, limit of quantification, limit of detection, accuracy, precision and specificity, where the analytical results were persuasive. The absorption spectrum of AZL (16 μg·mL- 1) in 0.1 M HCl. The absorption spectrum of AZL (16 μg·mL- 1) in 0.1 M NaOH. The difference absorption spectrum of AZL (16 μg·mL- 1) in 0.1 M NaOH vs 0.1 M HCl. The absorption spectrum of eosin binary complex with AZL (10 μg·mL- 1).

Assessment of prescribing practices among urban and rural general practitioners in Tamil Nadu.

PubMed

Gopalakrishnan, Sekharan; Ganeshkumar, Parasuraman; Katta, Ajitha

2013-01-01

Studying drug use pattern among medical practitioners is of vital importance in the present scenario where irrational drug use and development of drug resistance is becoming rampant. To assess, the pattern of prescribing practices among the general practitioners in a defined rural and urban area of Tamil Nadu. A community based descriptive study was conducted to collect 600 prescriptions from the catchment areas of rural and urban health training centers of a medical college using prescribing indicators as per the WHO "How to investigate drug use in health facilities" tool. This prescription study revealed that multivitamins (19.5%), antibiotics (19.3%), drugs for gastro-intestinal tract (GIT) (18%), analgesic non-steroidal anti-inflammatory drugs/ (NSAID's) (15.1%), and antihistaminic (12.5%) were prescribed frequently. Among the antibiotics, amoxicillin (49.2%) was the most commonly prescribed followed by gentamicin (31.7%). Percentage of prescriptions with an antibiotic was 55% and nearly 62% of the practitioners prescribed drugs by their generic names. As a practice of poly-pharmacy, it was observed that the average number of drugs prescribed in urban and rural area was nearly 5 and 4, respectively. Nearly 80% of the urban and rural practitioners were prescribing at least one injection. Study of the quality of prescriptions revealed that there was poor legibility, high usage of abbreviations, inadequate details of the drugs, and absence of signature by practitioners in the prescriptions. This study clearly highlights the practice of poly-pharmacy, low usage of generic drugs, injudicious usage of antibiotics and injections and low usage of drugs prescribed from essential drugs list.

Changes in gene expression induced by histamine, fexofenadine and osthole: Expression of histamine H1 receptor, COX-2, NF-κB, CCR1, chemokine CCL5/RANTES and interleukin-1β in PBMC allergic and non-allergic patients.

PubMed

Kordulewska, Natalia Karolina; Kostyra, Elżbieta; Cieślińska, Anna; Matysiewicz, Michał; Fiedorowicz, Ewa; Sienkiewicz-Szłapka, Edyta

2017-03-01

Fexofenadine (FXF) is a third-generation antihistamine drug and osthole is assumed as a natural antihistamine alternative. This paper compares results of histamine, FXF and osthole impact on HRH-1, COX-2, NF-κB-p50, CCR1 mRNA expression. We also measured mRNA expression of IL-1β and CCL5/RANTES in incubated peripheral blood mononuclear cells (PBMC) to compared how histamine, FXF and osthole had influence on expression level and interacts on product secretion. The purpose was to investigate expression pattern in asthma PBMC. The cultures were treated 72h with FXF and osthole. We measured mRNA expression of histamine HRH-1, COX-2, NF-κB-p50, CCR1, IL-1β and CCL5/RANTES with Real-Time PCR (RT-PCR). The present study suggest that osthole may be a potential inhibitor of histamine H 1 receptor activity. We also demonstrated that cells cultured with histamine increase COX-2 mRNA expression and osthole reduce it. Allergy remains one of the most common chronic diseases in Europe and it is rapidly approaching epidemic proportions; with current predictions estimating that the number of allergy-afflicted will equal the healthy population by 2020. It is therefore paramount to find new pharmaceuticals which successfully combat allergic disease. Copyright © 2016 Elsevier GmbH. All rights reserved.

Management of chronic spontaneous urticaria in the elderly.

PubMed

Ventura, Maria Teresa; Cassano, Nicoletta; Romita, Paolo; Vestita, Michelangelo; Foti, Caterina; Vena, Gino Antonio

2015-04-01

The guidelines for the management of urticaria in adults and children have been revised and updated recently. However, there are few data in the literature concerning several aspects of this disease in the elderly (e.g., epidemiology, etiopathogenesis, clinical aspects, association with co-morbidities, efficacy and safety profiles of treatments, and management strategies). This is an obvious deficiency in the data, as this disease causes a deterioration in quality of life, affecting the quality of sleep, everyday life habits and activities, and inducing severe disability. Chronic spontaneous urticaria (CSU) can also be associated with internal, infectious, autoimmune, or neoplastic diseases. It is therefore necessary to pay particular attention to these clinical issues through appropriate clinical examinations. At the same time, the specific features of medications used to treat CSU in the elderly should be carefully evaluated, as its pharmacological treatment raises a number of problems related both to the clinical condition of the patient and to concomitant diseases, as well as to the polypharmacotherapy, which is common in older subjects and may cause safety problems because of the drug interactions. Non-sedating new-generation antihistamines are the mainstay treatment of CSU for the elderly. The efficacy and safety of alternative treatment options have not been assessed in the geriatric population with CSU; corticosteroids and cyclosporine (ciclosporin) should be used by this population with extreme caution. Similarly, there are no data regarding the actual safety profile of the new-generation antihistamines at higher doses than those recommended in elderly patients.

[The effect of a new antiparkinson agent, Selegilin, on psychomotor performance in humans].

PubMed

Müller-Limmroth, W

1985-01-01

A combination of tests consisting of a compensation task with differential value indication, a tachystoscopic arrangement with verbal identification of characteristic features and an arrangement for a visually induced motor reaction was carried out on 12 healthy volunteers aged from 20-30 to determine psychomotor efficiency under the influence of the new antiparkinson drug selegiline (Eldepryl). The results were compared with the effects of the psychostimulant fenetylline and the depressant-antihistamine chlorphenoxamine, and with a placebo. While fenetylline and chlorphenoxamine produced the anticipated effects with regard to an improvement or deterioration in performance in all parameters, selegiline resulted in a slightly longer motor reaction time and an increase in control errors, and in a significantly longer mental processing time. In comparison with the placebo, selegiline increased the motor reaction time by 0.8 +/- 1.95% and mental processing time by 4.1 +/- 1.7%. This depressant effect of selegiline, however, only attained 1/8 and 2/3, resp., of the sedative effect of the normal dose of the antihistamine chlorophenoxamine. Under the influence of chlorphenoxamine, performance becomes less regular and under fenetylline more regular. Selegiline does not differ significantly from the placebo. In spite of selegiline metabolites 1-metamphetamine and 1-amphetamine, which act as mild stimulants, the slightly depressant effect of selegiline detected can be explained by the increased effect of dopamine inhibitory neurons, particularly in the inhibitory system of the formatio reticularis and the cortex frontalis as a result of a concentration of dopamine.

Prescription of Sedative Drugs During Hospital Stay: A Swiss Prospective Study.

PubMed

Schumacher, Laurence; Dobrinas, Maria; Tagan, Damien; Sautebin, Annelore; Blanc, Anne-Laure; Widmer, Nicolas

2017-12-01

In recent years, the number of prescriptions for sedative drugs has increased significantly, as has their long-term use. Moreover, sedative use is frequently initiated during hospital stays. This study aimed to describe new prescriptions of sedative drugs during hospital stays and evaluate their maintenance as discharge medication. This observational prospective study took place in an internal medicine ward of a Swiss hospital over a period of 3 months in 2014. Demographic (age, sex, diagnosis, comorbidities) and medication data [long-term use of sedative drugs, new regular or pro re nata ('as needed') prescriptions of sedative drugs, drug-related problems] were collected. Sedative medications included: benzodiazepines, Z-drugs, antihistamines, antidepressants, neuroleptics, herbal drugs, and clomethiazole. McNemar's test was used for comparison. Of 290 patients included, 212 (73%) were over 65 years old and 169 (58%) were women; 34% (n = 98) were using sedative drugs long term before their hospital stay, and 44% (n = 128) had a prescription for sedative drugs at discharge-a 10% increase (p < 0.05). Sedative drugs were newly prescribed to 37% (n = 108) of patients during their stay. Among these, 37% (n = 40) received a repeat prescription at discharge. Over half of the sedative drugs were prescribed within 24 h of admission. Drug-related problems were detected in 76% of new prescriptions, of which 90% were drug-drug interactions. This study showed that hospital stays increased the proportion of patients who were prescribed a sedative drug at discharge by 10% (absolute increase). These prescriptions may generate long-term use and expose patients to drug-related problems. Promoting alternative approaches for managing insomnia are recommended.

Efficacy of amoxicillin with and without decongestant-antihistamine for otitis media with effusion in children. Results of a double-blind, randomized trial.

PubMed

Mandel, E M; Rockette, H E; Bluestone, C D; Paradise, J L; Nozza, R J

1987-02-19

In a randomized, double-blind, placebo-controlled trial involving 518 infants and children who had otitis media with effusion ("secretory" otitis media), we evaluated the efficacy of a two-week course of amoxicillin (40 mg per kilogram of body weight per day) with and without a four-week course of an oral decongestant-antihistamine combination. Among the 474 subjects who were evaluated at the four-week end point, the rate of resolution of middle-ear effusion was twice as high in those treated with amoxicillin, either with or without the decongestant-antihistamine, as in those who received placebo (P less than 0.001), but 69.8 percent of the amoxicillin-treated subjects still had effusion. Among both the amoxicillin-treated subjects and the placebo-treated subjects, resolution was more likely in those with initially unilateral effusion, in those who had had effusion for eight weeks or less, and in those without an upper respiratory tract infection at the four-week end point. Side effects were reported more often in subjects who received decongestant-antihistamine than in those who did not. Among the subjects without effusion at the four-week end point, recurrent effusion developed in approximately half those in both the amoxicillin and placebo groups during the subsequent three months. We conclude that in infants and children with otitis media with effusion, amoxicillin treatment increases to some extent the likelihood of resolution.

Can increases in CHIP copayments reduce program expenditures on prescription drugs?

PubMed

Sen, Bisakha; Blackburn, Justin; Morrisey, Michael; Becker, David; Kilgore, Meredith; Caldwell, Cathy; Menachemi, Nir

2014-01-01

The primary aim is to explore whether prescription drug expenditures by enrollees changed in Alabama's CHIP program, ALL Kids, after copayment increases in fiscal year 2004. The subsidiary aim is to explore whether non-pharmaceutical expenditures also changed. Data on ALL Kids enrollees between 1999-2007, obtained from claims files and the state's administrative database. We used data on children who were enrolled between one and three years both before and after the changes to the copayment schedule, and estimate regression models with individual-level fixed effects to control for time-invariant heterogeneity at the child level. This allows an accurate estimate of how program expenditures change for the same individual following copayment changes. Primary outcomes of interest are expenditures for prescription drugs by class and brand-name and generic versions. We estimate models for the likelihood of any use of prescription drugs and expenditure level conditional on use. Following the copayment increase, the probability of any expenditure decline by 5.8%, brand name drugs by 6.9%, generic drugs by 7.4%. Conditional on any use, program expenditures decline by 7.9% for all drugs, by 9.6% for brand name drugs, and 6.2% for generic drugs. The largest declines are for antihistamine drugs; the least declines are for Central Nervous System agents. Declines are smaller and statistically weaker for children with chronic health conditions. Concurrent declines are also seen for non-pharmaceutical medical expenditures. Copayment increases appear to reduce program expenditures on prescription drugs per enrollee and may be a useful tool for controlling program costs.

Clinical Pharmacology in Sleep Medicine

PubMed Central

Proctor, Ashley; Bianchi, Matt T.

2012-01-01

The basic treatment goals of pharmacological therapies in sleep medicine are to improve waking function by either improving sleep or by increasing energy during wakefulness. Stimulants to improve waking function include amphetamine derivatives, modafinil, and caffeine. Sleep aids encompass several classes, from benzodiazepine hypnotics to over-the-counter antihistamines. Other medications used in sleep medicine include those initially used in other disorders, such as epilepsy, Parkinson's disease, and psychiatric disorders. As these medications are prescribed or encountered by providers in diverse fields of medicine, it is important to recognize the distribution of adverse effects, drug interaction profiles, metabolism, and cytochrome substrate activity. In this paper, we review the pharmacological armamentarium in the field of sleep medicine to provide a framework for risk-benefit considerations in clinical practice. PMID:23213564

Meclizine-induced enhanced glycolysis is neuroprotective in Parkinson disease cell models.

PubMed

Hong, Chien Tai; Chau, Kai-Yin; Schapira, Anthony H V

2016-05-05

Meclizine is a well-tolerated drug routinely used as an anti-histamine agent in the management of disequilibrium. Recently, meclizine has been assessed for its neuroprotective properties in ischemic stroke and Huntington disease models. We found that meclizine protected against 6-hydroxydopamine-induced apoptosis and cell death in both SH-SY5Y cells and rat primary cortical cultures. Meclizine increases the level of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), which activates phosphofructokinase, a rate-determining enzyme of glycolysis. This protection is therefore mediated by meclizine's ability to enhance glycolysis and increase mitochondrial hyperpolarization. Meclizine represents an interesting candidate for further investigation to re-purpose for its potential to be neuroprotective in Parkinson disease.

Pharmaceuticals in grocery market fish fillets by gas chromatography-mass spectrometry.

PubMed

Mottaleb, Musavvir Arafat; Stowe, Carly; Johnson, Daniel R; Meziani, Mohammed J; Mottaleb, M Abdul

2016-01-01

Occurrences of pharmaceuticals are evident in aquatic organisms. A reproducible gas chromatography-mass spectrometry (GC-MS) method using selected ion monitoring (SIM) has been used to determine the anti-histamine diphenhydramine (DPH), anti-anxiety diazepam (DZP), anti-seizure carbamazepine (CZP) drugs and their metabolites in grocery stores fish that were homogenized, extracted, pre-concentrated, cleaned up, and examined. Identifications of the compounds in extracts were obtained by comparing similar mass spectral features and retention properties with standards. Among nine frequently detected drugs, only DPH and DZP were observed and ranged from 0.61 to 6.21 and 1.99 to 16.57 ng/g, respectively, in fourteen fish species. These concentration values were lower than the environmental fish. Mean spike recoveries of analytes exceeded 75% with relative standard deviations (RSD)<10%. The statistically-derived method detection limits (MDLs) for nine compounds ranged from 0.13 to 5.56 ng/g. Average surrogate recoveries were 80-85% with 4-9% RSD. Copyright © 2015 Elsevier Ltd. All rights reserved.

New therapies for allergic rhinitis.

PubMed

Braido, Fulvio; Sclifò, Francesca; Ferrando, Matteo; Canonica, Giorgio Walter

2014-04-01

Because of its burden on patient's lives and its impact on asthma, allergic rhinitis must be treated properly with more effective and safer treatments. According to guidelines by Allergic Rhinitis and Its Impact on Asthma (ARIA), the classification, pathogenesis, and treatment of allergic rhinitis are well defined. Currently, second-generation antihistamines and inhaled steroids are considered the cornerstone of first-line therapy. However, new formulations of available drugs (e.g., loratadine and rupatadine oral solution, ebastine fast-dissolving tablets, and the combination of intranasal fluticasone propionate and azelastine hydrochloride), recently discovered molecules (e.g., ciclesonide, bilastine, and phosphodiesterase-4 inhibitors), immunologic targets (e.g., omalizumab), and unconventional treatments (e.g., homeopathic treatments) are currently under investigation and represent a new frontier in modern medicine and in allergic rhinitis management. The aim of this review is to provide an update on allergic rhinitis treatment, paying particular attention to clinical trials published within the past 20 months that assessed the efficacy and safety of new formulations of available drugs or new molecules.

Simultaneous screening for 238 drugs in blood by liquid chromatography-ion spray tandem mass spectrometry with multiple-reaction monitoring.

PubMed

Gergov, M; Ojanperä, I; Vuori, E

2003-09-25

A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method is presented for the qualitative screening for 238 drugs in blood samples, which is considerably more than in previous methods. After a two-step liquid-liquid extraction and C(18) chromatography, the compounds were introduced into a triple quadrupole mass spectrometer equipped with a turbo ion spray ion source operating in the positive ionization mode. Identification was based on the compound's absolute retention time, protonated molecular ion, and one representative fragment ion obtained by multiple reaction monitoring (MRM) at an individually selected collision energy of 20, 35, or 50 eV. The limit of detection (LOD) for the majority of the compounds (80%) was < or = 0.05 mg/l, ranging from 0.002 mg/l (e.g., antihistamines) to 5 mg/l (acidic compounds), and for malathion it was 10 mg/l. The LOD values were sufficiently low to allow the majority of compounds to be detected at therapeutic concentrations in the blood.

Enantioseparation of Six Antihistamines with Immobilized Cellulose Chiral Stationary Phase by HPLC

PubMed Central

Zhou, Jie; Luo, Pei; Chen, Shanshan; Meng, Lingchang; Sun, Chong; Du, Qiuzheng; Sun, Fang

2016-01-01

A stereoselective high performance liquid chromatography method has been developed for the chiral separation of the enantiomers of six antihistamines, doxylamine, carbinoxamine, dioxopromethazine, oxomemazine, cetirizine and hydroxyzine. The effects of mobile phase additive, column temperature and flow rate on the retention time and resolution were studied. Enantiomeric separation of cetirizine, doxylamine and hydroxyzine were achieved on cellulose tris-(3,5-dichlorophenylcarbamate) immobilized on silica gel chiral stationary phase known as Chiralpak IC (RS = 3.74, RS = 1.85 and RS = 1.74, respectively). PMID:26657408

Disease-modifying antirheumatic drugs other than methotrexate in rheumatoid arthritis and seronegative arthritis.

PubMed

Nandi, Pradip; Kingsley, Gabrielle H; Scott, David L

2008-05-01

To outline recent research findings with nonmethotrexate disease-modifying antirheumatic drugs in rheumatoid arthritis and seronegative arthritis spanning systematic reviews, randomized controlled trials, observational clinical practice trials and assessments of adverse effects. Systematic reviews show no important differences between methotrexate, leflunomide and sulfasalazine monotherapies; early disease-modifying antirheumatic drug therapy reduces erosive progression. Observational studies show that nonmethotrexate disease-modifying antirheumatic drugs are widely prescribed; their usage has increased in the biologic era. A systemic review also showed patients who failed monotherapy benefited from disease-modifying antirheumatic drug combinations without excess toxicity. Randomized controlled trials of intensive initial disease-modifying antirheumatic drug combinations showed they reduce synovitis and erosive damage, especially when used with steroids. The subsequent sequence of disease-modifying antirheumatic drugs and the value of changing disease-modifying antirheumatic drug monotherapies or stepping-up to combination disease-modifying antirheumatic drugs are, however, unresolved. The adverse risks of nonmethotrexate disease-modifying antirheumatic drugs have been evaluated, including infections and lung disease; patient-related risks seem more important than drug-related risks, though several disease-modifying antirheumatic drugs increase both types of adverse reactions. Two limitations of nonmethotrexate disease-modifying antirheumatic drugs are reduced impact on comorbidities like cardiovascular disease and reduced patient and clinician preferences for these treatments. Nonmethotrexate disease-modifying antirheumatic drugs are effective, relatively well tolerated and widely used. Their role in intensive treatment strategies in early rheumatoid arthritis appears of crucial importance.

Anticholinergic drugs and negative outcomes in the older population: from biological plausibility to clinical evidence.

PubMed

Collamati, Agnese; Martone, Anna Maria; Poscia, Andrea; Brandi, Vincenzo; Celi, Michela; Marzetti, Emanuele; Cherubini, Antonio; Landi, Francesco

2016-02-01

The use of medication with anticholinergic properties is widespread among older subjects. Many drugs of common use such as antispasmodics, bronchodilators, antiarrhythmics, antihistamines, anti-hypertensive drugs, antiparkinson agents, skeletal muscle relaxants, and psychotropic drugs have been demonstrated to have an anticholinergic activity. The most frequent adverse effects are dry mouth, nausea, vomiting, constipation, abdominal pain, urinary retention, blurred vision, tachycardia and neurologic impairment such as confusion, agitation and coma. A growing evidence from experimental studies and clinical observations suggests that drugs with anticholinergic properties can cause physical and mental impairment in the elderly population. However, the morbidity and management issues associated with unwanted anticholinergic activity are underestimated and frequently overlooked. Moreover, their possible relation with specific negative outcome in the elderly population is still not firmly established. The aim of the present review was to evaluate the relationship between the use of drugs with anticholinergic activity and negative outcomes in older persons. We searched PubMed and Cochrane combining the search terms "anticholinergic", "delirium", "cognitive impairment", "falls", "mortality" and "discontinuation". Medicines with anticholinergic properties may increase the risks of functional and cognitive decline, morbidity, institutionalization and mortality in older people. However, such evidences are still not conclusive probably due to possible confounding factors. In particular, more studies are needed to investigate the effects of discontinuation of drug with anticholinergic properties. Overall, minimizing anticholinergic burden should always be encouraged in clinical practice to improve short-term memory, confusion and delirium, quality of life and daily functioning.

Metabolic profiling using HPLC allows classification of drugs according to their mechanisms of action in HL-1 cardiomyocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strigun, Alexander; Wahrheit, Judith; Beckers, Simone

Along with hepatotoxicity, cardiotoxic side effects remain one of the major reasons for drug withdrawals and boxed warnings. Prediction methods for cardiotoxicity are insufficient. High content screening comprising of not only electrophysiological characterization but also cellular molecular alterations are expected to improve the cardiotoxicity prediction potential. Metabolomic approaches recently have become an important focus of research in pharmacological testing and prediction. In this study, the culture medium supernatants from HL-1 cardiomyocytes after exposure to drugs from different classes (analgesics, antimetabolites, anthracyclines, antihistamines, channel blockers) were analyzed to determine specific metabolic footprints in response to the tested drugs. Since most drugsmore » influence energy metabolism in cardiac cells, the metabolite 'sub-profile' consisting of glucose, lactate, pyruvate and amino acids was considered. These metabolites were quantified using HPLC in samples after exposure of cells to test compounds of the respective drug groups. The studied drug concentrations were selected from concentration response curves for each drug. The metabolite profiles were randomly split into training/validation and test set; and then analysed using multivariate statistics (principal component analysis and discriminant analysis). Discriminant analysis resulted in clustering of drugs according to their modes of action. After cross validation and cross model validation, the underlying training data were able to predict 50%-80% of conditions to the correct classification group. We show that HPLC based characterisation of known cell culture medium components is sufficient to predict a drug's potential classification according to its mode of action.« less

Critical appraisal of the unmet needs in the treatment of chronic spontaneous urticaria with omalizumab: an Italian perspective.

PubMed

Asero, Riccardo; Canonica, Giorgio W; Cristaudo, Antonio; Fierro, Maria T; Girolomoni, Giampiero; Marzano, Angelo V; Nettis, Eustachio; Pepe, Patrizia; Pigatto, Paolo; Rossi, Oliviero

2017-12-01

The humanized anti-IgE antibody omalizumab has been available for patients with chronic spontaneous urticaria (CSU) in Italy since 2015. This review summarizes the unresolved issues and unmet therapeutic needs associated with omalizumab and discusses practical recommendations for its use in the management of CSU. Although modern second-generation H1-antihistamines are the standard of care for patients with CSU, adjunctive treatments (including omalizumab) may be required for effective control of symptoms in many patients. Evidence from clinical trials and experience from daily clinical practice suggest that the use of omalizumab in patients with CSU who have inadequate response to H1-antihistamines remains challenging. Based on current international guidelines, omalizumab labelling information and our experience in clinical practice, we provide treatment recommendations regarding the use of omalizumab in patients with CSU. These include: optimal treatment duration, the use of concomitant antihistamine therapy, the definition and management of disease relapse after treatment, and the management of patients with late or no response to treatment.

Validated spectroflurimetric determination of some H1 receptor antagonist drugs in pharmaceutical preparations through charge transfer complexation.

PubMed

el-Din, Mohie K Sharaf; Ibrahim, Fawzia; Eid, Manal I; Wahba, Mary E K

2012-01-01

A validated simple, rapid, and selective spectrofluorimetric method was developed for the determination of some antihistaminic H(1) receptor antagonist drugs namely ebastine (EBS), cetirizine dihydrochloride (CTZ), and fexofenadine hydrochloride (FXD). The method is based on the reaction of the cited drugs with some Π acceptors namely p-chloranilic acid (CLA), tetracyanoethylene (TCNE), and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) to give highly fluorescent derivatives. The fluorescence intensity-concentration plots were rectilinear over the concentration ranges of 0.2-3.0, 0.2-2.5 and 0.15-2.0 μg/ml for EBS with CLA, DDQ, and TCNE respectively; 0.5-7.0, 0.5-6.0, and 0.2-4.0 μg/ml for CTZ with the previously mentioned reagents, and 0.2-3.5, 0.5-6.0, and 0.2-3.5 μg/ml for FXD. The factors affecting the formation of the reaction products were carefully studied and optimized. The method was applied for the determination of the studied drugs in their dosage forms. The results obtained were in good agreement with those obtained by the comparison methods. Reactions Stoichiometries of the complexes formed between the studied drugs and Π acceptors were defined by the Job's method of the continuous variation and found in 1:1 in all cases.

A class of tricyclic compounds blocking malaria parasite oocyst development and transmission.

PubMed

Eastman, Richard T; Pattaradilokrat, Sittiporn; Raj, Dipak K; Dixit, Saurabh; Deng, Bingbing; Miura, Kazutoyo; Yuan, Jing; Tanaka, Takeshi Q; Johnson, Ronald L; Jiang, Hongying; Huang, Ruili; Williamson, Kim C; Lambert, Lynn E; Long, Carole; Austin, Christopher P; Wu, Yimin; Su, Xin-Zhuan

2013-01-01

Malaria is a deadly infectious disease in many tropical and subtropical countries. Previous efforts to eradicate malaria have failed, largely due to the emergence of drug-resistant parasites, insecticide-resistant mosquitoes and, in particular, the lack of drugs or vaccines to block parasite transmission. ATP-binding cassette (ABC) transporters are known to play a role in drug transport, metabolism, and resistance in many organisms, including malaria parasites. To investigate whether a Plasmodium falciparum ABC transporter (Pf14_0244 or PfABCG2) modulates parasite susceptibility to chemical compounds or plays a role in drug resistance, we disrupted the gene encoding PfABCG2, screened the recombinant and the wild-type 3D7 parasites against a library containing 2,816 drugs approved for human or animal use, and identified an antihistamine (ketotifen) that became less active against the PfABCG2-disrupted parasite in culture. In addition to some activity against asexual stages and gametocytes, ketotifen was highly potent in blocking oocyst development of P. falciparum and the rodent parasite Plasmodium yoelii in mosquitoes. Tests of structurally related tricyclic compounds identified additional compounds with similar activities in inhibiting transmission. Additionally, ketotifen appeared to have some activity against relapse of Plasmodium cynomolgi infection in rhesus monkeys. Further clinical evaluation of ketotifen and related compounds, including synthetic new derivatives, in blocking malaria transmission may provide new weapons for the current effort of malaria eradication.

Pharmacy benefits management in the Veterans Health Administration: 1995 to 2003.

PubMed

Sales, Mariscelle M; Cunningham, Francesca E; Glassman, Peter A; Valentino, Michael A; Good, Chester B

2005-02-01

The Department of Veterans Affairs (VA) Pharmacy Benefits Management Strategic Healthcare Group (VA PBM) oversees the formulary for the entire VA system, which serves more than 4 million veterans and provides more than 108 million prescriptions per year. Since its establishment in 1995, the VA PBM has managed pharmaceuticals and pharmaceutical-related policies, including drug safety and efficacy evaluations, pharmacologic management algorithms, and criteria for drug use. These evidence-based practices promote, optimize, and assist VA providers with the safe and appropriate use of pharmaceuticals while allowing for formulary decisions that can result in substantial cost savings. The VA PBM also has utilized various contracting techniques to standardize generic agents as well as specific drugs and drug classes (eg, antihistamines, angiotensin-converting enzyme inhibitors, alpha-blockers, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors [statins]). These methods have enabled the VA to save approximately dollar 1.5 billion since 1996 even as drug expenditures continued to rise from roughly dollar 1 billion in fiscal year (FY) 1996 to more than dollar 3 billion in FY 2003. Furthermore, the VA PBM has established an outcomes research section to undertake quality-improvement and safety initiatives that ultimately monitor and determine the clinical impact of formulary decisions on the VA system nationwide. The experiences of this pharmacy benefits program, including clinical and contracting processes/procedures and their impact on the VA healthcare system, are described.

Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi.

PubMed

Planer, Joseph D; Hulverson, Matthew A; Arif, Jennifer A; Ranade, Ranae M; Don, Robert; Buckner, Frederick S

2014-07-01

An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper) have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's) in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM), a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM), and an antifolate drug (pyrimethamine, EC50 of 3.8 µM) and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease.

The use of a responder analysis to identify clinically meaningful differences in chronic urticaria patients following placebo- controlled treatment with rupatadine 10 and 20 mg.

PubMed

Giménez-Arnau, A; Izquierdo, I; Maurer, M

2009-09-01

According to the EAACI/GA(2)LEN/EDF guidelines for urticaria management, modern non-sedating H1-antihistamines are the first-line symptomatic treatment for chronic urticaria. Two previous randomized clinical trials demonstrated rupatadine efficacy and safety in chronic urticaria treatment. However, a responder analysis to identify clinically meaningful differences in patients with chronic urticaria has not yet been performed. This analysis includes the pooled data from two randomized, double-blind, placebo-controlled, multicentre studies in which chronic urticaria patients were treated with rupatadine at different doses. Responder rates were defined as the percentage of patients after 4 weeks of treatment who exhibited a reduction of symptoms by at least 50% or 75% as compared to baseline. The variables analysed were as follows: Mean Pruritus Score (MPS), Mean Number of Wheals (MNW), and Mean Urticaria Activity Score (UAS). A total of 538 patients were included. This responder analysis, using different response levels, shows that the efficacy of rupatadine 10 mg and 20 mg is significantly better as compared to placebo in the treatment of chronic urticaria patients. Notably, treatment with rupatadine 20 mg daily resulted in a higher percentage of patients with response of 75% symptom reduction or better than rupatadine 10 mg. Our results support the use of higher than standard doses of non sedating antihistamines in chronic urticaria. We strongly recommend performing and reporting responder analyses for established and new drugs used by patients with chronic urticaria.

Repeated-dose effects of mequitazine, cetirizine and dexchlorpheniramine on driving and psychomotor performance.

PubMed

Theunissen, Eef L; Vermeeren, Annemiek; Ramaekers, Johannes G

2006-01-01

Previous studies have demonstrated that the antihistamines mequitazine, cetirizine and dexchlorpheniramine produce mild sedation after single doses. It is unknown, however, whether acute sedation persists after repeated dosing. Therefore, this study assessed the effects of repeated dosing of these antihistamines on driving and psychomotor performance. Sixteen healthy volunteers were treated with mequitazine 10 mg q.a.m., cetirizine 10 mg q.a.m., dexchlorpheniramine Repetab 6 mg b.i.d. and placebo for four separate 8-day periods. Drug effects were assessed on days 1 and 8 using on-the-road driving tests (highway driving and car following), psychomotor tests (tracking and divided attention) and subjective questionnaires. Dexchlorpheniramine and mequitazine significantly impaired driving performance on the highway driving test on the first day; dexchlorpheniramine increased Standard Deviation of Lateral Position by 2 cm [95% confidence interval (CI) 0.5, 3.8] and mequitazine by 2.5 cm (CI 1.0, 4.3). These effects on driving performance disappeared after 8 days of treatment. No effect of treatment was found on car following, tracking and divided attention. Although subjective ratings confirmed that subjects knew their driving had been impaired in the mequitazine and dexchlorpheniramine condition after completion of the highway driving test on day 1, they did not expect their driving to be affected before the start of the test. Cetirizine did not impair performance on any of the tests. Single doses of mequitazine 10 mg and dexchlorpheniramine Repetab 6 mg cause mild driving impairment. However, when taken over several days, the impairing effect wears off, possibly as a result of tolerance.

Patient assessment of onset of action and overall satisfaction with ebastine fast-dissolving tablets in allergic rhinitis.

PubMed

Roger, Albert; Fortea, Josep; Mora, Sheila; Artés, Maite

2008-08-01

To evaluate patient perception of the onset of action and overall satisfaction with a fast-dissolving tablet (FDT) formulation of ebastine in patients with intermittent or persistent allergic rhinitis. This was a cross-sectional, multicenter, pharmacy-based survey involving adult patients (>18 years) with allergic rhinitis who presented with a prescription for ebastine FDT. Via a telephone interview, patients were asked to evaluate the characteristics of ebastine FDT in comparison with their previous experience with other antihistamines. 100 patients with allergic rhinitis were included in the study (41 had intermittent disease, 57 persistent disease and two with unknown disease states). Patients rated ebastine FDT very highly (mean scores: 4.5-4.7 out of a possible 5) for all characteristics related to convenience, such as easy to take, easy to carry around in a bag or pocket, suitable for taking anytime/anywhere, and convenient to use. A total of 85% of patients perceived ebastine FDTs onset of action to be fast or very fast, and 77% indicated that it acted faster than their usual antihistamine. A total of 96% were satisfied or very satisfied with ebastine FDT and 98% were interested in using the drug again. Patients with rhinitis rate ebastine FDT very highly in terms of its formulation, convenience of use and its rapid onset of action. These characteristics resulted in a high level of individual satisfaction with the new formulation and a clear preference by the majority of patients to use ebastine FDT in the future.

Antibiotic use in children and the use of medicines by parents.

PubMed

de Jong, Josta; Bos, Jens H J; de Vries, Tjalling W; de Jong-van den Berg, Lolkje T W

2012-06-01

Antibiotic drugs are frequently used for viral infections in children. It is probable that health beliefs and parental concern have great influence on the use of drugs in children. This study, performed in The Netherlands, investigates whether the use of antibiotics in children is associated with the use of medicines by parents. In this observational cohort study, the authors selected 6731 children from the prescription database IADB.nl who did not receive antibiotics until their fifth birthday and 1479 children who received at least one antibiotic prescription every year. The authors then selected parents for each group of children (5790 mothers and 4250 fathers for the children who did not receive antibiotics and 1234 mothers and 1032 fathers for the children who regularly received antibiotics). The authors compared the use of antibiotics and other medicines between the two groups of parents. Parents of children who received antibiotics recurrently were found to use more antibiotics themselves compared with parents of children who did not receive antibiotics. Moreover, this group also showed a higher percentage of chronic medication use: (11.3 vs 6.2% (mothers) and 13.1% vs 9.5% (fathers)). Mothers more often use antacids, non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, anxiolytics, hypnotics, antidepressants, drugs for treatment of asthma and antihistamines. Fathers use more antacids, cardiovascular drugs, NSAIDs and asthma drugs. The parents of children who receive antibiotic drugs regularly use more medicines compared with the parents of children who use no antibiotic drugs. Parents' medicine use may influence that of children and is a factor physicians and pharmacists should take into account.

Accidental poisoning in childhood: five year urban population study with 15 year analysis of fatality.

PubMed Central

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

1984-01-01

Patterns of accidental poisoning in children are changing dramatically. A five year population study (1977-81) was undertaken in urban children from Brisbane (population 1 000 000). A total of 2098 children were poisoned during this period with only one fatality, which represents a dramatic reduction in mortality. Over the past 15 years (1968-82) 13 children have died from accidental poisoning from this population, and two were murdered with drugs. A study of secular trends has indicated that peak incidence occurred in 1979, and the rate has been falling progressively since. The current age corrected rate of poisoning is 393 per 100 000 children per year (0-5 year olds). The rank order of poisons, drugs, and chemicals causing hospital admission and death is: petroleum distillates 13%; antihistamines 9%; benzodiazepines 9%; bleach and detergents 7%; and aspirin 6%. The ratio of fatalities to ingestions requiring hospital admission was calculated to give an index of a practical danger of noxious agents to which children are currently exposed and the rank order is: cardiotoxic drugs, one fatality to 25 ingestions; tricyclic antidepressants, one to 44; sympathomimetic drugs, one to 54; caustic soda, one to 68; aspirin, one fatality to 350 ingestions. Accidental poisoning of children leading to death has been reduced because patterns of drug prescriptions have changed, packaging of dangerous drugs has been made safer, and substances such as kerosene have been coloured blue. PMID:6140065

Medication exposure and spontaneous abortion: a case-control study using a French medical database.

PubMed

Abadie, D; Hurault-Delarue, C; Damase-Michel, C; Montastruc, J L; Lacroix, I

2015-01-01

Few studies have been conducted to investigate drug effects on spontaneous abortion risk. The objective of the present study was to evaluate the potential association between first trimester drug exposure and spontaneous abortion occurrence. The authors performed a nested case-control study using data from TERAPPEL, a French medical database. Cases were the women who had a spontaneous abortion (before the 22nd week of amenorrhea) and controls were women who gave birth to a child. Analyzed variables were: maternal age, obstetric history, tobacco, and alcohol and drug consumption during the first trimester of pregnancy. For comparison of drug exposures between cases and controls, the authors calculated odds ratios (ORs) by means of multivariate logistic regressions adjusted on age and on other drug exposures. The study included 838 cases and 4,508 controls that were identified in the database. In adjusted analyses, cases were more exposed than controls to "non-selective monoamine reuptake inhibitors" [OR=2.2 (CI 95% 1.5-3.3)], "antiprotozoals" [OR = 1.6 (CI 95% 1.1 - 2.5)] and "centrally acting antiobesity products" [OR = 3.4 (CI 95% 1.9 - 6.2)]. Conversely, controls were more exposed than cases to H1 antihistamines [OR = 0.6 (CI 95% 0.4 - 0.9)]. This exploratory study highlights some potential associations between first trimester drug exposure and risk of spontaneous abortion. Further studies have to be carried out to investigate these findings.

Controlling prescription drug expenditures: a report of success.

PubMed

Miller, David P; Furberg, Curt D; Small, Ronald H; Millman, Franklyn M; Ambrosius, Walter T; Harshbarger, Julia S; Ohl, Christopher A

2007-08-01

To determine whether a multi-interventional program can limit increases in prescription drug expenditures while maintaining utilization of needed medications. Quasi-experimental, pre-post design. The program included formulary changes, quantity limits, and mandatory pill splitting for select drugs implemented in phases. We assessed the short-term effects of each intervention by comparing class-specific drug spending and generic medication use before and after benefit changes. Long-term effects were determined by comparing overall spending with projected spending estimates, and by examining changes in the planwide use of generic medications over time. Effects on medication utilization were assessed by examining members' use of selected classes of chronic medications before and after the policy changes. Over 3 years, the plan and members saved $6.6 million attributed to the interventions. Most of the savings were due to the reclassification of select brand-name drugs to nonpreferred status (estimated annual savings, $941,000), followed by the removal of nonsedating antihistamines from the formulary (annual savings, $565,000), and the introduction of pill splitting (annual savings, $342,000). Limiting quantities of select medications had the smallest impact (annual savings, $135,000). Members' use of generic medications steadily increased from 40% to 57%. Although 17.5% of members stopped using at least 1 class of selected medications, members' total use of chronic medications remained constant. A combination of interventions can successfully manage prescription drug spending while preserving utilization of chronic medications. Additional studies are needed to determine the effect of these cost-control interventions on other health outcomes.

Electrochemotherapy-induced radiation recall in a cat.

PubMed

Spugnini, Enrico P; Dotsinsky, Ivan; Mudrov, Nikolay; Citro, Gennaro; Caruso, Giovanni; Cardelli, Pierluigi; Baldi, Alfonso

2008-01-01

Electrochemotherapy is gaining popularity for the treatment of malignancies of companion animals due to its efficacy and low cost. In this paper, we describe the successful treatment of a recurring fibrosarcoma in a cat by using cisplatin selectively driven within the tumor cells by trains of biphasic pulses. The cat's tumor did not recur over the following five months, however the cat did experience severe erythema at the site of previous irradiation, followed by moist desquamation and ulcer that required debridement and prolonged therapy with steroids and antihistaminic drugs. The symptoms and the response to symptomatic therapy were strongly suggestive of radiation recall. Electrochemotherapy (ECT) should be used with caution in previously irradiated areas. Further studies are warranted in this field due to its potential as a rescue for relapsing tumors.

Management of chronic spontaneous urticaria in routine clinical practice: A Delphi-method questionnaire among specialists to test agreement with current European guidelines statements.

PubMed

Giménez-Arnau, A; Ferrer, M; Bartra, J; Jáuregui, I; Labrador-Horrillo, M; Frutos, J Ortiz de; Silvestre, J F; Sastre, J; Velasco, M; Valero, A

Chronic spontaneous urticaria (CSU) is a frequent clinical entity that often presents a diagnostic and therapeutic challenge. To explore the degree of agreement that exists among the experts caring for patients with CSU diagnosis, evaluation, and management. An online survey was conducted to explore the opinions of experts in CSU, address controversial issues, and provide recommendations regarding its definition, natural history, diagnosis, and treatment. A modified Delphi method was used for the consensus. The questionnaire was answered by 68 experts (dermatologists, allergologists, and primary care physicians). A consensus was reached on 54 of the 65 items posed (96.4%). The experts concluded that CSU is a difficult-to-control disease of unpredictable evolution. Diagnostic tests should be limited and based on clinical history and should not be indiscriminate. Autoinflammatory syndromes and urticarial vasculitis must be ruled out in the differential diagnosis. A cutaneous biopsy is only recommended when wheals last more than 24h, to rule out urticarial vasculitis. The use of specific scales to assess the severity of the disease and the quality of life is recommended. In patients with severe and resistant CSU, second-generation H1-antihistamines could be used at doses up to four times the standard dose before giving second-line treatments. Omalizumab is a safe and effective treatment for CSU that is refractory to H1-antihistamines treatment. In general, diagnosis and treatment recommendations given for adults could be extrapolated to children. This work offers consensus recommendations that may be useful in the management of CSU. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Multinational experience with hypersensitivity drug reactions in Latin America.

PubMed

Jares, Edgardo José; Sánchez-Borges, Mario; Cardona-Villa, Ricardo; Ensina, Luis Felipe; Arias-Cruz, Alfredo; Gómez, Maximiliano; Barayazarra, Susana; Bernstein, Jonathan A; Serrano, Carlos D; Cuello, Mabel Noemi; Morfin-Maciel, Blanca María; De Falco, Alicia; Cherrez-Ojeda, Iván

2014-09-01

Epidemiologic drug allergy data from Latin America are scarce, and there are no studies on specific procedures focusing on this topic in Latin America. To assess the clinical characteristics and management of hypersensitivity drug reactions in different Latin American countries. An European Network of Drug Allergy questionnaire survey was implemented in 22 allergy units in 11 Latin American countries to report on consecutive patients who presented with a suspected hypersensitivity drug reaction. Each unit used its own protocols to investigate patients. Included were 868 hypersensitivity drug reactions in 862 patients (71% of adults and elderly patients were women and 51% of children were girls, P = .0001). Children presented with less severe reactions than adults and elderly patients (P < .0001). Urticaria and angioedema accounted for the most frequent clinical presentations (71%), whereas anaphylaxis was present in 27.3% of cases. There were no deaths reported. Nonsteroidal anti-inflammatory drugs (52.3%), β-lactam antibiotics (13.8%), and other antibiotics (10.1%) were the drugs used most frequently. Skin prick tests (16.7%) and provocation tests (34.2%) were the study procedures most commonly used. A large proportion of patients were treated in the emergency department (62%) with antihistamines (68%) and/or corticosteroids (53%). Only 22.8% of patients presenting with anaphylaxis received epinephrine. Nonsteroidal anti-inflammatory drugs and antibiotics were the drugs used in at least 75% of patients. More than half the reactions were treated in the emergency department, whereas epinephrine was administered in fewer than 25% of patients with anaphylaxis. Dissemination of guidelines for anaphylaxis among primary and emergency department physicians should be encouraged. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Targeted analysis of 116 drugs in hair by UHPLC-MS/MS and its application to forensic cases.

PubMed

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

2017-08-01

A multi-target method that can detect a broad range of drugs in human hair, such as hypnotics, anxiolytics, analgesics, benzodiazepines, antihistamines, antidepressants, antipsychotics, and anticonvulsants, was developed based on ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The drugs were extracted from 10 mg of washed hair by incubation for 18 h in a 25:25:50 (v/v/v) mixture of methanol/acetonitrile/2 mM ammonium formate (8% acetonitrile, pH 5.3). For 51% of the basic drugs, the lower limits of quantification (LLOQs) were in the range of 0.05-0.5 pg/mg, and the majority (98%) were ≤ 5 pg/mg. Linearity ranged from LLOQs to 100-500 pg/mg for all the basic drugs. For acid and neutral drugs, the LLOQs ranged from 0.4 to 500 pg/mg, and linearity ranged from LLOQs to 80-40 000 pg/mg. According to published reports on concentrations attained in single dose control studies, the present method is sensitive enough to detect single-dose drug exposure for many of the drugs. The accuracy was within 75-125% for the majority of drugs. Good precision was observed (relative standard deviations [RSD%] < 25%) for most of the compounds, including the prepared quality control (QC) hair samples. The method was applied to forensic cases and concentrations of rarely reported drugs in hair in 25 post-mortem forensic cases were presented. Hair concentrations of amisulpride, gabapentin, mianserin, mepyramine, orphenadrine, and xylometazoline have not been previously reported. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Allergic Rhinitis Control Test questionnaire is valuable in guiding step-down pharmacotherapy treatment of allergic rhinitis.

PubMed

Zhu, Rongfei; Wang, Jingru; Wu, Yuying; Yang, Yongshi; Huang, Nan; Yang, Yaqi; Zhang, Rui; Ma, Dongxia; Yang, Lin; Demoly, Pascal

2018-06-07

Allergic Rhinitis Control Test(ARCT) has been validated in allergic rhinitis(AR) step-up pharmacotherapy management approach. The aim of our study was to evaluate the potential of ARCT in AR step-down pharmacotherapy. In an open-labelled randomized controlled study, AR patients controlled with intranasal corticosteroid(INS) plus antihistamine(step 4) were included and randomized into an ARCT or a control group. In ARCT group, the patients were followed up every 15 days; if ARCT score was ≥20(controlled AR), the patient would step down to step 3(INS), step 2(daily antihistamine), step 1(antihistamine as needed) and step 0(no medication) consecutively; if ARCT score was strictly <20, the treatment would not be adjusted. In the control group, patients would be treated with step 4 medications during the whole study. Rhinitis Quality-of-Life Questionnaire(RQLQ), Morisky Questionnaire and Brief Illness-Perception-Questionnaire(B-IPQ) were completed at baseline and the end of the study. Medication use and side effects were recorded. A total of 255 AR patients were enrolled into the study, 27 patients dropped out. The control rates at D45 were 77.8% in ARCT group and 85.8% in control group(P>0.05). ARCT group had less mean medication use than control group(INS 1.27 vs. 2.22 bottle, antihistamines 35.9 vs. 61.4 tablets)(P<0.05). RQLQ, Morisky and B-IPQ score were significantly improved in both groups after treatment(P<0.05). Stepping down AR medications in controlled patients led to similar clinical outcomes at reduced cost compared with those who maintained their current treatment level. ARCT is an optimal tool for evaluating the step-down eligibility. Copyright © 2018. Published by Elsevier Inc.

Selecting the optimal oral antihistamine for patients with allergic rhinitis.

PubMed

Lehman, Jeffrey M; Blaiss, Michael S

2006-01-01

Allergic rhinitis (AR) is now recognised as a global health problem that affects 10-30% of adults and up to 40% of children. Each year, millions of patients seek treatment from their healthcare provider. However, the prevalence of AR maybe significantly underestimated because of misdiagnosis, under diagnosis and failure of patients to seek medical attention. In addition to the classical symptoms such as sneezing, nasal pruritus, congestion and rhinorrhoea, it is now recognised that AR has a significant impact on quality of life (QOL). This condition can lead to sleep disturbance as a result of nasal congestion, which leads to significant impairment in daily activities such as work and school. Traditionally, AR has been subdivided into seasonal AR (SAR) or perennial AR (PAR). SAR symptoms usually appear during a specific season in which aeroallergens are present in the outdoor air such as tree and grass pollen in the spring and summer and weed pollens in the autumn (fall); and PAR symptoms are present year-round and are triggered by dust mite, animal dander, indoor molds and cockroaches. Oral histamine H(1)-receptor antagonists (H(1) antihistamines) are one of the most commonly prescribed medications for the treatment of AR. There are several oral H(1) antihistamines available and it is important to know the pharmacology, such as administration interval, onset of action, metabolism and conditions that require administration adjustments. When prescribing oral H(1) antihistamines, the healthcare provider must take into account the clinical efficacy and weigh this against the risk of adverse effects from the agent. In addition to the clinical efficacy, potential for improvement in QOL with a particular treatment should also be considered.

Activity of ergoferon against lethal influenza A (H3N2) virus infection in mice.

PubMed

Skarnovich, Maria A; Emelyanova, Alexandra G; Petrova, Nataliia V; Borshcheva, Alena A; Gorbunov, Evgeniy A; Mazurkov, Oleg Yu; Skarnovich, Maksim O; Tarasov, Sergey A; Shishkina, Larisa N; Epstein, Oleg I

2017-01-01

The influenza A virus accounts for serious annual viral upper respiratory tract infections. It is constantly able to modify its antigenic structure, thus evading host defence mechanisms. Moreover, currently available anti-influenza agents have a rather limited application, emphasizing the further need for new effective treatments. One of them is ergoferon, a drug containing combined polyclonal antibodies - anti-interferon gamma, anti-CD4 receptor and anti-histamine - in released-active form. The purpose of the study was to assess ergoferon antiviral efficacy in mice challenged with the A/Aichi/2/68 (H3N2) influenza virus. The virus was inoculated intranasally at a 90% lethal dose. Ergoferon was administered at 0.4 ml/day per os in a preventive and therapeutic regimen - daily for 5 days prior to and for 16 days after the challenge. The reference product, Tamiflu (oseltamivir), was used as a positive control treatment - at 20 mg/kg/day for 5 days after the challenge. Mice in the negative control group received distilled water which had been utilized for test sample preparation; untreated control animals received no treatment. Antiviral efficacy was assessed by an increase in survival rate, average life expectancy and virus titre reduction in the challenged mouse lungs. Survival rate and average life expectancy values were increased significantly in groups treated with ergoferon and Tamiflu, as compared with controls. Lung virus titres were reduced in these groups as observed on days 2 and 4 post-inoculation. Ergoferon demonstrated antiviral activity by reducing the severity and duration of the major signs of induced influenza infection.

Management of Allergic Rhinitis

PubMed Central

Sausen, Verra O.; Marks, Katherine E.; Sausen, Kenneth P.; Self, Timothy H.

2005-01-01

Allergic rhinitis is the most common chronic childhood disease. Reduced quality of life is frequently caused by this IgE-mediated disease, including sleep disturbance with subsequent decreased school performance. Asthma and exercise-induced bronchospasm are commonly seen concurrently with allergic rhinitis, and poorly controlled allergic rhinitis negatively affects asthma outcomes. Nonsedating antihistamines or intranasal azelastine are effective agents to manage allergic rhinitis, often in combination with oral decongestants. For moderate to severe persistent disease, intranasal corticosteroids are the most effiective agents. Some patients require concomitant intranasal corticosteroids and nonsedating antihistamines for optimal management. Other available agents include leukotriene receptor antagonists, intranasal cromolyn, intranasal ipratropium, specific immunotherapy, and anti-IgE therapy. PMID:23118635

Identification of a coumarin-based antihistamine-like small molecule as an anti-filoviral entry inhibitor.

PubMed

Cheng, Han; Schafer, Adam; Soloveva, Veronica; Gharaibeh, Dima; Kenny, Tara; Retterer, Cary; Zamani, Rouzbeh; Bavari, Sina; Peet, Norton P; Rong, Lijun

2017-09-01

Filoviruses, consisting of Ebola virus, Marburg virus and Cuevavirus, cause severe hemorrhagic fevers in humans with high mortality rates up to 90%. Currently, there is no approved vaccine or therapy available for the prevention and treatment of filovirus infection in humans. The recent 2013-2015 West African Ebola epidemic underscores the urgency to develop antiviral therapeutics against these infectious diseases. Our previous study showed that GPCR antagonists, particularly histamine receptor antagonists (antihistamines) inhibit Ebola and Marburg virus entry. In this study, we screened a library of 1220 small molecules with predicted antihistamine activity, identified multiple compounds with potent inhibitory activity against entry of both Ebola and Marburg viruses in human cancer cell lines, and confirmed their anti-Ebola activity in human primary cells. These small molecules target a late-stage of Ebola virus entry. Further structure-activity relationship studies around one compound (cp19) reveal the importance of the coumarin fused ring structure, especially the hydrophobic substituents at positions 3 and/or 4, for its antiviral activity, and this identified scaffold represents a favorable starting point for the rapid development of anti-filovirus therapeutic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Drug-induced seizures in children and adolescents presenting for emergency care: current and emerging trends.

PubMed

Finkelstein, Y; Hutson, J R; Freedman, S B; Wax, P; Brent, J

2013-01-01

Seizures may be the presenting manifestation of acute poisoning in children. Knowledge of the etiologic agent, or likely drug-class exposure, is crucial to minimize morbidity and optimize care. To describe the agents most commonly responsible for pediatric drug-induced seizures, whose evaluation included a medical toxicology consultation in the United States. Using the 37 participating sites of the Toxicology Investigators Consortium (ToxIC) Case Registry, a cross-country surveillance tool, we conducted an observational study of a prospectively collected cohort. We identified all pediatric (younger than 18 years) reports originating from an Emergency Department (ED) which included a chemical or drug-induced seizure, and required a medical toxicology consultation between April 1, 2010 and March 31, 2012. Results. We identified 142 pediatric drug-induced seizure cases (56% male), which represent nearly 5% of pediatric cases requiring bedside consultation by medical toxicologists. One-hundred and seven cases (75%) occurred in children aged 13-18 years, and 86 (61%) resulted from intentional ingestions. Antidepressants were the most commonly identified agents ingested (n = 61; 42%), of which bupropion was the leading drug (n = 30; 50% of antidepressants), followed by anticholinergics/antihistamines (n = 31; 22%). All antidepressant-induced seizures in teenagers were intentional and represented self-harm behavior. Sympathomimetic agents, including street drugs, represent the most common agents in children younger than 2 years (n = 4/19). Antidepressants, and specifically bupropion, are presently the most common medications responsible for pediatric drug-induced seizures requiring medical toxicology consultation in the United States. In teenagers presenting with new-onset seizures of unknown etiology, the possibility of deliberate self-poisoning should be explored, since most drug-induced seizures in this age group resulted from intentional ingestion.

Development and validation of a rapid stability indicating HPLC-method using monolithic stationary phase and two spectrophotometric methods for determination of antihistaminic acrivastine in capsules

NASA Astrophysics Data System (ADS)

Gouda, Ayman A.; Hashem, Hisham; Jira, Thomas

2014-09-01

Simple, rapid and accurate high performance liquid chromatographic (HPLC) and spectrophotometric methods are described for determination of antihistaminic acrivastine in capsules. The first method (method A) is based on accurate, sensitive and stability indicating chromatographic separation method. Chromolith® Performance RP-18e column, a relatively new packing material consisting of monolithic rods of highly porous silica, was used as stationary phase applying isocratic binary mobile phase of ACN and 25 mM NaH2PO4 pH 4.0 in the ratio of 22.5:77.5 at flow rate of 5.0 mL/min and 40 °C. A diode array detector was used at 254 nm for detection. The elution time of acrivastine was found to be 2.080 ± 0.032. The second and third methods (methods B and C) are based on the oxidation of acrivastine with excess N-bromosuccinimide (NBS) and determination of the unconsumed NBS with, metol-sulphanilic acid (λmax: 520 nm) or amaranth dye (λmax: 530 nm). The reacted oxidant corresponds to the drug content. Beer’s law is obeyed over the concentration range 1.563-50, 2.0-20 and 1.0-10 μg mL-1 for methods A, B and C, respectively. The limits of detection and quantitation were 0.40, 0.292 and 0.113 μg mL-1 and 0.782, 0.973 and 0.376 μg mL-1 for methods A, B and C, respectively. The HPLC method was validated for system suitability, linearity, precision, limits of detection and quantitation, specificity, stability and robustness. Stability tests were done through exposure of the analyte solution for four different stress conditions and the results indicate no interference of degradants with HPLC-method. The proposed methods was favorably applied for determination of acrivastine in capsules formulation. Statistical comparison of the obtained results from the analysis of the studied drug to those of the reported method using t- and F-tests showed no significant difference between them.

Psychotropics in different causes of itch: systematic review with controlled studies*

PubMed Central

Brasileiro, Lízie Emanuelle Eulalio; Barreto, Dayanna Patrícia de Carvalho; Nunes, Emerson Arcoverde

2016-01-01

Among the wide range of symptoms neglected or resistant to conventional treatments in clinical practice, itch is emerging gradually as a theme to be studied. Itch complaints and the negative effects in the quality of life are observed in several medical fields. Although the partially obscure pathophysiology, some researchers decided to check and test the use of psychotropic drugs in resistant itch to conventional topical treatments and antihistamines. The objective of this study was to evaluate scientific evidence in psychotropic use in the treatment of itch of various causes. This is a systematic review of scientific literature. The following databases were used: PubMed, Web of Science, Scopus and Scielo. Randomized controlled trials that should focus on treatment with psychotropic drugs of pruritus of various causes were the inclusion criteria. All articles were analyzed by the authors, and the consensus was reached in cases of disagreement. Fifteen articles were included after analysis and selection in databases, with the majority of clinical trials focusing on psychopharmacological treatment of itch on account of chronic kidney disease. Clinical trials with psychotropic drugs mostly indicated significant improvement in the itching. In most trials of chronic kidney disease as basal disease for itch, greater effectiveness was observed with the use of psychotropic drugs compared with placebo or other antipruritic. However, the small amount of controlled trials conducted precludes the generalization that psychiatric drugs are effective for itch of various causes. PMID:28099602

[Frequency of prescriptions of off-label drugs and drugs not approved for pediatric use in primary health care in a southern municipality of Brazil].

PubMed

Gonçalves, Marcele Giacomin; Heineck, Isabela

2016-01-01

To determine the frequency of prescriptions of off-label drugs and drugs not approved for pediatric use in primary health care in medium-sized municipality of Rio Grande do Sul, Brazil. Cross-sectional study with retrospective data collection, which analyzed prescriptions issued to 326 patients from August to December/2012 in two basic health units in the city of Viamão, state of Rio Grande do Sul. It included all prescriptions of patients whose medical records or service records were available and complete in relation to the date of presence, weight and date of birth. Off-label prescriptions were those which, in relation to the drug leaflet, showed dose different the recommended range, frequency of prescription and/or different form of administration and younger age than the indicated range. Descriptive statistics with absolute frequencies, means and standard deviations were used. During the study period, a total of 731 drug prescriptions were issued and the frequency of off-label medications prescribed was 31.7%, especially antihistamines and antiasthmatics (32.3% and 31.5%, respectively). The main type of off-label prescription was dose (38.8%), followed by age range (31.5%) and frequency of administration (29.3%). Regarding the dose off-label prescription, overdose was more frequent (93.3%) than the underdose (6.7%). Prescriptions of unapproved drugs were not identified. The study showed that off label prescription is common in both assessed units. The observed percentage of off label prescription was higher than that reported by European studies carried out in primary care. On the other hand, the prescription of drugs not approved for children was not observed. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Frequency of prescriptions of off-label drugs and drugs not approved for pediatric use in primary health care in a southern municipality of Brazil

PubMed Central

Gonçalves, Marcele Giacomin; Heineck, Isabela

2016-01-01

Abstract Objective: To determine the frequency of prescriptions of off-label drugs and drugs not approved for pediatric use in primary health care in medium-sized municipality of Rio Grande do Sul, Brazil. Methods: Cross-sectional study with retrospective data collection, which analyzed prescriptions issued to 326 patients from August to December/2012 in two basic health units in the city of Viamão, state of Rio Grande do Sul. It included all prescriptions of patients whose medical records or service records were available and complete in relation to the date of presence, weight and date of birth. Off-label prescriptions were those which, in relation to the drug leaflet, showed dose different the recommended range, frequency of prescription and/or different form of administration and younger age than the indicated range. Descriptive statistics with absolute frequencies, means and standard deviations were used. Results: During the study period, a total of 731 drug prescriptions were issued and the frequency of off-label medications prescribed was 31.7%, especially antihistamines and antiasthmatics (32.3% and 31.5%, respectively). The main type of off-label prescription was dose (38.8%), followed by age range (31.5%) and frequency of administration (29.3%). Regarding the dose off-label prescription, overdose was more frequent (93.3%) than the underdose (6.7%). Prescriptions of unapproved drugs were not identified. Conclusions: The study showed that off label prescription is common in both assessed units. The observed percentage of off label prescription was higher than that reported by European studies carried out in primary care. On the other hand, the prescription of drugs not approved for children was not observed. PMID:26530249

Projected 24-hour post-dose ocular itching scores post-treatment with olopatadine 0.7% versus 0.2.

PubMed

Fidler, Matthew L; Ogundele, Abayomi; Covert, David; Sarangapani, Ramesh

2018-04-21

Olopatadine is an antihistamine and mast cell stabilizer used for treating allergic conjunctivitis. Olopatadine 0.7% has been recently approved for daily dosing in the US, which supersedes the previously approved 0.2% strength. The objective of this analysis was to characterize patients who have better itching relief at 24 h when taking olopatadine 0.7% treatment instead of olopatadine 0.2% (in terms of proportions of responses) and relate this to the severity of baseline itching as an indirect metric of a patient's sensitivity to antihistamines. A differential odds model was developed using data from two conjunctival allergen challenge (CAC) studies to characterize individual-level and population-level response to ocular itching following olopatadine treatment and the data was analyzed retrospectively. This modeling analysis was designed to predict 24 h ocular itching scores and to quantify the differences in 24 h itching relief following treatment with olopatadine 0.2% versus 0.7% in patients with moderate-to-high baseline itching. A one-compartment kinetic-pharmacodynamic E max model was used to determine the effect of olopatadine. Impact of baseline itching severity, vehicle effect and the drug effect on the overall itching scores post-treatment were explicitly incorporated in the model. The model quantified trends observed in the clinical data with regards to both mean scores and the proportions of patients responding to olopatadine treatment. The model predicts a higher proportion of patients in the olopatadine 0.7% versus 0.2% group will experience relief within 24 h. This prediction was confirmed with retrospective clinical data analysis. The number of allergy patients relieved with olopatadine 0.7% increased with higher baseline itching severity scores, when compared to olopatadine 0.2%.

Wastewater treatment plants as a pathway for aquatic contamination by pharmaceuticals in the ebro river basin (northeast Spain).

PubMed

Gros, Meritxell; Petrović, Mira; Barceló, Damià

2007-08-01

The occurrence of 28 pharmaceuticals of major human consumption in Spain, including analgesics and anti-inflammatories, lipid regulators, psychiatric drugs, antibiotics, antihistamines, and beta-blockers, was assessed along the Ebro river basin, one of the biggest irrigated lands in that country. Target compounds were simultaneously analyzed by off-line solid-phase extraction, followed by liquid chromatography-tandem mass spectrometry. The loads of detected pharmaceuticals and their removal rates were studied in seven wastewater treatment plants (WWTPs) located in the main cities along the basin. Total loads ranged from 2 to 5 and from 0.5 to 1.5 g/d/1,000 inhabitants in influent and effluent wastewaters, respectively. High removal rates (60-90%) were achieved mainly for analgesics and anti-inflammatories. The other groups showed lower rates, ranging from 20 to 60%, and in most cases, the antiepileptic carbamazepine, macrolide antibiotics, and trimethoprim were not eliminated at all. Finally, the contribution of WWTP effluents to the presence of pharmaceuticals in receiving river waters was surveyed. In receiving surface water, the most ubiquitous compounds were the analgesics and anti-inflammatories ibuprofen, diclofenac, and naproxen; the lipid regulators bezafibrate and gemfibrozil; the antibiotics erythromycin, azithromycin, sulfamethoxazole, trimethoprim, and less frequently, ofloxacin; the antiepileptic carbamazepine; the antihistamine ranitidine; and the beta-blockers atenolol and sotalol. Although levels found in WWTP effluents ranged from low microg/L to high ng/L, pharmaceuticals in river waters occurred at levels at least one order of magnitude lower (low ng/L range) because of dilution effect. From the results obtained, it was proved that WWTP are hot spots of aquatic contamination concerning pharmaceuticals of human consumption.

Characterizing the interaction between enantiomers of eight psychoactive drugs and highly sulfated-β-cyclodextrin by counter-current capillary electrophoresis.

PubMed

Asensi-Bernardi, Lucía; Escuder-Gilabert, Laura; Martín-Biosca, Yolanda; Sagrado, Salvador; Medina-Hernández, María José

2014-01-01

The estimation of apparent binding constants and limit mobilities of the complexes of the enantiomers that characterize the interaction of enantiomers with chiral selectors, in this case highly sulfated β-cyclodextrin, was approached using a simple and economic electrophoretic modality, the complete filling technique (CFT) in counter-current mode. The enantiomers of eight psychoactive drugs, four antihistamines (dimethindene, promethazine, orphenadrine and terfenadine) and four antidepressants (bupropion, fluoxetine, nomifensine and viloxazine) were separated for the first time for this cyclodextrin (CD). Estimations of thermodynamic and electrophoretic enantioselectivies were also performed. Results indicate that, in general, thermodynamic enantioselectivity is the main component explaining the high resolution found, but also one case suggests that electrophoretic enantioselectivity itself is enough to obtain a satisfactory resolution. CFT results advantageous compared with conventional capillary electrophoresis (CE) and partial filling technique (PFT) for the study of the interaction between drugs and chiral selectors. It combines the use of a simple fitting model (as in CE), when the enantiomers do not exit the chiral selector plug during the separation (i.e. mobility of electroosmotic flow larger than mobility of CD), and drastic reduction of the consumption (and cost; ~99.7%) of the CD reagent (as in PFT) compared with the conventional CE. Copyright © 2013 John Wiley & Sons, Ltd.

Structure-based discovery and binding site analysis of histamine receptor ligands.

PubMed

Kiss, Róbert; Keserű, György M

2016-12-01

The application of structure-based drug discovery in histamine receptor projects was previously hampered by the lack of experimental structures. The publication of the first X-ray structure of the histamine H1 receptor has been followed by several successful virtual screens and binding site analysis studies of H1-antihistamines. This structure together with several other recently solved aminergic G-protein coupled receptors (GPCRs) enabled the development of more realistic homology models for H2, H3 and H4 receptors. Areas covered: In this paper, the authors review the development of histamine receptor models and their application in drug discovery. Expert opinion: In the authors' opinion, the application of atomistic histamine receptor models has played a significant role in understanding key ligand-receptor interactions as well as in the discovery of novel chemical starting points. The recently solved H1 receptor structure is a major milestone in structure-based drug discovery; however, our analysis also demonstrates that for building H3 and H4 receptor homology models, other GPCRs may be more suitable as templates. For these receptors, the authors envisage that the development of higher quality homology models will significantly contribute to the discovery and optimization of novel H3 and H4 ligands.

Antihistamines, Decongestants, and Cold Remedies

MedlinePlus

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Circadian rhythms in effects of hypnotics and sleep inducers.

PubMed

Reinberg, A

1986-01-01

Chronopharmacology involves the investigation of drug effects as a function of biological time and the investigation of drug effects on rhythm characteristics. Three new concepts must be considered: (a) the chronokinetics of a drug, embracing rhythmic (circadian) changes in drug bioavailability (or pharmacokinetics) and its excretion (urinary among others); (b) the chronaesthesia of a biosystem to a drug, i.e. circadian changes in the susceptibility of any biosystem to a drug (including organ systems, parasites, etc.); skin and bronchial chronaesthesia to various agents have been documented in man; and (c) the chronergy of a drug, taking into consideration its chronokinetics and the chronaesthesia of the involved organismic biosystems. The term chronergy includes rhythmic changes in the overall effects and in the effectiveness of some drugs. Clinical chronopharmacology is useful for solving problems of drug optimization, i.e. enhancing the desired efficiency of a drug and reducing its undesired effects. Circadian rhythms can be demonstrated in various effects of drugs on sleep, anaesthesia and related processes. For example, in the rat the duration of sleep induced by substances such as pentobarbital, hexobarbital, Althesin (alphaxadone and alphadoline in castor oil) is circadian system stage-dependent. Time-dependent changes of liver enzymes (e.g. hexobarbital oxidase) play a role in these circadian rhythms. The clinical chronopharmacokinetics of benzodiazepines have been documented in man. Chronopharmacologic methods can be used to study desired and undesired hypnotic effects of substances. Such is the case of new antihistamines (anti-H1), which do not induce sleepiness, in either acute or chronic administration. Pertinent also is the problem of intolerance to shift-work. Intolerant shift-workers are subject to internal desynchronization between at least two rhythms (e.g. activity-rest cycle and body temperature). Clinically these workers suffer from sleep disturbances, persistent fatigue and are regular users of sleeping pills, which is also a symptom of intolerance. However, over the long-term, these drugs are of no help to intolerant shift-workers.

Effects of fexofenadine and hydroxyzine on brake reaction time during car-driving with cellular phone use.

PubMed

Tashiro, Manabu; Horikawa, Etsuo; Mochizuki, Hideki; Sakurada, Yumiko; Kato, Motohisa; Inokuchi, Takatoshi; Ridout, Fran; Hindmarch, Ian; Yanai, Kazuhiko

2005-10-01

Antihistamines are a mainstay treatment for allergic rhinitis; however, many older agents cause adverse events, including sedation and central nervous system (CNS) impairment. Research has shown sedating effects of antihistamines on driving; currently, no known study has examined whether cellular phone usage while driving further compounds impairment in individuals administered antihistamines. The aim of this study was to examine this endpoint. In a randomized, double-blind, placebo-controlled, three-way crossover study, healthy volunteers received fexofenadine HCl 120 mg, hydroxyzine HCl 30 mg and placebo. Brake reaction time (BRT) was used to examine driving performance across four conditions: driving only; driving while completing simple calculations; complex calculations; and conversing on a cellular phone. Subjective sedation assessments were also conducted. Brake reaction time with and without cellular phone usage in fexofenadine-treated subjects did not differ significantly from placebo in any condition. In contrast, hydroxyzine-treated subjects were significantly more sedated and had slower BRTs, suggesting slower hazard recognition and brake application, compared with the fexofenadine and placebo groups in all conditions. Importantly, cellular phone operation was an additive factor, increasing BRTs in hydroxyzine-treated volunteers. Fexofenadine did not impair CNS function in subjects involved in a divided attention task of driving and cellular phone operation. Copyright (c) 2005 John Wiley & Sons, Ltd.

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

PubMed

2008-10-01

(1) Most sleep complaints involve difficulties in getting to sleep or staying asleep, or not feeling refreshed on awakening. Misconceptions and worrying over the lack of sleep and its consequences can contribute to reinforcing these disorders; (2) How can patients who complain of poor-quality sleep be helped, without resorting to treatments that can have adverse effects? To answer this question, we conducted a systematic review of the literature based on the standard Prescrire procedure; (3) One effective approach is to explain the basic physiology of sleep, to discuss misconceptions, and to adopt a strategy of "stimulus control". This method has a similar efficacy to prescribing a benzodiazepine. and the effect is longer lasting; (4) Moderate, regular physical exercise, especially in the morning, seems to help some patients, but the evidence is weak; (5) Some clinical trials of phytotherapy have shown a positive risk-benefit balance of weak aqueous or hydroalcoholic valerian extracts. Efficacy is limited, however; (6) A meta-analysis of placebo-controlled trials showed that benzodiazepines and related drugs increase the duration of sleep and help patients to fall asleep sooner. However, none of these trials provides comparative data spanning periods of more than two weeks. Efficacy is uncertain in the longer term, as patients quickly develop a tolerance to the hypnotic effects of benzodiazepines; (7) The adverse effects of benzodiazepines include frequent memory disorders, daytime drowsiness, falls, fractures and road accidents, and a withdrawal syndrome after treatment cessation. Related drugs such as zolpidem and zopiclone provoke similar adverse effects; (8) Sedative antihistamines have not been as well-evaluated as benzodiazepines in this setting. Small comparative trials of doxylamine and diphenhydramine showed no major difference in efficacy versus benzodiazepines and related drugs. The main adverse effects of sedative antihistamines are daytime drowsiness and altered vigilance, and atropinic effects; (9) Case-control studies showed a statistical link between benzodiazepine use in early pregnancy and birth defects such as cleft lip. In contrast, data on the use of doxylamine during pregnancy are reassuring; (10) Other sedative psychotropics have not been adequately tested in this setting or have been shown to have a negative risk-benefit balance; (11) In practice, patients who complain of poor-quality sleep should be given appropriate information on the mechanisms of normal sleep and related misconceptions, on the best methods for getting to sleep, and on the dangers of sedative psychotropics (dependence, withdrawal syndrome). When prescribing or dispensing a benzodiazepine to a woman of child-bearing age, the risk of birth defects, although not clearly demonstrated, must be mentioned.

Medicines for sleep

MedlinePlus

Benzodiazepines; Sedatives; Hypnotics; Sleeping pills; Insomnia - medicines; Sleep disorder - medicines ... the-counter (OTC) sleeping pills contain antihistamines. These medicines are commonly used to treat allergies. While these ...

Antihistamines: Understanding Your OTC Options

MedlinePlus

... you can buy over the counter include: Brompheniramine (brand names include Children’s Dimetapp Cold) Chlorpheniramine (brand names include Chlor-Trimeton, Actifed Cold) Dimenhydrinate (brand ...

Sedative Effects of Levocetirizine: A Systematic Review and Meta-Analysis of Randomized Controlled Studies.

PubMed

Snidvongs, Kornkiat; Seresirikachorn, Kachorn; Khattiyawittayakun, Likhit; Chitsuthipakorn, Wirach

2017-02-01

As a substrate of P-glycoprotein, levocetirizine should not cause sedative effects. However, while cetirizine, a mixture of levocetirizine and dextrocetirizine, can slightly penetrate the blood brain barrier, the sedative effects of levocetirizine are still under study. The aim of this study was to investigate the sedative effects of levocetirizine. An electronic literature search was performed using Medline and EMBASE from January 01, 2001 through August 6, 2015. Randomized controlled trials (RCTs) comparing levocetirizine with other antihistamines or placebo for patients with allergy and healthy subjects were selected. Primary outcome was risk ratio between levocetirizine and comparators. Secondary outcome was change in psychomotor speed. Data were pooled for meta-analysis using a fixed-effect model. Forty-eight studies of 18,014 patients met the inclusion criteria. When compared to placebo, levocetirizine produced modest sedative effects (RR: 1.67; 95% CI 1.17, 2.38). However, when compared to other second-generation antihistamines, sedative effects of levocetirizine did not differ (RR: 1.23; 95% CI 0.96, 1.58). In subgroup analysis, there was no difference between the sedative effects of levocetirizine and fexofenadine (RR: 1.7; 95% CI 0.59, 4.88), desloratadine (RR: 1.58; 95% CI 0.9, 2.77), loratadine (RR: 1.56; 95% CI 0.28, 8.56), bilastine (RR: 1.17; 95% CI 0.48, 2.84), olopatadine (RR: 1.09; 95% CI 0.81, 1.47), azelastine (RR: 0.19; 95% CI 0.01, 3.68) and rupatadine (RR: 1.47; 95% CI 0.14, 15.72). When compared to first-generation antihistamines, levocetirizine had less sedative effects and less change of reaction time (mean difference: -250.76 s; 95% CI -338.53, -162.98). Levocetirizine has modest sedative effects with a risk ratio of 1.67 when compared with placebo. The sedative effects observed for levocetirizine are not different from other second-generation antihistamines.

Synergy Testing of FDA-Approved Drugs Identifies Potent Drug Combinations against Trypanosoma cruzi

PubMed Central

Ranade, Ranae M.; Don, Robert; Buckner, Frederick S.

2014-01-01

An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper) have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's) in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM), a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM), and an antifolate drug (pyrimethamine, EC50 of 3.8 µM) and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease. PMID:25033456

Antihistamines, Decongestants, and Cold Remedies

MedlinePlus

... Humanitarian Efforts International Outreach Advocacy Board of Governors Industry Programs Professional Development Home AcademyU Home Study Course Maintenance of Certification Conferences & Events Practice Management Home Resources ...

Risk of road accident associated with the use of drugs: a systematic review and meta-analysis of evidence from epidemiological studies.

PubMed

Elvik, Rune

2013-11-01

This paper is a corrigendum to a previously published paper where errors were detected. The errors have been corrected in this paper. The paper is otherwise identical to the previously published paper. A systematic review and meta-analysis of studies that have assessed the risk of accident associated with the use of drugs when driving is presented. The meta-analysis included 66 studies containing a total of 264 estimates of the effects on accident risk of using illicit or prescribed drugs when driving. Summary estimates of the odds ratio of accident involvement are presented for amphetamines, analgesics, anti-asthmatics, anti-depressives, anti-histamines, benzodiazepines, cannabis, cocaine, opiates, penicillin and zopiclone (a sleeping pill). For most of the drugs, small or moderate increases in accident risk associated with the use of the drugs were found. Information about whether the drugs were actually used while driving and about the doses used was often imprecise. Most studies that have evaluated the presence of a dose-response relationship between the dose of drugs taken and the effects on accident risk confirm the existence of a dose-response relationship. Use of drugs while driving tends to have a larger effect on the risk of fatal and serious injury accidents than on the risk of less serious accidents (usually property-damage-only accidents). The quality of the studies that have assessed risk varied greatly. There was a tendency for the estimated effects of drug use on accident risk to be smaller in well-controlled studies than in poorly controlled studies. Evidence of publication bias was found for some drugs. The associations found cannot be interpreted as causal relationships, principally because most studies do not control very well for potentially confounding factors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dimenhydrinate overdose

MedlinePlus

... this page: //medlineplus.gov/ency/article/002634.htm Dimenhydrinate overdose To use the sharing features on this page, please enable JavaScript. Dimenhydrinate is a type of medicine called an antihistamine. ...

Recent Patents and Emerging Therapeutics in the Treatment of Allergic Conjunctivitis

PubMed Central

Mishra, Gyan P.; Tamboli, Viral; Jwala, Jwala; Mitra, Ashim K.

2011-01-01

Ocular allergy is an inflammatory response of the conjunctival mucosa that also affects the cornea and eyelids. Allergic conjunctivitis includes seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC) and giant papillary conjunctivitis (GPC). In general, allergic conditions involve mast cell degranulation that leads to release of inflammatory mediators and activation of enzymatic cascades generating pro-inflammatory mediators. In chronic ocular inflammatory disorders associated with mast cell activation such as VKC and AKC constant inflammatory response is observed due to predominance of inflammatory mediators such as eosinophils and Th2-generated cytokines. Antihistamines, mast-cell stabilizers, non-steroidal anti-inflammatory agents, corticosteroids and immunomodulatory agents are commonly indicated for the treatment of acute and chronic allergic conjunctivitis. In recent years newer drug molecules have been introduced in the treatment of allergic conjunctivitis. This article reviews recent patents and emerging therapeutics in the treatment of allergic conjunctivitis. PMID:21171952

Nasal filters in prevention of seasonal rhinitis induced by allergenic pollen grains. Open clinical study.

PubMed

D'Amato, G; Liccardi, G; Salzillo, A; Russo, M; Narciso, P; Allegra, L

2012-04-01

Nasal filters (Sanispira) might represent a novel approach in preventing exacerbations of symptoms of seasonal allergic rhinitis by reducing pollen access to nasal cavities. Female and male voluntary patients between the ages of 18 and 64 years living in Naples area and affected by allergic rhinitis were recruited in an open clinical study. All were allergic to Parietaria pollen as assessed by skin-prick and/or RAST test with or without associated sensitization to other pollens such as Gramineae and Olea europaea. A pollen count was also carried out from 10th April until 30th of June 2011. The results of our study show positive statistical differences between the scores of common nasal symptoms and the reduced use of antihistaminic drugs in patients using nasal filters in comparison to non users. Nasal filters constitute a useful mean to reduce symptoms of seasonal allergic rhinitis in patients suffering from pollen allergy.

Delayed pressure urticaria: response to treatment with sulfasalazine in a case series of seventeen patients.

PubMed

Swerlick, Robert A; Puar, Neha

2015-01-01

We retrospectively identified 17 patients with delayed pressure urticaria (DPU), diagnosed by history and confirmed with provocative pressure testing. The average age in the cohort was 42.6 years with 10 women and seven men. The mean duration of disease before diagnosis was 19.7 months (range, 1-60 months). The diagnosis of DPU was not included in the differential diagnosis of referring physicians and was not a diagnostic consideration in any of seven biopsies obtained. None of the patients responded adequately to treatment with antihistamines, but all 17 responded transiently when treated with either oral or intramuscular steroids. Eleven patients experienced complete or near complete resolution of DPU with treatment with sulfasalazine (SZ). Four patients had a partial response while two were unable to continue therapy because of drug intolerance. SZ appears to be a low cost and effective treatment for DPU. © 2015 Wiley Periodicals, Inc.

Determination of 89 drugs and other micropollutants in unfiltered wastewater and freshwater by LC-MS/MS: an alternative sample preparation approach.

PubMed

Asimakopoulos, Alexandros G; Kannan, Pranav; Higgins, Sean; Kannan, Kurunthachalam

2017-10-01

A liquid chromatography-triple quadrupole-tandem mass spectrometry (LC-qQq-MS/MS) method was developed for simultaneous determination of 89 legal neuropsychiatric pharmaceuticals and illicit drugs (both parent compounds and metabolites) and other micropollutants in unfiltered wastewater and freshwater. The target chemicals fall under the classes of amphetamine-type stimulants, cocaine compounds, opiates and opioids, benzodiazepines, lysergic compounds, antipsychotics, anesthetics, antiepileptics, antidepressants, sympathomimetics, cannabinoids, blood thinners, antihistamines, β-blockers, caffeine derivatives, nicotine derivatives, z-drugs, new designer drugs, and Alzheimer medications. The sample preparation procedure was designed for unfiltered wastewater and freshwater without the need to separate the particulate matter (if any) from the aqueous phase prior to extraction. Samples were pre-concentrated by rotary evaporation in the presence of a solvent. Method precision (absolute values; N = 6 replicate analyses at the fortification level of 50 ng, k = 6 days) for 87 out of 89 target analytes ranged from 2.8 to 34% (RSD %). The limits of detection ranged from 0.11 to 202 ng L -1 , and the matrix effects ranged from +16 to -84%. A total of 10 samples, 8 wastewater, 1 drinking water, and 1 lake water, were collected from New York State, USA, and were analyzed for the target compounds to demonstrate the applicability of the developed method. This is the first study to report the analysis of multiple classes of pharmaceuticals, illicit drugs, and other micropollutants in unfiltered wastewater. Graphical abstract Analysis of 89 micropollutants in unfiltered wastewater by LC-MS/MS.

An in vitro and in vivo evaluation of new potential trans-sialidase inhibitors of Trypanosoma cruzi predicted by a computational drug repositioning method.

PubMed

Lara-Ramirez, Edgar E; López-Cedillo, Julio Cesar; Nogueda-Torres, Benjamin; Kashif, Muhammad; Garcia-Perez, Carlos; Bocanegra-Garcia, Virgilio; Agusti, Rosalía; Uhrig, María Laura; Rivera, Gildardo

2017-05-26

Chagas disease is one of the most important neglected parasitic diseases afflicting developed and undeveloped countries. There are currently limited options for inexpensive and secure pharmacological treatment. In this study, we employed a structure-based virtual screening protocol for 3180 FDA-approved drugs for repositioning of them as potential trans-sialidase inhibitors. In vitro and in vivo evaluations were performed for the selected drugs against trypomastigotes from the INC-5 and NINOA strains of T. cruzi. Also, inhibition of sialylation by the trans-sialidase enzyme reaction was evaluated using high-performance anion-exchange chromatography with pulse amperometric detection to confirm the mechanism of action. Results from the computational study showed 38 top drugs with the best binding-energies. Four compounds with antihistaminic, anti-hypertensive, and antibiotic properties showed better trypanocidal effects (LC 50 range = 4.5-25.8 μg/mL) than the reference drugs, nifurtimox and benznidazole (LC 50 range = 36.1-46.8 μg/mL) in both strains in the in vitro model. The anti-inflammatory, sulfasalazine showed moderate inhibition (37.6%) of sialylation in a trans-sialidase enzyme inhibition reaction. Sulfasalazine also showed the best trypanocidal effects in short-term in vivo experiments on infected mice. This study suggests for the first time that the anti-inflammatory sulfasalazine could be used as a lead compound to develop new trans-sialidase inhibitors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Validated sensitive spectrofluorimetric method for determination of antihistaminic drug azelastine HCl in pure form and in pharmaceutical dosage forms: application to stability study.

PubMed

El-Masry, Amal A; Hammouda, Mohammed E A; El-Wasseef, Dalia R; El-Ashry, Saadia M

2017-03-01

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of azelastine HCl (AZL) in either its pure state or pharmaceutical dosage form. The proposed method was based on measuring the native fluorescence of the studied drug in 0.2 M H 2 SO 4 at λ em  = 364 nm after excitation at λ ex  = 275 nm. Different experimental parameters were studied and optimized carefully to obtain the highest fluorescence intensity. The proposed method showed a linear dependence of the fluorescence intensity on drug concentration over a concentration range of 10-250 ng/mL, with a limit of detection of 1.52 ng/mL and limit of quantitation of 4.61 ng/mL. Moreover, the method was successfully applied to pharmaceutical preparations, with percent recovery values (± SD) of 99.96 (± 0.4) and 100.1 (± 0.52) for nasal spray and eye drops, respectively. The results were in good agreement with those obtained by the comparison method, as revealed by Student's t-test and the variance ratio F-test. The method was extended to study the stability of AZL under stress conditions, where the drug was exposed to neutral, acidic, alkaline, oxidative and photolytic degradation according to International Conference on Harmonization (ICH) guidelines. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Interchangeability, Safety and Efficacy of Modified-Release Drug Formulations in the USA: The Case of Opioid and Other Nervous System Drugs.

PubMed

Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Hansen, Richard

2016-04-01

Modified-release drugs may provide clinical advantages compared to immediate-release forms and improve convenience to the patient and health outcomes. Concerns have been raised regarding interchangeability, efficacy, and safety of modified-release formulations. This study analyses all US Food and Drug Administration (FDA)-approved modified-release formulations and market trends, and illustrates how bioequivalence and safety of generic modified-release products compare to their respective brand name drugs and other generic drugs with different formulation design characteristics. This study also examines major concerns related to modified-release formulations: safety of opioids and bioequivalence of generic bupropion and methylphenidate. Study data were derived from the FDA electronic versions of the FDA's Orange Book (OB) and the FDA safety communications web page. Medicare Part D utilization and expenditures data were extracted from the Centers for Medicare and Medicaid. In May 2015, 276 (11.9 %) of the 2325 active ingredients and fixed-dose combinations listed in the FDA's Orange Book had at least one modified-release form approved by the FDA. The number of approvals increased over time; 52.5 % of modified releases were approved in the period 2000-May 2015. The FDA required a risk evaluation and mitigation strategy (REMS) to ensure that the benefits of extended-release opioids outweighed its risks of overdose and abuse. The REMS involved 16 new drug applications and 25 abbreviated new drug applications. The FDA addressed interchangeability problems with generic modified-release alternatives of bupropion and methylphenidate including lack of bioequivalence, reduced efficacy, and increased incidence of adverse events. Systematic post-marketing surveillance studies are needed to assess differences in safety, interchangeability, and efficacy of drugs with modified- and immediate-release formulations.

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

PubMed

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

2008-05-01

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

The Effect of Schinus terebinthifolius Raddi (Anacardiaceae) Bark Extract on Histamine-Induced Paw Edema and Ileum Smooth Muscle Contraction.

PubMed

Nunes-Neto, Paulo Alexandre; Peixoto-Sobrinho, Tadeu José da Silva; da Silva Júnior, Edilson Dantas; Leopoldina da Silva, Jamilka; Rodrigo da Silva Oliveira, Alisson; Pupo, André Sampaio; Araújo, Alice Valença; da Costa-Silva, João Henrique; Wanderley, Almir Gonçalves

2017-01-01

Schinus terebinthifolius Raddi (Anacardiaceae), popularly known as red aroeira, is used in traditional medicine to treat inflammatory, gastric, and respiratory disorders. The aim of this study was to evaluate the antihistaminic activity of S. terebinthifolius (St) bark extract by using in vivo and in vitro experimental models. The effects of St were investigated on contractions induced by histamine, carbachol, and potassium chloride in isolated guinea pig ileum. St was also studied in response to hind paw edema induced by histamine in rats. Experiments revealed that although St (250, 500, and 1,000  µ g/mL) reduced the histamine-induced contractions by 9.1 ± 1.8, 50.2 ± 2.0, and 68.9 ± 2.0%, respectively, it did not inhibit contractions induced by carbachol or KCl. The association of St (250 and 500  µ g/mL) with hydroxyzine, an H 1 -antihistamine (0.125 and 0.250  µ M), increased the inhibitory effect to 67.0 ± 3.2 and 85.1 ± 2.1%, respectively. Moreover, St (100, 200, and 400 mg/kg) decreased paw edema from its peak by 33.9, 48.4, and 54.8%, respectively, whereas hydroxyzine (70 mg/kg) inhibited the peak edema by 56.5%. Altogether, the results suggest that the bark extract of S. terebinthifolius has an antihistaminic effect (H 1 ).

The Effect of Schinus terebinthifolius Raddi (Anacardiaceae) Bark Extract on Histamine-Induced Paw Edema and Ileum Smooth Muscle Contraction

PubMed Central

Nunes-Neto, Paulo Alexandre; da Silva Júnior, Edilson Dantas; Leopoldina da Silva, Jamilka; Rodrigo da Silva Oliveira, Alisson; Pupo, André Sampaio; Araújo, Alice Valença

2017-01-01

Schinus terebinthifolius Raddi (Anacardiaceae), popularly known as red aroeira, is used in traditional medicine to treat inflammatory, gastric, and respiratory disorders. The aim of this study was to evaluate the antihistaminic activity of S. terebinthifolius (St) bark extract by using in vivo and in vitro experimental models. The effects of St were investigated on contractions induced by histamine, carbachol, and potassium chloride in isolated guinea pig ileum. St was also studied in response to hind paw edema induced by histamine in rats. Experiments revealed that although St (250, 500, and 1,000 µg/mL) reduced the histamine-induced contractions by 9.1 ± 1.8, 50.2 ± 2.0, and 68.9 ± 2.0%, respectively, it did not inhibit contractions induced by carbachol or KCl. The association of St (250 and 500 µg/mL) with hydroxyzine, an H1-antihistamine (0.125 and 0.250 µM), increased the inhibitory effect to 67.0 ± 3.2 and 85.1 ± 2.1%, respectively. Moreover, St (100, 200, and 400 mg/kg) decreased paw edema from its peak by 33.9, 48.4, and 54.8%, respectively, whereas hydroxyzine (70 mg/kg) inhibited the peak edema by 56.5%. Altogether, the results suggest that the bark extract of S. terebinthifolius has an antihistaminic effect (H1). PMID:28928787

The history and progression of treatments for allergic rhinitis.

PubMed

Ostrom, Nancy K

2014-01-01

This article intends to place new treatments in the context of allergic rhinitis (AR) treatment history. The medical literature was searched for significant advances and changes in AR treatment. Historical data on AR treatment options and management were selected. Reviews of AR management published throughout the 20th century were included to provide context for treatment advances. Modern AR treatment began in the early 20th century with immunotherapy and was soon followed by the emergence of antihistamine therapy in the 1930s. Numerous treatments for AR have been used over the ensuing decades, including decongestants, mast cell stabilizers, and leukotriene receptor antagonists. Topical corticosteroid options were developed the 1950s, and, added to baseline antihistamine therapy, became the foundation of AR treatment. Treatment options were significantly impacted after the 1987 Montreal Protocol, which phased out the use of chlorofluorocarbon propellant aerosols because of environmental concerns. From the mid-1990s until recently, this left only aqueous solution options for intranasal corticosteroids (INSs). The approval of the first hydrofluoroalkane propellant aerosol INSs for AR in 2012 restored a "dry" aerosol treatment option. The first combination intranasal antihistamine/INSs was also approved in 2012, providing a novel treatment option for AR. Treatment of AR has progressed with new therapeutic options now available. This should continue to move forward with agents to alter the allergic mechanism itself and impact the disease burden that has a significant impact on patient outcomes.

Fexofenadine

MedlinePlus

... medications called antihistamines. It works by blocking the effects of histamine, a substance in the body that ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

DRESS syndrome associated with type 2 diabetes in a child

PubMed Central

Erdem, Semiha Bahceci; Bag, Ozlem; Karkiner, Canan Sule Unsal; Korkmaz, Huseyin Anil; Can, Demet

2016-01-01

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon, life-threatening drug reaction. The basic findings are skin rash, multiorgan involvement, and eosinophilia. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital and carbamazepine can induce DRESS. Herein we report a 14-year-old patient with DRESS syndrome related to carbamazepine use. The patient presented with signs of involvement of the skin, lungs, liver, and microscopic hematuria. Carbamazepine treatment was discontinued; antihistamines and steroids were started. Hyperglycemia, commencing on the first dose of the steroid given, persisted even after the discontinuation of steroids and improvement of other signs. There were no signs of pancreatitis or type 1 diabetes clinically in laboratory tests. Her blood glucose levels were regulated at first with insulin and later with metformin. Within 1 year of follow-up, still regulated with oral antidiabetics, she has been diagnosed with type 2 diabetes. Formerly, long-term sequelae related to “drug rash with eosinophilia and systemic symptoms syndrome” such as hepatic and renal failure, type 1 diabetes mellitus, Grave's disease, autoimmune hemolytic anemia, and lupus have also been reported. However, up to date, no cases with type 2 diabetes have been reported as long-term sequelae. To our knowledge, this is the first case in the literature presenting with type 2 diabetes as long-term sequelae. PMID:26862317

Acceptance survey of a fast dissolving tablet pharmaceutical formulation in allergic patients. Satisfaction and expectancies.

PubMed

Roger Reig, Albert; Plazas Fernández, M Josep; Galván Cervera, Jordi; Heras Navarro, Joan; Artés Ferragud, Maite; Gabarrón Hortal, Elia

2006-01-01

One of the factors affecting compliance is the pharmaceutical formulation used. Many patients find it difficult to swallow tablets or capsules. The fast dissolving tablet (FDT) formulation could help to enhance patient compliance, because of its ease of administration and because no liquid is required to help intake. A survey was conducted in patients diagnosed with allergic rhinitis or dermatitis (positive skin tests and/or specific IgE) and urticaria to asses the degree of acceptance of and preference for an FDT formulation. Of the 7,686 patients who participated in the survey, 90 % considered the initial flavor and 83 % considered the aftertaste to be very or quite satisfactory, 95 % were very satisfied with the disintegration time, 79 % were very satisfied with the form, 82 % with the size, 72 % with the packaging and 78 % with the instructions for use. Ninety-three percent considered that being able to take the drug at any time or place was very important or fairly important. Ninety-four percent considered the ease of use to be much better or better. If given the choice, 93 % would choose an FDT formulation. Eighty-eight percent of the patients would like to change their current antihistaminic drug for a new allergy drug in an FDT formulation. Most of the patients were highly satisfied with the characteristics of the FDT formulation and would choose it for the treatment of their allergies.

Treatment of the Hyperactive Child

ERIC Educational Resources Information Center

Wunderlich, Ray C.

1973-01-01

Described individually are the following forms of medical treatment for the hyperactive child: stimulants, tranquilizers, megavitamins, corticosteroids, antihistamines, anticonvulsants, food elimination, air filtration, allergic desensitization, perceptual motor training, and behavioral counseling. (DB)

Olopatadine Nasal Spray

MedlinePlus

... medications called antihistamines. It works by blocking the effects of histamine, a substance in the body that ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

Erosive and cariogenicity potential of pediatric drugs: study of physicochemical parameters

PubMed Central

2013-01-01

Background Pediatric medications may possess a high erosive potential to dental tissues due to the existence of acid components in their formulations. The purpose was to determine the erosive and cariogenic potential of pediatric oral liquid medications through the analysis of their physicochemical properties in vitro. Methods A total of 59 substances were selected from the drug reference list of the National Health Surveillance Agency (ANVISA), which belong to 11 therapeutic classes, as follows: analgesics, non-steroidal anti-inflammatory, corticosteroids, antihistamines, antitussives, bronchodilators, antibacterials, antiparasitics, antiemetics, anticonvulsants and antipsychotics. Measurement of pH was performed by potentiometry, using a digital pH meter. For the Total Titratable Acidity (TTA) chemical assay, a 0.1 N NaOH standard solution was used, which was titrated until drug pH was neutralized. The Total Soluble Solids Contents (TSSC) quantification was carried out by refractometry using Brix scale and the analysis of Total Sugar Content was performed according to Fehling’s method. In addition, it was analyzed the information contained in the drug inserts with regard to the presence of sucrose and type of acid and sweetener added to the formulations. Results All drug classes showed acidic pH, and the lowest mean was found for antipsychotics (2.61 ± 0.08). There was a large variation in the TTA (0.1% - 1.18%) and SST (10.44% - 57.08%) values. High total sugar contents were identified in the antitussives (53.25%) and anticonvulsants (51.75%). As described in the drug inserts, sucrose was added in 47.5% of the formulations, as well as citric acid (39.0%), sodium saccharin (36.4%) and sorbitol (34.8%). Conclusion The drugs analyzed herein showed physicochemical characteristics indicative of a cariogenic and erosive potential on dental tissues. Competent bodies’ strategies should be implemented in order to broaden the knowledge of health professionals, drug manufacturers and general consuming public about the risks from the consumption of medicines potentially harmful to dental tissues. PMID:24325544

Erosive and cariogenicity potential of pediatric drugs: study of physicochemical parameters.

PubMed

Xavier, Alidianne Fábia C; Moura, Eline F F; Azevedo, Waldeneide F; Vieira, Fernando F; Abreu, Mauro H N G; Cavalcanti, Alessandro L

2013-12-10

Pediatric medications may possess a high erosive potential to dental tissues due to the existence of acid components in their formulations. The purpose was to determine the erosive and cariogenic potential of pediatric oral liquid medications through the analysis of their physicochemical properties in vitro. A total of 59 substances were selected from the drug reference list of the National Health Surveillance Agency (ANVISA), which belong to 11 therapeutic classes, as follows: analgesics, non-steroidal anti-inflammatory, corticosteroids, antihistamines, antitussives, bronchodilators, antibacterials, antiparasitics, antiemetics, anticonvulsants and antipsychotics. Measurement of pH was performed by potentiometry, using a digital pH meter. For the Total Titratable Acidity (TTA) chemical assay, a 0.1 N NaOH standard solution was used, which was titrated until drug pH was neutralized. The Total Soluble Solids Contents (TSSC) quantification was carried out by refractometry using Brix scale and the analysis of Total Sugar Content was performed according to Fehling's method. In addition, it was analyzed the information contained in the drug inserts with regard to the presence of sucrose and type of acid and sweetener added to the formulations. All drug classes showed acidic pH, and the lowest mean was found for antipsychotics (2.61 ± 0.08). There was a large variation in the TTA (0.1% - 1.18%) and SST (10.44% - 57.08%) values. High total sugar contents were identified in the antitussives (53.25%) and anticonvulsants (51.75%). As described in the drug inserts, sucrose was added in 47.5% of the formulations, as well as citric acid (39.0%), sodium saccharin (36.4%) and sorbitol (34.8%). The drugs analyzed herein showed physicochemical characteristics indicative of a cariogenic and erosive potential on dental tissues. Competent bodies' strategies should be implemented in order to broaden the knowledge of health professionals, drug manufacturers and general consuming public about the risks from the consumption of medicines potentially harmful to dental tissues.

Bronchiolitis - discharge

MedlinePlus

... bronchiolitis. Your health care provider may prescribe such medicine for your child. DO NOT give your child decongestant nose drops, antihistamines, or any other cold medicines unless your child's doctor tells you to. When to Call the ...

Allergies and Hay Fever

MedlinePlus

... discomfort. Symptom control is most successful when multiple approaches are used together to manage the allergy. They may include reducing exposure to allergens, medications, and allergy shots or drops. If used properly, medications, including antihistamines, ...

Dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs with poor water solubility.

PubMed

Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Lee, Kyoung-Ho; Kim, Dong-Jin; Lee, Beom-Jin

2010-05-01

Although the solid dispersion method has been known to increase the dissolution rate of poorly water-soluble drugs by dispersing them in hydrophilic carriers, one obstacle of the solid dispersion method is its limited solubilization capacity, especially for pH-dependent soluble drugs. pH-modified solid dispersion, in which pH modifiers are incorporated, may be a useful method for increasing the dissolution rate of weakly acidic or basic drugs. Sufficient research, including the most recent reports, was undertaken in this review. How could the inclusion of the pH the pH modifiers in the solid dispersion system change drug structural behaviors, molecular interactions, microenvironmental pH, and/or release rate of pH modifiers, relating with the enhanced dissolution of weakly acidic or weakly basic drugs with poor water solubility? These questions have been investigated to determine the dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs. It is believed that step-by-step mechanistic approaches could provide the ultimate solution for solubilizing several poorly water-soluble drugs with pH-dependent solubility from a solid dispersion system, as well as provide ideas for developing future dosage systems.

Surveillance of contrast-media-induced hypersensitivity reactions using signals from an electronic medical recording system.

PubMed

Kim, Min-Hye; Park, Chang-Han; Kim, Duk-In; Kim, Kyung-Mook; Kim, Hui-Kyu; Lim, Kyu-Hyoung; Song, Woo-Jung; Lee, Sang-Min; Kim, Sae-Hoon; Kwon, Hyouk-Soo; Park, Heung-Woo; Yoon, Chang-Jin; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young; Chang, Yoon-Seok

2012-03-01

Contrast-media (CM) hypersensitivity is a well-known adverse drug reaction. Surveillance of adverse drug reactions usually depends on spontaneous reports. However, the rate of spontaneous reports is low. Recent progress in information technology enables the electronic search on signals of adverse drug reactions from electronic medical recording (EMR) systems. To analyze the incidence and clinical characteristics of CM hypersensitivity using an EMR-based surveillance system. The surveillance system used signals from standardized terms within the international classification of nursing practice terms that can indicate symptoms of CM hypersensitivity and from the order codes for procedures that used contrast media, antihistamine, and epinephrine. The search strategy was validated by allergists comparing the electronic search strategy versus manually reviewing medical charts over one month. The main study covered for one year period. Detection rate of the electronic search method was 0.9% (7/759), while that of the manual search method was 0.8% (6/759). EMR-based electronic search method was highly efficient: reduced the charts that needed to be reviewed by 96% (28/759). The sensitivity of electronic screening was 66.7%, specificity was 99.6%, and the negative predictive value was 99.7%. CM hypersensitivity reactions were noted in 266 among 12,483 cases (2.1%). Urticaria was the most frequent symptom (74.4%). CT was the most frequent procedure (3.6%) that induced CM hypersensitivity. A surveillance system using EMR may be a useful tool in the study of drug hypersensitivity epidemiology and may be used in an adverse drug reaction alarm system and as a clinical, decision making support system. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The treatment of chronic insomnia: drug indications, chronic use and abuse liability. Summary of a 2001 New Clinical Drug Evaluation Unit meeting symposium.

PubMed

Mendelson, Wallace B; Roth, Thomas; Cassella, James; Roehrs, Timothy; Walsh, James K; Woods, James H; Buysse, Daniel J; Meyer, Roger E

2004-02-01

This paper summarizes a group of presentations and panel discussions on chronic insomnia at the 2001 NCDEU meeting. The presentations and discussions focused on the twin issues of efficacy and concerns of abuse liability with long-term hypnotic therapy. The panel concluded that insomnia may be an epidemiological marker for a variety of difficulties including accidents, increased health care utilization and subsequent development of major depression. Whether or not treatment of insomnia will prevent these long-term problems has not yet been determined. Since the mid-1980s there has been a rapid rise in the off-label use of antidepressants, particularly trazodone, for treating insomnia. Some participants expressed concern at the lack of data for this practice, particularly the absence of dose-response and tolerance information, and noted that the small amount of efficacy data available is not encouraging. Similarly, there are minimal data to support the use of antihistamines as sleep aids; moreover, their side effect profile and interactions with other drugs may be under appreciated. The limited data available on nightly long-term usage of the newer non-benzodiazepine hypnotics, primarily of six-months' duration, suggest an absence of tolerance, but more data for both nightly and non-nightly administration are needed. Insomniacs tend to show therapy-seeking, rather than drug-seeking behavior, and patients without histories of drug abuse are unlikely to self-escalate dosage of currently available hypnotics. There is fairly good agreement on the characteristics of an ideal hypnotic. All currently available agents, while effective and safe, do not achieve this ideal. The next few years are likely to see the appearance of a variety of agents with new and promising mechanisms of action.

Multiple Myeloma: Patient Handbook

MedlinePlus

... incidence of deep vein thrombosis and pulmonar y embolism. • Patients must be pre-medicated with dexamethasone, antihistamine, ... foods that include processed sugars and artificial trans fats. Caution should be used in two areas: • Vitamin ...

21 CFR 177.1640 - Polystyrene and rubber-modified polystyrene.

Code of Federal Regulations, 2011 CFR

2011-04-01

... polystyrene and rubber-modified polystyrene used in food-packaging adhesives complying with § 175.105 of this... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Polystyrene and rubber-modified polystyrene. 177.1640 Section 177.1640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 177.1640 - Polystyrene and rubber-modified polystyrene.

Code of Federal Regulations, 2010 CFR

2010-04-01

... polystyrene and rubber-modified polystyrene used in food-packaging adhesives complying with § 175.105 of this... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Polystyrene and rubber-modified polystyrene. 177.1640 Section 177.1640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 177.1640 - Polystyrene and rubber-modified polystyrene.

Code of Federal Regulations, 2013 CFR

2013-04-01

... polystyrene and rubber-modified polystyrene used in food-packaging adhesives complying with § 175.105 of this... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Polystyrene and rubber-modified polystyrene. 177.1640 Section 177.1640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 177.1640 - Polystyrene and rubber-modified polystyrene.

Code of Federal Regulations, 2012 CFR

2012-04-01

... polystyrene and rubber-modified polystyrene used in food-packaging adhesives complying with § 175.105 of this... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Polystyrene and rubber-modified polystyrene. 177.1640 Section 177.1640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

Cholinergic urticaria with anaphylaxis: hazardous duty of a deployed US marine.

PubMed

Handfield, Kent S; Dolan, Christopher K; Kaplan, Michael

2015-04-01

Cholinergic urticaria (CU) is triggered by a rise in body temperature and can be complicated by bronchial hyperresponsiveness and anaphylaxis. It primarily affects young adults who actively engage in strenuous exercise, such as servicemen and servicewomen. If the patient reports a history of wheezing or difficulty breathing with urticaria, a water challenge test in a warm bath can be performed to confirm the presence of anaphylaxis. The test should be conducted in an environment in which the patient's airway can be secured and epinephrine can be administered if necessary. Nonsedating antihistamines commonly are used to treat CU, but few other treatments have been thoroughly evaluated for cases that are refractory to antihistamines. We present the case of a 27-year-old US Marine with CU and anaphylaxis confirmed by a water challenge test in a warm bath.

Inappropriate prescription of cough remedies among children hospitalised with respiratory illness over the period 2002-2015 in Kenya.

PubMed

Maina, Michuki; Akech, Samuel; Mwaniki, Paul; Gachau, Susan; Ogero, Morris; Julius, Thomas; Ayieko, Phillip; Irimu, Grace; English, Mike

2017-03-01

To examine trends in prescription of cough medicines over the period 2002-2015 in children aged 1 month to 12 years admitted to Kenyan hospitals with cough, difficulty breathing or diagnosed with a respiratory tract infection. We reviewed hospitalisation records of children included in four studies providing cross-sectional prevalence estimates from government hospitals for six time periods between 2002 and 2015. Children with an atopic illness were excluded. Amongst eligible children, we determined the proportion prescribed any adjuvant medication for cough. Active ingredients in these medicines were often multiple and were classified into five categories: antihistamines, antitussives, mucolytics/expectorants, decongestants and bronchodilators. From late 2006, guidelines discouraging cough medicine use have been widely disseminated and in 2009 national directives to decrease cough medicine use were issued. Across the studies, 17 963 children were eligible. Their median age and length of hospital stay were comparable. The proportion of children who received cough medicines shrank across the surveys: approximately 6% [95% CI: 5.4, 6.6] of children had a prescription in 2015 vs. 40% [95% CI: 35.5, 45.6] in 2002. The most common active ingredients were antihistamines and bronchodilators. The relative proportion that included antihistamines has increased over time. There has been an overall decline in the use of cough medicines among hospitalised children over time. This decline has been associated with educational, policy and mass media interventions. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

New model for prediction binary mixture of antihistamine decongestant using artificial neural networks and least squares support vector machine by spectrophotometry method

NASA Astrophysics Data System (ADS)

Mofavvaz, Shirin; Sohrabi, Mahmoud Reza; Nezamzadeh-Ejhieh, Alireza

2017-07-01

In the present study, artificial neural networks (ANNs) and least squares support vector machines (LS-SVM) as intelligent methods based on absorption spectra in the range of 230-300 nm have been used for determination of antihistamine decongestant contents. In the first step, one type of network (feed-forward back-propagation) from the artificial neural network with two different training algorithms, Levenberg-Marquardt (LM) and gradient descent with momentum and adaptive learning rate back-propagation (GDX) algorithm, were employed and their performance was evaluated. The performance of the LM algorithm was better than the GDX algorithm. In the second one, the radial basis network was utilized and results compared with the previous network. In the last one, the other intelligent method named least squares support vector machine was proposed to construct the antihistamine decongestant prediction model and the results were compared with two of the aforementioned networks. The values of the statistical parameters mean square error (MSE), Regression coefficient (R2), correlation coefficient (r) and also mean recovery (%), relative standard deviation (RSD) used for selecting the best model between these methods. Moreover, the proposed methods were compared to the high- performance liquid chromatography (HPLC) as a reference method. One way analysis of variance (ANOVA) test at the 95% confidence level applied to the comparison results of suggested and reference methods that there were no significant differences between them.

Clinical and histologic features of acute-onset erythroderma in dogs with gastrointestinal disease: 18 cases (2005-2015).

PubMed

Cain, Christine L; Bradley, Charles W; Mauldin, Elizabeth A

2017-12-15

OBJECTIVE To describe the clinical and histologic features of acute erythroderma in dogs with gastrointestinal disease. DESIGN Retrospective case series. ANIMALS 18 dogs with erythroderma and gastrointestinal disease. PROCEDURES Medical records and biopsy specimens were reviewed. Information collected from medical records included signalment, clinical signs, physical examination and diagnostic test results, treatment, and outcome. The Naranjo algorithm was used to estimate the probability of an adverse drug reaction for each dog. RESULTS All dogs had an acute onset of erythematous macules or generalized erythroderma. Histologic features of skin biopsy specimens had 3 patterns representing a progressive spectrum of inflammation. Most dogs had vomiting (n = 17) and hematochezia (10). Signs of gastrointestinal disease became evident before, after, or concurrent with the onset of skin lesions in 10, 3, and 5 dogs, respectively. Inflammatory bowel disease, pancreatitis, and adverse food reaction were diagnosed in 5, 3, and 3 dogs, respectively. The cause of the gastrointestinal signs was not identified for 8 dogs. Eight dogs had a Naranjo score consistent with a possible adverse drug reaction. Treatment of skin lesions included drug withdrawal (n = 15), antihistamines (16), and corticosteroids (14). Signs of gastrointestinal disease and skin lesions resolved at a mean of 4.6 days and 20.8 days, respectively, after onset. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated acute erythroderma may be associated with > 1 gastrointestinal disease or an adverse drug reaction in some dogs. Recognition of the clinical and histologic features of this syndrome is essential for accurate diagnosis.

Hey! A Brown Recluse Spider Bit Me!

MedlinePlus

... like antibiotics, antihistamines, or pain medicines. Rarely, a skin graft might be needed if the skin is really damaged at the area of the bite. (A skin graft is when a small amount of skin is ...

Snoring and Nasal Congestion

MedlinePlus

... treat the various causes of nasal congestion include: Topical nasal steroid spray Topical nasal antihistamine spray Oral antibiotic (in case of ... include more than just the decrease in oxygen levels at night during the apnea episodes. They also ...

IC Treatment: Antihistamines

MedlinePlus

... Us Magazine Store Donor Resources My Profile Login Social Media Twitter YouTube Facebook Pinterest Community ShareThis Google Search ... Federal Campaign ICA Resources for Donors Corporate Contributions Social Media Twitter YouTube Facebook Pinterest Community ShareThis Google Search ...

Allergy Diagnosis and Treatment | NIH MedlinePlus the Magazine

MedlinePlus

... breathe is loaded with allergens, such as ragweed pollen. Various over-the-counter or prescription medications can ... for example, 6 weeks for ragweed or grass pollen seasons) Treatment Cold Airborne Allergy Antihistamines Decongestants Nonsteroidal ...

Indometh acin-antihistamine combination for gastric ulceration control

NASA Technical Reports Server (NTRS)

Brown, P. A.; Vernikos, J. (Inventor)

1980-01-01

An anti-inflammatory and analgesic composition containing indomethacin and an H2 histamine receptor antagonist in an amount sufficient to reduce gastric distress caused by the indomethacin was developed. Usable antagonists are metiamide and cimetidine.

Modified Chaihu Shugan Powder for Functional Dyspepsia: Meta-Analysis for Randomized Controlled Trial

PubMed Central

Yang, Nan; Jiang, Xuehua; Hu, Zhiqiang; Wang, Ling; Song, Minxian

2013-01-01

Context. Modified Chaihu Shugan powder (MCSP) is a popular traditional Chinese herbal formula for functional dyspepsia, which is revised from Chaihu Shugan San and recorded in a medical classic works of China. However, its role and effect in treating functional dyspepsia have not been well established. Objective. To assess the effect and safety of modified Chaihu Shugan powder for functional dyspepsia. Methods. We searched the published and unpublished studies up to August 2012. Only RCTs of modified Chaihu Shugan powder with or without prokinetic drugs versus prokinetic drugs in the patients diagnosed with functional dyspepsia were included. Results. Twenty-two clinical trials involving 1998 participants were included. There were evidences that modified Chaihu Shugan powder (RR = 1.20, 95%, CI 1.14 to 1.27) and modified Chaihu Shugan powder plus prokinetic drugs (RR = 1.18, 95%, CI 1.11 to 1.25) were significantly better treatment options than prokinetic drugs alone in improving symptoms. No serious adverse events were described in the included trials. Conclusions. This meta-analysis showed that modified Chaihu Shugan powder alone or in combination with prokinetic drugs might be more effective than prokinetic drugs alone. However, with poor methodological quality, all the included trials were at high risk of bias. Further large-scale high-quality trials are required for assessment. PMID:23762161

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moritz, MichaL; Laniecki, Marek, E-mail: laniecki@amu.edu.pl

A series of modified SBA-15 materials were applied in drug delivery systems. The internal surface of siliceous hexagonal structure of SBA-15 was modified with different amount of (3-mercaptopropyl)trimethoxysilane (MPTMS) and oxidized in the presence of hydrogen peroxide. The sulfonated material was loaded with metoprolol tartrate or papaverine hydrochloride. Both drugs indicated strong chemical interaction with modified mesoporous surface. The characteristic of the obtained materials was performed with XRD and DRUV-vis spectrometry, themogravimetry and nitrogen adsorption (BET) measurements. The obtained results show that modification of the mesoporous materials leads towards significant decrease of the drug delivery rate. - Graphical abstract: XRDmore » and DSC of the -SO{sub 3}H modified SBA-15 loaded with metoprolol. Highlights: > Modification of SBA-15 internal channels with SO{sub 3}H groups. > Adsorption of metoprolol and papaverine on modified SBA-15. > Uniform and homogeneous distribution of the drugs inside the mesoporous structure of SBA-15. > Release of the supported drugs.« less

Inorganically modified diatomite as a potential prolonged-release drug carrier.

PubMed

Janićijević, Jelena; Krajišnik, Danina; Calija, Bojan; Dobričić, Vladimir; Daković, Aleksandra; Krstić, Jugoslav; Marković, Marija; Milić, Jela

2014-09-01

Inorganic modification of diatomite was performed with the precipitation product of partially neutralized aluminum sulfate solution at three different mass ratios. The starting and the modified diatomites were characterized by SEM-EDS, FTIR, thermal analysis and zeta potential measurements and evaluated for drug loading capacity in adsorption batch experiments using diclofenac sodium (DS) as a model drug. In vitro drug release studies were performed in phosphate buffer pH6.8 from comprimates containing: the drug adsorbed onto the selected modified diatomite sample (DAMD), physical mixture of the drug with the selected modified diatomite sample (PMDMD) and physical mixture of the drug with the starting diatomite (PMDD). In vivo acute toxicity testing of the modified diatomite samples was performed on mice. High adsorbent loading of the selected modified diatomite sample (~250mg/g in 2h) enabled the preparation of comprimates containing adsorbed DS in the amount near to its therapeutic dose. Drug release studies demonstrated prolonged release of DS over a period of 8h from both DAMD comprimates (18% after 8h) and PMDMD comprimates (45% after 8h). The release kinetics for DAMD and PMDMD comprimates fitted well with Korsmeyer-Peppas and Bhaskar models, indicating that the release mechanism was a combination of non-Fickian diffusion and ion exchange process. Copyright © 2014 Elsevier B.V. All rights reserved.

21 CFR 522.2615 - Tripelennamine hydrochloride injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... use—(1) Amount—(i) Dogs, cats, and horses. For intramuscular use only at a dose of 0.5 milligram per... antihistaminic therapy may be expected to lead to alleviation of some signs of disease. (3) Limitations. Do not...

21 CFR 522.2615 - Tripelennamine hydrochloride injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... use—(1) Amount—(i) Dogs, cats, and horses. For intramuscular use only at a dose of 0.5 milligram per... antihistaminic therapy may be expected to lead to alleviation of some signs of disease. (3) Limitations. Do not...

Dry Mouth Treatment: Tips for Controlling Dry Mouth

MedlinePlus

... Dry Mouth Mouthwash, which also offer protection against tooth decay. Avoid using over-the-counter antihistamines and decongestants ... and drinks because they increase your risk of tooth decay. Brush with a fluoride toothpaste — ask your dentist ...

Seasonal Allergies: Symptoms, Diagnosis, and Treatment | NIH MedlinePlus the Magazine

MedlinePlus

... for example, 6 weeks for ragweed or grass pollen seasons) Treatment Antihistamines Decongestants Nonsteroidal anti-inflammatory medicines ... things that you are allergic to, such as pollen, house dust mites, mold, pet dander, cockroaches Complications ...

Suppression of reactions to certain cosmetics.

PubMed

Fisher, A A

1977-08-01

Reactions to hair dyes and bleaches may be "suppressed" with corticosteroids and antihistamines. Reactions to nail polish may be prevented by a "drying" or "polymerizing" technique. Sensitization to certain perfume ingredients may be inhibited by a "quenching" phenomenon.

Removal of diphenhydramine from water by swelling clay minerals.

PubMed

Li, Zhaohui; Chang, Po-Hsiang; Jiang, Wei-Teh; Jean, Jiin-Shuh; Hong, Hanlie; Liao, Libing

2011-08-01

Frequent detection of pharmaceuticals in surface water and wastewater attracted renewed attention on studying interactions between pharmaceuticals and sludge or biosolids generated from wastewater treatment. Less attention was focused on studying interactions between pharmaceuticals and clay minerals, important soil and sediment components. This research targeted on investigating interactions between diphenhydramine (DPH), an important antihistamine drug, and a montmorillonite, a swelling clay, in aqueous solution. Stoichiometric desorption of exchangeable cations accompanying DPH adsorption confirmed that cation exchange was the most important mechanism of DPH uptake by the swelling clay. When the solution pH was below the pK(a) of DPH, its adsorption on the swelling clay was less affected by pH. Increasing solution pH above the pK(a) value resulted in a decrease in DPH adsorption by the clay. An increase in d(001) spacing at a high DPH loading level suggested interlayer adsorption, thus, intercalation of DPH. The results from this study showed that swelling clays are a good environmental sink for weak acidic drugs like DPH. In addition, the large cation exchange capacity and surface area make the clay a good candidate to remove cationic pharmaceuticals from the effluent of wastewater treatment facilities. Copyright © 2011 Elsevier Inc. All rights reserved.

[Drug-facilitated crimes: prospective data collection in a forensic unit in Paris].

PubMed

Questel, Franck; Sec, Isabelle; Sicot, Romain; Pourriat, Jean-Louis

2009-01-01

Little is known about the rate of crimes that are facilitated by the administration of psychoactive products without the victim's knowledge. This study analyzes the cases collected over a two-year period in a forensic unit in Paris. The study covers the period from January 1, 2005 and December /31, 2006. It includes crime victims who consulted for toxicological testing in the forensic unit of the Hôtel Dieu in Paris, after filing a criminal complaint describing symptoms suggestive of chemical submission (amnesia, impaired vigilance or behavior) and whose toxicological tests indicated the presence of a psychoactive product that they had not been aware of taking. The tests used chromatographic techniques on blood, urine, hair, and food or drink residue. Toxicological testing identified 52 cases of drug-facilitated crimes, primarily for theft and sexual abuse (including rape). The psychoactive products were most often incorporated in drinks, half of them alcoholic beverages. Benzodiazepines accounted for 77% of the cases. Other substances, found more rarely, included antihistamines, neuroleptics, and GHB. Appropriate samples must be taken from victims rapidly to enable toxicological analysis. Chromatographic analysis must supplement immunological analysis, which is not sufficiently specific or sensitive. The collection of this information must continue in order to quantify the phenomenon and monitor the emergence of new products.

Anaphylaxis in dogs and cats.

PubMed

Shmuel, Daniella L; Cortes, Yonaira

2013-01-01

To review and summarize current information regarding the pathophysiology and clinical manifestations associated with anaphylaxis in dogs and cats. The etiology, diagnosis, treatment, and prognosis is discussed. Anaphylaxis is a systemic, type I hypersensitivity reaction that often has fatal consequences. Many of the principal clinical manifestations involve organs where mast cell concentrations are highest: the skin, the lungs, and the gastrointestinal tract. Histamine and other deleterious inflammatory mediators promote vascular permeability and smooth muscle contraction; they are readily released from sensitized mast cells and basophils challenged with antigen. Anaphylaxis may be triggered by a variety of antigens including insect and reptile venom, a variety of drugs, vaccines, and food. Anaphylaxis is a clinical diagnosis made from a collection of signs and symptoms. It is most commonly based on pattern recognition. Differential diagnoses include severe asthma, pheocromocytoma, and mastocytosis. Epinephrine is considered the drug of choice for the treatment of anaphylaxis. It acts primarily as a vasopressor in improving hemodynamic recovery. Adjunctive treatments include fluid therapy, H1 and H2 antihistamines, corticosteroids, and bronchodilators; however, these do not substitute for epinephrine. Prognosis depends on the severity of the clinical signs. The clinical signs will vary among species and route of exposure. The most severe clinical reactions are associated when the antigen is administered parenterally. © Veterinary Emergency and Critical Care Society 2013.

Effects of central nervous system drugs on driving: speed variability versus standard deviation of lateral position as outcome measure of the on-the-road driving test.

PubMed

Verster, Joris C; Roth, Thomas

2014-01-01

The on-the-road driving test in normal traffic is used to examine the impact of drugs on driving performance. This paper compares the sensitivity of standard deviation of lateral position (SDLP) and SD speed in detecting driving impairment. A literature search was conducted to identify studies applying the on-the-road driving test, examining the effects of anxiolytics, antidepressants, antihistamines, and hypnotics. The proportion of comparisons (treatment versus placebo) where a significant impairment was detected with SDLP and SD speed was compared. About 40% of 53 relevant papers did not report data on SD speed and/or SDLP. After placebo administration, the correlation between SDLP and SD speed was significant but did not explain much variance (r = 0.253, p = 0.0001). A significant correlation was found between ΔSDLP and ΔSD speed (treatment-placebo), explaining 48% of variance. When using SDLP as outcome measure, 67 significant treatment-placebo comparisons were found. Only 17 (25.4%) were significant when SD speed was used as outcome measure. Alternatively, for five treatment-placebo comparisons, a significant difference was found for SD speed but not for SDLP. Standard deviation of lateral position is a more sensitive outcome measure to detect driving impairment than speed variability.

Epidemiological evaluation of cat health at a first-response animal shelter in Fukushima, following the Great East Japan Earthquakes of 2011.

PubMed

Tanaka, Aki; Kass, Philip H; Martinez-Lopez, Beatriz; Hayama, Shinichi

2017-01-01

The Great East Japan Earthquakes of March 11, 2011 caused immense harm to the community and subsequent nuclear accident in Fukushima Prefecture extended the damage. Local residents were forced to evacuated without pets and the left behind animals were rescued from the restricted zone one month later. Unplanned animal rescue and unregulated sheltering caused secondary damage to animals such as disease epidemics at impounded animal shelter. The purpose of this study was to retrospectively evaluate the incidence of upper respiratory infection (URI) and diarrhea in cats at the first response animal shelter in Fukushima, and investigate factors affecting the duration of disease and determinants of treatments performed. Eighty percent and 59% of impounded cats developed URI, 71% and 54% of cats developed diarrhea, and 91% and 83% of cats had at least one disease in 2011 and 2012, respectively. Uses of multiple drug administration (more than five drugs) was associated with prolonged URI and diarrhea. Multiple antibiotics, antihistamines, interferon, and steroids were associated with relapse of and prolonged URI. Developing a standardized treatment protocol for commonly observed diseases at Japanese animal shelters to prevent and control diseases, to promote animal welfare, and protect public health in the face of future disasters is overdue.

Biological mechanisms underlying voice changes due to dehydration.

PubMed

Verdolini, Katherine; Min, Young; Titze, Ingo R; Lemke, Jon; Brown, Kice; van Mersbergen, Miriam; Jiang, Jack; Fisher, Kim

2002-04-01

Four vocally untrained healthy adults, 2 men and 2 women, completed the study. A double-blind placebo-controlled approach was used to administer three treatments to each participant on separate days. Drugs treatments involved a single 60-mg dose of a diuretic, Lasix (LA), on one day, and a single 50-mg dose of an oral antihistamine, diphenhydramine hydrochloride (DH), on another day. A third day involved the administration of a placebo, sugar pills (SP). Critical posttreatment measures were weight (kg), which estimated systemic dehydration, saliva viscosity (centipoise), which estimated secretion dehydration, and phonation threshold pressure (PTP, in cm H2O), at high pitches, which indicated pulmonary drive for phonation. The central experimental question was: Does systemic dehydration, or secretory dehydration, or both, mediate increases in PTP that are known to occur following dehydration treatments? The results showed that LA induced systemic dehydration, as shown by a decrease in total body mass of about 1%. Weight losses were seen during a 1- to 4-hour block following drug administration and persisted for at least 8 hours thereafter. PTPs also increased in that condition, about 23% relative to baseline, but only several hours after whole-body dehydration was initially seen (5-12 hours after drug administration). In contrast, no evidence was seen that DH accomplished either secretory dehydration or PTP shifts. The results indicate that systemic dehydration can mediate PTP increases. The influence of secretory dehydration on PTP is unclear.

Enantioseparation of cetirizine by chromatographic methods and discrimination by 1H-NMR.

PubMed

Taha, Elham A; Salama, Nahla N; Wang, Shudong

2009-03-01

Cetirizine is an antihistaminic drug used to prevent and treat allergic conditions. It is currently marketed as a racemate. The H1-antagonist activity of cetirizine is primarily due to (R)-levocetirizine. This has led to the introduction of (R)-levocetirizine into clinical practice, and the chiral switching is expected to be more selective and safer. The present work represents three methods for the analysis and chiral discrimination of cetirizine. The first method was based on the enantioseparation of cetirizine on silica gel TLC plates using different chiral selectors as mobile phase additives. The mobile phase enabling successful resolution was acetonitrile-water 17: 3, (v/v) containing 1 mM of chiral selector, namely hydroxypropyl-beta-cyclodextrin, chondroitin sulphate or vancomycin hydrochloride. The second method was a validated high performance liquid chromatography (HPLC), based on stereoselective separation of cetirizine and quantitative determination of its eutomer (R)-levocetirizine on a monolithic C18 column using hydroxypropyl-beta-cyclodextrin as a chiral mobile phase additive. The resolved peaks of (R)-levocetirizine and (S)-dextrocetirizine were confirmed by further mass spectrometry. The third method used a (1)H-NMR technique to characterize cetirizine and (R)-levocetirizine. These methods are selective and accurate, and can be easily applied for chiral discrimination and determination of cetirizine in drug substance and drug product in quality control laboratory. Moreover, chiral purity testing of (R)-levocetirizine can also be monitored by the chromatographic methods. Copyright 2009 John Wiley & Sons, Ltd.

23 years of toxicology testing fatally injured pilots: Implications for aviation and other modes of transportation.

PubMed

McKay, Mary Pat; Groff, Loren

2016-05-01

Use of over-the-counter, prescription, and illicit drugs is increasing in the United States (US). Many of these drugs are psychoactive and can affect the user's ability to safely operate a vehicle. However, data about drug use by vehicle operators is typically limited to a small proportion of operators and a short list of drugs. For instance, required testing for commercial vehicle operators following most accidents is limited to a urine test for 11 drugs. By comparison, the Federal Aviation Administration (FAA), routinely tests fatally injured pilots' blood and tissues for hundreds of compounds. This study used the results from these tests to assess drug use in aviation. Using matched data from the FAA's Civil Aerospace Medical Institute toxicology database and the National Transportation Safety Board's (NTSB's) aviation accident database, this study examined trends in the prevalence of over-the-counter, prescription, and illicit drugs identified in toxicology tests of fatally injured pilots between 1990 and 2012. Cases that failed to match or where toxicology testing had not been performed were excluded. Pilots identified by the NTSB investigation as being the "flying pilot" at the time of the accident and results from blood or tissues were included. Toxicology results for ethanol and other alcohols were not included. Positive test results were categorized by drug type and potential for causing impairment. Analysis used SPSS Version 19.1 to perform linear by linear chi-squared statistics. The study included 6677 pilots or 87% of the eligible subjects. The large majority were male (98%) and flying general aviation operations (96%) at the time of their fatal accident. There were increasing trends in pilots' use of all drugs, potentially impairing drugs, drugs used to treat potentially impairing conditions, drugs designated as controlled substances, and illicit drugs. The most common potentially impairing drug pilots had used was diphenhydramine, a sedating antihistamine that is an active ingredient in many over-the-counter allergy formulations, cold medicines, and sleep aids in the US. Although evidence of illicit drug use was found only in a small number of cases, the percentage of pilots testing positive for marijuana use increased during the study period, mostly in the last 10 years. Published by Elsevier Ltd.

Chlorpheniramine Analogues Reverse Chloroquine Resistance in Plasmodium falciparum by Inhibiting PfCRT.

PubMed

Deane, Karen J; Summers, Robert L; Lehane, Adele M; Martin, Rowena E; Barrow, Russell A

2014-05-08

The emergence and spread of malaria parasites that are resistant to chloroquine (CQ) has been a disaster for world health. The antihistamine chlorpheniramine (CP) partially resensitizes CQ-resistant (CQR) parasites to CQ but possesses little intrinsic antiplasmodial activity. Mutations in the parasite's CQ resistance transporter (PfCRT) confer resistance to CQ by enabling the protein to transport the drug away from its site of action, and it is thought that resistance-reversers such as CP exert their effect by blocking this CQ transport activity. Here, a series of new structural analogues and homologues of CP have been synthesized. We show that these compounds (along with other in vitro CQ resistance-reversers) inhibit the transport of CQ via a resistance-conferring form of PfCRT expressed in Xenopus laevis oocytes. Furthermore, the level of PfCRT-inhibition was found to correlate well with both the restoration of CQ accumulation and the level of CQ resensitization in CQR parasites.

[Atopic dermatitis and urticaria: for the prevention and cure via disease control and management].

PubMed

Furukawa, Fukumi

2009-11-01

Standard ways of management are introduced through guidelines. The present standard therapies for atopic dermatitis consist of the use of topical steroids and tacrolimus ointment for inflammation as well as emollients for dry and barrier-disrupted skin as the first-line topical application, systemic anti-histamines and anti-allergic drugs for pruritus, avoidance of apparent exacerbating factors and so on. The importance of correct selection of topical steroids according to the severity of the lesion is also emphasized. As for urticaria, the use of oral histamine H1-receptor antagonists is the first line treatment, regardless of the groups, provided that sufficient efforts to eliminate the cause and/or aggravating factors are taken. Several options for the treatment are suggested as the second and/or the third line treatments, but the aim of examinations and treatments should be determined according to the type and severity of the diseases. Standard therapies and elimination of the cause and/or aggravating factors are the best way for the cure and prevention.

[Cutaneous mastocytosis: A case report].

PubMed

Zegpi-Trueba, María Soledad; Hasbún-Acuña, Paula; Berroeta-Mauriziano, Daniela

2016-01-01

Mastocytosis represents a group of diseases characterised by an excesive accumulation of mastocytes in one or multiple tissues. It can affect only the skin, or have a systemic involvement. It has a low prevalence, and the prognosis is benign in children. To report a case of urticaria pigmentosa as a subtype of cutaneous mastocytosis, and present a literature review focused on clinical findings, diagnosis and initial basic management. A child of six months of age presenting with multiple blemishes and light brown papules located on the trunk, arms and legs. The symptoms were compatible with urticaria pigmentosa, and was confirmed by biopsy. Tests to rule out systemic involvement were requested. The patient was treated with general measures, education, and antihistamines, with favourable results. Cutaneous mastocytosis is a rare disease with a good prognosis. In childhood general measures and education are usually enough to obtain favourable results. Histamine H1 antagonists are the first line drug treatment. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Diagnosis and management of nasal congestion: the role of intranasal corticosteroids.

PubMed

Benninger, Michael

2009-01-01

Nasal congestion is considered the most bothersome of allergic rhinitis (AR) symptoms and can significantly impair ability to function at work, home, and school. Effective management of AR-related nasal congestion depends on accurate diagnosis and appropriate treatment. Many individuals with AR and AR-related congestion remain undiagnosed and do not receive prescription medication. However, new tools intended to improve the diagnosis of nasal congestion have been developed and validated. Intranasal corticosteroids (INSs) are recommended as first-line therapy for patients with moderate-to-severe AR and also when nasal congestion is a prominent symptom. Double blind, randomized clinical trials have demonstrated greater efficacy of INSs versus placebo, antihistamines, or montelukast for relief of all nasal symptoms, especially congestion. Patient adherence to treatment also affects outcomes, and this may be influenced by patient preferences for the sensory attributes of an individual drug. Increased awareness of the effects of AR-related nasal congestion, the efficacy and safety of available pharmacotherapies, and barriers to adherence may improve clinical outcomes.

[Cold-induced urticaria].

PubMed

Delorme, N; Drouet, M; Thibaudeau, A; Verret, J L

2002-09-01

Cold urticaria is characterized by the development of urticaria, usually superficial and/or angioedematous reaction after cold contact. It was found predominantly in young women. The diagnosis is based on the history and ice cube test. Patients with a negative ice cube test may have represented systemic cold urticaria (atypical acquired cold urticaria) induced by general body cooling. The pathogenesis is poorly understood. Cold urticaria can be classified into acquired and familial disorders, with an autosomal dominant inheritance. Idiopathic cold urticaria is most common type but the research of a cryopathy is necessary. Therapy is often difficult. It is essential that the patient be warned of the dangers of swimming in cold water because systemic hypotension can occur. H1 antihistamines can be used for treatment of cold urticaria but the clinical responses are highly variable. The combination with an H2 antagonists is more effective. Doxepin may be useful in the treatment. Leukotriene receptor antagonists may be a novel, promising drug entity. In patients who do not respond to previous treatments, induction of cold tolerance may be tried.

Clinical efficacy of herbal Padmapatradi yoga in bronchial asthma (Tamaka Swasa)

PubMed Central

Panda, Ashok Kumar; Doddanagali, S. R.

2011-01-01

Ayurveda refers to bronchial asthma as Tamaka Swasa and it is well explained in Charaka Samhita. It contributes several modalities of the treatment for Swasa roga(asthma). Among all modalities of treatment, polyherbal combinations are said to be well-accepted, safe and effective in asthma. A study was carried out in 40 patients of either sex in between the age of 15-65 years to assure the clinical response of Padmapatradi yoga in bronchial asthma (Tamaka Swasa) at P.G. department of Kayachikitsa, D.G.M. Ayurvedic Medical College, Gadag, Karnataka. The sum total properties of Padmapatradi yoga is tikta katu rasa, laghu and tikna guna (light and penetrating properties), ushna virya (hot potency) and vatakaphagna (decrease vata and kapha dosa) Padmapatradi yoga is effective in increased peak expiratory flow rate, breath holding time, and reduces the absolute eosinophil count of studied cases and also found statistically highly significant at p<0.001 level. The drug is quite safe and acts as a bronchodilator, antihistaminic and anti-inflammatory. PMID:21760694

Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: Anti-inflammatory, antihistaminic, and skin barrier protection properties.

PubMed

Facchini, Gustavo; Eberlin, Samara; Clerici, Stefano Piatto; Alves Pinheiro, Ana Lucia Tabarini; Costa, Adilson

2017-12-01

Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response. In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g). We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient. Ultraviolet A was chosen as exogenous agent to induce allergic and inflammatory response. Both PTZ and DCP promoted increases in interleukin-1 (IL-1) synthesis in response to ultraviolet A (UVA) radiation compared to control. However, the increase observed with PTZ was significantly greater than the DCP, indicating that the latter has a lower irritant potential. DCP also demonstrated a protective effect on UVA-induced leukotriene B4 and nuclear factor kappa B (NF-κB) synthesis. Conversely, PTZ demonstrates more robust UVA antihistaminic activity. Likewise, PTZ promoted a significantly greater increase in the production of involucrin and keratin 14, both associated with protective skin barrier property. In conclusion, these data suggest possible diverging UVA response mechanisms of DCP and PTZ, which gives greater insight into the contrasting photosensitizing potential between DCP and PTZ observed in the patients. © 2017 Wiley Periodicals, Inc.

Anticholinergic, antihistaminic, and antiserotonergic activity of n-hexane extract of Zanthoxylum alatum seeds on isolated tissue preparations: An ex vivo study.

PubMed

Saikia, Beenita; Barua, Chandana Choudhury; Haloi, Prakash; Patowary, Pompy

2017-01-01

The aim of this study was to evaluate anticholinergic, antihistaminic, and antiserotonergic activity of the n-hexane extract of the seeds of Zanthoxylum alatum (ZAHE) on isolated ileum of rat and guinea pig and fundus of rat. ZAHE was prepared using soxhlet extraction and cumulative concentration response curves were constructed using various doses on the tissues for acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and histamine with or without n-hexane extract. Atropine, ketanserin, and pheniramine maleate were used as antagonists for ACh, serotonin, and histamine, respectively. ZAHE-induced concentration-dependent inhibition of isolated ileum and fundus in rat and ileum of guinea pig. The half maximal effective concentration (EC 50 ) of ACh in the presence of atropine (10 -6 M; P < 0.05) and ZAHE (1000 μg/ml; P < 0.01) was significantly higher than EC 50 of ACh alone. The EC 50 of 5-HT in the presence of ketanserin (10 -5 M; P < 0.01) and ZAHE (1000 μg/ml; P < 0.05) was higher than EC 50 of 5-HT alone. Similarly, the EC 50 of histamine in the presence of pheniramine maleate (10 -6 M; P < 0.01) and ZAHE (300 μg/ml; P < 0.01 and 1000 μg/ml; P < 0.05) was also significantly higher than EC 50 of histamine alone. From the study, it was observed that ZAHE shows significant anticholinergic, antiserotonergic, and antihistaminic activity. The study provides sufficient evidence that the seeds can be used in gastric disorders, cough, chest infection, etc., as per folklore claims.

Study of Drug Utilization Pattern for Skin Diseases in Dermatology OPD of an Indian Tertiary Care Hospital - A Prescription Survey

PubMed Central

Pathak, Anuj Kumar; Kumar, Subodh; Kumar, Manish; Dikshit, Harihar

2016-01-01

Introduction Skin diseases are the major contributors of disease burden in society. It affects individuals of all ages, neonates to elderly. Owing to its chronic nature, it causes serious impact on quality of life and financial status of the sufferer and his family. The problem gets compounded with the inappropriate and irrational use of medicines. Periodic prescription audit in form of drug utilization study is a way to improve the quality of prescription and curb the menace of irrational prescribing which has become a global phenomenon. Aim This study aims to determine the drug utilization pattern and assess the economic burden of the patient with skin disease. Materials and Methods It was a prospective, cross-sectional study conducted over a period of three months from January to March 2015 in newly diagnosed cases attending outpatient department of Skin and VD, IGIMS, Patna. The prescriptions were analysed with the help of descriptive statistics and results were expressed in percentage. Results Total 752 prescriptions were analysed during the study. Male patients were lesser as compared to female as male to female ratio was 0.88. Over 50% of patients were in adolescent age group i.e. 21-40 years. Acne (17.95%) was most common disease in the study population followed by eczema and Dermatophytosis. Among the drugs, antihistaminics (24.13%) were prescribed most frequently followed by antifungals and antibiotics. Topical agents constituted almost 60% of the total prescription and average number of drugs per prescription was 5.13, irrespective of the dosage forms prescribed. Conclusion This drug utilization study provides an insight to the prescriber regarding various issues related to polypharmacy, cost analysis and prevalent disease pattern in the region. This study also suggests periodic evaluation of prescription pattern to monitor and improve quality of prescription in other departments of the hospital. PMID:27042479

Factors driving customers to seek health care from pharmacies for acute respiratory illness and treatment recommendations from drug sellers in Dhaka city, Bangladesh

PubMed Central

Chowdhury, Fahmida; Sturm-Ramirez, Katharine; Mamun, Abdullah Al; Iuliano, A Danielle; Bhuiyan, Mejbah Uddin; Chisti, Mohammod Jobayer; Ahmed, Makhdum; Haider, Sabbir; Rahman, Mahmudur; Azziz-Baumgartner, Eduardo

2017-01-01

Background Pharmacies in Bangladesh serve as an important source of health service. A survey in Dhaka reported that 48% of respondents with symptoms of acute respiratory illness (ARI) identified local pharmacies as their first point of care. This study explores the factors driving urban customers to seek health care from pharmacies for ARI, their treatment adherence, and outcome. Methods A cross-sectional study was conducted among 100 selected pharmacies within Dhaka from June to December 2012. Study participants were patients or patients’ relatives aged >18 years seeking care for ARI from pharmacies without prescription. Structured interviews were conducted with customers after they sought health service from drug sellers and again over phone 5 days postinterview to discuss treatment adherence and outcome. Results We interviewed 302 customers patronizing 76 pharmacies; 186 (62%) sought care for themselves and 116 (38%) sought care for a sick relative. Most customers (215; 71%) were males. The majority (90%) of customers sought care from the study pharmacy as their first point of care, while 18 (6%) had previously sought care from another pharmacy and 11 (4%) from a physician for their illness episodes. The most frequently reported reasons for seeking care from pharmacies were ease of access to pharmacies (86%), lower cost (46%), availability of medicine (33%), knowing the drug seller (20%), and convenient hours of operation (19%). The most commonly recommended drugs were acetaminophen dispensed in 76% (228) of visits, antihistamine in 69% (208), and antibiotics in 42% (126). On follow-up, most (86%) of the customers had recovered and 12% had sought further treatment. Conclusion People with ARI preferred to seek care at pharmacies rather than clinics because these pharmacies were more accessible and provided prompt treatment and medicine with no service charge. We recommend raising awareness among drug sellers on proper dispensing practices and enforcement of laws and regulations for drug sales. PMID:28293104

Factors driving customers to seek health care from pharmacies for acute respiratory illness and treatment recommendations from drug sellers in Dhaka city, Bangladesh.

PubMed

Chowdhury, Fahmida; Sturm-Ramirez, Katharine; Mamun, Abdullah Al; Iuliano, A Danielle; Bhuiyan, Mejbah Uddin; Chisti, Mohammod Jobayer; Ahmed, Makhdum; Haider, Sabbir; Rahman, Mahmudur; Azziz-Baumgartner, Eduardo

2017-01-01

Pharmacies in Bangladesh serve as an important source of health service. A survey in Dhaka reported that 48% of respondents with symptoms of acute respiratory illness (ARI) identified local pharmacies as their first point of care. This study explores the factors driving urban customers to seek health care from pharmacies for ARI, their treatment adherence, and outcome. A cross-sectional study was conducted among 100 selected pharmacies within Dhaka from June to December 2012. Study participants were patients or patients' relatives aged >18 years seeking care for ARI from pharmacies without prescription. Structured interviews were conducted with customers after they sought health service from drug sellers and again over phone 5 days postinterview to discuss treatment adherence and outcome. We interviewed 302 customers patronizing 76 pharmacies; 186 (62%) sought care for themselves and 116 (38%) sought care for a sick relative. Most customers (215; 71%) were males. The majority (90%) of customers sought care from the study pharmacy as their first point of care, while 18 (6%) had previously sought care from another pharmacy and 11 (4%) from a physician for their illness episodes. The most frequently reported reasons for seeking care from pharmacies were ease of access to pharmacies (86%), lower cost (46%), availability of medicine (33%), knowing the drug seller (20%), and convenient hours of operation (19%). The most commonly recommended drugs were acetaminophen dispensed in 76% (228) of visits, antihistamine in 69% (208), and antibiotics in 42% (126). On follow-up, most (86%) of the customers had recovered and 12% had sought further treatment. People with ARI preferred to seek care at pharmacies rather than clinics because these pharmacies were more accessible and provided prompt treatment and medicine with no service charge. We recommend raising awareness among drug sellers on proper dispensing practices and enforcement of laws and regulations for drug sales.

Gender and age differences in medications dispensed from a national chain drugstore.

PubMed

Anthony, Marietta; Lee, Kwan Y; Bertram, Carl T; Abarca, Jacob; Rehfeld, Rick A; Malone, Daniel C; Freeman, Marlene; Woosley, Raymond L

2008-06-01

Our objective was to compare sex and age differences in the medications dispensed in pharmacies from a large national drugstore chain. Using a list for the 200 most commonly prescribed medicines, we assessed prescriptions dispensed by a large national chain drug store over 1 year (2002-2003). The analysis used U.S. census data adjusted for the population by sex and age and weighted by the number of pharmacies per state. Results are reported as an odds ratio (OR) of prescriptions dispensed to females and males. Under age 18, 24 drug classes were dispensed more commonly to females (OR > 1) and 18 drug classes more commonly to males (OR < 1). In the 18-24 age group, 48 of 53 drug classes were dispensed more frequently to females. Across other adult groups, females were dispensed more medications than males for 156 of 180 medications. There was greater dispensing to females of antibiotics (OR = 1.74, 95% confidence interval [CI] 1.74-1.74), analgesics (OR = 1.70, 95% CI 1.70-1.70), antihistamines and sympathomimetics (OR = 1.46, 95% CI 1.45-1.46), benzodiazapines (OR = 2.08, 95% CI 2.07-2.08), antidepressants (OR = 2.40, 95% CI 2.39-2.40), diuretics (OR = 1.9328, 95% CI 1.93-1.94), and thyroid drugs (OR = 4.80, 95% CI 4.78-4.82). However, males had higher dispensing of antianginal drugs (OR = 0.84, 95% CI 0.83-0.85), anticoagulants (OR = 0.89, 95% CI 0.88-0.90), glycosides (OR = 0.80, 95% CI 0.79-0.81), and antihypertensives (OR = 0.91, 95% CI 0.91-0.91). More females were dispensed propoxyphene with acetaminophen (OR = 2.23, 95% CI 2.23-2.24), which has been associated with adverse outcomes (hospitalizations, emergency department visits, and deaths). Females, especially during the reproductive years, are dispensed more medications than males.

Optimization of tetracycline hydrochloride adsorption on amino modified SBA-15 using response surface methodology.

PubMed

Hashemikia, Samaneh; Hemmatinejad, Nahid; Ahmadi, Ebrahim; Montazer, Majid

2015-04-01

Several researchers are focused on preparation of mesoporous silica as drug carriers with high loading efficiency to control or sustain the drug release. Carriers with highly loaded drug are utilized to minimize the time of drug intake. In this study, amino modified SBA-15 was synthesized through grafting with amino propyl triethoxy silane and then loaded with tetracycline hydrochloride. The drug loading was optimized by using the response surface method considering various factors including drug to silica ratio, operation time, and temperature. The drug to silica ratio indicated as the most influential factor on the drug loading yield. Further, a quadratic polynomial equation was developed to predict the loading percentage. The experimental results indicated reasonable agreement with the predicted values. The modified and drug loaded mesoporous particles were characterized by FT-IR, SEM, TEM, X-ray diffraction (XRD), elemental analysis and N2 adsorption-desorption. The release profiles of tetracycline-loaded particles were studied in different pH. Also, Higuchi equation was used to analyze the release profile of the drug and to evaluate the kinetic of drug release. The drug release rate followed the conventional Higuchi model that could be controlled by amino-functionalized SBA-15. Further, the drug delivery system based on amino modified SBA-15 exhibits novel features with an appropriate usage as an anti-bacterial drug delivery system with effective management of drug adsorption and release. Copyright © 2014 Elsevier Inc. All rights reserved.

Investigation of anti-motion sickness drugs in the squirrel monkey

NASA Technical Reports Server (NTRS)

Cheung, B. S.; Money, K. E.; Kohl, R. L.; Kinter, L. B.

1992-01-01

Early attempts to develop an animal model for anti-motion sickness drugs, using dogs and cats; were unsuccessful. Dogs did not show a beneficial effect of scopolamine (probably the best single anti-motion sickness drug for humans thus far) and the findings in cats were not definitive. The authors have developed an animal model using the squirrel monkey (Saimiri sciureus) of the Bolivian phenotype. Unrestrained monkeys in a small lucite cage were tested in an apparatus that induces motion sickness by combining vertical oscillation and horizontal rotation in a visually unrestricted laboratory environment. Signs of motion sickness were scored using a rating scale. Ten susceptible monkeys (weighing 800-1000 g) were given a total of five tests each, to establish the baseline susceptibility level. Based on the anticholinergic activity of scopolamine, the sensitivity of squirrel monkey to scopolamine was investigated, and the appropriate dose of scopolamine for this species was determined. Then various anti-motion sickness preparations were administered in subsequent tests: 100 ug scopolamine per monkey; 140 ug dexedrine; 50 ug scopolamine plus 70 ug dexedrine; 100 ug scopolamine plus 140 ug dexedrine; 3 mg promethazine; 3 mg promethazine plus 3 mg ephedrine. All these preparations were significantly effective in preventing motion sickness in the monkeys. Ephedrine, by itself, which is marginally effective in humans, was ineffective in the monkeys at the doses tried (0.3-6.0 mg). The squirrel monkey appears to be a good animal model for antimotion sickness drugs. Peripherally acting antihistamines such as astemizole and terfenadine were found to be ineffective, whereas flunarizine, and an arginine vasopressin V1 antagonist, showed significant activity in preventing motion sickness.

Differential binding of /sup 3/H-imipramine and /sup 3/H-mianserin in rat cerebral cortex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dumbrille-Ross, A.; Tang, S.W.; Coscina, D.V.

1981-11-16

Drug competition profiles, effect of raphe lesion, and sodium dependency of the binding of two antidepressant drugs /sup 3/H-imipramine and /sup 3/H-mianserin to rat cerebral cortex homogenate were compared to examine whether the drugs bound to a common ''antidepressant receptor.'' Of the neurotransmitters tested, only serotonin displaced binding of both /sup 3/H-imipramine and /sup 3/H-mianserin. /sup 3/H-Mianserin binding was potently displaced by serotonin S/sub 2/ antagonists and exhibited a profile similar to that of /sup 3/H-spiperone binding. In the presence of the serotonin S/sub 2/ antagonist spiperone, antihistamines (H/sub 1/) potently displaced /sup 3/H-mianserin binding. /sup 3/H-Imipramine binding was displacedmore » potently by serotonin uptake inhibitors. The order of potency of serotonergic drugs in displacing /sup 3/H-imipramine binding was not similar to their order in displacing /sup 3/H-spiperone or -3H-serotonin binding. Prior midbrain raphe lesions greatly decreased the binding of /sup 3/H-imipramine but did not alter binding of /sup 3/H-mianserin. Binding of /sup 3/H-imipramine but not /sup 3/H-mianserin was sodium dependent. These results show that /sup 3/H-imipramine and /sup 3/H-mianserin bind to different receptors. /sup 3/H-Imipramine binds to a presynaptic serotonin receptor which is probably related to a serotonin uptake recognition site, the binding of which is sodium dependent. /sup 3/H-Mianserin binds to postsynaptic receptors, possibly both serotonin S/sub 2/ and histamine H/sub 1/ receptors, the binding of which is sodium independent.« less

Don't Sweat the Small Stuff: Food Allergy Sufferer Lives a Cautious but Normal Life

MedlinePlus

... normal life Follow us Don’t Sweat the Small Stuff Food allergy sufferer lives a cautious but ... stings. The show recommended giving your child a small dose of antihistamine if you feared an allergic ...

Modeling covalent-modifier drugs.

PubMed

Awoonor-Williams, Ernest; Walsh, Andrew G; Rowley, Christopher N

2017-11-01

In this review, we present a summary of how computer modeling has been used in the development of covalent-modifier drugs. Covalent-modifier drugs bind by forming a chemical bond with their target. This covalent binding can improve the selectivity of the drug for a target with complementary reactivity and result in increased binding affinities due to the strength of the covalent bond formed. In some cases, this results in irreversible inhibition of the target, but some targeted covalent inhibitor (TCI) drugs bind covalently but reversibly. Computer modeling is widely used in drug discovery, but different computational methods must be used to model covalent modifiers because of the chemical bonds formed. Structural and bioinformatic analysis has identified sites of modification that could yield selectivity for a chosen target. Docking methods, which are used to rank binding poses of large sets of inhibitors, have been augmented to support the formation of protein-ligand bonds and are now capable of predicting the binding pose of covalent modifiers accurately. The pK a 's of amino acids can be calculated in order to assess their reactivity towards electrophiles. QM/MM methods have been used to model the reaction mechanisms of covalent modification. The continued development of these tools will allow computation to aid in the development of new covalent-modifier drugs. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman. Copyright © 2017 Elsevier B.V. All rights reserved.

Validation and Clinical Utility of the hERG IC50:Cmax Ratio to Determine the Risk of Drug-Induced Torsades de Pointes: A Meta-Analysis.

PubMed

Lehmann, David F; Eggleston, William D; Wang, Dongliang

2018-03-01

Use of the QT interval corrected for heart rate (QTc) on the electrocardiogram (ECG) to predict torsades de pointes (TdP) risk from culprit drugs is neither sensitive nor specific. The ratio of the half-maximum inhibitory concentration of the hERG channel (hERG IC50) to the peak serum concentration of unbound drug (C max ) is used during drug development to screen out chemical entities likely to cause TdP. To validate the use of the hERG IC50:C max ratio to predict TdP risk from a culprit drug by its correlation with TdP incidence. Medline (between 1966 and March 2017) was accessed for hERG IC50 and C max values from the antihistamine, fluoroquinolone, and antipsychotic classes to identify cases of drug-induced TdP. Exposure to a culprit drug was estimated from annual revenues reported by the manufacturer. Inclusion criteria for TdP cases were provision of an ECG tracing that demonstrated QTc prolongation with TdP and normal serum values of potassium, calcium, and magnesium. Cases reported in patients with a prior rhythm disturbance and those involving a drug interaction were excluded. The Meta-Analysis of Observational Studies in Epidemiology checklist was used for epidemiological data extraction by two authors. Negligible risk drugs were defined by an hERG IC50:C max ratio that correlated with less than a 5% chance of one TdP event for every 100 million exposures (relative risk [RR] 1.0). The hERG IC50:C max ratio correlated with TdP risk (0.312; 95% confidence interval 0.205-0.476, p<0.0001), a ratio of 80 (RR 1.0). The RR from olanzapine is on par with loratadine; ziprasidone is comparable with ciprofloxacin. Drugs with an RR greater than 50 include astemizole, risperidone, haloperidol, and thioridazine. The hERG IC50:C max ratio was correlated with TdP incidence for culprit drugs. This validation provides support for the potential use of the hERG IC50:C max ratio for clinical decision making in instances of drug selection where TdP risk is a concern. © 2018 Pharmacotherapy Publications, Inc.

Drug Reaction with Eosinophilia and Systemic Symptoms: Retrospective Analysis of 104 Cases over One Decade

PubMed Central

Wang, Li; Mei, Xue-Ling

2017-01-01

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, life-threatening disorder caused by drugs. In the present study, we tried to explore the types of DRESS-inducing drugs, incubation period, features of skin rashes, accompanying visceral damage, and effectiveness of glucocorticoid therapy so as to inform clinical practice. Methods: Patients diagnosed with a drug-induced rash, dermatitis, and DRESS admitted to our hospital from January 2006 to December 2015 were included in the study. The diagnosis followed the criteria and scoring system set by the European Registry of Severe Cutaneous Adverse Reactions. Statistical analyses were carried out using SPSS version 17.0 (IBM, Armonk, NY, USA), and a value of P < 0.05 was considered statistically significant. Results: Among 104 patients, 38 were male and 66 female (aged 18–83 years). The latent period was 13 (interquartile range [IQR]: 10–17) days. The most common allergy-inducing drugs were antibiotics (n = 37, 35.6%), followed by antiepileptic drugs and traditional Chinese medicines (TCMs). Eighty-two cases (78.8%) had rash with area >50% body surface area (BSA). Liver damage occurred in 90% of cases. Patients were divided into oral antihistamine group and glucocorticoid/immunosuppressive agent/intravenous immunoglobulin (IVIG) group. Sex, age, incubation period, duration of hospital stay, and the number of patients with body temperature ≥38.5°C were not significantly different between the two groups. However, the number of patients meeting the criteria of “definite” and “probable” (χ2 = 5.852, P = 0.016), with an eosinophilic granulocyte count of ≥1.5 × 109/L (χ2 = 7.129, P = 0.008), and with rash area of >50% BSA (χ2 = 4.750, P = 0.029), was significantly different. Conclusions: Antibiotics were associated with allergic reactions, but TCMs also had an important role. Allergy resulting from repeat use of the same drug was more severe with a shorter incubation period. The most typical rash was widespread erythematous papules. Liver damage accounted for >90% of cases. PMID:28397724

Indomethacin-antihistamine combination for gastric ulceration control

NASA Technical Reports Server (NTRS)

Brown, P. A.; Danellis, J. V. (Inventor)

1981-01-01

An anti-inflammatory and analgesic composition containing indomethacin and an H sub 1 or an H sub 2 histamine receptor antagonist in an amount sufficient to reduce gastric distress caused by the indomethacin is described. Usable antagonists include pyrilamine, promethazine, metiamide and cimetidine.

Hyaluronic Acid-Based pH-Sensitive Polymer-Modified Liposomes for Cell-Specific Intracellular Drug Delivery Systems.

PubMed

Miyazaki, Maiko; Yuba, Eiji; Hayashi, Hiroshi; Harada, Atsushi; Kono, Kenji

2018-01-17

For the enhancement of therapeutic effects and reduction of side effects derived from anticancer drugs in cancer chemotherapy, it is imperative to develop drug delivery systems with cancer-specificity and controlled release function inside cancer cells. pH-sensitive liposomes are useful as an intracellular drug delivery system because of their abilities to transfer their contents into the cell interior through fusion or destabilization of endosome, which has weakly acidic environment. We earlier reported liposomes modified with various types of pH-sensitive polymers based on synthetic polymers and biopolymers as vehicles for intracellular drug delivery systems. In this study, hyaluronic acid (HA)-based pH-sensitive polymers were designed as multifunctional polymers having not only pH-sensitivity but also targeting properties to cells expressing CD44, which is known as a cancer cell surface marker. Carboxyl group-introduced HA derivatives of two types, MGlu-HA and CHex-HA, which have a more hydrophobic side chain structure than that of MGlu-HA, were synthesized by reaction with various dicarboxylic anhydrides. These polymer-modified liposomes were stable at neutral pH, but showed content release under weakly acidic conditions. CHex-HA-modified liposomes delivered their contents into CD44-expressing cells more efficiently than HA-modified or MGlu-HA-modified liposomes or unmodified liposomes, whereas the same liposomes were taken up only slightly by cells expressing CD44 proteins less. Competition assay using free HA or other polymers revealed that HA derivative-modified liposomes might be recognized by CD44. Therefore, HA-derivative-modified liposomes are useful as cell-specific intracellular drug delivery systems.

Prevalence and Clinical Characteristics of Chronic Spontaneous Urticaria in Pediatric Patients.

PubMed

Balp, Maria-Magdalena; Weller, Karsten; Carboni, Veruska; Chirilov, Alexandra; Papavassilis, Charis; Severin, Thomas; Tian, Haijun; Zuberbier, Torsten; Maurer, Marcus

2018-04-21

Data on the prevalence and disease management of chronic urticaria (CU) and chronic spontaneous urticaria (CSU) in the pediatric population are scarce. The present study assessed the prevalence of CU and CSU, and disease management among pediatric patients (0-17 years). A physician-based online survey was conducted in 5 European countries (United Kingdom, Germany, Italy, France, and Spain) assessing the annual diagnosed prevalence, disease characteristics and treatment patterns in the target population. Results are based on physician responses and analyzed using descriptive statistics. Prevalence estimates were calculated based on the number of CU/CSU pediatric patients seen, treated and referred by the respondents and extrapolated to the total pediatric population from each country. Across 5 European countries, the one-year diagnosed prevalence of CU and CSU in pediatric patients was 1.38% (95% CI, 0.94-1.86) and 0.75% (95% CI, 0.44-1.08), respectively. Angioedema was reported in 6%-14% of patients. A large proportion of CSU pediatric patients (40%-60%) were treated with H1-antihistamines at approved dose and 16% to 51% received H1-antihistamines at higher doses. Approximately 1/3 of pediatric CSU patients remained uncontrolled with H1- antihistamines at approved/higher doses. Other prescribed treatments were oral corticosteroids (10% to 28%) and topical creams (15% to 26%). This study revealed a prevalence of CSU among pediatric population comparable to adults and also suggested an unmet need for approved treatments for inadequately-controlled pediatric CSU patients. It is truly of concern that harmful (oral steroids) or insufficient (topical creams) treatments were frequently used despite of better and guideline recommended alternatives. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Anticholinergic, antihistaminic, and antiserotonergic activity of n-hexane extract of Zanthoxylum alatum seeds on isolated tissue preparations: An ex vivo study

PubMed Central

Saikia, Beenita; Barua, Chandana Choudhury; Haloi, Prakash; Patowary, Pompy

2017-01-01

Objectives: The aim of this study was to evaluate anticholinergic, antihistaminic, and antiserotonergic activity of the n-hexane extract of the seeds of Zanthoxylum alatum (ZAHE) on isolated ileum of rat and guinea pig and fundus of rat. Materials and Methods: ZAHE was prepared using soxhlet extraction and cumulative concentration response curves were constructed using various doses on the tissues for acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and histamine with or without n-hexane extract. Atropine, ketanserin, and pheniramine maleate were used as antagonists for ACh, serotonin, and histamine, respectively. Results: ZAHE-induced concentration-dependent inhibition of isolated ileum and fundus in rat and ileum of guinea pig. The half maximal effective concentration (EC50) of ACh in the presence of atropine (10−6 M; P < 0.05) and ZAHE (1000 μg/ml; P < 0.01) was significantly higher than EC50of ACh alone. The EC50of 5-HT in the presence of ketanserin (10−5 M; P < 0.01) and ZAHE (1000 μg/ml; P < 0.05) was higher than EC50of 5-HT alone. Similarly, the EC50of histamine in the presence of pheniramine maleate (10−6 M; P < 0.01) and ZAHE (300 μg/ml; P < 0.01 and 1000 μg/ml; P < 0.05) was also significantly higher than EC50of histamine alone. Conclusion: From the study, it was observed that ZAHE shows significant anticholinergic, antiserotonergic, and antihistaminic activity. The study provides sufficient evidence that the seeds can be used in gastric disorders, cough, chest infection, etc., as per folklore claims. PMID:28458421

A new class of nitric oxide-releasing derivatives of cetirizine; pharmacological profile in vascular and airway smooth muscle preparations

PubMed Central

Larsson, A-K; Fumagalli, F; DiGennaro, A; Andersson, M; Lundberg, J; Edenius, C; Govoni, M; Monopoli, A; Sala, A; Dahlén, S-E; Folco, G C

2007-01-01

Background and purpose: The pharmacological properties of compounds NCX 1512 and NCX 1514, synthesized by linking the histamine H1-receptor antagonist cetirizine to NO-releasing spacer groups, are reported. The aim was to establish if the compounds retained the antihistamine action of the parent compound, to assess their efficacy as NO donors and to test if they had broader antiallergic activity than cetirizine in the lung. Experimental approach: Antihistamine activity of NCX 1512 and NCX 1514 was investigated in vitro in the guinea pig ileum, in tracheal rings (GPTR) and lung parenchymal strips (GPLP) of the guinea-pig. The NO-releasing capacity was investigated in vascular preparations; the isolated rabbit and guinea-pig aorta and guinea-pig pulmonary artery. Kinetics of NO release were assessed in a rat whole blood assay. Key results: Both NCX 1512 and NCX 1514 retained activity as H1-receptor antagonists in the guinea pig ileum and airway preparations. The NO-releasing NCX compounds relaxed the rabbit aorta, an action prevented by the guanylyl cyclase inhibitor ODQ (10 μM). NCX 1512 and NCX 1514 did not relax the antigen (ovalbumin) pre-contracted GPTR, whereas the NO donors NCX 2057 and DEA-NONOate relaxed guinea-pig pre-contracted vascular and tracheal preparations. Cetirizine (1–100 μM) and NCX 1512 (1–100 μM) reduced the cumulative (0.01–100 μg ml−1) ovalbumin-induced constriction in GPTR, but had no significant effect in GPLP. Conclusions and implications: NCX 1512 and NCX 1514 act as antihistamines and NO donors. However, there was no improved effect compared to cetirizine on antigen-induced constriction of the central and peripheral lung. PMID:17351654

21 CFR 172.892 - Food starch-modified.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Food starch-modified. 172.892 Section 172.892 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION...

21 CFR 172.892 - Food starch-modified.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Food starch-modified. 172.892 Section 172.892 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION...

21 CFR 172.892 - Food starch-modified.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Food starch-modified. 172.892 Section 172.892 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.892 Food...

21 CFR 177.1600 - Polyethylene resins, carboxyl modified.

Code of Federal Regulations, 2010 CFR

2010-04-01

... resins used in food-packaging adhesives complying with § 175.105 of this chapter. ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Polyethylene resins, carboxyl modified. 177.1600 Section 177.1600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 177.1600 - Polyethylene resins, carboxyl modified.

Code of Federal Regulations, 2011 CFR

2011-04-01

... resins used in food-packaging adhesives complying with § 175.105 of this chapter. ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Polyethylene resins, carboxyl modified. 177.1600 Section 177.1600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 177.1600 - Polyethylene resins, carboxyl modified.

Code of Federal Regulations, 2012 CFR

2012-04-01

... resins used in food-packaging adhesives complying with § 175.105 of this chapter. ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Polyethylene resins, carboxyl modified. 177.1600 Section 177.1600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 177.1600 - Polyethylene resins, carboxyl modified.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Polyethylene resins, carboxyl modified. 177.1600 Section 177.1600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and Repeated...

21 CFR 177.1600 - Polyethylene resins, carboxyl modified.

Code of Federal Regulations, 2013 CFR

2013-04-01

... resins used in food-packaging adhesives complying with § 175.105 of this chapter. ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Polyethylene resins, carboxyl modified. 177.1600 Section 177.1600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 177.1640 - Polystyrene and rubber-modified polystyrene.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Polystyrene and rubber-modified polystyrene. 177.1640 Section 177.1640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and...

Applications of Natural Polymeric Materials in Solid Oral Modified-Release Dosage Forms.

PubMed

Li, Liang; Zhang, Xin; Gu, Xiangqin; Mao, Shirui

2015-01-01

Solid oral modified-release dosage forms provide numerous advantages for drug delivery compared to dosage forms where the drugs are released and absorbed rapidly following ingestion. Natural polymers are of particular interest as drug carriers due to their good safety profile, biocompatibility, biodegradability, and rich sources. This review described the current applications of important natural polymers, such as chitosan, alginate, pectin, guar gum, and xanthan gum, in solid oral modified-release dosage forms. It was shown that natural polymers have been widely used to fabricate solid oral modified-release dosage forms such as matrix tablets, pellets and beads, and especially oral drug delivery systems such as gastroretentive and colon drug delivery systems. Moreover, chemical modifications could overcome the shortcomings associated with the use of natural polymers, and the combination of two or more polymers presented further advantages compared with that of single polymer. In conclusion, natural polymers and modified natural polymers have promising applications in solid oral modified-release dosage forms. However, commercial products based on them are still limited. To accelerate the application of natural polymers in commercial products, in vivo behavior of natural polymers-based solid oral modified-release dosage forms should be deeply investigated, and meanwhile quality of the natural polymers should be controlled strictly, and the influence of formulation and process parameters need to be understood intensively.

A technical feasibility study of surfactant-free drug suspensions using octenyl succinate-modified starches.

PubMed

Kuentz, Martin; Egloff, Peter; Röthlisberger, Dieter

2006-05-01

Many new drugs exhibit poor wetting behaviour and low aqueous solubility. This is particularly an issue for preclinical studies like toxicological trials, in which considerably higher doses and volumes are being administered compared to clinical studies. Preclinical vehicles typically contain high levels of surfactants that can exert biological effects. However, the biological inertness of vehicles is pivotal for the application in preclinical studies stressing the need in finding new excipients to solve formulation problems of today's drug discovery. The present study investigated the technical feasibility of surfactant-free suspensions using a new poorly soluble drug as model. It was shown that octenyl succinate-modified starches adequately wetted the drug and homogenous tasteless suspensions were obtained. The polymer xanthan gum was identified as macroscopically compatible gelling agent. Concentration effects of xanthan, drug and different modified starches were studied in a D-optimal design with respect to rheological properties. The suspensions were also tested in an analytical centrifuge using NIR transmission profiles to obtain a measure of sedimentation stability under accelerated conditions. The modified starches exhibited only little influence on the viscosity as well as on the yield point in contrast to the rheological effects of xanthan gum. This gelling agent was the main stabilising excipient as the modified starches hindered to a lesser extent sedimentation. The most stable suspensions displayed convenient flow properties. The viscosity at 100 s(-1) and 25 degrees C was in technically acceptable range of 120-140 mPa s in view of a application via gavage or a syringe in animal studies. The results demonstrated that surfactant-free drug suspensions with excellent technical performance can be obtained using octenyl succinate-modified starches. The vehicles were tasteless and based on the experience of modified starches in the food industry, the vehicles should exhibit good tolerability. The future use of such surfactant-free drug suspensions in toxicological, pharmacokinetic and pharmacodynamic studies will have to determine their advantage in terms of biological inertness.

Modified SBA-15 as the carrier for metoprolol and papaverine: Adsorption and release study

NASA Astrophysics Data System (ADS)

Moritz, MichaŁ; łaniecki, Marek

2011-07-01

A series of modified SBA-15 materials were applied in drug delivery systems. The internal surface of siliceous hexagonal structure of SBA-15 was modified with different amount of (3-mercaptopropyl)trimethoxysilane (MPTMS) and oxidized in the presence of hydrogen peroxide. The sulfonated material was loaded with metoprolol tartrate or papaverine hydrochloride. Both drugs indicated strong chemical interaction with modified mesoporous surface. The characteristic of the obtained materials was performed with XRD and DRUV-vis spectrometry, themogravimetry and nitrogen adsorption (BET) measurements. The obtained results show that modification of the mesoporous materials leads towards significant decrease of the drug delivery rate.

The effects of altitude and two decongestant-antihistamine preparations on physiological functions and performance.

DOT National Transportation Integrated Search

1978-04-01

Fourteen men were studied to determine the combined effects of two altitudes (ground level (1,274 ft) and 12,500 ft), and three preparations (lactose placebo, Compound A (Actifed - Registered Trade Name), and Compound B (Dristan - Registered Trade Na...

Lesson of the month 2: The limitations of steroid therapy in bradykinin-mediated angioedema attacks.

PubMed

Ismail, Sharif; Cheng, Leo; Grigoriadou, Sofia; Laffan, James; Menon, Manoj

2015-02-01

Acute angioedema attacks are conventionally treated with antihistamines and steroids, in line with a presumed mechanism of disease involving overwhelming mast-cell degranulation. This approach overlooks a small but important minority of cases in which attacks are bradykinin driven and exhibit poor responsiveness to steroid or anti-histamine therapy. These patients may have a family history of angioedema (hereditary angioedema), or a past medical history including B-cell lymphoproliferative disorders or autoimmune disease (acquired angioedema). Rather than steroid therapy, they respond to administration of a bradykinin inhibitor, or more commonly, a C1 esterase inhibitor substitute, to control acute symptoms and reduce the probability of invasive airway insertion. In the long-term, they require C1 esterase inhibitor sparing therapy and a treat-the-cause approach to reduce the risk of recurrent attacks. We present here a case of a middle-aged woman who presented with recurrent angioedema of initially uncertain aetiology. © 2015 Royal College of Physicians.

Apolipoprotein E modifies the CNS response to injury via a histamine-mediated pathway.

PubMed

Mace, Brian E; Wang, Haichen; Lynch, John R; Moss, Jason; Sullivan, Patrick; Colton, Heidi; Morgan, Kevin; Renauld, Jean-Christophe; Laskowitz, Daniel T

2007-04-01

Recent evidence demonstrates that apolipoprotein E (apoE) influences the central nervous system (CNS) response to both acute and chronic injury. To address the mechanisms by which apoE influences neurological disease, we examined differential gene expression in the brains of apoE transgenic mice after closed head injury. Apart from confirming the knockout of apoE, the largest differential gene expression occurred for the interleukin-9 receptor (IL-9R), which was > 100-fold up-regulated in apoE-deficient versus wild-type mice. We observed a similar pattern of posttraumatic IL-9R up-regulation in APOE4 targeted replacement mice as compared with their APOE3 counterparts. This difference in gene expression was associated with increased neuronal protein expression of IL-9R in E4 animals compared with E3 as demonstrated by immunohistochemistry. The consequence of IL-9R binding in mast cells is the induction of proliferation and differentiation. This indirectly favors degranulation and release of histamine and inflammatory mediators, which have previously been demonstrated to exacerbate secondary neuronal injury. We found that apoE-deficient animals had increased levels of systemic histamine after injury and that pre-treatment with antihistamines improved functional outcomes in apoE-deficient but not wild-type animals after head injury. These results suggest that apoE modifies secondary neuronal injury caused by histamine release and are consistent with previous observations that apoE affects the CNS inflammatory response in an isoform-specific manner.

Adenylate Kinase Release as a High-Throughput-Screening-Compatible Reporter of Bacterial Lysis for Identification of Antibacterial Agents

PubMed Central

Jacobs, Anna C.; DiDone, Louis; Jobson, Jennielle; Sofia, Madeline K.

2013-01-01

Adenylate kinase (AK) is a ubiquitous intracellular enzyme that is released into the extracellular space upon cell lysis. We have shown that AK release serves as a useful reporter of bactericidal agent activity and can be exploited for antimicrobial screening purposes. The AK assay exhibits improved sensitivity over that of growth-based assays and can detect agents that are active against bacteria in clinically relevant growth states that are difficult to screen using conventional approaches, such as small colony variants (SCV) and bacteria within established biofilms. The usefulness of the AK assay was validated by screening a library of off-patent drugs for agents that exhibit antimicrobial properties toward a variety of bacterial species, including Escherichia coli and all members of the “ESKAPE” pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The assay detected antibiotics within the library that were expected to be active against the organism screened. Moreover, 38 drugs with no previously reported antibacterial activity elicited AK release. Four of these were acquired, and all were verified to exhibit antimicrobial activity by standard susceptibility testing. Two of these molecules were further characterized. The antihistamine, terfenadine, was active against S. aureus planktonic, SCV population, and biofilm-associated cells. Tamoxifen, an estrogen receptor antagonist, was active toward E. faecium in vitro and also reduced E. faecium pathogenesis in a Galleria mellonella infection model. Our data demonstrate that the AK assay provides an attractive screening approach for identifying new antimicrobial agents. Further, terfenadine and tamoxifen may represent novel antimicrobial drug development scaffolds. PMID:23027196

Modified local diatomite as potential functional drug carrier--A model study for diclofenac sodium.

PubMed

Janićijević, Jelena; Krajišnik, Danina; Čalija, Bojan; Vasiljević, Bojana Nedić; Dobričić, Vladimir; Daković, Aleksandra; Antonijević, Milan D; Milić, Jela

2015-12-30

Diatomite makes a promising candidate for a drug carrier because of its high porosity, large surface area, modifiable surface chemistry and biocompatibility. Herein, refined diatomite from Kolubara coal basin, which complied with the pharmacopoeial requirements for heavy metals content and microbiological quality, was used as a starting material. Inorganic modification of the starting material was performed through a simple, one-step procedure. Significant increase in adsorbent loading with diclofenac sodium (DS) was achieved after the modification process (∼373mg/g) which enabled the preparation of comprimates containing therapeutic dose of the adsorbed drug. Adsorption of DS onto modified diatomite resulted in the alteration of the drug's XRD pattern and FTIR spectrum. In vitro drug release studies in phosphate buffer pH 7.5 demonstrated prolonged DS release over 8h from comprimates containing DS adsorbed on modified diatomite (up to 37% after 8h) and those containing physical mixture of the same composition (up to 45% after 8h). The results of in vivo toxicity testing on mice pointed on potential safety of both unmodified (starting) and modified diatomite. All these findings favor the application of diatomite as a potential functional drug carrier. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of discharge medication orders following automatic therapeutic substitution of commonly exchanged drug classes.

PubMed

Glaholt, Sarah; Hayes, Genevieve L; Wisniewski, Christopher S

2014-04-01

Automatic therapeutic substitution (ATS) is a mechanism that, upon patient hospitalization, prompts the pharmacist to exchange an equivalent formulary drug for a nonformulary medication, typically without prescriber contact. In facilities utilizing ATS, there is the possibility that physicians and patients may be unaware of the substitution, potentially leading to drug-drug interactions, therapeutic duplication, and/or increased patient expense following discharge should the original regimen not be resumed. The purpose of this study was to determine the frequency with which hospitalized patients subjected to an ATS protocol were not returned to outpatient drug therapy. A retrospective chart review of adult patients admitted to an academic medical center between January 1 and June 30, 2011, was conducted. Patients were included if they were admitted on angiotensin-converting enzyme (ACE) inhibitors, antidepressants, nonsedating antihistamines, histamine (H2) receptor antagonists, or proton pump inhibitors (PPIs), and were then prescribed a different agent via ATS. Admission and discharge medication reconciliation documents, dictated discharge summaries, and patient education documentation reports were reviewed for drug therapies and doses, as well as medication counseling evidence. The primary endpoint was the percentage of patients not returned to original outpatient therapy following ATS. Secondary endpoints included prescribing events in patients not returned to original therapy, the rate and source of drug therapy counseling at discharge, and the number of patients discharged on a potentially cost-prohibitive drug, defined as any drug available only as a branded product during the study period. A total of 317 interventions were identified through review of pharmacy records. Of these, 47 patients (15%) were not returned to original outpatient therapy. Within this subsection, 15 patients (32%) were discharged on the substituted drug, eight patients (17%) resumed initial therapy but received a dosage adjustment from previous outpatient therapy, and three patients (6%) were discharged on a drug that was neither the substituted product nor the previous outpatient therapy. The remaining 21 patients had therapy discontinued (n = 12/47, 26%) or lacked documentation of discharge therapy (9/47, 19%). Nursing staff provided medication counseling to 288 of the 317 patients (91%). Overall, 51 patients (16%) were identified as receiving a cost-prohibitive drug. Patients subject to ATS of commonly substituted drug classes were returned to their original outpatient drug therapy more than 85% of the time following inpatient hospitalizations, with similar rates of medication counseling at discharge. The prescribing of cost-prohibitive drugs has been identified as a potential area for pharmacist intervention at discharge.

Tannate complexes of antihistaminic drug: sustained release and taste masking approaches.

PubMed

Rahman, Ziyaur; Zidan, Ahmed S; Berendt, Robert T; Khan, Mansoor A

2012-01-17

The aim of this investigation was to evaluate the complexation potential of brompheniramine maleate (BPM) and tannic acid (TA) for sustained release and taste masking effects. The complexes (1:1-1:7 TA to BPM ratio) were prepared by the solvent evaporation method using methanol, phosphate buffer pH 6.8 or 0.1N HCl as common solvents. The complexes were characterized microscopically by scanning electron microscopy (SEM), chemically by Fourier transform infrared (FTIR) and solid-state NMR (SSNMR), thermally by differential scanning calorimetry (DSC), for crystallinity by powder X-ray powder diffraction (PXRD), for organoleptic evaluation by electronic tongue (e-tongue), and for solubility in 0.1N HCl and phosphate buffer pH 6.8. The dissolution studies were carried out using the USP II method at 50 rpm in 500 ml of dissolution media (0.1N HCl or phosphate buffer pH 6.8). SEM images revealed that the morphology of complexes were completely different from the individual components, and all complexes had the same morphological characteristics, irrespective of the solvent used for their preparation, pH or ratio of BPM and TA. The FTIR spectra showed the presence of chemical interactions between the TA and BPM. DSC, PXRD and SSNMR indicated that the drug lost its crystalline nature by formation of the complex. Complexation has significantly reduced the solubility of BPM and sustained the drug release up to 24h in phosphate buffer pH 6.8 media. The bitter taste of the BPM was completely masked which was indicated by Euclidean distance values which was far from the drug but near to its placebo in the complexes in all ratios studied. The taste masked complexes can be potentially developed as suitable dosage forms for pediatric use. In summary, complexation of BPM and TA effectively sustained the dissolution and masked the bitter taste of drug for the development of suitable dosage forms for pediatric use. Published by Elsevier B.V.

The opinions and experiences of family physicians regarding direct-to-consumer advertising.

PubMed

Lipsky, M S; Taylor, C A

1997-12-01

The use of direct-to-consumer advertising (DTCA) by pharmaceutical companies is increasing. Our study examines the opinions and experiences of family physicians concerning DTCA. A survey instrument designed to elicit the opinions, experiences, and perceptions of family physicians about DTCA was sent to a 2% (N = 880) systematic sampling of active physician members of the American Academy of Family Physicians. Descriptive statistics were used to analyze responses with t tests and chi 2 tests for independence used to examine subgroup response differences. Four hundred fifty-four (52%) physicians responded to the survey. Most physicians (95%) had encountered DTCA personally, and had been approached by an average of 7 patients over the previous 6 months with requests for specific prescription drugs. Prescription antihistamines and antihypertensive drugs were the most commonly requested. Overall, 80% of the physician respondents believed that print DTCA was not a good idea, while 84% expressed negative feelings about television and radio advertising. Both groups cited "misleading biased view" and "increased costs" as the most common disadvantages. Some reported benefits included "better informed patients" and "promoting physician-patient communication." Overall, the study group physicians had negative feelings about DTCA in both print and electronic media. Studies directly examining patient perspectives, as well as cost benefits, are necessary to test the validity of the physicians' perceptions about DTCA.

Oxidation of cetirizine, fexofenadine and hydrochlorothiazide during ozonation: Kinetics and formation of transformation products.

PubMed

Borowska, Ewa; Bourgin, Marc; Hollender, Juliane; Kienle, Cornelia; McArdell, Christa S; von Gunten, Urs

2016-05-01

The efficiency of wastewater ozonation for the abatement of three nitrogen-containing pharmaceuticals, two antihistamine drugs, cetirizine (CTR) and fexofenadine (FXF), and the diuretic drug, hydrochlorothiazide (HCTZ), was investigated. Species-specific second-order rate constants for the reactions of the molecular, protonated (CTR, FXF) or deprotonated (HCTZ) forms of these compounds with ozone were determined. All three compounds are very reactive with ozone (apparent second order rate constants at pH 7: kO3,pH7 = 1.7·10(5) M(-1)s(-1), 8.5·10(4) M(-1)s(-1) and 9.0·10(3) M(-1)s(-1) for CTR, HCTZ and FXF, respectively). Transformation product (TP) structures were elucidated using liquid chromatography coupled with high-resolution tandem mass spectrometry, including isotope-labeled standards. For cetirizine and hydrochlorothiazide 8 TPs each and for fexofenadine 7 TPs were identified. The main TPs of cetirizine and fexofenadine are their respective N-oxides, whereas chlorothiazide forms to almost 100% from hydrochlorothiazide. In the bacteria bioluminescence assay the toxicity was slightly increased only during the ozonation of cetirizine at very high cetirizine concentrations. The main TPs detected in bench-scale experiments were also detected in full-scale ozonation of a municipal wastewater, for >90% elimination of the parent compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Buffer salt effects in off-line coupling of capillary electrophoresis and mass spectrometry.

PubMed

Marák, Jozef; Stanová, Andrea

2014-05-01

In this work, the impact of buffer salts/matrix effects on the signal in direct injection MS with an electrospray interface (DI-ESI-MS) following pITP fractionation of the sample was studied. A range of buffers frequently used in CE analyses (pH 3-10) was prepared containing 10, 50, and 90% v/v of ACN, respectively. The sets of calibration solutions of cetirizine (an antihistaminic drug with an amphiprotic character) within a 0.05-2.0 mg/L concentration range were prepared in different buffers. The greatest enhancements in the MS signal (in terms of change in the slope of the calibration line) were obtained for the beta-alanine buffer (pH 3.5) in positive ionization and for the borate buffer (pH 9.2) in negative ionization, respectively. The procedure was successfully applied to the analysis of buserelin (a peptidic drug). The slope of the calibration line for solutions containing the beta-alanine buffer with 50% of ACN was 4 times higher than for water or urine, respectively. This study clearly demonstrates that the buffer salt/matrix effects in an offline combination of pITP and DI-ESI-MS can also play a positive role, as they can enhance the signal in MS. A similar influence of the above effects can also be presumed in the CE techniques combined on-line with ESI-MS.

Alpinia calcarata Roscoe: a potent antiinflammatory agent.

PubMed

Arawwawala, L D A M; Arambewela, L S R; Ratnasooriya, W D

2012-02-15

Alpinia calcarata Roscoe (Family: Zingiberaceae) rhizomes are often used in Sri Lankan traditional systems of medicine as a remedy for bronchitis, cough, respiratory ailments, diabetics, asthma and arthritis. Generally drugs that are used for arthritis have antinociceptive and antiinflammatory properties. However, validity of the antiinflammatory activity has not been scientifically investigated so far. Therefore, the aim of this study was to investigate the antiinflammatory potential of Alpinia calcarata rhizomes using hot water extract (AWE) and hot ethanolic extract (AEE). The antiinflammatory activity of Alpinia calcarata was evaluated by use of the carrageenan-induced paw oedema model in rats. In addition, the mechanism/s by which Alpinia calcarata is mediated the antinflammatory activity was assessed by determining its effects on (a) membrane stabilizing, (b) antihistamine and (c) prostaglandin synthesis inhibition activity. All the tested doses of AWE and AEE (250, 500, 750, and 1000 mg/kg) produced a significant (P≤0.05) inhibition of the inflammation, most pronounced at 4h after the injection of carrageenan. The antiinflammatory effect induced by 500 mg/kg of AEE was superior than the reference drug, indomethacin at 4h. Inhibition of histamine and prostaglandin synthesis production is probable mechanisms by which Alpinia calcarata mediates its antiinflammatory action. These findings rationalize the traditional usage of Alpinia calcarata as an antiinflammatory agent for the first time. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Microenvironmental pH-modification to improve dissolution behavior and oral absorption for drugs with pH-dependent solubility.

PubMed

Taniguchi, Chika; Kawabata, Yohei; Wada, Koichi; Yamada, Shizuo; Onoue, Satomi

2014-04-01

Drug release and oral absorption of drugs with pH-dependent solubility are influenced by the conditions in the gastrointestinal tract. In some cases, poor oral absorption has been observed for these drugs, causing insufficient drug efficacy. The pH-modification of a formulation could be a promising approach to overcome the poor oral absorption of drugs with pH-dependent solubility. The present review aims to summarize the pH-modifier approach and strategic analyses of microenvironmental pH for formulation design and development. We also provide literature- and patent-based examples of the application of pH-modification technology to solid dosage forms. For the pH-modification approach, the microenvironmental pH at the diffusion area can be altered by dissolving pH-modifying excipients in the formulation. The modulation of the microenvironmental pH could improve dissolution behavior of drugs with pH-dependent solubility, possibly leading to better oral absorption. According to this concept, the modulated level of microenvironmental pH and its duration can be key factors for improvement in drug dissolution. The measurement of microenvironmental pH and release of pH-modifier would provide theoretical insight for the selection of an appropriate pH-modifier and optimization of the formulation.

Eye itching in ophthalmology and its treatment.

PubMed

Mikuni, I

1984-12-01

Itching in the field of ophthalmology is detailed in its physiopathology and a few other aspects were described. The therapeutic modalities which have been practiced are explained. In addition to steroids and antihistaminics which are commonly used, INTAL and others, suppressors of chemical transmitter substance release, are described.

In vivo antimuscarinic actions of the third generation antihistaminergic agent, desloratadine.

PubMed

Howell, G; West, L; Jenkins, C; Lineberry, B; Yokum, D; Rockhold, R

2005-08-18

Muscarinic receptor mediated adverse effects, such as sedation and xerostomia, significantly hinder the therapeutic usefulness of first generation antihistamines. Therefore, second and third generation antihistamines which effectively antagonize the H1 receptor without significant affinity for muscarinic receptors have been developed. However, both in vitro and in vivo experimentation indicates that the third generation antihistamine, desloratadine, antagonizes muscarinic receptors. To fully examine the in vivo antimuscarinic efficacy of desloratadine, two murine and two rat models were utilized. The murine models sought to determine the efficacy of desloratadine to antagonize muscarinic agonist induced salivation, lacrimation, and tremor. Desloratadine's effect on the cardiovascular system was explored in both rodent models. In the pithed rat, both desloratadine (1.0 mg/kg, i.v.) and the muscarinic M2 selective antagonist, methoctramine (0.5 mg/kg, i.v.), inhibited negative inotropic (left ventricular dP/dt) effects caused by oxotremorine, a nonselective muscarinic agonist (p < 0.05). Negative chronotropic effects caused by oxotremorine were inhibited by desloratadine, methoctramine, and the muscarinic M3 selective antagonist, 4-DAMP (1.0 mg/kg, i.v.). A late positive inotropic event observed after the initial decrease was inhibited by all three test compounds with desloratadine and 4-DAMP being the most efficacious. In the conscious animal, inhibition of baroreflex-mediated bradycardia was evaluated. Unlike atropine (0.5 mg/kg, i.v.), desloratadine did not alter this bradycardia. The antimuscarinic action of desloratadine on salivation, lacrimation, and tremor was also explored. In urethane-anesthetized (1.5 g/kg, i.p.) male ICR mice (25-35 g) desloratadine (1.0, 5.0 mg/kg) did not inhibit oxotremorine-induced (0.5 mg/kg, s.c.) salivation, unlike atropine (0.5 mg/kg) and 4-DAMP (1.0 mg/kg). In conscious mice, desloratadine failed to inhibit oxotremorine-induced (0.5 mg/kg, s.c.) salivation, lacrimation, and tremor. However, desloratadine did inhibit oxotremorine-induced tremor in phenylephrine pretreated animals. The presented data demonstrate that the third generation antihistamine, desloratadine, does not significantly antagonize peripheral muscarinic receptors mediating salivation and lacrimation, therefore, xerostomia and dry eyes should not be observed with therapeutic use of desloratadine. Our data also indicate when administered to a patient with a compromised blood-brain barrier, desloratadine may cause sedation. Patients with compromised cardiovascular systems should be closely monitored when administered desloratadine based on our results that desloratadine has the ability to interfere with normal cardiovascular function mediated by muscarinic receptors.

In vivo antimuscarinic actions of the third generation antihistaminergic agent, desloratadine

PubMed Central

Howell, G; West, L; Jenkins, C; Lineberry, B; Yokum, D; Rockhold, R

2005-01-01

Background Muscarinic receptor mediated adverse effects, such as sedation and xerostomia, significantly hinder the therapeutic usefulness of first generation antihistamines. Therefore, second and third generation antihistamines which effectively antagonize the H1 receptor without significant affinity for muscarinic receptors have been developed. However, both in vitro and in vivo experimentation indicates that the third generation antihistamine, desloratadine, antagonizes muscarinic receptors. To fully examine the in vivo antimuscarinic efficacy of desloratadine, two murine and two rat models were utilized. The murine models sought to determine the efficacy of desloratadine to antagonize muscarinic agonist induced salivation, lacrimation, and tremor. Desloratadine's effect on the cardiovascular system was explored in both rodent models. Results In the pithed rat, both desloratadine (1.0 mg/kg, i.v.) and the muscarinic M2 selective antagonist, methoctramine (0.5 mg/kg, i.v.), inhibited negative inotropic (left ventricular dP/dt) effects caused by oxotremorine, a nonselective muscarinic agonist (p < 0.05). Negative chronotropic effects caused by oxotremorine were inhibited by desloratadine, methoctramine, and the muscarinic M3 selective antagonist, 4-DAMP (1.0 mg/kg, i.v.). A late positive inotropic event observed after the initial decrease was inhibited by all three test compounds with desloratadine and 4-DAMP being the most efficacious. In the conscious animal, inhibition of baroreflex-mediated bradycardia was evaluated. Unlike atropine (0.5 mg/kg, i.v.), desloratadine did not alter this bradycardia. The antimuscarinic action of desloratadine on salivation, lacrimation, and tremor was also explored. In urethane-anesthetized (1.5 g/kg, i.p.) male ICR mice (25–35 g) desloratadine (1.0, 5.0 mg/kg) did not inhibit oxotremorine-induced (0.5 mg/kg, s.c.) salivation, unlike atropine (0.5 mg/kg) and 4-DAMP (1.0 mg/kg). In conscious mice, desloratadine failed to inhibit oxotremorine-induced (0.5 mg/kg, s.c.) salivation, lacrimation, and tremor. However, desloratadine did inhibit oxotremorine-induced tremor in phenylephrine pretreated animals. Conclusion The presented data demonstrate that the third generation antihistamine, desloratadine, does not significantly antagonize peripheral muscarinic receptors mediating salivation and lacrimation, therefore, xerostomia and dry eyes should not be observed with therapeutic use of desloratadine. Our data also indicate when administered to a patient with a compromised blood-brain barrier, desloratadine may cause sedation. Patients with compromised cardiovascular systems should be closely monitored when administered desloratadine based on our results that desloratadine has the ability to interfere with normal cardiovascular function mediated by muscarinic receptors. PMID:16109168

[Application of fuzzy mathematics on modifying taste of oral solution of traditional Chinese drug].

PubMed

Wang, Youjie; Feng, Yi; Zhang, Bo

2009-01-01

To apply Fuzzy mathematical methods to choose the best taste modifying prescription of oral solution of traditional Chinese drug. Jin-Fukang oral solution was used as a model drug. The oral solution was prepared in different taste modifying prescriptions, whose tastes were evaluated by the fuzzy quality synthetic evaluation system. Compound-sweeteners with Sucralose and Erythritol was the best choice. Fuzzy integrated evaluation can be used to evaluate the taste of traditional Chinese medicinal pharmaceuticals, which overcame the artificial factors and achieve more objective conclusion.

Sustained release and permeation of timolol from surface-modified solid lipid nanoparticles through bioengineered human cornea.

PubMed

Attama, A A; Reichl, S; Müller-Goymann, C C

2009-08-01

The aim of the study was to formulate and evaluate surface-modified solid lipid nanoparticles sustained delivery system of timolol hydrogen maleate, a prototype ocular drug using a human cornea construct. Surface-modified solid lipid nanoparticles containing timolol with and without phospholipid were formulated by melt emulsification with high-pressure homogenization and characterized by particle size, wide-angle X-ray diffraction, encapsulation efficiency, and in vitro drug release. Drug transport studies through cornea bioengineered from human donor cornea cells were carried out using a modified Franz diffusion cell and drug concentration analyzed by high-performance liquid chromatography. Results show that surface-modified solid lipid nanoparticles possessed very small particles (42.9 +/- 0.3 nm, 47.2 +/- 0.3 nm, 42.7 +/- 0.7 nm, and 37.7 +/- 0.3 nm, respectively for SM-SLN 1, SM-SLN 2, SM-SLN 3, and SM-SLN 4) with low polydispersity indices, increased encapsulation efficiency (> 44%), and sustained in vitro release compared with unmodified lipid nanoparticles whose particles were greater than 160 nm. Permeation of timolol hydrogen maleate from the surface-modified lipid nanoparticles across the cornea construct was sustained compared with timolol hydrogen maleate solution in distilled water. Surface-modified solid lipid nanoparticles could provide an efficient way of improving ocular bioavailability of timolol hydrogen maleate.

A Forehead-Mounted Measure of O2 Saturation: The Potential for in Cockpit Hypoxia Early Detection and Warning

DTIC Science & Technology

2010-07-09

past 24 hours. (circle all that apply) a. None b. Sedatives/Tranquilizers c. Aspirin/ Tylenol /any analgesic d. Antihistamines...e. Decongestants f. Other (please specify) 6. Do you take any over the counter medications (e.g., antacids, Benadryl, Tylenol , etc

[Interactions of food and drug metabolism].

PubMed

Delzenne, N M; Verbeeck, R K

2001-01-01

The nutritional state, and/or the ingestion of specific nutrients, is/are able to modify drug disposition, by interfering with drug absorption, distribution, storage, and metabolism. Recent data report that nutrients interfere with drug metabolism either by modifying key enzymes of phase I (cytochromeP450 dependent mixed function oxidase) and II (glucuronosyl, sulfonyl- ... transferases), or by modulating coenzymes availability (NADPH, UDPglucuronic acid...). Food components involved in drug metabolism modifications are either macro-nutrients (carbohydrates, lipids, proteins, ethanol), micronutriments (vitamins, minerals), or phytochemicals. Drug-nutrients interactions may be beneficials, and thus could constitute, i.e. a way to improve drug therapeutic index, or generate adverse effects.

Original research paper. Characterization and taste masking evaluation of microparticles with cetirizine dihydrochloride and methacrylate-based copolymer obtained by spray drying.

PubMed

Amelian, Aleksandra; Szekalska, Marta; Ciosek, Patrycja; Basa, Anna; Winnicka, Katarzyna

2017-03-01

Taste of a pharmaceutical formulation is an important parameter for the effectiveness of pharmacotherapy. Cetirizine dihydrochloride (CET) is a second-generation antihistamine that is commonly administered in allergy treatment. CET is characterized by extremely bitter taste and it is a great challenge to successfully mask its taste; therefore the goal of this work was to formulate and characterize the microparticles obtained by the spray drying method with CET and poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate 1:2:1 copolymer (Eudragit E PO) as a barrier coating. Assessment of taste masking by the electronic tongue has revealed that designed formulations created an effective taste masking barrier. Taste masking effect was also confirmed by the in vivo model and the in vitro release profile of CET. Obtained data have shown that microparticles with a drug/polymer ratio (0.5:1) are promising CET carriers with efficient taste masking potential and might be further used in designing orodispersible dosage forms with CET.

[Perception of body weight by pharmacists and pharmaceutical laboratory assistants in Slovakia I].

PubMed

Kolář, Jozef; Zabolyová, Stefánia

2013-10-01

The paper presents the results of a questionnaire poll carried out in the workers in pharmacies in the Slovak Republic in the year 2012. Altogether 1,884 questionnaires were distributed, of which 492 (26.1%) were returned. The poll aimed to find the perception of and attitudes to overweight and obesity in pharmacists and pharmaceutical laboratory assistants. The average BMI values in pharmacists were 25.08, in pharmaceutical laboratory assistants 24.86. Overweight and/or obesity were recorded in 36.6% of respondents, BMI 25 was found in 5.2 % men and 33.7% women. An absence of a chronic disease was reported in 61.8% of respondents, and 38.8% of respondents reported medication - most frequently administration of antihistamines, hormones of the thyroid gland, and antihypertensive drugs. In 220 (44.7%) of respondents, overweight/obesity existed in the family. Physical exercise carried out more than 3 times a week was reported by 9.6% of respondents. Drinking regime was evaluated as good in 52.1% of respondents, and 14.6% of participants compensated stress with food.

Extended suicide using an atypical stud gun.

PubMed

Hagemeier, L; Schyma, C; Madea, B

2009-08-10

Suicides with stud guns are uncommon, but are well documented in the literature. On rare occasions, stud guns are also used as a homicide weapon. This case report describes an extended suicide in which a husband killed his wife and their two dogs, which lived on the property. The husband then committed suicide with a shot from the stud gun into his skull. He was a 70-year-old pensioner, a retired butcher, who was found by his son. He was lying in a supine position on a carpet in the living room, with the stud gun stuck in his skull. During autopsy, high concentrations of an antihistamine were found in the blood of each corpse; this drug is used as a soporific. In contrast to the literature, which mainly describes powder deposits due to the use of conventional stud guns, in this case a stud gun was used in which the expanding gases and powder escaped together with the central bolt at the front of the device; powder drains were not involved. Detailed findings of the autopsy are given with reference to this type of stud gun.

Desensitization to clopidogrel: a tailor-made protocol.

PubMed

Barreira, P; Cadinha, S; Malheiro, D; Moreira da Silva, J P

2014-01-01

Clopidogrel is an antiplatelet drug widely used for treatment and prevention of a variety of cardiovascular diseases. We report a successful desensitization to clopidogrel in a 70-year-old Caucasian man with delayed hypersensitivity (HS) reaction. He developed lip, hand and foot swelling, erythematous papular non-pruritic lesions and arthralgias 2 weeks after starting treatment with clopidogrel 75 mg/d. A 3-hour desensitization protocol was started, achieving a cumulative dose of 154 mg without any reaction, and a daily dose of 75 mg was recommended. On the 4th day, the patient developed skin lesions similar to the previously described. He was treated with topical steroids and oral antihistamines, and the daily dose of clopidogrel was reduced to 20 mg. A new desensitization protocol was established, with a slow dose increment, according to the patient's response. It was only possible to achieve the dose of 75 mg/d after 2 months. Although well tolerated by most patients, HS reactions with clopidogrel may occur and desensitization is rising as a safe alternative in those patients. In delayed reactions with cutaneous lesions, a slower desensitization protocol may be necessary, as in this case.

Histopathological effects of intranasal phototherapy and nasal corticosteroids in allergic rhinitis in a rabbit model.

PubMed

Yurttas, Veysel; Şereflican, Murat; Erkoçoğlu, Mustafa; Terzi, Elçin Hakan; Kükner, Aysel; Oral, Mesut

2015-08-01

Allergic rhinitis is one of the most common health problems and has a major effect on quality of life. Although new-generation antihistamines and nasal steroids are the main treatment options, complete resolution cannot be obtained in some patients. Besides common side effects such as nasal irritation and epistaxis, the use of these drugs is controversial in some patients, such as pregnant or breastfeeding women. These findings highlight the need for new treatment options. Although phototherapy has been successfully used in the treatment of atopic dermatitis, which is an IgE-mediated disease and shares several common pathogenic features with allergic rhinitis, there are limited studies about its role in the treatment of allergic rhinitis. In this study, we aimed to evaluate and compare the histopathological effects of intranasal phototherapy (Rhinolight) and nasal corticosteroid treatment on the nasal mucosa in allergic rhinitis in a rabbit model and we found that both treatment options significantly reduced inflammation in the nasal mucosa without increasing apoptosis of mucosal cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Pathogenesis and treatment of skin lesions caused by sulfur mustard.

PubMed

Poursaleh, Zohreh; Ghanei, Mostafa; Babamahmoodi, Farhang; Izadi, Morteza; Harandi, Ali Amini; Emadi, Seyed Emad; Taghavi, Nez'hat-o-Sadat; Sayad-Nouri, Seyede Somaye; Emadi, Seyed Naser

2012-09-01

Sulfur mustard (SM) exposure intensely causes lesions that range in severity from mild erythema to blister formation and necrosis. This review will discuss acute and long-term skin consequences due to exposure to SM and different kinds of medical prophylaxis and therapeutics against SM-induced skin lesions. Literature survey of medical case reports, clinical studies, and original articles was performed using PubMed, Medline, and the Cochrane Database (1917-2011 March). Key words included sulfur mustard, skin, toxicity, pathogenesis, cancer, treatment. SM-induced damage to the skin is characterized by edema, inflammation, and cell death mainly of the basal keratinocyte layer, with varying immunological and pathological changes in the acute phase. Also, xerosis, hypo or hyper pigmentation, scars, and rarely, skin cancers are long-term cutaneous effects. So far,the combination therapy of topical drugs and oral antihistamines, also iodine and antitumor necrosis factor alpha antibodies, are effective remedies in the treatment of skin lesions. The requirement for preparedness in the dermatological community concerning SM exposure is underlined. Novel treatments for prevention and therapeutics against SM toxicity and carcinogenicity are reviewed.

Psychotropic medication patterns among youth in juvenile justice.

PubMed

Lyons, Camilla L; Wasserman, Gail A; Olfson, Mark; McReynolds, Larkin S; Musabegovic, Hana; Keating, Joseph M

2013-03-01

This paper aims to determine the prevalence, patterns, and demographic and diagnostic correlates of psychotropic medication use in a sample of youth in one state's post-adjudicatory secure facilities. The health records database of the facilities was the source of linked demographic, diagnostic and pharmacy information for the 1-year period ending June 30, 2008. Age, gender, race, offense, prior petitions and diagnoses were examined across groups, and concomitant psychotropic pharmacotherapy patterns were identified. Period prevalence was 10.2% for youth ranging in age from 12 through 22 years who had any psychotropic drug prescribed during the first 30 days after intake to the facility. Among medicated youths, almost half received concomitant therapy. Medicated youth were significantly less likely to be Hispanic and more likely to endorse one or more diagnoses. Antidepressants, antipsychotics and antihistamines were the most commonly dispensed agents. Our findings revealed that the rate of psychotropic medication use was low, concomitant medication use was common, and ethnic/race differences in psychopharmacologic treatment were present in this sample of youths in post-adjudicatory secure facilities.

Synthesis and characterization of chitosan-coated magnetite nanoparticles and their application in curcumin drug delivery

NASA Astrophysics Data System (ADS)

Nui Pham, Xuan; Phuoc Nguyen, Tan; Nhung Pham, Tuyet; Thuy Nga Tran, Thi; Van Thi Tran, Thi

2016-12-01

In this work anti-cancer drug curcumin-loaded superparamagnetic iron oxide (Fe3O4) nanoparticles was modified by chitosan (CS). The magnetic iron oxide nanoparticles were synthesized by using reverse micro-emulsion (water-in-oil) method. The magnetic nanoparticles without loaded drug and drug-loaded magnetic nanoparticles were characterized by XRD, FTIR, TG-DTA, SEM, TEM, and VSM techniques. These nanoparticles have almost spherical shape and their diameter varies from 8 nm to 17 nm. Measurement of VSM at room temperature showed that iron oxide nanoparticles have superparamagnetic properties. In vitro drug loading and release behavior of curcumin drug-loaded CS-Fe3O4 nanoparticles were studied by using UV-spectrophotometer. In addition, the cytotoxicity of the modified nanoparticles has shown anticancer activity against A549 cell with IC50 value of 73.03 μg/ml. Therefore, the modified magnetic nanoparticles can be used as drug delivery carriers on target in the treatment of cancer cells.

Synthesis and characterization of modified starch/polybutadiene as novel transdermal drug delivery system.

PubMed

Saboktakin, Mohammad Reza; Akhyari, Shahab; Nasirov, Fizuli A

2014-08-01

Transdermal drug delivery systems are topically administered medicaments in the form of patches that deliver drugs for systemic effects at a predetermined and controlled rate. It works very simply in which drug is applied inside the patch and it is worn on skin for long period of time. Polymer matrix, drug, permeation enhancers are the main components of transdermal drug delivery systems. The objective of the present study was to develop the modified starch and 1,4-cis polybutadiene nanoparticles as novel polymer matrix system. We have been studied the properties of a novel transdermal drug delivery system with clonidine as drug model. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing

PubMed Central

Liu, Hongzhuo; Feng, Liang; Tolia, Gaurav; Liddell, Mark R.; Hao, Jinsong; Li, S. Kevin

2013-01-01

A convenient and efficient in vitro diffusion cell method to evaluate formulations for inner ear delivery via the intratympanic route is currently not available. The existing in vitro diffusion cell systems commonly used to evaluate drug formulations do not resemble the physical dimensions of the middle ear and round window membrane. The objectives of this study were to examine a modified in vitro diffusion cell system of a small diffusion area for studying sustained release formulations in inner ear drug delivery and to identify a formulation for sustained drug delivery to the inner ear. Four formulations and a control were examined in this study using cidofovir as the model drug. Drug release from the formulations in the modified diffusion cell system was slower than that in the conventional diffusion cell system due to the decrease in the diffusion surface area of the modified diffusion cell system. The modified diffusion cell system was able to show different drug release behaviors among the formulations and allowed formulation evaluation better than the conventional diffusion cell system. Among the formulations investigated, poly(lactic-co-glycolic acid)–poly(ethylene glycol)–poly(lactic-co-glycolic acid) triblock copolymer systems provided the longest sustained drug delivery, probably due to their rigid gel structures and/or polymer-to-cidofovir interactions. PMID:23631539

Preparation of hollow magnetite microspheres and their applications as drugs carriers

PubMed Central

2012-01-01

Hollow magnetite microspheres have been synthesized by a simple process through a template-free hydrothermal approach. Hollow microspheres were surface modified by coating with a silica nanolayer. Pristine and modified hollow microparticles were characterized by field-emission electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, FT-IR and Raman spectroscopy, and VSM magnetometry. The potential application of the modified hollow magnetite microspheres as a drug carrier was evaluated by using Rhodamine B and methotrexate as model drugs. The loading and release kinetics of both molecules showed a clear pH and temperature dependent profile. Graphical abstract Hollow magnetite microspheres have been synthesized. Load-release experiments with Rhodamine-B as a model drug and with Methotrexate (chemotherapy drug used in treating certain types of cancer) demonstrated the potential applications of these nanostructures in biomedical applications. PMID:22490731

Cationic surfactants-modified natural zeolites: improvement of the excipients functionality.

PubMed

Krajisnik, Danina; Milojević, Maja; Malenović, Anđelija; Daković, Aleksandra; Ibrić, Svetlana; Savić, Snezana; Dondur, Vera; Matijasević, Srđan; Radulović, Aleksandra; Daniels, Rolf; Milić, Jela

2010-10-01

In this study an investigation of cationic surfactants-modified natural zeolites as drug formulation excipient was performed. The aim of this work was to carry out a study of the purified natural zeolitic tuff with high amount of clinoptilolite as a potential carrier for molecules of pharmaceutical interest. Two cationic surfactants (benzalkonium chloride and hexadecyltrimethylammonium bromide) were used for modification of the zeolitic surface in two levels (equal to and twice as external cation-exchange capacity of the zeolitic tuff). Prepared samples were characterized by Fourier transform infrared spectroscopy, thermogravimetric, high-performance liquid chromatography analysis, and powder flow determination. Different surfactant/zeolite composites were used for additional investigation of three model drugs: diclofenac diethylamine, diclofenac sodium, and ibuprofen by means of adsorption isotherm measurements in aqueous solutions. The modified zeolites with two levels of surfactant coverage within the short activation time were prepared. Determination of flow properties showed that modification of zeolitic surface reflected on powder flow characteristics. Investigation of the model drugs adsorption on the obtained composites revealed that a variation between adsorption levels was influenced by the surfactant type and the amount present at the surface of the composites. In vitro release profiles of the drugs from the zeolite-surfactant-drug composites revealed that sustained drug release could be attained over a period of 8 hours. The presented results for drug uptake by surfactant-zeolite composites and the afterward drug release demonstrated the potential use of investigated modified natural zeolite as excipients for advanced excipients in drug formulations.

Cyclodextrin modified hydrogels of PVP/PEG for sustained drug release.

PubMed

Nielsen, Anne Louise; Madsen, Flemming; Larsen, Kim Lambertsen

2009-02-01

Hydrogels are water swollen networks of polymers and especially hydrogels consisting of poly vinylpyrrolidone/poly ethyleneglycol-dimethacrylate (PVP/PEG-DMA) blends show promising wound care properties. Enhanced functionality of the hydrogels can be achieved by incorporating drugs and other substances that may assist wound healing into the gel matrix. Controlling the release of active compounds from the hydrogels may be possible by carefully modifying the polymer matrix. For this purpose, cyclodextrins (CD) were grafted to the polymer matrix in 4-5 w/w% in an attempt to retard the release of water-soluble drugs. Ibuprofenate (IBU) was chosen as model drug and loaded in IBU/CD ratios of 0.6, 1.2, and 2.5. Vinyl derivatives of alpha-, beta- and gamma-CD were produced, added to the prepolymer blend and cured by UV-light. During this curing process the CD derivatives were covalently incorporated into the hydrogel matrix. The modified hydrogels were loaded with ibuprofenate by swelling. The release of the model drug from CD modified hydrogels show that especially covalently bonded beta-cyclodextrin can change both the release rate and the release profile of ibuprofen.

RGD peptide-mediated chitosan-based polymeric micelles targeting delivery for integrin-overexpressing tumor cells.

PubMed

Cai, Li-Li; Liu, Ping; Li, Xi; Huang, Xuan; Ye, Yi-Qing; Chen, Feng-Ying; Yuan, Hong; Hu, Fu-Qiang; Du, Yong-Zhong

2011-01-01

Solid tumors need new blood vessels to feed and nourish them as well as to allow tumor cells to escape into the circulation and lodge in other organs, which is termed "angiogenesis." Some tumor cells within solid tumors can overexpress integrins α(v)β(3) and α(v)β(5), which can specifically recognize the peptide motif Arg-Gly-Asp (RGD). Thus, the targeting of RGD-modified micelles to tumor vasculature is a promising strategy for tumor-targeting treatment. RGD peptide (GSSSGRGDSPA) was coupled to poly(ethylene glycol)-modified stearic acid-grafted chitosan (PEG-CS-SA) micelles via chemical reaction in the presence of N,N'-Disuccinimidyl carbonate. The critical micelle concentration of the polymeric micelles was determined by measuring the fluorescence intensity of pyrene as a fluorescent probe. The micelle size, size distribution, and zeta potential were measured by light scattering and electrophoretic mobility. Doxorubicin (DOX) was chosen as a model anticancer drug to investigate the drug entrapment efficiency, in vitro drug-release profile, and in vitro antitumor activities of drug-loaded RGD-PEG-CS-SA micelles in cells that overexpress integrins (α(ν)β(3) and α(ν)β(5)) and integrin-deficient cells. Using DOX as a model drug, the drug encapsulation efficiency could reach 90%, and the in vitro drug-release profiles suggested that the micelles could be used as a controlled-release carrier for the hydrophobic drug. Qualitative and quantitative analysis of cellular uptake indicated that RGD-modified micelles could significantly increase the DOX concentration in integrin-overexpressing human hepatocellular carcinoma cell line (BEL-7402), but not in human epithelial carcinoma cell line (Hela). The competitive cellular-uptake test showed that the cellular uptake of RGD-modified micelles in BEL-7402 cells was significantly inhibited in the presence of excess free RGD peptides. In vitro cytotoxicity tests demonstrated DOX-loaded RGD-modified micelles could specifically enhance the cytotoxicity against BEL-7402 compared with DOX-loaded PEG-CS-SA and doxorubicin hydrochlorate. This study suggests that RGD-modified PEG-CS-SA micelles are promising drug carriers for integrin-overexpressing tumor active targeting therapy.

The effect of cyclodextrin on both the agglomeration and the in vitro characteristics of drug loaded and targeted silica nanoparticles

NASA Astrophysics Data System (ADS)

Khattabi, Areen M.; Alqdeimat, Diala A.

2018-02-01

One of the problems in the use of nanoparticles (NPs) as carriers in drug delivery systems is their agglomeration which mainly appears due to their high surface energy. This results in formation of NPs with different sizes leading to differences in their distribution and bioavailability. The surface coating of NPs with certain compounds can be used to prevent or minimize this problem. In this study, the effect of cyclodextrin (CD) on the agglomeration state and hence on the in vitro characteristics of drug loaded and targeted silica NPs was investigated. A sample of NPs was loaded with anticancer agents, then modified with a long polymer, carboxymethyl-β-cyclodextrin (CM-β-CD) and folic acid (FA), respectively. Another sample was modified similarly but without CD. The surface modification was characterized using fourier transform infrared spectroscopy (FT-IR). The polydispersity (PD) was measured using dynamic light scattering (DLS) and was found to be smaller for CD modified NPs. The results of the in vitro drug release showed that the release rate from both samples exhibited similar pattern for the first 5 hours, however the rate was faster from CD modified NPs after 24 hours. The in vitro cell viability assay confirmed that CD modified NPs were about 30% more toxic to HeLa cells. These findings suggest that CD has a clear effect in minimizing the agglomeration of such modified silica NPs, accelerating their drug release rate and enhancing their targeting effect.

Functionalized bimodal mesoporous silicas as carriers for controlled aspirin delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao Lin; Sun Jihong, E-mail: jhsun@bjut.edu.cn; Li Yuzhen

The bimodal mesoporous silica modified with 3-aminopropyltriethoxysilane was performed as the aspirin carrier. The samples' structure, drug loading and release profiles were characterized with X-ray diffraction, scanning electron microscopy, N{sub 2} adsorption and desorption, Fourier transform infrared spectroscopy, TG analysis, elemental analysis and UV-spectrophotometer. For further exploring the effects of the bimodal mesopores on the drug delivery behavior, the unimodal mesoporous material MCM-41 was also modified as the aspirin carrier. Meantime, Korsmeyer-Peppas equation f{sub t}=kt{sup n} was employed to analyze the dissolution data in details. It is indicated that the bimodal mesopores are beneficial for unrestricted drug molecules diffusing andmore » therefore lead to a higher loading and faster releasing than that of MCM-41. The results show that the aspirin delivery properties are influenced considerably by the mesoporous matrix, whereas the large pore of bimodal mesoporous silica is the key point for the improved controlled-release properties. - Graphical abstract: Loading (A) and release profiles (B) of aspirin in N-BMMs and N-MCM-41 indicated that BMMs have more drug loading capacity and faster release rate than that MCM-41. Highlights: > Bimodal mesoporous silicas (BMMs) and MCM-41 modified with amino group via post-treatment procedure. > Loading and release profiles of aspirin in modified BMMs and MCM-41. > Modified BMMs have more drug loading capacity and faster release rate than that modified MCM-41.« less

77 FR 4758 - Foreign-Trade Zone 59-Lincoln, Nebraska, Application for Temporary/Interim Manufacturing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-31

... authority to produce over-the-counter (OTC) pharmaceutical products, such as analgesics, cough/cold medicine, antihistamines/decongestants, and penicillin-based antibiotics (HTSUS 3004.10, 3004.40, 3004.90--duty free). Foreign ingredients that would be used in production (representing 25% of the value of the finished...

Academic Functioning and Quality of Life of Children and Adolescents with Allergic Rhinitis--Part II

ERIC Educational Resources Information Center

McCabe, Paul C.

2008-01-01

This article is the second of a two-part series on allergic rhinitis (AR). Treatments for AR are now widely available in both prescription and over-the-counter form. The medication therapies include antihistamines, decongestants, leukotriene receptor antagonists, cromolyn sodium, and immunotherapy. Corticosteroids are also used via nasal…

Fatal overdose from Bendectin.

PubMed

Bayley, M; Walsh, F M; Valaske, M J

1975-05-01

A three-year old male ingested approximately 100 tablets of Bendectin. He developed tonic-clonic seizures followed by cardiac arrest. Toxicologic analysis yielded high levels of doxylamine, dicyclomine, and pyridoxine in blood, peritoneal fluid, and tissue homogenates. The antihistamine, doxylamine succinate appears to be the toxic constituent. Analytical methods used to document the case are herein described.

Efficacy of Armodafinil for Maintaining Vigilance Among Navy Air Traffic Controllers Eight to Twelve Hours Post-Dose

DTIC Science & Technology

2009-04-12

circle all that apply) a. None b. Sedatives/Tranquilizers c. Aspirin/ Tylenol /any analgesic 31 d. Antihistamines e. Decongestants f. Other (please specify...4. Do you take any over the counter medications (e.g., antacids, Benadryl, Tylenol , etc.) two (2) or more times a month

Enhanced anti-cancer efficacy to cancer cells by doxorubicin loaded water-soluble amino acid-modified β-cyclodextrin platinum complexes.

PubMed

Zhao, Mei-Xia; Zhao, Meng; Zeng, Er-Zao; Li, Yang; Li, Jin-Ming; Cao, Qian; Tan, Cai-Ping; Ji, Liang-Nian; Mao, Zong-Wan

2014-08-01

The effective targeted delivery of insoluble anticancer drugs to increase the intracellular drug concentration has become a focus in cancer therapy. In this system, two water-soluble amino acid-modified β-cyclodextrin (β-CD) platinum complexes were reported. They showed preferable binding ability to DNA and effective inhibition to cancer cells, and they could bind and unwind pBR322 DNA in a manner which was similar to cisplatin. Besides, our platinum complexes could effectively deliver the anticancer drug doxorubicin (Dox) into cells and had higher cell inhibition ratio, but less toxicity on the normal cells, compared with cancer cells. In this combination system, Dox was encapsulated into the hydrophobic cavities of β-CD at the optimum molar ratio of 1:1, which were validated by UV-visible (UV-vis) absorption spectroscopy, fluorescence spectroscopy and MTT experiments. Moreover, the combination system had higher cell inhibition ratio than free Dox and amino acid-modified β-CD platinum complexes, and the results of high content screening (HCS) showed that Dox-loaded amino acid-modified β-CD platinum complexes could permeate the cell membrane and enter cells, suggesting the efficient transport of Dox across the membranes with the aid of the β-CD. We expect that the amino acid-modified β-CD platinum complexes will deliver the antitumor drug Dox to enhance intracellular drug accumulation and such combination system showed great potential as an antitumor drug. Copyright © 2014 Elsevier Inc. All rights reserved.

Simultaneous detection and quantification of select nitromusks, antimicrobial agent, and antihistamine in fish of grocery stores by gas chromatography-mass spectrometry.

PubMed

Foltz, James; Abdul Mottaleb, M; Meziani, Mohammed J; Rafiq Islam, M

2014-07-01

Continually detected biologically persistent nitromusks; galaxolide (HHCB), tonalide (AHTN) and musk ketone (MK), antimicrobial triclosan (TCS), and antihistamine diphenhydramine (DPH) were examined for the first time in edible fillets originating from eight fish species grown in salt- and fresh-water. The sampled fish collected from local grocery stores were homogenized, extracted, pre-concentrated and analyzed by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM). The presence of the target compounds in fish extracts was confirmed based on similar mass spectral features and retention behavior with standards. Internal standard based calibration plots were used for quantification. The HHCB, AHTN, TCS and DPH were consistently observed with concentration of 0.163-0.892, 0.068-0.904, 0.189-1.182, and 0.942-7.472 ng g(-1), respectively. These values are at least 1-3 orders of magnitude lower than those obtained in environmental fish specimens. The MK was not detected in any fish. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pilots using selective serotonin reuptake inhibitors compared to other fatally injured pilots.

PubMed

Rogers, Paul; Hileman, Christy; Salazar, Guillermo; Cliburn, Kacey; Paskoff, Lawrence; Hathaway, William; Gildea, Kevin; Tejera Villalaz, Victor Hugo

2017-10-01

Selective Serotonin Reuptake Inhibitors (SSRI) were a disqualifying medication for U.S. civil pilots before April 5, 2010. After this date, a Federal Aviation Administration policy was created that allowed airmen, on select SSRIs, a pathway to hold a valid medical certificate. The purpose of this study was to provide a detailed look at SSRIs in the U.S. pilot population since the inception of this new policy. We examined the toxicology results from fatally injured airmen in addition to outcomes concerning pilots who are participating in the program. This study examined data from the Civil Aerospace Medical Institute's Bioaeronautical Sciences Research Laboratory in conjunction with the Medical Analysis Tracking Registry and the Document Imaging and Workflow System. A count-based regression model quantified the relationships between positive SSRI findings with additional factors of interest. These factors included pilot rating, ethanol, and first generation antihistamines. There were 1484 fatally injured airmen over the six year study period, of which 44-tested positive for an SSRI. First-generation antihistamines were statistically associated with positive findings of SSRIs. Published by Elsevier Ltd.

Improved Completion Rates and Characterization of Drug Reactions with an Intensive Chagas Disease Treatment Program in Rural Bolivia

PubMed Central

Tornheim, Jeffrey A.; Lozano Beltran, Daniel F.; Gilman, Robert H.; Castellon, Mario; Solano Mercado, Marco A.; Sullca, Walter; Torrico, Faustino; Bern, Caryn

2013-01-01

Background Chagas disease treatment is limited by drug availability, adverse side effect profiles of available medications, and poor adherence. Methods Adult Chagas disease patients initiating 60-days of benznidazole were randomized to weekly or twice-weekly evaluations of medication adherence and screening for adverse drug events (ADEs). Mid-week evaluations employed phone-based evaluations. Adherence was measured by self-report, pill counts with intentional over-distribution, and Medication Event Monitoring Systems (MEMS). Prospective data were compared to historical controls treated with benznidazole at the same hospital. Results 162 prospective patients were compared to 172 historical patients. Pill counts correlated well with MEMS data (R = 0.498 for 7-day intervals, R = 0.872 for intervals >7 days). Treatment completion rates were higher among prospective than historical patients (82.1% vs. 65.1%), primarily due to lower abandonment rates. Rates of ADEs were lower among prospective than historical patients (56.8% vs. 66.9%). Twice-weekly evaluations increased identification of mild ADEs, prompting higher suspension rates than weekly evaluations. While twice-weekly evaluations identified ADEs earlier, they did not reduce incidence of moderate or severe ADEs. Many dermatologic ADEs were moderately severe upon presentation (35.6%), were not reduced by use of antihistamines, occurred among adult patients of all ages, and occurred throughout treatment, rather than the first few weeks alone. Conclusions Intensive management improved completion and identified more ADEs, but did not reduce moderate or severe ADEs. Risk of dermatologic ADEs cannot be reduced by selecting younger adults or monitoring only during the first few weeks of treatment. Pill counts and phone-based encounters are reliable tools for treatment programming in rural Bolivia. PMID:24069472

Management of Anesthesia in Adult and Pediatric Mastocytosis: A Study of the Spanish Network on Mastocytosis (REMA) Based on 726 Anesthetic Procedures.

PubMed

Matito, Almudena; Morgado, José Mario; Sánchez-López, Paula; Álvarez-Twose, Iván; Sánchez-Muñoz, Laura; Orfao, Alberto; Escribano, Luis

2015-01-01

The role of anesthesia as an elicitor of mast cell (MC) mediator release symptoms in mastocytosis is poorly investigated. To determine the frequency and type of MC mediator release symptoms during anesthetic procedures in mastocytosis patients. Medical records were reviewed regarding the anesthetic techniques for 501 mastocytosis patients (459 adults and 42 children; 95 and 5% with systemic involvement, respectively) who were subjected to 676 and 50 anesthetic techniques, respectively. General, sedation, epidural, and local anesthetic techniques were used in 66 (10%), 67 (10%), 76 (11%), and 515 (76%) adult patients and in 24 (48%), 8 (16%), 2 (4%), and 25 (50%) pediatric patients. The frequency of perioperative MC mediator-related symptoms and anaphylaxis was 2 and 0.4% in the adult series and 4 and 2% among children. In the adult series, this frequency was significantly higher in patients who previously presented with anaphylaxis (p = 0.03), underwent major surgeries (p < 0.001) and general anesthesia (p = 0.02), and were not given prophylactic antimediator therapy (PAT) 1 h before the anesthesia (H1/H2 antihistamines and benzodiacepines; p = 0.002).Hypersensitivity and/or allergy to the involved drugs and latex allergy were ruled out in all but one symptomatic case; when PAT was given and sedation was added, some cases later tolerated the same anesthetic drugs. The frequency of perioperative anaphylaxis appears to be higher in mastocytosis patients than in the general population. Mastocytosis should not be a contraindication for anesthesia since PAT and adequate anesthetic management using the drugs with the safest profile appears to be effective in preventing/controlling MC mediator-associated symptoms. © 2015 S. Karger AG, Basel.

A rapid screening procedure for drugs and poisons in gastric contents by direct injection-HPLC analysis.

PubMed

Politi, Lucia; Groppi, Angelo; Polettini, Aldo; Montagna, Maria

2004-05-10

A high performance liquid chromatographic method for toxicological drug screening of gastric content has been developed. The samples were diluted (1:3-1:30) in 0.01 N hydrochloric acid and injected into a reverse phase column for separation by gradient elution. Mobile phase consisted of solvent A (acetonitrile/water 90:10, 0.01 M sodium dodecylsulphate, 0.5% v/v glacial acetic acid) and solvent B (water/acetonitrile 90:10, 0.01 M sodium dodecylsulphate, 0.5% v/v glacial acetic acid); the gradient was programmed from 20 to 80% A in 30 min. The flow was kept constant at 1.5 ml/min. Two home-made internal standards, butyrylsalicylic acid and diacetyltubocurarine with retention times of 5.6 and 21.4 min, respectively, were used. Drugs are identified by matching their relative retention times and UV spectra (200-400 nm) with those contained in a home made library of more than 340 reference compounds (9 analgesics, 22 antidepressants, 30 antihistamines, 14 antihypertensives, 21 antirheumatics, 15 beta-blockers, 9 bronchodilators, 10 Ca antagonists, 14 diuretics, 26 neuroleptics, 25 tranquilizers, and other significant xenobiotic compounds). The fluorometric (FLD) emission spectrum (280-700 nm; excitation wavelength, 230 nm) was used as a further identification. At 50mg/l analyte concentrations, the injection of gastric content after dilution (1:3) produced S/N ratios in the range 8-140. The method is simple, rapid, rather inexpensive and proved to be a useful means of investigation if used in combination with GC-MS screening in blood. On the other hand, the system suffers from a relatively limited sensitivity for compounds with a low UV absorption and from interferences due to the presence in the matrix of some highly UV- and FL-responsive compounds (e.g. tryptophan).

[Breast-feeding (part IV): Therapeutic uses, dietetic and addictions--guidelines for clinical practice].

PubMed

Marcellin, L; Chantry, A A

2015-12-01

To describe the practical aspects of the use of the most commonly prescribed drugs during the postpartum period, the dietetic measures and the management of breast-feeding in case of addictive behaviors. Review of the literature between 1972 and May 2015 from the databases Medline, Google Scholar, Cochrane Library, and international recommendations of learned societies. The precaution to stop breast-feeding when drugs are necessary is not justified in many situations (professional consensus). Aspirin at antiaggregant dose is allowed during breast-feeding while high doses are not recommended; NSAIDs with short half-life can be used (professional consensus). Precautions are needed in cases of use of morphonics (professional consensus). There is no justification to delay the initiation of breast-feeding in case of locoregional or general analgesia or for caesarean section. Antibiotic treatment does not justify discontinuing breast-feeding (professional consensus). Anxiolytics of the class of antihistaminic sedating H1 such as hydroxyzine (Atarax®) should not be prescribed in case of breast-feeding (professional consensus). Imaging does not justify to stop breast-feeding (professional consensus). Tobacco consumption is discouraged but is not a contraindication to breast-feed (professional consensus). It is recommended to avoid the consumption of alcohol (professional consensus). In case of occasional and moderate consumption of alcohol, delaying breast-feeding for a minimum of two hours is recommended (professional consensus). Cocaine consumption is a contraindication of breast-feeding (professional agreement), and breast-feeding is not recommended in case of cannabis use (professional consensus). Few drug treatments are not compatible with breast-feeding that can be continued in most of the cases. Copyright © 2015. Published by Elsevier Masson SAS.

Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells

PubMed Central

Mehbuba Hossain, Sultana; Chowdhury, Ezharul Hoque

2018-01-01

Biodegradable inorganic apatite-based particle complex is popular for its pH-sensitivity at the endosomal acidic environment to facilitate drug release following cellular uptake. Despite being a powerful anticancer drug, doxorubicin shows severe off-target effects and therefore would need a carrier for the highest effectiveness. We aimed to chemically modify carbonate apatite (CA) with Krebs cycle intermediates, such as citrate and succinate in order to control the growth of the resultant particles to more efficiently carry and transport the anticancer drug into the cancer cells. Citrate- or succinate-modified CA particles were synthesized with different concentrations of sodium citrate or sodium succinate, respectively, in the absence or presence of doxorubicin. The drug loading efficiency of the particles and their cellular uptake were observed by quantifying fluorescence intensity. The average diameter and surface charge of the particles were determined using Zetasizer. Cell viability was assessed by MTT assay. Citrate-modified carbonate apatite (CMCA) exhibited the highest (31.38%) binding affinity for doxorubicin and promoted rapid cellular uptake of the drug, leading to the half-maximal inhibitory concentration 1000 times less than that of the free drug in MCF-7 cells. Hence, CMCA nanoparticles with greater surface area enhance cytotoxicity in different breast cancer cells by enabling higher loading and more efficient cellular uptake of the drug. PMID:29534497

Modulation of venlafaxine hydrochloride release from press coated matrix tablet.

PubMed

Gohel, M C; Soni, C D; Nagori, S A; Sarvaiya, K G

2008-01-01

The aim of present study was to prepare novel modified release press coated tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and hydroxypropylmethylcellulose K100M were used as release modifier in core and coat, respectively. A 3(2) full factorial design was adopted in the optimization study. The drug to polymer ratio in core and coat were chosen as independent variables. The drug release in the first hour and drug release rate between 1 and 12 h were chosen as dependent variables. The tablets were characterized for dimension analysis, crushing strength, friability and in vitro drug release. A check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat respectively, was prepared. The tablets of check point batch were subjected to in vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The kinetics of drug release was best explained by Korsmeyer and Peppas model (anomalous non-Fickian diffusion). The systematic formulation approach enabled us to develop modified release venlafaxine hydrochloride tablets.

Drug delivery systems with modified release for systemic and biophase bioavailability.

PubMed

Leucuta, Sorin E

2012-11-01

This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

A modified Plasmodium falciparum growth inhibition assay (GIA) to assess activity of plasma from malaria endemic areas.

PubMed

Mlambo, Godfree; Kumar, Nirbhay

2007-02-01

Plasma samples from patients undergoing treatment in malaria endemic countries often contain anti-malaria drugs, that may overstate effects of specific antibodies in growth inhibition assays (GIA). We describe a modified assay that uses drug resistant P. falciparum parasites (W2) that circumvents the requirement for dialyzing samples that may likely contain drugs such as chloroquine and sulfadoxine/pyrimethamine (SP).

Palonosetron and Hydroxyzine Pre-treatment Reduces the Objective Signs of Experimentally-Induced Acute Opioid Withdrawal in Humans: A Double-Blinded, Randomized, Placebo-Controlled Crossover Study

PubMed Central

Erlendson, Matthew; D'Arcy, Nicole; Encisco, Ellen; Yu, Jeff; Rincon-Cruz, Lorena; Peltz, Gary; Clark, J. David

2017-01-01

Background Treatments for reducing opioid withdrawal are limited and prone to problematic side effects. Laboratory studies, clinical observations, and limited human trial data suggest 5-HT3-receptor antagonists and antihistamines may be effective. Objectives This double-blind, crossover, placebo-controlled study employing an acute physical dependence model evaluated whether (i) treatment with a 5-HT3-receptor antagonist (palonosetron) would reduce opioid withdrawal symptoms, and (ii) co-administration of an antihistamine (hydroxyzine) would enhance any treatment effect. Methods At timepoint T=0, healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either a) placebo, b) palonosetron IV (0.75 mg), or c) palonosetron IV (0.75 mg) and hydroxyzine PO (100 mg) in a crossover study design. This was followed at T=30 by intravenous morphine (10mg/70kg). At T=165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T=170, 180, respectively). Baseline measurements were recorded at T=-30 and T=-15. Results Comparison of average baseline OOWS scores with OOWS scores obtained fifteen minutes after naloxone was significant (p=0.0001). Scores from fifteen minutes post-naloxone infusion showed significant differences in OOWS scores between treatment groups: placebo, 3.7 ± 2.4; palonosetron, 1.5± 0.97; and palonosetron with hydroxyzine, 0.2 ± .1333. Conclusions Pretreatment with palonosetron significantly reduced many signs of experimental-induced opioid withdrawal. Co-administration with hydroxyzine further reduced opioid withdrawal severity. These results suggest that 5-HT3 receptor antagonists, alone or in combination with an antihistamine, may be useful in the treatment of opioid withdrawal. PMID:27712113

[Efficacy and safety of astemizole in the treatment of allergic rhinitis and urticaria: a systematic review with meta-analysis].

PubMed

Gutiérrez Castrellón, Pedro; Ramírez Mayans, Jaime; López Pérez, Gerardo

2005-01-01

To compare astemizole with other first or second generation antihistaminics in the treatment of allergic rhinitis or urticaria. Systematic revision of clinical, controlled and randomized tests. 36 controlled, randomized, clinical, double or simple blind tests were made in 6,446 patients; 4,513 of them were assigned to astemizole and 1,933 to other first or second generation antihistaminics. Analyzed outcomes: Rate of global success; global scoring improvement of rhinitis; ocular, nasal or pharingeal pruritus; watering; nasal obstruction; sneeze; urticaria; cutaneous response to histamine; time to get a satisfactory improvent; frequency of sedation and headache. In connection to global success there were significant differences in favor of astemizole (OR 6.72, CI95% 5.36 to 8.41, p 0.0001); alike global scoring improvement of rhinitis (SMD -0.82, CI95% -1.70 to 0.06, p 0.04); rhinorrhea (SMD of -0.70, CI95% -1.47 to -0.03, p 0.02); nasal, pharingeal or ocular pruritus (SMD -0.64, CI95% -1.63 to 0.35, p 0.03); urticaria (SMD of -3.53, CI95% -4.11 to -2.94, p 0.0001), and reduction of cutaneous response to histamine (SMD -2.02, CI95% -2.47 to -1.57, p 0.0001). Differences for watering, nasal obstruction or sneeze were not observed. Finally, the safety area was analyzed considering the existence of sedation and headache; it was demonstrated less sedation (OR 0.23, CI95% 0.18 to 0.30, p 0.0001) and less headache (OR 0.58, CI95% 0.40 to 0.85, p 0.005) in the group treated with astemizole. The available evidence shows a therapeutic superiority of astemizole versus other antihistaminics in relation to the percentage of global success and the global scoring improvement of rhinitis, rhinorrhea, pruritus in general, urticaria symptoms and of the reduction of response to histamine, with a smaller frequency of headache or sedation.

21 CFR 184.1287 - Enzyme-modified fats.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Enzyme-modified fats. 184.1287 Section 184.1287... GRAS § 184.1287 Enzyme-modified fats. (a) Enzyme-modified refined beef fat, enzyme-modified butterfat, and enzyme-modified steam-rendered chicken fat are prepared from refined beef fat; butterfat or...

21 CFR 184.1287 - Enzyme-modified fats.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Enzyme-modified fats. 184.1287 Section 184.1287... Listing of Specific Substances Affirmed as GRAS § 184.1287 Enzyme-modified fats. (a) Enzyme-modified refined beef fat, enzyme-modified butterfat, and enzyme-modified steam-rendered chicken fat are prepared...

21 CFR 184.1287 - Enzyme-modified fats.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Enzyme-modified fats. 184.1287 Section 184.1287... Listing of Specific Substances Affirmed as GRAS § 184.1287 Enzyme-modified fats. (a) Enzyme-modified refined beef fat, enzyme-modified butterfat, and enzyme-modified steam-rendered chicken fat are prepared...

21 CFR 184.1287 - Enzyme-modified fats.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Enzyme-modified fats. 184.1287 Section 184.1287... Listing of Specific Substances Affirmed as GRAS § 184.1287 Enzyme-modified fats. (a) Enzyme-modified refined beef fat, enzyme-modified butterfat, and enzyme-modified steam-rendered chicken fat are prepared...

21 CFR 184.1287 - Enzyme-modified fats.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Enzyme-modified fats. 184.1287 Section 184.1287... Listing of Specific Substances Affirmed as GRAS § 184.1287 Enzyme-modified fats. (a) Enzyme-modified refined beef fat, enzyme-modified butterfat, and enzyme-modified steam-rendered chicken fat are prepared...

Direct Detection of Drug-Resistant Hepatitis B Virus in Serum Using a Dendron-Modified Microarray

PubMed Central

Kim, Doo Hyun; Kang, Hong Seok; Hur, Seong-Suk; Sim, Seobo; Ahn, Sung Hyun; Park, Yong Kwang; Park, Eun-Sook; Lee, Ah Ram; Park, Soree; Kwon, So Young; Lee, Jeong-Hoon

2018-01-01

Background/Aims Direct sequencing is the gold standard for the detection of drug-resistance mutations in hepatitis B virus (HBV); however, this procedure is time-consuming, labor-intensive, and difficult to adapt to high-throughput screening. In this study, we aimed to develop a dendron-modified DNA microarray for the detection of genotypic resistance mutations and evaluate its efficiency. Methods The specificity, sensitivity, and selectivity of dendron-modified slides for the detection of representative drug-resistance mutations were evaluated and compared to those of conventional slides. The diagnostic accuracy was validated using sera obtained from 13 patients who developed viral breakthrough during lamivudine, adefovir, or entecavir therapy and compared with the accuracy of restriction fragment mass polymorphism and direct sequencing data. Results The dendron-modified slides significantly outperformed the conventional microarray slides and were able to detect HBV DNA at a very low level (1 copy/μL). Notably, HBV mutants could be detected in the chronic hepatitis B patient sera without virus purification. The validation of our data revealed that this technique is fully compatible with sequencing data of drug-resistant HBV. Conclusions We developed a novel diagnostic technique for the simultaneous detection of several drug-resistance mutations using a dendron-modified DNA microarray. This technique can be directly applied to sera from chronic hepatitis B patients who show resistance to several nucleos(t)ide analogues. PMID:29271185

Tracing pharmaceuticals in a municipal plant for integrated wastewater and organic solid waste treatment.

PubMed

Jelic, Aleksandra; Fatone, Francesco; Di Fabio, Silvia; Petrovic, Mira; Cecchi, Franco; Barcelo, Damia

2012-09-01

The occurrence and removal of 42 pharmaceuticals, belonging to different therapeutic groups (analgesics and anti-inflammatory drugs, anti-ulcer agent, psychiatric drugs, antiepileptic drug, antibiotics, ß-blockers, diuretics, lipid regulator and cholesterol lowering statin drugs and anti-histamines), were studied in the wastewater and sewage sludge trains of a full scale integrated treatment plant. The plant employs a biological nutrient removal (BNR) process for the treatment of municipal wastewater, and a single-stage mesophilic anaerobic co-digestion for the treatment of wasted activated sludge mixed with the organic fraction of municipal solid waste (OFMSW), followed by a short-cut nitrification-denitrification of the anaerobic supernatant in a sequential batch reactor. Influent and effluent wastewater, as well as thickened, digested and treated sludge were sampled and analyzed for the selected pharmaceuticals in order to study their presence and fate during the treatment. Twenty three compounds were detected in influent and effluent wastewater and eleven in sludge. Infiltration of groundwater in the sewer system led to a dilution of raw sewage, resulting in lower concentrations in wastewater (up to 0.7 μg/L in influent) and sludge (70 ng/g d.w.). Due to the dilution, overall risk quotient for the mixture of pharmaceuticals detected in effluent wastewater was less than one, indicating no direct risk for the aquatic environment. A wide range of removal efficiencies during the treatment was observed, i.e. <20% to 90%. The influent concentrations of the target pharmaceuticals, as polar compounds, were undoubtedly mostly affected by BNR process in the wastewater train, and less by anaerobic-co-digestion. Mass balance calculations showed that less than 2% of the total mass load of the studied pharmaceuticals was removed by sorption. Experimentally estimated distribution coefficients (<500 L/kg) also indicated that the selected pharmaceuticals preferably remain in the aqueous phase, and that biodegradation/transformation is the primary removal mechanism for these compounds during wastewater treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

Cognitive enhancers (Nootropics). Part 3: drugs interacting with targets other than receptors or enzymes. Disease-modifying drugs. Update 2014.

PubMed

Froestl, Wolfgang; Pfeifer, Andrea; Muhs, Andreas

2014-01-01

Scientists working in the field of Alzheimer's disease and, in particular, cognitive enhancers, are very productive. The review "Drugs interacting with Targets other than Receptors or Enzymes. Disease-modifying Drugs" was accepted in October 2012. In the last 20 months, new targets for the potential treatment of Alzheimer's disease were identified. Enormous progress was realized in the pharmacological characterization of natural products with cognitive enhancing properties. This review covers the evolution of research in this field through May 2014.

Epidemiology of angioedema without wheals in an allergy and immunology center.

PubMed

Malbrán, Eloisa; Fernández Romero, Diego; Juri, Maria Cecilia; Larrauri, Blas J; Malbrán, Alejandro

2015-01-01

We describe the diagnostic epidemiology, the clinical course, the family history and the response to treatment of patients with angioedema without wheals (AWW) at an Allergy and Immunology Clinical Center. We reviewed the case records of all patients at our office from January 1997 to April 2013. We recorded sex, age, age at onset of symptoms, family history of angioedema, number of visits to the office, type of angioedema, and response to treatment from those patients with angioedema without wheals. We classified angioedema according to its pathophysiology. We also describe those patients with angioedema mimics. From a total of 17,823 new patients, 303 had a presumptive diagnosis of angioedema without wheals. Twenty-three patients had an angioedema mimic. Forty percent were male and 60% were female. Average age at first visit was 40.6. Average number of visits was 2.4. Fifty-seven patients referred a family history. We attributed idiopathic angioedema to 55.7% of patients, 24.3% were drug related, 15.7% were due to C1 inhibitor deficiency, 2.1% were drug related+idiopathic angioedema, 1.4% were type III and 0.7% had exercise-induced angioedema. Ninety six percent of 53 evaluable idiopathic angioedema patients referred a benefit with anti-histamine therapy. AWW was a rare cause of consultation. Most of our patients had anti H1 responsive idiopathic angioedema and none had allergic angioedema. Women cases prevailed over men's. Family history and average age of onset of symptoms were different among the different types of angioedema.

The SLCO (former SLC21) superfamily of transporters.

PubMed

Hagenbuch, Bruno; Stieger, Bruno

2013-01-01

The members of the organic anion transporting polypeptide superfamily (OATPs) are classified within the SLCO solute carrier family. All functionally well characterized members are predicted to have 12 transmembrane domains and are sodium-independent transport systems that mediate the transport of a broad range of endo- as well as xenobiotics. Substrates are mainly amphipathic organic anions with a molecular weight of more than 300Da, but some of the known transported substrates are also neutral or even positively charged. Among the well characterized substrates are numerous drugs including statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antibiotics, antihistaminics, antihypertensives and anticancer drugs. Based on their amino acid sequence identities, the different OATPs cluster into families (in general with more than 40% amino acid sequence identity) and subfamilies (more than 60% amino acid identity). With the sequencing of genomes from different species and the computerized prediction of encoded proteins more than 300 OATPs can be found in the databases, however only a fraction of them have been identified in humans, rodents, and some additional species important for pharmaceutical research like the rhesus monkey (Macaca mulatta), the dog (Canis lupus familiaris) and the pig (Sus scrofa). These OATPs form 6 families (OATP1-OATP6) and 13 subfamilies. In this review we try to summarize what is currently known about OATPs with respect to endogenous substrates, tissue distribution, transport mechanisms, regulation of expression, structure-function relationship and mutations and polymorphisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

Determination of drug lipophilicity by phosphatidylcholine-modified microemulsion high-performance liquid chromatography.

PubMed

Xuan, Xueyi; Xu, Liyuan; Li, Liangxing; Gao, Chongkai; Li, Ning

2015-07-25

A new biomembrane-mimetic liquid chromatographic method using a C8 stationary phase and phosphatidylcholine-modified (PC-modified) microemulsion mobile phase was used to estimate unionized and ionized drugs lipophilicity expressed as an n-octanol/water partition coefficient (logP and logD). The introduction of PC into sodium dodecyl sulfate (SDS) microemulsion yielded a good correlation between logk and logD (R(2)=0.8). The optimal composition of the PC-modified microemulsion liquid chromatography (PC-modified MELC) mobile phase was 0.2% PC-3.0% SDS-6.0% n-butanol-0.8% ethyl acetate-90.0% water (pH 7.0) for neutral and ionized molecules. The interactions between the analytes and system described by this chromatographic method is more similar to biological membrane than the n-octanol/water partition system. The result in this paper suggests that PC-modified MELC can serve as a possible alternative to the shake-flask method for high-throughput unionized and ionized drugs lipophilicity determination and simulation of biological processes. Copyright © 2015 Elsevier B.V. All rights reserved.

Fasudil and DETA NONOate, Loaded in a Peptide-Modified Liposomal Carrier, Slow PAH Progression upon Pulmonary Delivery.

PubMed

Rashid, Jahidur; Nahar, Kamrun; Raut, Snehal; Keshavarz, Ali; Ahsan, Fakhrul

2018-05-07

We investigated the feasibility of a combination therapy comprising fasudil, a Rho-kinase inhibitor, and DETA NONOate (diethylenetriamine NONOate, DN), a long-acting nitric oxide donor, both loaded in liposomes modified with a homing peptide, CAR (CARSKNKDC), in the treatment of pulmonary arterial hypertension (PAH). We first prepared and characterized unmodified and CAR-modified liposomes of fasudil and DN. Using individual drugs alone or a mixture of fasudil and DN as controls, we studied the efficacy of the two liposomal preparations in reducing mean pulmonary arterial pressure (mPAP) in monocrotaline (MCT) and SUGEN-hypoxia-induced PAH rats. We also conducted morphometric studies (degree of muscularization, arterial medial wall thickness, and collagen deposition) after treating the PAH rats with test and control formulations. When the rats were treated acutely and chronically, the reduction in mPAP was more pronounced in the liposomal formulation-treated rats than in plain drug-treated rats. CAR-modified liposomes were more selective in reducing mPAP than unmodified liposomes of the drugs. Both drugs, formulated in CAR-modified liposomes, reduced the degree of muscularization, medial arterial wall thickness, and collagen deposition more than the combination of plain drugs did. As seen with the in vivo data, CAR-modified liposomes of fasudil or DN increased the levels of the vasodilatory signaling molecule, cGMP, in the smooth muscle cells of PAH-afflicted human pulmonary arteries. Overall, fasudil and DN, formulated in liposomes, could be used as a combination therapy for a better management of PAH.

21 CFR 872.3480 - Polyacrylamide polymer (modified cationic) denture adhesive.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Polyacrylamide polymer (modified cationic) denture... polymer (modified cationic) denture adhesive. (a) Identification. A polyacrylamide polymer (modified cationic) denture adhesive is a device composed of polyacrylamide polymer (modified cationic) intended to...

21 CFR 177.1480 - Nitrile rubber modified acrylonitrile-methyl acrylate copolymers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Nitrile rubber modified acrylonitrile-methyl... Nitrile rubber modified acrylonitrile-methyl acrylate copolymers. Nitrile rubber modified acrylonitrile... rubber modified acrylonitrile-methyl acrylate copolymers consist of basic copolymers produced by the...

21 CFR 872.3480 - Polyacrylamide polymer (modified cationic) denture adhesive.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Polyacrylamide polymer (modified cationic) denture... polymer (modified cationic) denture adhesive. (a) Identification. A polyacrylamide polymer (modified cationic) denture adhesive is a device composed of polyacrylamide polymer (modified cationic) intended to...

21 CFR 872.3480 - Polyacrylamide polymer (modified cationic) denture adhesive.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Polyacrylamide polymer (modified cationic) denture... polymer (modified cationic) denture adhesive. (a) Identification. A polyacrylamide polymer (modified cationic) denture adhesive is a device composed of polyacrylamide polymer (modified cationic) intended to...

21 CFR 872.3480 - Polyacrylamide polymer (modified cationic) denture adhesive.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Polyacrylamide polymer (modified cationic) denture... polymer (modified cationic) denture adhesive. (a) Identification. A polyacrylamide polymer (modified cationic) denture adhesive is a device composed of polyacrylamide polymer (modified cationic) intended to...

21 CFR 872.3480 - Polyacrylamide polymer (modified cationic) denture adhesive.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Polyacrylamide polymer (modified cationic) denture... polymer (modified cationic) denture adhesive. (a) Identification. A polyacrylamide polymer (modified cationic) denture adhesive is a device composed of polyacrylamide polymer (modified cationic) intended to...

Encapsulation of Naproxen in Lipid-Based Matrix Microspheres: Characterization and Release Kinetics

PubMed Central

Bhoyar, PK; Morani, DO; Biyani, DM; Umekar, MJ; Mahure, JG; Amgaonkar, YM

2011-01-01

The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix. PMID:21731354

Encapsulation of naproxen in lipid-based matrix microspheres: characterization and release kinetics.

PubMed

Bhoyar, P K; Morani, D O; Biyani, D M; Umekar, M J; Mahure, J G; Amgaonkar, Y M

2011-04-01

The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix.

Development of ketoconazole nanovesicular system using 1,2-hexanediol and 1,4-cyclohexanediol for dermal targeting delivery: physicochemical characterization and in vitro/in vivo evaluation

NASA Astrophysics Data System (ADS)

Wang, Jinping; Guo, Fang; Ma, Man; Li, Nan; Tan, Fengping

2014-07-01

The present study was aimed at the encapsulation of ketoconazole (KCZ) in the novel modified nanovesicles for dermal targeting delivery. To this purpose, innovative modified vesicles were prepared with soy phospholipid and aqueous solutions containing different concentrations of two targeting modifiers, 1,2-hexanediol and 1,4-cyclohexanediol. Conventional liposomes, with soy phospholipid and cholesterol, were used as control. The prepared formulations were characterized in terms of entrapment efficiency, size distribution, morphology, and stability. Dermal KCZ targeting delivery from modified vesicles was investigated in vitro and in vivo through newborn pig and rat skin, respectively. All vesicles showed a mean size ranging from 58 to 147 nm with fairly narrow size distribution and drug entrapment efficiency between 20 and 75 %. Results of in vitro and in vivo studies indicated that modified vesicles provided an improved KCZ targeting delivery into skin layers. Images of the confocal laser scanning microscopy analyses supported the conclusion that modified vesicles could enhance the drug deposition into the skin strata and reduce the drug permeation into the blood, due to a synergic effect of phospholipid and modifiers. Finally, histological evaluation showed that KCZ-loaded modified vesicles caused no irritation to the skin. The results obtained encouraged the use of the KCZ-loaded modified vesicles as the formulation for the potential topical treatment of fungal infections.

New H1/H3 antagonists for treating allergic rhinitis: WO2010094643.

PubMed

Norman, Peter

2011-03-01

This application claims dual receptor specificity antihistamines, active as H(1) and H(3) antagonists, which additionally have a long duration of action that renders them suitable for once daily administration via inhalation for the treatment of allergic rhinitis. The compounds lack CNS penetration and have a high affinity for both histamine receptors.

FDA's proposed rules on patent listing requirements for new drug and 30-month stays on ANDA approval (proposed Oct. 24, 2002).

PubMed

Hui, Yuk Fung

2003-01-01

In order to close the loophole in the generic drug approval process that allows a brand name drug patent holder to delay or defeat generic drug application merely by technicality, the FDA recently proposed to modify its regulations. Those proposals affect the patent listing requirements of a new drug application, and the duration of time that a generic drug application could be put on hold in the event of a patent infringement suit. With the modified rules, the FDA expects to see an increase in the availability of generic drugs, which eventually will lead to lower drug costs. Ms. Hui discusses the contents of the proposed regulations and provides an analysis of the proposed rule's legal authority, implications on patent rights, and impact on the pharmaceutical industry.

Magnetic nanoparticles for bio-analytical applications

NASA Astrophysics Data System (ADS)

Yedlapalli, Sri Lakshmi

Magnetic nanoparticles are widely being used in various fields of medicine, biology and separations. This dissertation focuses on the synthesis and use of magnetic nanoparticles for targeted drug delivery and analytical separations. The goals of this research include synthesis of biocompatible surface modified monodisperse superparamagnetic iron oxide nanoparticles (SPIONs) by novel techniques for targeted drug delivery and use of SPIONs as analytical sensing tools. Surface modification of SPIONs was performed with two different co-polymers: tri block co-polymer Pluronics and octylamine modified polyacrylic acid. Samples of SPIONs were subsequently modified with 4 different commercially available, FDA approved tri-block copolymers (Pluronics), covering a wide range of molecular weights (5.75-14.6 kDa). A novel, technically simpler and faster phase transfer approach was developed to surface modify the SPIONs with Pluronics for drug delivery and other biomedical applications. The hydrodynamic diameter and aggregation properties of the Pluronic modified SPIONs were studied by dynamic light scattering (DLS). The coverage of SPIONs with Pluronics was supported with IR Spectroscopy and characterized by Thermo gravimetric Analysis (TGA). The drug entrapment capacity of SPIONs was studied by UV-VIS spectroscopy using a hydrophobic carbocyanine dye, which serves as a model for hydrophobic drugs. These studies resulted in a comparison of physical properties and their implications for drug loading capacities of the four types of Pluronic coated SPIONs for drug delivery assessment. These drug delivery systems could be used for passive drug targeting. However, Pluronics lack the functional group necessary for bioconjugation and hence cannot achieve active targeting. SPIONs were functionalized with octylamine modified polyacrylic acid-based copolymer, providing water solubility and facile biomolecular conjugation. Epirubicin was loaded onto SPIONs and the drug entrapment was studied by UVVIS spectrophotometry. In this study, the antisense oligonucleotide sequence to the anti-apoptopic protein survivin was coupled to SPIONs to provide molecular targeting and potential therapy for cancer cells. Successful coupling of antisense survivin to SPIONs was demonstrated by circular dichroism studies of the conjugate and its complementary sequence. Such multifunctional SPIONs can be used as active targeting agents for cancer cells, producing enhanced magnetic resonance imaging contrast and releasing chemotherapeutic agents to targeted cells. SPIONs also serve as an excellent platform for analytical sensing. Streptavidin modified SPIONs were used as substrates to immobilize biotinylated aptamers (single-stranded DNA). The binding affinity of such aptamers to its target was achieved by quantifying the amount of target released from the aptamer. This quantification was achieved using pH-mediated stacking capillary electrophoresis. SPIONs were shown to be more efficient compared to magnetic microbeads as the sensing elements. The binding affinity constant of the aptamer determined was almost 8-fold better than that obtained using magnetic microbeads.

Drug prescriptions in Danish out-of-hours primary care: a 1-yearpopulation-based study

PubMed Central

Christensen, Morten Bondo; Nørøxe, Karen Busk; Moth, Grete; Vedsted, Peter; Huibers, Linda

2016-01-01

Objective General practitioners are the first point of contact in Danish out-of-hours (OOH) primary care. The large number of contacts implies that prescribing behaviour may have considerable impact on health-care expenditures and quality of care. The aim of this study was to examine the prevailing practices for medication prescription in Danish OOH with a particular focus on patient characteristics and contact type. Design and setting A one-year population-based retrospective observational study was performed of all contacts to OOH primary care in the Central Denmark Region using registry data. Main outcome measures Prescriptions were categorised according to Anatomical Therapeutic Chemical Classification (ATC) codes and stratified for patient age, gender and contact type (telephone consultation, clinic consultation or home visit). Prescription rates were calculated as number of prescriptions per 100 contacts. Results Of 644,777 contacts, 154,668 (24.0%) involved medication prescriptions; 21.9% of telephone consultations, 32.9% of clinic consultations and 14.3% of home visits. Around 53% of all drug prescriptions were made in telephone consultations. Anti-infective medications for systemic use accounted for 45.5% of all prescriptions and were the most frequently prescribed drug group for all contact types, although accounting for less than 1/3 of telephone prescriptions. Other frequently prescribed drugs were ophthalmological anti-infectives (10.5%), NSAIDs (6.4%), opioids (3.9%), adrenergic inhalants (3.0%) and antihistamines (2.3%). Conclusion About 25% of all OOH contacts involved one or more medication prescriptions. The highest prescription rate was found for clinic consultations, but more than half of all prescriptions were made by telephone. KEY POINTSAs the out-of-hours (OOH) primary care services cover more than 75% of all hours during a normal week, insight into the extent and type of OOH drug prescription is important.General practitioners (GPs) are responsible for more than 80% of all drug prescriptions in Denmark.Of all contacts 24.0% involved medication prescriptions; 21.9% of telephone consultations, 32.9% of clinic consultations and 14.3% of home visits.Of all prescriptions, 53% were made in telephone consultations.Anti-infective medications for systemic use accounted for 45.5% of all prescriptions, thereby being the most frequently prescribed drug group for all three contact types. PMID:27804314

Drug prescriptions in Danish out-of-hours primary care: a 1-yearpopulation-based study.

PubMed

Christensen, Morten Bondo; Nørøxe, Karen Busk; Moth, Grete; Vedsted, Peter; Huibers, Linda

2016-12-01

General practitioners are the first point of contact in Danish out-of-hours (OOH) primary care. The large number of contacts implies that prescribing behaviour may have considerable impact on health-care expenditures and quality of care. The aim of this study was to examine the prevailing practices for medication prescription in Danish OOH with a particular focus on patient characteristics and contact type. A one-year population-based retrospective observational study was performed of all contacts to OOH primary care in the Central Denmark Region using registry data. Prescriptions were categorised according to Anatomical Therapeutic Chemical Classification (ATC) codes and stratified for patient age, gender and contact type (telephone consultation, clinic consultation or home visit). Prescription rates were calculated as number of prescriptions per 100 contacts. Of 644,777 contacts, 154,668 (24.0%) involved medication prescriptions; 21.9% of telephone consultations, 32.9% of clinic consultations and 14.3% of home visits. Around 53% of all drug prescriptions were made in telephone consultations. Anti-infective medications for systemic use accounted for 45.5% of all prescriptions and were the most frequently prescribed drug group for all contact types, although accounting for less than 1/3 of telephone prescriptions. Other frequently prescribed drugs were ophthalmological anti-infectives (10.5%), NSAIDs (6.4%), opioids (3.9%), adrenergic inhalants (3.0%) and antihistamines (2.3%). About 25% of all OOH contacts involved one or more medication prescriptions. The highest prescription rate was found for clinic consultations, but more than half of all prescriptions were made by telephone. KEY POINTS As the out-of-hours (OOH) primary care services cover more than 75% of all hours during a normal week, insight into the extent and type of OOH drug prescription is important. General practitioners (GPs) are responsible for more than 80% of all drug prescriptions in Denmark. Of all contacts 24.0% involved medication prescriptions; 21.9% of telephone consultations, 32.9% of clinic consultations and 14.3% of home visits. Of all prescriptions, 53% were made in telephone consultations. Anti-infective medications for systemic use accounted for 45.5% of all prescriptions, thereby being the most frequently prescribed drug group for all three contact types.

21 CFR 184.1063 - Enzyme-modified lecithin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Enzyme-modified lecithin. 184.1063 Section 184... as GRAS § 184.1063 Enzyme-modified lecithin. (a) Enzyme-modified lecithin is prepared by treating... percent of total phosphatides as determined by “Determination of Lysolecithin Content of Enzyme-Modified...

21 CFR 184.1063 - Enzyme-modified lecithin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Enzyme-modified lecithin. 184.1063 Section 184... Listing of Specific Substances Affirmed as GRAS § 184.1063 Enzyme-modified lecithin. (a) Enzyme-modified... Lysolecithin Content of Enzyme-Modified Lecithin: Method I,” dated 1985, which is incorporated by reference in...

21 CFR 178.3520 - Industrial starch-modified.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Industrial starch-modified. 178.3520 Section 178... § 178.3520 Industrial starch-modified. Industrial starch-modified may be safely used as a component of..., transporting, or holding food, subject to the provisions of this section. (a) Industrial starch-modified is...

[Non-antiretroviral drugs uses among HIV-infected persons receiving antiretroviral therapy in Senegal: Costs and factors associated with prescription].

PubMed

Diouf, A; Youbong, T J; Maynart, M; Ndoye, M; Diéye, F L; Ndiaye, N A; Koita-Fall, M B; Ndiaye, B; Seydi, M

2017-08-01

In addition to antiretroviral therapy, non-antiretroviral drugs are necessary for the appropriate care of people living with HIV. The costs of such drugs are totally or partially supported by the people living with HIV. We aimed to evaluate the overall costs, the costs supported by the people living with HIV and factors associated with the prescription of non-antiretroviral drugs in people living with HIV on antiretroviral therapy in Senegal. We conducted a retrospective cohort study on 331 people living with HIV who initiated antiretroviral therapy between 2009 and 2011 and followed until March 2012. The costs of non-antiretroviral drugs were those of the national pharmacy for essential drugs; otherwise they were the lowest costs in the private pharmacies. Associated factors were identified through a logistic regression model. The study population was 61 % female. At baseline, 39 % of patients were classified at WHO clinical stage 3 and 40 % at WHO clinical stage 4. Median age, body mass index and CD4 cells count were 41 years, 18kg/m 2  and 93 cells/μL, respectively. After a mean duration of 11.4 months of antiretroviral therapy, 85 % of patients received at least one prescription for a non-antiretroviral drug. Over the entire study period, the most frequently prescribed non-antiretroviral drugs were cotrimoxazole (78.9 % of patients), iron (33.2 %), vitamins (21.1 %) and antibiotics (19.6 %). The mean cost per patient was 34 Euros and the mean cost supported per patient was 14 Euros. The most expensive drugs per treated patient were antihypertensives (168 Euros), anti-ulcer agents (12 Euros), vitamins (8.5 Euros) and antihistamines (7 Euros). The prescription for a non-antiretroviral drug was associated with advanced clinical stage (WHO clinical stage 3/4 versus stage 1/2): OR=2.25; 95 % CI=1.11-4.57 and viral type (HIV-2 versus HIV-1/HIV-1+HIV-2): OR=0.36; 95 % CI=0.14-0.89. Non-antiretroviral drugs are frequently prescribed to people living with HIV in developing countries; mainly those infected with HIV-1 and those at an advanced clinical stage. Their costs can be a barrier to appropriate care and necessary efforts must made to make them available. However, early initiation of antiretroviral therapy and the registration of some non-antiretroviral drugs on the list of essential drugs, as well as social protection systems, should reduce their use and costs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Evaluation of abuse and dependence on drugs used for self-medication: a pharmacoepidemiological pilot study based on community pharmacies in France.

PubMed

Orriols, Ludivine; Gaillard, Julia; Lapeyre-Mestre, Maryse; Roussin, Anne

2009-01-01

Drugs that can be obtained without a medical prescription in community pharmacies are used to treat minor pathologies that can easily be diagnosed by the patient. Some of these drugs contain psychoactive substances with a potential for abuse and dependence. However, there is a lack of data concerning their problematic use in a wide population. To explore the feasibility of a pharmacoepidemiological method to investigate misuse, non-medical use, abuse and dependence on drugs used for self-medication. This cross-sectional pilot study, conducted during a 2-month period (from 15 January to 15 March 2007), was based on the participation of community pharmacies in the Midi-Pyrénées region of France to collect patient data. Patients requesting one drug from a list of available drugs used for self-medication and containing psychoactive substances (codeine in analgesics, pseudoephedrine, dextromethorphan and histamine H(1) receptor antagonists [antihistamines]) were included in the study. A control group was set up that consisted of patients requesting antacid drugs. The pharmacy staff proposed to the patients that they filled in an anonymous questionnaire. The questionnaire was designed to investigate patterns of drug use and the harmful consequences of overuse (abuse). In addition, questions on lack of control over drug use were adapted from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for evaluation of dependence. Thirty-two percent (n = 74) of the solicited pharmacies participated in the survey. Only 4.8% of the solicited patients (n = 817) refused to complete the questionnaire distributed by the pharmacy staff. The questionnaire was completed inside the pharmacy by 53.3% of the patients. The other patients took the questionnaire away from the pharmacy and 31.7% of them returned it in a prepaid envelope. The patient participation rate was 64.9%, and was higher for the psychoactive substance groups than the control group. Statistically significant differences on misuse (and/or non-medical use), abuse and dependence were obtained between the codeine and antacid groups. In the codeine group, among the patients having used the product in the previous month (n = 53), 15.1% misused the drug and/or used the drug for a non-medical reason, 7.5% were cases of abuse and 7.5% presented criteria of lack of control over drug use related to dependence on the substance for the psychoactive effects or for pain relief. The results obtained in this pilot study indicate that using anonymous self-administered questionnaires offered to patients by pharmacy staff is a reliable method to obtain information on the problematic use of drugs containing psychoactive substances purchased in a pharmacy for self-medication.

Graft polymerization of guar gum with acryl amide irradiated by microwaves for colonic drug delivery.

PubMed

Shahid, Muhammad; Bukhari, Shazia Anwer; Gul, Yousra; Munir, Hira; Anjum, Fozia; Zuber, Mohammad; Jamil, Tahir; Zia, Khalid Mahmood

2013-11-01

This article is aimed to discuss the modification of guar gum through microwave irradiation by varying the time of irradiation. The characterization of the modified products was carried out using FTIR spectroscopic analysis. The FT-IR spectrum of the pure guar gum (GG) sample showed a broad peak at 3298 cm(-1) while the modified GG sample displayed a peak at 1541 cm(-1) which was absent in the crude sample. The X-ray diffraction (XRD) analysis confirmed the increase in crystallinity due to grafting of the sample with polyacrylamide (GG-g-PAM). Scanning electron microscope (SEM) images revealed that granular form of guar gum was changed into fibrillar structure after grafting. Thermo-gravimetric analysis of the modified samples was also carried out and discussed. The role of guar gum as a matrix for controlled release of drug triamcinolone was evaluated. The GG-acrylamide grafted samples presented a correlation between drug release and time of microwave exposure. The results revealed that such modified product has potential applications in colonic drug delivery system. Copyright © 2013 Elsevier B.V. All rights reserved.

3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets.

PubMed

Goyanes, Alvaro; Buanz, Asma B M; Hatton, Grace B; Gaisford, Simon; Basit, Abdul W

2015-01-01

The aim of this study was to explore the potential of fused-deposition 3-dimensional printing (FDM 3DP) to produce modified-release drug loaded tablets. Two aminosalicylate isomers used in the treatment of inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA, mesalazine) and 4-aminosalicylic acid (4-ASA), were selected as model drugs. Commercially produced polyvinyl alcohol (PVA) filaments were loaded with the drugs in an ethanolic drug solution. A final drug-loading of 0.06% w/w and 0.25% w/w was achieved for the 5-ASA and 4-ASA strands, respectively. 10.5mm diameter tablets of both PVA/4-ASA and PVA/5-ASA were subsequently printed using an FDM 3D printer, and varying the weight and densities of the printed tablets was achieved by selecting the infill percentage in the printer software. The tablets were mechanically strong, and the FDM 3D printing was shown to be an effective process for the manufacture of the drug, 5-ASA. Significant thermal degradation of the active 4-ASA (50%) occurred during printing, however, indicating that the method may not be appropriate for drugs when printing at high temperatures exceeding those of the degradation point. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) of the formulated blends confirmed these findings while highlighting the potential of thermal analytical techniques to anticipate drug degradation issues in the 3D printing process. The results of the dissolution tests conducted in modified Hank's bicarbonate buffer showed that release profiles for both drugs were dependent on both the drug itself and on the infill percentage of the tablet. Our work here demonstrates the potential role of FDM 3DP as an efficient and low-cost alternative method of manufacturing individually tailored oral drug dosage, and also for production of modified-release formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

Artificial neural networks in evaluation and optimization of modified release solid dosage forms.

PubMed

Ibrić, Svetlana; Djuriš, Jelena; Parojčić, Jelena; Djurić, Zorica

2012-10-18

Implementation of the Quality by Design (QbD) approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE) as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM) is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN) in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms.

Artificial Neural Networks in Evaluation and Optimization of Modified Release Solid Dosage Forms

PubMed Central

Ibrić, Svetlana; Djuriš, Jelena; Parojčić, Jelena; Djurić, Zorica

2012-01-01

Implementation of the Quality by Design (QbD) approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE) as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM) is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN) in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms. PMID:24300369

Systematic assessment of different solvents for the extraction of drugs of abuse and pharmaceuticals from an authentic hair pool.

PubMed

Madry, Milena M; Kraemer, Thomas; Baumgartner, Markus R

2018-01-01

Hair analysis has been established as a prevalent tool for retrospective drug monitoring. In this study, different extraction solvents for the determination of drugs of abuse and pharmaceuticals in hair were evaluated for their efficiency. A pool of authentic hair from drug users was used for extraction experiments. Hair was pulverized and extracted in triplicate with seven different solvents in a one- or two-step extraction. Three one- (methanol, acetonitrile, and acetonitrile/water) and four two-step extractions (methanol two-fold, methanol and methanol/acetonitrile/formate buffer, methanol and methanol/formate buffer, and methanol and methanol/hydrochloric acid) were tested under accurately equal experimental conditions. The extracts were directly analyzed by liquid chromatography-tandem mass spectrometry for opiates/opioids, stimulants, ketamine, selected benzodiazepines, antidepressants, antipsychotics, and antihistamines using deuterated internal standards. For most analytes, a two-step extraction with methanol did not significantly improve the yield compared to a one-step extraction with methanol. Extraction with acetonitrile alone was least efficient for most analytes. Extraction yields of acetonitrile/water, methanol and methanol/acetonitrile/formate buffer, and methanol and methanol/formate buffer were significantly higher compared to methanol. Highest efficiencies were obtained by a two-step extraction with methanol and methanol/hydrochloric acid, particularly for morphine, 6-monoacetylmorphine, codeine, 6-acetylcodeine, MDMA, zopiclone, zolpidem, amitriptyline, nortriptyline, citalopram, and doxylamine. For some analytes (e.g., tramadol, fluoxetine, sertraline), all extraction solvents, except for acetonitrile, were comparably efficient. There was no significant correlation between extraction efficiency with an acidic solvent and the pka or log P of the analyte. However, there was a significant trend for the extraction efficiency with acetonitrile to the log P of the analyte. The study demonstrates that the choice of extraction solvent has a strong impact on hair analysis outcomes. Therefore, validation protocols should include the evaluation of extraction efficiency of drugs by using authentic rather than spiked hair. Different extraction procedures may contribute to the scatter of quantitative results in inter-laboratory comparisons. Harmonization of extraction protocols is recommended, when interpretation is based on same cut-off levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification and Prioritization of Important Attributes of Disease-Modifying Drugs in Decision Making among Patients with Multiple Sclerosis: A Nominal Group Technique and Best-Worst Scaling.

PubMed

Kremer, Ingrid E H; Evers, Silvia M A A; Jongen, Peter J; van der Weijden, Trudy; van de Kolk, Ilona; Hiligsmann, Mickaël

2016-01-01

Understanding the preferences of patients with multiple sclerosis (MS) for disease-modifying drugs and involving these patients in clinical decision making can improve the concordance between medical decisions and patient values and may, subsequently, improve adherence to disease-modifying drugs. This study aims first to identify which characteristics-or attributes-of disease-modifying drugs influence patients´ decisions about these treatments and second to quantify the attributes' relative importance among patients. First, three focus groups of relapsing-remitting MS patients were formed to compile a preliminary list of attributes using a nominal group technique. Based on this qualitative research, a survey with several choice tasks (best-worst scaling) was developed to prioritize attributes, asking a larger patient group to choose the most and least important attributes. The attributes' mean relative importance scores (RIS) were calculated. Nineteen patients reported 34 attributes during the focus groups and 185 patients evaluated the importance of the attributes in the survey. The effect on disease progression received the highest RIS (RIS = 9.64, 95% confidence interval: [9.48-9.81]), followed by quality of life (RIS = 9.21 [9.00-9.42]), relapse rate (RIS = 7.76 [7.39-8.13]), severity of side effects (RIS = 7.63 [7.33-7.94]) and relapse severity (RIS = 7.39 [7.06-7.73]). Subgroup analyses showed heterogeneity in preference of patients. For example, side effect-related attributes were statistically more important for patients who had no experience in using disease-modifying drugs compared to experienced patients (p < .001). This study shows that, on average, patients valued effectiveness and unwanted effects as most important. Clinicians should be aware of the average preferences but also that attributes of disease-modifying drugs are valued differently by different patients. Person-centred clinical decision making would be needed and requires eliciting individual preferences.

Identification and Prioritization of Important Attributes of Disease-Modifying Drugs in Decision Making among Patients with Multiple Sclerosis: A Nominal Group Technique and Best-Worst Scaling

PubMed Central

Kremer, Ingrid E. H.; van der Weijden, Trudy; van de Kolk, Ilona

2016-01-01

Objectives Understanding the preferences of patients with multiple sclerosis (MS) for disease-modifying drugs and involving these patients in clinical decision making can improve the concordance between medical decisions and patient values and may, subsequently, improve adherence to disease-modifying drugs. This study aims first to identify which characteristics–or attributes–of disease-modifying drugs influence patients´ decisions about these treatments and second to quantify the attributes’ relative importance among patients. Methods First, three focus groups of relapsing-remitting MS patients were formed to compile a preliminary list of attributes using a nominal group technique. Based on this qualitative research, a survey with several choice tasks (best-worst scaling) was developed to prioritize attributes, asking a larger patient group to choose the most and least important attributes. The attributes’ mean relative importance scores (RIS) were calculated. Results Nineteen patients reported 34 attributes during the focus groups and 185 patients evaluated the importance of the attributes in the survey. The effect on disease progression received the highest RIS (RIS = 9.64, 95% confidence interval: [9.48–9.81]), followed by quality of life (RIS = 9.21 [9.00–9.42]), relapse rate (RIS = 7.76 [7.39–8.13]), severity of side effects (RIS = 7.63 [7.33–7.94]) and relapse severity (RIS = 7.39 [7.06–7.73]). Subgroup analyses showed heterogeneity in preference of patients. For example, side effect-related attributes were statistically more important for patients who had no experience in using disease-modifying drugs compared to experienced patients (p < .001). Conclusions This study shows that, on average, patients valued effectiveness and unwanted effects as most important. Clinicians should be aware of the average preferences but also that attributes of disease-modifying drugs are valued differently by different patients. Person-centred clinical decision making would be needed and requires eliciting individual preferences. PMID:27812117

Modified titanium implant as a gateway to the human body: the implant mediated drug delivery system.

PubMed

Park, Young-Seok; Cho, Joo-Youn; Lee, Shin-Jae; Hwang, Chee Il

2014-01-01

The aim of this study was to investigate the efficacy of a proposed new implant mediated drug delivery system (IMDDS) in rabbits. The drug delivery system is applied through a modified titanium implant that is configured to be implanted into bone. The implant is hollow and has multiple microholes that can continuously deliver therapeutic agents into the systematic body. To examine the efficacy and feasibility of the IMDDS, we investigated the pharmacokinetic behavior of dexamethasone in plasma after a single dose was delivered via the modified implant placed in the rabbit tibia. After measuring the plasma concentration, the areas under the curve showed that the IMDDS provided a sustained release for a relatively long period. The result suggests that the IMDDS can deliver a sustained release of certain drug components with a high bioavailability. Accordingly, the IMDDS may provide the basis for a novel approach to treating patients with chronic diseases.

Anti-transferrin receptor-modified amphotericin B-loaded PLA-PEG nanoparticles cure Candidal meningitis and reduce drug toxicity.

PubMed

Tang, Xiaolong; Liang, Yong; Zhu, Yongqiang; Xie, Chunmei; Yao, Aixia; Chen, Li; Jiang, Qinglin; Liu, Tingting; Wang, Xiaoyu; Qian, Yunyun; Wei, Jia; Ni, Wenxuan; Dai, Jingjing; Jiang, Zhenyou; Hou, Wei

2015-01-01

Fatal fungal infections in central nervous system (CNS) can occur through hematogenous spread or direct extension. At present, hydrophobic amphotericin B (AMB) is the most effective antifungal drug in clinical trials. However, AMB is hydrophobic and therefore penetrates poorly into the CNS, and therapeutic levels of AMB are hard to achieve. The transferrin receptor (TfR/CD71) located at the blood-brain barrier mediates transferrin transcytosis. In order to enhance the receptor-mediated delivery of AMB into CNS with therapeutic level, an anti-TfR antibody (OX26)-modified AMB-loaded PLA (poly[lactic acid])-PEG (polyethylene glycol)-based micellar drug delivery system was constructed. The prepared OX26-modified AMB-loaded nanoparticles (OX26-AMB-NPs) showed significant reduction of CNS fungal burden and an increase of mouse survival time. In conclusion, OX26-AMB-NPs represent a promising novel drug delivery system for intracerebral fungal infection.

Rapeseed oil-rich diet alters in vitro menadione and nimesulide hepatic mitochondrial toxicity.

PubMed

Monteiro, João P; Silva, Ana M; Jurado, Amália S; Oliveira, Paulo J

2013-10-01

Diet-induced changes in the lipid composition of mitochondrial membranes have been shown to influence physiological processes. However, the modulation effect of diet on mitochondrially-active drugs has not yet received the deserved attention. Our hypothesis is that modulation of membrane dynamics by diet impacts drug-effects on liver mitochondrial functioning. In a previous work, we have shown that a diet rich in rapeseed oil altered mitochondrial membrane composition and bioenergetics in Wistar rats. In the present work, we investigated the influence of the modified diet on hepatic mitochondrial activity of two drugs, menadione and nimesulide, and FCCP, a classic protonophore, was used for comparison. The results showed that the effects of menadione and nimesulide were less severe on liver mitochondria for rats fed the modified diet than on rats fed the control diet. A specific effect on complex I seemed to be involved in drug-induced mitochondria dysfunction. Liver mitochondria from the modified diet group were more susceptible to nimesulide effects on MPT induction. The present work demonstrates that diet manipulation aimed at modifying mitochondrial membrane properties alters the toxicity of mitochondria active agents. This work highlights that diet may potentiate mitochondrial pharmacologic effects or increase drug-induced liabilities. Copyright © 2013 Elsevier Ltd. All rights reserved.

77 FR 59930 - Clinical Development Programs for Disease-Modifying Agents for Peripheral Neuropathy; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

... for comments. SUMMARY: The Food and Drug Administration (FDA), Center for Drug Evaluation and Research... Contacts: Randi Clark, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New..., Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver...

Recreational use of dextromethorphan, "Robotripping"-A brief review.

PubMed

Stanciu, Cornel N; Penders, Thomas M; Rouse, Eden M

2016-08-01

Dextromethorphan (DXM) in combination with antihistamines and/or pseudoephedrine is widely available as an over-the counter remedy commonly used for relief of colds and cough. In supra-therapeutic amounts, DXM has psychoactive effects. These cough preparations have been adopted by many young users of recreational drugs for these effects. This paper aims to highlight the increasingly prevalent practice of Robotripping, review pharmacokinetic and dynamic data and discuss potential tolerance and withdrawal from the substance as well as treatment modalities. A Medline search (1985-2015) for literature concerning the DXM was conducted. This was supplemented by references gleaned from recent epidemiological surveys and credible online sources to ensure most up to date information is gathered. Use in amounts exceeding those recommended, a practice known as "Robotripping", may result in a toxidrome of psychomotor agitation, hallucinations and paranoia best characterized as Intoxication Delirium. Increasing misuse places greater numbers at risk. Providers should be alert to such presentations and be aware of methods for managing the symptoms. With chronic use, tolerance and withdrawal has been noted along with prolonging psychiatric sequelae. (Am J Addict 2016;25:374-377). © 2016 American Academy of Addiction Psychiatry.

[Xanthelasmoid mastocytosis: a rare form of cutaneous mastocytosis].

PubMed

Ramid, Hind; Hali, Fouzia

2017-01-01

Mastocytosis is a rare disease characterized by the abnormal accumulation of mast cells in the skin and possibly in other organs. It can occur in a variety of forms; xanthelasmoid mastocytosis(XM) is a very rare form classified as papulo-nodular. Clinically, it appears as buff-yellow soft papules or nodules of variable size. Triggerings are those of classic mastocytosis. Darier's sign is often absent. Histology shows dense infiltrate of mast cells in the deep dermis. This clinical form can be singled out because of the persistence of lesions beyond puberty without the additional risk of systemic involvement. We here report the case of a 18-month old female infant, with no previous medical history. Maculopapular, intensely pruritic, ovalaires, brownish lesions with a buff-yellow centre, with elastic consistency and different sizes first occurred at the age of 8 months. The initial interview of parents revealed that the infant had had episode of flush especially caused by warmth. Darrier's sign was negative. Skin biopsy showed dermal infiltrate of mast cells, allowing to retain the diagnosis of xanthelasmoid mastocytosis. Complementary examinations as well as trypsin dosage were normal. Treatment was based on the exclusion of drugs and of factors participating in mast cells degranulation and antihistamines.

[Outbreak of dermatitis caused by pine processionary caterpillar (Thaumetopoea pityocampa) in schoolchildren].

PubMed

Artola-Bordás, F; Arnedo-Pena, A; Romeu-García, M A; Bellido-Blasco, J B

2008-01-01

To describe a dermatitis outbreak caused by exposure to pine processionary caterpillar (Thaumetopoea pityocampa ) that took place on March 15th, 2006, in schoolchildren during their stay at a rural farm holiday centre in Villahermosa del Río (Castellón). A cross sectional epidemiological study was carried out on seventy schoolchildren, average age 10 years, and 3 teachers from Castellón. A specific questionnaire was used to be filled in by the schoolchildren. Six cases of dermatitis (attack rate 8.6%: 6/70) took place after children had swum in the heated farm pool and dried themselves with towels that had been left outside the heated pool enclosure, where they had come into contact with Thaumetopoea pityocampa. The cases needed medical attention, with prescription of antihistamine drugs, corticosteroids, and cold showers. The risk of dermatitis from contact with Thaumetopoea pityocampa was very high (Odds Ratio=157.2 Confidence Interval 95% 18.4-inf). Thaumetopoea pityocampa were collected near the swimming pool and Thaumetopoea pityocampa nests were observed on nearby pines. The presence of Thaumetopoea pityocampa near rural centres can cause outbreaks. Health education for schoolchildren and the removal of Thaumetopoea pityocampa nests near these centres are required.

21 CFR 184.1063 - Enzyme-modified lecithin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Enzyme-modified lecithin. 184.1063 Section 184.1063... Listing of Specific Substances Affirmed as GRAS § 184.1063 Enzyme-modified lecithin. (a) Enzyme-modified... Lysolecithin Content of Enzyme-Modified Lecithin: Method I,” dated 1985, which is incorporated by reference in...

Scombroid poisoning.

PubMed

Lange, W R

1988-04-01

The symptoms of scombroid poisoning resemble an acute allergic reaction. Tuna, albacore, mackerel and bonito are implicated, as are nonscombroid fish such as mahi-mahi and bluefish. The histamine content of affected fish is high, but the pathophysiology is more complex than the mere ingestion of histamine. Antihistamines and cimetidine appear to be effective in controlling symptoms. Prevention consists of prompt and adequate refrigeration of dark-meated fish.

Anaphylactic deaths in asthmatic patients.

PubMed

Settipane, G A

1989-01-01

We reviewed seven documented deaths to peanuts and two near deaths. We excluded hearsay undocumented deaths to peanuts. Peanut allergy is one of the most common food allergies and probably the most common cause of death by food anaphylaxis in the United States. About one-third of peanut-sensitive patients have severe reactions to peanuts. Asthmatics with peanut sensitivity appear more likely to develop fatal reactions probably because of the exquisite sensitivity that asthamatics have to chemical mediators of anaphylaxis. Severe reactions occur within a few minutes of ingestion and these patients must carry preloaded epinephrine syringes, antihistamines, and medic-alert bracelets. Treatment should include repeated doses of epinephrine, antihistamines and corticosteroids as well as availability of oxygen, mechanical methods to open airways, vasopressors, and intravenous fluids. Hidden sources of peanuts such as chili, egg rolls, cookies, candy, and pastry should be recognized and identified. Scratch/prick test to peanuts are highly diagnostic. Peanut is one of the most sensitive food allergens known requiring only a few milligrams to cause a reaction. In some individuals, even contact of peanut with unbroken skin can cause an immediate local reaction. Unfortunately, peanut reaction is not outgrown and remains a life-long threat.

Photodegradation of the antihistamine cetirizine in natural waters.

PubMed

Mead, Ralph N; Barefoot, Seth; Helms, John R; Morgan, Jeremy B; Kieber, Robert J

2014-10-01

The photodegradation rate of the anti-histamine cetirizine (Zyrtec®) was investigated in various water matrices. The average observed first-order photodegradation rate coefficient (kobs ), obtained by linear regression of the logarithmic-transformed cetirizine concentrations versus irradiation time in simulated sunlight, was 0.024 h(-1) (n = 6; standard deviation ± 0.004) in deionized water corresponding to a half-life of approximately 30 h. There was no statistical difference in the kobs of cetirizine photodegradation in coastal seawater compared with deionized water or deionized water amended with dissolved chromophoric organic matter. The quantum yield of cetirizine photodegradation decreased dramatically with increasing wavelength and decreasing energy of incoming radiation, with the average value ranging from 5.28 × 10(-4) to 6.40 × 10(-3) in the ultraviolet wavelength range (280-366 nm). The activation energy of cetirizine photodegradation was 10.3 kJ mol(-1) with an observed increase in cetirizine photodegradation as temperature increased. This is a significant environmental factor influencing half-life and an important consideration, given that cetirizine has been detected in wastewater and receiving waters from different locations globally. © 2014 SETAC.

Cost-Effectiveness of Second-Generation Antihistamines and Montelukast in Relieving Allergic Rhinitis Nasal Symptoms

PubMed Central

Goodman, Michael J.; Jhaveri, Mehul; Saverno, Kim; Meyer, Kellie; Nightengale, Brian

2008-01-01

Objective Allergic rhinitis imposes a significant health and economic burden both on individuals and the healthcare system. Second-generation prescription antihistamines, levocetirizine, fexofenadine, and desloratadine, and the leukotriene receptor antagonist, montelukast, differ in their ability to relieve common rhinitis symptoms. The purpose of this study was to compare the cost-effectiveness of prescription agents based on their effectiveness in relieving nasal symptoms. Methods Effectiveness was measured as the composite of nasal symptoms, including congestion, rhinorrhea, and sneezing, from clinical studies that compared each of the 4 comparators to placebo. Direct costs included prescription therapy and rhinitis-related physician office visits. Physician office visit costs were collected from an analysis of the PharMetrics insurance claims database. Sensitivity analyses were conducted using a Monte Carlo simulation to assess the robustness of the average and incremental cost-effectiveness ratios. Results The cost per clinically significant improvement of nasal symptoms for levocetirizine was less than for the other model comparator agents. The incremental cost-effectiveness ratio for levocetirizine dominated montelukast and desloratadine and was lower than either branded or generic fexofenadine. Conclusion Levocetirizine is a cost-effective therapy for the relief of nasal symptoms of allergic rhinitis. PMID:25126257

The burden of allergies--and the capacity of medications to reduce this burden-in a heavy manufacturing environment.

PubMed

Bunn, William B; Pikelny, Dan B; Paralkar, Sadhna; Slavin, Thomas; Borden, Spencer; Allen, Harris M

2003-09-01

This article addresses the observational findings of the first systematic study undertaken by a manufacturer to address the impact of allergies and use of allergy medications on health, safety, and productivity. It provides background for 3 other papers from the same project, including an evaluation of an intervention to promote appropriate medication use among affected employees, which appear in this issue. The observational data are developed on 10,714 employees from: 1) 2 employee surveys; 2) administrative databases monitoring employee absenteeism, workers compensation, short-term disability, and group health. The results show that health, productivity, absenteeism, workplace injury, and workers compensation measures register consistent declines as allergy severity levels increase. This pattern is present but less pronounced for the short-term disability and group health measures. In addition, among the 16 measures registering a significant allergy burden, 6 posted significant advantages for the use of nonsedating antihistamines relative to other medication regimens that included sedative antihistamines. These results document the burden of allergies and the capacity of medications to reduce this burden. Effective intervention programs that target this condition can achieve improved health, productivity, and related outcomes.

Targeted Cellular Drug Delivery using Tailored Dendritic Nanostructures

NASA Astrophysics Data System (ADS)

Kannan, Rangaramanujam; Kolhe, Parag; Kannan, Sujatha; Lieh-Lai, Mary

2002-03-01

Dendrimers and hyperbranched polymers possess highly branched architectures, with a large number of controllable, tailorble, ‘peripheral’ functionalities. Since the surface chemistry of these materials can be modified with relative ease, these materials have tremendous potential in targeted drug and gene delivery. The large number of end groups can also be tailored to create special affinity to targeted cells, and can also encapsulate drugs and deliver them in a controlled manner. We are developing tailor-modified dendritic systems for drug delivery. Synthesis, in-vitro drug loading, in-vitro drug delivery, and the targeting efficiency to the cell are being studied systematically using a wide variety of experimental tools. Polyamidoamine and Polyol dendrimers, with different generations and end-groups are studied, with drugs such as Ibuprofen and Methotrexate. Our results indicate that a large number of drug molecules can be encapsulated/attached to the dendrimers, depending on the end groups. The drug-encapsulated dendrimer is able to enter the cells rapidly and deliver the drug. Targeting strategies being explored

A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered drug release.

PubMed

Wu, Daocheng; Wan, Mingxi

2008-01-01

Controlled drug release, especially tumor-targeted drug release, remains a great challenge. Here, we prepare a novel fluoride anion-modified gelatin nanogel system and investigate its characteristics of ultrasound-triggered drug release. Adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) was prepared by a modified co-precipitation method with fluoride anion and sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic agent adriamycin (ADM) were measured by high performance liquid chromatography (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and photo-correlation spectroscopy. The size distribution and drug release efficiency of ADM-GNMF, before and after sonication, were measured by two designed measuring devices that consisted of either a submicron particle size analyzer and an ultrasound generator as well as an ultrasound generator, automatic sampler, and HPLC. The ADM-GNMF was stable in solution with an average diameter of 46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and 6.38%, respectively. The ultrasound-triggered drug release and size change were most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF was released within 2~3 min without sonication, and only negligible size changes were found. The ADM-GNMF system efficiently released the encompassed drug in response to ultrasound, offering a novel and promising controlled drug release system for targeted therapy for cancer or other diseases.

Gelatin modified lipid nanoparticles for anti- viral drug delivery.

PubMed

K S, Joshy; S, Snigdha; Kalarikkal, Nandakumar; Pothen, Laly A; Thomas, Sabu

2017-10-01

The major challenges to clinical application of zidovudine are its moderate aqueous solubility and relative short half-life and serious side effects due to frequent administrations. We investigated the preparation of zidovudine-loaded nanoparticles based on lipids which were further modified with the polymer gelatin. Formulation and stability of the modified nanoparticles were analysed from the physico-chemical characterizations. The interactions of nanoparticles with blood components were tested by haemolysis and aggregation studies. The drug content and entrapment efficiencies were assessed by UV analysis. The effect of nanoparticles on protein adsorption was assessed by native polyacrylamide gel electrophoresis (PAGE). In vitro release studies showed a sustained release profile of zidovudine. In vitro cytotoxicity and cellular uptake of the zidovudine-loaded nanoparticles were performed in MCF-7 and neuro 2a brain cells. The enhanced cellular internalization of drug loaded modified nanoparticles in both the cell lines were revealed by fluorescence microscopy. Hence the present study focuses on the feasibility of zidovudine-loaded polymer modified lipid nanoparticles as carriers for safe and efficient HIV/AIDS therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmaceutical cocrystals as an opportunity to modify drug properties: From the idea to application. A review.

PubMed

Sokal, Agnieszka; Pindelska, Edyta

2017-12-26

The properties of many drugs which have been available on the pharmaceutical market for a long time still need to be improved. Cocrystals are the solid state drug modification which can improve such properties as low solubility, stability and mechanical properties (e.g. compressibility). In this paper examples how to use cocrystals to modify properties of API (Active Pharmaceutical Ingredient) will be reported. Additionally, in this review the way from an idea of the new cocrystal to drug dosage form registration will be shortly described. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Zolpidem is independently associated with increased risk of inpatient falls.

PubMed

Kolla, Bhanu Prakash; Lovely, Jenna K; Mansukhani, Meghna P; Morgenthaler, Timothy I

2013-01-01

Inpatient falls are associated with significant morbidity and increased healthcare costs. Zolpidem has been reported to decrease balance and is associated with falls. Yet, it is a commonly used hypnotic agent in the inpatient setting. Zolpidem use in hospitalized patients may be a significant and potentially modifiable risk factor for falling. To determine whether inpatients administered zolpidem are at greater risk of falling. Retrospective cohort study. Adult non-intensive care unit (non-ICU) inpatients at a tertiary care center. Adult inpatients who were prescribed zolpidem were identified. Electronic medical records were reviewed to capture demographics and other risk factors for falls. The fall rate was compared in those administered zolpidem versus those only prescribed zolpidem. Multivariate analyses were performed to determine whether zolpidem was independently associated with falls. The fall rate among patients who were prescribed and received zolpidem (n = 4962) was significantly greater than among patients who were prescribed but did not receive zolpidem (n = 11,358) (3.04% vs 0.71%; P < 0.001). Zolpidem use continued to remain significantly associated with increased fall risk after accounting for age, gender, insomnia, delirium status, dose of zolpidem, Charlson comorbidity index, Hendrich's fall risk score, length of hospital stay, presence of visual impairment, gait abnormalities, and dementia/cognitive impairment (adjusted odds ratio [OR] 4.37, 95% confidence interval [CI] = 3.34-5.76; P < 0.001). Additionally, patients taking zolpidem who experienced a fall did not differ from other hospitalized adult patients who fell in terms of age, opioids, antidepressants, sedative-antidepressants, antipsychotics, benzodiazepine, or antihistamine use. Zolpidem use was a strong, independent, and potentially modifiable risk factor for inpatient falls. Copyright © 2012 Society of Hospital Medicine.

Copper-free route to triazole-modified peptidomimetic by the combination of two multicomponent reactions in one pot.

PubMed

Niu, Teng-fei; Gu, Lin; Yi, Wen-bin; Cai, Chun

2012-05-14

An efficient copper-free protocol for the synthesis of 5-methyl-1H-1,2,3-triazole-modified peptidomimetics through the combination of Ugi four-component reaction with a three-component cycloaddition, has been developed. The copper-free straightforward process is suitable for drug discovery. The chemoselective preparation of 1,4-disubstituted, triazole-modified peptidomimetics by using alkynyl substituted amines may have potential biological and synthetic application. At last, a "Lapinski type" analysis of the physical properties was performed, which is expected to help drug discovery.

21 CFR 520.522 - Cyclosporine.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.522 Cyclosporine. (a) Specifications...) cyclosporine. (2) Each milliliter of cyclosporine oral solution, USP (MODIFIED) contains 100 mg cyclosporine...

21 CFR 520.522 - Cyclosporine.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.522 Cyclosporine. (a) Specifications...) cyclosporine. (2) Each milliliter of cyclosporine oral solution, USP (MODIFIED) contains 100 mg cyclosporine...

21 CFR 520.522 - Cyclosporine.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.522 Cyclosporine. (a) Specifications...) cyclosporine. (2) Each milliliter of cyclosporine oral solution, USP (MODIFIED) contains 100 mg cyclosporine...

Evaluation of in-vitro cytotoxicity and cellular uptake efficiency of zidovudine-loaded solid lipid nanoparticles modified with Aloe Vera in glioma cells.

PubMed

K S, Joshy; Sharma, Chandra P; Kalarikkal, Nandakumar; Sandeep, K; Thomas, Sabu; Pothen, Laly A

2016-09-01

Zidovudine loaded solid lipid nanoparticles of stearic acid modified with Aloe Vera (AV) have been prepared via simple emulsion solvent evaporation method which showed excellent stability at room temperature and refrigerated condition. The nanoparticles were examined by Fourier transform infrared spectroscopy (FT-IR), which revealed the overlap of the AV absorption peak with the absorption peak of modified stearic acid nanoparticles. The inclusion of AV to stearic acid decreased the crystallinity and improved the hydrophilicity of lipid nanoparticles and thereby improved the drug loading efficacy of lipid nanoparticles. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging revealed that, the average particle size of unmodified (bare) nanoparticles was 45.66±12.22nm and modified solid lipid nanoparticles showed an average size of 265.61±80.44nm. Solid lipid nanoparticles with well-defined morphology were tested in vitro for their possible application in drug delivery. Cell culture studies using C6 glioma cells on the nanoparticles showed enhanced growth and proliferation of cells without exhibiting any toxicity. In addition, normal cell morphology and improved uptake were observed by fluorescence microscopy images of rhodamine labeled modified solid lipid nanoparticles compared with unmodified nanoparticles. The cellular uptake study suggested that these nanoparticles could be a promising drug delivery system to enhance the uptake of antiviral drug by brain cells and it could be a suitable drug carrier system for the treatment of HIV. Copyright © 2016 Elsevier B.V. All rights reserved.

Surface-Engineered Multifunctional Eu:Gd2O3 Nanoplates for Targeted and pH-Responsive Drug Delivery and Imaging Applications.

PubMed

Saha, Arindam; Mohanta, Subas Chandra; Deka, Kashmiri; Deb, Pritam; Devi, Parukuttyamma Sujatha

2017-02-01

In this paper, we report the synthesis of surface-engineered multifunctional Eu:Gd 2 O 3 triangular nanoplates with small size and uniform shape via a high-temperature solvothermal technique. Surface engineering has been performed by a one-step polyacrylate coating, followed by controlled conjugation chemistry. This creates the desired number of surface functional groups that can be used to attach folic acid as a targeting ligand on the nanoparticle surface. To specifically deliver the drug molecules in the nucleus, the folate density on the nanoparticle surface has been kept low. We have also modified the drug molecules with terminal double bond and ester linkage for the easy conjugation of nanoparticles. The nanoparticle surface was further modified with free thiols to specifically attach the modified drug molecules with a pH-responsive feature. High drug loading has been encountered for both hydrophilic drug daunorubicin (∼69% loading) and hydrophobic drug curcumin (∼75% loading) with excellent pH-responsive drug release. These nanoparticles have also been used as imaging probes in fluorescence imaging. Some preliminary experiments to evaluate their application in magnetic resonance imaging have also been explored. A detailed fluorescence imaging study has confirmed the efficient delivery of drugs to the nuclei of cancer cells with a high cytotoxic effect. Synthesized surface-engineered nanomaterials having small hydrodynamic size, excellent colloidal stability, and high drug-loading capacity, along with targeted and pH-responsive delivery of dual drugs to the cancer cells, will be potential nanobiomaterials for various biomedical applications.

Clinical pharmacology of novel anti-Alzheimer disease modifying medications.

PubMed

Caraci, Filippo; Bosco, Paolo; Leggio, Gian Marco; Malaguarnera, Michele; Drago, Filippo; Bucolo, Claudio; Salomone, Salvatore

2013-01-01

In recent years, efforts have been directed to develop "disease-modifying" medications to treat Alzheimer's disease (AD), able to halt or slow the pathological process. Because the earlier the treatment starts, the greater is the possibility of efficacy, it is important to set up biomarkers for early diagnosis of functional brain abnormalities, before the clinical manifestation of the overt disease. Up to now, strategies to develop disease-modifying drugs have mainly targeted β amyloid (Aβ, accumulation, aggregation, clearance) and/or tau protein (phosphorylation and aggregation). Active and passive immunotherapy is the main strategy aimed at increasing Aβ clearance. Unfortunately several candidate diseasemodifying drugs have failed in phase III clinical trials conducted in mild to moderate AD. More recently, in phase III studies, bapineuzumab has been discontinued because it did not prove clinically effective (despite its significant effect on biomarkers), while solaneuzumab has been found effective in slowing AD progression. Several methological problems have been recently pointed out to explain the lack of clinical efficacy of novel disease-modifying drug-treatments; moreover, new insights in pathophysiology of AD give the premise to develop novel drug targeting. Clinical trials recently completed and/or still ongoing are discussed in the present review.

Poloxamer surface modified trimethyl chitosan nanoparticles for the effective delivery of methotrexate in osteosarcoma.

PubMed

Li, Shenglong; Xiong, Yuyuan; Zhang, Xiaojing

2017-06-01

The present work is an effort to explore the poloxamer-modified trimethyl chitosan (TMC) encapsulated MTX for osteosarcoma treatment in order to improve the therapeutic efficacy and minimize severe toxicity associated with the clinical usage of MTX. The methotrexate-loaded pluronic-chitosan nanoparticles (MTCN) was nanosized and exhibited a controlled release of drug from the carrier system. The MTCN showed higher accumulation in cell cytoplasm region evident by the high red fluorescence indicating its uptake through energy-dependent endocytosis process. MTCN exhibited the increased cytotoxicity in MG63 cells compared free MTX due to its enhanced cellular uptake. Especially, MTCN exhibited a superior apoptosis effect with bright chromatin condensation and nuclear fragmentation was observed and showed remarkably higher apoptosis (∼48%) compared to that of free drug. The results of this investigation clearly demonstrate that the poloxamer-modified trimethyl chitosan (TMC) seems to have a great potential as a drug carrier in cancer chemotherapy. The present research work offers immense scope for further exploitation of poloxamer-modified trimethyl chitosan (TMC) in future for the development of nanoparticulate drug delivery system for cancer chemotherapy. Copyright © 2017. Published by Elsevier Masson SAS.

21 CFR 178.3520 - Industrial starch-modified.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Industrial starch-modified. 178.3520 Section 178... SANITIZERS Certain Adjuvants and Production Aids § 178.3520 Industrial starch-modified. Industrial starch... provisions of this section. (a) Industrial starch-modified is identified as follows: (1) A food starch...

21 CFR 178.3520 - Industrial starch-modified.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Industrial starch-modified. 178.3520 Section 178... SANITIZERS Certain Adjuvants and Production Aids § 178.3520 Industrial starch-modified. Industrial starch... provisions of this section. (a) Industrial starch-modified is identified as follows: (1) A food starch...

Deconstructing Quinoline-Class Antimalarials to Identify Fundamental Physicochemical Properties of Beta-Hematin Crystal Growth Inhibitors.

PubMed

Olafson, Katy N; Nguyen, Tam Q; Vekilov, Peter G; Rimer, Jeffrey D

2017-10-04

A versatile approach to control crystallization involves the use of modifiers, which are additives that interact with crystal surfaces and alter their growth rates. Elucidating a modifier's binding specificity to anisotropic crystal surfaces is a ubiquitous challenge that is critical to their design. In this study, we select hematin, a byproduct of malaria parasites, as a model system to examine the complementarity of modifiers (i.e., antimalarial drugs) to β-hematin crystal surfaces. We divide two antimalarials, chloroquine and amodiaquine, into segments consisting of a quinoline base, common to both drugs, and side chains that differentiate their modes of action. Using a combination of scanning probe microscopy, bulk crystallization, and analytical techniques, we show that the base and side chain work synergistically to reduce the rate of hematin crystallization. In contrast to general observations that modifiers retain their function upon segmentation, we show that the constituents do not act as modifiers. A systematic study of quinoline isomers and analogues shows how subtle rearrangement and removal of functional moieties can create effective constituents from previously ineffective modifiers, along with tuning their inhibitory modes of action. These findings highlight the importance of specific functional moieties in drug compounds, leading to an improved understanding of modifier-crystal interactions that could prove to be applicable to the design of new antimalarials. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Implications of protein- and Peptide-based nanoparticles as potential vehicles for anticancer drugs.

PubMed

Elzoghby, Ahmed O; Elgohary, Mayada M; Kamel, Nayra M

2015-01-01

Protein-based nanocarriers have gained considerable attention as colloidal carrier systems for the delivery of anticancer drugs. Protein nanocarriers possess various advantages including their low cytotoxicity, abundant renewable sources, high drug-binding capacity, and significant uptake into the targeted tumor cells. Moreover, the unique protein structure offers the possibility of site-specific drug conjugation and tumor targeting using various ligands modifying the surface of protein nanocarriers. In this chapter, we highlight the most important applications of protein nanoparticles (NPs) for the delivery of anticancer drugs. We examine the various techniques that have been utilized for the preparation of anticancer drug-loaded protein NPs. Finally, the current chapter also reviews the major outcomes of the in vitro and in vivo investigations of surface-modified tumor-targeted protein NPs. © 2015 Elsevier Inc. All rights reserved.

Acute and subchronic toxicity analysis of surface modified paclitaxel attached hydroxyapatite and titanium dioxide nanoparticles.

PubMed

Venkatasubbu, Gopinath Devanand; Ramasamy, S; Gaddam, Pramod Reddy; Kumar, J

2015-01-01

Nanoparticles are widely used for targeted drug delivery applications. Surface modification with appropriate polymer and ligands is carried out to target the drug to the affected area. Toxicity analysis is carried out to evaluate the safety of the surface modified nanoparticles. In this study, paclitaxel attached, folic acid functionalized, polyethylene glycol modified hydroxyapatite and titanium dioxide nanoparticles were used for targeted drug delivery system. The toxicological behavior of the system was studied in vivo in rats and mice. Acute and subchronic studies were carried out. Biochemical, hematological, and histopathological analysis was also done. There were no significant alterations in the biochemical parameters at a low dosage. There was a small change in alkaline phosphatase (ALP) level at a high dosage. The results indicate a safe toxicological profile.

Enhanced amperometric detection of metronidazole in drug formulations and urine samples based on chitosan protected tetrasulfonated copper phthalocyanine thin-film modified glassy carbon electrode.

PubMed

Meenakshi, S; Pandian, K; Jayakumari, L S; Inbasekaran, S

2016-02-01

An enhanced electrocatalytic reduction of metronidazole antibiotic drug molecule using chitosan protected tetrasulfonated copper phthalocyanine (Chit/CuTsPc) thin-film modified glassy carbon electrode (GCE) has been developed. An irreversible reduction occurs at -0.47V (vs. Ag/AgCl) using Chit/CuTsPc modified GCE. A maximum peak current value is obtained at pH1 and the electrochemical reduction reaction is a diffusion controlled one. The detection limit is found to be 0.41nM from differential pulse voltammetry (DPV) method. This present investigation method is adopted for electrochemical detection of metronidazole in drug formulation and urine samples by using DPV method. Copyright © 2015 Elsevier B.V. All rights reserved.

Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone

PubMed Central

Ban, Junfeng; Zhang, Yan; Huang, Xin; Deng, Guanghan; Hou, Dongzhi; Chen, Yanzhong; Lu, Zhufen

2017-01-01

Drug delivery carriers can maintain effective therapeutic concentrations in the eye. To this end, we developed lipid nanoparticles (L/NPs) in which the surface was modified with positively charged chitosan, which engaged in hydrogen bonding with the phospholipid membrane. We evaluated in vitro corneal permeability and release characteristics, ocular irritation, and drug dynamics of modified and unmodified L/NPs in aqueous humor. The size of L/NPs was uniform and showed a narrow distribution. Corneal permeation was altered by the presence of chitosan and was dependent on particle size; the apparent permeability coefficient of dexamethasone increased by 2.7 and 1.8 times for chitosan-modified and unmodified L/NPs, respectively. In conclusion, a chitosan-modified system could be a promising method for increasing the ocular bioavailability of unmodified L/NPs by enhancing their retention time and permeation into the cornea. These findings provide a theoretical basis for the development of effective drug delivery systems in the treatment of ocular disease. PMID:28243093

Controversies in Alzheimer's disease drug development.

PubMed

Cummings, Jeffrey L

2008-08-01

Understanding of the pathophysiological basis of Alzheimer's disease (AD) is increasing rapidly and a variety of potential treatment modalities have emerged based on these improved mechanistic insights. The optimal way of proceeding with disease-modifying drug development remains to be clarified and controversies have emerged regarding the definition of Alzheimer's disease, the participation of mild cognitive impairment patients in clinical trials, the definition of disease modification, the potential impediments to satisfaction from patients receiving disease-modifying therapy, the importance of add-on therapy with symptomatic agents, the optimal clinical trial design to demonstrate disease modification, the best means of minimizing time spent in Phase II of drug development, the potential role of adaptive designs in clinical trials, the use of enrichment designs in clinical trials, the role of biomarkers in clinical trials, the treatment of advanced patients with disease-modifying agents, and distinctions between disease modification and disease prevention. The questions surrounding these issues must be resolved as disease-modifying therapies for AD are advanced. These controversies are framed and potential directions towards resolution described.

Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone.

PubMed

Ban, Junfeng; Zhang, Yan; Huang, Xin; Deng, Guanghan; Hou, Dongzhi; Chen, Yanzhong; Lu, Zhufen

2017-01-01

Drug delivery carriers can maintain effective therapeutic concentrations in the eye. To this end, we developed lipid nanoparticles (L/NPs) in which the surface was modified with positively charged chitosan, which engaged in hydrogen bonding with the phospholipid membrane. We evaluated in vitro corneal permeability and release characteristics, ocular irritation, and drug dynamics of modified and unmodified L/NPs in aqueous humor. The size of L/NPs was uniform and showed a narrow distribution. Corneal permeation was altered by the presence of chitosan and was dependent on particle size; the apparent permeability coefficient of dexamethasone increased by 2.7 and 1.8 times for chitosan-modified and unmodified L/NPs, respectively. In conclusion, a chitosan-modified system could be a promising method for increasing the ocular bioavailability of unmodified L/NPs by enhancing their retention time and permeation into the cornea. These findings provide a theoretical basis for the development of effective drug delivery systems in the treatment of ocular disease.

Comprehensive analysis of "bath salts" purchased from California stores and the internet.

PubMed

Schneir, A; Ly, B T; Casagrande, K; Darracq, M; Offerman, S R; Thornton, S; Smollin, C; Vohra, R; Rangun, C; Tomaszewski, C; Gerona, R R

2014-08-01

To analyze the contents of "bath salt" products purchased from California stores and the Internet qualitatively and quantitatively in a comprehensive manner. A convenience sample of "bath salt" products were purchased in person by multiple authors at retail stores in six California cities and over the Internet (U.S. sites only), between August 11, 2011 and December 15, 2011. Liquid chromatography-time-of-flight mass spectrometry was utilized to identify and quantify all substances in the purchased products. Thirty-five "bath salt" products were purchased and analyzed. Prices ranged from $9.95 to 49.99 (U.S. dollars). Most products had a warning against use. The majority (32/35, 91%) had one (n = 15) or multiple cathinones (n = 17) present. Fourteen different cathinones were identified, 3,4-methylenedioxypyrovalerone (MDPV) being the most common. Multiple drugs found including cathinones (buphedrone, ethcathinone, ethylone, MDPBP, and PBP), other designer amines (ethylamphetamine, fluoramphetamine, and 5-IAI), and the antihistamine doxylamine had not been previously identified in U.S. "bath salt" products. Quantification revealed high stimulant content and in some cases dramatic differences in either total cathinone or synthetic stimulant content between products with the same declared weight and even between identically named and outwardly appearing products. Comprehensive analysis of "bath salts" purchased from California stores and the Internet revealed the products to consistently contain cathinones, alone, or in different combinations, sometimes in high quantity. Multiple cathinones and other drugs found had not been previously identified in U.S. "bath salt" products. High total stimulant content in some products and variable qualitative and quantitative composition amongst products were demonstrated.

A Survey of Clinical Features of Allergic Rhinitis in Adults

PubMed Central

Frati, Franco; Dell’Albani, Ilaria; Passalacqua, Giovanni; Bonini, Sergio; Rossi, Oliviero; Senna, Gianenrico; Incorvaia, Cristoforo

2014-01-01

Background Allergic rhinitis (AR) has high prevalence and substantial socio-economic burden. Material/Methods The study included 35 Italian Centers recruiting an overall number of 3383 adult patients with rhinitis (48% males, 52% females, mean age 29.1, range 18–45 years). For each patient, the attending physician had to fill in a standardized questionnaire, covering, in particular, some issues such as the ARIA classification of allergic rhinitis (AR), the results of skin prick test (SPT), the kind of treatment, the response to treatment, and the satisfaction with treatment. Results Out of the 3383 patients with rhinitis, 2788 (82.4%) had AR: 311 (11.5%) had a mild intermittent, 229 (8.8%) a mild persistent, 636 (23.5%) a moderate-severe intermittent, and 1518 (56.1%) a moderate-severe persistent form. The most frequently used drugs were oral antihistamines (77.1%) and topical corticosteroids (60.8%). The response to treatment was judged as excellent in 12.2%, good in 41.3%, fair in 31.2%, poor in 14.5%, and very bad in 0.8% of subjects. The rate of treatment dissatisfaction was significantly higher in patients with moderate-to-severe AR than in patients with mild AR (p<0.0001). Indication to allergen immunotherapy (AIT) was significantly more frequent (p<0.01) in patients with severe AR than with mild AR. Conclusions These findings confirm the appropriateness of ARIA guidelines in classifying the AR patients and the association of severe symptoms with unsuccessful drug treatment. The optimal targeting of patients to be treated with AIT needs to be reassessed. PMID:25366169

A survey of clinical features of allergic rhinitis in adults.

PubMed

Frati, Franco; Dell'Albani, Ilaria; Passalacqua, Giovanni; Bonini, Sergio; Rossi, Oliviero; Senna, Gianenrico; Incorvaia, Cristoforo

2014-11-04

Allergic rhinitis (AR) has high prevalence and substantial socio-economic burden. The study included 35 Italian Centers recruiting an overall number of 3383 adult patients with rhinitis (48% males, 52% females, mean age 29.1, range 18-45 years). For each patient, the attending physician had to fill in a standardized questionnaire, covering, in particular, some issues such as the ARIA classification of allergic rhinitis (AR), the results of skin prick test (SPT), the kind of treatment, the response to treatment, and the satisfaction with treatment. Out of the 3383 patients with rhinitis, 2788 (82.4%) had AR: 311 (11.5%) had a mild intermittent, 229 (8.8%) a mild persistent, 636 (23.5%) a moderate-severe intermittent, and 1518 (56.1%) a moderate-severe persistent form. The most frequently used drugs were oral antihistamines (77.1%) and topical corticosteroids (60.8%). The response to treatment was judged as excellent in 12.2%, good in 41.3%, fair in 31.2%, poor in 14.5%, and very bad in 0.8% of subjects. The rate of treatment dissatisfaction was significantly higher in patients with moderate-to-severe AR than in patients with mild AR (p<0.0001). Indication to allergen immunotherapy (AIT) was significantly more frequent (p<0.01) in patients with severe AR than with mild AR. These findings confirm the appropriateness of ARIA guidelines in classifying the AR patients and the association of severe symptoms with unsuccessful drug treatment. The optimal targeting of patients to be treated with AIT needs to be reassessed.

Demographic and clinical profiles in patients with acute urticaria.

PubMed

Sánchez-Borges, M; Capriles-Hulett, A; Caballero-Fonseca, F

2015-01-01

Urticaria is a common cause for consultation in general and specialised medical practices. There is scarce information on the characteristics of patients suffering acute urticaria in Latin America. To investigate demographic and clinical features of patients with acute urticaria attending two allergy clinics in Caracas, Venezuela. A prospective study of all new patients who consulted during a three-year period because of acute urticaria. Information on age, gender, symptom duration, previous medical history, body distribution of wheals and angio-oedema, laboratory investigations, skin prick tests, and pharmacological treatment, was collected. Patients were classified according to their age as children/adolescents and adults. Two hundred and forty eight patients (177 adults and 71 children) were studied. Acute urticaria was more frequent in middle-aged atopic female patients. Lesions more often involved upper and lower limbs and head, and 31% of patients exhibited generalised urticaria. Laboratory investigations, performed only in selected cases, did not contribute to the final diagnosis. Most frequent subtypes of acute urticaria were spontaneous, dermographic, papular, and drug-induced urticaria. Most patients were treated with non-sedating antihistamines, with increased use of cetirizine and levocetirizine in children, while 5.6% of children and 20.3% of adults required the addition of short courses of systemic corticosteroids. Acute urticaria is a frequent cause of consultation for allergists, affecting more often middle-aged female atopic patients. The use of extensive complementary tests does not seem to be cost-effective for this clinical condition. Spontaneous, dermographic, papular and drug-induced urticaria are the most common subtypes. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

Treating nausea and vomiting in palliative care: a review

PubMed Central

Glare, Paul; Miller, Jeanna; Nikolova, Tanya; Tickoo, Roma

2011-01-01

Nausea and vomiting are portrayed in the specialist palliative care literature as common and distressing symptoms affecting the majority of patients with advanced cancer and other life-limiting illnesses. However, recent surveys indicate that these symptoms may be less common and bothersome than has previously been reported. The standard palliative care approach to the assessment and treatment of nausea and vomiting is based on determining the cause and then relating this back to the “emetic pathway” before prescribing drugs such as dopamine antagonists, antihistamines, and anticholinergic agents which block neurotransmitters at different sites along the pathway. However, the evidence base for the effectiveness of this approach is meager, and may be in part because relevance of the neuropharmacology of the emetic pathway to palliative care patients is limited. Many palliative care patients are over the age of 65 years, making these agents difficult to use. Greater awareness of drug interactions and QTc prolongation are emerging concerns for all age groups. The selective serotonin receptor antagonists are the safest antiemetics, but are not used first-line in many countries because there is very little scientific rationale or clinical evidence to support their use outside the licensed indications. Cannabinoids may have an increasing role. Advances in interventional gastroenterology are increasing the options for nonpharmacological management. Despite these emerging issues, the approach to nausea and vomiting developed within palliative medicine over the past 40 years remains relevant. It advocates careful clinical evaluation of the symptom and the person suffering it, and an understanding of the clinical pharmacology of medicines that are available for palliating them. PMID:21966219

Treatment of systemic mast cell disorders.

PubMed

Worobec, A S

2000-06-01

The heterogeneous nature of disease manifestations in mastocytosis requires the individualization of therapy to each patient's clinical presentation and prognosis. The mainstay of treatment for most categories of mastocytosis are H1 and H2 antihistamines with the addition of corticosteroids for more severe symptoms. This article presents a summary of treatment strategies for indolent and aggressive forms of mastocytosis along with a discussion of future therapeutic directions.

Section V: Conclusions

DTIC Science & Technology

2001-06-01

aeromedical issues. The section concludes with a sample review of a candidate medication, in this case losartan potassium, with a possible approach to...as losartan , Allergic rhinitis is a very common condition appear to hold promise for use in aircrew and generally compatible with military aircrew...evaluating the aeromedical suitability of HI antihistamines for this condition in aircrew losartan led our group to designate losartan as a because of

Comparative Effects of Antihistamines on Aircrew Mission Effectiveness under Sustained Operations

DTIC Science & Technology

1992-06-01

measures consist mainly of process measures. Process measures are measures of activities used to accomplish the mission and produce the final results...They include task completion times and response variability, and information processing rates as they relate to unique task assignment. Performance...contains process measures that assess the Individual contributions of hardware/software and human components to overall system performance. Measures

EAACI/GA(2)LEN/EDF/WAO guideline: management of urticaria.

PubMed

Zuberbier, T; Asero, R; Bindslev-Jensen, C; Walter Canonica, G; Church, M K; Giménez-Arnau, A M; Grattan, C E H; Kapp, A; Maurer, M; Merk, H F; Rogala, B; Saini, S; Sánchez-Borges, M; Schmid-Grendelmeier, P; Schünemann, H; Staubach, P; Vena, G A; Wedi, B

2009-10-01

This guideline, together with its sister guideline on the classification of urticaria (Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Giménez-Arnau AM et al. EAACI/GA(2)LEN/EDF/WAO Guideline: definition, classification and diagnosis of urticaria. Allergy 2009;64: 1417-1426), is the result of a consensus reached during a panel discussion at the Third International Consensus Meeting on Urticaria, Urticaria 2008, a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2)LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). As members of the panel, the authors had prepared their suggestions regarding management of urticaria before the meeting. The draft of the guideline took into account all available evidence in the literature (including Medline and Embase searches and hand searches of abstracts at international allergy congresses in 2004-2008) and was based on the existing consensus reports of the first and the second symposia in 2000 and 2004. These suggestions were then discussed in detail among the panel members and with the over 200 international specialists of the meeting to achieve a consensus using a simple voting system where appropriate. Urticaria has a profound impact on the quality of life and effective treatment is, therefore, required. The recommended first line treatment is new generation, nonsedating H(1)-antihistamines. If standard dosing is not effective, increasing the dosage up to four-fold is recommended. For patients who do not respond to a four-fold increase in dosage of nonsedating H(1)-antihistamines, it is recommended that second-line therapies should be added to the antihistamine treatment. In the choice of second-line treatment, both their costs and risk/benefit profiles are most important to consider. Corticosteroids are not recommended for long-term treatment due to their unavoidable severe adverse effects. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

Bilastine vs. hydroxyzine: occupation of brain histamine H1-receptors evaluated by positron emission tomography in healthy volunteers

PubMed Central

Farré, Magí; Pérez-Mañá, Clara; Papaseit, Esther; Menoyo, Esther; Pérez, Marta; Martin, Soraya; Bullich, Santiago; Rojas, Santiago; Herance, José-Raúl; Trampal, Carlos; Labeaga, Luis; Valiente, Román

2014-01-01

Aim A close correlation exists between positron emission tomography (PET)-determined histamine H1-receptor occupancy (H1RO) and the incidence of sedation. Antihistamines with H1RO <20% are classified as non-sedating. The objective was to compare the H1RO of bilastine, a second generation antihistamine, with that of hydroxyzine. Methods This randomized, double-blind, crossover study used PET imaging with [11C]-doxepin to evaluate H1RO in 12 healthy males (mean age 26.2 years), after single oral administration of bilastine (20 mg), hydroxyzine (25 mg) or placebo. Binding potentials and H1ROs were calculated in five cerebral cortex regions of interest: frontal, occipital, parietal, temporal, insula. Plasma bilastine concentrations, subjective sedation (visual analogue scale), objective psychomotor performance (digital symbol substitution test), physiological variables and safety (adverse events, AEs), were also evaluated. Results The mean binding potential of all five regions of interest (total binding potential) was significantly greater with bilastine than hydroxyzine (mean value 0.26 vs. 0.13, P < 0.01; mean difference and 95% CI −0.130 [−0.155, 0.105]). There was no significant difference between bilastine and placebo. Overall H1RO by bilastine was significantly lower than that by hydroxyzine (mean value −3.92% vs. 53.95%, P < 0.01; mean difference and 95% CI 57.870% [42.664%, 73.075%]). There was no significant linear relationship between individual bilastine plasma concentrations and total binding potential values. No significant between-treatment differences were observed for sedation and psychomotor performance. Twenty-six non-serious AEs were reported. Sleepiness or sedation was not reported with bilastine but appeared in some subjects with hydroxyzine. Conclusions A single oral dose of bilastine 20 mg had minimal H1RO, was not associated with subjective sedation or objective impairment of psychomotor performance and was devoid of treatment-related sedative AEs, thus satisfying relevant subjective, objective and PET criteria as a non-sedating antihistamine. PMID:24833043

Bilastine vs. hydroxyzine: occupation of brain histamine H1 -receptors evaluated by positron emission tomography in healthy volunteers.

PubMed

Farré, Magí; Pérez-Mañá, Clara; Papaseit, Esther; Menoyo, Esther; Pérez, Marta; Martin, Soraya; Bullich, Santiago; Rojas, Santiago; Herance, José-Raúl; Trampal, Carlos; Labeaga, Luis; Valiente, Román

2014-11-01

A close correlation exists between positron emission tomography (PET)-determined histamine H1 -receptor occupancy (H1 RO) and the incidence of sedation. Antihistamines with H1 RO <20% are classified as non-sedating. The objective was to compare the H1 RO of bilastine, a second generation antihistamine, with that of hydroxyzine. This randomized, double-blind, crossover study used PET imaging with [(11) C]-doxepin to evaluate H1 RO in 12 healthy males (mean age 26.2 years), after single oral administration of bilastine (20 mg), hydroxyzine (25 mg) or placebo. Binding potentials and H1 ROs were calculated in five cerebral cortex regions of interest: frontal, occipital, parietal, temporal, insula. Plasma bilastine concentrations, subjective sedation (visual analogue scale), objective psychomotor performance (digital symbol substitution test), physiological variables and safety (adverse events, AEs), were also evaluated. The mean binding potential of all five regions of interest (total binding potential) was significantly greater with bilastine than hydroxyzine (mean value 0.26 vs. 0.13, P < 0.01; mean difference and 95% CI -0.130 [-0.155, 0.105]). There was no significant difference between bilastine and placebo. Overall H1 RO by bilastine was significantly lower than that by hydroxyzine (mean value -3.92% vs. 53.95%, P < 0.01; mean difference and 95% CI 57.870% [42.664%, 73.075%]). There was no significant linear relationship between individual bilastine plasma concentrations and total binding potential values. No significant between-treatment differences were observed for sedation and psychomotor performance. Twenty-six non-serious AEs were reported. Sleepiness or sedation was not reported with bilastine but appeared in some subjects with hydroxyzine. A single oral dose of bilastine 20 mg had minimal H1 RO, was not associated with subjective sedation or objective impairment of psychomotor performance and was devoid of treatment-related sedative AEs, thus satisfying relevant subjective, objective and PET criteria as a non-sedating antihistamine. © 2014 The British Pharmacological Society.

The relationship between birch pollen, air pollution and weather types and their effect on antihistamine purchase in two Swedish cities.

PubMed

Grundström, Maria; Dahl, Åslög; Ou, Tinghai; Chen, Deliang; Pleijel, Håkan

2017-01-01

Exposure to elevated air pollution levels can aggravate pollen allergy symptoms. The aim of this study was to investigate the relationships between airborne birch ( Betula ) pollen, urban air pollutants NO 2 , O 3 and PM 10 and their effects on antihistamine demand in Gothenburg and Malmö, Sweden, 2006-2012. Further, the influence of large-scale weather pattern on pollen-/pollution-related risk, using Lamb weather types (LWTs), was analysed. Daily LWTs were obtained by comparing the atmospheric pressure over a 16-point grid system over southern Sweden (scale ~3000 km). They include two non-directional types, cyclonic (C) and anticyclonic (A) and eight directional types depending on the wind direction (N, NE, E…). Birch pollen levels were exceptionally high under LWTs E and SE in both cities. Furthermore, LWTs with dry and moderately calm meteorological character (A, NE, E, SE) were associated with strongly elevated air pollution (NO 2 and PM 10 ) in Gothenburg. For most weather situations in both cities, simultaneously high birch pollen together with high air pollution had larger over-the-counter (OTC) sales of antihistamines than situations with high birch pollen alone. LWTs NE, E, SE and S had the highest OTC sales in both cities. In Gothenburg, the city with a higher load of both birch pollen and air pollution, the higher OTC sales were especially obvious and indicate an increased effect on allergic symptoms from air pollution. Furthermore, Gothenburg LWTs A, NE, E and SE were associated with high pollen and air pollution levels and thus classified as high-risk weather types. In Malmö, corresponding high-risk LWTs were NE, E, SE and S. Furthermore, occurrence of high pollen and air pollutants as well as OTC sales correlated strongly with vapour pressure deficit and temperature in Gothenburg (much less so in Malmö). This provides evidence that the combination of meteorological properties associated with LWTs can explain high levels of birch pollen and air pollution. Our study shows that LWTs represent a useful tool for integrated daily air quality forecasting/warning.

Older Americans' risk-benefit preferences for modifying the course of Alzheimer disease.

PubMed

Hauber, A Brett; Johnson, F Reed; Fillit, Howard; Mohamed, Ateesha F; Leibman, Christopher; Arrighi, H Michael; Grundman, Michael; Townsend, Raymond J

2009-01-01

Alzheimer disease (AD) is a progressive, ultimately fatal neurodegenerative illness affecting millions of patients, families, and caregivers. Effective disease-modifying therapies for AD are desperately needed, but none currently exist on the market. Thus, accelerating the discovery, development, and approval of new disease-modifying drugs for AD is a high priority for individuals, physicians, and medical decision makers. Potentially disease-modifying drugs likely will have significant therapeutic benefits but also may have treatment-related risks. We quantified older Americans' treatment-related risk tolerance by eliciting their willingness to accept the risk of treatment-related death or permanent severe disability in exchange for modifying the course of AD. A stated-choice survey instrument was administered to 2146 American residents 60 years of age and older. On average, subjects were willing to accept a 1-year risk of treatment-related death or permanent severe disability from stroke of over 30% for a treatment that prevents AD from progressing beyond the mild stage. Thus, most people in this age cohort are willing to accept considerable risks in return for disease-modifying benefits of new AD drugs. These results are consistent with other studies indicating that individuals view AD as a serious, life threatening illness that imposes heavy burdens on both patients and caregivers.

Dosing of antirheumatic drugs in renal disease and dialysis.

PubMed

Swarup, Areena; Sachdeva, Namita; Schumacher, H Ralph

2004-08-01

Many patients with rheumatic diseases have their management complicated by renal problems. Renal failure modifies the metabolism of many drugs, especially by retention. Questions often arise about the effects of renal failure on the handling of drugs commonly used in rheumatology. For which drugs must we be especially concerned about increased toxicity? Patients on chronic dialysis may also need a variety of drugs for rheumatic disease. How are our drugs dialyzed, and which of these can be safety used and how best to use them?Decisions about dosing of rheumatic drugs are often required for the patients with chronic renal insufficiency or on long-term dialysis, although many drugs have not been formally studied in these settings. Patients with renal insufficiency are excluded from most drug trials. Data for some of these drugs have to be extrapolated based on the information available about the pharmacokinetics of the drug.This review addresses dosing of commonly used drugs in rheumatology in patients with chronic renal insufficiency or failure. It is compiled from a MEDLINE search of papers dealing with renal handling of antirheumatic drugs and suggestions for dose adjustments for these drugs. Drugs reviewed include commonly used disease-modifying antirheumatic drugs (DMARDS), drugs used for treatment of gout, commonly used nonsteroidal antnflammatory drugs (NSAIDS) and the newer COX-2 inhibitors.

Needle-free and microneedle drug delivery in children: a case for disease-modifying antirheumatic drugs (DMARDs).

PubMed

Shah, Utpal U; Roberts, Matthew; Orlu Gul, Mine; Tuleu, Catherine; Beresford, Michael W

2011-09-15

Parenteral routes of drug administration have poor acceptability and tolerability in children. Advances in transdermal drug delivery provide a potential alternative for improving drug administration in this patient group. Issues with parenteral delivery in children are highlighted and thus illustrate the scope for the application of needle-free and microneedle technologies. This mini-review discusses the opportunities and challenges for providing disease-modifying antirheumatic drugs (DMARDs) currently prescribed to paediatric rheumatology patients using such technologies. The aim is to raise further awareness of the need for age-appropriate formulations and drug delivery systems and stimulate exploration of these options for DMARDs, and in particular, rapidly emerging biologics on the market. The ability of needle-free and microneedle technologies to deliver monoclonal antibodies and fusion proteins still remains largely untested. Such an understanding is crucial for future drug design opportunities. The bioavailability, safety and tolerance of delivering biologics into the viable epidermis also need to be studied. Copyright © 2011 Elsevier B.V. All rights reserved.

Comedications alter drug-induced liver injury reporting frequency: Data mining in the WHO VigiBase™

PubMed Central

Suzuki, Ayako; Yuen, Nancy A.; Ilic, Katarina; Miller, Richard T.; Reese, Melinda J.; Brown, H. Roger; Ambroso, Jeffrey I.; Falls, J. Gregory; Hunt, Christine M.

2015-01-01

Polypharmacy is common, and may modify mechanisms of drug-induced liver injury. We examined the effect of these drug–drug interactions on liver safety reports of four drugs highly associated with hepatotoxicity. In the WHO VigiBase™, liver event reports were examined for acetaminophen, isoniazid, valproic acid, and amoxicillin/clavulanic acid. Then, we evaluated the liver event reporting frequency of these 4 drugs in the presence of co-reported medications. Each of the 4 primary drugs was reported as having more than 2000 liver events, and co-reported with more than 600 different medications. Overall, the effect of 2275 co-reported drugs (316 drug classes) on the reporting frequency was analyzed. Decreased liver event reporting frequency was associated with 245 drugs/122 drug classes, including anti-TNFα, opioids, and folic acid. Increased liver event reporting frequency was associated with 170 drugs/82 drug classes; in particular, halogenated hydrocarbons, carboxamides, and bile acid sequestrants. After adjusting for age, gender, and other co-reported drug classes, multiple co-reported drug classes were significantly associated with decreased/increased liver event reporting frequency in a drug-specific/unspecific manner. In conclusion, co-reported medications were associated with changes in the liver event reporting frequency of drugs commonly associated with hepatotoxicity, suggesting that comedications may modify drug hepatic safety. PMID:25988394

A Method of Retrospective Computerized System Validation for Drug Manufacturing Software Considering Modifications

NASA Astrophysics Data System (ADS)

Takahashi, Masakazu; Fukue, Yoshinori

This paper proposes a Retrospective Computerized System Validation (RCSV) method for Drug Manufacturing Software (DMSW) that relates to drug production considering software modification. Because DMSW that is used for quality management and facility control affects big impact to quality of drugs, regulatory agency required proofs of adequacy for DMSW's functions and performance based on developed documents and test results. Especially, the work that explains adequacy for previously developed DMSW based on existing documents and operational records is called RCSV. When modifying RCSV conducted DMSW, it was difficult to secure consistency between developed documents and test results for modified DMSW parts and existing documents and operational records for non-modified DMSW parts. This made conducting RCSV difficult. In this paper, we proposed (a) definition of documents architecture, (b) definition of descriptive items and levels in the documents, (c) management of design information using database, (d) exhaustive testing, and (e) integrated RCSV procedure. As a result, we could conduct adequate RCSV securing consistency.

Enhanced cellular transport and drug targeting using dendritic nanostructures

NASA Astrophysics Data System (ADS)

Kannan, R. M.; Kolhe, Parag; Kannan, Sujatha; Lieh-Lai, Mary

2003-03-01

Dendrimers and hyperbranched polymers possess highly branched architectures, with a large number of controllable, tailorable, peripheral' functionalities. Since the surface chemistry of these materials can be modified with relative ease, these materials have tremendous potential in targeted drug delivery. The large density of end groups can also be tailored to create enhanced affinity to targeted cells, and can also encapsulate drugs and deliver them in a controlled manner. We are developing tailor-modified dendritic systems for drug delivery. Synthesis, drug/ligand conjugation, in vitro cellular and in vivo drug delivery, and the targeting efficiency to the cell are being studied systematically using a wide variety of experimental tools. Results on PAMAM dendrimers and polyol hyperbranched polymers suggest that: (1) These materials complex/encapsulate a large number of drug molecules and release them at tailorable rates; (2) The drug-dendrimer complex is transported very rapidly through a A549 lung epithelial cancel cell line, compared to free drug, perhaps by endocytosis. The ability of the drug-dendrimer-ligand complexes to target specific asthma and cancer cells is currently being explored using in vitro and in vivo animal models.

Are baby boomer women unique? The moderating effect of birth cohort on age in substance use patterns during midlife.

PubMed

Sarabia, Stephanie Elias; Martin, James I

2016-01-01

This study examined the relationships of age to use of alcohol, marijuana, and illicit drugs, and misuse of prescription drugs, among midlife women and whether these relationships are modified by birth cohort. Structural Equation Modeling was used to analyze National Survey on Drug Use and Health data, which included 2,035 baby boomer and silent generation cohort women, ages 30 to 55. Midlife women across cohorts reduced alcohol and marijuana use, but not illicit and prescription drug misuse, as they aged. A modifying effect of birth cohort was not supported, but findings did support differential aging effects across substances. Implications are discussed.

Biomedical Properties Study of Modified Chitosan Nanoparticles for Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Saboktakin, Mohammad Reza

2013-09-01

The purpose of this review is to discuss and summarize some of the interesting findings and applications of modified chitosan (MCS) and their derivatives in different areas of drug delivery. This review highlights the important applications of MCS in the design of various novel delivery systems like liposomes, microspheres, microcapsules, and nanoparticles. In addition to their well-known effects on drug solubility and dissolution, bioavailability, safety, and stability, their uses as recipients in drug formulation are also discussed. This review also focuses on various factors influencing inclusion complex formation because an understanding of the same is necessary for proper handling of these versatile materials. Some important considerations in selecting MCS in drug formulation such as their commercial availability, regulatory status, and patent status are also summarized.

Studies on Aspirin Crystals Generated by a Modified Vapor Diffusion Method.

PubMed

Mittal, Amit; Malhotra, Deepak; Jain, Preeti; Kalia, Anupama; Shunmugaperumal, Tamilvanan

2016-08-01

The objectives of the current investigation were (1) to study the influence of selected two different non-solvents (diethylether and dichloromethane) on the drug crystal formation of a model drug, aspirin (ASP-I) by the modified vapor diffusion method and (2) to characterize and compare the generated crystals (ASP-II and ASP-III) using different analytical techniques with that of unprocessed ASP-I. When compared to the classical vapor diffusion method which consumes about 15 days to generate drug crystals, the modified method needs only 12 h to get the same. Fourier transform-infrared spectroscopy (FT-IR) reveals that the internal structures of ASP-II and ASP-III crystals were identical when compared with ASP-I. Although the drug crystals showed a close similarity in X-ray diffraction patterns, the difference in the relative intensities of some of the diffraction peaks (especially at 2θ values of around 7.7 and 15.5) could be attributed to the crystal habit or crystal size modification. Similarly, the differential scanning calorimetry (DSC) study speculates that only the crystal habit modifications might occur but without involving any change in internal structure of the generated drug polymorphic form I. This is further substantiated from the scanning electron microscopy (SEM) pictures that indicated the formation of platy shape for the ASP-II crystals and needle shape for the ASP-III crystals. In addition, the observed slow dissolution of ASP crystals should indicate polymorph form I formation. Thus, the modified vapor diffusion method could routinely be used to screen and legally secure all possible forms of other drug entities too.

In vitro assessment of biopolymer-modified porous silicon microparticles for wound healing applications.

PubMed

Mori, Michela; Almeida, Patrick V; Cola, Michela; Anselmi, Giulia; Mäkilä, Ermei; Correia, Alexandra; Salonen, Jarno; Hirvonen, Jouni; Caramella, Carla; Santos, Hélder A

2014-11-01

The wound healing stands as very complex and dynamic process, aiming the re-establishment of the damaged tissue's integrity and functionality. Thus, there is an emerging need for developing biopolymer-based composites capable of actively promoting cellular proliferation and reconstituting the extracellular matrix. The aims of the present work were to prepare and characterize biopolymer-functionalized porous silicon (PSi) microparticles, resulting in the development of drug delivery microsystems for future applications in wound healing. Thermally hydrocarbonized PSi (THCPSi) microparticles were coated with both chitosan and a mixture of chondroitin sulfate/hyaluronic acid, and subsequently loaded with two antibacterial model drugs, vancomycin and resveratrol. The biopolymer coating, drug loading degree and drug release behavior of the modified PSi microparticles were evaluated in vitro. The results showed that both the biopolymer coating and drug loading of the THCPSi microparticles were successfully achieved. In addition, a sustained release was observed for both the drugs tested. The viability and proliferation profiles of a fibroblast cell line exposed to the modified THCPSi microparticles and the subsequent reactive oxygen species (ROS) production were also evaluated. The cytotoxicity and proliferation results demonstrated less toxicity for the biopolymer-coated THCPSi microparticles at different concentrations and time points comparatively to the uncoated counterparts. The ROS production by the fibroblasts exposed to both uncoated and biopolymer-coated PSi microparticles showed that the modified PSi microparticles did not induce significant ROS production at the concentrations tested. Overall, the biopolymer-based PSi microparticles developed in this study are promising platforms for wound healing applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Uptake Mechanism of ApoE-Modified Nanoparticles on Brain Capillary Endothelial Cells as a Blood-Brain Barrier Model

PubMed Central

Wagner, Sylvia; Zensi, Anja; Wien, Sascha L.; Tschickardt, Sabrina E.; Maier, Wladislaw; Vogel, Tikva; Worek, Franz; Pietrzik, Claus U.; Kreuter, Jörg; von Briesen, Hagen

2012-01-01

Background The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. Methodology/Principal Findings In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor. Conclusions/Significance This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier. PMID:22396775

Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model.

PubMed

Wagner, Sylvia; Zensi, Anja; Wien, Sascha L; Tschickardt, Sabrina E; Maier, Wladislaw; Vogel, Tikva; Worek, Franz; Pietrzik, Claus U; Kreuter, Jörg; von Briesen, Hagen

2012-01-01

The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor. This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier.