Generation Antihistamines Research Articles

The Aeromedical Management of Allergic Rhinitis.

Allergic rhinitis is a prevalent condition warranting special aeromedical consideration due to its potential for acute and painful manifestations involving the middle ear or paranasal sinuses during rapid barometric pressure changes. Although second generation antihistamines and intranasal steroids are safe and effective treatments for this common condition, aeromedical management varies. An aeromedical policy review of 14 public access civil and military data repositories was undertaken. Policy within a convenience sample of nine countries (Australia, Canada, Croatia, France, New Zealand, Norway, Sweden, United Kingdom, and United States) was further ascertained through subject matter expert consultation. A convenience sample of recent primary care review articles and ENT guidelines were reviewed in order to substantiate the evidence basis for aeromedical practices. Policies range from disqualification of flight applicants with any history of allergic rhinitis to the authorization of short-term, select undeclared medication use for the management of mild symptoms, with military authorities applying a more conservative approach. A range of intranasal and oral therapies are approved and requirements for waiver vary across most authorities. Variation in practices must be considered when managing flight crews as part of military coalition peacetime and combat operations, as well as for international civil aviation missions conducted in support of natural disaster relief, rescue, and other stability efforts. Standardization of approved therapies for allergic rhinitis could be a useful starting point for the harmonization of aeromedical global policies in the future. Beneficial national specific policy updates may be undertaken on the basis of international experience.Powell-Dunford N, Reese C, Bushby A, Munkeby BH, Coste S, Pezer VL, Rosenkvist L. The aeromedical management of allergic rhinitis. Aerosp Med Hum Perform. 2018; 89(5):453-463.

The treatment outcomes and dose de‐escalation of desloratadine up‐dosing in chronic spontaneous urticaria

An increase in dosages up to fourfold of second generation antihistamines is recommended for recalcitrant chronic spontaneous urticaria (CSU). No regimen guidelines about dose de-escalation, however, are mentioned once the disease is controlled. To demonstrate the treatment outcomes and dose reduction in desloratadine assessed using the urticarial activity score over 7 consecutive days. Medical records of all patients with CSU treated with desloratadine were collected retrospectively during a period from January 2010 to December 2013. Sixty-seven (94.4%) patients had remission of the disease with variable doses of desloratadine. The patients who had CSU concomitant with antithyroid antibodies or high erythrocyte sedimentation rates had a greater tendency not to respond to the standard dose. Once the disease was completely controlled, 67 patients finished the treatment, but 63 (94%) patients had recurrent symptoms. Sixty-three patients took the same dose that induced the response for a further 4 weeks before stopping or reducing the dose, 41/63 (65.1%), however developed urticaria again. Forty-one patients took the same dose for a further 8 weeks; only 2/41 (4.9%) patients developed the rash again. The mean follow-up period after the disease was controlled was 7.5 months. Most patients need higher than the standard doses to obtain remission. Once the disease is completely controlled, however, maintenance of the same dosage for at least 8 weeks before dose reduction is suggested in order to avoid recurrence of the symptoms.

Management of chronic spontaneous urticaria: a worldwide perspective

Background The approaches to the diagnosis and treatment of chronic spontaneous urticaria (CSU) differ in various parts of the world. We sought to determine the adherence to international and national urticaria guidelines as well as the motives to deviate from the guidelines among physicians worldwide.Methods A web-based questionnaire was created and launched via e-mail by the World Allergy Organization (WAO) to representatives of all WAO Member Societies, the members of the American Academy of Allergy, Asthma & Immunology (AAAAI) and the members of the WAO Junior Members Group (JMG), regardless of the specialty, affiliation, or nationality in March 2017.Results We received 1140 completed surveys from participating physicians from 99 countries. Virtually all participants (96%) were aware of at least one urticaria guideline and reported that they follow a guideline. However, one in five physicians who follow a guideline (22%) reported to deviate from it. Reliance on own clinical experience is the most frequent reason for deviation from guidelines or not following them (44%). Young (< 40 years) and less experienced physicians more often follow a guideline and less often deviate than older and experienced ones. Physicians who follow a urticaria guideline showed higher rates of routinely ordering a complete blood count, the erythrocyte sedimentation rate, C-reactive protein, anti-thyroid antibodies, and thyroid-stimulating hormone and of performing the autologous serum skin test as compared to those who do not. Physicians who follow a urticaria guideline showed higher rates of using second generation antihistamines as their first-line treatment of CSU (p = 0.001) and more frequently observed higher efficacy of these drugs (or had more confidence that it would work, p < 0.019) as compared to those who do not follow the guidelines.Conclusions Physicians’ characteristics (e.g. age, clinical experience, and specialty) and country specifics and regional features (e.g. availability of drugs for CSU treatment) importantly influence adherence to urticaria guidelines and CSU patient care and should be addressed in more detail in future research.

Randomized Controlled Study Comparing the Efficacy and Tolerance of Bepotastine, a New 2nd Generation Antihistamine, to Fexofenadine, in Symptomatic Relief of Patients with Pruritic Cutaneous Disorders

Randomized Controlled Study Comparing the Efficacy and Tolerance of Bepotastine, a New 2nd Generation Antihistamine, to Fexofenadine, in Symptomatic Relief of Patients with Pruritic Cutaneous Disorders

Stability Indicating HPLC Method Using Core Shell Stationary Phase for the Determination of Related Substances in Levocetirizine Dihydrochloride Oral Solution

Abstract: Rationale: Levocetirizine (LCZ) is a new generation antihistamine drug used for the allergic symptoms resulting from various diseases. The present research work focuses on the development of a simple and precise HPLC method for the effective separation and quantitative determination of LCZ and its impurities. Experimental: Eight potential related impurities of LCZ were separated and identified in the bulk drug as well as oral solution dosage form. The separation was achieved on a core shell stationary phase Kinetex bipheyl (250, 4.6×5 μm) column with mobile phase of sodium perchlorate in water and acetonitrile in a gradient elution. Results:The results were monitored and analytes were quantified at 230 nm. The method was validated as per ICH guidelines for specificity, linearity, precision, accuracy and robustness. The proposed method finds its application in the routine analysis of LCZ in bulk drug and various dosage forms. Key words: HPLC, Core shell, Related Substances, Levocetirizine dihydrochloride.

Subcutaneous infiltration of doxylamine on cutaneous analgesia in rats.

We aimed to evaluate the effect of doxylamine, a first generation antihistamine, as a local analgesic agent by comparing its effect to bupivacaine. After blocking the cutaneous trunci muscle reflex (CTMR) by subcutaneous injection of doxylamine, we assessed doxylamine's cutaneous analgesic effect in rats. The dose-related effect and duration of doxylamine on infiltrative cutaneous analgesia were compared with that of bupivacaine. We demonstrated that doxylamine, as well as the local anesthetic bupivacaine produced the cutaneous analgesic effects in a dose-related fashion. At the equipotent dose (50% effective doses (ED50)), the relative potency was bupivacaine (0.41 (0.36-0.48) mmol)> doxylamine (7.39 (6.91-7.91)mmol) (p<0.01). On an equipotent basis (ED25, ED50 and ED75), subcutaneous doxylamine resulted in greater duration of action (p<0.01) than bupivacaine at producing cutaneous analgesia. The result of this experiment indicated that doxylamine has the local anesthetic property less potent than bupivacaine, but its nociceptive block duration is longer than that of bupivacaine at an equianalgesic dose.

FEATURES OF THERAPY WITH ANTIHISTAMINES IN PATIENTS WITH CHRONIC URTICARIA

This article is devoted to the role of the second generation antihistamines in the treatment of chronic urticaria. The features of the regimen for the use of the second generation antihistamines in this disease are highlighted. Particular attention is paid to the new representative of this group of drugs - bilastin. High efficacy and safety of the drug in patients with chronic urticaria is highlighted.

THE ROLE OF MODERN ANTIHISTAMINES IN THE TREATMENT OF ALLERGIC DISEASES

Allergic rhinitis and urticaria - are common diseases which influence on the quality of life of patients reducing day activity and educability. The second generation of antihistamines are the first choice in the treatment of these diseases. At Russian pharmaceutical market a few dozens of different preparations of this group are available. Most of them are generic forms. The purpose of this article is to show the place of modern antihistamines in allergic rhinitis and urticaria therapy and to find out the best equivalent of generic antihistamine drug in comparison with the original one.

Achievments of control of seasonal allergic rhinitis symptoms: the results of open, randomized comparative study of second generation antihistamines

Seasonal allergic rhinitis (SAR) is one of the most common allergic diseases. The first choice for control of SAR symptoms is the second-generation antihistamines (AHP-II). The aim of this study was to evaluate the comparative efficacy of ebastine 20 mg/day, cetirizine 10 mg/day, and loratadine 10 mg/day in adult patients with mild symptoms of SAR due to pollen grass allergy. 30 patients aged 18 to 65 years who received treatment for 14 days took part in the study. The duration of the study for one patient varied from 25 to 28 days. As a result, the efficiency of all three AHP II in the control of mild symptoms of SAR was demonstrated. However, the analysis of the scales (TNSS and TNNSS) after the end of the 14-day treatment period revealed that compared to patients treated with loratadine and cetirizine (TNSS scale (p=0,0303), TNNSS (p=0,0091) the best results were observed in the group of patients taking ebastine. Moreover, patients who received the ebastine experienced a statistically insignificant but steady tendency to decrease the level of eosinophilic cationic protein (ECP) in nasal flushing (-37,9% of the baseline values), in contrast to loratadine and cetirizine. All drugs showed a high safety profile. To conclude, the investigated AHPs -II are effective and safe in control of mild symptoms of SAR in adult patients, though the rate of onset of the effect and its level for nasal and non nasal symptoms was significantly higher in patients receiving ebastine 20 mg compared to cetirizine 10 mg and loratadine 10 mg.

Pilots using selective serotonin reuptake inhibitors compared to other fatally injured pilots

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.

FEATURES OF PRESCRIBING ANTIHISTAMINES IN PEDIATRIC PRACTICE

Objective of the Review: Illustrate the use of antihistamines in the treatment of allergic diseases in children.Key Points: Due to the increasing frequency of occurrence of allergic diseases in the population, including among children, the questions of approaches to therapy and the choice of effective and safe drugs acquire particular urgency. Today the usual drugs of choice are antihistamines of the second generation. Their efficacy was proven over the years, and a large amount of data ontheir use has been accumulated. They have firmly occupied their niche in the pharmacotherapy of allergic diseases. And yet antihistamines of the first generation still find their use in certain clinical situations in pediatrics.Conclusion: This article is devoted to the review of the first generation of antihistamines and their use in pediatric practice.

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

Fexofenadine, a potent antagonist to human histamine 1 (H1) 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 H1 receptor, the similar studies on non-human pet H1 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 H1 receptors were built based on the crystal structure of human H1 receptor bound to antagonist doxepin (PDB 3RZE) and fexofenadine was subsequently docked to human, dog and cat H1 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 H1 related allergic conditions of dog and cat. Nonetheless, subtle systemic differences among human, dog and cat H1 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.

Chlorpheniramine and escitalopram: Similar antidepressant and nitric oxide lowering roles in a mouse model of anxiety.

There is a crosstalk between mood disorders and oxidative stress. Chlorpheniramine (CPA), a first generation antihistamine, is hypothesized to have an anxiolytic role at high doses; however, its antidepressant and antioxidant roles have not previously been investigated. The aim of the current study was to evaluate the antidepressant and anxiolytic effects of CPA treatment in association with nitric oxide (NO) and super oxide dismutase (SOD) activity in a mouse model of anxiety. BALB/c mice were divided into unstressed (naïve), control, and CPA- (0.5 mg/kg) and escitalopram- (ESC; 10 mg/kg) treated groups for 3 weeks. Subsequently, they were immobilized for 6 h and subjected to behavioural paradigms as follows: The open field test, the elevated plus maze (EPM) and the forced swim test to investigate motor function, anxiety and depression, respectively. The mice were sacrificed and serum was obtained to detect NO and SOD activity. Compared with the control group, the CPA-treated group demonstrated an antidepressant effect similar to that of the ESC-treated group. In addition, CPA prevented stress-induced NO without affecting SOD activity. CPA did not improve anxiety-like behaviour in the EPM, nor did it improve stress-induced locomotion and rearing, as demonstrated by the OFT. Thus, to the best of our knowledge, this is the first study to evaluate the antidepressant role of CPA in association with NO metabolism. However, further studies are required to elucidate the underlying mechanism.

Study of embryotoxic effects of intranasally administred desloratadine on laboratory animals.

The study was conducted to detect possible changes in embryogenesis and negative effects of third generation antihistamine – desloratadine – after intranasal administration of 1.3 mg/m 3 and 13.0 mg/m 3 of the substance to laboratory animals during their prenatal period. In these circumstances, desloratadine does not cause any significant changes of embryogenesis parameters . Macroscopic examination of the fetus and placenta in animals of experimental groups did not reveal any pathology or physiological deviations from the norm. 13.0 mg/m 3 concentration of the drug caused a decrease in the weight of embryos in comparison with control group of animals and physiological data , despite a well developed, without visible pat h ology, placenta. This neces ­ sitates a n in-depth study o f possible teratogenic effects of intranasally administred desloratadine to laboratory animals.

General Aviation Pilots Over 70 Years Old.

Currently it is not unusual for general aviation pilots in the United States to continue to fly beyond the age of 70, even into their 80s and 90s. Pilots have regular examinations according to protocols which do not specify special or additional requirements for pilots over 70 yr of age. Additionally, the third class medical reforms passed by the U.S. Senate on 15 July 2016 could potentially result in even less stringent medical certification requirements for general aviation pilots. Accident rates, medical parameters, autopsy findings, and toxicological findings from the U.S. National Transportation Safety Board (NTSB) general aviation (GA) accident database were analyzed to assess potential risk factors with accident outcomes. During 2003-2012, there were 114 (113 men, 1 woman) general aviation fatal accidents involving pilots ages 70 to 92 yr. A combination of 3 or more drugs were found in 13 (13%) of deceased pilots. The most frequent drugs were first generation antihistamines and antidepressants represented the next highest proportion of possible performance-affecting medications. This study indicates that there are critical medical factors that may contribute to fatal accidents among elderly pilots. Polypharmacy use should be taken into consideration, especially during periodic health examinations and fatal aviation investigations involving elderly pilots.Vuorio A, Asmayawati S, Budowle B, Griffiths R, Strandberg T, Kuoppala J, Sajantila A. General aviation pilots over 70 years old. Aerosp Med Hum Perform. 2017; 88(2):142-145.

Knowledge and management of chronic spontaneous urticaria in Latin America: a cross-sectional study in Ecuador

Background The current EAACI/GA2LEN/EDF/WAO guideline for urticaria provide specific recommendations for the diagnostic workup and treatment of patients with chronic spontaneous urticaria (CsU). This study explored if physicians in Ecuador know these recommendations and implement them in their actual clinical practice for CsU.Methods We investigated physicians who treat CsU patients in a cross-sectional study using a standardized questionnaire. Descriptive statistics were employed, adjusted logistic regression was performed to assess the link of guideline knowledge and use of therapy.Results Seven hundred forty surveys were collected and analyzed. The mean age of physicians was 42.3 (±12.5) years. Most of the participants (65.1%) were general physicians (GP), 13.7% were pediatricians, 11.0% internists, 6.8% dermatologists or allergists (D/A). Only 18.8% knew the EAACI/GA2LEN/EDF/WAO guideline. 44.5% of GPs searched for CsU etiology in contrast to 90% of D/A. Most common diagnostic test was total serum IgE (83.5%). Most common first line symptomatic treatment was oral corticoids (46.3%), followed by second generation antihistamines (sgAHs, 36.8%). A/D prescribed more sgAHs (regular doses) (74.1 vs 28.6% of GP) (p < 0.05). Experience with omalizumab was reported only by 3.5%, of physicians, and higher rates among who were familiar with the guideline.Conclusion This study shows that the knowledge of guideline recommendations in physicians who treat urticaria patients in Ecuador is low. The diagnostic workup and treatment of CsU patients are largely not in line with guideline recommendations in real life practice settings. We were able to compare results between German and Ecuadorian physicians and found that Ecuadorian physicians have lower awareness of the current guideline (33 vs 18%). Only one-third of physicians reported using regular doses of sgAHs as the first line treatment. Also, only 12.9% of physicians use sgAHs in higher doses and physicians still use fgAHs, particularly pediatricians (42.9%). Our results suggest that disparities in knowledge between physicians from different countries could influence the management of CsU. Knowledge of the guidelines is linked to better choices of treatments. Awareness of guidelines needs to be promoted for better management of chronic urticaria.

Trends in potentially inappropriate medication prescribing to nursing home patients: comparison of three cross-sectional studies.

The aim of this study was to examine trends in potentially inappropriate medication (PIM) prescribing in Norwegian nursing homes. Patients aged ≥70 years were included from three cross-sectional studies conducted in 1997, 2005 and 2011. PIMs were analyzed according to the Norwegian General Practice-Nursing Home criteria (NORGEP-NH), use of single substances to avoid, combinations to avoid, and deprescribing items. Associations between sample and use of PIMs were examined by logistic regression, adjusted for age, gender, and ward. We established Pearsons r for correlations between numbers of drugs and PIMs. Altogether, 4373 patients (mean age 85.7 years, 73.5% women) were included. The mean overall number of drugs per patient increased from 4.7 in 1997 to 6.9 in 2011 (p < 0.001). Use of any single substances to avoid increased from 36.8% in 1997 to 39.5% in 2011 (p = 0.002), use of any combinations to avoid from 16.3% to 27.0% (p < 0.001), and use of any deprescribing items from 46.0% to 55.3% (p < 0.001). Use of codeine-analgesics, nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, long-acting benzodiazepines, and first generation antihistamines decreased significantly, while use of short-acting benzodiazepines, z-hypnotics, statins, and anti-dementia drugs increased significantly. A moderate strong correlation was detected between number of drugs and the three above-mentioned PIM categories, r = 0.34, r = 0.43, r = 0.37, respectively (all p < 0.001). Although several PIMs were less commonly prescribed in recent years, increased overall use of PIMs may suggests worsening of prescribing quality for nursing home patients in Norway. Copyright © 2016 John Wiley & Sons, Ltd.

Pharmacokinetics, Safety and Cognitive Function Profile of Rupatadine 10, 20 and 40 mg in Healthy Japanese Subjects: A Randomised Placebo-Controlled Trial.

IntroductionRupatadine is a marketed second generation antihistamine, with anti-PAF activity, indicated for symptomatic treatment of allergic rhinitis and urticaria. This study was conducted to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of rupatadine in healthy Japanese subjects after single and multiple oral doses.MethodsIn this randomised, double-blind, placebo-controlled study, 27 male and female healthy Japanese subjects were administered single and multiple escalating rupatadine dose of 10, 20 and 40 mg or placebo. Blood samples were collected at different time points for PK measurements and subjects were assessed for safety and tolerability. The effect of rupatadine on cognitive functioning was evaluated by means of computerized cognitive tests: rapid visual information processing (RVP), reaction time (RT), spatial working memory (SWM) and visual analogue scales (VAS).ResultsExposure to rupatadine as measured by Cmax and AUC was found to increase in a dose dependent manner over the dose range of 10–40 mg for both single and multiple dose administration. The safety assessments showed that all treatment related side effects were of mild intensity and there were no serious adverse events (SAEs) or withdrawals due to treatment–emergent adverse events (TEAEs) in this study. The therapeutic dose of rupatadine did not show any CNS impairment in any of the cognitive tests.ConclusionsThis study demonstrated that rupatadine is safe and well tolerated by Japanese healthy subjects. The PK-PD profile confirmed previous experience with rupatadine.

Recent cardiac ion channel data helped to better understand the QT prolongation/Torsades de Pointes risk of hydroxyzine (Atarax®), a first generation antihistamine

Recent cardiac ion channel data helped to better understand the QT prolongation/Torsades de Pointes risk of hydroxyzine (Atarax®), a first generation antihistamine

Cognitive Performance Effects of Bilastine 20 mg During 6 Hours at 8000 ft Cabin Altitude.

Bilastine is a new oral, second generation antihistamine used in the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. It is considered a nonsedating antihistamine and might be recommended for use in pilots, pending research on the effects on flying-related performance under hypobaric conditions that prevail in an airliner. We assessed the effects of a single dose of bilastine 20 mg on alertness and complex task performance of healthy volunteers in a hypobaric chamber at 75.2 kPa (8000 ft/2438 m cabin altitude). In a randomized, double-blind, crossover study, 24 volunteers received a single dose of bilastine 20 mg, hydroxyzine 50 mg (active control), and placebo. Using the Vigilance and Tracking Task, Multi-Attribute Task Battery, and Stanford Sleepiness Scale, assessments were made before and up to 6 h after intake of the study medication. Bilastine 20 mg had no impairing effects on sleepiness levels, vigilance, or complex task performance for up to 6 h post-dose. Hydroxyzine 50 mg (active control) was associated with significant sleepiness and impaired performance across this time period, confirming the sensitivity of the tests. Bilastine 20 mg did not cause sleepiness or impaired performance on tasks related to flying. It is anticipated that a single dose of bilastine 20 mg will not affect flying performance. Bilastine may provide a safe therapeutic alternative for pilots suffering from allergic rhinitis or urticaria. Our findings might also have implications for the treatment of allergic disorders of personnel involved in other safety-sensitive jobs. Valk PJL, Simons R, Jetten AM, Valiente R, Labeaga L. Cognitive performance effects of bilastine 20 mg during 6 hours at 8000 ft cabin altitude. Aerosp Med Hum Perform. 2016; 87(7):622-627.