First-generation H1-antihistamines Research Articles

Correlation between the expression of the iNOS, caspase-3 and α-SMA genes in the parotid glands of albino rats following the administration of two antihistamines from two different generations.

Several medications, including antihistamines, can alter salivary gland function, causing dry mouth or xerostomia. Antihistamines are commonly used for treating allergic rhinitis. The aim of the present study was to compare and correlate the effects of first-generation vs. second-generation H1-antihistamines on the parotid glands of rats. Twelve adult male albino rats were used; 4 rats served as a control group (group I) and the remaining rats were divided into 2 groups: group II received promethazine hydrochloride; and group III received cetirizine dihydrochloride for 3 weeks. The parotid salivary glands were dissected, and examined histologically and analyzed histomorphometrically for the acinar area percentage. In addition, mRNA gene expression of iNOS, caspase-3 and α-SMA was assessed using quantitative realtime polymerase chain reaction (qRT-PCR). Finally, all the obtained data was statistically analyzed. Histologically, group I showed the typical architecture of the gland. In group II, degenerative changes were noticed, including acinar degeneration and shrinkage with widened connective tissue septa, intracellular vacuolization, and increased inflammatory cell infiltration. In group III, similar histological features were detected as in group II, but to a lesser extent. Histomorphometric results revealed significant differences in the acinar area percentage between various groups. In addition, qRT-PCR results showed a significant increase in iNOS expression in both groups II and III as compared to group I, caspase-3 gene expression was significantly increased in group II, while in group III, it increased non-significantly. Finally, α-SMA gene expression non-significantly decreased in both groups II and III. A significant positive correlation was observed between caspase-3 and iNOS gene expression, while an inverse correlation was noticed between caspase-3 and α-SMA gene expression. The administration of antihistamines resulted in changes in the rat salivary glands, which could be due to the induction of oxidative stress and the resultant apoptotic effect. These changes were suggested to occur mainly through action on muscarinic receptors; yet, action on histamine receptors could not be excluded. However; these effects were less marked with the second-generation antihistamine.

Does diphenhydramine exert a sex-dependent effect on sudomotor responses during exertional heat stress?

Introduction: The first-generation H1 antihistamine diphenhydramine hydrochloride (DPH) is a potent antimuscarinic agent which may compromise sweat output during heat stress. DPH consumption prior to exertional heat stress could further suppress the sweating response in females due to their lower postjunctional cholinergic sensitivity of the sweat glands relative to males. Objective and Hypothesis: The purpose of the present study was to test the hypothesis that DPH would reduce sweating to a greater extent in females relative to males due to differences in cholinergic sensitivity at the sweat gland. Methods: Equal groups (10 per group) of males (24±3 y; 82.6±10.1 kg; 182±5 cm) and females (22±3 y, 67.7±7.8 kg, 171±6 cm) completed two experimental trials presented in a randomized double-blind fashion. Upon arrival to lab, participants consumed either i) a placebo (PLA) pill or ii) 50 mg DPH and then rested in a room maintained at ~29.5°C & 35% RH for 2 hours before conducting a 60-minute treadmill march at a fixed rate of heat production relative to body surface area (~245 W/m2). Rectal temperature (Trec), local sweat rate of the forearm (LSR), and whole body sweat loss (WBSL) were measured. Sex-segregated analysis was conducted for each outcome variable as the difference between PLA and DPH. Results: Baseline Trec did not differ within sex between PLA and DPH (males: -0.10±0.26°C; females: -0.05±0.33°C, P=0.70), however a higher absolute baseline Trec was observed in females compared to males (P=0.006). In comparison to PLA, DPH did not exert a sex-dependent effect on ΔTrec following 60-min of exercise (males: 0.04±0.11°C; females: 0.02±0.37°C, P=0.90). No sex-dependent effect on the onset of sweating was observed between DPH and PLA (males: -0.4±2.6 min; females: 0.6±2.4 min, P=0.34). DPH did not exert a sex-dependent effect on LSR at steady-state (males: 0.03±0.25 mg/cm2/min; females: -0.01±0.21 mg/cm2/min, P=0.71). Lastly, no sex-dependent effect on WBSL was observed between PLA and DPH (males: 14±34 g; females: 6±43 g, P=0.98). Conclusion: Current evidence suggests that sex does not independently modulate the sweating response during exertional heat stress following the consumption of 50 mg of DPH. This research is supported by Dr. Ravanelli’s Research Seed Grant from the Centre for Research in Occupational Safety & Health, and Dr. Ravanelli’s Natural Sciences and Engineering Research Council of Canada Discovery Grant (PIN#2022-05096). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Unraveling the Structure of Meclizine Dihydrochloride with MicroED.

Meclizine (Antivert, Bonine) is a first-generation H1 antihistamine used in the treatment of motion sickness and vertigo. Despite its wide medical use for over 70 years, its crystal structure and the details of protein-drug interactions remained unknown. Single-crystal X-ray diffraction (SC-XRD) is previously unsuccessful for meclizine. Today, microcrystal electron diffraction (MicroED) enables the analysis of nano- or micro-sized crystals that are merely a billionth the size needed for SC-XRD directly from seemingly amorphous powder. In this study, MicroED to determine the 3D crystal structure of meclizine dihydrochloride is used. Two racemic enantiomers (R/S) are found in the unit cell, which is packed as repetitive double layers in the crystal lattice. The packing is made of multiple strong N-H-Cl- hydrogen bonding interactions and weak interactions like C-H-Cl- and pi-stacking. Molecular docking reveals the binding mechanism of meclizine to the histamine H1 receptor. A comparison of the docking complexes between histamine H1 receptor and meclizine or levocetirizine (a second-generation antihistamine) shows the conserved binding sites. This research illustrates the combined use of MicroED and molecular docking in unraveling elusive drug structures and protein-drug interactions for precision drug design and optimization.

Association between First-Generation Antihistamine Use in Children and Cardiac Arrhythmia and Ischemic Heart Disease: A Case-Crossover Study.

Cardiotoxicity from first-generation H1-antihistamines has been debated since the 1990s. However, large-scale studies on this topic in a general pediatric population are lacking. This study aimed to assess the association between first-generation H1-antihistamine use and cardiovascular events in a nationwide pediatric population. In this case-crossover study, the main cohort included children with cardiovascular events from the National Health Insurance Service database (2008-2012 births in Korea) until 2018. The second cohort excluded children with specific birth histories or underlying cardiovascular diseases from the main cohort. Cardiovascular events of interest included cardiac arrhythmia and ischemic heart disease. Odds ratios (ORs) of cardiovascular events were estimated using conditional logistic regression models, comparing first-generation H1-antihistamine use during 0-15 days before cardiovascular events (hazard period) with use during 45-60 and 75-90 days before events (control periods). Among the participants, 1194 (59.9%) were aged 24 months to 6 years, and 1010 (50.7%) were male. Cardiovascular event risk was increased among users of first-generation H1-antihistamines (adjusted OR [aOR], 1.201; 95% confidence interval, 1.13-1.27). Significant odds of cardiovascular events persisted within 10 and 5 days (aOR, 1.25 and 1.25). In the second cohort, the association was comparable with that in the main cohort. Our findings indicate that cardiovascular event risk is increased in children who are administered first-generation H1-antihistamines.

Are antimuscarinic effects common in hydroxyzine overdose? A cohort analysis of antimuscarinic effects in hydroxyzine and diphenhydramine-poisoned patients

Introduction Exposures to hydroxyzine, a first-generation H1 antihistamine, have increased rapidly over the last two decades. Many assumptions about hydroxyzine poisoning are based on other antihistamines, like diphenhydramine. However, the receptor affinities of hydroxazine suggest that there should be fewer antimuscarinic findings than diphenhydramine. Methods This was a cohort study that compared hydroxyzine and diphenhydramine exposures reported to the National Poison Data System between January 1, 2000, and December 31, 2020, and the Toxicologic Investigators Consortium Core Registry between January 1, 2010, and December 31, 2020. The primary outcome was to assess for antimuscarinic findings in hydroxyzine-poisoned patients, using diphenhydramine-poisoned patients as a comparison group. The secondary outcomes were to assess for markers of overall toxicity. Inclusion criteria were single-substance exposures with known outcomes. Exclusion criteria for National Poison Data System exposures were chronic exposures, unintentional exposures, and patients younger than 12 years old. There were no exclusion criteria for exposures reported to the Toxicologic Investigators Consortium Core Registry. Results There were 17,265 hydroxyzine and 102,354 diphenhydramine exposures reported to the National Poison Data System and 134 hydroxyzine and 1,484 diphenhydramine exposures reported to the Toxicologic Investigators Consortium Core Registry that met inclusion criteria. In both datasets, hydroxyzine-poisoned patients had lower rates and relative risk of developing antimuscarinic findings or receiving physostigmine, with the exception of hyperthermia in the Toxicologic Investigators Consortium Core Registry dataset. Coma/central nervous system depression (major), respiratory depression, seizures, ventricular dysrhythmias, intubation, and benzodiazepine administration were less likely in hydroxyzine-poisoned patients, but central nervous system depression (mild) was more likely in exposures reported to the National Poison Data System. The mortality in hydroxyzine-poisoned patients was rare: 0.02% and 0.8% of exposures reported to the National Poison Data System and Toxicologic Investigators Consortium Core Registry, respectively. Discussion The clinical manifestations of hydroxyzine exposures are consistent with the pharmacology of hydroxazine. The clinical effects were consistent across two United States national datasets. Clinicians should not generalize the illness script of diphenhydramine exposures to hydroxyzine exposures. Conclusions Hydroxyzine-poisoned patients were less likely to develop antimuscarinic findings than diphenhydramine-poisoned patients. Hydroxyzine-poisoned patients were more likely to have mild central nervous system depression than an antimuscarinic toxidrome.

Efficacy and Safety of Autologous Serum Therapy in Chronic Spontaneous Urticaria in the Pediatric Population: A Prospective Pilot Study.

Chronic spontaneous urticaria (CSU) in children is mostly spontaneous in onset (57%). Treatment comprises long-term antihistaminic therapy without need for elaborate investigations. A subset of such patients don't respond to conventional treatment and novel therapies to help reduce pill burden is the need of the hour. To determine the efficacy and safety of autologous serum therapy (AST) in pediatric patients with chronic spontaneous urticaria. All pediatric patients, aged between 6-16 years, attended to our OPD from March 2019 to March 2020 were recruited. Clinico-demographic data and baseline investigations of all patients were performed. Two-weekly AST therapy was given for 8 visits with levocetrizine tablet 5mg on an on-demand basis. Urticaria activity score (UAS) sheet was provided to record and return every 2 weeks. Statistical analysis was done using the IBM SPSS 26 software package. Autologous serum skin test (ASST) was positive in 63% patients. Both the ASST positive and ASST negative group showed significant reduction in UAS7 score at week 14 compared to baseline. The reduction in mean UAS7 score was associated with a decreased pill burden and positive response in the patient and physician global assessment scale. No statistically significant difference between the two groups in terms of mean UAS7 reduction was found. This study has explored the efficacy and safety of autologous serum therapy in the pediatric CSU patients. Both ASST positive and ASST negative group respond to AST therapy.

Case series of chronic spontaneous urticaria following COVID-19 vaccines: an unusual skin manifestation.

BackgroundUrticaria following the COVID-19 vaccine was rarely reported and had a short self-limited resolution. However, there has been relatively little literature published on CSU induced by COVID-19 vaccines.PurposeWe describe a case series of patients who experienced CSU after SARS-CoV-2 vaccination.MethodsA retrospective case series of 10 patients referred to the Department of Clinical Pharmacology of the University of Monastir (January 2021–January 2022) and included for evaluation of urticaria after COVID-19 vaccination.ResultsThe median age was 31 years and patients were mostly female. Atopy was presented in 3 patients and urticaria was accompanied by angioedema in 6 patients. The median time interval between vaccination and the onset of urticaria was 28.5 h. The offended dose was the first one in 8 patients. The resolution of the eruption was observed at least 2 months later, despite the regular use of a full dose of antihistamine in nine patients. Polynuclear leucocytosis was identified in 5 patients. Anti-TPOAb was positive in one patient after receiving the BNT162b2 vaccine. Total serum IgE was elevated in 4 patients. Skin tests for the suspected vaccine as well as the vaccine excipient were negative.ConclusionWe add to the medical literature ten new cases of chronic spontaneous urticarial reactions following COVID-19 vaccines uncontrolled with high-dose first-generation H1 antihistamines.

Safety of Cyproheptadine, an Orexigenic Drug. Analysis of the French National Pharmacovigilance Data-Base and Systematic Review.

Objectives: Cyproheptadine is a first-generation H1-antihistamine drug first that was distributed in the 1960s. While its orexigenic effect was observed early, cyproheptadine is not yet authorized for this indication in all countries today. There is an increasing medical interest and demand for the orexigenic effect of cyproheptadine, especially in children with poor appetite. As cyproheptadine might be evaluated in future clinical trials, we wanted to assess its safety profile.Methods: Using the French national pharmacovigilance database, we retrospectively analyzed all pediatric and adult reports of adverse effects of cyproheptadine recorded since its first distribution in France. Next, we performed a systematic review of the literature of cyproheptadine adverse effects.Results: Since 1985, 93 adverse effects were reported in the French pharmacovigilance database (adults 81.7%, children 18.3%); these were mainly neurological symptoms (n = 38, adults 71%, children 28.9%), and hepatic complications (n = 15, adults 86.7%, children 13.3%). In the literature, the most frequent adverse effect reported was drowsiness in adults or children, and five case reports noted liver complications in adults. We estimated the frequency of hepatic adverse effects at 0.27 to 1.4/1000, regardless of age.Conclusion: Cyproheptadine can be considered a safe drug. Mild neurological effects appear to be frequent, and hepatotoxicity is uncommon to rare. Randomized controlled trials are needed to evaluate the safety and efficacy of cyproheptadine before authorization for appetite stimulation, especially in young children as studies at this age are lacking. Possible hepatic complications should be monitored, as very rare cases of liver failure have been reported.

Ефективність антигістамінних препаратів I покоління при лікуванні алергічних захворювань у дітей

У статті викладені сучасні відомості про клінічне застосування, ефективність та безпеку використання представника першого покоління Н1-антигістамінних препаратів — диметиндена малеату. Подана стисла характеристика препарату, вказані основні показники його фармакокінетики та фармакодинаміки. Акцентовано увагу на основних фармакологічних механізмах клінічних ефектів препарату. Проведено аналіз результатів клінічних досліджень із застосуванням диметиндена малеату при алергічних та інфекційних захворюваннях шкіри у дітей. Надані основні фармакологічні властивості та характеристика препарату Фенокіт, який нещодавно з’явився на фармацевтичному ринку України, обґрунтовані основні показання до призначення препарату.

Do Pediatric Emergency Physicians Comply With Guideline Recommendations in Management of Patients With Acute Urticaria?

To determine the level of knowledge and practical preferences of pediatricians regarding acute urticaria (AU) management and to assess the effects of training provided in accordance with the current urticaria guideline recommendations on pediatricians who work in the pediatric emergency department (PED). A theoretical training was provided to pediatricians regarding the diagnosis and treatment of AU in line with current urticaria guideline recommendations. Before the training, pediatricians completed a 10-item questionnaire. This prospective study assesses their treatment approaches in patients admitted to PED because of AU during the 6-month period before and the 1-year period after training. Four hundred seventeen children in the pretraining and 1085 children in the posttraining periods were treated for AU in PED. Forty-eight pediatricians participated in the training. According to their questionnaire responses, 35% of them used only H1 antihistamine (AH) treatment, 50% used second-generation H1 AH (2nd-GAH) as AHs, 75% preferred the oral route of administration, and 85.4% did not administer systemic corticosteroid (sCS) to all patients. Comparing the practice approaches of the pediatricians in the pretraining and posttraining periods, first-generation H1 antihistamine (1st-GAH) preference rate decreased from 68.4% to 30.3% and the sCS preference rate decreased from 58.5% to 25.7%, while the 2nd-GAH preference rate increased from 31.7% to 69.7% (P < 0.001 for all). No treatments were prescribed for 10.8% of patients before the training and 3% after the training during discharge at home (P < 0.05). Comparing the home treatment choices of the pediatricians in the pretraining and posttraining periods, 1st-GAH preference rate decreased from 11.5% to 5%, while the 2nd-GAH preference rate increased from 78.7% to 91.5% (for both parameters, P < 0.001). Practical treatment preferences of pediatricians in the treatment of children with AU differ considerably from both current guideline recommendations and their own theoretical knowledge, and training can enhance pediatricians' compliance with current guideline recommendations.

Symptomatic Dermographism: A Systematic Review of Treatment Options

Symptomatic dermographism (SD), the most common form of chronic inducible urticaria, presents with transient wheals accompanied by itching in response to scratching. Little is known about available treatment options and their efficacy in SD. To systematically review the efficacy of treatment options for patients with SD. Using predefined search terms, we searched for relevant literature published until September 2019. The systematic review process was consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. The 23 studies identified included 15 randomized controlled trials; 22 and 17 assessed treatment responses in patients with SD by provocation/threshold testing and patient/physician clinical assessment, respectively. Thirteen different treatments were investigated in a total of 430 adult patients. The most frequently studied therapy, first-generation H1-antihistamines, showed variable efficacy and significant side effects. In contrast, second-generation H1-antihistamines (2ndAH1), in all studies, were effective and well tolerated. Monotherapy with an H2-antihistamine (AH2) was not effective, whereas adding an AH2 increased the efficacy of treatment with an H1-antihistamine (AH1). SD improved with omalizumab. All other treatments were only investigated in small, unrepeated, and/or uncontrolled studies. There are no studies on updosing of 2ndAH1. The available SD studies are heterogeneous, mostly monocentric, old, small, and unrepeated, pointing to a high need for more and better studies. We suggest that 2ndAH1 should be the first-line treatment. In uncontrolled cases, the combination of AH1 and AH2 may be tried. Even though there is no evidence of its efficacy over standard dosage, updosing of 2ndAH1 may be considered based on the extrapolation of evidence from chronic spontaneous urticaria; omalizumab should be added in recalcitrant patients.

Хронічний свербіж при захворюваннях шкіри в дітей

The article presents modern information on the clinical use and safety of the first-generation H1-antihistamine – dimetindene maleate. Pruritus (itch) mediators act both peripherally (histamine, proteases) and centrally (opioids) and has several mechanisms. Pruritus is the dominant symptom of skin diseases; almost all inflamamatory skin diseases can have associated pruritus. Doctors have focused on the almost one dermatosis with signs of itching – atopic dermatitis. At the same time, the range of diseases, both dermatological and systemic, accompanied by itching, is much wider.

A retrospective analysis omalizumab treatment patterns in patients with chronic spontaneous urticaria: a real-world study in Belgium.

BackgroundChronic spontaneous urticaria (CSU) is characterized by the repeated occurrence of persistent hives and/or angioedema for ≥6 weeks, without specific external stimuli. H1‐antihistamines have long been the standard of care of CSU, but many patients remain uncontrolled even at 4× the approved dose. Add‐on therapy with omalizumab has proven effective in clinical trials, but little is known about omalizumab treatment in Belgium.ObjectiveTo collect real‐world clinical data on omalizumab treatment in adults with CSU in Belgium.MethodsThis was an observational, retrospective chart review of adults with CSU, who initiated omalizumab treatment between August 2014 and December 2016 (maximum 28 months follow‐up).ResultsIn total, 235 patients were included (median time from symptom onset to diagnosis, 5.4 months; median time from diagnosis to commencing omalizumab, 6.7 months). Treatments used before/after commencing omalizumab did not always adhere to guidelines; many patients (26.4%/11.1%) received first‐generation H1‐antihistamines, while 20.4% used omalizumab monotherapy after initiating treatment. The mean interval between omalizumab administrations was 4.8 (SD 1.7) weeks; 67.8% of patients had ≥1 interval prolongation and/or shortening. Mean baseline 7‐day Urticaria Activity Score (UAS7) was 32.0 (SD 6.05); this improved to 12.6 (SD 11.2) after 1 month of omalizumab. About 67.2% of patients reached UAS7 ≤ 6 (well controlled) during the study. A total of 87 patients stopped omalizumab and never restarted before the end of the observation period; the most prevalent reason was remission of symptoms (49.4% of patients), followed by lack of effect (12.6%), lost to follow‐up (6.9%) and adverse events (3.4%). Headache was the most common adverse event (n = 8/82). No anaphylaxis was reported.ConclusionsThis study revealed that patients initiated on omalizumab in Belgium had severe CSU at baseline, and showed substantial improvements after 1 month of treatment. Greater adherence to the prescription of guideline‐recommended medications is needed for the treatment of CSU.

The potential impact of 1st and 2nd generation antihistamines on male fertility

Histamine antagonists are medications used to block the action of histamine at histamine receptors. H1 antagonists are mainly taken to reverse the effects of histamine during allergic reactions. Cetirizine hydrochloride and pheniramine maleate are the most clinically used H1 antihistamines; they have common tolerable side effects such as sedation, dizziness, fatigue, dry mouth, and nausea. The effect of H1 antagonists on male hormones and its outcomes on male fertility are still unclear. The aim of the present study was to evaluate the possible effects of both cetirizine and pheniramine maleate on male fertility. Measurement of prolactin, FSH, and LH serum levels and sperm count during chronic use. Cetirizine hydrochloride significantly increased prolactin levels compared with pheniramine maleate and control groups. Hyperprolactinemia significantly decreased FSH and LH levels and sperm count in the cetirizine hydrochloride treated group. In conclusion, this study reports that the second-generation antihistamine cetirizine hydrochloride has potent and significant effects on male fertility compared with the first-generation H1 antihistamine pheniramine maleate through its changes in prolactin, LH, and FSH levels. These hormonal changes decreased spermatogenesis and sperm count.

THE LEVEL OF THE QUALITY OF EMERGENCY AND INPATIENT MEDICAL CARE FOR CHILDREN WITH ACUTE ALLERGIC PATHOLOGY

The acute allergic condition may carry life-threatening character and requires the provision of the immediate medical assistance, which is governed by approved standards and clinical guidelines on appropriate forms of pathology. There are presented data concerning the routing of patients with allergic forms of pathology through stages from emergency medical assistance, evacuation of the patient till the discharge from the hospital with recommendations for outpatient care, with the purpose of the analysis of correspondence of medical aid in acute allergic pathology to existing algorithms and clinical guidelines at different stages of the management of patients. There was performed an analysis of the data of 1327 children with acute allergic pathology requesting emergency medical assistance. 78% of patients were left in place with recommendations for further referral to specialists, 22% of patients were evacuated to various clinics for specialized medical care (SMC). At the stage of the rendering of SMC 69% of children received corticosteroids in 2014, 66% - in 2015. 60% of children were prescribed first-generation H1-antihistamines in 2014, 63%-in 2015; 25% of children were administered the lytic mixture. Only 4% of children received inhalation therapy. At the stationary stage in 2014, all children with broncho-pulmonary disease and laryngotracheitis received antibiotic therapy, 89% and 59% - in 2015, respectively Conclusion The quality of rendering of medical aid to children with acute allergic pathology at prehospital and hospital stages is not always consistent with clinical recommendations.

Surveillance of First-Generation H1-Antihistamine Use for Older Patients with Dementia in Japan: A Retrospective Cohort Study.

Background This study aimed to investigate the rate of first-generation H1-antihistamines use for older adults with dementia in Japan. Methods The study design was retrospective cohort using claims data between fiscal years 2010 and 2013. Subjects were 75 years or older, diagnosed with dementia, and given H1-antihistamines orally during the study period after being diagnosed with dementia. We investigated the cumulative number of oral H1-antihistamines administered and the relationship between first-generation H1-antihistamine use and each explanatory variable using crude and adjusted odds ratio. Results The cumulative total for use of first-generation H1-antihistamine for older adults with dementia accounted for 32.1% of all antihistamine medication. The majority of first-generation H1-antihistamine prescriptions were indicated for cold treatment. Those with upper respiratory infection or asthma had a significantly positive relationship with first-generation H1-antihistamine use. ConclusionThe study showed that first-generation H1-antihistamine drugs were highly prescribed in older adults with dementia in Japan.

Chronic Urticaria in Special Populations: Children, Pregnancy, Lactation and Elderly People

Chronic urticaria can occur at any age and in both sexes. Regardless of the different populations affected, a stepwise treatment approach is recommended, beginning with non-sedating antihistamines, from licensed doses to a “controlled overdose” up to fourfold, followed by a change to a different antihistamine and/or addition of a leukotriene antagonist if symptoms persist; systemic corticosteroids in short courses (3 to 7 days) can be used for exacerbations. As a third-line therapy in adults, omalizumab is now considered of choice and only in nonresponsive cases to omalizumab cyclosporin or other options should be used. First-generation H1-antihistamines are no longer recommended, either in adults, in children, in pregnant women, or in the elderly because of their high potential to cause sedation and to impair school/work performance and vehicle driving. Among the second-generation H1-antihistamines, most of them have proven efficacy and safety, but there are important concerns for special populations with nearly every medication used in chronic spontaneous urticaria (CSU) treatment.

Are antihistamines effective in children? A review of the evidence

Background and aimsDuring the last decades, much attention has been paid to off-label and unlicensed prescriptions in paediatrics. However, on-label prescribing can also cause health issues. In this paper, the...

HOW SAFE IS ON-LABEL DRUG USE IN PAEDIATRICS? THE CASE OF FIRST GENERATION H1-ANTIHISTAMINES

BackgroundFor obvious reasons, much attention has recently been paid to off-label prescriptions in paediatrics. However, on-label prescribing can cause health issues too: we discuss the case of first generation H1-antihistamines (FGAs). These have been in use for over 70 years, for a variety of indications such as relief of allergic conditions, cough and insomnia.Materials and methodsThe FGAs were listed using their International Nonproprietary Names (INN). For each formulation, the information of the Summary of Product Characteristics issued in five selected European countries (Belgium, France, Germany, the Netherlands and United Kingdom) was collected. This was plotted against the published evidence on efficacy and safety of each FGA.Results16 different FGAs are currently marketed in single-drug oral preparations in the evaluated countries. When investigating each drug separately, a huge variability in labelled indications, licensing age for paediatric use, and availability characteristics in the different countries is observed. Most of the indications are not supported by evidence from published clinical trials.ConclusionBoth health care professionals and consumers generally assume that all approved H1-antihistamines have been shown to be efficacious and safe, but many in this class – in particular those introduced before 1985 – have not been optimally studied. This might explain the inconsistencies in indications and licensing ages of the evaluated drugs in different countries. Moreover, many of the antihistamines are sold over the counter, which may contribute to overuse. Such overuse can be a serious problem, as sedation is a known side effect of all FGAs.

The effect of a first-generation H1-antihistamine on postural control: a preliminary study in healthy volunteers

First-generation H1-antihistamines are known to cause fatigue and drowsiness, due to their poor receptor selectivity and their high penetration rate of the blood-brain barrier. However, little is known about the effects of first-generation H1-antihistamines on postural stability. The purpose of this study was to evaluate the effects of d-chlorpheniramine on postural stability using posturography with and without foam rubber. A double-blind study with three parallel groups was conducted. Twenty-seven healthy young volunteers (mean age 21.9years) were recruited and orally administered d-chlorpheniramine, 2 or 4mg, or placebo. Postural sway was measured every hour up to 8h after administration. Two-legged stance tasks were performed by each subject in four conditions: eyes open or eyes closed and with or without foam rubber. Inter-group comparisons showed that the group receiving 4-mg d-chlorpheniramine showed significantly larger sway in the eyes open with foam rubber condition (visual and vestibular information available, somatosensory information reduced). Inter-subject analysis in the 4-mg d-chlorpheniramine group showed that the effect of d-chlorpheniramine on postural control was variable. Our results suggest that among the three main sensory systems responsible for postural control (visual, vestibular, and somatosensory), d-chlorpheniramine may have a larger effect on the visual and/or vestibular systems in susceptible individuals.