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1.
J Allergy Clin Immunol ; 154(2): 340-354, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38685482

ABSTRACT

BACKGROUND: There is insufficient systematized evidence on the effectiveness of individual intranasal medications in allergic rhinitis (AR). OBJECTIVES: We sought to perform a systematic review to compare the efficacy of individual intranasal corticosteroids and antihistamines against placebo in improving the nasal and ocular symptoms and the rhinoconjunctivitis-related quality of life of patients with perennial or seasonal AR. METHODS: The investigators searched 4 electronic bibliographic databases and 3 clinical trials databases for randomized controlled trials (1) assessing adult patients with seasonal or perennial AR and (2) comparing the use of intranasal corticosteroids or antihistamines versus placebo. Assessed outcomes included the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. The investigators performed random-effects meta-analyses of mean differences for each medication and outcome. The investigators assessed evidence certainty using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS: This review included 151 primary studies, most of which assessed patients with seasonal AR and displayed unclear or high risk of bias. Both in perennial and seasonal AR, most assessed treatments were more effective than placebo. In seasonal AR, azelastine-fluticasone, fluticasone furoate, and fluticasone propionate were the medications with the highest probability of resulting in moderate or large improvements in the Total Nasal Symptom Score and Rhinoconjunctivitis Quality-of-Life Questionnaire. Azelastine-fluticasone displayed the highest probability of resulting in moderate or large improvements of Total Ocular Symptom Score. Overall, evidence certainty was considered "high" in 6 of 46 analyses, "moderate" in 23 of 46 analyses, and "low"/"very low" in 17 of 46 analyses. CONCLUSIONS: Most intranasal medications are effective in improving rhinitis symptoms and quality of life. However, there are relevant differences in the associated evidence certainty.


Subject(s)
Administration, Intranasal , Adrenal Cortex Hormones , Histamine Antagonists , Quality of Life , Rhinitis, Allergic , Humans , Histamine Antagonists/therapeutic use , Histamine Antagonists/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Rhinitis, Allergic/drug therapy , Rhinitis, Allergic, Seasonal/drug therapy , Randomized Controlled Trials as Topic , Treatment Outcome , Anti-Allergic Agents/therapeutic use , Anti-Allergic Agents/administration & dosage , Rhinitis, Allergic, Perennial/drug therapy
2.
J Allergy Clin Immunol ; 154(1): 184-194, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38431226

ABSTRACT

BACKGROUND: Chronic spontaneous urticaria (CSU) is a chronic inflammatory disease characterized by recurrent pruritic wheals (hives) and/or angioedema. Patients with CSU could remain symptomatic despite standard-of-care H1 antihistamines (H1-AH) or anti-IgE (omalizumab) treatment. Dupilumab blocks IL-4/IL-13 signaling and is approved for multiple type 2/atopic indications. OBJECTIVE: We conducted two phase 3, randomized, placebo-controlled, double-blind trials comparing dupilumab with placebo in patients with symptomatic CSU despite H1-AH. METHODS: In LIBERTY-CSU CUPID Study A, patients were omalizumab-naive (n = 138, aged ≥6 years). In Study B, patients were omalizumab-intolerant/incomplete responders (n = 108, aged ≥12 years). The primary end point was either change from baseline over 7 days in the Urticaria Activity Score (UAS7) or Itch Severity Score (ISS7) at week 24, with the other as a key secondary end point, depending on regional regulatory requirements. Studies were pooled for safety assessment. RESULTS: In Study A, UAS7 and ISS7 improved with dupilumab versus placebo (difference -8.5 [95% CI, -13.2 to -3.9; P = .0003] and -4.2 [95% CI, -6.6 to -1.8; P = .0005]). In Study B, tested at α = 0.043 after interim analysis, UAS7 improved (difference -5.8 [95% CI, -11.4 to -0.3; P = .0390]), with a numerical trend in ISS7 (difference -2.9 [95% CI, -5.7 to -0.07; nominal P = .0449, not significant]). Pooled safety data were consistent between dupilumab and placebo and with the known dupilumab safety profile. CONCLUSIONS: Dupilumab reduced urticaria activity by reducing itch and hives severity in omalizumab-naive patients with CSU uncontrolled with H1-AH. Although the primary end point for Study B was not met, dupilumab effects were small in patients who were omalizumab-intolerant/incomplete responders.


Subject(s)
Antibodies, Monoclonal, Humanized , Chronic Urticaria , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Adult , Female , Middle Aged , Chronic Urticaria/drug therapy , Male , Double-Blind Method , Adolescent , Omalizumab/therapeutic use , Omalizumab/adverse effects , Young Adult , Treatment Outcome , Aged , Child , Pruritus/drug therapy , Anti-Allergic Agents/therapeutic use
3.
Exp Dermatol ; 33(8): e15168, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39175304

ABSTRACT

In a double-blind, randomized controlled trial, we investigated the effectiveness of adding antiplatelet drugs to up-dosing antihistamines for the treatment of chronic spontaneous urticaria (CSU) in patients with elevated D-dimer levels who had an inadequate response to conventional antihistamine doses. Twenty patients with Urticaria Activity Score over 7 days (UAS7) ≥16 and D-dimer >500 ng/mL were randomized to receive either antiplatelet therapy (cilostazol 150 mg/day + dipyridamole 50 mg/day) with antihistamine (desloratadine 20 mg/day) or antihistamine alone for 4 weeks. The antiplatelet group demonstrated a greater decrease in UAS7 compared to the control group (28.10 to 8.90 vs. 22.90 to 16.40, p < 0.001 vs. p = 0.054). Both groups experienced improved quality of life (DLQI), but the improvement was greater in the antiplatelet group (p = 0.046). D-dimer levels decreased only in the antiplatelet group (1133.67 ng/mL to 581.89 ng/mL, p = 0.013) with no significant change observed in the control group. This suggests that combining dipyridamole and cilostazol with up-dosing antihistamines may be more effective for CSU patients with high D-dimer levels compared to up-dosing antihistamines alone. This could be due to a reduction in platelet activation, as evidenced by the decrease in D-dimer levels observed in the antiplatelet group.


Subject(s)
Chronic Urticaria , Cilostazol , Dipyridamole , Drug Therapy, Combination , Fibrin Fibrinogen Degradation Products , Loratadine , Platelet Aggregation Inhibitors , Adult , Female , Humans , Male , Middle Aged , Chronic Urticaria/drug therapy , Cilostazol/administration & dosage , Cilostazol/therapeutic use , Dipyridamole/administration & dosage , Dipyridamole/therapeutic use , Double-Blind Method , Fibrin Fibrinogen Degradation Products/metabolism , Fibrin Fibrinogen Degradation Products/analysis , Histamine Antagonists/administration & dosage , Histamine Antagonists/therapeutic use , Loratadine/administration & dosage , Loratadine/therapeutic use , Loratadine/analogs & derivatives , Platelet Aggregation Inhibitors/administration & dosage , Quality of Life , Tetrazoles/administration & dosage , Tetrazoles/therapeutic use , Treatment Outcome
4.
Curr Allergy Asthma Rep ; 24(7): 347-360, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38869807

ABSTRACT

PURPOSE OF REVIEW: The aim of this review, is to present an updated revision of topical management of SAC and PAC, based on the available scientific evidence and focused on the impact of ophthalmic solution formulations on eye surface. RECENT FINDINGS: Physicians treating ocular allergy should be aware of tear film and tear film disruption in SAC and PAC, and how eye drop composition and additives affect the physiology of the allergic eye. Seasonal and perennial allergic conjunctivitis (SAC and PAC) are the most frequent causes of ocular allergy (OA), and both conditions are underdiagnosed and undertreated. SAC and PAC are immunoglobulin E (IgE)-mediated hypersensitivity reactions. The additional tear film disruption caused by the release of inflammatory mediators increases and exacerbates the impact of signs and symptoms and may trigger damage of the ocular surface. Comorbidities are frequent, and dry eye disease in particular must be considered. Clinical guidelines for the management of SAC and PAC recommend topical therapy with antihistamines, mast cells stabilizers or dualaction agents as first-line treatment, but care should be taken, as many medications contain other compounds that may contribute to ocular surface damage.


Subject(s)
Conjunctivitis, Allergic , Ophthalmic Solutions , Humans , Conjunctivitis, Allergic/drug therapy , Conjunctivitis, Allergic/immunology , Ophthalmic Solutions/therapeutic use , Histamine Antagonists/therapeutic use , Tears
5.
Environ Sci Technol ; 58(12): 5512-5523, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38478581

ABSTRACT

The investigation of pharmaceuticals as emerging contaminants in marine biota has been insufficient. In this study, we examined the presence of 51 pharmaceuticals in edible oysters along the coasts of the East and South China Seas. Only nine pharmaceuticals were detected. The mean concentrations of all measured pharmaceuticals in oysters per site ranged from 0.804 to 15.1 ng g-1 of dry weight, with antihistamines being the most common. Brompheniramine and promethazine were identified in biota samples for the first time. Although no significant health risks to humans were identified through consumption of oysters, 100-1000 times higher health risks were observed for wildlife like water birds, seasnails, and starfishes. Specifically, sea snails that primarily feed on oysters were found to be at risk of exposure to ciprofloxacin, brompheniramine, and promethazine. These high risks could be attributed to the monotonous diet habits and relatively limited food sources of these organisms. Furthermore, taking chirality into consideration, chlorpheniramine in the oysters was enriched by the S-enantiomer, with a relative potency 1.1-1.3 times higher when chlorpheniramine was considered as a racemate. Overall, this study highlights the prevalence of antihistamines in seafood and underscores the importance of studying enantioselectivities of pharmaceuticals in health risk assessments.


Subject(s)
Environmental Monitoring , Ostreidae , Pharmaceutical Preparations , Water Pollutants, Chemical , Animals , Humans , Brompheniramine/analysis , China , Chlorpheniramine/analysis , Histamine Antagonists/analysis , Oceans and Seas , Ostreidae/chemistry , Pharmaceutical Preparations/analysis , Promethazine/analysis , Water Pollutants, Chemical/analysis
6.
J Am Acad Dermatol ; 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38280680

ABSTRACT

Multiple recently approved medications have been added to our treatment armamentarium for various dermatologic conditions. Herein, we have reviewed the literature, consolidated available safety data, and offered recommendations based upon available evidence as a reference guide for clinicians treating patients for dermatologic conditions during lactation.

7.
Adv Exp Med Biol ; 1447: 131-138, 2024.
Article in English | MEDLINE | ID: mdl-38724790

ABSTRACT

The treatment of atopic dermatitis (AD) with oral treatments has been limited in the past due to the increased risk of adverse effects associated with oral agents. However, in recent years, a shift toward the minimization of adverse effects has been explored. Although existing treatment options like oral corticosteroids and Immunosuppressive therapies have been utilized for acute flare-ups of AD, their long-term use is limited by adverse effects and the need for lab monitoring. New systemic treatment options such as Janus kinase (JAK) inhibitors are emerging as a promising therapy, due to their quick onset and antipruritic features. However, the black box warning associated with this medication class requires careful selection of appropriate candidates and patient education despite early favorable safety profiles seen in AD trials. Discussion of other oral agents, like antibiotics and antihistamines, and their role in AD management are also clarified.


Subject(s)
Dermatitis, Atopic , Humans , Administration, Oral , Dermatitis, Atopic/drug therapy , Histamine Antagonists/therapeutic use , Histamine Antagonists/adverse effects , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Janus Kinase Inhibitors/adverse effects , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/adverse effects
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(2): 182-189, 2024 Feb 28.
Article in English, Zh | MEDLINE | ID: mdl-38755714

ABSTRACT

Histamine receptors are classified into 4 types: H1, H2, H3, and H4, each mediating distinct physiological effects and possessing its corresponding antagonistshat that can be used for the prevention and treatment of various diseases. Among them, H1 antihistamines are the fundamental medications in dermatology and are widely used in many diseases such as urticaria and atopic dermatitis. In recent years, with the emergence of novel antihistamines and the discovery of new potential indications for traditional H1 antihistamines, the clinical application of antihistamines is facing new challenges. Further investigation of the novel mechanism for H1 antihistamines, the use of multiple doses of common drugs and potential indications will furnish vital insights for practical clinical application.


Subject(s)
Dermatitis, Atopic , Histamine H1 Antagonists , Urticaria , Humans , Histamine H1 Antagonists/therapeutic use , Histamine H1 Antagonists/pharmacology , Urticaria/drug therapy , Dermatitis, Atopic/drug therapy , Skin Diseases/drug therapy
9.
Vestn Otorinolaringol ; 89(4): 68-77, 2024.
Article in Russian | MEDLINE | ID: mdl-39171880

ABSTRACT

Allergic rhinitis (AR) can significantly reduce the quality of life of patients leading to increased fatigue, mood changes, cognitive impairment, and depression. In clinical practice, insufficient effectiveness of initial AR monotherapy is often noted, and a significant proportion of patients referring for medical care have moderate-severe AR. In this regard, the issues of optimization of combined pharmacological treatment of AR are becoming more and more urgent. This paper provides analysis of the opportunities of combined pharmacotherapy within the framework of current management strategy of AR. Based on the results of some studies and known pharmacological properties of medications it is being discussed the advantages of combined use of intranasal corticosteroids and leukotriene receptor antagonists, in particular mometasone furoate and montelukast, in the therapy of AR, including such comorbidities as bronchial asthma, chronic polyposis rhinosinusitis and pharyngeal tonsil hyperplasia. Some aspects of combination therapy with montelukast and second-generation systemic antihistamines as an alternative approach in case of inability to take intranasal corticosteroids, including the reasonability of using a fixed combination of montelukast and levocetirizine, are analyzed from the perspective of rational pharmacotherapy. The problem of interchangeability of brand-name and generic drugs for the treatment of AR is discussed, considering the almost complete absence of studies of their therapeutic equivalence.


Subject(s)
Administration, Intranasal , Drug Therapy, Combination , Leukotriene Antagonists , Rhinitis, Allergic , Humans , Rhinitis, Allergic/drug therapy , Leukotriene Antagonists/administration & dosage , Leukotriene Antagonists/therapeutic use , Anti-Allergic Agents/administration & dosage , Histamine Antagonists/administration & dosage , Adrenal Cortex Hormones/administration & dosage , Treatment Outcome , Cyclopropanes/administration & dosage , Cyclopropanes/therapeutic use , Quinolines/administration & dosage , Quinolines/therapeutic use , Sulfides/administration & dosage , Acetates/therapeutic use , Acetates/administration & dosage
10.
J Am Acad Dermatol ; 89(1): e1-e20, 2023 07.
Article in English | MEDLINE | ID: mdl-36641009

ABSTRACT

BACKGROUND: New evidence has emerged since the 2014 guidelines that further informs the management of atopic dermatitis (AD) with topical therapies. These guidelines update the 2014 recommendations for management of AD with topical therapies. OBJECTIVE: To provide evidence-based recommendations related to management of AD in adults using topical treatments. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: The workgroup developed 12 recommendations on the management of AD in adults with topical therapies, including nonprescription agents and prescription topical corticosteroids (TCS), calcineurin inhibitors (TCIs), Janus kinase (JAK) inhibitors, phosphodiesterase-4 inhibitors (PDE-4), antimicrobials, and antihistamines. LIMITATIONS: The pragmatic decision to limit the literature review to English-language randomized trials may have excluded data published in other languages and relevant long-term follow-up data. CONCLUSIONS: Strong recommendations are made for the use of moisturizers, TCIs, TCS, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines.


Subject(s)
Anti-Infective Agents, Local , Dermatitis, Atopic , Dermatologic Agents , Adult , Humans , Dermatitis, Atopic/drug therapy , Calcineurin Inhibitors/therapeutic use , Dermatologic Agents/therapeutic use , Administration, Topical , Glucocorticoids/therapeutic use , Anti-Infective Agents, Local/therapeutic use , Histamine Antagonists/therapeutic use
11.
J Am Acad Dermatol ; 89(1): 128-129, 2023 07.
Article in English | MEDLINE | ID: mdl-36623556

ABSTRACT

These guidelines update the 2014 recommendations for management of atopic dermatitis in adults with topical therapies. A multidisciplinary workgroup employed best practices for guideline development, including a systematic review of the evidence and application of the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading recommendations. The evidence on atopic dermatitis treatment supported strong recommendations for the use of nonprescription moisturizers, topical calcineurin inhibitors, topical corticosteroids, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines.


Subject(s)
Dermatitis, Atopic , Dermatologic Agents , Dermatology , Adult , Humans , Dermatitis, Atopic/drug therapy , Calcineurin Inhibitors/therapeutic use , Dermatologic Agents/therapeutic use , Glucocorticoids
12.
J Investig Allergol Clin Immunol ; 33(6): 439-445, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38095493

ABSTRACT

Tear dysfunction syndrome, also known as dry eye disease (DED), is a multifactorial disease of the ocular surface characterized by the loss of tear film homeostasis. DED shows a significant clinical overlap with ocular allergy (OA), which alters tear film homeostasis, thus predisposing the patient to DED. Both conditions constitute the most common ocular surface disorders and have a potentially severe impact on patients' quality of life. Clinical practice guidelines recommend topical therapies as first-line treatment for OA. However, eye drop formulations may contain additional substances that can contribute to ocular surface damage and the development of DED. Therefore, physicians treating ocular allergy should be aware of problems affecting the tear film, the role of tear film disruption in OA, and topical treatment to prevent or minimize DED. The aim of this review is to present an updated overview of the topic.


Subject(s)
Conjunctivitis, Allergic , Dry Eye Syndromes , Humans , Conjunctivitis, Allergic/drug therapy , Quality of Life , Dry Eye Syndromes/drug therapy , Tears , Ophthalmic Solutions
13.
J Enzyme Inhib Med Chem ; 38(1): 2188147, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36912265

ABSTRACT

Carbonic anhydrases (CAs) are important regulators of pH homeostasis and participate in many physiological and pathological processes. CA activators (CAAs) are becoming increasingly important in the biomedical field since enhancing CA activity may have beneficial effects at neurological level. Here, we investigate selected antihistamines, phenothiazine-based antipsychotics, and tricyclic antidepressants (TCAs) as potential activators of human CAs I, II, IV, and VII. Our findings indicate that these compounds are more effective at activating hCA II and VII compared to hCA I and IV. Overall, hCA VII was the most efficiently activated isoform, particularly by phenothiazines and TCAs. This is especially relevant since hCA VII is the most abundant isoform in the central nervous system (CNS) and is implicated in neuronal signalling and bicarbonate balance regulation. This study offers additional insights into the pharmacological profiles of clinically employed drugs and sets the ground for the development of novel optimised CAAs.


Subject(s)
Antipsychotic Agents , Carbonic Anhydrases , Humans , Antipsychotic Agents/pharmacology , Antidepressive Agents, Tricyclic/pharmacology , Carbonic Anhydrases/metabolism , Protein Isoforms/metabolism , Phenothiazines , Histamine Antagonists/pharmacology , Carbonic Anhydrase Inhibitors/pharmacology , Structure-Activity Relationship , Molecular Structure
14.
Eur Ann Allergy Clin Immunol ; 55(1): 9-18, 2023 01.
Article in English | MEDLINE | ID: mdl-33949172

ABSTRACT

Summary: Background. Chronic urticaria (CU) is a frequent disease, with a prevalence of at least 1%. It is characterized by pruritic wheals, angioedema or both for a period longer than 6 weeks. Objective. Identify the demographic, clinical, laboratory and therapeutic profile of patients treated in a Portuguese Urticaria Center of Reference and Excellence (UCARE) and compare it with international series. Methods. Retrospective analysis of database of patients observed in a specialized urticaria outpatient clinic, from January 2017 through September 2019, of a UCARE center in Portugal. Demographic and clinical features, laboratory findings and pharmacological treatment were obtained from the records. Descriptive analyses were performed for all variables. Chi square and fisher's exact tests were applied to analyze the independence of variables and the fit of distribution. P less than 0.05 was considered significant. Results. During this period, 477 patients were observed, of whom 429 (90%) were diagnosed with chronic urticaria. Mean age (years) at the onset of symptoms was 43.7 (standard deviation (SD) 17.6, range 6-88) and at diagnosis 46.7 (SD 17.8, range 6-88) resulting in an average diagnostic delay of 3 years (range 0-25). Median follow-up period since first attendance in the specialized outpatient clinic was 1.7 years (interquartile range (IQR) 0.79, range 0.1-2.75) . Concerning the whole group of CU patients, 347 (81%) had chronic spontaneous urticaria (CSU) - 79% female, 39 (9%) had isolated chronic inducible urticaria (CIndU) and 43 (10%) had CSU with CIndU. Autologous serum skin test (ASST) was done in 76 patients (positive in 24 (32%)) and basophil activation test (BAT) was done in 38 (positive in 13 (34%)). At the moment of study, 204 (48%) of CU patients were medicated with a second-generation H1-antihistamine (sgAH) daily (first-line therapy), 99 (23%) with sgAH up to four times the standard dose (second-line therapy) and 126 (29%) with omalizumab (third-line therapy). Additionally, 7 (2%) patients were completing a short course of systemic corticosteroids for management of disease exacerbation. Disease control was achieved in 316 of CSU patients (81%). Conclusions. Referral to a specialized urticaria outpatient clinic is important for a proper assessment of the disease and adequately symptom control.


Subject(s)
Chronic Urticaria , Histamine H1 Antagonists, Non-Sedating , Urticaria , Humans , Female , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Male , Portugal/epidemiology , Retrospective Studies , Delayed Diagnosis , Urticaria/diagnosis , Urticaria/drug therapy , Urticaria/epidemiology , Chronic Urticaria/drug therapy , Omalizumab/therapeutic use , Histamine H1 Antagonists, Non-Sedating/therapeutic use , Chronic Inducible Urticaria , Chronic Disease
15.
Int J Mol Sci ; 24(9)2023 Apr 25.
Article in English | MEDLINE | ID: mdl-37175525

ABSTRACT

The sleep-wake cycle is a complex multifactorial process involving several neurotransmitters, including acetylcholine, norepinephrine, serotonin, histamine, dopamine, orexin and GABA, that can be, in turn, regulated by different nutrients involved in their metabolic pathways. Although good sleep quality in children has been proven to be a key factor for optimal cognitive, physical and psychological development, a significant and ever-increasing percentage of the pediatric population suffers from sleep disorders. In children, behavioral interventions along with supplements are recommended as the first line treatment. This systematic review was conducted, according to the PRISMA guidelines, with the purpose of assessing the principal nutrients involved in the pathways of sleep-regulating neurotransmitters in children and adolescents. Our focus was the utilization of over the counter (OTC) products, specifically iron, hydroxytryptophan, theanine and antihistamines in the management of different pediatric sleep disorders with the intention of providing a practical guide for the clinician.


Subject(s)
Sleep Initiation and Maintenance Disorders , Sleep Wake Disorders , Adolescent , Humans , Child , Sleep/physiology , Histamine/metabolism , Histamine Antagonists , Neurotransmitter Agents , Sleep Wake Disorders/drug therapy
16.
Int J Mol Sci ; 24(15)2023 Aug 02.
Article in English | MEDLINE | ID: mdl-37569714

ABSTRACT

Parkinson's disease (PD) is a movement disorder caused by a dopamine deficit in the brain. Current therapies primarily focus on dopamine modulators or replacements, such as levodopa. Although dopamine replacement can help alleviate PD symptoms, therapies targeting the underlying neurodegenerative process are limited. The study objective was to use artificial intelligence to rank the most promising repurposed drug candidates for PD. Natural language processing (NLP) techniques were used to extract text relationships from 33+ million biomedical journal articles from PubMed and map relationships between genes, proteins, drugs, diseases, etc., into a knowledge graph. Cross-domain text mining, hub network analysis, and unsupervised learning rank aggregation were performed in SemNet 2.0 to predict the most relevant drug candidates to levodopa and PD using relevance-based HeteSim scores. The top predicted adjuvant PD therapies included ebastine, an antihistamine for perennial allergic rhinitis; levocetirizine, another antihistamine; vancomycin, a powerful antibiotic; captopril, an angiotensin-converting enzyme (ACE) inhibitor; and neramexane, an N-methyl-D-aspartate (NMDA) receptor agonist. Cross-domain text mining predicted that antihistamines exhibit the capacity to synergistically alleviate Parkinsonian symptoms when used with dopamine modulators like levodopa or levodopa-carbidopa. The relationship patterns among the identified adjuvant candidates suggest that the likely therapeutic mechanism(s) of action of antihistamines for combatting the multi-factorial PD pathology include counteracting oxidative stress, amending the balance of neurotransmitters, and decreasing the proliferation of inflammatory mediators. Finally, cross-domain text mining interestingly predicted a strong relationship between PD and liver disease.


Subject(s)
Parkinson Disease , Humans , Parkinson Disease/drug therapy , Levodopa/therapeutic use , Antiparkinson Agents/pharmacology , Dopamine/therapeutic use , Artificial Intelligence , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Histamine Antagonists/therapeutic use
17.
Cutan Ocul Toxicol ; 42(1): 8-11, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36469932

ABSTRACT

BACKGROUND: Literature on the effects of second-generation H1-antihistamines on angiogenesis is limited. OBJECTIVES: To investigate the effects of cetirizine, desloratadine, and rupatadine (second-generation H1-antihistamines commonly used in dermatology clinics) on angiogenesis in an in vivo chick chorioallantoic membrane (CAM) model. METHODS: The study was approved by the local ethics committee on animal experimentation. Forty fertilized specific pathogen free eggs were incubated and kept under appropriate temperature and humidity control. Drug solutions were prepared in identical concentrations by dissolving powders in phosphate-buffered saline (PBS). On the third day of the incubation, a small window was opened on the CAM and 0.1 mL desloratadine (1.5 µg/0.1 mL) in the first group, 0.1 mL cetirizine (1.5 µg/0.1 mL) in the second group, 0.1 mL rupatadine in the third group (1.5 µg/0.1 mL), and PBS (0.1 mL) in the fourth group were administered by injection. On the eighth day of incubation, the vascular structures of the CAMs were macroscopically examined and standard digital photographs were taken. The digital images were analyzed and data including mean vessel density, thickness, and number were compared between groups. p < 0.05 was considered statistically significant. RESULTS: Vessel densities were similar in the desloratadine, cetirizine, and control groups, whereas they were significantly less in the rupatadine group (p = 0.01). Furthermore, the rupatadine group had significantly lower vessel thickness and number compared with the other groups (p < 0.05 for both). CONCLUSIONS: Rupatadine showed anti-angiogenic effects in the chick CAM model, compared with desloratadine and cetirizine. The anti-angiogenic effect of rupatadine could be due to its platelet-activating factor (PAF) receptor inhibition. Thus, rupatadine could be a treatment agent in pathological processes in which angiogenesis is responsible. Further studies with larger series are needed to clarify this potential.


Subject(s)
Cetirizine , Histamine H1 Antagonists, Non-Sedating , Animals , Cetirizine/pharmacology , Cetirizine/therapeutic use , Chorioallantoic Membrane , Chickens
18.
Curr Issues Mol Biol ; 44(4): 1597-1609, 2022 Apr 08.
Article in English | MEDLINE | ID: mdl-35723367

ABSTRACT

Antihistamines have potent efficacy to alleviate COVID-19 (Coronavirus disease 2019) symptoms such as anti-inflammation and as a pain reliever. However, the pharmacological mechanism(s), key target(s), and drug(s) are not documented well against COVID-19. Thus, we investigated to decipher the most significant components and how its research methodology was utilized by network pharmacology. The list of 32 common antihistamines on the market were retrieved via drug browsing databases. The targets associated with the selected antihistamines and the targets that responded to COVID-19 infection were identified by the Similarity Ensemble Approach (SEA), SwissTargetPrediction (STP), and PubChem, respectively. We described bubble charts, the Pathways-Targets-Antihistamines (PTA) network, and the protein-protein interaction (PPI) network on the RPackage via STRING database. Furthermore, we utilized the AutoDock Tools software to perform molecular docking tests (MDT) on the key targets and drugs to evaluate the network pharmacological perspective. The final 15 targets were identified as core targets, indicating that Neuroactive ligand-receptor interaction might be the hub-signaling pathway of antihistamines on COVID-19 via bubble chart. The PTA network was constructed by the RPackage, which identified 7 pathways, 11 targets, and 30 drugs. In addition, GRIN2B, a key target, was identified via topological analysis of the PPI network. Finally, we observed that the GRIN2B-Loratidine complex was the most stable docking score with -7.3 kcal/mol through molecular docking test. Our results showed that Loratadine might exert as an antagonist on GRIN2B via the neuroactive ligand-receptor interaction pathway. To sum up, we elucidated the most potential antihistamine, a key target, and a key pharmacological pathway as alleviating components against COVID-19, supporting scientific evidence for further research.

19.
Exp Dermatol ; 31(7): 993-1004, 2022 07.
Article in English | MEDLINE | ID: mdl-35538735

ABSTRACT

Antihistamines, especially H1 antihistamines, are widely used in the treatment of allergic diseases such as urticaria and allergic rhinitis, mainly for reversing elevated histamine and anti-allergic effects. Antihistamines are generally safe, but some patients experience adverse reactions, such as cardiotoxicity, central inhibition and anticholinergic effects. There are also individual differences in antihistamine efficacy in clinical practice. The concept of individualized medicine has been deeply rooted in people's minds since it was put forward. Pharmacogenomics is the study of the role of inheritance in individual variations in drug response. In recent decades, pharmacogenomics has been developing rapidly, which provides new ideas for individualized medicine. Polymorphisms in the genes encoding metabolic enzymes, transporters and target receptors have been shown to affect the efficacy of antihistamines. In addition, recent evidence suggests that gene polymorphisms influence urticaria susceptibility and antihistamine therapy. Here, we summarize current reports in this area, aiming to contribute to future research in antihistamines and clinical guidance for antihistamines use in individualized medicine.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Urticaria , Histamine/pharmacology , Histamine Antagonists/adverse effects , Histamine H1 Antagonists/therapeutic use , Humans , Pharmacogenetics
20.
Exp Dermatol ; 31(2): 242-247, 2022 02.
Article in English | MEDLINE | ID: mdl-34558729

ABSTRACT

Chronic spontaneous urticaria (CSU) is a mast cell-driven disease with many advances in its aetiology and pathogenesis over the past years. The main treatment of CSU is oral second-generation antihistamines. However, only an average of 50% of CSU patients responded adequately to conventional or quadruple doses of non-sedative antihistamines. Meanwhile, gut microbiota can affect the efficacy of drugs. The purpose of this study was to investigate the relationship between gut microbiota and the efficacy of antihistamines in patients with CSU. The patients with CSU were divided into responders and non-responders according to the efficacy of antihistamine monotherapy. The gut microbiota of faecal samples from 15 responders and 15 non-responders was detected by 16S rDNA sequencing, and the differential bacterial species between the two groups were verified by quantitative polymerase chain reaction (qPCR). Additional faecal samples from 30 responders and 30 non-responders were used as an extended cohort to further verify the above differential bacterial species by qPCR. Lachnospiraceae and its subordinate taxa were found to be the main differences in gut microbiota between responders and non-responders. The abundance of Lachnospira in responders was higher than that in non-responders. Lachnospira exhibits moderate diagnostic value in evaluating the efficacy of antihistamine. Lachnospira is a signature for predicting the efficacy of antihistamine in patients with CSU.


Subject(s)
Chronic Urticaria , Gastrointestinal Microbiome , Urticaria , Bacteria , Chronic Disease , Chronic Urticaria/drug therapy , Feces/microbiology , Histamine Antagonists/therapeutic use , Histamine H1 Antagonists/therapeutic use , Humans , Urticaria/drug therapy
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