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Skin Testing in Drug Hypersensitivity
Published in Kirsti Kauppinen, Kristiina Alanko, Matti Hannuksela, Howard Maibach, Skin Reactions to Drugs, 2020
Antihistamines weaken skin reactivity to histamine. Astemizole should be discontinued at least 4 weeks and terfenadine 2 weeks before skin testing for immediate allergy. The corresponding time for other antihistamines is (2-)4 days. Inhaled steroids have an insignificant effect on skin reactivity. Systemic steroids (prednisone more than 10 mg a day) and topical steroids also reduce the size of immediate reactions.
Pharmacokinetic-Pharmacodynamic Correlations of Antihistamines
Published in Hartmut Derendorf, Günther Hochhaus, Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Eric Snoeck, Achiel Van Peer, Jos Heykants
Astemizole is an orally potent, long-acting and specific histamine H1-receptor antagonist, free of central effects and anticholinergic action.80–82 Astemizole binds to the peripheral H1-receptor sites with far greater affinity than any other existing antihistamine.83 Clinical studies demonstrated efficacy in seasonal allergic rhinitis and conjunctivitis,84,86 perennial allergic rhinitis,87 and chronic urticaria.88
Respiratory disorders
Published in Anne Lee, Sally Inch, David Finnigan, Therapeutics in Pregnancy and Lactation, 2019
The risks of antihistamines appear to be low.21 The sedating antihistamine chlorpheniramine has been used for many years with no evidence of teratogenicity in man, including use specifically for morning sickness. There is some doubt about brompheniramine, for which the American Collaborative Perinatal Project22 found a statistically significant association with congenital malformations, but good supporting evidence is lacking. Caution suggests that an older antihistamine should be used in preference to newer agents, though the risk of drowsiness may make this impracticable. The newer but widely used terfenadine has the advantage of being non-sedating; there is no evidence suggesting it is associated with malformations but its safety is unconfirmed.23 High doses of astemizole (now discontinued in the UK) are associated with defects in animals and the manufacturer recommends avoidance during pregnancy. The frequency of congenital anomalies was not increased among 104 infants whose mothers had taken astemizole in the first trimester in a cohort study.24 Astemizole has a long half-life and patients are advised to avoid conception for several weeks after the last dose.
Histamine antagonists promote cancer immunosurveillance
Published in OncoImmunology, 2023
Peng Liu, Guido Kroemer, Oliver Kepp
Altogether, the aforementioned data indicate that astemizole enhances ICD-ignited adaptive anticancer immunity by increasing the immune tone of T cells through antagonizing a latent inhibition of TCR signaling imposed by HRH1 (Figure 1b). These findings are in line with reports showing that HRH1 antagonists amplify the efficacy of PD-1/PD-L1-targeted ICIs in murine models of breast carcinomas, colorectal cancers and melanomas9. Moreover, retrospective epidemiological data revealed that the use of HRH1 antagonists correlated with overall survival in patients with localized ovarian cancer or metastatic disease and generally ameliorated the response to anticancer immunotherapy10,11. These findings have been corroborated in a recent basket trial revealing that circulating histamine levels inversely correlate with clinical response to PD-1-targeted ICI9. Prospective clinical trials evaluating the combination effect of HRH1 antagonists with (ICD-mediated) immunotherapy are urgently awaited.
Overview of gene expression techniques with an emphasis on vitamin D related studies
Published in Current Medical Research and Opinion, 2023
Jeffrey Justin Margret, Sushil K. Jain
Several studies have compared the gene expression patterns between different cell types. The effect of astemizole treatment in mice showed similar gene expression patterns in heart tissue and PBMC48. Min et al.49 studied gene expression patterns in five different cell types from six individuals and found higher gene expression in PAXgene cells (cells that stabilize intercellular RNA of all cell types in WB) than in others, suggesting the suitability of PAXgene cells for large scale epidemiological studies. Most of the genes were expressed differently across three RNAs isolated from lymphoblastoid cell lines (LCL), WB using PAXgene tubes, and PBMC studied to identify the biomarkers related to cardiovascular disease. However, their association with each of the traits was also different, which emphasizes the importance of selecting suitable cells for gene expression studies50. Gene expression profiling of advanced heart failure patients showed similar patterns in WB and PBMC. Although PBMC was more accurate in predicting high-risk groups, WB cells were better at predicting moderate and high-risk groups51.
The clinical relationship between histamine-1 receptor antagonists and risk of cancer: a systematic review and meta-analysis
Published in Expert Review of Anticancer Therapy, 2023
Elham Bakhtiari, Nasrin Moazzen, Amir Amirabadi, Hamid Ahanchian
Another possible explanation might be Enhancer of Zester Homolog 2 (EZH2) which is dysregulated in most cancer cell lines [23]. Some recent evidence showed promising cancer-suppressive properties with inhibition of component. There is enhanced proliferation of cancer cell lines when this protein is overexpressed, while there is increased apoptosis of cancer cells with inhibition of it [24]. This oncogenic methyl transferase especially over expressed on aggressive and difficult to treat prostate and breast cancer [25,26]. So it can be considered as a new promising target for treatment of cancer [26]. In a recent animal study, ebastine, which is a second-generation anti-histamine with low or absent potential of transferring to the brain, was investigated for inhibition of EZH2 and compared with chlorpheniramine, fexofenadine, and some other antihistamines. The result has shown that ebastine like astemizole was effective in attenuating EZH2 levels. While fexofenadine or chlorpheniramine was not effective even in higher doses [23]. Targeting this component with antihistamine may be helpful in some cancer treatments; however, some drugs like astemizole and ebastine may cause unwanted events like cardiac arrhythmias [27,28]. So recommending this treatment in the absence of allergic diseases or other clinical indication may not be appropriate.