The histamine H₄ receptor (H₄R) is expressed on cells of the immune system including eosinophils, dendritic cells, and T cells and plays an important role in the pathogenesis of bronchial asthma, atopic dermatitis, and pruritus. Analysis of the H₄R in these diseases depends on the use of animal models. However, there are substantial pharmacological differences between various H₄R species orthologs. The purpose of this study was to analyze the pharmacological properties of canine, rat, and murine H₄R in comparison to human H₄R expressed in Sf9 insect cells. Only hH₄R and cH₄R exhibited a sufficiently high [³H]histamine affinity for radioligand binding studies. Generally, cH₄R exhibited lower ligand-affinities than hH₄R. Similarly, in high-affinity GTPase studies, ligands were more potent at hH₄R than at other H₄R species orthologs. Unlike the other H₄R species orthologs, hH₄R exhibited high agonist-independent (constitutive) activity. Most strikingly, the prototypical H₄R antagonist (1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine) (JNJ7777120) exhibited partial agonistic activity at cH₄R, rH₄R, and mH₄R, whereas at hH₄R, JNJ7777120 was a partial inverse agonist. H₄R agonists from the class of N ( G )-acylated imidazolylpropylguanidines and cyanoguanidines exhibited substantial differences in terms of affinity, potency, and efficacy among H₄R species orthologs, too. The species-dependent pharmacological profiles are not due to the highly variable amino acid sequence position 341. Finally, H₄R species orthologs differ from each other in terms of regulation by NaCl. Collectively, there are profound pharmacological differences between H₄R species orthologs. Most importantly, caution must be exerted when interpreting pharmacological effects of "the prototypical H₄R antagonist" JNJ7777120 as H₄R antagonism.
Only a few studies concerning HAE were found, but they did not obtain any consistent conclusions. HAE impact was supposed particularly on treatment outcomes that may be easier affected by patient behaviour. However, researchers and clinicians should be still aware of HAE, interpret results carefully and verified them in further studies.
Despite relatively high adherence to the treatment, most patients do not follow dosing instructions. Reduced bioavailability, particularly of monthly ibandronate, can be expected in clinical practice. Adherence-related outcomes are associated with beliefs about the oral treatment with bisphosphonates.
Background Guidelines on the management of orally anticoagulated patients are continuously evolving, leading to an increased need for pharmacists to be fully integrated in care provision. Objective To identify self-reported gaps in confidence among practicing pharmacists in the area of anticoagulation. Setting Pharmacists in different work settings in different countries. Method Cross-sectional international survey from October 2015 till November 2016 among pharmacists working in different settings to assess their level of confidence when delivering anticoagulants as well as to identify possible educational needs regarding this medication class. Validation of the survey was ensured. Results Responses from 4212 pharmacists originating from 18 countries were obtained. Pharmacists’ level of confidence was significantly higher (p < 0.001) when advising patients on vitamin K antagonists (VKAs) versus non-vitamin K antagonists (NOACs). In general, hospital pharmacists displayed higher confidence levels compared to community pharmacists when advising patients on anticoagulation (p < 0.001). Two distinct patterns of confidence levels emerged relating to basic and advanced pharmaceutical care. Confidence levels when providing advanced pharmaceutical care were significantly higher for Oceania and lower for South America (p < 0.005). Conclusions Pharmacists felt more confident in supporting patients receiving VKAs compared to the more recently introduced NOACs. With the increasing use of NOACs and the risks pertaining to anticoagulation therapy, it is essential to invest in education for pharmacists to address their knowledge gaps enabling them to confidently support patients receiving oral anticoagulants.Electronic supplementary materialThe online version of this article (10.1007/s11096-017-0551-2) contains supplementary material, which is available to authorized users.
This study proved MARS-CZ as an acceptable self-reported adherence measure. In routine clinical practice, MARS-CZ could be helpful to reveal medication non-adherence before the alteration of drug regimen and thereby contributing to enhancement of statin therapy management.
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