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Annals of Family Medicine Jan 2023CONTEXT: Patients taking direct-acting oral anticoagulants (DOACs) may be at risk for bleeding if they take interacting over-the-counter (OTC) products, yet little...
CONTEXT: Patients taking direct-acting oral anticoagulants (DOACs) may be at risk for bleeding if they take interacting over-the-counter (OTC) products, yet little information exists about why patients may or may not seek information about potential interactions. OBJECTIVE: To investigate perspectives of patients taking apixaban (a commonly prescribed DOAC) regarding seeking information about OTC products. STUDY DESIGN and ANALYSIS: Semi-structured interviews were analyzed using thematic analysis. SETTING: Two large academic medical centers. POPULATION: English-, Mandarin-, Cantonese-, or Spanish-speaking adults taking apixaban. OUTCOME MEASURES: Themes associated with information-seeking about potential apixaban-OTC product interactions. RESULTS: Forty-six patients aged 28-93 years (35% Asian, 15% Black, 24% Hispanic, and 20% White; 58% women), were interviewed. Respondents took 172 total OTC products, of which the most common were: vitamin D and/or calcium (15%), non-vitamin non-mineral dietary supplements (13%), acetaminophen (12%), NSAIDS/aspirin (9%), and multivitamins (9%). Themes related to lack of information-seeking about OTC products included: 1) failure to recognize that apixaban-OTC product interactions might exist; 2) beliefs that providers are responsible for disseminating information about interactions; 3) previous suboptimal interactions with providers; 4) infrequent OTC product use; and 5) lack of prior problems with OTC product use (with or without concomitant apixaban use). Conversely, themes associated with seeking information included: 1) believing that patients are responsible for their own medication-related safety; 2) greater trust in providers; 3) unfamiliarity with the OTC product; and 4) prior medication-related problems. Patients noted that information sources ranged from in-person sources (e.g., physicians, pharmacists) to online and written materials. CONCLUSIONS: Patients taking apixaban raised reasons for information-seeking about OTC products related to their perceptions of OTC products, provider-patient interactions, and their prior experiences with and frequency of OTC product use. Greater patient education about the need for information-seeking about potential DOAC-OTC product interactions may be needed at the time of prescribing.
Topics: Adult; Humans; Female; Male; Information Seeking Behavior; Nonprescription Drugs; Aspirin; Pyrazoles
PubMed: 36972532
DOI: 10.1370/afm.21.s1.4239 -
Blood Advances Nov 2022
Topics: Benzaldehydes; Pyrazines; Pyrazoles
PubMed: 35984638
DOI: 10.1182/bloodadvances.2022007702 -
International Journal of Molecular... Aug 2023Pyrazole derivatives, as a class of heterocyclic compounds, possess unique chemical structures that confer them with a broad spectrum of pharmacological activities. They... (Review)
Review
Pyrazole derivatives, as a class of heterocyclic compounds, possess unique chemical structures that confer them with a broad spectrum of pharmacological activities. They have been extensively explored for designing potent and selective anticancer agents. In recent years, numerous pyrazole derivatives have been synthesized and evaluated for their anticancer potential against various cancer cell lines. Structure-activity relationship studies have shown that appropriate substitution on different positions of the pyrazole ring can significantly enhance anticancer efficacy and tumor selectivity. It is noteworthy that many pyrazole derivatives have demonstrated multiple mechanisms of anticancer action by interacting with various targets including tubulin, EGFR, CDK, BTK, and DNA. Therefore, this review summarizes the current understanding on the structural features of pyrazole derivatives and their structure-activity relationships with different targets, aiming to facilitate the development of potential pyrazole-based anticancer drugs. We focus on the latest research advances in anticancer activities of pyrazole compounds reported from 2018 to present.
Topics: Antineoplastic Agents; Pyrazoles; Cell Line; Structure-Activity Relationship; Tubulin
PubMed: 37628906
DOI: 10.3390/ijms241612724 -
Molecules (Basel, Switzerland) Nov 2019Based on medicinal chemistry tools, new compounds for malaria treatment were designed. The scaffolds of the drugs used to treat malaria, such as chloroquine, primaquine,... (Review)
Review
Based on medicinal chemistry tools, new compounds for malaria treatment were designed. The scaffolds of the drugs used to treat malaria, such as chloroquine, primaquine, amodiaquine, mefloquine and sulfadoxine, were used as inspiration. We demonstrated the importance of quinoline and non-quinoline derivatives in vitro with activity against the W2 chloroquine-resistant (CQR) clone strain and in vivo against -infected mouse model. Among the quinoline derivatives, new hybrids between chloroquine and sulfadoxine were designed, which gave rise to an important prototype that was more active than both chloroquine and sulfadoxine. Hybrids between chloroquine-atorvastatin and primaquine-atorvastatin were also synthesized and shown to be more potent than the parent drugs alone. Additionally, among the quinoline derivatives, new mefloquine derivatives were synthesized. Among the non-quinoline derivatives, we obtained excellent results with the triazolopyrimidine nucleus, which gave us prototype that inspired the synthesis of new heterocycles. The pyrazolopyrimidine derivatives stood out as non-quinoline derivatives that are potent inhibitors of the dihydroorotate dehydrogenase (DHODH) enzyme. We also examined the pyrazolopyridine and pyrazolopyrimidine nuclei.
Topics: Animals; Antimalarials; Chemistry Techniques, Synthetic; Dose-Response Relationship, Drug; Drug Development; Humans; Malaria; Molecular Structure; Plasmodium; Pyrazoles; Pyridines; Quinolines
PubMed: 31766184
DOI: 10.3390/molecules24224095 -
Molecules (Basel, Switzerland) Apr 2021Cannabinoids comprise different classes of compounds, which aroused interest in recent years because of their several pharmacological properties. Such properties include... (Review)
Review
Cannabinoids comprise different classes of compounds, which aroused interest in recent years because of their several pharmacological properties. Such properties include analgesic activity, bodyweight reduction, the antiemetic effect, the reduction of intraocular pressure and many others, which appear correlated to the affinity of cannabinoids towards CB and/or CB receptors. Within the search aiming to identify novel chemical scaffolds for cannabinoid receptor interaction, the CB antagonist/inverse agonist pyrazole-based derivative rimonabant has been modified, giving rise to several tricyclic pyrazole-based compounds, most of which endowed of high affinity and selectivity for CB or CB receptors. The aim of this review is to present the synthesis and summarize the SAR study of such tricyclic pyrazole-based compounds, evidencing, for some derivatives, their potential in the treatment of neuropathic pain, obesity or in the management of glaucoma.
Topics: Cannabinoids; Molecular Structure; Protein Binding; Pyrazoles; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Structure-Activity Relationship
PubMed: 33917187
DOI: 10.3390/molecules26082126 -
Targeted Oncology Dec 2020Oral darolutamide (Nubeqa™) is a novel second-generation, nonsteroidal, selective androgen receptor (AR) inhibitor indicated for the treatment of non-metastatic... (Review)
Review
Oral darolutamide (Nubeqa™) is a novel second-generation, nonsteroidal, selective androgen receptor (AR) inhibitor indicated for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). In the pivotal multinational, phase 3 ARAMIS trial in men with nmCRPC, relative to placebo plus ongoing androgen deprivation therapy (ADT), darolutamide (+ ADT) significantly prolonged metastasis-free survival (MFS) at the time of the primary analysis and overall survival (OS) at the time of the final OS analysis and was generally well tolerated in extended follow-up. Albeit long-term data from the real-world setting are required to fully define the safety profile of darolutamide, current evidence from the final ARAMIS analysis indicates that darolutamide has a low propensity for CNS-related adverse events (AEs) associated with other currently approved second-generation AR inhibitors. Given the efficacy and safety evidence from the final ARAMIS analysis and the key role of second-generation AR inhibitors in the management of nmCRPC, darolutamide + ADT represents an important emerging option for the treatment of men with nmCRPC who are at high risk of developing metastatic prostate cancer.
Topics: Double-Blind Method; Humans; Male; Prostatic Neoplasms, Castration-Resistant; Pyrazoles
PubMed: 33237495
DOI: 10.1007/s11523-020-00779-x -
Clinical and Applied... 2021Apixaban is indicated for the prevention of ischemic stroke in non-valvular atrial fibrillation (NVAF), as well as for the prevention and treatment of venous...
Apixaban is indicated for the prevention of ischemic stroke in non-valvular atrial fibrillation (NVAF), as well as for the prevention and treatment of venous thromboembolism (VTE). Dose adjustment is based on age, weight, and serum creatinine in NVAF, while there are no recommended adjustment criteria for VTE. Such adjustment is unconventional compared to other commonly used medications. The objective of this manuscript is to critically analyze each apixaban dosing adjustment criterion and its associated outcomes. PubMed articles from March 2013 to March 2020 were selected with search terms "apixaban," and "dose adjustment," "adjustment," or "adjustment criteria." Pharmacokinetic studies demonstrated increased apixaban exposure in patients >65 years of age, those with extreme body weights, and those with advanced renal impairment, though post-hemodialysis dosing may off-set the elevated apixaban exposure. However, clinical data show that among patients 75 years, 60 kg, and with estimated glomerular filtration rate <50 mL/min, including those on dialysis, there is no reduction in apixaban safety or efficacy. Published literature describes variable dosing strategies utilized in clinical practice. Overall, apixaban dose adjustment criteria may need to be re-evaluated.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Young Adult
PubMed: 34075813
DOI: 10.1177/10760296211021158 -
Molecules (Basel, Switzerland) Feb 2021The remarkable prevalence of pyrazole scaffolds in a versatile array of bioactive molecules ranging from apixaban, an anticoagulant used to treat and prevent blood clots... (Review)
Review
The remarkable prevalence of pyrazole scaffolds in a versatile array of bioactive molecules ranging from apixaban, an anticoagulant used to treat and prevent blood clots and stroke, to bixafen, a pyrazole-carboxamide fungicide used to control diseases of rapeseed and cereal plants, has encouraged both medicinal and organic chemists to explore new methods in developing pyrazole-containing compounds for different applications. Although numerous synthetic strategies have been developed in the last 10 years, there has not been a comprehensive overview of synthesis and the implication of recent advances for treating neurodegenerative disease. This review first presents the advances in pyrazole scaffold synthesis and their functionalization that have been published during the last decade (2011-2020). We then narrow the focus to the application of these strategies in the development of therapeutics for neurodegenerative diseases, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD).
Topics: Alzheimer Disease; Animals; Humans; Molecular Structure; Parkinson Disease; Pyrazoles
PubMed: 33668128
DOI: 10.3390/molecules26051202 -
Leukemia Apr 2021
Topics: COVID-19; Humans; Neoplasms; Nitriles; Pyrazoles; Pyrimidines; SARS-CoV-2
PubMed: 33731851
DOI: 10.1038/s41375-021-01214-4 -
Haematologica May 2020
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Nitriles; Pyrazoles; Pyrimidines
PubMed: 31515353
DOI: 10.3324/haematol.2019.222471