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1.
BMJ Open ; 11(9): e048000, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479934

RESUMO

OBJECTIVE: To examine sex differences in age-standardised rates (ASR) of overall and drug-specific drug poisoning deaths in Ireland between 2004 and 2017. DESIGN: Repeated cross-sectional study. SETTING: Drug poisoning deaths in Ireland. PARTICIPANTS: National Drug-Related Deaths Index and pharmacy claims database (Primary Care Reimbursement Service-General Medical Services) data from 2004 to 2017. OUTCOME MEASURES: The primary outcome was trends in drug poisoning death rates by sex. The secondary outcomes were trends in drug poisoning death rates involving (1) any CNS (Central Nervous System) depressants, (2) ≥2 CNS depressants and (3) specific drugs/drug classes (eg, prescription opioids, benzodiazepines, antidepressants, alcohol, cocaine and heroin) by sex. Joinpoint regression was used to examine trends, stratified by sex, in the ASR of drug poisoning deaths (2004-2017), change points over time and average annual percentage changes (AAPCs) with 95% CI. RESULTS: Increased ASR for all drug poisoning deaths from 6.86 (95% CI 6.01 to 7.72) per 100 000 in 2004 to 8.08 (95% CI 7.25 to 8.91) per 100 000 in 2017 was mainly driven by increasing deaths among men (AAPC 2.6%, 95% CI 0.2 to 5.1), with no significant change observed among women. Deaths involving ≥2 CNS depressants increased for both men (AAPC 5.6%, 95% CI 2.4 to 8.8) and women (AAPC 4.0%, 95% CI 1.1 to 6.9). Drugs with the highest significant AAPC increases for men were cocaine (7.7%, 95% CI 2.2 to 13.6), benzodiazepines (7.2%, 95% CI 2.9 to 11.6), antidepressants (6.1%, 95% CI 2.4 to 10.0) and prescription opioids (3.5%, 95% CI 1.6 to 5.5). For women, the highest AAPC was for antidepressants (4.2%, 95% CI 0.2 to 8.3), benzodiazepines (3.3%, 95% CI 0.1 to 6.5) and prescription opioids (3.0%, 95% CI 0.7 to 5.3). CONCLUSION: Drugs implicated in drug poisoning deaths vary by sex. Policy response should include prescription monitoring programmes and practical harm reduction information on polydrug use, especially CNS depressant drugs.


Assuntos
Overdose de Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Preparações Farmacêuticas , Envenenamento , Analgésicos Opioides , Estudos Transversais , Feminino , Humanos , Irlanda/epidemiologia , Masculino
2.
J Hazard Mater ; 416: 125891, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492829

RESUMO

CoP nanoparticle-loaded N-doped graphitic C3N4 nanosheets (CoP/N-g-C3N4) were fabricated via a facile three-step method to degrade pharmaceuticals and personal care products (PPCPs) via a visible-light-driven (VLD) peroxymonosulfate (PMS) activation system. 2 ppm carbamazepine (CBZ) can be removed completely within 10 min by the VLD-PMS system with a kinetic constant of k = 0.29128 min-1, as 25.8 times compared to that under dark conditions (k = 0.01128 min-1). The experimental and theoretical results showed that the doped graphitic N atoms could modulate the electronic properties of the g-C3N4 nanosheets. Subsequently, the Density Functional Theory (DFT) explained that CoP showed preference to bonding with the nitrogen atoms involved in the newly formed NË­N bond, and the Co‒N bond dramatically enhanced the transfer of photo-generated electrons from the N-g-C3N4 nanosheets. Electron paramagnetic resonance (EPR) tests show that singlet oxygen (1O2) plays a leading role in this case. Moreover, PMS molecules are also tended to be absorbed onto the electron-deficient carbon atoms near the newly formed NË­N bonds for PMS reduction, synergistically enhancing the degradation efficiency for CBZ and benzophenone-3 (BZP). The newly established VLD-PMS activation system was shown to treat the actual sewage in Hong Kong sewage treatment plants (STPs) very well. This work supplements the fundamental theory of radical and non-radical pathways in the sulfate radical (SO4•-)-based advanced oxidation process (SR-AOP) for environmental cleanup purposes.


Assuntos
Cosméticos , Grafite , Nanopartículas , Preparações Farmacêuticas , Peróxidos , Oxigênio Singlete
3.
Nanoscale ; 13(35): 15085-15099, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533154

RESUMO

The discovery of effective anticancer drug delivery systems and elucidation of the mechanism are enormous challenges. Using two drug administration-approved biomaterials, we constructed a natural medicine (NM)-loaded ternary supramolecular nanocomplex (TSN) suitable for large-scale production. The TSN has a better effect against cancer cells/stem cells than NM with differentially upregulated (27 versus 59) and downregulated (165 versus 66) proteins, respectively. Treatment with the TSN induced apoptosis and G2/M arrest, inhibited cell proliferation, metastasis and invasion, reduced colony/sphere formation, and decreased the frequency of side population cells and CD133+CD44+ABCG2+ cells. These results were revealed by multiple analyses (proteomic analysis, transwell migration and colony/sphere formation assays, biomarker profiling, etc.). We first reported the proteomic analysis of small lung cancer cells responding to a drug or its nanovesicles. We first conducted a proteomic evaluation of tumor cells responding to a drug supramolecular nanosystem. The supramolecular conformation of the TSN and the interactions of the TSN with albumin were verified by molecular docking experiments. The dominant binding forces in the TSN complexation process were electrostatic interactions, van der Waalsinteractions and bond stretching. The TSN binds to albumin more readily than NM does. The TSN has good in situ absorptive and in vitro/vivo kinetic properties. The relative bioavailability of the TSN to EA was 458.39%. The NM-loaded TSN is a supramolecular vesicle that can be produced at an industrial scale for efficient cancer therapy.


Assuntos
Apoptose , Preparações Farmacêuticas , Linhagem Celular Tumoral , Pontos de Checagem da Fase G2 do Ciclo Celular , Simulação de Acoplamento Molecular , Proteômica
4.
Nanoscale ; 13(32): 13835-13844, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34477658

RESUMO

Herbal medicines are potential candidates for the treatment of various diseases, but their medication safety remains poorly regulated. Current screening methods for the herbal medicine-induced nephrotoxic effects include histological and serological assessments, which often fail to reflect the kidney dysfunction instantly. Here we report a ratiometric fluorescence approach for the rapid and facile screening of drug-induced acute kidney injury using chromophore-modified gold nanoclusters. These gold nanoclusters are highly sensitive to reactive oxygen species (ROS), with a detection limit of 14 nM for ˙OH. After passing through the glomerular filtration barrier, the gold nanocluster-based probes can quantify the fluctuation of the ROS level in the kidneys and evaluate the risk of drug-induced nephrotoxicity. We further employed nephrotoxic triptolide as the model drug and the screening of drug-induced early renal injury was demonstrated using the nanoprobes, which is unattainable by conventional diagnostic approaches. Our fluorescent probes also allow the identification of other nephrotoxic components from herbal medicine such as aristolochine, providing a high-throughput strategy for the screening of herbal supplement-induced nephrotoxicity.


Assuntos
Nanopartículas Metálicas , Preparações Farmacêuticas , Corantes Fluorescentes , Ouro , Nanopartículas Metálicas/toxicidade , Espectrometria de Fluorescência
5.
Nanoscale ; 13(33): 13943-13961, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34477676

RESUMO

Drug-radiotherapy is a common and effective combinational treatment for cancer. This study aimed to explore the ionizing radiation-optimized drug treatment based on nanomaterials so as to improve the synergistic efficacy of drug-radiotherapy against cancer and limit the adverse effect on healthy organs. In this review, these emerging strategies were divided into four parts. First, the delivery of the drug-loaded nanoparticles was optimized owing to the strengthened passive targeting process, active targeting process, and cell targeting process of nanoparticles after ionizing radiation exposure. Second, nanomaterials were designed to respond to the ionizing radiation, thus leading to the release of the loading drugs controllably. Third, radiation-activated pro-drugs were loaded onto nanoparticles for radiation-triggered drug therapy. In particular, nontoxic nanoparticles with radiosensitization capability and innocuous radio-dynamic contrast agents can be considered as radiation-activated drugs, which were discussed in this review. Fourth, according to the various synergetic mechanisms, radiotherapy could improve the drug response of cancer, obtaining optimized drug-radiotherapy. Finally, relative suggestions were provided to further optimize these aforementioned strategies. Therefore, a novel topic was selected and the emerging strategies in this region were discussed, aiming to stimulate the inspiration for the development of ionizing radiation-optimized drug treatment based on nanomaterials.


Assuntos
Nanopartículas , Nanoestruturas , Neoplasias , Preparações Farmacêuticas , Humanos , Neoplasias/tratamento farmacológico , Radiação Ionizante
6.
BMJ Case Rep ; 14(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479878

RESUMO

A 64-year-old man with diabetes mellitus was diagnosed with a non-ST-segment elevation myocardial infarction and was treated with stent implantation. Four days later, he developed an electrical storm (ES) that persisted despite antiarrhythmic drugs and sedation. External defibrillation was performed more than 100 times over 2 hours. After ruling out the common causes of polymorphic ventricular tachycardia, an ES was considered because of brady-dependent R-on-T phenomenon, presumably precipitated by antiarrhythmic drugs. Temporary transvenous atrial overdrive pacing allowed complete suppression of premature ventricular complexes and ventricular fibrillation.


Assuntos
Infarto do Miocárdio , Preparações Farmacêuticas , Complexos Ventriculares Prematuros , Estimulação Cardíaca Artificial , Eletrocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Fibrilação Ventricular/terapia
7.
BMJ Case Rep ; 14(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479901

RESUMO

Carbamazepine (CBZ) is a medication used commonly in epilepsy. Decreases in free T4 levels simulating central hypothyroidism have been reported, although the clinical significance is still unclear. We present a 24-year-old man with Bardet-Biedl syndrome (BBS) who was found to have isolated biochemical central hypothyroidism. BBS is a ciliopathy occasionally associated with anterior pituitary dysfunction. While taking CBZ for epilepsy, his TSH was 1.73 mIU/L (reference range: 0.20-4.00 mIU/L) with a low free T4 of 6.6 pmol/L (reference range: 10.0-26.0 pmol/L). Pituitary MRI was normal. Although treated with levothyroxine initially, his apparent biochemical central hypothyroidism was later recognised as secondary to CBZ drug effect. This was confirmed with a normal free T4 of 12.2 pmol/L while he was off CBZ and levothyroxine. Despite the association between CBZ and biochemical central hypothyroidism, nearly all patients remain clinically euthyroid. This effect is reversible and recognition could lead to reductions in unnecessary thyroid replacement therapy if CBZ is discontinued.


Assuntos
Síndrome de Bardet-Biedl , Hipotireoidismo , Preparações Farmacêuticas , Adulto , Carbamazepina/efeitos adversos , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/diagnóstico , Masculino , Tireotropina , Adulto Jovem
8.
Anal Chim Acta ; 1177: 338797, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34482885

RESUMO

Single cell - tandem ICP-mass spectrometry (SC-ICP-MS/MS) was used for the determination of the absolute amount of Pt (coming from exposure to various concentration levels of cisplatin as a chemotherapeutic drug) and five endogenous elements (P, S, Fe, Cu and Zn) in individual human cells of three different types - Raji, Jurkat and Y79. Optimum conditions were obtained by using a sample introduction unit transporting cell suspension containing approx. 5 × 104 cells per mL at a flow rate of 10 µL min-1 to a nebulizer with narrow internal diameter (250 µm i.d.), mounted onto a total consumption spray chamber. Interference-free conditions were obtained in tandem MS mode (i) for P and S by pressurizing the collision/reaction cell (CRC) with O2 and monitoring the PO+ and SO + reaction product ions and (ii) for Fe by pressurizing the CRC with NH3 and monitoring the Fe(NH3)2+ reaction product ion. The quantification approach was validated by comparison of the absolute amounts of the target elements (in fg per cell) as obtained using SC-ICP-MS/MS with those obtained after acid digestion of approx. 2 × 106 cells and subsequent solution ICP-MS/MS analysis ("bulk" analysis). A higher Pt cell content was observed upon increasing the concentration of the cisplatin solution the cells were exposed to during 24 h. The Pt mass per cell (fg) increased linearly as a function of the cisplatin concentration, but a higher Pt uptake was found in the case of Jurkat cells compared to the other cell types. A cell viability assay showed a lack of chemosensitivity to cisplatin below 200 µM for the Raji and Y79 cell line, but an IC50 value of 11.1 ± 1.3 µM for Jurkat cells. This difference in chemo-responsiveness between the different cell types supported the difference in Pt uptake as indicated via SC-ICP-MS analysis. The increasing level of Pt did not have a marked effect on the contents of the endogenous elements monitored in Raji and Y79 cells, but a decrease in the P and S cell content upon increasing cisplatin treatment was observed for Jurkat cells. This can most likely be attributed to stress induced by the chemotherapeutic treatment in cells showing chemosensitivity towards cisplatin. The results also indicate differences in the absolute amount of endogenous element per cell between different cell types, suggesting the potential of SC-ICP-MS as a "metallo-fingerprinting" tool.


Assuntos
Preparações Farmacêuticas , Espectrometria de Massas em Tandem , Cisplatino , Humanos , Análise Espectral
9.
Anal Chim Acta ; 1177: 338742, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34482886

RESUMO

The reliable analysis of various compounds from tissue requires a tedious sample preparation. The sample pretreatment usually involves proper homogenization that facilitates extraction of target analytes, followed by an appropriate sample clean-up preventing matrix effects. Electromembrane extraction (EME) seems to have a significant potential to streamline the whole procedure. In this study, the applicability of EME for direct isolation of analytes from animal tissues was investigated for the first time. Extraction conditions were systematically optimized to isolate model analytes (daunorubicin and its metabolite daunorubicinol) from various tissues (myocardium, skeletal muscle and liver) coming from a pharmacokinetic study in rabbits. The relative recoveries of daunorubicin and its metabolite in all tissues, determined by the UHPLC-MS/MS method, were higher than 66 and 75%, respectively. Considerably low matrix effects (0 ± 8% with CV lower than 6%) and negligible content of phospholipids detected in EME extracts demonstrate the exceptional effectiveness of this microextraction approach in purification of tissue samples. The difference in the concentrations of the analytes determined after EME and reference liquid-liquid extraction of real tissue samples was lower than 12%, which further emphasized the trustworthiness of EME. Moreover, the considerable time reduction needed for sample treatment in case of EME must be emphasized. This study proved that EME is a simple, effective and reliable microextraction technique capable of direct extraction of the analytes from pulverized tissues without the need for an additional homogenization or purification step.


Assuntos
Preparações Farmacêuticas , Espectrometria de Massas em Tandem , Animais , Membranas Artificiais , Fosfolipídeos , Coelhos
10.
BMC Res Notes ; 14(1): 350, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496969

RESUMO

OBJECTIVE: The public health message 'move for health' is relevant given the high prevalence of insufficient physical activity, particularly in African countries. The call for behaviour modification including limiting unhealthy dietary patterns in these settings is therefore critical; however, there is limited knowledge on the adoption of health promotion strategies in the workplace. This study aimed to investigate workers' perceptions of physical activity and healthy eating. RESULTS: Five focus groups were conducted with 28 participants employed in a South African pharmaceutical manufacturing company to explore perceptions of physical activity and healthy eating. Results showed that two categories emerged: physical activity and unhealthy behaviours. Participants recognised the importance of obtaining sufficient physical activity in various domains, however believed that contemporary lifestyle limited opportunities for movement. Likewise, participants viewed healthy eating as unrealistic due to financial constraints. There was however agreement that total physical activity time could be increased during recreational pursuits outside of vocational time and may include intermittent walking for travel. These findings are important for workplace interventions and provide a more robust understanding of workers' perceptions of physical activity and healthy eating.


Assuntos
Dieta Saudável , Preparações Farmacêuticas , Exercício Físico , Promoção da Saúde , Humanos , Percepção , Pesquisa Qualitativa
11.
Braz J Biol ; 83: e247604, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495156

RESUMO

In the current report, we studied the possible inhibitors of COVID-19 from bioactive constituents of Centaurea jacea using a threefold approach consisting of quantum chemical, molecular docking and molecular dynamic techniques. Centaurea jacea is a perennial herb often used in folk medicines of dermatological complaints and fever. Moreover, anticancer, antioxidant, antibacterial and antiviral properties of its bioactive compounds are also reported. The Mpro (Main proteases) was docked with different compounds of Centaurea jacea through molecular docking. All the studied compounds including apigenin, axillarin, Centaureidin, Cirsiliol, Eupatorin and Isokaempferide, show suitable binding affinities to the binding site of SARS-CoV-2 main protease with their binding energies -6.7 kcal/mol, -7.4 kcal/mol, -7.0 kcal/mol, -5.8 kcal/mol, -6.2 kcal/mol and -6.8 kcal/mol, respectively. Among all studied compounds, axillarin was found to have maximum inhibitor efficiency followed by Centaureidin, Isokaempferide, Apigenin, Eupatorin and Cirsiliol. Our results suggested that axillarin binds with the most crucial catalytic residues CYS145 and HIS41 of the Mpro, moreover axillarin shows 5 hydrogen bond interactions and 5 hydrophobic interactions with various residues of Mpro. Furthermore, the molecular dynamic calculations over 60 ns (6×106 femtosecond) time scale also shown significant insights into the binding effects of axillarin with Mpro of SARS-CoV-2 by imitating protein like aqueous environment. From molecular dynamic calculations, the RMSD and RMSF computations indicate the stability and dynamics of the best docked complex in aqueous environment. The ADME properties and toxicity prediction analysis of axillarin also recommended it as safe drug candidate. Further, in vivo and in vitro investigations are essential to ensure the anti SARS-CoV-2 activity of all bioactive compounds particularly axillarin to encourage preventive use of Centaurea jacea against COVID-19 infections.


Assuntos
COVID-19 , Centaurea , Preparações Farmacêuticas , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases , SARS-CoV-2
12.
Rev Med Suisse ; 17(749): 1521-1525, 2021 Sep 08.
Artigo em Francês | MEDLINE | ID: mdl-34495588

RESUMO

Urinary incontinence is a common urological condition. It is classified into several subtypes, among which most frequently encountered are stress, urgency and mixed incontinence. Urinary continence depends on many physiological factors, some of which can potentially be influenced by numerous medications. The most commonly implicated drugs in urinary incontinency are antipsychotics, antidepressants, benzodiazepines, alpha blockers, diuretics, and hormone replacement therapy for menopause. Although the prescription of these types of drugs continues to increase, their effect on continence has received little attention from prescribers.


Assuntos
Preparações Farmacêuticas , Incontinência Urinária por Estresse , Incontinência Urinária , Feminino , Humanos , Menopausa , Incontinência Urinária/induzido quimicamente , Incontinência Urinária/tratamento farmacológico , Incontinência Urinária/epidemiologia , Incontinência Urinária de Urgência
13.
Rinsho Ketsueki ; 62(8): 978-987, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497238

RESUMO

Recurrence in acute myeloid leukemia (AML) is a major barrier in patients who achieve complete remission after induction of remission and consolidation therapy and desire long-term survival. Allogeneic hematopoietic stem cell transplantation lowers recurrence risk in patients; however, recurrence is common even after transplantation. Many maintenance therapies for AML aim to lower recurrence risk; therefore, research has focused on identifying drugs with a tolerable adverse-effect profile. Thus far, many trials of cytotoxic anticancer drugs used in maintenance therapy have showed no improvement in survival rates. In contrast, recent studies on immunomodulation, epigenetics, molecular-targeted drugs, etc. have demonstrated promising results. Therefore, we plan to review various maintenance therapies, such as immunotherapy, demethylating agents, and targeted therapies (including fms-like tyrosine kinase 3 inhibitors in particular) based on the current evidence. Moreover, we describe a new strategy that incorporates the assessment of measurable minimal residual disease.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Preparações Farmacêuticas , Humanos , Japão , Leucemia Mieloide Aguda/tratamento farmacológico , Uso Off-Label , Indução de Remissão
14.
BMC Bioinformatics ; 22(1): 418, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479477

RESUMO

BACKGROUND: Prediction of the drug-target interaction (DTI) is a critical step in the drug repurposing process, which can effectively reduce the following workload for experimental verification of potential drugs' properties. In recent studies, many machine-learning-based methods have been proposed to discover unknown interactions between drugs and protein targets. A recent trend is to use graph-based machine learning, e.g., graph embedding to extract features from drug-target networks and then predict new drug-target interactions. However, most of the graph embedding methods are not specifically designed for DTI predictions; thus, it is difficult for these methods to fully utilize the heterogeneous information of drugs and targets (e.g., the respective vertex features of drugs and targets and path-based interactive features between drugs and targets). RESULTS: We propose a DTI prediction method DTI-HeNE (DTI based on Heterogeneous Network Embedding), which is specifically designed to cope with the bipartite DTI relations for generating high-quality embeddings of drug-target pairs. This method splits a heterogeneous DTI network into a bipartite DTI network, multiple drug homogeneous networks and target homogeneous networks, and extracts features from these sub-networks separately to better utilize the characteristics of bipartite DTI relations as well as the auxiliary similarity information related to drugs and targets. The features extracted from each sub-network are integrated using pathway information between these sub-networks to acquire new features, i.e., embedding vectors of drug-target pairs. Finally, these features are fed into a random forest (RF) model to predict novel DTIs. CONCLUSIONS: Our experimental results show that, the proposed DTI network embedding method can learn higher-quality features of heterogeneous drug-target interaction networks for novel DTIs discovery.


Assuntos
Desenvolvimento de Medicamentos , Preparações Farmacêuticas , Interações Medicamentosas , Reposicionamento de Medicamentos , Aprendizado de Máquina
15.
FP Essent ; 508: 18-24, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34491708

RESUMO

New drug approvals and safety information are constantly being released. Staying up-to-date can be a daunting task for family physicians. Several electronic resources provide valuable, concise information directly. It is important to be well informed about new drugs, and drug mechanisms, indications, and administration routes. Pertinent new drug mechanisms include calcitonin gene-related peptide receptor antagonists for migraine prevention, selective inhibitors of influenza cap-dependent endonuclease, and adenosine triphosphate-citrate lyase inhibitors for hypercholesterolemia. Dapagliflozin recently gained approval for heart failure with reduced ejection fraction with or without type 2 diabetes. Newly approved administration routes include oral semaglutide and intranasal esketamine and glucagon. Drug accessibility, cost, and advantages over existing drugs should be considered. Physicians also should search formularies and promptly respond to prior authorization requests. Physicians should be knowledgeable about drug safety updates, such as adverse events and drug recalls. When a drug has been recalled, it is imperative for prescribers to provide accurate patient advice and therapeutic alternatives. Clinical pharmacists are excellent resources for new drug information, formulary and cost savings management, and drug recall navigation.


Assuntos
Diabetes Mellitus Tipo 2 , Preparações Farmacêuticas , Prescrições de Medicamentos , Medicina de Família e Comunidade , Humanos
16.
FP Essent ; 508: 25-32, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34491709

RESUMO

Drug-drug interactions (DDIs) occur when one drug adds to or diminishes the effect of another drug (ie, pharmacodynamic interaction) or affects the absorption, distribution, metabolism, or excretion of another drug (ie, pharmacokinetic interaction). Such interactions cause 26% of all adverse drug events (ADEs) and are associated with a significant burden on the health care system through increased hospitalizations. Some of the most common DDIs result from alterations in drug metabolism through interactions with cytochrome P450 enzymes and absorption through interactions with P-glycoproteins. Other common DDIs occur because of additive effects, including combinations of drugs that increase the risk of seizures, prolong the QT interval, increase central nervous system depression, and increase the risk of serotonin syndrome. Drug-related clinical decision support has been shown to improve the quality of patient care and decrease ADE rates. However, alerts generated by such systems should be interpreted using clinical judgment to determine the risks and benefits of certain drugs on a patient-specific basis. Family physicians can prevent clinically significant DDIs and optimize drug safety by using drug interaction software, along with a general understanding of common DDI mechanisms and collaboration with pharmacists.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Preparações Farmacêuticas , Interações Medicamentosas , Prescrições de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos
17.
ACS Infect Dis ; 7(9): 2637-2649, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34467755

RESUMO

As the existing therapeutic modalities for the treatment of cryptococcal meningitis (CM) have suboptimal efficacy, repurposing existing drugs for the treatment of CM is of great interest. The FDA-approved anthelmintic benzimidazoles, albendazole, mebendazole, and flubendazole, have demonstrated potent but variable in vitro activity against Cryptococcus neoformans, the predominant fungal species responsible for CM. We performed molecular docking studies to ascertain the interaction of albendazole, mebendazole, and flubendazole with a C. neoformans ß-tubulin structure, which revealed differential binding interactions and explained the different in vitro efficacies reported previously and observed in this investigation. Despite their promising in vitro efficacy, the repurposing of anthelmintic benzimidazoles for oral CM therapy is significantly hampered due to their high crystallinity, poor pharmaceutical processability, low and pH-dependent solubility, and drug precipitation upon entering the intestine, all of which result in low and variable oral bioavailability. Here, we demonstrate that the anthelmintic benzimidazoles can be transformed into partially amorphous low-melting ionic liquids (ILs) with a simple metathesis reaction using amphiphilic sodium docusate as a counterion. In vitro efficacy studies on a laboratory reference and a clinical isolate of C. neoformans showed 2- to 4-fold lower IC90 values for docusate-based ILs compared to the pure anthelmintic benzimidazoles. Furthermore, using a C. neoformans strain with green fluorescent protein (GFP)-tagged ß-tubulin and albendazole and its docusate IL as model candidates, we showed that the benzimidazoles and their ILs reduce the viability of C. neoformans by interfering with its microtubule assembly. Unlike pure anthelmintic benzimidazoles, the docusate-based ILs showed excellent solubility in organic solvents and >30-fold higher solubility in bioavailability-enhancing lipid vehicles. Finally, the docusate ILs were successfully incorporated into SoluPlus, a self-assembling biodegradable polymer, which upon dilution with water formed polymeric micelles with a size of <100 nm. Thus, the development of docusate-based ILs represents an effective approach to improve the physicochemical properties and potency of anthelmintic benzimidazoles to facilitate their repurposing and preclinical development for CM therapy.


Assuntos
Anti-Helmínticos , Cryptococcus neoformans , Líquidos Iônicos , Preparações Farmacêuticas , Anti-Helmínticos/farmacologia , Benzimidazóis/farmacologia , Ácido Dioctil Sulfossuccínico , Simulação de Acoplamento Molecular , Solubilidade
18.
Acta Biomed ; 92(4): e2021267, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34487061

RESUMO

BACKGROUND AND AIM OF THE WORK: Illicit drug (ID) use/abuse represent a social and economic burden for most countries worldwide which, in spite of the efforts to prevent this phenomena, is often a growing habit especially in the young adults. Preventive measurements, are needed to reduce the adverse health and social consequences of ID use/abuse. METHODS: This study investigated the relationship between coping strategies and ID use in students (N=12316) from the University of Parma, Italy. Information about the ID use in the past 12 months and coping strategies were collected with a cross-sectional research design using an online questionnaire. RESULTS: More than 25% of the participants used ID in the past year; men were more likely to use drugs than female; the likelihood of using drugs was inversely related to age. The relationship between coping strategies and ID use was analyzed with a multilevel logistic model taking into account the within-department nested structure of data. Analysis revealed that transcendence-orientation and problem-orientation were associated with a reduction of the likelihood to have used drugs. Conversely, avoidance and positive attitude were associated with an increase of the likelihood to have used drugs. Finally, seeking social support revealed a positive but modest association with increasing in drug use. CONCLUSIONS: The ID use association factors identified in this study could be utilized by the appropriate institutions/authorities as a critical review in order to develop relevant public health policies and preventive measures aimed at minimizing the use of ID in this critical age group.


Assuntos
Preparações Farmacêuticas , Universidades , Adaptação Psicológica , Estudos Transversais , Feminino , Humanos , Itália/epidemiologia , Masculino , Estudantes , Inquéritos e Questionários
19.
J Hazard Mater ; 416: 126184, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492955

RESUMO

Pharmaceuticals and other contaminants of emerging concern (CECs) are continuously introduced into the agroecosystem via reclaimed wastewater irrigation, a common agricultural practice in water-scarce regions. Although reclaimed wastewater irrigated crops are sold and consumed, only limited information is available on the occurrence of pharmaceuticals and other CECs in edible produce. Here, we report data on CECs in irrigation water, soils, and crops collected from 445 commercial fields irrigated with reclaimed wastewater in Israel. The following produce were analyzed: leafy greens, carrot, potato, tomato, orange, tangerine, avocado, and banana. Pharmaceuticals and CECs were found in quantifiable levels in all irrigation water, soils, and plants (>99.6%). Leafy greens exhibited the largest number and the highest concentration of pharmaceuticals. Within the same crop, contamination levels varied due to wastewater source and quality of treatment, and soil characteristics. Anticonvulsants (carbamazepine, lamotrigine, and gabapentin) were the most dominant therapeutic group found in the reclaimed wastewater-soil-plant continuum. Antimicrobials were detected in ~85% of the water and soil samples, however they exhibited low detection frequencies and concentrations in produce. Irrigation with reclaimed wastewater should be limited to crops where the risk for pharmaceutical transfer to the food chain is minimal.


Assuntos
Preparações Farmacêuticas , Águas Residuárias , Irrigação Agrícola , Produtos Agrícolas , Israel , Águas Residuárias/análise
20.
Cad Saude Publica ; 37(8): e00061120, 2021.
Artigo em Português | MEDLINE | ID: mdl-34495089

RESUMO

The study analyzes interactions between drug treatment adherence, blood pressure targets, and depression in a probabilistic sample of hypertensive individuals treated in the Family Health Strategy in Governador Valadares, Minas Gerais State, Brazil. This is a cross-sectional study with 641 hypertensive individuals 40 years or older, residing in the urban area of Governador Valadares. Structured scripts were used to collect data in home interviews, with a focus on the following indicators: Medication Assessment Questionnaire (MAQ), Beck Depression Inventory (BDI), and blood pressure measurement. Due to the simultaneity of the target events (depression, blood pressure target, and adherence), we applied a system of recursive and simultaneous nonlinear equations. The results suggest that the odds of meeting the blood pressure target increase significantly with adherence to treatment; they also suggest that individuals that meet the blood pressure target show 2.6 higher odds of treatment adherence. Adherence has a protective effect against depression: individuals with minimal adherence show 8.4 higher odds of developing depressive symptoms when compared to those with maximum adherence. Drug treatment adherence is related simultaneously to blood pressure control and lower levels of depression. Promoting drug treatment adherence is essential for ensuring that individuals remain normotensive, with the potential for reducing levels of depression. These positive externalities can reduce pressure on the health system, with simultaneous gains in quality of life for hypertensive individuals.


Assuntos
Hipertensão , Preparações Farmacêuticas , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Brasil , Estudos Transversais , Depressão , Saúde da Família , Humanos , Hipertensão/tratamento farmacológico , Adesão à Medicação , Qualidade de Vida
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