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1.
Aquat Toxicol ; 230: 105673, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33221665

RESUMO

The negative effects induced in marine organisms by Climate Change related abiotic factors consequences, namely ocean warming, are well-known. However, few works studied the combined impacts of ocean warming and contaminants, as pharmaceutical drugs. Carbamazepine (CBZ) and cetirizine (CTZ) occur in the marine environment, showing negative effects in marine organisms. This study aimed to evaluate the impacts of ocean warming on the effects of CBZ and CTZ, when acting individually and combined (drug vs drug), in the edible clam Ruditapes philippinarum. For that, drugs concentration, bioconcentration factors and biochemical parameters, related with clam's metabolic capacity and oxidative stress, were evaluated after 28 days exposure to environmentally relevant scenarios of these stressors. The results showed limited impacts of the drugs (single and combined) at control and warming condition. Indeed, it appeared that warming improved the oxidative status of contaminated clams (higher reduced to oxidized glutathione ratio, lower lipid peroxidation and protein carbonylation levels), especially when both drugs were combined. This may result from clam's defence mechanisms activation and reduced metabolic capacity that, respectively, increased elimination and limited production of reactive oxygen species. At low stress levels, defence mechanisms were not activated which resulted into oxidative stress. The present findings highlighted that under higher stress levels clams may be able to activate defence strategies that were sufficient to avoid cellular damages and loss of redox homeostasis. Nevertheless, low concentrations were tested in the present study and the observed responses may greatly change under increased pollution levels or temperatures. Further research on this topic is needed since marine heat waves are increasing in frequency and intensity and pollution levels of some pharmaceuticals are also increasing in coastal systems.


Assuntos
Anticonvulsivantes/toxicidade , Bivalves/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Água do Mar/química , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/metabolismo , Bivalves/metabolismo , Mudança Climática , Interações Medicamentosas , Modelos Teóricos , Oceanos e Mares , Temperatura
2.
Res Social Adm Pharm ; 17(2): 483-486, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32327397

RESUMO

Background: Combinations of hydroxychloroquine (HCQ) and azithromycin have been promoted as treatments for COVID-19 based on small, uncontrolled clinical trials that have not assessed potential risks. Risks of treatment include QT segment prolongation, Torsades de Pointes (TdP), and death. This comparative pharmacovigilance analysis evaluated the risk of these events. Methods: Data from the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) (>13 million total reports) were used. Queries extracted reports based on exposures of HCQ/chloroquine (CQ) alone, azithromycin alone, HCQ/CQ + azithromycin, amoxicillin alone, HCQ/CQ + amoxicillin alone. Amoxicillin served as a control. Events of interest included death and TdP/QT prolongation as well as accidents/injuries and depression as control events. Proportional Reporting Ratios (PRR) and 95% confidence intervals (CI) were calculated where a lower limit of the of 95% CI (Lower95CI) value of ≥2.0 is interpreted as a potential safety signal. Results: Lower95CIs for HCQ/CQ alone showed no potential safety signals for TdP/QT prolongation, death, or any of the control events included. The PRRs and 95% CIs for TdP/QT prolongation was 1.43 (1.29-2.59) with HCQ/CQ use alone and 4.10 (3.80-4.42) for azithromycin alone. For the combined HCQ/CQ + azithromycin group, the PRR and 95% CI was 3.77 (1.80-7.87). For the control of amoxicillin, there were no safety signals when used alone or in combination with HCQ/CQ. Conclusions: HCQ/CQ use was not associated with a safety signal in this analysis of FAERS data. However, azithromycin used alone was associated with TdP/QT prolongation events and should be used with caution.


Assuntos
Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Cloroquina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Síndrome do QT Longo/induzido quimicamente , Torsades de Pointes/induzido quimicamente , Antivirais/efeitos adversos , Azitromicina/efeitos adversos , /tratamento farmacológico , Cloroquina/efeitos adversos , Interações Medicamentosas , Quimioterapia Combinada , Humanos , Hidroxicloroquina/efeitos adversos , Síndrome do QT Longo/mortalidade , Farmacovigilância , Torsades de Pointes/mortalidade , Estados Unidos/epidemiologia
3.
Eur J Pharmacol ; 891: 173694, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33130275

RESUMO

In the context of the current SARS-CoV-2 pandemic, associations of drugs which interfere with specific steps of the viral infectious cycle are currently being exploited as therapeutic strategies since a specific treatment by vaccination is still unavailable. A widespread association of repurposed agents is the combination of the antimalarial drug Hydroxychloroquine and the macrolide antibiotic Azithromycin in the setting of clinical trials. But a closer analysis of their mechanism of action suggests that their concomitant administration may be impractical, and this is supported by experimental data with other agents of the same classes. However a sequential administration of the lysosomotropic antimalarial with the addition of the macrolide proton pump inhibitor after the first has reached a certain threshold could better exploit their antiviral potential.


Assuntos
Azitromicina/farmacologia , Reposicionamento de Medicamentos , Hidroxicloroquina/farmacologia , Antibacterianos/farmacologia , Antimaláricos/farmacologia , /virologia , Interações Medicamentosas/fisiologia , Reposicionamento de Medicamentos/métodos , Reposicionamento de Medicamentos/tendências , Humanos , /fisiologia
4.
Transplantation ; 105(1): 138-150, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32941394

RESUMO

BACKGROUND: The epidemiological and clinical characteristics of solid organ transplant (SOT) patients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic remains unclear. We conducted a matched retrospective cohort study to compare clinical outcomes among SOT recipients with the general population and to assess immunosuppression management. METHODS: Adult SOT recipients with laboratory polymerase chain reaction-confirmed SARS-CoV-2 infection admitted to a tertiary-care hospital in Barcelona, Spain, from March 11 to April 25, 2020, were matched to controls (1:4) on the basis of sex, age, and age-adjusted Charlson's Index. Patients were followed for up to 28 days from admission or until censored. Primary endpoint was mortality at 28 days. Secondary endpoints included admission to the intensive care unit and secondary complications. Drug-drug interactions (DDI) between immunosuppressants and coronavirus disease 2019 (COVID-19) management medication were collected. RESULTS: Forty-six transplant recipients and 166 control patients were included. Mean (SD) age of transplant recipients and controls was 62.7 (12.6) and 66.0 (12.7) years, 33 (71.7%) and 122 (73.5%) were male, and median (interquartile range) Charlson's Index was 5 (3-7) and 4 (2-7), respectively. Mortality was 37.0% in SOT recipients and 22.9% in controls (P = 0.51). Thirty-three (71.7%) patients underwent transitory discontinuation of immunosuppressants due to potential or confirmed DDI. CONCLUSIONS: In conclusion, hospitalized SOT recipients with COVID-19 had a trend toward higher mortality compared with controls, although it was not statistically significant, and a notable propensity for DDI.


Assuntos
/complicações , Imunossupressores/uso terapêutico , Transplante de Órgãos/mortalidade , Idoso , Idoso de 80 Anos ou mais , Interações Medicamentosas , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplantados
7.
Xenobiotica ; 51(1): 122-125, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32048540

RESUMO

1. Challenges and opportunities within peptide ADME (absorption, distribution, metabolism and elimination) were presented and discussed at the 1st peptide workshop of the Peptide ADME Discussion Group in Gothenburg, Sweden (15th of October 2018). This article summarises the presentations and discussions from this 1st workshop. The following topics were covered: Background science presentation on peptidases Presentation of various peptide ADME packages Peptide drug-drug interactions (DDI).


Assuntos
Descoberta de Drogas , Peptídeos , Simulação por Computador , Interações Medicamentosas , Humanos , Modelos Biológicos
8.
Xenobiotica ; 51(1): 1-4, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32571130

RESUMO

Challenges and opportunities within peptide ADME (absorption, distribution, metabolism and elimination) were presented and discussed at the 2nd workshop of the Peptide ADME Discussion Group in Cambridge, UK (17th of September 2019). This article summarises the presentations and discussions from this workshop. The following topics were covered: Peptide drug-drug interactions (DDIs) Regulatory perspectives on peptide ADME studies Bioavailability of therapeutic peptides impacted by metabolism and oligomerization in the subcutaneous compartment Regulated bioanalysis of parent peptide and active metabolites by immunoaffinity LC-MS/MS Peptide radiopharmaceutical development.


Assuntos
Peptídeos/metabolismo , Disponibilidade Biológica , Cromatografia Líquida , Interações Medicamentosas , Humanos , Espectrometria de Massas em Tandem
9.
J Med Vasc ; 45(6S): 6S31-6S38, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33276942

RESUMO

Cancer-associated thrombosis (CAT) is the second leading cause of death in cancer patients after tumor progression. The treatment of CAT is challenging because of a high risk of VTE recurrence, a high risk of bleeding, common presence of comorbidities, poly-medication, and potential drug-drug interactions (DDI). Since 2018, direct oral anticoagulants (DOACs) represent a promising therapeutic alternative and have been recently included into the 2019 update of the International Initiative on Thrombosis and Cancer (ITAC-CME) clinical practice guidelines for management of CAT. However, pharmacokinetic studies suggest that concomitant treatment with P-gp or CYP3A4 inhibitors will result in an increased exposure to rivaroxaban and apixaban, but the clinical relevance of these studies is unknown. In addition, there is an important inter-individual variability in drug absorption, distribution, metabolism and elimination, even more in cancer patients. Overall, the risk of pharmacokinetic DDI should be estimated based on several individual (patient age, renal and liver function, number of comedications) and diseases-related factors, including inflammation, sarcopenia, and low body weight. In this context, DDI with clinical implications could be expected with anti-neoplastic agents or supportive care treatments, especially with drugs known to be moderate or strong inhibitors/inducers of CYP3A4 and P-gp. Consequently, in the presence of potential DDIs through CYP3A4, and/or P-gp, LMWHs remain the first-line anticoagulant of choice for the long-term treatment of CAT. Multidisciplinary consultation meetings and therapeutic patient education should be emphasized in the complex management of CAT.


Assuntos
Interações Medicamentosas , Inibidores do Fator Xa/efeitos adversos , Neoplasias/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Administração Oral , Tomada de Decisão Clínica , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/farmacocinética , Humanos , Neoplasias/sangue , Neoplasias/epidemiologia , Polimedicação , Medição de Risco , Fatores de Risco , Tromboembolia Venosa/sangue , Tromboembolia Venosa/epidemiologia
10.
Med Hypotheses ; 144: 110198, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33254507

RESUMO

Chloroquine (CQ) and hydroxychloroquine (HCQ) were among the first drugs repurposed for the treatment of SARS-CoV-2 infection. A few in vitro studies confirmed that both drugs exhibited dose dependent anti-SARS-CoV-2 activities. These observations and the encouraging results from early poorly conducted observational studies created a major hype about the therapeutic potential of these drugs in the treatment of COVID-19 disease. This was further catalyzed by media and political influences leading to a widespread use of these agents. Subsequent randomized trials revealed lack of efficacy of these agents in improving the outcomes of COVID-19 or in preventing infection in post-exposure prophylaxis studies. Nevertheless, many ongoing trials continue to actively recruit tens of thousands of patients to receive HCQ worldwide. In this perspective, we address the possible mechanisms behind the lack of efficacy and the increased risk of cardiac toxicity of HCQ in COVID-19 disease. For the lack of efficacy, we discuss the fundamental differences of treatment initiation between in vitro and in vivo studies, the pitfalls of the pharmacological calculations of effective blood drug concentrations and related dosing regimens, and the possible negative effect of HCQ on the antiviral type-I interferon response. Although it has been repeatedly claimed that HCQ has a longstanding safety track record for many decades in use, we present counterarguments for this contention due to disease-drug and drug-drug interactions. We discuss the molecular mechanisms and the cumulative epidemiological evidence of HCQ cardiac toxicity.


Assuntos
/tratamento farmacológico , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Animais , Antivirais , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/mortalidade , Azitromicina/farmacologia , Bradicardia/induzido quimicamente , Bradicardia/mortalidade , Morte Súbita Cardíaca , Interações Medicamentosas , Coração/efeitos dos fármacos , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/mortalidade , Humanos , Interferon Tipo I/metabolismo , Camundongos , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco
11.
Medicine (Baltimore) ; 99(50): e23695, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327360

RESUMO

BACKGROUND: Randomized trials and observation studies have revealed conflicting results regarding the interaction between clopidogrel and proton pump inhibitors (PPIs). The aim of our study was to provide laboratory evidence regarding whether PPIs blunt the antiplatelet reactivity of clopidogrel. METHODS: We included records of Asian patients who received clopidogrel treatment for cardiovascular or cerebrovascular events and the VerifyNow P2Y12 assay for platelet reactivity monitoring. The responsiveness of antiplatelet effect to clopidogrel was analyzed according to 3 criteria:Results: Patients treated without PPIs did not differ significantly from those concomitantly treated with PPIs in terms of levels of PI (25.7% ± 24.3% vs 23.0 ± 25.3%, P = .4315), PRU (187.3 ± 74.0 vs 197.4 ±â€Š77.3, P = .3373), or responsiveness to antiplatelet (adjusted absolute risk, 3.5%; 95% confidence interval, - 10.7 to 17.7%; P = .6297). Patients treated with lansoprazole, esomeprazole, pantoprazole, and rabeprazole exhibited no significant differences in PRU or PI levels compared with those treated without PPIs. By contrast, patients treated with dexlansoprazole exhibited a significantly decreased level of PI (25.7% ±â€Š24.3% vs 14.0% ±â€Š21.6%, P = .0297) and responsiveness to clopidogrel under the criterion PI > 20% (adjusted absolute risk: 10.5%; 95% confidence interval: 2.6% to 43.6%; P = .0274). CONCLUSION: No robust interaction between clopidogrel and PPIs was found, but caution should be exercised in the concomitant use of dexlansoprazole and clopidogrel in Asians.


Assuntos
Clopidogrel/farmacocinética , Inibidores da Agregação de Plaquetas/farmacocinética , Inibidores da Bomba de Prótons/farmacologia , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Comorbidade , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Fatores Sexuais
12.
Sci Rep ; 10(1): 21508, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33299085

RESUMO

To increase the success in Covid 19 treatment, many drug suggestions are presented, and some clinical studies are shared in the literature. There have been some attempts to use some of these drugs in combination. However, using more than one drug together may cause serious side effects on patients. Therefore, detecting drug-drug interactions of the drugs used will be of great importance in the treatment of Covid 19. In this study, the interactions of 8 drugs used for Covid 19 treatment with 645 different drugs and possible side effects estimates have been produced using Graph Convolutional Networks. As a result of the experiments, it has been found that the hematopoietic system and the cardiovascular system are exposed to more side effects than other organs. Among the focused drugs, Heparin and Atazanavir appear to cause more adverse reactions than other drugs. In addition, as it is known that some of these 8 drugs are used together in Covid-19 treatment, the side effects caused by using these drugs together are shared. With the experimental results obtained, it is aimed to facilitate the selection of the drugs and increase the success of Covid 19 treatment according to the targeted patient.


Assuntos
Sulfato de Atazanavir/uso terapêutico , /metabolismo , Heparina/uso terapêutico , /metabolismo , Sulfato de Atazanavir/efeitos adversos , Interações Medicamentosas , Heparina/efeitos adversos , Humanos
13.
J Psychiatr Pract ; 26(6): 485-492, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33275385

RESUMO

The goal of this column is to provide information to health care professionals about drug-drug interactions (DDIs) and why DDIs are important to consider in those at serious risk of illness with Coronavirus Disease 2019 (COVID-19). Important considerations discussed in this column include the frequency and complexity of multiple medication use, particularly important for the older patient who often has multiple comorbid illnesses. The column covers the following issues: (1) Why patients at high risk for serious illness from COVID-19 are also at high risk for DDIs. (2) Application of results of pharmacoepidemiological studies to the population at risk for serious COVID-19 illness. (3) Mechanisms underlying DDIs, frequency and potential complexity of DDIs, and how DDIs can present clinically. (4) Methods for preventing or mitigating DDIs. (5) An introduction to the University of Liverpool drug interaction checker as a tool to reduce the risk of adverse DDIs while treating patients for COVID-19. Commentary is also provided on issues related to specific psychiatric and nonpsychiatric medications a patient may be taking. A subsequent column will focus on DDIs between psychiatric medications and emerging COVID-19 treatments, as a detailed discussion of that topic is beyond the scope of this column.


Assuntos
/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Polimedicação , Detecção do Abuso de Substâncias/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Interações Medicamentosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Pessoa de Meia-Idade , Risco , Adulto Jovem
14.
Nat Commun ; 11(1): 6136, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262326

RESUMO

We present comboFM, a machine learning framework for predicting the responses of drug combinations in pre-clinical studies, such as those based on cell lines or patient-derived cells. comboFM models the cell context-specific drug interactions through higher-order tensors, and efficiently learns latent factors of the tensor using powerful factorization machines. The approach enables comboFM to leverage information from previous experiments performed on similar drugs and cells when predicting responses of new combinations in so far untested cells; thereby, it achieves highly accurate predictions despite sparsely populated data tensors. We demonstrate high predictive performance of comboFM in various prediction scenarios using data from cancer cell line pharmacogenomic screens. Subsequent experimental validation of a set of previously untested drug combinations further supports the practical and robust applicability of comboFM. For instance, we confirm a novel synergy between anaplastic lymphoma kinase (ALK) inhibitor crizotinib and proteasome inhibitor bortezomib in lymphoma cells. Overall, our results demonstrate that comboFM provides an effective means for systematic pre-screening of drug combinations to support precision oncology applications.


Assuntos
Antineoplásicos/farmacologia , Aprendizado de Máquina , Bortezomib/farmacologia , Linhagem Celular Tumoral , Crizotinibe/farmacologia , Interações Medicamentosas , Humanos , Linfoma/tratamento farmacológico , Medicina de Precisão
15.
Sci Rep ; 10(1): 20958, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262433

RESUMO

The impact of drug-drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI 69-85%) patients, and in 33 (26%, 95% CI 19-35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p = 0.010). After adjustment, only the Charlson index was independently associated with death [adjusted OR (95% CI) for Charlson index ≥ 5: 85 (10-731), p < 0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04-0.53), p = 0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age and comorbidities. Patients managed by the Infectious Diseases Unit had lower risk of major DDI.


Assuntos
Antivirais/efeitos adversos , Lopinavir/efeitos adversos , Lopinavir/uso terapêutico , Inibidores de Proteases/efeitos adversos , Ritonavir/efeitos adversos , Ritonavir/uso terapêutico , Idoso , Antivirais/uso terapêutico , Estudos Transversais , Combinação de Medicamentos , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteases/uso terapêutico , Espanha
16.
S D Med ; 73(10): 480-483, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33264528

RESUMO

INTRODUCTION: Multiplying the effects of central nervous system and respiratory depression, benzodiazepines are involved in 30 percent of opioid overdoses. The mortality rate in co-administration of both medications is 10 times higher than those taking only opioids. The medication labels even contain direct instructions or "black box" labels warning against their use in conjunction. However, opioids and benzodiazepines are commonly prescribed together by providers, regardless of these contraindications. The purpose of this manuscript was to bring further attention to the opioid crisis and to study the effect of a simple and cost-effective intervention in reducing the co-administration of benzodiazepines and opioids. METHODS: A didactic clinical presentation along with handouts outlining the epidemiology of co-administration of benzodiazepines and opioids, side effects of each medication class, alternatives to consider prior to initiating therapy, guidelines on how to avoid medication misuse, recommendations for when to taper medications, and examples of how to taper these medications was made to attendings and residents of one family medicine clinic in a small, midwestern community. The number of patients co-prescribed these medications at this clinic was determined by searching the electronic medical record, the intervention was given, and three months later the number was measured again for comparison. RESULTS: The intervention did not result in a significant decrease in those co-prescribed benzodiazepines and opioids. CONCLUSIONS: This study opens the door to future studies investigating longer time frames, decreases in dosages, and patients appropriately prescribed these medications. Alternative interventions such as medical record notifications and more frequent education sessions provide direction for continued research in an effort to impact the epidemic our country is facing with the use of opioids, benzodiazepines and other prescription pain medications.


Assuntos
Analgésicos Opioides , Benzodiazepinas , Epidemia de Opioides , Padrões de Prática Médica , Medicamentos sob Prescrição , Analgésicos Opioides/uso terapêutico , Benzodiazepinas/uso terapêutico , Interações Medicamentosas , Registros Eletrônicos de Saúde , Humanos , Prescrições
17.
Adv Chronic Kidney Dis ; 27(5): 434-441, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33308510

RESUMO

Coronavirus disease 2019, the disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was first identified in the Hubei Province of China in late 2019. Currently, the only role for therapy is treatment of the disease, as opposed to postexposure prophylaxis, however multiple clinical trials are currently ongoing for both treatment and prophylaxis. Treating coronavirus disease 2019 relies on two components; the first is inhibition of the viral entrance and replication within the body and the second is inhibition of an exacerbated immune response which can be seen in patients with severe disease. Many drugs have shown in vitro antiviral activity; however, clinical trials have not been as promising. This review summarizes the current data for the most commonly used drugs for coronavirus disease 2019 and will cover the unique factors that may affect the dosing of these medications in patients with CKD. While clinical trials are ongoing, most are in patients with normal kidney function. During a pandemic, when patients with CKD are at higher risk of both infection and death, it is imperative to include patients these patients in the clinical trials.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Insuficiência Renal Crônica/metabolismo , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , /prevenção & controle , /uso terapêutico , Cloroquina/uso terapêutico , Creatinina/metabolismo , Citidina/análogos & derivados , Citidina/uso terapêutico , Dexametasona/uso terapêutico , Combinação de Medicamentos , Interações Medicamentosas , Humanos , Hidroxicloroquina/uso terapêutico , Hidroxilaminas/uso terapêutico , Imunização Passiva , Interferons/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Lopinavir/uso terapêutico , Pirazinas/uso terapêutico , Eliminação Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Terapia de Substituição Renal , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico
18.
Rev. esp. cardiol. Supl. (Ed. impresa) ; 20(supl.E): 33-39, dic. 2020. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-195345

RESUMO

La búsqueda de tratamientos eficaces contra la pandemia actual por COVID-19 ha supuesto un desafïo enorme para la comunidad científica. De hecho, no existe todavía un tratamiento claramente efectivo, además de las medidas de soporte, contra el SARS-CoV-2. Los esfuerzos se han centrado en recuperar fármacos antivirales empleados previamente contra otras infecciónes viricas y en el uso de antiinflamatorios, dado el estado hiperinflamatorio que pueden sufrir los pacientes con COVID-19 y que se asocia con un peor pronóstico de la enfermedad. Sin embargo, estos fármacos, usados en ocasiones de manera compasiva, pueden causar efectos secundarios graves o interacciones farmacológicas que se debe conocer. El objetivo de este artículo es revisar el estado actual del conocimiento sobre los tratamientos farmacológicos más usados contra la COVID-19 en nuestro medio, prestando una especial atención a los efectos secundarios y las interacciones farmacológicas relacionadas con el sistema cardiovascular


The search for effective treatments against COVID-19 in the current pandemic has presented the scientific community with an enormous challenge. In fact, there is still no effective treatment for SARS-CoV-2 infection, apart from supportive measures. Research has focused on re-examining antiviral drugs that were previously used against other viral infections and on the use of anti-inflammatories, since COVID-19 patients can develop a hyperinflammatory state, which is associated with a poorer disease prognosis. However, these drugs, sometimes administered on a compassionate-use basis, can cause serious side effects or drug interactions that we should be aware of. The aim of this article is to provide an overview of what is currently known about the pharmacological therapies most frequently used against COVID-19 in our field, while paying particular attention to the adverse events and drug interactions that can affect the cardiovascular system


Assuntos
Humanos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Pandemias , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Sistema Cardiovascular/efeitos dos fármacos , Interações Medicamentosas
19.
Neurología (Barc., Ed. impr.) ; 35(9): 628-632, nov.-dic. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-192758

RESUMO

INTRODUCCIÓN: En los últimos meses han surgido dudas por parte de pacientes, médicos de familia y neurólogos sobre la posibilidad de que algunos de los fármacos que habitualmente se utilizan en cefaleas y neuralgias puedan facilitar o complicar la infección por el SARS-CoV-2. MATERIAL Y MÉTODOS: Hemos recabado información sobre el posicionamiento de sociedades científicas, así como de las distintas Agencias de Medicamentos (americana, europea y española) para poder esclarecer dudas respecto al uso de fármacos como lisinopril, candesartán, ibuprofeno, corticoides, carbamazepina, anticuerpos monoclonales contra el péptido relacionado con el gen de la calcitonina (CGRP) durante la pandemia por COVID-19. RESULTADOS: Planteamos recomendaciones acerca del uso de fármacos habituales en el tratamiento de las cefaleas en el contexto de la pandemia por COVID-19, basándonos en las evidencias de las que disponemos en el momento actual. CONCLUSIONES: Actualmente no existe ningún argumento científico robusto para contraindicar formalmente ninguno de los tratamientos que se emplean en cefaleas y neuralgias


INTRODUCTION: In recent months, doubts have arisen among patients, general practitioners, and neurologists as to whether some drugs commonly used in patients with headaches and neuralgia may favour or complicate the disease caused by SARS-CoV-2. MATERIAL AND METHODS: We collected information on the opinions of scientific societies and medicines agencies (American, European, and Spanish) to clarify doubts regarding the use of drugs such as lisinopril, candesartan, ibuprofen, corticosteroids, carbamazepine, and monoclonal antibodies targeting the calcitonin generelated peptide in the context of the COVID-19 pandemic. RESULTS: We make recommendations about the use of standard headache treatments in the context of the COVID-19 pandemic, based on the current scientific evidence. CONCLUSIONS: At present, there is no robust scientific argument to formally contraindicate any of the standard treatments employed for headaches and neuralgias


Assuntos
Humanos , Sociedades Médicas , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pandemias , Cefaleia/tratamento farmacológico , Cefaleia/virologia , Neuralgia/tratamento farmacológico , Neuralgia/virologia , Espanha , Interações Medicamentosas
20.
Seizure ; 83: 181-186, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33171342

RESUMO

OBJECTIVE: We aimed to evaluate the influence of concomitant antiepileptic drugs (AEDs) on serum perampanel concentration and to correlate the concentration with clinical response and tolerability. METHODS: A total of 4224 serum samples were obtained from 763 pediatric, adolescent, and adult patients for routine therapeutic drug monitoring. We compared the extent of enzyme induction between cytochrome P450 3A4 (CYP3A4) inducer regimens and built a statistical model to estimate the serum perampanel concentration that considered use of CYP3A4 inducers and inhibitors. To assess the tolerability and clinical effectiveness of perampanel therapy, we used the nested case-control approach. The case group was matched with the control group for age, sex, epilepsy type, and perampanel exposure periods. RESULTS: Concomitant use of the inducers phenytoin, carbamazepine, and phenobarbital dose-dependently reduced the perampanel concentration by 51 %, 67 %, and 37 %, respectively. The estimate model showed a good correlation between the predicted and measured concentrations (r2 = 0.62, p < 0.001). In 206 patients, the seizure reduction from baseline was > 50 % and the median perampanel concentration was 351 ng/mL (interquartile range, 191-603 ng/mL). Adverse events, such as somnolence, dizziness, and irritability, were experienced by 185 patients. The responder odds ratio was 5.1-fold higher in patients with a serum concentration > 600 ng/mL than in those with a serum concentration < 200 ng/mL; however, the former group had a 7.9-fold higher incidence of adverse events. CONCLUSION: Therapeutic drug monitoring is clinically useful to assess drug interactions between perampanel and CYP3A4 inducers and inhibitors. We recommend that the target concentration of perampanel is initially set at 200-600 ng/mL. Serum concentrations > 600 ng/mL were associated with greater anti-seizure effects but had an increased risk of adverse events.


Assuntos
Anticonvulsivantes/uso terapêutico , Quimioterapia Combinada , Epilepsia/tratamento farmacológico , Resultado do Tratamento , Adolescente , Adulto , Anticonvulsivantes/administração & dosagem , Carbamazepina/uso terapêutico , Criança , Interações Medicamentosas/fisiologia , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Japão , Masculino , Fenobarbital/uso terapêutico , Fenitoína/uso terapêutico , Convulsões/tratamento farmacológico
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