Digoxin and warfarin

BACKGROUND: High-alert medication (HAM) is more predictable to cause significant harm to the patient, even when used as intended. The damage related to the HAM lead not only suffering to the patient, but also raise the additional costs associated with care. OBJECTIVE: Evaluate the incidence of drug-related adverse events related to the use of high-alert medications. METHODS: It was conducted an active search for information through COCHRANE databases, LILACS, SciELO, SCOPUS, PubMed/MEDLINE and WEB OF SCIENCE...

In vitro systems that accurately model in vivo conditions in the gastrointestinal tract may aid the development of oral drugs with greater bioavailability. Here we show that the interaction profiles between drugs and intestinal drug transporters can be obtained by modulating transporter expression in intact porcine tissue explants via the ultrasound-mediated delivery of small interfering RNAs and that the interaction profiles can be classified via a random forest model trained on the drug-transporter relationships...

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug absorption, potentially affecting pharmacokinetics, particularly in the case of medications with a narrow therapeutic index. PURPOSE: The purpose of this systematic review is to summarize data on drug-drug interactions between GLP1RAs and oral drugs. DATA SOURCES: The PubMed and EMBASE databases were searched up to November, 1st 2023...

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Vericiguat, a novel soluble guanylate cyclase (sGC) stimulator, is approved for the treatment of heart failure (HF) with reduced ejection fraction (HFrEF). Decreased nitric oxide (NO) availability, sGC desensitization to NO, sGC deficiency, and reduced cyclic guanosine monophosphate (cGMP) signaling are potential contributing factors for HF disease progression. Vericiguat works via stimulation of sGC in the critical NO-sGC-cGMP pathway. Vericiguat is primarily metabolized by glucuronidation via uridine diphosphate-glucuronosyltransferase (UGT) isoforms UGT1A1 and UGT1A9...

The current recommendations for monitoring digoxin, a narrow therapeutic index drug, are limited to confirming medication use or investigating suspicion of toxicity and fail our oath to do no harm. Numerous meta-analyses evaluating digoxin use consistently recommend frequent monitoring to maintain the level of 0.5 to ≤1.0 ng/ml because higher levels lead to increased morbidity and mortality without benefit. Data from the United States National Poison Control Center (2012-2020) show annual deaths due to digoxin of 18-36 compared to lithium's 1-7, and warfarin's 0-2 respectively...

Effective therapy for patients with chronic cardiac failure (CCF) entails significant lifestyle modifications as well as often complex pharmaceutical regimes to alleviate symptoms, which, however, do not actually cure many patients. The gradual loss of cardiac function is impeded but not halted by such complicated pharmacological therapy, which primarily includes angiotensin-converting enzyme inhibitors, beta-blockers and diuretics, and sometimes digoxin, aspirin, warfarin, and anti-arrhythmic agents. Patients may be advised to track their weight and modify their diuretic prescription accordingly to avoid fluid overload or dehydration as part of the treatment plan...

Background: Individualized pharmaceutical care, which consists of therapeutic drug monitoring (TDM), pharmacogenetic (PGx) testing and pharmacist-managed clinic (PMC), is one of the most important trends in clinical pharmacy development in the future. While relevant studies in China were primarily single-center or regional. This study aims to explore the current status of individualized pharmaceutical care in China, find out the existing problems and provide references for its further development. Methods: An electronic questionnaire was used and national hospitals' pharmaceutical administration data from January to December 2019 were collected...

The blood-brain barrier (BBB) protects the brain from toxins but hinders the penetration of neurotherapeutic drugs. Therefore, the blood-to-brain permeability of chemotherapeutics must be carefully evaluated. Here, we aimed to establish a workflow to generate primary cultures of human brain microvascular endothelial cells (BMVECs) to study drug brain permeability and bioavailability. Furthermore, we characterized and validated this BBB model in terms of quantitative expression of junction and drug-transport proteins, and drug permeability...

BACKGROUND: Isolated left ventricular apical hypoplasia (ILVAH) is a rare, probably congenital, cardiac condition recently reported in the last two decades. Although most cases are asymptomatic or mildly symptomatic, some severe and fatal cases have been reported, leading to more efforts for appropriate diagnosis and treatment. We describe the first, and severe, case of this pathology in Peru and Latin America. CASE SUMMARY: A 24-year-old male with a history of long-standing alcohol and illicit drug use presented with symptoms of heart failure (HF) and atrial fibrillation (AF)...

PURPOSE/BACKGROUND: Glycine transporter-1 inhibitors may ameliorate cognitive deficits in schizophrenia. This study evaluated potential drug-drug interactions with the glycine transporter-1 inhibitor BI 425809. METHODS/PROCEDURES: Interactions with cytochromes P450 (CYP) and P-glycoprotein (P-gp) were assessed in in vitro assays using human hepatocytes and Caco-2 cells, respectively. Pharmacokinetic characteristics of probe drugs were subsequently assessed in a Phase I, open-label, single-sequence crossover study in healthy male participants...

BACKGROUND: Drug-drug interactions (DDIs) can lead to medication-related harm, and the older population is at greatest risk. We conducted a systematic review and meta-analysis to estimate DDI prevalence and identify common DDIs in older community-dwelling adults. METHODS: PubMed and EMBASE were searched for observational studies published between 01/01/2010 and 10/05/2021 reporting DDI prevalence in community-dwelling individuals aged ≥ 65 years. Nursing home and inpatient hospital studies were excluded...

The prevalence of atrial fibrillation (AF) is increasing as the population ages. AF treatment-related complications also increase markedly in older adults (defined as ≥75 years of age for this review). The older AF population has a high risk of stroke, bleeding, and death. Syncope and fall-related injuries are the most common reasons for nonprescription of oral anticoagulation (OAC), and are more common in older adults when OACs are used with antiarrhythmic drugs. Digoxin may be useful for rate control, but associations with increased mortality limit its use...

CC-90001 is predominantly metabolised via glucuronidation, while oxidative metabolism is a minor pathway in human hepatocytes and liver microsomes. In vitro , CC-90001 glucuronidation was catalysed by UGT1A9, UGT1A4, and UGT1A1, while oxidative metabolism was primarily mediated by CYP3A4/5 with minor contributions from CYP1A2, CYP2C9, CYP2B6, and CYP2D6.CC-90001 in vitro inhibits CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4 ≤ 55% at 100 μM, and the inhibition was negligible at ≤30 μM. CC-90001 is not a time-dependent CYP inhibitor...

PURPOSE: To best promote drug tolerability and efficacy in the clinic, data from drug-drug interaction (DDI) evaluations and subsequent translation of the results to DDI prevention and/or management strategies must be incorporated into the US Food and Drug Administration (FDA) product labeling in a consistent manner because differences in language might result in varied interpretations. This analysis aimed to assess the consistency in DDI labeling language in New Drug Applications (NDAs)...

BACKGROUND: To study the various factors affecting the anticoagulant effect of warfarin, and to promote the rational use of warfarin. METHODS: We collected the medical records of 125 hospitalized patients who used warfarin from January 2018 to December 2019. Statistical analysis was performed on characteristics such as gender, age, treatment, diabetes, hyperlipidemia, hyperthyroidism, hypothyroidism, hepatitis, renal insufficiency, and nephritis; along with other pathological factors, such as aspirin, clopidogrel, spironolactone, amiodarone, amlodipine, trimetazidine, bisoprolol, isosorbide, atorvastatin, furosemide, digoxin, metoprolol, acarbose, levamlodipine, enoxaparin, moxifloxacin, levofloxacin, other drug interactions, and comorbidities...

During the last several decades, there have been major advances in the evolution of drug therapies for the rate management of atrial fibrillation (AF). Initially, the drug of choice was digoxin but currently, the drug of choice is beta-adrenergic blockers. Drug therapies for stroke prevention in AF have also evolved. Initially, the drug of choice was aspirin, then became warfarin, and now in the current era, there are newer oral anticoagulants, such as apixaban, which are the preferred drugs. In this case report, we present the details of a 79-year-old athletic man who developed palpitations due to rapid AF at age 31...

INTRODUCTION: Gastrointestinal bleeding (GIB) remains a common and vexing complication of left ventricular assist device (LVAD) support. Recent single-center analyses suggest that ACE inhibitors (ACEi)/angiotensin receptor blockers (ARB) and digoxin may prevent GIB in LVAD patients. Here we evaluate the effect of guideline-directed medical therapies (GDMT) for heart failure (HF) on rates of GIB through analysis of the INTERMACS registry database. METHODS: Thirteen thousand seven hundred thirty-two patients who received a continuous-flow LVAD and were on antiplatelet therapy and anticoagulation with warfarin after 3 months of pump support were included in the analysis...

Ivosidenib is a potent, targeted, orally active, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1) that has been approved in the United States for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) who are greater than or equal to 75 years of age or ineligible for intensive chemotherapy, and those with relapsed or refractory AML, with a susceptible IDH1 mutation. Ivosidenib is an inducer of the CYP2B6, CYP2C8, CYP2C9, and CYP3A4 and an inhibitor of P-glycoprotein (P-gp), organic anion transporting polypeptide-1B1/1B3 (OATP1B1/1B3), and organic anion transporter-3 (OAT3) in vitro...

AIM: To assess the potential effects of zanubrutinib on the activity of cytochrome P450 (CYP) enzymes and drug transporter proteins using a cocktail probe approach. METHODS: Patients received single oral doses of probe drugs alone and after at least 8 days of treatment with zanubrutinib 160 mg twice daily in a single-sequence study in 18 healthy male volunteers. Simultaneous doses of 10 mg warfarin (CYP2C9) and 2 mg midazolam (CYP3A) were administrated on Day 1 and Day 14, 0...