Statin Drug Interactions in Patients with Comorbidities and on Multiple Medications

2012 ◽  
Vol 08 (02) ◽  
pp. 104 ◽  
Author(s):  
Matthew K Ito ◽  
Keyword(s):  
Drug Interactions ◽  
Drug Transport ◽  
Organic Anion ◽  
The Elderly ◽  
Statin Treatment ◽  
Glycoprotein P ◽  
Beneficial Effects ◽  
Drug Classes ◽  
Wide Range ◽  
Statin Drug

Extensive clinical evidence has demonstrated the efficacy of statin treatment in the prevention of cardiovascular disease (CVD). However, nearly half of patients taking statins discontinue their use, largely as a result of side effects. Many patients receiving statins are elderly, and/or have comorbid conditions, increasing the potential for drug-drug interactions (DDIs). Statin DDIs are largely the result of altered drug metabolism via cytochrome P450s (CYPs), glucuronidation or altered drug transport via organic anion-transporting polypeptides (OATPs) and P-glycoprotein (P-gp). There is a need for discussion and education about DDIs within the clinical consultation. Statins that are not significantly metabolized via the CYP system have a reduced risk of DDIs. To date, pitavastatin has shown a low rate of DDIs compared to other available statins metabolized by CYP3A4 isozymes. Its potential for CYP-mediated DDIs has been studied in combination with a wide range of drug classes known to be CYP inhibitors and has been clinically evaluated in patients populations where multiple medications are used, including the elderly, those high risk of CVD, and those taking protease inhibitors. It may also have beneficial effects on parameters of glucose metabolism, and has shown improved outcomes in patients with chronic kidney disease. Knowledge of statin pharmacokinetics, their dose limitations and contraindications, and their mechanisms of DDI allows improved therapeutic choices, avoiding adverse interactions without compromising patient care.

scholarly journals Medicinal Cannabis - Potential Drug Interactions

2018 ◽  
Author(s):  
Muhammad A. Alsherbiny ◽  
Chun G. Li
Keyword(s):  
Drug Interactions ◽  
The Elderly ◽  
Short Review ◽  
Pain Modulation ◽  
Potential Drug ◽  
Cancer Resistance ◽  
Glycoprotein P ◽  
Physiological Processes ◽  
Medicinal Cannabis ◽  
Few Data

Endocannbinoids system (ECS) engrossed a considerable interest as potential therapeutic targets in various carcinomas and cancer related conditions alongside with neurodegenerative diseases. Cannabinoids are implemented in several physiological processes such as appetite stimulation, energy balance, pain modulation and the control of chemotherapy induced nausea and vomiting (CINV). However, pharmacokinetics and pharmacodynamics interactions could be perceived in drug combinations, so in this short review we tried to shed the light over the potential drug interactions of medicinal cannabis. Hitherto, few data have been provided to the healthcare practitioners about the drug-drug interactions of cannabinoids with other prescription medications. In general, cannabinoids are usually well tolerated, but the bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (glycoprotein p, breast cancer resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP- glucuronosyltransferases). The caveats should be undertaken to closely monitor the responses of cannabis users with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions.

Renal Drug Transport and Drug-Drug Interactions

2002 ◽  
Vol 15 (6) ◽  
pp. 490-503 ◽  
Author(s):  
Patrick T. Ronaldson ◽  
Reina Bendayan
Keyword(s):  
Drug Interactions ◽  
Glomerular Filtration ◽  
Drug Transport ◽  
Organic Anion ◽  
Significant Risk ◽  
Tubular Secretion ◽  
Vital Role ◽  
Transport Systems ◽  
Transport Pathways ◽  
Cellular Expression

The kidney plays a vital role in the elimination of xenobiotics including drugs, toxins, and endogenous metabolites. Renal drug elimination involves 3 major processes: glomerular filtration, tubular secretion, and tubular reabsorption. Although glomerular filtration is a simple unidirectional diffusion process, renal tubular secretion and/or reabsorption can involve saturable processes mediated by multiple highly specialized membrane transport systems. Current research has identified that these transport proteins play a significant role in the efficient removal and/or reabsorption of pharmacological agents. Since the majority of membrane transporters have broad substrate specificity, there is a significant risk for drug-drug interactions through competition for similar transport pathways. This article will focus on the cellular expression, localization, and transport properties of various renal drug transport systems (ie, organic anion, organic cation, nucleoside, and adenosine triphosphate [ATP]-dependent efflux transporters). Specific examples of drugs that are transported by each of these mechanisms will be provided. Clinically relevant drug-drug interactions involving renal drug transporters will be discussed to guide the clinician in understanding and preventing these interactions.

scholarly journals Evaluation of Chinese-Herbal-Medicine-Induced Herb-Drug Interactions: Focusing on Organic Anion Transporter 1

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Chang-Ching Lin ◽  
Hsien-Yuan Fan ◽  
Chien-Wen Kuo ◽  
Li-Heng Pao
Keyword(s):  
Drug Interactions ◽  
Mrna Expression ◽  
Prescription Drugs ◽  
Drug Transport ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Chinese Herbal ◽  
Anion Transporter

The consumption of Chinese herbal medicines (CHMs) is increasing exponentially. Many patients utilize CHMs concomitantly with prescription drugs in great frequency. Herb-drug interaction has hence become an important focus of study. Transporter-mediated herb-drug interactions have the potential to seriously influence drug efficacy and toxicity. Since organic anion transporter 1 (OAT1) is crucial in renal active secretion and drug-drug interactions, the possibility of modulation of OAT1-mediated drug transport should be seriously concerned. Sixty-three clinically used CHMs were evaluated in the study. An hOAT1-overexpressing cell line was used for thein vitroCHMs screening, and the effective candidates were administered to Wistar rats to access renal hemodynamics. The regulation of OAT1 mRNA expression was also examined for further evidence of CHMs affecting OAT1-mediated transport. Among all the 63 CHMs, formulae Gui Zhi Fu Ling Wan (GZ) and Chia Wei Hsiao Yao San (CW) exhibited significant inhibitions on hOAT1-mediated [3H]-PAH uptakein vitroand PAH clearance and net secretionin vivo. Moreover, GZ showed concentration-dependent manners bothin vitroandin vivo, and the decrease of rOAT1 mRNA expression indicated that GZ not only inhibited function of OAT1 but also suppressed expression of OAT1.

scholarly journals Imbalance of Drug Transporter-CYP450s Interplay by Diabetes and Its Clinical Significance

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 348 ◽  
Author(s):  
Yiting Yang ◽  
Xiaodong Liu
Keyword(s):  
Drug Transport ◽  
Drug Disposition ◽  
Organic Anion ◽  
Efflux Transporters ◽  
Cancer Resistance ◽  
Cytochrome P450 Enzymes ◽  
Organic Anion Transporting Polypeptides ◽  
Glycoprotein P ◽  
Anion Transporters ◽  
Associated Proteins

The pharmacokinetics of a drug is dependent upon the coordinate work of influx transporters, enzymes and efflux transporters (i.e., transporter-enzyme interplay). The transporter–enzyme interplay may occur in liver, kidney and intestine. The influx transporters involving drug transport are organic anion transporting polypeptides (OATPs), peptide transporters (PepTs), organic anion transporters (OATs), monocarboxylate transporters (MCTs) and organic cation transporters (OCTs). The efflux transporters are P-glycoprotein (P-gp), multidrug/toxin extrusions (MATEs), multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). The enzymes related to drug metabolism are mainly cytochrome P450 enzymes (CYP450s) and UDP-glucuronosyltransferases (UGTs). Accumulating evidence has demonstrated that diabetes alters the expression and functions of CYP450s and transporters in a different manner, disordering the transporter–enzyme interplay, in turn affecting the pharmacokinetics of some drugs. We aimed to focus on (1) the imbalance of transporter-CYP450 interplay in the liver, intestine and kidney due to altered expressions of influx transporters (OATPs, OCTs, OATs, PepTs and MCT6), efflux transporters (P-gp, BCRP and MRP2) and CYP450s (CYP3As, CYP1A2, CYP2E1 and CYP2Cs) under diabetic status; (2) the net contributions of these alterations in the expression and functions of transporters and CYP450s to drug disposition, therapeutic efficacy and drug toxicity; (3) application of a physiologically-based pharmacokinetic model in transporter–enzyme interplay.

DSM-5 alcohol use disorder features among treatment-seeking older adults

2018 ◽  
Vol 64 (4) ◽  
pp. 185-196 ◽  
Author(s):  
Silke Behrendt ◽  
Barbara Braun ◽  
Randi Bilberg ◽  
Gerhard Bühringer ◽  
Michael Bogenschutz ◽  
...  
Keyword(s):  
Older Adults ◽  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
The Elderly ◽  
Treatment Seeking ◽  
Controlled Clinical Trial ◽  
Dsm 5 ◽  
Wide Range ◽  
And Gender ◽  
International Multicenter

Abstract. Background: The number of older adults with alcohol use disorder (AUD) is expected to rise. Adapted treatments for this group are lacking and information on AUD features in treatment seeking older adults is scarce. The international multicenter randomized-controlled clinical trial “ELDERLY-Study” with few exclusion criteria was conducted to investigate two outpatient AUD-treatments for adults aged 60+ with DSM-5 AUD. Aims: To add to 1) basic methodological information on the ELDERLY-Study by providing information on AUD features in ELDERLY-participants taking into account country and gender, and 2) knowledge on AUD features in older adults seeking outpatient treatment. Methods: baseline data from the German and Danish ELDERLY-sites (n=544) were used. AUD diagnoses were obtained with the Mini International Neuropsychiatric Interview, alcohol use information with Form 90. Results: Lost control, desired control, mental/physical problem, and craving were the most prevalent (> 70 %) AUD-symptoms. 54.9 % reported severe DSM-5 AUD (moderate: 28.2 %, mild: 16.9 %). Mean daily alcohol use was 6.3 drinks at 12 grams ethanol each. 93.9 % reported binging. More intense alcohol use was associated with greater AUD-severity and male gender. Country effects showed for alcohol use and AUD-severity. Conclusion: European ELDERLY-participants presented typical dependence symptoms, a wide range of severity, and intense alcohol use. This may underline the clinical significance of AUD in treatment-seeking seniors.

Transcending Time and Space with Digital Emotional Support

2020 ◽  
Author(s):  
Tyler Colasante ◽  
Lauren Lin ◽  
Kalee DeFrance ◽  
Tom Hollenstein
Keyword(s):  
Emotional Support ◽  
Negative Emotion ◽  
Negative Emotions ◽  
Good News ◽  
Social Avoidance ◽  
Time And Space ◽  
Beneficial Effects ◽  
Digital Devices ◽  
Wide Range ◽  
Socially Isolated

In the current digital age, emotional support is increasingly received through digital devices. However, virtually all studies assessing the benefits of emotional support have focused on in-person support. Using an experience sampling methodology, we assessed participants’ negative emotions, digital and in-person support for those emotions, and success in regulating them three times per day for 14 days, thus covering a wide range of digital support scenarios (N = 164 participants with 6,530 collective measurement occasions). We also considered whether participants were alone versus with others at the time of their negative emotion and higher versus lower in social avoidance as plausible moderators of when digital support was utilized and effective. We expected more pronounced use and efficacy of digital support when participants were alone and higher in trait social avoidance. However, digital support was used and perceived as effective for regulating negative emotions regardless of these factors and its beneficial effects were on par with those of traditional in-person support. The unique benefits of digital support may not be restricted to socially isolated or socially avoidant users. These findings are timely given the widespread anxiety and isolation under the current COVID-19 pandemic. If transcending time and space with digital emotional support is the new norm, the good news is that it seems to be working.

Relation between cognitive disorders and type of physical activity: Results of the FréLE cohort

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
C Dupré ◽  
N Barth ◽  
A El Moutawakkil ◽  
F Béland ◽  
F Roche ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cognitive Decline ◽  
Proportional Hazards ◽  
Cognitive Disorders ◽  
The Elderly ◽  
Cognitive Status ◽  
Global Test ◽  
Professional Activities ◽  
Beneficial Effects ◽  
The Impact

Abstract Background Few previous cohorts have studied the different type of physical activities and the degree of cognitive decline. The objective of this work was to analyze the leisure, domestic and professional activities with mild and moderate cognitive disorders in older people living in community. Methods The study used data from the longitudinal and observational study, FrèLE (FRagility: Longitudinal Study of Expressions). The collected data included: socio-demographic variables, lifestyle, and health status (frailty, comorbidities, cognitive status, depression). Cognitive decline was assessed by using: MMSE (Mini-Mental State Examination) and MoCA (Montreal Cognitive Assessment). MoCA was used with two cut-offs (26 and 17) so as to define mild and moderate cognitive disorders Physical activity was assessed by the PASE (Physical Activity Scale for the Elderly), structured in three sections: leisure, domestic and professional activities. Spline and proportional hazards regression models (Cox) were used to estimate the risk of cognitive disorders. Results At baseline, 1623 participants were included and the prevalence of cognitive disorders was 6.9% (MMSE) and 7.2% (MoCA), mild cognitive disorders was 71.3%. The mean age was 77 years, and 52% of the participants were women. After a 2 years long follow-up, we found 6.9% (MMSE) and 6% (MoCA) cognitive disorders on participants. Analyses showed that domestic activities were associated to cognitive decline (HR = 0.52 [0.28-0.94] for MMSE and HR = 0.48 [0.28-0.80] for MoCA). No association were found with leisure and professional activities, and no spline were significant with mild cognitive disorders. Conclusions Analysis showed a relationship between cognitive disorders and type of physical activity, thanks to the use of specific questionnaire of elderly and two global test of cognition. These findings will contribute to the debate on the beneficial effects of physical activity on cognition. Key messages This work allowed to compare two test of cognition and their link with physical activity. It contributes to the debate on the beneficial effects of physical activity on cognition. The work allowed us to see the effect of the different types of physical activity and the impact of the statistical method on the results.

Remimazolam: A Novel Option for Procedural Sedation in High Risk Patients

2021 ◽  
pp. 089719002110273
Author(s):  
Megan M. Pantos ◽  
Daniel R. Kennedy ◽  
Eric C. Nemec
Keyword(s):  
Drug Interactions ◽  
The Elderly ◽  
Volume Of Distribution ◽  
Procedural Sedation ◽  
Dose Titration ◽  
Onset Of Action ◽  
Elimination Half ◽  
Risk Patients ◽  
Require Dose ◽  
Drug Review

Purpose: The purpose of this drug review was to explore the safety and efficacy of the newly approved benzodiazepine, remimazolam, in order to evaluate its place in therapy. Summary: Remimazolam has a faster onset of action and recovery time than midazolam when given as single IV doses. Additionally, it has no known CYP450 interactions that would contribute to drug-drug interactions. Patients with severe hepatic impairment may require dose titration as well as the elderly who should be closely monitored. Although remimazolam vials should be protected from light and must be reconstituted immediately before use, the reconstituted vial may be stored for later use at room temperature for up to 8 hours. Remimazolam is more expensive than current options used in practice, as such individual institutional formulary and provider preference will require review to see if its advantages are worth the additional cost and to determine its place in therapy. Conclusion: Remimazolam is a novel option when choosing a benzodiazepine for procedural sedation that has pharmacokinetic and pharmacodynamic advantages when compared to other commonly prescribed sedatives. Remimazolam has proved superior to midazolam when analyzing drug-drug interactions, onset, and time to alertness. Remimazolam also has a shorter elimination half-life and decreased volume of distribution when compared to midazolam.

scholarly journals Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects

2021 ◽  
Vol 22 (11) ◽  
pp. 5863
Author(s):  
Giuseppe Palmiero ◽  
Arturo Cesaro ◽  
Erica Vetrano ◽  
Pia Clara Pafundi ◽  
Raffaele Galiero ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glucose Transporter ◽  
The Elderly ◽  
Intracellular Sodium ◽  
Clinical Effects ◽  
Glucose Lowering ◽  
Beneficial Effects ◽  
Glucose Transporter 2 ◽  
Function Impairment

Heart failure (HF) affects up to over 20% of patients with type 2 diabetes (T2DM), even more in the elderly. Although, in T2DM, both hyperglycemia and the proinflammatory status induced by insulin resistance are crucial in cardiac function impairment, SGLT2i cardioprotective mechanisms against HF are several. In particular, these beneficial effects seem attributable to the significant reduction of intracellular sodium levels, well-known to exert a cardioprotective role in the prevention of oxidative stress and consequent cardiomyocyte death. From a molecular perspective, patients’ exposure to gliflozins’ treatment mimics nutrient and oxygen deprivation, with consequent autophagy stimulation. This allows to maintain the cellular homeostasis through different degradative pathways. Thus, since their introduction in the clinical practice, the hypotheses on SGLT2i mechanisms of action have changed: from simple glycosuric drugs, with consequent glucose lowering, erythropoiesis enhancing and ketogenesis stimulating, to intracellular sodium-lowering molecules. This provides their consequent cardioprotective effect, which justifies its significant reduction in CV events, especially in populations at higher risk. Finally, the updated clinical evidence of SGLT2i benefits on HF was summarized. Thus, this review aimed to analyze the cardioprotective mechanisms of sodium glucose transporter 2 inhibitors (SGLT2i) in patients with HF, as well as their clinical impact on cardiovascular events.

Sign in / Sign up

Export Citation Format

Share Document