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Amlodipine alters hemorheological parameters: Increased efficacy at the cost of edema?

ABSTRACT: BACKGROUND:Despite several decades of use of calcium channel blockers, the side effect of edema persists as a class effect, and its mechanism is unresolved. Amlodipine has effects on hemorheology (HR), and its hemodilutory property may partly contribute to its antihypertensive action. This aspect is not well studied, and the literature is sparse in this regard. OBJECTIVE:This experiment was planned to determine effect of a single-dose administration of amlodipine on HR parameters in normal human volunteers. METHODS AND RESULTS:Amlodipine (5 mg) or S (-) amlodipine (2.5 mg) was administered to 27 normal human volunteers. Whole-blood viscosity (WBV) at different shear rates, plasma viscosity (PV), red cell rigidity (RCR), red cell aggregation (RCA), hematocrit (Hct), plasma hemoglobin, along with plasma drug concentration were determined at time intervals, t = 0, 4, 8, 12, and 24 h. Statistically significant reductions were observed at tmax = 4 h in WBV at shear rates of 0.512 s-1 (p < 0.005), WBV at shear rates of 5.26 s-1 (p < 0.01), PV (p < 0.05), and Hct (p < 0.01). At t = 8 h, as drug concentration reduced, some of the changes persisted and later slowly decreased with the decreasing drug concentration till t = 24 h. Red blood cell-related parameters such as RCA and RCR remained unaltered. WBV values at all shear rates, when corrected for Hct = 0.45, did not show deviation from their original values at any time. CONCLUSIONS:Amlodipine causes a reduction in Hct and blood viscosity, along with hemodilution. These effects persist as long as the drug remains in plasma. Edema resulting from chronic dosing may be explained by the aforementioned effects. It is possible that antihypertensive action of the drug may be due to a combination of vasodilatation and an improvement in the HR properties.

SUBMITTER: Ravindra RP

PROVIDER: S-EPMC6477139 | biostudies-literature | 2019 Jan - Feb

REPOSITORIES: biostudies-literature

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Amlodipine alters hemorheological parameters: Increased efficacy at the cost of edema?

Ravindra R P RP Arunkumar S S Puniyani R R RR Padgaonkar K K Vadivelu Ramalingam R Sharma Rajeev R Panicker Gopi G Lokhandwala Yash Y

Indian heart journal 20181204 1

<h4>Background</h4>Despite several decades of use of calcium channel blockers, the side effect of edema persists as a class effect, and its mechanism is unresolved. Amlodipine has effects on hemorheology (HR), and its hemodilutory property may partly contribute to its antihypertensive action. This aspect is not well studied, and the literature is sparse in this regard.<h4>Objective</h4>This experiment was planned to determine effect of a single-dose administration of amlodipine on HR parameters ...[more]

PMID: 31000180

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Project description:BACKGROUND AND DESIGN:In this study we set out to determine the effects of long-term physical training on hemorheological, laboratory parameters, exercise tolerability, psychological factors in cardiac patients participating in an ambulatory rehabilitation program. METHODS:Before physical training, patients were examined by echocardiography, tested on treadmill by the Bruce protocol, and blood was drawn for laboratory tests. The enrolled 79 ischemic heart disease patients joined a 24-week cardiac rehabilitation training program. Blood was drawn to measure hematocrit (Hct), plasma and whole blood viscosity (PV, WBV), red blood cell (RBC) aggregation and deformability. Hemorheological, clinical chemistry and psychological measurements were repeated 12 and 24 weeks later, and a treadmill test was performed at the end of the program. RESULTS:After 12 weeks Hct, PV, WBV and RBC aggregation were significantly decreased, RBC deformability exhibited a significant increase (p<0.05). Laboratory parameters (triglyceride, uric acid, hsCRP and fibrinogen) were significantly decreased (p<0.05). After 24 weeks the significant results were still observed. By the end of the study, IL-6 and TNF-α levels displayed decreasing trends (p<0.06). There was a significant improvement in MET (p<0.001), and the BMI decrease was also significant (p<0.05). The vital exhaustion parameters measured on the fatigue impact scale indicated a significant improvement in two areas of the daily activities (p<0.05). CONCLUSIONS:Regular physical training improved the exercise tolerability of patients with ischemic heart disease. Previous publications have demonstrated that decreases in Hct and PV may reduce cardiovascular risk, while a decrease in RBC aggregation and an increase in deformability improve the capillary flow. Positive changes in laboratory parameters and body weight may indicate better oxidative and inflammatory circumstances and an improved metabolic state. The psychological findings point to an improvement in the quality of life.

Project description:Background: Vasodilatory edema is a frequently encountered side effect among hypertensive patients using antihypertensive drugs. This dose-dependent adverse effect is seen more commonly with amlodipine, so low-dose combination therapy is often used and preferred in practice. Pedal edema following use of amlodipine is scarcely studied in Nepalese population so far. Objectives: To find out the prevalence of amlodipine-associated pedal edema and its relation with other variables among patients presenting to a tertiary care center of Kathmandu, Nepal. Methods: A prospective cross-sectional study was conducted among hypertensive patients using amlodipine in combination with or without other antihypertensive medications under regular follow-up in an outpatient department of internal medicine of Shree Birendra Hospital, Kathmandu, Nepal, during the 7-month period from September 2017 to March 2018. The prevalence of pedal edema and its relation with amlodipine dose, duration, and other factors were studied using χ2 test and logistic regression using SPSS version 22. Results: A total of 505 patients were observed during the study period, with the mean age of the population being 61.5 ± 13.4 years. Among the cases studied, edema was present in 79 (15.6%) cases. Use of amlodipine longer than 5 years was 21.65 (confidence interval [CI] = 9.575-48.970, P ˂ .001) times more likely to exhibit pedal edema; similarly, there was 2.149 (CI = 1.209-3.820, P = .009) times higher risk of having pedal edema in hypertensive individuals with other comorbidities. Increasing the dose of amlodipine has increased the likelihood of having pedal edema, but it is not statistically significant (odds ratio = 2.804, CI = 0.423-18.584, P = .285). Conclusion and Relevance: Significant number of hypertensive patients using amlodipine developed pedal edema. Likelihood of vasodilatory edema increases with the presence of comorbidities, higher dose, along with longer duration of amlodipine use.

Project description:ObjectiveAnti-vascular endothelial growth factor therapies have revolutionized the treatment of clinically significant diabetic macular edema (CSDME); yet these agents are expensive, and whether they are cost-effective is unclear. The purpose of this study is to determine the most cost-effective treatment option for patients with newly diagnosed CSDME: focal laser photocoagulation alone (L), focal laser plus intravitreal ranibizumab (L+R), focal laser plus intravitreal bevacizumab (L+B), or focal laser plus intravitreal triamcinolone (L+T) injections.DesignCost-effectiveness analysis.ParticipantsHypothetical cohort of 57-year-old patients with newly diagnosed CSDME.MethodsBy using a Markov model with a 25-year time horizon, we compared the incremental cost-effectiveness of treating patients with newly diagnosed CSDME using L, L+R, L+B, or L+T. Data came from the DRCRnet randomized controlled trial, the Medicare fee schedule, and the medical literature.Main outcome measuresCosts, quality-adjusted life years (QALYs), and incremental costs per QALY gained.ResultsCompared with L, the incremental cost-effectiveness of L+R and L+B was $89903/QALY and $11138/QALY, respectively. L+T was dominated by L. A probabilistic sensitivity analysis demonstrated that, at a willingness to pay (WTP) of $50000/QALY, L was approximately 70% likely to be the preferred therapy over L+R and L+T. However, at a WTP of $100000/QALY, more than 90% of the time, L+R therapy was the preferred therapy compared with L and L+T. In the probabilistic sensitivity analysis, L+B was found to be the preferred therapy over L and L+T for any WTP value >$10000/QALY. Sensitivity analyses revealed that the annual risk of cerebrovascular accident would have to be at least 1.5% higher with L+B than with L+R for L+R to be the preferred treatment. In another sensitivity analysis, if patients require <8 injections per year over the remainder of the 25-year time horizon, L+B would cost <$100000/QALY, whereas L+R would be cost-effective at a WTP of $100000/QALY if patients require fewer than 0.45 injections per year after year 2.ConclusionsWith bevacizumab and ranibizumab assumed to have equivalent effectiveness and similar safety profiles when used in the management of CSDME, bevacizumab therapy confers the greatest value among the different treatment options for CSDME.Financial disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Amlodipine alters hemorheological parameters: Increased efficacy at the cost of edema?

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Amlodipine alters hemorheological parameters: Increased efficacy at the cost of edema?

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