Retinoids in Lymphoma
Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish in Retinoids in Dermatology, 2019
Bexarotene can also cause hyperlipidemia and hypercholesterolemia (28). Prior to initiating oral bexarotene, baseline lipid levels should be established. If there are abnormalities, they should be corrected prior to initiation. Once oral bexarotene has begun, close monitoring should occur. The most common lipid abnormality is hypertriglyceridemia at 79% (28). To combat this, patients are started on fenofibrate. If LDL cholesterol levels also rise, atorvastatin can be initiated; however, we preemptively initiate atorvastatin 40 mg at baseline. Finally, with the possibility of hepatotoxicity, liver enzymes should be monitored. Additional side effects may be peripheral edema and nausea, with pancreatitis rarely occurring but also being avoidable by monitoring triglyceride levels.
Diabetes mellitus and cardiovascular disease in the elderly
Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich in Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Multiple clinical trials have demonstrated the beneficial effects of statin therapy on CV outcomes in patients with diabetes and history of CAD and have suggested potential benefits in primary prevention for cardiovascular disease (107). The Collaborative Atorvastatin Diabetes Study evaluated the use of atorvastatin for primary prevention of cardiovascular disease in patients with type 2 diabetes. The trial was stopped 2 years early when a prespecified early stopping rule for efficacy was met. The atorvastatin treated patients demonstrated a 37% relative risk reduction in major cardiovascular events compared to placebo. This trial and others support the use of statin therapy in patients with diabetes to lower their LDL. The use of HDL raising therapies (specifically niacin) is less promising. A systematic review in 2007 evaluated 31 trials looking at therapies to raise HDL and found only modest evidence to support aggressively raising HDL beyond what can be achieved with lifestyle modifications alone (108). Fibrates have also been evaluated as potential therapeutic agents to treat dyslipidemia in patients with diabetes. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study examined the long-term use of fenofibrate in patients with type 2 diabetes. Use of fenofibrate in this population with diabetes and no statin use at entry was not associated with a reduction in overall cardiovascular outcomes (109).
The Diabetic/Obese Hypertensive Patient (Including Metabolic Syndrome)
Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei in Manual of Hypertension of the European Society of Hypertension, 2019
Atherogenic dyslipidemia is one of the major risk factors for CV disease in people with type 2 DM. Dyslipidemia in obesity is a cluster of lipid and lipoprotein abnormalities with elevated triglycerides, apoB and small dense LDL combined with low HDL and apoA1. The primary target of hypolipidemic treatment is the reduction of LDL levels with lifestyle interventions, weight loss treatment and the use of statins and ezetimibe (30). In high-risk obese patients with serum triglycerides >2.5 mmol/L (especially in those with simultaneously low HDL cholesterol levels) despite appropriate well-tolerated statin therapy, fenofibrate can be used in combination with statins. Statin treatment is associated with body weight gain and drug-induced new-onset DM, but these effects are minor when compared to life that will be saved with stain treatment from CV disease.
Successes, failures, and future prospects of prodrugs and their clinical impact
Published in Expert Opinion on Drug Discovery, 2019
Anas Najjar, Rafik Karaman
Statins are the agents of choice for the treatment of dyslipidaemia. They are structurally similar to hydroxymethylglutaryl CoA (HMG-CoA) and exhibit their pharmacological action by HMG- CoA reductase inhibition leading to reduced production of melavonic acid, a precursor of cholesterol. Lovastatin and simvastatin are lactone prodrugs hydrolysed to their active forms. Lovastatin was one of the lead compounds for the development of synthetic statins such as atorvastatin, rosuvastatin, and fluvastatin, and is now less prescribed. Simvastatin, however, continues to be a favourable choice when initiating treatment with statins [18,19]. This is due to relatively cheap cost and moderate potency. However, this makes simvastatin the most switched statin due to statin induced myalgia [20]. Similarly, fenofibrate is an antilipemic agent also used in the management of elevated cholesterol and triglyceride levels. Fenofibrate is a prodrug which undergoes hydrolysis to provide the active parent drug, fenofibric acid, which is an activator of peroxisome proliferator activated receptor a (PPARa) [21].
Efficacy and safety of coenzyme A versus fenofibrate in patients with hyperlipidemia: a multicenter, double-blind, double-mimic, randomized clinical trial
Published in Current Medical Research and Opinion, 2020
Ya-Qin Chen, Shui-ping Zhao, Hui-Jun Ye
The dyslipidemias may necessitate an almost lifelong administration. Many people prefer natural products instead of chemical drugs because they believe these products are natural, safer, cheaper and easier to ingest24. With the wider use of fibrates, more side effects have been detected. The most frequent side effects are liver dysfunction, gastrointestinal tract symptoms and musculoskeletal symptoms. In the present trial, the incidence of side effects caused by fenofibrate is significantly higher than that caused by CoA. There was no occurrence of myopathy or obvious damage of liver and kidney function in the CoA group. Furthermore, the incidence of gastrointestinal tract symptoms and complications by CoA therapy was rare. All of this evidence demonstrated that CoA is a well tolerated lipid-lowering agent.
Effect of Fenofibrate on the Expression of Inflammatory Mediators in a Diabetic Rat Model
Published in Current Eye Research, 2019
Po-Ting Yeh, Lu-Chun Wang, Shu-Wen Chang, Wei-Shiung Yang, Chung-May Yang, Chang-Hao Yang
The most concerned issue of fenofibrate treatment is its hepatotoxicity. Impaired liver functions caused by fenofibrate have been found in animal and human studies.38,40 In our study, fenofibrate 30 mg/kg/day and 100 mg/kg/day were given to diabetic rats according to the previous reports.20,21 Compared with the treatment dose in the FIELD study (200 mg daily in human), we used a relatively large dose in our study. No hepatotoxicity was observed in the experimental animals except mild fatty liver. In the FIELD and ACCORD eye study, type 2 diabetic patients who received long-term fenofibrate treatment were evaluated. In contrast, the in vivo animal experiments can only demonstrated the short-term effect. STZ injection causes type 1 diabetes, which results in acute elevation of blood sugar and acute inflammatory reaction within retina of diabetic rats. Relative large dose of fenofibrate with short-term treatment (3 months) should be applied to suppress the acute inflammatory reaction within diabetic retina in this animal model. Although our short-term, large-dose fenofibrate treatment only indicated mild fatty liver, long-term usage may result in adverse effects such as hepatotoxicity and gallstones.38,40 To confirm this treatment in preventing DR progression and possible side effects clinically, more animal studies with type 2 diabetes model and human clinical trials are necessary to further delineate the safety dosage and exact treatment guidelines of fenofibrate.
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