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Hypolipidemic agents, or antihyperlipidemic agents, are a diverse group of pharmaceuticals that are used in the treatment of high levels of fats (lipids), such as cholesterol, in the blood (hyperlipidemia). They are called lipid-lowering drugs.
Contents
1Classes
1.1Established
2Research
3References
4See also
Classes
The several classes of hypolipidemic drugs may differ in both their impact on the cholesterol profile and adverse effects. For example, some may lower the "bad cholesterol" low density lipoprotein (LDL) more so than others, while others may preferentially increase high density lipoprotein (HDL), "the good cholesterol". Clinically, the choice of an agent depends on the patient's cholesterol profile, cardiovascular risk, and the liver and kidney functions of the patient, evaluated against the balancing of risks and benefits of the medications. In the United States, this is guided by the evidence-based guideline most recently updated in 2018 by the American College of Cardiology & American Heart Association. [1]
Established
Statins are particularly well suited for lowering LDL, the cholesterol with the strongest links to vascular diseases. In studies using standard doses, statins have been found to lower LDL-C by 18% to 55%, depending on the specific statin being used. A risk exists of severe muscle damage (myopathy and rhabdomyolysis) with statins. Hypercholesterolemia is not a risk factor for mortality in persons older than 70 years and risks from statin drugs are more increased after age 85.[2]
Fibrates are indicated for hypertriglyceridemia. Fibrates typically lower triglycerides by 20% to 50%. Level of the good cholesterol HDL is also increased. Fibrates may decrease LDL, though generally to a lesser degree than statins. Similar to statins, the risk of severe muscle damage exists.
Niacin, like fibrates, is also well suited for lowering triglycerides by 20–50%. It may also lower LDL by 5–25% and increase HDL by 15–35%. Niacin may cause hyperglycemia and may also cause liver damage. The niacin derivative acipimox is also associated with a modest decrease in LDL.
Lecithin has been shown to effectively decrease cholesterol concentration by 33%, lower LDL by 38% and increase HDL by 46%. [3]
Bile acid sequestrants (resins, e.g. cholestyramine) are particularly effective for lowering LDL-C by sequestering the cholesterol-containing bile acids released into the intestine and preventing their reabsorption from the intestine. It decreases LDL by 15–30% and raises HDL by 3–5%, with little effect on triglycerides, but can cause a slight increase. Bile acid sequestrants may cause gastrointestinal problems and may also reduce the absorption of other drugs and vitamins from the gut.
Ezetimibe is a selective inhibitor of dietary cholesterol absorption.
Lomitapide is a microsomal triglyceride transfer protein inhibitor.
Phytosterols may be found naturally in plants. Similar to ezetimibe, phytosterols reduce the absorption of cholesterol in the gut, so they are most effective when consumed with meals. However, their precise mechanism of action differs from ezetimibe.
Omega-3 supplements taken at high doses can reduce levels of triglycerides.[4]
Research
Investigational classes of hypolipidemic agents:
CETP inhibitors (cholesteryl ester transfer protein), 1 candidate is in trials. It is expected that these drugs will mainly increase HDL while lowering LDL
Squalene synthase inhibitor
ApoA-1 Milano
succinobucol(AGI-1067), a novel antioxidant, failed a phase-III trial.
Apoprotein-B inhibitor mipomersen (approved by the FDA in 2013 homozygous familial hypercholesterolemia.[5][6]).
PCSK9 monoclonal antibody inhibitors [7][8]
Bempedoic acid, an ATP citrate lyase inhibitor
References
^Alenghat, Francis J.; Davis, Andrew M. (2019). "Management of Blood Cholesterol". JAMA. doi:10.1001/jama.2019.0015. ISSN 0098-7484.
^AMDA – The Society for Post-Acute and Long-Term Care Medicine (February 2014), "Ten Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation, AMDA – The Society for Post-Acute and Long-Term Care Medicine, retrieved 20 April 2015.
^Wójcicki, J.; Pawlik, A.; Samochowiec, L.; Kaldo??Ska, M.; Myśliwiec, Z. (1995). "Clinical evaluation of lecithin as a lipid-lowering agent". Phytotherapy Research. 9 (8): 597–599. doi:10.1002/ptr.2650090814.
^"Omega-3 Supplements: In Depth". NCCIH. 2009-07-01. Retrieved 2019-08-12.
^Pollack, Andrew (29 January 2013) F.D.A. Approves Genetic Drug to Treat Rare Disease The New York Times, Retrieved 31 January 2013
^Staff (29 January 2013) FDA approves new orphan drug Kynamro to treat inherited cholesterol disorder U.S. Food and Drug Administration, Retrieved 31 January 2013
^Koren MJ, Scott R, Kim JB et al Lancet 2012; 380:1995-2006
^Gugliano RP, Desai NR, Kohli P et al Lancet 2012; 380:2007-17
4. 心血管疾患の二次予防としての低比重リポタンパク（LDL-C）の管理 management of low density lipoprotein cholesterol ldl c in secondary prevention of cardiovascular disease
5. スタチン：作用、副作用、および投与 statins actions side effects and administration
English Journal
Conformational dynamics of human FXR-LBD ligand interactions studied by hydrogen/deuterium exchange mass spectrometry: Insights into the antagonism of the hypolipidemic agent Z-guggulsterone.
Yang L1, Broderick D1, Jiang Y2, Hsu V3, Maier CS4.
Biochimica et biophysica acta.Biochim Biophys Acta.2014 Sep;1844(9):1684-93. doi: 10.1016/j.bbapap.2014.06.007. Epub 2014 Jun 18.
Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of transcription factors that plays a key role in the regulation of bile acids, lipid and glucose metabolisms. The regulative function of FXR is governed by conformational changes of the ligand binding domain (LBD) upon ligan
Dengue is the most common mosquito borne viral disease in humans. The infection with any of the 4 dengue virus serotypes (DENV) can either be asymptomatic or manifest in two clinical forms, the mild dengue fever or the more severe dengue hemorrhagic fever that may progress into dengue shock syndrome
Hypolipidemic effect of the polysaccharides from Porphyra yezoensis.
Qian L1, Zhou Y2, Ma JX3.
International journal of biological macromolecules.Int J Biol Macromol.2014 Jul;68:48-9. doi: 10.1016/j.ijbiomac.2014.04.004. Epub 2014 Apr 13.
This study was performed to investigate the hypolipidemic effect of the polysaccharides extracted from Porphyra yezoensis. Male Sprague-Dawley rats were divided into three groups and orally treated with diets containing either high fat, P. yezoensis polysaccharides (PPs), or normal fat. Treatment of
… The present study was conducted to evaluate hypolipidemic effects of <i>meso</i>-dihydroguaiaretic acid (MDA), anti-oxidative and anti-inflammatory compound isolated from the <i>Myristica fragrans</i> … Taken together, these findings show that MDA inhibits insulin-induced lipid accumulation in human HepG2 cells by suppressing expression of lipogenic proteins through AMPK signaling, suggesting a potent lipid-lowering agent. …
47 A hypolipidemic agent, probucol lowers plasma and liver levels of lipids in mice fed a high-fat diet Satoe Suzuki1, Hideki Kudo1, Hiroyuki Kikuchi2, Nahoko Nemoto3, Shuji Sassa4, Shinobu Sakamoto4 1 Department of Clinical ...
In this article, we present our therapeutic approach with the hypolipidemic agent, simvastatin, in a 12-year-old boy followed up with a diagnosis of hyperimmunoglobulinemia D and periodic fever syndrome.
Hypolipidemic drug, any agent the reduces the level of lipids and lipoproteins (lipid-protein complexes) in the blood. Lipoproteins bind cholesterol and can accumulate in blood vessels. High levels of specific lipoproteins, namely, low ...