Hypolipidemic agent
Encyclopedia
Hypolipidemic agents, or antihyperlipidemic agents, are a diverse group of pharmaceuticals
that are used in the treatment of hyperlipidemia
s. They are called lipid-lowering drugs (LLD) or agents.
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 will depend 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 from the National Cholesterol Education Program
(NCEP) Adult Treatment Panel III (ATPIII).
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
that are used in the treatment of hyperlipidemia
Hyperlipidemia
Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood...
s. They are called lipid-lowering drugs (LLD) or agents.
Classes of hypolipidemic drugs
There are several classes of hypolipidemic drugs. They may differ in both their impact on the cholesterolCholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
profile and adverse effects. For example, some may lower the "bad cholesterol" low density lipoprotein
Low density lipoprotein
Low-density lipoprotein is one of the five major groups of lipoproteins, which in order of size, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, that enable transport of cholesterol within the water-based bloodstream...
(LDL) more so than others, while others may preferentially increase high density lipoprotein
High density lipoprotein
High-density lipoprotein is one of the five major groups of lipoproteins, which, in order of sizes, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, which enable lipids like cholesterol and triglycerides to be transported within the water-based bloodstream...
(HDL), "the good cholesterol". Clinically, the choice of an agent will depend on the patient's cholesterol profile
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
, 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
Evidence-based medicine
Evidence-based medicine or evidence-based practice aims to apply the best available evidence gained from the scientific method to clinical decision making. It seeks to assess the strength of evidence of the risks and benefits of treatments and diagnostic tests...
guideline from the National Cholesterol Education Program
National Cholesterol Education Program
The National Cholesterol Education Program is a program managed by the National Heart, Lung and Blood Institute, a division of the National Institutes of Health. Its goal is to reduce increased cardiovascular disease rates due to hypercholesterolemia in the United States of America...
(NCEP) Adult Treatment Panel III (ATPIII).
Established
- statinStatinStatins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
s are particularly well-suited for lowering LDL, the cholesterol with the strongest links to cardiovascular 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. There is a risk of severe muscle damage (myopathyMyopathyIn medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease...
& rhabdomyolysisRhabdomyolysisRhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
) with statins. - fibrateFibrateIn pharmacology, the fibrates are a class of amphipathic carboxylic acids. They are used for a range of metabolic disorders, mainly hypercholesterolemia , and are therefore hypolipidemic agents.- Members :...
s are indicated for hypertriglyceridemiaHypertriglyceridemiaIn medicine, hypertriglyceridemia denotes high blood levels of triglycerides, the most abundant fatty molecule in most organisms. It has been associated with atherosclerosis, even in the absence of hypercholesterolemia . It can also lead to pancreatitis in excessive concentrations In medicine,...
. 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, there is a risk of severe muscle damage (myopathyMyopathyIn medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease...
& rhabdomyolysisRhabdomyolysisRhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
) with fibrates. - niacinNiacin"Niacin" redirects here. For the neo-fusion band, see Niacin .Niacin is an organic compound with the formula and, depending on the definition used, one of the forty to eighty essential human nutrients.Niacin is one of five vitamins associated with a pandemic deficiency disease: niacin deficiency...
, 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 hyperglycemiaHyperglycemiaHyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
, and may also cause liver damageHepatotoxicityHepatotoxicity implies chemical-driven liver damage.The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure...
. - bile acid sequestrantBile acid sequestrantThe bile acid sequestrants are a group of medications used to bind certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of bile acids by sequestering them and preventing their reabsorption from the gut. In general, they are classified as hypolipidemic...
s (resins) 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%. It has 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. - ezetimibeEzetimibeEzetimibe is a drug that lowers cholesterol. It acts by decreasing cholesterol absorption in the intestine. It may be used alone , when other cholesterol-lowering medications are not tolerated, or together with statins when statins alone do not control cholesterol.Even though ezetimibe decreases...
(Zetia) is a selective inhibitor of dietary cholesterol absorption. - phytosterolPhytosterolPhytosterols, which encompass plant sterols and stanols, are steroid compounds similar to cholesterol which occur in plants and vary only in carbon side chains and/or presence or absence of a double bond. Stanols are saturated sterols, having no double bonds in the sterol ring structure. More than...
s may be found naturally in plants. Similar to ezetimibe, phytosterols reduce the absorption of cholesterol in the gut. Hence, they are most effective when consumed with meals. However, the precise mechanism of action of phytosterols differs from ezetimibe. - OrlistatOrlistatOrlistat , also known as tetrahydrolipstatin, is a drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet, thereby reducing caloric intake...
(Xenical): Its primary function is to prevent the absorption of about 30%of fats from the human diet; thereby reducing caloric intake (a drug designed to treat obesityObesityObesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
) is by inhibiting Pancreatic lipasePancreatic lipasePancreatic lipase, also known as pancreatic triacylglycerol lipase, is secreted from the pancreas, and is the primary lipase that hydrolyzes dietary fat molecules in the human digestive system, converting triglyceride substrates found in ingested oils to monoglycerides and free fatty acids.Bile...
- an enzyme that breaks down triglycerides in the intestine. - AcipimoxAcipimoxAcipimox is a niacin derivative used as a hypolipidemic agent.It is used in low doses and may have less marked adverse effects, although it is unclear whether the recommended dose is as effective as are standard doses of nicotinic acid . These drug inhibit hepatic triglyceride production and VLDL...
Investigational
Investigational classes of hypolipidemic agents:- CETP Inhibitors (cholesteryl ester transfer protein inhibitors) are still under development. It is expected that these drugs will mainly increase HDL while lowering LDL.
- squalene synthase inhibitor
- ApoA-1 MilanoApoA-1 MilanoApoA-1 Milano is a naturally occurring mutated variant of the apolipoprotein A1 protein found in human HDL, the lipoprotein particle that carries cholesterol from tissues to the liver and is associated with protection against cardiovascular disease. ApoA1 Milano was first identified by Dr...
- AGI-1067
- mipomersenMipomersenMipomersen is a cholesterol-reducing drug candidate. It is an antisense therapeutic that targets the messenger RNA for apolipoprotein B...
(completed 4 phase III trials - may file NDA in 2011)