Cholesterol absorption inhibitors are a class of compounds that prevent the uptake of

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

from the small intestine into the circulatory system. Most of these molecules are

monobactams Monobactams are monocyclic and bacterially-produced β-lactam antibiotics. The β-lactam ring is not fused to another ring, in contrast to most other β-lactams. Monobactams are effective only against aerobic Gram-negative bacteria (e.g., ''Nei ...

but show no

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...

activity. An example is

ezetimibe Ezetimibe is a medication used to treat high blood cholesterol and certain other lipid abnormalities. Generally it is used together with dietary changes and a statin. Alone, it is less preferred than a statin. It is taken by mouth. It is also ...

(SCH 58235) Another example is Sch-48461. The "Sch" is for

Schering-Plough Schering-Plough Corporation was an American pharmaceutical company. It was originally the U.S. subsidiary of the German company Schering AG, which was founded in 1851 by Ernst Christian Friedrich Schering. As a result of nationalization, it becam ...

, where these compounds were developed.

Phytosterols Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. They encompass plant sterols and stanols. More than 250 sterols and related compounds have been identified. Free phytos ...

are also cholesterol absorption inhibitors.

Physiology

There are two sources of cholesterol in the upper intestine: dietary (from food) and

biliary A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. It ...

(from bile). Dietary cholesterol, in the form of

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...

emulsions, combines with

bile salts Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primary b ...

, to form bile salt

micelles A micelle () or micella () (plural micelles or micellae, respectively) is an aggregate (or supramolecular assembly) of surfactant amphipathic lipid molecules dispersed in a liquid, forming a colloid, colloidal suspension (also known as associat ...

from which cholesterol can then be absorbed by the intestinal

enterocyte Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase its ...

. Once absorbed by the enterocyte, cholesterol is reassembled into intestinal

lipoproteins A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, sur ...

called

chylomicrons Chylomicrons (from the Greek χυλός, chylos, meaning ''juice'' (of plants or animals), and micron, meaning ''small particle''), also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85 ...

. These

chylomicron Chylomicrons (from the Greek χυλός, chylos, meaning ''juice'' (of plants or animals), and micron, meaning ''small particle''), also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85 ...

s are then secreted into the

lymphatics The lymphatic vessels (or lymph vessels or lymphatics) are thin-walled vessels (tubes), structured like blood vessels, that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vessel ...

and circulated to the liver. These cholesterol particles are then secreted by the liver into the blood as

VLDL Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins (chylomicrons, VLDL, intermediate-density lipoprotein, low-density lipo ...

particles, precursors to

LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

. As a class, cholesterol absorption inhibitors block the uptake of micellar cholesterol, thereby reducing the incorporation of cholesterol esters into chylomicron particles. By reducing the cholesterol content in chylomicrons and chylomicron remnants, cholesterol absorption inhibitors effectively reduce the amount of cholesterol that is delivered back to the liver. The reduced delivery of cholesterol to the liver increases hepatic LDL receptor activity and thereby increases clearance of circulating LDL. The net result is a reduction in circulating LDL particles.

Importance

Managing cholesterol at the site of absorption is an increasingly popular strategy in the treatment of

hypercholesterolemia Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia (high levels of lipids in the blood), hyperlipoproteinemia (high levels of lipoproteins in the blood), ...

. Cholesterol absorption inhibitors are known to have a synergistic effect when combined a class of antihyperlipidemics called

statins Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low- ...

, to achieve an overall serum cholesterol target. For statin-resistant or statin-sensitive populations that are characterized by low one-year compliance rates, such a combination therapy is proving to be especially effective .

References

{{Lipid modifying agents Hypolipidemic agents

Physiology

Importance

See also

References