Antihyperlipidemic Drugs
Example: Triglyceride, Cholesterol, lipoprotein, phospholipid, glycolipid.
Cholesterol: Cholesterol is a lipid that the body requires as a building block for cell membranes and for hormones like estrogen and testosterone. The liver produces about 80% of the body's cholesterol and the rest comes from dietary sources like meat, poultry, eggs, fish, and dairy products. Foods derived from plants contain no cholesterol. It travels around the body in lipoproteins
.
Triglycerides: One of the lipids that circulate in blood. When we eat, our body converts any calories it doesn't need to use right away into triglycerides. The triglycerides are stored in your fat cells. Later, hormones release triglycerides for energy between meals.
Triglycerides and cholesterols are insoluble in water and must be bound to a lipid- containing protein (lipoprotein) for transportation throughout the body.
Low-density lipoproteins (LDL) transport cholesterol from liver to the peripheral cells. When the cells have all of the cholesterol they need, the excess cholesterol is discarded into the blood. This can result in an excess of cholesterol, which can penetrate the walls of the arteries, resulting in atherosclerotic plaque formation.
Elevation of the LDL increases the risk for heart disease.
High-density lipoproteins (HDL) take cholesterol from the peripheral cells and bring it to the liver, where it is metabolized and excreted. The higher the HDL, the lower the risk for development of atherosclerosis. Therefore, it is desirable to see an increase in the HDL (the “good” lipoprotein) because of the protective nature of its properties against the development of atherosclerosis and a decrease in the LDL.
Total cholesterol (TC) score is the sum of HDL cholesterol, LDL cholesterol and 20%
of triglycerides as determined by a blood test.
TC= LDL+HDL+20%TG
Hyperlipidemia is an increase in the lipids, which are a group of fats or fat like substances in the blood. Cholesterol and the triglycerides are the two lipids in the blood. Elevation of one or both of these lipids is seen in hyperlipidemia.
Classification
Hyperlipidemias are also classified according to which types of lipids are elevated, that is hypercholesterolemia, hypertriglyceridemia or both in combined hyperlipidemia. Elevated levels of Lipoprotein (a) may also be classified as a form of hyperlipidemia.
Hyperlipidemias may basically be classified as
• Primary: caused by specific genetic abnormalities
• Secondary: also called acquired that result from another underlying disorder which leads to alterations in plasma lipid and lipoprotein metabolism.
• Idiopathic: that is without a known cause
The various types of Antihyperlipidemic Drugs are:
ACTIONS
1. HMG-CoA Reductase Inhibitors
Another group of antihyperlipidemic drugs are called HMG-CoA reductase inhibitors.
HMG-CoA (3-Hydroxy-3-methyglutaryl coenzyme A) reductase is an enzyme that is a catalyst (a substance that accelerates a chemical reaction without itself undergoing a change) in the manufacture of cholesterol. This drug activity lowers the blood levels of cholesterol and serum triglycerides and increases blood levels of HDLs. Examples of these drugs are fluvastatin, lovastatin, atorvastatin, rosuvastatin and simvastatin.
Mechanism of action:
Vit D
Cell membrane Sex hormones Brain
Steroid hormones Bile
Adverse effects:
Myalgia: pain in a muscle or group of muscles.
Myositis: refers to any condition causing inflammation in muscles. Weakness, swelling, and pain are the most common symptoms.
Rhabdomyolysis: is a serious syndrome due to a direct or indirect muscle injury. It results from the death of muscle fibers and release of their contents into the bloodstream. This can lead to serious complications such as renal (kidney) failure. This means the kidneys cannot remove waste and concentrated urine.
Increased risk of diabetes mellitus & Neuropathy.
2. Fibric Acid Derivatives
Fibric acid derivatives, the third group of antihyperlipidemic drugs, work in a variety of ways.
Eg. Clofibrate, Fenofibrate and Gemfibrozil.
Fibrates activate PPAR (peroxisome proliferator-activated receptors), especially PPARα. Activating PPARs induces the transcription of a number of genes that facilitate lipid metabolism.
Therapeutic uses:
While the fibric acid derivatives have antihyperlipidemic effects, their use varies depending on the drug.
Clofibrate and gemfibrozil are used to treat individuals with very high serum triglyceride levels who present a risk of abdominal pain and pancreatitis and who do not experience a response to diet modifications. Clofibrate is not used for the treatment of other types of hyperlipidemia and is not thought to be effective for prevention of coronary heart disease.
Fenofibrate (Tricor) is used as adjunctive treatment for the reduction of LDL, total cholesterol, and triglycerides in patients with hyperlipidemia.
Apolipoprotein C-III (apo-C3) is a protein that is secreted by the liver as well as the small intestine, and is found on triglyceride-rich lipoproteins such as chylomicrons, very low density lipoprotein (VLDL).
APOC3 inhibits lipoprotein lipase and hepatic lipase; Overexpression of Apo-CIII in humans contributes to atherosclerosis. In persons with type 2 diabetes, elevated plasma Apo-CIII is associated with higher plasma triglycerides and greater coronary artery calcification.
Apolipoprotein A-V is a protein that is significantly expressed in liver and an an activator of lipoprotein lipase (which is a key enzyme in triglyceride catabolism) and, through this process, enhances the metabolism of TG-rich particles.
Apo A1 and A2 helps to clear fats, including cholesterol, from white blood cells within artery.
walls,
Apolipoprotein B is responsible for carrying fat molecules.
3. Bile Acid Sequestrants
Example: Cholestyramine and colestipol
Bile, which is manufactured and secreted by the liver and stored in the gallbladder, emulsifies fat and lipids as these products pass through the intestine.
Once emulsified, fats and lipids are readily absorbed in the intestine.
These drugs bind to bile acids to form an insoluble substance that cannot be absorbed by the intestine, so it is secreted in the feces.
With increased loss of bile acids, the liver uses cholesterol to manufacture more bile.
This is followed by a decrease in cholesterol levels.
4. Cholesterol absorption inhibitors:
5. Niacin
Niacin is used as adjunctive therapy for the treatment of very high serum triglyceride levels in patients who present a risk of pancreatitis (inflammation of the pancreas) and who do not experience an adequate response to dietary control.
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