Cholesterol and Drugs

How can high cholesterol be controlled?

High cholesterol affects many people throughout the world. High cholesterol levels can greatly increase the risk of heart disease, including potentially fatal heart attacks. Exercise, weight loss, and a diet low in cholesterol and saturated fats can help lower cholesterol levels. However, when these measures fail, cholesterol-lowering medications are usually needed. In this slideshow we'll discuss cholesterol basics, and review the classes of drugs prescribed to lower cholesterol.

What is cholesterol?

Cholesterol is a waxy, fat-like substance that your body needs to function normally. The cholesterol in a person's blood originates from two major sources; the diet and the liver. Dietary cholesterol comes primarily from meat, poultry, fish, and dairy products. Cholesterol is naturally present in cell walls or membranes everywhere in the body, including the brain, nerves, muscles, skin, liver, intestines, and heart. Your body uses cholesterol to produce many hormones, vitamin D, and the bile acids that help to digest fat. It takes only a small amount of cholesterol in the blood to meet these needs. If you have too much cholesterol in your bloodstream, the excess may be deposited in arteries, including the coronary (heart) arteries, where it contributes to the narrowing and blockages that cause the signs and symptoms of heart disease.

 

What are LDL cholesterol, HDL cholesterol, and triglycerides?

Cholesterol is carried in the blood as particles of differing sizes and densities along with lipoproteins, proteins that associate with cholesterol. Cholesterol carried in particles of low density (LDL cholesterol) is referred to as the "bad" cholesterol because elevated levels of LDL cholesterol are associated with an increased risk of coronary heart disease. LDL lipoprotein deposits cholesterol on the artery walls, causing the formation of a hard, thick, substance called cholesterol plaque. Over time, cholesterol plaque causes thickening of the arterial walls and narrowing of the arteries, a process called atherosclerosis.

Cholesterol carried in particles of high density (HDL cholesterol) is referred to as the "good cholesterol" because HDL cholesterol particles prevent atherosclerosis by extracting cholesterol from the arterial walls and disposing of it through the liver. Thus, high levels of LDL cholesterol and low levels of HDL cholesterol (high LDL/HDL ratios) are risk factors for atherosclerosis, while low levels of LDL cholesterol and high levels of HDL cholesterol (low LDL/HDL ratios) are desirable.

Triglyceride is a fatty substance composed of three fatty acids. Like cholesterol, triglyceride in the blood comes from the diet or liver.

What types of cholesterol drugs are available?

Medications can be used to lower blood levels of undesirable lipids such as LDL cholesterol and triglycerides, and increase blood levels of desirable lipids such as HDL cholesterol. Several classes of medications are available in the United States, including statins (HMG CoA reductase inhibitors), nicotinic acid (niacin), fibric acid derivatives (fibrates), bile acid sequestrants, and cholesterol absorption inhibitors. Some of these medications can also be combined to more aggressively lower LDL, as well as lower LDL and increase HDL cholesterol levels at the same time.

What are statins?

Statins are a class of drugs that lower the level of cholesterol in the blood by reducing the production of cholesterol by the liver. Statins block the enzyme in the liver that controls the production of cholesterol. Most patients are placed on statins because of high levels of cholesterol; however, statins are also used for preventing and treating atherosclerosis that causes chest pain, heart attacks, strokes, and intermittent claudication in individuals who have or are at risk for atherosclerosis.

Risk factors for atherosclerosis include:

• abnormally elevated cholesterol levels,
• a family history of heart attacks (particularly at a young age),
• increasing age,
• diabetes, and
• high blood pressure.

The next several slides are examples of statins currently prescribed to lower cholesterol.

atorvastatin (Lipitor)

Drug Class: Statins
Prescription: Yes
Generic: No
Preparations: Tablets of 10, 20, 40, and 80 mg.

Prescribed for: Atorvastatin (Lipitor) is used for the treatment of elevated total cholesterol, LDL, triglycerides, and to elevate HDL cholesterol. The effectiveness of atorvastatin (Lipitor) in lowering cholesterol is dose-related, meaning that higher doses reduce cholesterol more.

Side effects: Atorvastatin (Lipitor) is generally well-tolerated. Minor side effects include constipation, diarrhea, fatigue, gas, heartburn, and headache. Atorvastatin (Lipitor) may cause liver and muscle damage.

rosuvastatin (Crestor)

Drug Class: Statins
Prescription: Yes
Generic: No
Preparations: Tablets of 5, 10, 20, and 40 mg.

Prescribed for: Rosuvastatin (Crestor) is used for the reduction of blood total cholesterol, LDL cholesterol and triglyceride levels, and to increase HDL cholesterol levels.

Side effects: The most common side effects of rosuvastatin (Crestor) are headache, nausea, vomiting, diarrhea, and muscle pain. The most serious side effects are liver failure, muscle breakdown (rhabdomyolysis) and kidney failure

simvastatin (Zocor)

Drug Class: Statins
Prescription: Yes
Generic: Yes
Preparations: Tablets of 5, 10, 20, 40, and 80 mg.

Prescribed for: Simvastatin (Zocor) is used for reducing total cholesterol, LDL cholesterol, and triglycerides, and for increasing HDL cholesterol. In patients with coronary heart disease, diabetes, peripheral vessel disease, or history of stroke or other cerebrovascular disease.

Side effects: The most common side effects of simvastatin (Zocor) are headache, nausea, vomiting, diarrhea, abdominal pain, muscle pain, and abnormal liver tests. Hypersensitivity reactions have also been reported. The most serious potential side effects are liver damage and muscle inflammation or breakdown.

pravastatin (Pravachol)

Drug Class: Statins
Prescription: Yes
Generic: Yes
Preparations: Tablets of 10, 20, 40, and 80 mg.

Prescribed for: Pravastatin (Pravachol) is used for the reduction of total and LDL cholesterol as well as triglycerides, and to increase HDL cholesterol. It has been suggested that pravastatin may reduce the occurrence of heart attacks, strokes, and death caused by coronary artery disease.

Side Effects: The most common side effects of pravastatin (Pravachol) are headache, nausea, vomiting, diarrhea, muscle pain, and abnormal liver tests. The most serious potential side effects are liver damage and muscle inflammation or breakdown.

lovastatin (Mevacor)

Drug Class: Statins
Prescription: Yes
Generic: Yes
Preparations: Tablets of 10, 20, and 40 mg.

Prescribed for: Lovastatin (Mevacor) is used to treat high LDL cholesterol. Effectiveness of the medication in lowering cholesterol is dose-related. Blood cholesterol determinations are performed in regular intervals during treatment so that dosage adjustments can be made. A reduction in LDL cholesterol level can be seen two weeks after starting therapy.

Side Effects: Side effects of lovastatin (Mevacor) are rare. Minor side effects include constipation, diarrhea, gas, heartburn, headache, and insomnia. Major side effects include abdominal pain or cramps, blurred vision, dizziness, itching, muscle pain or cramps, rash, or yellowing of the skin or eyes

fluvastatin (Lescol)

Drug Class: Statins
Prescription: Yes
Generic: No
Preparations: Tablets of 20 and 40 mg.

Prescribed for: Fluvastatin (Lescol) is used to treat high LDL cholesterol. Effectiveness of the medication in lowering cholesterol is dose-related. Blood cholesterol determinations are performed in regular intervals during treatment so that dosage adjustments can be made.

Side effects: Side effects of fluvastatin (Lescol) are rare. Minor side effects include constipation, diarrhea, gas, heartburn, headache, and insomnia. Major side effects include abdominal pain or cramps, blurred vision, dizziness, itching, muscle pain or cramps, rash, or yellowing of the skin or eyes.

What are fibric acid derivatives (fibrates)?

Fibrates are effective medications that lower blood triglyceride levels. Fibrates lower blood triglyceride levels by inhibiting production in the liver of VLDL (particles in the blood that carry triglycerides and lipoproteins), and by speeding up the removal of triglycerides from the blood.

Fibrates also are modestly effective in increasing blood HDL cholesterol levels; however, fibrates are not effective in lowering LDL cholesterol. Doctors may consider combining a fibrate with a statin. Such a combination will not only lower the LDL cholesterol, but will also lower blood triglycerides and increase HDL cholesterol levels.

Fibrates also have been used alone to prevent heart attacks in patients with elevated blood triglycerides and low HDL cholesterol levels.

fenofibrate (Tricor)

Drug Class: Fibrates
Prescription: Yes
Generic: No
Preparations: Tablets of 48 and 145 mg.

Prescribed for: Fenofibrate (Tricor) is used along with a non-drug program (including diet changes) to treat elevated cholesterol and triglyceride levels.

Side effects: Common side effects of fenofibrate (Tricor) include upset stomach, constipation, headache, dizziness or trouble sleeping. Muscle damage may occur, and muscle pain, tenderness, weakness and fever should be reported promptly to the responsible physician. Decreased sexual drive, yellowing of the eyes or skin (jaundice), and stomach pain may occur and also should be reported.

gemfibrozil (Lopid)

Drug Class: Fibrates
Prescription: Yes
Generic: No
Preparations: Tablet of 600 mg.

Prescribed for: Gemfibrozil (Lopid) is used for persons with either low HDL cholesterol and/or high triglyceride concentrations to reduce the risk of heart attacks. It also is used in persons with very high triglyceride levels that may cause pancreatitis (inflammation of the pancreas).

Side effects: Side effects of gemfibrozil (Lopid) include upset stomach (1 in 5 patients), diarrhea (1 in 14 patients), tiredness (1 in 30 patients) and nausea or vomiting (1 in 40 patients). Additional patients may experience dizziness, tiredness, tingling in the extremities, headache, decreased sexual drive, impotence, depression, or blurred vision. Less common side effects are muscle aches, pains, weakness or tenderness.

What are bile acid sequestrants?

Bile acid sequestrants bind bile acids in the intestine and cause more of the bile acids to be excreted in the stool. This reduces the amount of bile acids returning to the liver and forces the liver to produce more bile acids to replace the bile acids lost in the stool. In order to produce more bile acids, the liver converts more cholesterol into bile acids, which lowers the level of cholesterol in the blood.

Bile acid sequestrants have modest LDL cholesterol-lowering effects. However, bile acid sequestrants are most useful in combination with a statin or niacin to aggressively lower LDL cholesterol levels. The statin-bile acid sequestrant combination can lower LDL cholesterol levels by approximately 50%, lower than a statin alone. A statin-niacin combination also can substantially elevate HDL cholesterol.

colesevelam (Welchol)

Drug Class: Bile acid sequestrants
Prescription: Yes
Generic: No
Preparations: Tablet of 625 mg.

Prescribed for: Colesevelam (Welchol) is used to treat high blood cholesterol levels, especially high levels of LDL cholesterol. It does not lower cholesterol as much as the statin class of drugs, but when used in combination with a statin, it lowers cholesterol levels further than the statin alone.

Colesevelam (Welchol) also is used in combination with other drugs for treating type 2 diabetes such as metformin (Glucophage), sulfonylureas, or insulin to further lower blood sugar levels.

Side effects: Colesevelam (Welchol) usually is well-tolerated. Patients may experience constipation, upset stomach, indigestion, headache, stomach pain, or diarrhea.

colestipol (Colestid)

Drug Class: Bile acid sequestrants
Prescription: Yes
Generic: No
Preparations: Tablet of 1 gm. Granules in 5gm packets or bulk.

Prescribed for: Colestipol (Colestid) is used for the treatment of high cholesterol in conjunction with dietary control; for the treatment of diarrhea due to increased intestinal bile acids after some types of surgery; for the treatment of itching associated with partial obstruction to the flow of bile due to liver disease.

Side effects: Side effects of colestipol (Colestid) include constipation, stomach upset, heartburn, belching, gas, nausea, loss of appetite, aggravated hemorrhoids, change of taste, headache, or itching. If patients experience unusual bruising or bleeding, severe stomach aches, or vomiting they should notify their physicians.

cholestyramine (Questran)

Drug Class: Bile acid sequestrants
Prescription: Yes
Generic: Yes
Preparations: Powder

Prescribed for: Cholestyramine (Questran) is used for reducing cholesterol levels in the blood, to relieve the itching of liver and biliary disease, and to treat overdoses of digoxin or thyroid hormone.

Side effects: The most common side effects are constipation, abdominal pain, bloating, vomiting, diarrhea, weight loss, and excessive passage of gas (flatulence). Long-term use of cholestyramine may cause a deficiency of vitamins A, D, E, and K.

What is nicotinic acid (vitamin B3 or niacin)?

Nicotinic acid (vitamin B3 or niacin) is a B vitamin. An average American diet contains 15-30 mg of niacin per day. However, in treating blood cholesterol and triglyceride disorders, high doses (1-3 grams a day) of nicotinic acid are necessary. Nicotinic acid is available in several preparations. Prescription nicotinic acid includes immediate release niacin or sustained release niacin. Over-the-counter (OTC) nicotinic acid is available as sustained release niacin. OTC preparations are not federally regulated, and some OTC preparations may have no active ingredient and are ineffective in lowering LDL or raising HDL cholesterol.

Nicotinic acid is most effective in increasing HDL cholesterol, and modestly effective in lowering LDL cholesterol and triglyceride levels. Used alone, it can raise HDL cholesterol levels by 30% or more. However, it is not as effective as a statin in lowering LDL cholesterol

niacin, nicotinic acid, vitamin B3
(Niacor, Niaspan, Slo-Niacin)

Prescription: Yes and over-the-counter (OTC)
Generic: Yes
Preparations: Tablets of 50, 100, 250, 500 and 750 mg. Capsules of 125, 250, 400, 500, 750 and 1000 mg.

Prescribed for: Nicotinic acid (vitamin B3 or niacin) is used for treating niacin deficiency and elevated blood cholesterol and/or triglyceride levels and for increasing HDL cholesterol.

Side effects: The most common side effects of nicotinic acid (vitamin B3 or niacin) are stomach upset, flushing, headache, itching and tingling sensations of the extremities. Rare cases of liver failure or muscle injury have occurred from the use of nicotinic acid.

What are cholesterol absorption inhibitors?

This relatively new class of cholesterol-lowering medication works by preventing the absorption of cholesterol from the intestine. Selective cholesterol absorption inhibitors are most effective at lowering the LDL (bad) cholesterol but may also have modest effects on lowering triglycerides (blood fats), and raising HDL (good) cholesterol.

ezetimibe (Zetia)

Drug Class: Cholesterol absorption inhibitors
Prescription: Yes
Generic: No
Preparations: Tablets of 10 mg.

Prescribed for: Ezetimibe (Zetia) lowers blood cholesterol by reducing the absorption of cholesterol from the intestine. Used in combination with statins, it reduces levels of total cholesterol, LDL cholesterol, and triglycerides. It also may raise HDL cholesterol. Combining ezetimibe with a statin is more effective than either drug alone.

Side effects: Ezetimibe (Zetia) usually is well-tolerated. Diarrhea, abdominal pain, back pain, joint pain, and sinusitis were the most commonly reported side effects, occurring in one in every 25 to 30 patients. Hypersensitivity reactions, including angioedema (swelling of the skin and underlying tissues of the head and neck that can be life-threatening) and skin rash occur rarely. Nausea, pancreatitis, muscle damage (myopathy or rhabdomyolysis), and hepatitis have been reported.

Combining drugs to fight high cholesterol.

As noted on the previous slides, some medications are primarily useful in lowering LDL cholesterol, others in lowering triglycerides, and some in elevating HDL cholesterol. Doctors may also prescribe two medications from two different drug classes to more aggressively lower LDL, as well as increase HDL cholesterol levels at the same time.

ezetimibe/simvastatin (Vytorin)

Prescription: Yes
Generic: No
Preparations: Tablets of 10/10, 10/20, 10/40, 10/80 mg. (ezetimibe/simvastatin)

Prescribed for: Ezetimibe/simvastatin (Vytorin) is a combination of ezetimibe (Zetia) and simvastatin (Zocor) that is used for treating high levels of cholesterol in the blood. Vytorin reduces total cholesterol and LDL cholesterol while it increases HDL cholesterol.

Side effects: The most common side effects of ezetimibe/simvastatin (Vytorin) are headache, nausea, vomiting, diarrhea, muscle pain, and abnormal liver tests. Hypersensitivity reactions have also been reported. The most serious potential side effects are liver damage and muscle inflammation or breakdown.

niacin and lovastatin (Advicor)

Prescription: Yes
Generic: No
Preparations: Tablet of 500/20 and 1000/20 mg (niacin/lovastatin).

Prescribed for: Niacin and lovastatin (Advicor) is used for treating elevated blood levels of total cholesterol, LDL cholesterol, and triglycerides, and for raising low levels of HDL cholesterol.

Side effects: Please refer to the individual slides for niacin and lovastatin.

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holesterol-altering drugs overview

This chart provides a textual overview of the various cholesterol drugs discussed in this slideshow. It lists each of the medication classes, examples within each class, and their areas of beneficial effectiveness.