Antilipemic Drugs: Lowering Lipid Levels

Antilipemic Drugs

• Antilipemic drugs lower lipid levels and are used as an adjunct to diet therapy.
• Drug choice is based on the specific lipid profile of the patient.
• Non-drug means of controlling blood cholesterol levels should be tried for at least 6 months before drug therapy.

Triglycerides and Cholesterol

• Lipids are water-insoluble fats that must be bound to apolipoproteins.
• Apolipoproteins are specialized lipid-carrying proteins.
• The liver is the major organ of lipid metabolism and cholesterol production.
• Lipoprotein is the combination of triglyceride or cholesterol with apolipoprotein.
• Very-low-density lipoprotein (VLDL) is produced by the liver and transports endogenous lipids.
• Low-density lipoprotein (LDL) lab levels decrease.
• High-density lipoprotein (HDL) lab levels increase, and is responsible for "recycling" cholesterol, also known as “good cholesterol".
• Low HDL levels are less than 40 mg/dL.
• Total cholesterol levels of 300 mg/dL are three to four times greater than in patients with levels less than 200 mg/dL.
• As cholesterol increases, the incidence of death from coronary heart disease rises.

Types of Antilipemics

• HMG-CoA reductase inhibitors (HMGs, or statins)
• Bile acid sequestrants
• Niacin (vitamin B3, nicotinic acid)
• Fibric acid derivatives (fibrates)
• Cholesterol absorption inhibitor (Zetia)
• Herbal medications

HMG-CoA Reductase Inhibitors (HMGs, or statins)

• These are the most potent LDL reducers.
• Examples: pravastatin (Pravachol), simvastatin (Zocor), atorvastatin (Lipitor), fluvastatin (Lescol), rosuvastatin (Crestor), pitavastatin (Livalo).
• All are given orally, preferably with the evening meal.
• Baseline cholesterol, HDL, LDL, triglycerides, renal and liver function tests should be monitored before and periodically during therapy.
• Results are seen in 6-8 weeks.
• They inhibit HMG-CoA reductase, used by the liver to produce cholesterol.
• They lower the rate of cholesterol production.
• They are the first-line drug therapy for hypercholesterolemia.
• Outcomes include reduced LDL levels, increased HDL levels, and reduced triglycerides.
• Side Effects; mild GI disturbances, rash, headache, myopathy (muscle pain), which can lead to rhabdomyolysis, elevations in liver enzymes or liver disease and peripheral neuropathy.
• Interactions: oral anticoagulants, erythromycin, antifungals (requires lots of liver function), verapamil, diltiazem, HIV protease inhibitors, amiodarone, and grapefruit juice (delays metabolism of the statin).

Bile Acid Sequestrants

• Bile acid sequestrants may be used along with statins.
• Examples: cholestyramine (Questran), colestipol hydrochloride (Colestid), colesevelam (Welchol, taken orally in tablet form).
• Colesevelam (Welchol) should be taken with food and 8oz of water, and not with other medications.
• They prevent reabsorption of bile acids from the small intestine and bile acids are necessary for absorption of cholesterol.
• Side Effects: constipation, heartburn, nausea, belching, and bloating (generally get better over time).

Niacin (Nicotinic Acid/Vitamin B3)

• Niacin is effective, inexpensive, and often used in combination with other lipid-lowering drugs.
• It decreases triglycerides, total serum cholesterol, and LDL levels, while increasing HDL levels.
• It increases the activity of lipase, breaking down lipids.
• It reduces the metabolism of cholesterol and triglycerides.
• Side Effects: flushing (caused by histamine release; and NSAIDs help), pruritus (due to histamine release), GI distress, hyperglycemia, and hepatotoxicity.

Fibric Acid Derivatives (Fibrates)

• Examples: gemfibrozil (Lopid), fenofibrate (Tricor).
• Outcomes: decreases triglyceride levels and increases HDL.
• Activates lipase and breaks down cholesterol
• Suppresses the release of free fatty acid from adipose tissue.
• Inhibits synthesis of triglycerides in the liver.
• Increases secretion of cholesterol in the bile.
• Side Effects: abdominal discomfort, diarrhea, nausea, blurred vision, headache, increased risk of gallstones, prolonged prothrombin time, abnormal liver studies, and myopathy.
• Interactions: oral anticoagulants and statins, which increase the risk for myositis, myalgias, and rhabdomyolysis.
• Affects lab test reactions, including decreased hemoglobin level, hematocrit value, and white blood cell count, as well as increased activated clotting time, lactate dehydrogenase level, and bilirubin level.

Cholesterol Absorption Inhibitor

• Ezetimibe (Zetia) is often combined with a statin drug.
• It is currently recommended only when patients have not responded to other therapies.
• Outcomes: decreases total cholesterol, LDL and triglyceride levels while increasing HDL levels.
• Action: inhibits absorption of cholesterol secreted in the bile and from food.
• Side Effects: hepatitis and myopathy.
• It is contraindicated in patients who have mild to severe liver disorder.

Herbal Products

• Omega-3 Fatty Acids: used to reduce cholesterol and may cause rash, belching, allergic reactions, and/or potential interactions with anticoagulant drugs.
• Garlic: used as a lipid reducer. Adverse effects include dermatitis, vomiting, diarrhea, flatulence, and antiplatelet activity. Possible interactions with warfarin and diazepam. May enhance bleeding when taken with NSAIDs.
• Flax: Both the seed and oil of the plant are used for hypercholesterolemia. May cause diarrhea and allergic reactions. Possible interactions: antidiabetic drugs and anticoagulant drugs.

Nursing Implications

• Contraindications: include biliary obstruction, liver dysfunction, active liver disease
• Obtain baseline liver function studies
• Patients on long-term therapy may need supplemental fat-soluble vitamins (A, D, K)
• Take medicine with meals to decrease GI upset
• Powder forms must be taken with a liquid, mixed thoroughly (but not stirred), and never taken dry
• Other medications should be taken 1 hour before or 4-6 hours after meals to avoid interference with absorption
• To minimize adverse effects of niacin, start on a low initial dose, increase gradually, and take with meals.
• Small doses of aspirin or NSAIDs may be taken 30 minutes before niacin to minimize cutaneous flushing.
• Inform patients that several weeks are needed to show effectiveness.
• Instruct patients to report persistent GI upset, constipation, abnormal or unusual bleeding, and yellow discoloration of the skin.
• Monitor for adverse effects, including increased liver enzyme studies.
• Monitor for therapeutic effects and reduced cholesterol and triglyceride levels.