Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. CHAPTER 28 Antilipemic Drugs

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antilipemics Drugs used to lower lipid levels

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Triglycerides and Cholesterol  Two primary forms of lipids in the blood  Water-insoluble fats that must be bound to apolipoproteins, specialized lipid-carrying proteins  Lipoprotein is the combination of triglyceride or cholesterol with apolipoprotein

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Lipoproteins  Very-low-density lipoprotein (VLDL)  Produced by the liver  Transports endogenous lipids to the cells  Low-density lipoprotein (LDL)  High-density lipoprotein (HDL)  Responsible for “recycling” of cholesterol  Also known as “good cholesterol”

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.

Coronary Heart Disease The risk of CHD in patients with cholesterol levels of 300 mg/dL is three to four times greater than that in patients with levels less than 200 mg/dL

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Coronary Heart Disease Positive Risk Factors  Age  Male 45 years or older  Female 55 years or older, or women with premature menopause not on estrogen replacement therapy  Family history: history of premature CHD  Current cigarette smoker

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Coronary Heart Disease Positive Risk Factors (cont’d)  Hypertension  BP 140/90 or higher, or on antihypertensive medication  Low HDL levels: less than 35 mg/dL  Diabetes mellitus

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Coronary Heart Disease Negative (Beneficial) Risk Factor  High HDL (“good” cholesterol): 60 mg/dL or higher

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Treatment Guidelines  Antilipemic drugs are used as an adjunct to diet therapy  Drug choice based on the specific lipid profile of the patient

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Treatment Guidelines (cont’d)  All reasonable non-drug means of controlling blood cholesterol levels (e.g., diet, exercise) should be tried for at least 6 months and found to fail before drug therapy is considered

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antilipemics  HMG-CoA reductase inhibitors (HMGs, or statins)  Bile acid sequestrants  Niacin (nicotinic acid)  Fibric acid derivatives  Cholesterol absorption inhibitor  Combination drugs

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Antilipemics: HMG-CoA Reductase Inhibitors (HMGs, or statins) Most potent LDL reducers  lovastatin (Mevacor)  pravastatin (Pravachol)  simvastatin (Zocor)  atorvastatin (Lipitor)  fluvastatin (Lescol)

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. HMG-CoA Reductase Inhibitors (cont’d) Mechanism of action  Inhibit HMG-CoA reductase, which is used by the liver to produce cholesterol  Lower the rate of cholesterol production

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. HMG-CoA Reductase Inhibitors (cont’d) Indications  First-line drug therapy for hypercholesterolemia  Treatment of types IIa and IIb hyperlipidemias  Reduce LDL levels by 30% to 40%  Increase HDL levels by 2% to 15%  Reduce triglycerides by 10% to 30%

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. HMG-CoA Reductase Inhibitors (cont’d) Adverse effects  Mild, transient GI disturbances  Rash  Headache  Myopathy (muscle pain), possibly leading to the serious condition rhabdomyolysis  Elevations in liver enzymes or liver disease

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Bile Acid Sequestrants  cholestyramine (Questran)  colestipol hydrochloride (Colestid)  colesevelam (tablet form)  Also called bile acid–binding resins and ion-exchange resins

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Bile Acid Sequestrants (cont’d) Mechanism of action  Prevent resorption of bile acids from small intestine  Bile acids are necessary for absorption of cholesterol

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Bile Acid Sequestrants (cont’d) Indications  Type II hyperlipoproteinemia  Relief of pruritus associated with partial biliary obstruction (cholestyramine)  May be used along with statins

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Bile Acid Sequestrants (cont’d) Adverse effects  Constipation  Heartburn, nausea, belching, bloating  These adverse effects tend to disappear over time

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Niacin (Nicotinic Acid)  Vitamin B 3  Lipid-lowering properties require much higher doses than when used as a vitamin  Effective, inexpensive, often used in combination with other lipid-lowering drugs

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Niacin (Nicotinic Acid) (cont’d) Mechanism of action  Thought to increase activity of lipase, which breaks down lipids  Reduces the metabolism or catabolism of cholesterol and triglycerides

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Niacin (Nicotinic Acid) (cont’d) Indications  Effective in lowering triglyceride, total serum cholesterol, and LDL levels  Increases HDL levels  Effective in the treatment of types IIa, IIb, III, IV, and V hyperlipidemias

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Niacin (Nicotinic Acid) (cont’d) Adverse effects  Flushing (due to histamine release)  Pruritus  GI distress

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Fibric Acid Derivatives Also known as fibrates  gemfibrozil (Lopid)  fenofibrate (Tricor)

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Fibric Acid Derivatives (cont’d) Mechanism of action  Believed to work by activating lipase, which breaks down cholesterol  Also suppress release of free fatty acid from the adipose tissue, inhibit synthesis of triglycerides in the liver, and increase the secretion of cholesterol in the bile

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Fibric Acid Derivatives (cont’d) Indications  Treatment of types III, IV, and V hyperlipidemias Drug Effects  Decrease the triglyceride levels  Increase HDL by as much as 25%

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Fibric Acid Derivatives (cont’d) Adverse effects  Abdominal discomfort, diarrhea, nausea  Blurred vision, headache  Increased risk of gallstones  Prolonged prothrombin time  Liver studies may show increased function

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Cholesterol Absorption Inhibitor ezetimibe (Zetia)  Inhibits absorption of cholesterol and related sterols from the small intestine  Results in reduced total cholesterol, LDL, triglylceride levels  Also increases HDL levels  Works well when taken with a statin drug

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications  Before beginning therapy, obtain a thorough health and medication history  Assess dietary patterns, exercise level, weight, height, VS, tobacco and alcohol use, family history  Assess for contraindications, conditions that require cautious use, and drug interactions

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  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 with meals to decrease GI upset

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Patient must be counseled concerning diet and nutrition on an ongoing basis  Instruct on proper procedure for taking the medications  Powder forms must be taken with a liquid, mixed thoroughly but not stirred, and NEVER taken dry

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Other medications should be taken 1 hour before or 4 to 6 hours after meals to avoid interference with absorption  Clofibrate often causes constipation; instruct patients to increase fiber and fluid intake to offset this effect

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  To minimize adverse effects of niacin, start on low initial dose and gradually increase it, and take with meals  Small doses of aspirin or NSAIDs may be taken 30 minutes before niacin to minimize cutaneous flushing  Inform patients that these drugs may take several weeks to show effectiveness

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  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  Reduced cholesterol and triglyceride levels