Pharmacy & Therapeutics - May 2008 - (Page 271) DRUG FORECAST Omega-3-acid Ethyl Esters (Lovaza) For Severe Hypertriglyceridemia Renee R. Koski, PharmD, CACP INTRODUCTION Hypertriglyceridemia is an independent risk factor for coronary heart disease (CHD), according to the guidelines from the Third Report of the National Cholesterol Education Program Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III).1 High triglyceride (TG) levels are frequently found in combination with insulin resistance, obesity, and low levels of high-density lipoproteincholesterol (HDL-C) in patients with the metabolic syndrome. Extremely high TG concentrations can cause a number of medical problems, including CHD and acute pancreatitis. The primar y causes of hypertriglyceridemia include cigarette smoking, ver y-high-carbohydrate diets, disease (i.e., diabetes, nephrotic syndrome), certain drugs (i.e., corticosteroids, protease inhibitors), and genetic factors. Excess acute alcohol intake can also raise TG levels, especially when alcohol is consumed with food.1,2 TG levels are classified as follows: normal (below 150 mg/dL), borderline–high (150–199 mg/dL), high (200–499 mg/ dL), or very high (500 mg/dL or more).1 Approximately five to six million people in the U.S. have TG levels exceeding 500 mg/dL. NCEP ATP III guidelines endorse pharmacological treatment of hypertriglyceridemia above this value. The underlying principles in treating very high TG levels are to prevent acute Disclosure: The author has no conflict of interest or financial interest with regard to this manuscript. Dr. Koski is Associate Professor of Pharmacy Practice at Ferris State University College of Pharmacy in Big Rapids, Michigan. Drug Forecast is a regular column coordinated by Alan Caspi, PhD, PharmD, MBA, President of Caspi & Associates in New York, New York. pancreatitis and CHD. Standard treatments include: 1 • diet and exercise • smoking and alcohol cessation • medications: • niacin (e.g., Niaspan, Kos) • fibric acids: gemfibrozil (Lopid, Pfizer); fenofibrate (TriCor, Abbott) • HMG–CoA reductase inhibitors (statins) • fish oil For more than 30 years, it was recognized that certain ethnic populations, such as the Native Alaskans, had much lower mortality rates from cardiovascular disease (CVD). Further examination revealed that their diets were high in polyunsaturated fatty acids.3,4 Small obser vational and large epidemiological studies have since confirmed that ingesting omega-3 fatty acids (a type of longchain polyunsaturated fatty acid) was associated with a reduced rate of premature deaths from CVD.5,6 Omega-3 and omega-6 fatty acids are essential, because humans do not synthesize them. The omega-6 fatty acids include linolenic acid, gamma-linolenic acid, and arachidonic acid. The three main types of omega-3 fatty acids are alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic HOOC acid (DHA) (Figure 1). Chemically, ALA, EPA, and DHA are carboxylic acids with 18, 20, and 22 carbons and three, five, and six double bonds, respectively (see Figure 1).7 Humans produce only small amounts of omega-3 fatty acids via conversion of ALA to EPA and DHA. EPA and DHA are found in breast milk. Thus, omega-3 fatty acids must be ingested through the diet. ALA omega-3 fatty acids occur naturally in plant foods such as flaxseed, walnuts, and canola oil. EPA and DHA omega-3 fatty acids are found in all fish, and the quantity is highest in oily fish (salmon, rainbow trout, mackerel, tuna, and herring). They are also available alone and in combination in over-thecounter dietary supplements.4,8–10 DHA, the primary structural fatty acid in the gray matter of the brain and the retina, is essential for mental functioning and vision.11 Both DHA and EPA act as precursors for eicosanoids (prosta glandin, thromboxane, and leukotriene) and are thought to play a role in reducing inflammation. In clinical trials, they also worked together in reducing TG levels and mortality rates from CVD. It is unclear whether the effects on CVD would result if either agent were taken alone.7 The “Revision 2000” American Heart Association (AHA) Dietary Guidelines recommend two servings of fatty fish per week for healthy people without CVD. Alpha-linolenic acid (ALA) HOOC Eicosapentaenoic acid (EPA) HOOC Docosahexaenoic acid (DHA) Figure 1 Chemical structures of omega-3 fatty acids. (From www.wikipedia.com.7) Vol. 33 No. 5 • May 2008 • P&T® 271 http://www.wikipedia.com
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