Dyslipidemia PDF

1/16/24, 10:22 PM Realizeit for Student Introduction Hyperlipidemia refers to an increase in the level of lipids (cholesterol and triglycerides) in the blood, which increases a person’s risk for the development of CAD, arteriosclerosis and atherosclerosis. Fats are taken into the body as dietary f...

1/16/24, 10:22 PM Realizeit for Student Introduction Hyperlipidemia refers to an increase in the level of lipids (cholesterol and triglycerides) in the blood, which increases a person’s risk for the development of CAD, arteriosclerosis and atherosclerosis. Fats are taken into the body as dietary fats and then broken down in the stomach to fatty acids, lipids, and cholesterol. The enzyme HMG–CoA reductase controls the early rate-limiting step in the production of cellular cholesterol; HMG–CoA is active in every cell. In this section, you will build on your knowledge of hypertension and review the specific antihypertensive medication treatment options. Bile acids act like detergents to break down or metabolize fats into small molecules called micelles, which are absorbed into the intestinal wall and combined with proteins to become chylomicrons to allow transport throughout the circulatory system. Cholesterol is a fat that is used to make bile acids; all cells can produce cholesterol, which is the base for steroid hormones and cell membrane structure. Supplemental agents include fibrates, cholesterol absorption inhibitors, PCSK9 inhibitors, miscellaneous dyslipidemic agents, and combination therapy. Prevention Certain medications that supplement dietary modification and exercise are used to reduce blood lipid levels. Current evidence-based guidelines established by the American College of Cardiology and the American Heart Association (ACC/AHA) recommend 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as first-line therapy in patients with PAD for secondary prevention and cardiovascular risk reduction (Conte, Bradbury, Kolh, et al., 2019). These statins may include medications such as atorvastatin, lovastatin, pitavastatin, pravastatin, simvastatin, fluvastatin, and rosuvastatin. Several other classes of medications used to reduce lipid levels include bile acid sequestrants (cholestyramine, colesevelam, colestipol), nicotinic acid (niacin), fibric acid inhibitors (gemfibrozil, fenofibrate), and cholesterol absorption inhibitors (ezetimibe). Patients receiving long-term therapy with these medications require close monitoring. Overview of Dyslipidemia Management Lifestyle Changes Herbs and foods reported to have an effect on serum cholesterol and triglyceride levels. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 1/14 1/16/24, 10:22 PM Realizeit for Student Herbs and Foods Reported to Have Evidence-Based Effects on Cholesterol and Triglyceride Levels Flaxseed Low-density lipoprotein (LDL) cholesterol: decreased with flaxseed and flaxseed lignans; no apparent decrease with flaxseed oil. Triglycerides: no apparent effect. Absorption of all medications may be decreased when taken with flax, resulting in a less than therapeutic effect. Garlic LDL cholesterol: no significant effect. Triglycerides: no significant effect. Bleeding may be increased when garlic is combined with anticoagulants, and insulin doses may need to be decreased as a result of the hypoglyc Red Yeast Rice Total and LDL cholesterol: decreased. Triglycerides: no significant effect. Dosage standardization is a concern, and information about long-term safety is unavailable. Soy LDL cholesterol: benefit at most small. Triglycerides: no significant effect. Intake of soy proteins may have other beneficial vascular effects. Drug Therapy Clinical data suggest that drug therapy may be efficacious even for those with mild to moderate elevations of LDL cholesterol, particularly with preexisting cardiovascular disease. Dyslipidemic drugs act by altering the production, absorption, metabolism, or removal of lipids and lipoproteins. Depending on cardiovascular risk, drug therapy is initiated after 6 months of dietary and other lifestyle changes fail to decrease dyslipidemia to an acceptable level. It is also recommended for patients with signs and symptoms of coronary heart disease, a strong family history of coronary heart disease or dyslipidemia, or other risk factors for atherosclerotic vascular disease (e.g., hypertension, diabetes mellitus, cigarette smoking). Although several dyslipidemic drugs are available, none is effective in all types of dyslipidemia, so drug selection is based on the type of dyslipidemia and its severity. To lower cholesterol using a single drug, a statin is preferred. To lower cholesterol and triglycerides, a statin, a cholesterol absorption inhibitor, gemfibrozil, or a fibrate may be used. To lower triglycerides, gemfibrozil, ezetimibe, or a cholesterol absorption inhibitor may be given. Alternatively, in specific clinical situations (triglyceride level greater than 500 mg/dL), the vitamin niacin may be used. Categories of drugs are described in upcoming sections. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 2/14 1/16/24, 10:22 PM Realizeit for Student Figure 10.1. Sites of action of dyslipidemic drugs. HMG-CoA Reductase Inhibitors Atorvastatin (Lipitor), one of the most widely used drugs in the United States, is the prototype of the class of drugs called the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins. By decreasing production of cholesterol, the statins decrease total serum cholesterol, LDL cholesterol, VLDL cholesterol, and triglycerides. They reduce LDL cholesterol within 2 weeks and reach maximal effects in approximately 4 to 6 weeks. HDL cholesterol levels remain unchanged or may increase. The most commonly prescribed statin, atorvastatin, is useful for treating dyslipidemia and is an overall tool in the primary prevention of cardiovascular disease. Several clinical trials have supported the beneficial effects of statins in women with coronary artery disease. In addition, studies have suggested that atorvastatin may possess some benefits that other statins do not. Research has focused on multiple outcomes, including intimal thickness, results of imaging studies, mortality, incidence of stroke, and progression of lesions, but there continue to be questions about the benefit profiles of individual statin drugs. Pharmacokinetics Atorvastatin is rapidly absorbed following oral administration and undergoes extensive first-pass metabolism by the liver, which results in low levels of drug available for general circulation. Peak effect occurs in 1 to 2 hours. Food decreases the rate and extent of absorption. Metabolism occurs in the liver, with 80% to 85% of drug metabolites excreted in feces and the remaining products excreted in urine. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 3/14 1/16/24, 10:22 PM Realizeit for Student Action The statins inhibit an enzyme (HMG-CoA reductase) required for hepatic synthesis of cholesterol. In part, metabolism involves one or more hepatic cytochrome P450 enzymes (including CYP2D6), leading to an increased risk of drug interactions and problems with certain foods (e.g., grapefruit juice). Additionally, some of the variability in the response to statins and associated adverse effects statins may relate to genetic differences in the rate of drug metabolism. For example, a CYP2D6 functional deficiency is present in about 7% of Caucasians and African Americans, and this deficiency is rare in people of Asian descent. Use Atorvastatin and the other statins are indicated for the treatment of hypercholesterolemia and reducing cardiovascular events in people with multiple risk factors. The statins are the most powerful drug class for reduction of LDL cholesterol. They result in an 18% to 55% decrease in LDL levels, as well as a 5% to 15% increase in HDL levels and a 7% to 30% decrease in triglycerides. QSEN Alert: Evidence-Based Practice Over the past century, evidence has shown that LDLs are the major risk factor for arteriosclerotic cardiovascular disease. In fact, in every mammalia LDL levels produce atherosclerosis ( Goldstein & Brown, 2015 ). At any level of LDL, the likelihood of a myocardial infarction is increased in the pres such as cigarette smoking and hypertension. Researchers linked the contribution of the compound 3-hydroxy-3-methylglutarate attached to coenz cholesterol, which led to a revolution in the management of hypercholesterolemia. This discovery then led to the broad use of HMG-CoA reductase multiple studies regarding statins has demonstrated that the frequency of myocardial infarctions can be significantly reduced by lowering LDL even present. Although these contributory factors are important, they all require LDL to initiate the lesion. Use in Children Statins are now considered first-line therapy in the treatment of dyslipidemia in children. As with adults, the management of children with dyslipidemia focuses on lifestyle modifications. Use in Older Adults As in younger adults, diet, exercise, and weight control should be tried first to reduce cholesterol levels. When drug therapy is required, statins are effective for lowering LDL cholesterol and usually are well tolerated by older adults. Use in Patients With Renal Impairment In renal impairment, plasma levels are not affected, and dosage reductions are not necessary. Use in Patients With Hepatic Impairment Atorvastatin and other statins, which are metabolized in the liver, may accumulate in patients with impaired hepatic function. Thus, they are contraindicated in patients with active liver disease or unexplained elevations of serum aspartate aminotransferase or alanine aminotransferase. These drugs should be used cautiously, in reduced dosages, for patients who ingest substantial amounts of alcohol or who have a history of liver disease. Use in Patients Receiving Home Care Because liver enzymes may be elevated during atorvastatin use, patients need liver function tests and repeat lipid profile testing on a routine basis. Increasing availability of home cholesterol-monitoring devices will require additional patient teaching about technique and interpretation of the results. Patients should notify their health care provider if unexplained muscle pain or tenderness occurs. Adverse Effects Statins are usually well tolerated; the most common adverse effects (nausea, constipation, diarrhea, abdominal cramps or pain, headache, skin rash) are usually mild and transient. Hepatic dysfunction has been a source of concern, although the actual risk appears to be small. Myopathies are important adverse effects and can range from discreet muscle pain to rhabdomyolysis. Statins can injure muscle tissue, resulting in muscle ache, pain, or weakness. Factors that increase the risk of rhabdomyolysis include advanced age, frail or small body frame, high dosage of statins, concomitant use of drugs that interfere with CPY3A4 including fibrates, hypothyroidism, and multiple systemic diseases such as renal insufficiency secondary to diabetic nephropathy. QSEN Alert: Safety https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 4/14 1/16/24, 10:22 PM Realizeit for Student When women of childbearing age are treated with drug therapy for dyslipidemia, adequate patient education is critical to minimize complications as risk of teratogenicity with the use of statins appears to be relatively small; however, the use of birth control measures with statin use is essential in s consideration should be given if potential benefits warrant use of the drug class in pregnant women despite potential risks. The nurse advocates in Contraindications Statins are potentially teratogenic (pregnancy category X). Careful consideration is necessary if potential benefits warrant use of these drugs in pregnant women. Additional contraindications include lactation because the drugs are secreted in breast milk and hypersensitivity to statins. Nursing Implications The statins are the most effective dyslipidemic agents for improving clinical outcomes when used for primary and secondary prevention of cardiovascular disease. The choice and use of statins are based on a number of factors, including the degree of dyslipidemia, a specific drug's actions, drug interactions, the presence of renal or liver impairment, and cost. Preventing Interactions Many medications and herbs interact with atorvastatin, increasing or decreasing its effect. Drug Interactions: Atorvastatin Drugs That Increase the Effects of Atorvastatin Magnesium- and aluminum-containing antacids Interfere with absorption; administer atorvastatin 2 hours before or after antacids. Amiodarone and colchicine Decrease metabolism Azole antifungals Increase the risk of myopathy; it is recommended that statin therapy be interrupted temporarily if systemic azole antifungals are needed. Cyclosporine, CYP3A inhibitors, diltiazem, fibric acid derivatives, niacin, and verapamil Increase the risk of severe myopathy or rhabdomyolysis Erythromycin, macrolide antibiotics, nefazodone, and protease inhibitors Decrease elimination Drugs That Decrease the Effects of Atorvastatin Cholestyramine Decreases rate of bioavailability; administer atorvastatin at least 4 hours after this bile acid sequestrant. Colestipol Decreases plasma levels Herb and Dietary Interactions: Atorvastatin Herbs and Foods That Increase the Effects of Atorvastatin Grapefruit juice, pomegranate juice, red yeast rice, sitostanol, and vitamin B3 Herbs and Foods That May Decrease the Effects of Atorvastatin Fibers such as oat bran and pectin Administering the Medication Because the bulk of cholesterol synthesis appears to occur at night, administration of statins normally takes place in the evening or at bedtime. However, atorvastatin has a long half-life, and evidence suggests that the drug can be given without regard to time of day. There is no definitive global recommendation for the entire class; thus, the timing of administration of statins should be based on manufacturer recommendations. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 5/14 1/16/24, 10:22 PM Realizeit for Student Assessing for Therapeutic Effects The nurse monitors lipid response to therapy, looking for decreased levels of total serum cholesterol, LDL cholesterol, and triglycerides, as well as increased levels of HDL cholesterol. Effects occur in 1 to 2 weeks, with maximum effects in 4 to 6 weeks. Assessing for Adverse Effects Common adverse effects include nausea, diarrhea, abdominal pain, dyspepsia, and elevated liver function tests. The nurse monitors for signs or symptoms of muscle pain or weakness, mainly during the first months of therapy and when dosages are adjusted upward. If unexplained severe muscle symptoms, fatigue, or cola-colored urine develop, the statin should be held, and the prescriber notified to address the possibility of rhabdomyolysis. Patient Teaching Women of childbearing age should receive contraceptive counseling to enhance awareness of the risks associated with statin use. In addition, education should focus on the importance of monitoring liver function on a regular basis. Liver function tests are recommended before starting a statin, at 12 weeks after starting the drug, at every increase in dose, and then periodically. The nurse monitors patients with increased serum aminotransferases until the abnormal values resolve. If the increases are more than three times the upper limit of normal levels and persist, it is necessary to reduce the dose or change the drug. Patient Teaching Guidelines for Dyslipidemic Drugs As you probably know, heart and blood vessel disease causes a great deal of illness and many deaths. The basic problem is usually atherosclero blocked by cholesterol deposits. Cholesterol, a waxy substance made in the liver, is necessary for normal body functioning. However, excessive likelihood of having a heart attack, stroke, or leg pain from inadequate blood flow. One type of cholesterol (LDL or “bad”) attaches to artery walls blood flow. The other type (high-density lipoprotein [HDL] or “good”) carries cholesterol away from the artery and back to the liver, where it can b cholesterol levels in adults are low total cholesterol (less than 200 mg/dL), low LDL (less than 130 mg/dL), and high HDL (greater than 35 mg/dL). type of fat, are also unhealthy. Dyslipidemic drugs are given to lower high concentrations of fats (total cholesterol, LDL cholesterol, and triglycerides) in your blood. The goal of stroke, and peripheral arterial disease. If you already have heart and blood vessel disease, the drugs can improve your symptoms, activity level, a Eating a low-fat diet can help. This is often the first step in treating high cholesterol or triglyceride levels and may be prescribed for 6 months or l drug therapy is prescribed, the diet should be continued. An important part is reducing the amount of saturated fat (from meats, dairy products). daily can help lower cholesterol by 5% to 10%. Diet counseling by a dietitian or nutritionist can be helpful in developing guidelines that fit your ne weight may decrease or cancel the lipid-lowering effects of the drugs. Make other lifestyle changes to help improve cholesterol levels that include regular aerobic exercise (raises HDL), losing weight (raises HDL, lowe smoking (HDL levels are higher in nonsmokers). As an adult, have measurements of total cholesterol and HDL cholesterol at least once ever every 5 years. People with a personal or family histor cardiovascular disease should be tested more often. Techniques for home monitoring of cholesterol levels are improving and are more available for self-use. You may receive instructions about perfo results to your health care provider. Other Drugs in the Class Absorption following oral administration varies depending on the drug. Lovastatin and pravastatin are poorly absorbed, and fluvastatin has the highest rate of absorption. Most of the statins undergo extensive first-pass metabolism by the liver, which results in low levels of drug available for general circulation. Patients may take pravastatin or simvastatin with or without food in the evening. They may take fluvastatin on an empty stomach or at bedtime. It is important to avoid taking them with grapefruit juice. Note that concurrent use of cimetidine, ranitidine, and omeprazole increases the effects of fluvastatin Bile Acid Sequestrants Cholestyramine (Prevalite, Questran), the prototype bile acid sequestrant, has the ability to reduce LDL cholesterol. It has little or no effect on HDL cholesterol and either no effect or an increased effect on triglyceride levels. There is no evidence that cholestyramine can be used as monotherapy, but it can play a role as an add-on drug with statins or niacin in combination therapy. Pharmacokinetics https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 6/14 1/16/24, 10:22 PM Realizeit for Student Cholestyramine is not absorbed when taken orally. Therefore, the drug is excreted in feces essentially unchanged. Action Cholestyramine binds bile acids in the intestinal lumen, causing the bile acids to be excreted in feces, preventing recirculation to the liver. Loss of bile acids stimulates hepatic synthesis of more bile acids from cholesterol. As more hepatic cholesterol is used to produce bile acids, more serum cholesterol moves into the liver to replenish the supply, thereby lowering serum cholesterol (primarily LDL). LDL cholesterol levels decrease within a week of starting cholestyramine and other bile acid sequestrants and reach maximal reductions within a month. When the drugs are stopped, pretreatment LDL cholesterol levels return within a month. Use Cholestyramine reduces LDL cholesterol levels (15%–30%) and produces a minimal elevation in HDL cholesterol (3%–5%). Use in Children Cholestyramine and other bile acid sequestrants are safe and moderately effective in children and adolescents ages 6 to 18 years and decrease both total cholesterol and LDL cholesterol levels. A modest elevation in triglyceride levels has been reported. Children do not tolerate the reported gastrointestinal adverse effects well. Use in Older Adults Cholestyramine and other bile acid sequestrants are effective in older adults, although these individuals do not tolerate the adverse effects well. Use in Patients With Renal Impairment Extended use of cholestyramine in patients with renal impairment requires caution because the drug releases chloride. This effect can increase the risk of hyperchloremic metabolic acidosis. Use in Patients With Hepatic Impairment Cholestyramine can further raise serum cholesterol. Therefore, its use in people with primary biliary cirrhosis warrants caution. Adverse Effects Cholestyramine is not absorbed systemically, so the main adverse effects are gastrointestinal (GI) ones (abdominal fullness, flatulence, diarrhea, and constipation). Constipation is especially common, and a bowel program may be necessary to control this problem. Contraindications Cholestyramine is contraindicated in people with complete biliary obstruction because bile is not secreted into the intestine. The drug can bind with vitamin K; thus, use in individuals with any coagulopathy requires caution. Nursing Implications Preventing Interactions Cholestyramine may decrease absorption of many oral medications (e.g., digoxin, folic acid, glipizide, propranolol, tetracyclines, thiazide diuretics, thyroid hormones, fat-soluble vitamins, and warfarin). Apparently, no drugs significantly affect cholestyramine. Herbs and foods that increase the effects of cholestyramine include fibers such as oat bran and pectin. No herbs and foods seem to decrease the effects of cholestyramine. In a patient who is taking cholestyramine in addition to other drugs, the dosage of the interactive drug may need to be changed when the bile acid sequestrant is added or withdrawn. Also, because cholestyramine binds bile acids, cholestyramine may interfere with normal fat digestion and absorption and therefore may prevent absorption of the fat-soluble vitamins A, D, E, and K. Administering the Medication It is necessary to mix cholestyramine powder with water or other fluids, soups, cereals, or fruits such as applesauce and to follow with more fluid. The nurse ensures that the drug is not taken in a dry form. It is essential that cholestyramine not be given with other drugs; to minimize altered absorption, people should take the other drugs 1 hour before or 4 to 6 hours after cholestyramine. Assessing for Therapeutic Effects The nurse observes for decreased levels of total serum cholesterol, LDL cholesterol, and triglycerides and increased levels of HDL cholesterol. Maximum effects occur in approximately 1 month. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 7/14 1/16/24, 10:22 PM Realizeit for Student Assessing for Adverse Effects The most common adverse effect is constipation. Other conditions relate to GI effects: abdominal discomfort or pain, nausea, vomiting, flatulence, diarrhea, anorexia, and steatorrhea. Increased bleeding tendencies may result from vitamin K malabsorption. Patient Teaching The nurse assesses the adequacy of levels of fat-soluble vitamins A, D, E, and K; supplementation may be required. Good dental hygiene is important because holding the mixture in the mouth can damage the teeth. Some products may contain aspartame or sugar, so caution is necessary in patients with phenylketonuria or diabetes mellitus. Also, the nurse teaches patients that these drugs are used mainly to reduce LDL cholesterol further in those who are already taking a statin drug. The inhibition of cholesterol synthesis by a statin drug makes bile acid-binding drugs more effective. In addition, the combination increases HDL cholesterol and can further reduce the risk of cardiovascular disorders. Other Drugs in the Class In patients with elevated LDL cholesterol, colesevelam (Welchol) and colestipol (Colestid) may be used along with diet modifications to reduce serum cholesterol. Colesevelam is also used as an adjunct agent to improve glycemic control in adults with type 2 diabetes mellitus. Like cholestyramine, colesevelam and colestipol are not absorbed systemically but may interfere with absorption of fat-soluble vitamins A, D, E, and K. These drugs are not expected to be excreted in breast milk, but they may affect vitamin levels in nursing infants. Some products may contain phenylalanine. Patients who take the granular form of colestipol should not swallow the granules dry. Patients who take the tablet form of either drug should swallow tablets whole, without cutting, crushing, or chewing. The adverse effects profile and interactions are similar for all bile acid sequestrants. Fibrates Fibrates are derivatives of fibric acid and are similar to endogenous fatty acids. The first fibrate to be developed, clofibrate, has essentially been replaced by other fibrates and is not discussed. Therefore, fenofibrate (TriCor) serves as the prototype in this discussion. Pharmacokinetics Fenofibrate is administered orally and is highly protein-bound, primarily to albumin. The time-to-peak effect is 6 to 8 hours. Metabolism occurs in the liver and excretion is by urinary elimination. Action Fenofibrate and other fibrates increase the oxidation of fatty acids in the liver and muscle tissue. Thus, they decrease hepatic production of triglycerides, decrease VLDL cholesterol, and increase HDL cholesterol. Use Fibrates are the most effective drugs for reducing serum triglyceride values, and their main indication for use is high serum triglycerides (greater than 500 mg/dL); they may result in a 20% to 50% decrease in triglyceride levels. They are also helpful for patients with low HDL cholesterol levels (10%–20% increase). Additionally, fibrates are the drug of choice for hypertriglyceridemia associated with diabetes, gout, gastritis, or ulcer disease. There are no specific recommendations for use of these drugs in patients who are critically ill; drug interactions and adverse effects may restrict their use in critical illness. Use in Children Published studies of the use of fenofibrate and other fibrates in children are limited. Thus, the safety and efficacy of fibrates in children are unclear. Use in Older Adults Caution is warranted with dosage determination. For fenofibrate, lower starting dosages are recommended (67 mg/d). Use in Patients With Renal Impairment As previously stated, fibrates are excreted mainly by the kidneys; therefore, they accumulate in the serum of patients with renal impairment. Fenofibrate is contraindicated in patients with severe renal impairment, and the recommended starting dose is 67 mg/day in patients with a creatinine clearance of less than 50 mL/minute. It is necessary to evaluate the effects of this dose effects on renal function and to check triglyceride levels before increasing this dose. Fibrates may cause a reversible elevated serum creatinine. Patients with diabetes mellitus require close monitoring because renal disease is a serious complication in this population. Use in Patients With Hepatic Impairment https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 8/14 1/16/24, 10:22 PM Realizeit for Student Fibrates may cause hepatotoxicity. Abnormal elevations of serum aminotransferases have occurred with both gemfibrozil and fenofibrate, but they usually subside after the drug is discontinued. Contraindications to fenofibrate include severe hepatic impairment, including primary biliary cirrhosis, and persistent elevations in liver function tests and preexisting gallbladder disease. In addition, hepatitis (hepatocellular, chronic active, and cholestatic) has reportedly occurred after use of fenofibrate from a few weeks to several years. It is necessary to monitor liver function during the first year of drug administration. Discontinuation of the drug is warranted if elevated enzyme levels persist at more than three times the normal limit. Use in Patients Receiving Home Care Because liver enzyme tests are recommended, patients who are housebound may need assistance in obtaining blood tests (e.g., lipids, liver function tests). The nurse advises patients to notify their health care provider if unexplained muscle pain or tenderness occurs. Increasing availability of home cholesterol-monitoring devices will require additional patient teaching about technique and interpretation of the results. Adverse Effects The main adverse effects are GI discomfort and diarrhea, which may occur less often with fenofibrate than with other fibrates. Fibrates may also increase cholesterol concentration in the biliary tract and formation of gallstones. Contraindications Contraindications include hypersensitivity to fibrates, hepatic or (severe) renal impairment, preexisting gallbladder disease, primary biliary cirrhosis, or persistent liver function abnormalities of unknown origin. Nursing Implications Preventing Interactions Fenofibrate and other fibric acid derivatives may enhance the hypoprothrombinemic effect of warfarin-type oral anticoagulants, increasing the risk of bleeding. Patients receiving warfarin concurrently require a substantially decreased dosage of warfarin because fibrates displace warfarin from binding sites on serum albumin. No herbal interactions have been identified. Drug Interactions: Fenofibrate Drugs That Increase the Effects of Fenofibrate Statins Increase the risk of severe myopathy or rhabdomyolysis Cyclosporine Mechanism for increase is unknown. Drugs That Decrease the Effects of Fenofibrate Bile acid sequestrant drugs Decrease absorption; to avoid, take fenofibrate about 1 hour before or 4 to 6 hours after the bile acid sequestrant. Administering the Medication It is necessary to give fenofibrate with food to increase drug absorption. Assessing for Therapeutic Effects The nurse assesses for decreased levels of total serum cholesterol, LDL cholesterol, and triglycerides and increased levels of HDL cholesterol. With fibrates, effects occur in approximately 1 month. Assessing for Adverse Effects GI disturbances, as well as elevated liver function tests, are common. Reportedly, hypersensitivity reactions, myopathy, rhabdomyolysis, blood dyscrasias, hepatotoxicity, cholelithiasis, cholestatic jaundice, pancreatitis, and reduced libido also occur, although these effects are rare. The risk of myopathy increases with concomitant use of statins. Patient Teaching The nurse instructs patients to report signs and symptoms of adverse effects to the health care provider. Throughout drug therapy, patients should have periodic blood tests. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 9/14 1/16/24, 10:22 PM Realizeit for Student Other Drugs in the Class It is necessary to give gemfibrozil on an empty stomach, about 30 minutes before the morning and evening meal. Cholesterol Absorption Inhibitor Ezetimibe (Zetia) is the prototype of the newest class of dyslipidemic drugs, which act in the small intestine to inhibit absorption of cholesterol and decrease the delivery of intestinal cholesterol to the liver, resulting in reduced hepatic cholesterol stores and increased clearance of cholesterol from the blood. This distinct mechanism is complementary to that of HMG-CoA reductase inhibitors, producing synergistic cholesterol-lowering effects when these drugs are used in combination. Ezetimibe reduces total cholesterol and triglycerides and increases HDL cholesterol. Pharmacokinetics Ezetimibe is significantly protein bound, is metabolized in the small intestine and liver, and is excreted predominately in feces. The time-topeak effect is 4 to 12 hours. Action Ezetimibe blocks biliary and dietary cholesterol absorption at the brush border of the intestine without affecting the absorption of fat-soluble vitamins and triglycerides. Use Ezetimibe is used together with dietary management for the treatment of primary dyslipidemia. The drug may result in a 14% to 17% decrease in LDL levels. It can be used as monotherapy in combination with a statin. When given as monotherapy (without a statin), ezetimibe does not require dosage reduction in geriatric patients. Use in Children Safety and efficacy in children younger than 10 years of age have not been established. Use in Patients With Hepatic Impairment Dosage adjustment of ezetimibe is necessary in patients with mild hepatic impairment. The drug is not recommended in patients with moderate to severe hepatic impairment. Adverse Effects The most common adverse effects of ezetimibe include headache, diarrhea, and hypersensitivity reactions, such as rash and nausea. Contraindications Contraindications include pregnancy and lactation. Additional contraindications are hypersensitivity to ezetimibe or concomitant use with a statin in people with active hepatic disease. Nursing Implications The nurse instructs patients to maintain a low-cholesterol diet during ezetimibe therapy. Patients should report side effects to their health care providers. Preventing Interactions Some medications interact with ezetimibe, increasing or decreasing its effect. Apparently, no herbs interact with this drug. Drug Interactions: Ezetimibe Drugs That Increase the Effects of Ezetimibe Cyclosporine Increases blood levels Drugs That Decrease the Effects of Ezetimibe https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 10/14 1/16/24, 10:22 PM Realizeit for Student Bile acid sequestrant drugs Mechanism for decrease is unknown. Administering the Medication Ezetimibe may be administered with or without food. The patient takes the drug: At the same time each day. At night if used in combination with a statin. Ezetimibe may be given at the same time as a statin. Either 2 hours before or 4 hours after bile sequestrants to prevent altered absorption. Assessing for Therapeutic Effects The nurse monitors lipid response to therapy with ezetimibe. Desired results include decreases in total cholesterol, LDL cholesterol, and triglycerides, with increases in HDL cholesterol. A therapeutic response occurs within 2 weeks of initiation of therapy and lasts as long as the drug is continued. Assessing for Adverse Effects The nurse observes for headache, dizziness, fatigue, diarrhea, and abdominal pain. Patient Teaching The nurse instructs patients to report signs and symptoms of adverse effects to the health care provider. Throughout drug therapy, patients should have periodic blood tests. PCSK9 Inhibitors PCSK9 inhibitors are monoclonal antibodies that inactivate a protein in the liver called proprotein convertase subtilisin/kexin 9 (PCSK9) that regulates the lifespan of the cholesterol clearing receptors on the liver. The inhibition of PCSK9 significantly lowers LDL cholesterol levels. Alirocumab (Praluent) serves as the prototype of this new class of drugs. Pharmacokinetics Alirocumab is administered subcutaneously every 2 to 4 weeks, and at recommended dosages, median times to maximum serum concentrations are 3 to 7 days. Following subcutaneous injection, the drug is distributed primarily in the circulatory system. As a protein, the drug degrades to small peptides and individual amino acids. At low concentrations, the drug is eliminated through binding to the PCSK9 receptors; at higher concentrations, it is eliminated principally through nonsaturable proteolysis. Action Unlike statins that lower cholesterol by inhibiting the synthesis of cholesterol, the PCSK9 inhibitors promote modulation of the receptor that clears cholesterol, thereby prolonging the receptor activity and promoting the clearance of cholesterol. Use Alirocumab is indicated in adults with ASCVD or familial hypercholesterolemia who require additional lowering of LDL cholesterol when diet and maximally tolerated statin therapy have not produced the desired therapeutic response. The ability of alirocumab to reduce the outcomes of myocardial infarction or cerebrovascular accident has not been determined, although clinical trials are ongoing. Early results suggest that cardiovascular events could be decreased with PCSK9 inhibitors. Use in Children Safety and efficacy in children and adolescents have not been established. Use in Older Adults There is no reported need for adjustments in drug dosage in older adults. Use in Patients With Renal Impairment https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 11/14 1/16/24, 10:22 PM Realizeit for Student No adjustment to dosage is required in patients with mild to moderate renal impairment. No data are available for use in individuals with severe renal impairment. Use in Patients With Hepatic Impairment No adjustment to dosage is required in patients with mild to moderate hepatic impairment. No data are available for use in individuals with severe hepatic impairment. Use in Patients Receiving Home Care Patients who are housebound may need assistance in obtaining serum lipid blood tests or instructed on home-monitoring techniques. The nurse advises patients to notify their health care provider if adverse effects occur or if they become pregnant. Patients should be advised to seek emergency treatment should signs of an allergic reaction occur. Patients should be supported to maximize lifestyle modification, including diet, exercise, and smoking cessation, to reduce cholesterol while taking alirocumab. Adverse Effects Alirocumab appears to be well-tolerated, but nasopharyngitis, itching, influenza, injection site reactions, muscle pain, diarrhea, and serious allergic reactions have been reported with the use of the drug. Contraindications Contraindications include known hypersensitivity to the drug or a component to the formulation. Limited information is available regarding additional contraindications. Nursing Implications Preventing Interactions No interactions have been reported that increase or decrease the therapeutic or adverse effects of the drug. Administering the Medication The drug should be administered by subcutaneous injection into the upper arm, abdomen, or thigh. The injection site should be rotated with each injection. Other drugs should not be given at the same injection site at the same time. The prefilled syringe or pen should be warmed to room temperature for 30 to 40 minutes before use. Note that it may take 20 seconds to inject the drug subcutaneously. Assessing for Therapeutic Effects The nurse monitors lipid response to therapy, looking for decreased levels of LDL cholesterol. Maximum effects begin in approximately 1 week; monitoring should occur within 4 to 8 weeks of initiation or dosage adjustment. Assessing for Adverse Effects The nurse should determine that no injection site reactions are present. In addition, it is necessary to observe that the patient manifests no signs or symptoms of influenza, cough, muscle pain, diarrhea, or allergic reaction to the drug. Patient Teaching Patients (and providers) need to read patient information and instructions each time the patient administers alirocumab in case new information is available. The nurse provides guidance to patients and caregivers regarding the proper subcutaneous injection technique, including aseptic technique and how to use the prefilled syringe or pen correctly. Patient instruction regarding discarding needles and syringes in a puncture-resistant disposal container is necessary. Women should notify their health care provider if they become pregnant while taking alirocumab. Other Drugs in the Class The only other drug currently approved as a PCSK9 inhibitor is evolocumab (Repatha). To date, the indications and drug profile of evolocumab appear similar to alirocumab. As further clinical trials proceed, the benefit of one drug over another in the class may be identified. Because evolocumab is administered as a 420-mg dose, three separate 140-mg injections consecutively within a 30-minute period must be administered. Both drugs in the class are expensive, possibly limiting use in patients who might benefit from a PCSK9 inhibitor. Miscellaneous Dyslipidemic Agent Niacin (nicotinic acid) is a vitamin that is no longer recommended as a dyslipidemic agent except in patients with high triglyceride levels (greater than 500 mg/dL) who have not been able to achieve the desired response or do not tolerate other drug therapy. For decreasing LDL cholesterol, other drugs (evolocumab or ezetimibe) are more effective when added to statin therapy. Although niacin does significantly https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 12/14 1/16/24, 10:22 PM Realizeit for Student increase HDL cholesterol, there is no evidence that the increase leads to improved patient outcomes. Serious concerns have been raised about the safety and efficacy of this vitamin in combination with statin therapy. Some formulations of sustained-release over-the-counter (OTC) niacin have been associated with an increased risk of hepatotoxicity. Niacin also increases blood glucose, causing possible problems with glucose control for people with diabetes. Poor tolerability often limits the use of niacin; the high doses required for dyslipidemic effects result in adverse effects. Niacin commonly causes skin flushing, pruritus, and gastric irritation, and it may lead to tachycardia, hypotension, dizziness, hyperglycemia, hyperuricemia, elevated liver aminotransferases, and hepatitis. Nicotinamide, another common form of niacin, does not have the lipid-lowering properties of nicotinic acid. OTC preparations of niacin are not federally regulated in the United States, and preparations that are marketed as causing “no flush” may have no free nicotinic acid and are therefore ineffective in treating dyslipidemia. Combination Therapy Used to Treat Dyslipidemia When monotherapy is not effective in attaining target LDL cholesterol levels, combination therapies with lipid-lowering drugs that have different mechanisms of action are recommended. In general, the drug combinations that are most effective in reducing total and LDL cholesterol are (1) a statin with a cholesterol absorption inhibitor or a bile acid sequestrant or (2) niacin with a bile acid sequestrant. When a goal of therapy is to increase the level of HDL cholesterol, a fibrate, cholesterol absorption inhibitor, or niacin may be used. However, because niacin is no longer recommended except in specific situations, drug therapy may be more successful and better controlled with administration of individual drugs in combination. However, a fibrate–statin combination should be avoided because of increased risks of severe myopathy, and a niacin–statin combination increases the risks of hepatotoxicity. Adverse reactions from combination statin and cholesterol absorption inhibitor therapy are reported to be similar to those from statins alone. Combination preparations are not intended for initial therapy. The adverse effects and contraindications associated with individual drugs also apply when they are used in combination. All combinations, like individual preparations, should be used in conjunction with a cholesterol-reducing diet. The Nursing Process A concept map outlines the nursing process related to drug therapy considerations in this chapter. Additional nursing implications related to the disease process should also be considered in care decisions. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 13/14 1/16/24, 10:22 PM Realizeit for Student https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=lqf9HhURQ5RqpgqAkzH2zbfuwFjUs0mdxkPeVey4KH2F7i%2fH0LC0NH7inQLoUzK%2f… 14/14