Abstract and Introduction

Abstract

Coronary heart disease (CHD) is a leading cause of morbidity and mortality, and high blood cholesterol is a major risk factor for CHD. In its third report, the Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults of the National Cholesterol Education Program guidelines for screening and management of high blood cholesterol have been updated to further identify and treat patients at risk. Therapeutic lifestyle changes are stressed as therapy for all patients. Pharmacologic therapy is indicated for all people not meeting low-density lipoprotein target goals. Although 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are well tolerated and the most frequently used hypolipidemic agents, a variety of agents can be used, including nicotinic acid derivatives, bile acid sequestrants, and fibric acid derivatives.
Introduction

Coronary heart disease (CHD) includes the clinical conditions of acute myocardial infarction, angina pectoris, and heart failure. It is estimated that CHD affect 12.2 million Americans.[1] In addition, CHD causes more than 466,000 deaths annually in the United States.[2] Approximately 1.1 million Americans had a myocardial infarction in the year 2000, and more than 40% died as a result. Sixteen percent of men and 35% of women will experience a second myocardial infarction within 6 years of the first.[1] The economic impact of CHD is enormous. In 1999, the direct costs of CHD (costs for hospitalization, nursing home care, physician services, medications, home healthcare) in the United States amounted to $55.2 billion; the indirect costs for lost productivity, morbidity, and mortality were $118.2 billion. Although 88% of persons younger than 65 years are able to return to work after a myocardial infarction, CHD is the leading cause of early, permanent disability in the US workforce.[1] It accounts for 19% of disability allowances paid by the Social Security Administration.[1]

High blood levels of cholesterol (particularly low-density lipoprotein cholesterol [LDL-C]) increase the risk of CHD, and lowering total cholesterol and LDL-C levels reduces this risk.[2] Clinical management of persons without CHD (eg, interventions to prevent the development of or reduce risk factors for CHD) is referred to as primary prevention; treatment of elevated LDL-C levels in patients with a history of CHD (or other atherosclerotic disease associated with lipid accumulation in the blood vessel walls) is considered secondary prevention.[2,3] Thus, it is of critical importance that our patients with lipid disorders be identified and treated appropriately and aggressively to reduce their risk of CHD. Table 1 outlines the risk factors for CHD. Pathophysiology
Cholesterol Metabolism

Cholesterol is an essential component of cell membranes and a metabolic precursor of bile acids and steroid hormones (eg, adrenocortical and sex hormones).[4,5] It is obtained from the diet and synthesized in the liver, intestinal mucosa, and other cells. The ratelimiting step in cholesterol synthesis involves the enzyme 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase, which converts HMG-CoA to mevalonate.[6] Cholesterol and other lipids (eg, triglycerides, which are made up of free fatty acids and glycerol) are transported in the systemic circulation as a component of lipoproteins. Lipoproteins are particles composed of (1) a hydrophobic lipid core made up of cholesterol esters and triglycerides and (2) a hydrophilic outer coat made up of phospholipids, flee cholesterol, and apolipoproteins.[5,7] Apolipoproteins are proteins that provide structural stability to lipoproteins, bind with cell receptors, and play a vital role in regulating lipid transport and lipoprotein metabolism.[5,7] Lipoproteins are classified on the basis of their density as chylomicrons, very low-density lipoproteins (VLDLs), LDLs, intermediate-density lipoproteins (IDLs), and high-density lipoproteins (HDLs). Most of the cholesterol in the serum (60%-70%) is found in LDL particles; HDL particles contain 20% to 30% of the total serum cholesterol; and VLDL particles contain 10% to 15% (as well as most of the triglycerides during fasting conditions).[2] Chylomicrons transport cholesterol and fatty acids from the intestines (ie, dietary cholesterol and that synthesized locally in the mucosa) to the liver.[5]

In the liver, cholesterol and triglycerides are synthesized and incorporated into VLDL particles, which deliver cholesterol to the peripheral tissues when the particles are released into the bloodstream. The triglyceride content of VLDL particles initially is high and decreases progressively as the result of enzyme activity in the bloodstream. This enzyme activity converts the particles sequentially to VLDL remnants, IDL, and LDL. The LDL particles are small and high in cholesterol content.[5] The LDL receptors on peripheral and hepatic cells bind with apolipoproteins on the surfaces of LDL, resulting in uptake of cholesterol into the cells (ie, clearance of LDL from the bloodstream), where it is subsequently degraded.[5,6] Low intracellular cholesterol concentrations stimulate the synthesis of LDLreceptors, thereby increasing cellular uptake of LDL.[5] The HDL particles transport cholesterol from peripheral cells to the liver, a process known as reverse cholesterol transport.[5] High HDL levels promote clearance of cholesterol from peripheral tissues. Lipoprotein(a) (Lp[a])] is similar to LDL, but it contains apolipoprotein(a), a protein similar to plasminogen; Lp(a) is formed when apolipoprotein(a) binds to apolipoprotein B on LDL.[5,7] Apolipoprotein B is the only apolipoprotein on LDL particles, whereas other lipoproteins have multiple apolipoproteins on their surfaces.[5] High levels of LDL-C, triglycerides, apolipoprotein B, and Lp(a) and low levels of HDL and apolipoprotein A-I (an apolipoprotein associated with HDL synthesis) are associated with high risk of CHD.[2,5,7]
Hypercholesterolemia

The cholesterol level in blood is determined by a combination of factors, including inheritance (ie, genetic abnormalities in lipoprotein metabolism), age, and acquired factors (eg, lifestyle factors such as dietary intake of saturated fat and cholesterol, physical activity). Secondary causes of hypercholesterolemia and lipoprotein abnormalities include poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver disease, drug therapy (eg, cyclosporine, glucocorticoids), and alcoholism.[7] Atherosclerosis

High blood levels of cholesterol play a leading role in atherosclerotic lesion formation in the walls of coronary arteries. Atherosclerosis begins with accumulation of lipoproteins (primarily LDL) within the inner layer of the arterial wall, where they no longer come in contact with antioxidants and other constituents in the bloodstream.[8] Chemical modification (particularly oxidation) of lipoproteins leads to a local inflammatory reaction involving macrophages, which ingest oxidized lipoproteins and form foam cells. Accumulation of foam cells contributes to fatty lesion formation. Reverse cholesterol transport out of the tissues mediated by HDL may also occur. Over time, fatty lesions progress to fibrous plaques. Fissures may develop in a plaque, exposing the underlying tissues to platelets and other constituents of blood. Platelet adhesion, activation, and aggregation lead to thrombus (clot) formation, partially or completely occluding the vessel lumen and causing clinical symptoms of CHD (eg, myocardial ischemia or infarction).[8] Diagnosis and Classification It is recommended that a complete fasting lipoprotein profile (as opposed to only total cholesterol and HDL-C) be measured in all adults 20 years and older at least once every 5 years.[2] A fasting lipoprotein profile includes total cholesterol, LDL-C, HDL-C, and triglycerides. Measurement of the LDL-C on initial screening provides more information for risk assessment. Although LDL-C testing is more precise, advantages of testing for total cholesterol over a complete fasting lipoprotein profile include greater availability of the test, lower cost, and lack of a requirement that the patient fast before the test.[9] As a result, it may not be practical in all situations to have a full fasting profile performed. If the testing opportunity is nonfasting (fasting defined as nothing by mouth with caloric value in the preceding 9 to 12 hours), only total cholesterol and HDL will be usable and should be measured. However, LDL-C may be calculated from the results of these tests in patients with a total triglyceride level of 400 mg/dL or less using the following equation[2]: LDL-C = total cholesterol - (HDL-C + triglycerides)/5. In patients with total triglyceride levels higher than 400 mg/dL, LDL-C

should be measured directly by preparative ultracentrifugation because calculating LDL-C from total cholesterol, total triglyceride, and HDL-C values is inaccurate in this situation. In general, LDL-C levels less than 100 mg/dL are optimal; levels of 100 to 120 mg/dL are near optimal; the range 130 to 159 mg/dL is considered borderline high risk; and 160 mg/dL or greater is high risk.[2] Cholesterol ratios (total cholesterol/HDL-C and LDL-C /HDL-C) are also strong predictors of CHD.[9] Other measures that are not performed routinely but may provide insight into a patient's risk for CHD include Lp(a) and apolipoproteins B and A-I. Hypercholesterolemia may be isolated or accompanied by hypertriglyceridemia. If the triglyceride value is greater than or equal to 200 mg/dL, the non-HDL-C level should be assessed: non-HDL-C = total cholesterol - HDL. Identified as a secondary target of therapy by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) in patients with high triglyceride levels, non-HDL levels reflect the sum of LDL and VLDL (triglyceride-rich remnant lipoprotein) levels. Hyperlipoproteinemias are classified according to the scheme in Table 2 .[10] Advanced Practice Nurse and Pharmacist Roles Cardiovascular disease accounts for nearly 50% of all deaths in the United States. Clinical trials and pathophysiologic evidence support the use of aggressive therapy in patients with arteriosclerotic vascular disease and in those with several risk factors for the disease. Pharmacists and advanced practice nurses can have a large impact on the health of their patients by conducting cholesterol screening programs and obtaining patient histories to determine if the patient is at risk for CHD. Patient education is also a vital component of the entire healthcare team for patients with hypercholesterolemia. Patients should be counseled on the role of dietary therapy, exercise, and drug therapy. Healthcare practitioners must consider hypolipidemic drug therapy to achieve the target LDL-C goal when necessary. Conscientious attention to therapeutic lifestyle changes and pharmaceutical care of patients with lipid disorders will improve patient adherence to the treatment plan and the ultimate patient outcomes.

Disclosure

Sandra Chase, BS, PharmD, has disclosed that she has received grants for educational activities with Astra Zeneca, Merck Co Inc, GlaxoSmithKline, Bristol Myers Squibb, Scios Inc, and Millennium Pharmaceuticals, Inc. She discusses the investigational product rosuvastatin in this article.

HEPATI TIS
A.Latar Belakang Hepatitis virus akut merupakan penyakit infeksi yang penyebarannya luas dalam tubuh walaupun efek yang menyolok terjadi pada hepar. Telah ditemukan 5 kategori virus yang menjadi agen penyebab yaitu Virus Hepatitis A (HAV), Virus Hepatitis B (HBV), Virus Hepatitis C (HVC), Virus Hepatitis D (HDV), Virus Hepatitis E (HEV). Walaupun kelima agen ini dapat dibedakan melalui petanda antigeniknya, tetapi kesemuanya memberikan gambaran klinis yang mirip, ya ng dapat bervariasi dari keadaan sub klinis tanpa gejala hingga keadaan infeksi akut yang total. Bentuk hepatitis yang dikenal adalah HAV ( Hepatitis A ) dan HBV (Hepatitis B). kedua istilah ini lebih disukai daripada istilah lama yaitu hepatitis infeksiosa dan hepatitis serum, sebab kedua penyakit ini dapat ditularkan secara

parenteral dan non parenteral. Hepatitis virus yang tidak dapat digolongkan sebagai Hepatitita A atau B melalui pemeriksaan serologi disebut sebagai Hepatitis non-A dan non-B (NANBH) dan saat ini disebut Hepatitis C (Dienstag, 1990). Selanjutnya ditemukan bahwa jenis hepatitis ini ada 2 macam, yang pertama dapat ditularkan secara parenteral (Parenterally Transmitted) atau disebut PT-NANBH dan yang kedua dapat ditularkan secara enteral (Entericall y Transmitted) disebut ET -NANBH (Bradley, 1990; Centers for Disease Control, 1990). Tata nama terbaru menyebutkan PT-NANBH sebagai Hepatitis C dan ET-NANBH sebagai Hepatitia E (Bradley,1990; Purcell, 1990). Virus delta atau virus Hepatitis D (H DV) merupakan suatu partikel virus yang menyebabkan infeksi hanya bila sebelumnya telah ada infeksi Hepatitis B, HDV dapat timbul sebagai infeksi pada seseorang pembawa HBV. Hepatitis menjadi masalah kesehatan masyarakat yang penting tidak hanya di Amerika tetapi juga diseluruh Dunia. Penyakit ini menduduki peringkat ketiga diantara semua penyakit menular yang dapat dilaporkan di Amerika Serikat (hanya dibawah penyakit kelamin dan cacar air dan merupakan penyakit epidemi di kebanyakan negara -negara dunia ketiga. Sekitar 60.000 kasus telah dilaporkan ke Center for Disease Control di Amerika Serikat setiap tahun, tetapi jumlah yang sebenarnya dari penyakit ini diduga beberapa kali lebih banyak. Walaupun mortalitas Authorized www.ruslanpinrang.blogspot.com 1

akibat hepatitis virus ini rendah, tetapi penyakit ini sering dikaitkan dengan angka morbiditas dan kerugian ekonomi yang besar. Authorized www.ruslanpinrang.blogspot.com 2

BAB II TINJAUAN PUSTAKA A.P ENGERT IAN Hepatitis adalah Suatu peradangan pada hati yang terjadi karena toksin seperti; kimia atau obat atau agen penyakit infeksi (Asuhan keperawatan pada anak, 2002; 131) Hepatitis adalah keadaan radang/cedera pada hati, sebagai reaksi terhadap virus, obat atau alkohol (Ptofisiologi untuk keperawatan, 2000;145) B.ETIOLOGI DAN FAKTOR RES IKO 1.Hepatitis A

a . V i r u s h e p e t i t i s A ( H AV ) t e r d i r i d a r i R N A b e r b e n t u k b u l a t tidak berselubung berukuran 27 nm b.Ditularkan melalui jalur fekal oral, sanitasi yang jelek, kontak antara manusia, dibawah oleh air dan makanan c.Masa inkubasinya 15 49 hari dengan rata rata 30 hari d.Infeksi ini mudah terjadi didalam lingkungan dengan higiene dan sanitasi yang buruk dengan penduduk yang sangat padat. 2.Hepetitis B (HBV) a.Virus hepatitis B (HBV) merup akan virus yang bercangkang ganda yang memiliki ukuran 42 nm b.Ditularkan melalui parenteral atau lewat dengan karier atau penderita infeksi akut, kontak seksual dan fekal-oral. Penularan perinatal dari ibu kepada bayinya. c.Masa inkubasi 26 160 hari dengan rata- rata 70 80 hari. d.Faktor resiko bagi para dokter bedah, pekerja laboratorium, dokter gigi, perawat dan terapis respiratorik, staf dan pasien dalam unit hemodialisis serta onkologi laki-laki biseksual serta homoseksual yang aktif dalam hubunga n seksual dan para pemaki obat-obat IV juga beresiko. 3.Hepatitis C (HCV) a . Vi r u s h e p a t i t i s C ( H C V ) m e r u p a k a n v i r u s R N A k e c i l , terbungkus lemak yang diameternya 30 60 nm. b.Ditularkan melalui jalur parenteral dan kemungkinan juga disebabkan juga oleh kontak seksual. c.Masa inkubasi virus ini 15 60 hari dengan rata 50 hari Authorized www.ruslanpinrang.blogspot.com