Chapter 15: Drugs for Hyperlipidemia

Clinical management strategies are grounded in the National Cholesterol Education Program (NCEP) guidelines, which recommend specific LDL targets based on patient risk profiles and prioritize therapeutic lifestyle changes such as diet and exercise before pharmacological intervention. A significant portion of the chapter focuses on HMG-CoA reductase inhibitors, or statins (including atorvastatin, simvastatin, and rosuvastatin), detailing their mechanism of blocking the rate-limiting enzyme in cholesterol biosynthesis to upregulate hepatic LDL receptors and clear circulating cholesterol. The summary explores the pharmacokinetics of statins, including CYP enzyme interactions, and adverse effects such as myopathy and rhabdomyolysis. It also examines bile acid-binding resins like cholestyramine and colesevelam, which sequester bile acids in the gut to prevent reabsorption, and ezetimibe, which inhibits dietary and biliary cholesterol absorption at the intestinal brush border. Furthermore, the text covers niacin (nicotinic acid) for its ability to inhibit VLDL secretion and raise HDL levels, despite side effects like cutaneous flushing, and fibric acid derivatives (fibrates) like gemfibrozil that activate peroxisome proliferator-activated receptor-alpha (PPAR-alpha) to stimulate lipoprotein lipase and reduce triglycerides. The discussion concludes with newer agents for familial hypercholesterolemia, including PCSK9 inhibitors (monoclonal antibodies), antisense oligonucleotides like mipomersen, and microsomal triglyceride transfer protein inhibitors like lomitapide, offering a complete overview of current pharmacotherapy for dyslipidemia.