Lipid regulation in special populations and the application of novel drugs: bile acid sequestrants, absorption inhibitors, and principles of lipid regulation in the elderly.

Bile Acid Separators

What are bile acid separators? How do they work? Bile acid separators (anion exchange resins), also known as bile acid separators, bind to bile acids in the intestine, blocking the enterohepatic circulation of bile acids. This accelerates the breakdown of cholesterol in the liver into bile acids, which then bind to the resin and are excreted in the feces, thus lowering blood cholesterol levels. Clinically used drugs in this class include cholestyramine and colestipol. They can lower LDL-C by 15%–20% and increase HDL-C by 3%–5%, with no effect on TG or an increase in TG. They are mainly used for hypercholesterolemia.

What are the adverse reactions of bile acid sequestrants? What precautions should be taken when taking them? Bile acid sequestrants are not absorbed orally and have no systemic adverse reactions. Common adverse reactions include abdominal distension, mild nausea, and constipation. Rare adverse reactions include diarrhea, steatorrhea, intestinal obstruction, and severe abdominal pain. The following precautions should be taken when taking this class of drugs:

① These drugs only lower cholesterol and do not lower triglycerides (TG). Therefore, when treating mixed dyslipidemia, they must be used in combination with other lipid-lowering drugs.

② The absolute contraindications for this class of drugs are abnormal β-lipoproteinemia and TG > 4.5 mmol/L.

③ Patients with intestinal diseases and intractable constipation should not use them. ④ This class of drugs can interfere with the absorption of folic acid, digoxin, warfarin, phenoxyfenac (fibrates), and fat-soluble vitamins. Therefore, when taking these drugs long-term, supplements with vitamin A, vitamin D, and vitamin K are necessary.

What are some commonly used bile acid sedatives? What are their characteristics? How should they be used? ① Cholestyramine: also known as cholestyramine. Its chloride form is commonly used. It is not absorbed orally. In the intestinal lumen, its CI- ions exchange with bile acids, forming non-absorbable complexes that are excreted in the feces. This can increase the amount of bile acids excreted in the feces by 3 to 10 times, thus blocking the enterohepatic circulation of bile acids and preventing their repeated absorption and utilization. Due to the reduction of bile acids in the liver, the rate-limiting enzymes that promote the conversion of cholesterol to bile acids are more actively activated, leading to the conversion of more cholesterol into bile acids, which are continuously excreted from the body, thereby effectively reducing the levels of circulating cholesterol and LDL-C. The usual starting dose for adults is 5.7g (equivalent to 4g of anhydrous cholestyramine resin), 1 to 2 times daily. If a dose increase is needed, it should be done at 4-week intervals. The maintenance dose is 11.4–22.8g daily, divided into 2 doses, suspended in warm water before administration.

②Coletepol: Also known as cholestyramine. Its action is the same as cholestyramine. Plasma cholesterol concentration begins to decrease 24-48 hours after administration, reaching maximum efficacy within one month. The usual adult dosage is 15-90g daily, divided into 2-4 doses, taken before meals with a small amount of water or beverage. Cholesterol Absorption Inhibitors

What are cholesterol absorption inhibitors? Which drug was the first to be used clinically? How does it exert its lipid-regulating effect? ​​Drugs that inhibit cholesterol absorption in the intestine are called cholesterol absorption inhibitors. The first drug used clinically was ezetimibe. It acts on the brush border of the small intestinal villi, selectively inhibiting the absorption of cholesterol from bile and food, reducing the transport of cholesterol from the small intestine to the liver, thus reducing the liver's cholesterol storage and increasing the clearance of cholesterol from the blood. Ezetimibe does not increase bile secretion (like bile acid sequestrants) nor inhibit cholesterol synthesis in the liver (like statins). A daily dose of 10mg of this product can inhibit approximately 54% of cholesterol absorption, reducing LDL-C by about 18%. The recommended dose of this product is 10 mg once daily. It can be taken alone or in combination with statins. It can be taken on an empty stomach or with food.

What are the adverse reactions and precautions for using ezetimibe? Ezetimibe has a relatively good safety profile. The most common adverse reactions are headache, abdominal pain, and diarrhea. Other adverse reactions include gastrointestinal disturbances, hypersensitivity reactions (including eczema and angioedema), and fatigue, chest pain, and joint pain have also been reported. Occasionally, elevated liver enzymes, hepatitis, pancreatitis, thrombocytopenia, cholelithiasis, and cholecystitis have been observed. Myalgia may occur when used alone or in combination with fibrates. The following points should be noted when using this product:

① Contraindicated in patients with active liver disease or unexplained persistent elevation of transaminases; use with caution in pregnant women, not suitable for breastfeeding women, and not recommended for children under 10 years of age.

② When used in combination with bile acid sequestrants, this product should be taken at least 2 hours before or 4 hours after taking the sequestrant; combination with fibrates is not recommended; this product should be used with caution while using cyclosporine. When used in combination with statins, liver function should be checked before treatment.

③ When using this product, patients should be informed of the risk of developing myopathy. Selection and Application of Lipid-Lowering Drugs for Special Populations

Why should lipid-lowering therapy be emphasized in the elderly? How is lipid-lowering therapy performed? Dyslipidemia is one of the common problems in the elderly. Dyslipidemia poses a greater risk of cardiovascular disease in the elderly; therefore, regulating blood lipids is far more meaningful for the elderly than for younger adults. Lipid-lowering therapy can reduce the incidence and mortality risk of coronary heart disease, and the higher the age, the greater the risk reduction. Compared to those over 65, lipid-lowering therapy can reduce the incidence of coronary heart disease by 19% and mortality by 11% in individuals under 65, and by 62% and 45% in those over 65. This demonstrates the importance of managing dyslipidemia in the elderly. In terms of drug-based lipid regulation, dyslipidemia is mainly divided into two types: hypercholesterolemia and hypertriglyceridemia. For the former, statins are the first-line treatment, such as lovastatin, simvastatin, pravastatin, fluvastatin, and atorvastatin; for the latter, fibrates are the first-line treatment, such as gemfibrozil and finasteride. Other options include lipid-lowering drugs like niacin and lipofuscin. These are currently the most effective and safest medications available; patients only need to adhere to their medication regimen under the guidance of a doctor to control their blood lipids within the ideal range.

What precautions should be taken when elderly people use lipid-lowering drugs? Many elderly patients require other medications to treat other diseases while receiving lipid-lowering therapy. Therefore, it is necessary to use lipid-lowering drugs rationally and pay attention to adverse reactions caused by combined medication. Currently, commonly used lipid-lowering drugs are statins and fibrates. For safe use, elderly people should pay attention to the following issues:

① The lipid-lowering level should not be too low. Blood lipids are essential physiological substances for the human body. They not only participate in energy production and storage but are also raw materials for hormone synthesis. Low blood lipid levels will affect the body's physiological activities. Therefore, low cholesterol is not good for the elderly. For people over 70 years of age, the risk of cholesterol below 4.16 mmol/L is comparable to that of cholesterol above 6.24 mmol/L. If serum cholesterol is below 3.64 mmol/L, the incidence of cerebral hemorrhage will be higher, shortening lifespan. Therefore, the lipid-lowering level should be determined according to the patient's cardiovascular risk factors.

② Exclude factors that may affect blood lipid levels. In the elderly, many factors influence blood lipids, such as age-related hypothyroidism, decreased metabolic rate, and cardiovascular disease in 70%–80% of cases, often accompanied by atherosclerosis and a risk of coronary heart disease. Early detection and treatment of thyroid dysfunction and correction of abnormal blood lipids are crucial to prevent and reduce the occurrence and development of cardiovascular diseases.

③ Individualized treatment with lipid-lowering drugs. The initial dosage is determined based on blood lipid levels and cardiovascular risk stratification, and then adjusted according to treatment response. Safety indicators, such as liver transaminases, creatine kinase, and blood lipids, should be rechecked 4–6 weeks after the first dose. These indicators should be rechecked every 3–6 months thereafter. If the requirements are met, the rechecking period should be changed to 6–12 months.

④ Prevention of myopathy. If creatine kinase (CK) exceeds 10 times the upper limit of normal, medication should be discontinued immediately to avoid myopathy. ⑤ Mixed dyslipidemia: This type requires combined use of statins and fibrates or niacin. Choose medications with fewer adverse reactions, starting with low doses of each, and closely monitor for adverse reactions, liver function, and creatine kinase levels.

⑥ While undergoing lipid-lowering therapy, it is important to correct other risk factors for atherosclerosis, such as hypertension, diabetes or impaired glucose tolerance, smoking, overweight, or obesity.