Lipid-lowering strategies using fibrates and niacin: triglyceride management, drug interactions and prevention.

Fibrates (Fibrates)

What are fibrates? How do they work?
Fibrates are also known as fibrinolates, phenoxyarabinates, or methoxyacids. Many of these drugs have "fibrate" in their translated names, such as fenofibrate and bezafibrate, hence the common term "fibrate lipid-lowering drugs." Their primary effect is a significant reduction in triglycerides. Their mechanism of action involves increasing the activity of lipoprotein lipase and hepatic lipase, leading to the breakdown and increased metabolism of triglyceride-containing lipoproteins, and reducing the secretion of very low-density lipoprotein (VLDL). Their triglyceride-lowering effect is stronger than their cholesterol-lowering effect. These drugs can lower LDL-C by 5%–20%, TG by 20%–50%, and increase HDL-C by 10%–20%. Major adverse reactions include gallstones and myopathy. In addition, studies have found that besides primarily exerting their anti-atherosclerotic effect by correcting dyslipidemia, these drugs can also exert their anti-atherosclerotic effect through preventing blood clotting, promoting thrombolysis, and reducing atherosclerotic inflammation. Therefore, they can be used clinically for the prevention and treatment of atherosclerosis.

What are the main adverse reactions of fibrates? The most common adverse reactions of fibrates are gastrointestinal discomfort, mostly mild nausea, diarrhea, and bloating, which are usually short-lived and do not require discontinuation of the drug. Occasionally, skin itching, urticaria, rash, hair loss, headache, insomnia, and decreased libido may occur; these reactions are generally mild, do not require discontinuation of the drug, and will disappear spontaneously. Long-term use of these drugs should be monitored for potential liver and kidney damage. Some patients may develop myopathy or even rhabdomyolysis, especially when these drugs are used in combination with statins. In addition, fibrates can increase the incidence of gallstones, possibly because these drugs increase the amount of cholesterol excreted into bile, promoting gallstone formation. Fibrates are toxic to the embryo and can delay embryonic growth; therefore, pregnant women should avoid them, and women of childbearing age, breastfeeding women, and children should generally not use these drugs.

What precautions should be taken when taking fibrates for lipid regulation?

① Contraindicated in patients with gallbladder disease, cholelithiasis, liver dysfunction, primary biliary cirrhosis, severe renal insufficiency, or nephrotic syndrome causing decreased serum albumin.

② Contraindicated in pregnant and breastfeeding women; not suitable for children; elderly people with poor renal function should reduce the dosage or avoid use.

③ Regularly monitor complete blood count, platelet count, liver function, blood lipids, and creatine kinase (CK) during medication.
④ If treatment is ineffective after 2-3 months, discontinue use immediately.

⑤ Discontinue use if abnormal liver function, gallstones, or myositis occur after medication.

⑥ Avoid concomitant use with drugs that interact with this class of medications.

Which drugs have adverse interactions with fibrates?

① Fibrates have plasma protein binding capacity. When used concomitantly with coumarin anticoagulants, they can compete for protein binding, causing the coumarin to become free, increasing blood concentrations and potentially leading to bleeding tendencies. Similarly, sulfonylureas, phenytoin, and furosemide can all increase blood concentrations when used with fibrates; in such cases, the dosage of these drugs should be adjusted.

② Fibrates require cytochrome P450-3A4 for metabolism. Therefore, concomitant use with statins, which also require P450-3A4 metabolism, may cause myopathy.

③ Fibrates are primarily excreted through the kidneys. Concomitant use with immunosuppressants such as cyclosporine may lead to worsening renal function; in such cases, the dosage should be reduced or the medication discontinued. ④ When fibrates are used in combination with bile acid binding resins (such as cholestyramine), the fibrates should be taken at least 1 hour before or 4-6 hours after taking these substances.

What are some commonly used fibrates for lowering lipids? What are their characteristics? How should they be used?

① Fenofibrate: Brand name: Lipingzhi. Its sustained-release capsules are also known as Meripote. This product is a phenoxyaromatic acid derivative that can significantly lower triglycerides and very low LDL cholesterol, as well as lower cholesterol and LDL cholesterol, and increase HDL cholesterol. This product is mainly used for patients with high triglycerides, and can also be used for patients with dyslipidemia accompanied by diabetes, hypertension, or other cardiovascular diseases. The usual adult dose is 100mg three times a day; or 100-200mg twice a day. After the blood lipids have significantly decreased, the dose can be reduced to 100mg twice a day. If using sustained-release capsules, take 250mg with dinner daily, swallowed with water, and do not chew.

② Gemfibrozil: Brand name: Novogene. It inhibits peripheral lipolysis and reduces free fatty acid levels in the liver, thereby reducing TG production in the liver. This product also inhibits very low-density lipoprotein cholesterol (VLDL-C), leading to a reduction in VLDL-C production. This product primarily achieves its lipid-regulating effect by lowering TG and total cholesterol. Its lipid-regulating effect is stronger than fenofibrate, and it is less likely to form gallstones. It can also more effectively increase high-density lipoprotein cholesterol levels, thus reducing the incidence and mortality of coronary heart disease. This product is mainly used for primary and secondary dyslipidemia, such as hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and hyperlipidemia caused by diabetes. Usual dosage: Oral: 600mg twice daily, half an hour before meals. The domestic clinically used dosage is 300mg three times daily. Alternatively, 900mg once daily.

③ Benzafibrate: Brand name: Bislipidase. Its effects are basically the same as fenofibrate but stronger. It can enhance the activity of TC enzymes, promote the degradation of TC-rich lipoproteins, and enhance the breakdown of LDL in tissue cells, thus significantly reducing serum cholesterol and LDL-C concentrations; it can also reduce TC and TG concentrations and increase plasma HDL-C; it also has antithrombotic effects, reducing platelet aggregation and blood viscosity. It is mainly used for various types of dyslipidemia, especially suitable for patients with significantly elevated TG. Usual dosage: Adults take 200mg of the regular tablet three times a day after meals. Sustained-release tablets take 400mg once daily. Patients with impaired renal function need to reduce the dosage. Niacin-based lipid-regulating drugs 37. What are niacin-based lipid-regulating drugs? How do they exert their lipid-regulating effect? ​​Niacin belongs to the B vitamins, and high doses can have a significant lipid-regulating effect. Niacin-based drugs inhibit the formation of cyclic adenosine monophosphate (cAMP), leading to a decrease in triglyceride enzyme activity, inhibiting the breakdown of adipose tissue and reducing the synthesis of very low-density lipoprotein cholesterol in the liver, thus reducing intermediate-density lipoprotein and low-density lipoprotein. Niacin can combine with glycine to synthesize niacinurate, thereby hindering hepatocytes from using coenzyme A to synthesize cholesterol. In addition, it can also increase high-density lipoprotein cholesterol.

What are some commonly used niacin-based lipid-lowering drugs? How are they used?

① Niacin: High-dose niacin, as a lipid-lowering drug, affects cholesterol transport in the blood by inhibiting the synthesis of very low-density lipoprotein. Clinically, it is used for mixed dyslipidemia and hypertriglyceridemia. Long-term use can reduce the incidence and mortality of coronary heart disease, myocardial infarction, and other cardiovascular and cerebrovascular diseases. Niacin is available in three dosage forms: regular tablets, extended-release tablets, and extended-release capsules. a. Regular tablets: 50mg or 150mg per tablet. When used for lipid regulation, start with 100mg orally three times a day; after 4-7 days, the dose can be increased to 1-2g three times a day. b. Extended-release tablets: 500mg per tablet. The dose for 1-4 weeks is 500mg once a day; the dose for 5-8 weeks is 1000mg once a day, all taken before bedtime. After 8 weeks, gradually increase the dose based on patient efficacy and tolerability. If necessary, the maximum dose can be increased to 2000 mg daily, taken at bedtime. c. Sustained-release capsules: 250 mg per capsule, taken orally at bedtime. Recommended dose: 500 mg once in weeks 1-4; 1000 mg once in weeks 5-8; 1500 mg once from week 9 onwards. The maximum dose can be increased to 2000 mg daily.

② Acipimox: Also known as oxymetapyrazine. A derivative of nicotinic acid, it inhibits lipolysis, reduces the production of free fatty acids, and thus reduces the synthesis of triglycerides (TG) in the liver. In addition, it inhibits the synthesis of low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C), thereby lowering plasma triglyceride and total cholesterol levels. This product can also significantly increase HDL-C levels, thus exerting an anti-atherosclerotic effect. Usual dosage: Adults, 250 mg orally, 2-3 times daily, after meals. Dosage can be adjusted as needed, with a maximum daily dose not exceeding 1250 mg.

What are the adverse reactions of niacin? Niacin has almost no toxic effects when kidney function is normal. Its common adverse reactions include a feeling of warmth throughout the body, flushing of the skin, especially the face and neck, and headache. These adverse reactions occur in 60%–90% of patients, and in most cases, the symptoms disappear or lessen after continued use for 2–6 weeks. Niacin also has some rarer, more serious adverse reactions, such as worsening of gastric and duodenal ulcers, increased blood uric acid, and joint pain; niacin can also cause skin allergies (rashes and urticaria), hyperglycemia, arrhythmia, and elevated liver transaminases.

What precautions should be taken when taking niacin?

① Contraindicated in patients with severe liver disease or severe gout;

② Use with caution in patients with diabetes, glaucoma, hyperuricemia, peptic ulcer, hypotension, or unstable angina;

③ Use with caution in pregnant and breastfeeding women;

④ Sustained-release formulations should generally not be taken on an empty stomach. They should be taken after a small, low-fat meal, before bedtime, and swallowed whole;

⑤ Monitor liver function and blood sugar levels during medication;

⑥ When used in combination with statins, the benefits and risks should be carefully weighed, and it is best to take them at different times.