What Are Antihyperlipidemic Agents?

Drugs that can lower plasma triglycerides or lower plasma cholesterol. There are many types of hypolipidemic drugs, and classification is also difficult. According to its main function of lowering blood lipids, it can be divided into four categories: total cholesterol lowering, main total cholesterol lowering and triglyceride lowering, triglyceride lowering, main triglyceride lowering and total cholesterol lowering. In summary, it can prevent the absorption of bile acid or cholesterol from the intestine, and promote the excretion of bile acid or cholesterol with feces. Inhibit the synthesis of cholesterol in the body, or promote the conversion of cholesterol, promote the expression of LDL receptors on cell membranes, and accelerate the breakdown of lipoproteins. Activates lipoprotein metabolism enzymes and promotes the hydrolysis of triglycerides. Prevent the synthesis of other lipids in the body, or promote the metabolism of other lipids.

Drugs that can lower plasma triglycerides or lower plasma cholesterol. There are many types of hypolipidemic drugs, and classification is also difficult. According to its main function of lowering blood lipids, it can be divided into four categories: total cholesterol lowering, main total cholesterol lowering and triglyceride lowering, triglyceride lowering, main triglyceride lowering and total cholesterol lowering. In summary, it can prevent the absorption of bile acid or cholesterol from the intestine, and promote the excretion of bile acid or cholesterol with feces. Inhibit the synthesis of cholesterol in the body, or promote the conversion of cholesterol, promote the expression of LDL receptors on cell membranes, and accelerate the breakdown of lipoproteins. Activates lipoprotein metabolism enzymes and promotes the hydrolysis of triglycerides. Prevent the synthesis of other lipids in the body, or promote the metabolism of other lipids.
Drug Name
Antihyperlipidemic drugs
Main indications
Hyperlipidemia
Dosage form
Tablets, capsules
Whether to include health insurance
Incorporate

Antihyperlipidemic Drug Classification

1 Hypolipidemic drugs (1) Drugs that affect lipid synthesis, metabolism, and clearance

According to its chemical structure and mechanism of action, it can be divided into: [1]
Niacin and its derivatives
(1) Nicotinic Acid (also known as Niacin) belongs to the B vitamins. When the amount exceeds the dose that acts as a vitamin, it can have a significant effect on regulating blood lipids.
(2) Acipimox
Also known as oxmepyrazine and olbetam. It is a new artificially synthesized niacin derivative. Its application range is similar to that of niacin, but compared with niacin, it has the advantages of longer duration of anti-lipolysis and stronger efficacy.
(3) Inositol Hexanicotinate
It is an ester composed of 1 molecule of inositol and 6 molecules of niacin.
Clobetin and phenoxyacetic acid:
Fitus [Fibrates]
(I) Clofibrate In recent years, it has been discovered that some derivatives of clofibrate can maintain its advantages such as lowering blood lipids, while the side effects such as gallstones are significantly reduced. These derivatives vary widely in their ability to regulate blood lipids and in dosage. For example: Lifibrate (also known as Xinantoum); Alufibrate and Simfibrate; EtofyllineClofibrate, also known as Doulip, Lonita; Benzabate ( Bezafibrate) is also known as lipid-lowering; there are also two types of long-acting bezafibrate, with the trade names BezalipRetard and Zhikangping; Fenofibrate is also known as Lipanthyl Gemfibrozil, which is similar in chemical structure to this class of drugs, is also known as Lopid, Xiangjiang Nuobit, Kanglizhi, Gemnpid.
Hydroxymethylglutaric acid coenzyme A (HMG-CoA) reductase inhibitor
The discovered 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor can inhibit cholesterol biosynthesis. HMG-CoA reductase inhibitor alone, or combined with bile acid integrator, has a more obvious effect on hypercholesterolemia. HMG-CoA reductase inhibitors are a new class of promising hypolipidemic drugs. Most of the statins are methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors. The current formulations include lovastatin, pravastatin, pravastatin, and atorvastatin.

2 Hypolipidemic drugs (2) Drugs that affect cholesterol and bile acid absorption

Cholic Acid Integrator
The common lipid-lowering mechanism of these drugs is to prevent bile acid or cholesterol from the intestine
Antihyperlipidemic drugs
Absorption, promote the excretion of bile acid or cholesterol with feces, and promote the degradation of cholesterol. Such drugs include resins, neomycins, sitosterol, and activated carbon. Neomycins and sitosterol have actually been eliminated due to their large toxic or side effects or poor efficacy. Activated carbon has been recently used in clinical trials, and its exact efficacy and safety need to be further confirmed. Anionic basic resins have been reported in the literature for more clinical applications. This class of drugs is suitable for any type of hypercholesterolemia except homozygous familial hypercholesterolemia (FH). Ineffective against any type of hypertriglyceridemia. For mixed hyperlipidemia with elevated serum total cholesterol (TC) and triglycerides (TG), it must be combined with other types of lipid-lowering drugs to be effective. The main bile acid integrator is ChoIestyramine (also known as cholestyramine); CoIestipol (also known as cholestyramine); Dividistamine (Divistyramine), all are resins.
Probucol
Probucol, also known as probucol, is highly lipid soluble and can accumulate in adipose tissue, which is gradually released from adipose tissue after discontinuation. The effect can be maintained for several weeks. After 6 months of withdrawal, the drug can still be detected in adipose tissue and blood. The drug is mainly excreted from the feces with bile. Probucol has been shown to reduce TC and LDL-C in animals and humans, but it can also reduce serum HDL-C levels. No effect on TG. The mechanism of its regulation of blood lipids has not yet been elucidated.

3 Antihyperlipidemic drugs (3) Polyene fatty acid drugs

Such as: linoleic acid, eicosapentaenoic acid, etc.
Linoleic acid
It is an unsaturated acid that can combine with cholesterol to form an ester, which may further promote its degradation to bile acid and excretion. Therefore, it is important to reduce plasma Z because linoleic acid can reduce blood cholesterol and prevent atherosclerosis. Studies have found that cholesterol must be combined with linoleic acid for normal functioning and metabolism in the body. If linoleic acid is lacking, cholesterol will be combined with some saturated fatty acids, metabolic disorders will occur, deposit on the blood vessel wall, and gradually form atherosclerosis, causing cardiovascular and cerebrovascular diseases.
Omega-3 fatty acids
A variety of concentrated fish oil preparations have been produced and sold in China, but they can be officially used.
Antihyperlipidemic drugs
There are three main types of medicines used in clinical applications: 1. Duokenjiao Pills; 2. Mailekang; 3. Yuyoukang.
In addition to lowering blood lipids, marine fish oil preparations also have the effect of inhibiting platelet aggregation and delaying thrombosis. Some data suggest that omega-3 fatty acids can help prevent coronary artery restenosis after PTCA, but its reliability needs to be further verified.
other
In addition, natural hirudin can reduce lipids. Intragastric administration of experimental decoctions of hirudin can reduce the levels of triglycerides and lipoproteins in the blood of rats. It can also reduce cholesterol and triglycerides in the blood of rabbits with food-induced hyperlipidemia. Content, the aorta and coronary atherosclerotic plaques of experimental animals disappeared, cholesterol crystals decreased. [2]
Other classes of drugs, such as calcium antagonists, also have a role in regulating lipid metabolism.

Clinical application of antihyperlipidemic drugs

Neomycins and -sitosterol have large toxic or side effects or have poor curative effects. These resins have an irreversible combination with bile acid in the intestine, and these resins cannot be absorbed in the intestine, so that bile acid is removed from the intestine. Resorption is reduced, and bile acid excreted from the intestine with feces is increased, thereby prompting liver cells to increase bile acid synthesis. Since cholesterol is the raw material for the synthesis of bile acid by liver cells, the increase in bile acid synthesis increases the cholesterol consumption in hepatocytes, and the amount of cholesterol in hepatocytes decreases. Through the feedback mechanism, hepatic cell membranes are stimulated to accelerate the synthesis of LDL receptors and make liver cell membranes The number of LDL receptors is increased and the activity is enhanced to bind more with LDL in the bloodstream and ingest it in liver cells for metabolism, finally reducing LDL in the blood; about 45% of the weight of LDL is cholesterol, and thus serum LDL- C and TC levels decreased. In addition, in the process of absorbing cholesterol from the intestine, bile acid is required to emulsify. Bile acid is absorbed by the resin and discharged from the intestine with feces, which will definitely affect the digestion and absorption of cholesterol from the intestine. Therefore, after taking resins, the general TC can be reduced by 10% -20%, the LDL-C can be reduced by 15% -25%, the TG slightly increases or has no obvious change, and the HDL-C may increase moderately.
Antihyperlipidemic drugs
This class of drugs is suitable for any type of hypercholesterolemia except homozygous familial hypercholesterolemia (FH). Ineffective against any type of hypertriglyceridemia. For mixed hyperlipidemia with elevated serum TC and TG, it must be combined with other types of lipid-lowering drugs to be effective. The main bile acid integrators are described below.
(A) ChoIestyramine
Also known as cholestyramine. The drug is a styrenic basic anion exchange resin, usually with its chloride, molecular weight exceeding 1 million, and insoluble in water. Its chemical structural formula:
[Common dosage] 4-5g / time, 1-6 times / d, the total amount does not exceed 24g per day. When taking the medicine, you can start with a small dose and reach the maximum tolerated amount within 1-3 months.
The TC lowering effect of cholestyramine and the effect of reducing the morbidity and mortality of coronary heart disease have been confirmed by a large series of long-term observations. A double-blind, placebo-controlled trial in a multi-medical center was reported in the United States. It included 35-59-year-old males with type II hyperlipoproteinemia and was randomly divided into two groups. One group took placebo and the other took colestamin. The maximum dose was 20-24 g per person per day. The observation period was 7-10 years, with an average of 7.4 years. The TC in the treatment group decreased by 13.4%, and the LDL-C decreased by 20.3%, which was 8.5% and 12.6% more than the placebo group, respectively. Coronary heart disease mortality in the treatment group was reduced by 24%. In addition, cholestyramine can increase serum HDL-C levels.
The main disadvantages of cholestyramine are poor taste and constipation. Poor taste can be corrected with flavoring agents. Eating more fiber can relieve constipation. In addition, cholestyramine can interfere with the absorption of folic acid, digoxin, warfarin, Probuc01, Fibrates, Statins, and fat-soluble vitamins. Those who are taking the test during the growth period should take folic acid 5mg daily. Pregnant women and lactating adults need more supplements. Folic acid is taken 1 to 2 hours before taking lenemine, and other drugs are taken 1-4 hours before taking lenemine or 4 hours after taking leneamine. Those with normal gastrointestinal and liver functions generally do not cause clinically significant vitamin deficiency. Those who take cholestyramine for a long time can add vitamins A, D, K and calcium appropriately. Other rare
Side effects are diarrhea, lipolysis, severe abdominal pain, and intestinal obstruction.
(B) CoIestipol
Also known as Jiangdanning. The drug is an anion exchange resin.
[Common dosage] 10-20g / time, 1-2 times / d. The efficacy and side effects are basically similar to cholestyramine, but the price is cheaper.
(3) Dividistyramine
This is an anion exchange resin with pharmacological action.
[Common dose] 6-12g / d. The drug's hypolipidemic indications and side effects are similar to cholestyramine, but its clinical application is not as extensive as cholestyramine and cholestyramine.
Resin-based bile acid integrators cholestyramine and cholestepor have many clinical studies and applications abroad, and have been used as first-line drugs to lower TC. The previous cholestyramine used in the country relies on imports from abroad. It is expensive, coupled with large amounts, bad taste, and easy to cause constipation. Therefore, it has been used in a few large hospitals for individual special cases and has only scattered clinical experience. .
Domestic Shishantou Pharmaceutical Factory in China has been able to produce cholestyramine, and the affiliated hospital of Zhenjiang Medical College has given domestic cholestyramine 16g to 164 patients daily, and 94 patients with hyperlipidemia to take fenolide daily. Bet 300mg, for 2 months of comparative observation. The results confirmed that compared with before treatment, TC, LDL-C, TG, and TC / HDL-C in the cholestyramine group decreased by 25.1%, 42.2%, 4.8%, and 37.3%, respectively. HDL-C increased by 17.5% (except for TGP> 0.05, other P <0.01). Decrease in TC, LDL-C, TC / HDL-C and increase in HDL-C were significantly better in the cholestyramine group
Fenofibrate group (P <0.01). During the treatment, the main side effects seen in the cholestyramine group were abdominal distension (22.5%) and constipation (11.1%), but they were tolerated and successfully completed the course of treatment. Because HMG-CoA reductase inhibitors have stronger TC-lowering effects and fewer side effects than bile acid integrators, bile acid integrators are no longer used as first-line drugs for TC reduction even abroad.
Antihyperlipidemic drugs
Clinical application of HMG-CoA reductase inhibitor
The effect of bile acid integrator on TC is recognized, but it is difficult for patients to stick to it for a long time due to many side effects. Although the taste of bile acid integrator has been improved, some side effects can be overcome, but they can only prevent the absorption of bile acid and cholesterol from the intestinal tract, and have no inhibitory effect on the synthesis of cholesterol in the body. TC in blood mainly comes from in vivo synthesis. Therefore, the use of bile acid integrator alone has not yet achieved the desired effect. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor was found to inhibit cholesterol biosynthesis.
(1) History and chemical structure of HMG-CoA reductase inhibitor
Cholesterol biosynthesis inhibitors have actually been put into clinical use more than 20 years ago and have been discontinued due to side effects. In 1976, Endova et al. Found Mevastatin (formerly known as Compactin), also known as Mevatin, in an extract of Penicillium Citrium in Japan. Other researchers have shown that it has a significant effect on lowering serum TC levels in animals and patients with hypercholesterolemia. Later, it was rumored in Japan that it could cause morphological changes in the small intestine of dogs and stopped clinical application. Later in the United States, Lovastatin (formerly known as Mevinolin) was obtained from the soil Aspergillus medium, also known as Lovastatin and Metricolin. Extensive research in North America, Western Europe, Australia, and Japan has confirmed that it is an HMG-CoA reductase inhibitor that can safely and effectively reduce serum TC levels in patients with hypercholesterolemia. In 1987, it was approved by the United States Food and Drug Administration Bureau approval, put into clinical application. Simvastatin (formerly known as Synvino1in), also known as Sevastopin and Shu Jiangzhi; and Pravastatin (formerly known as CS514 and SQ31000), also known as Pavastatin, Pragu, and Merbella, they are respectively It is a methylated and methylated derivative of mevastatin. It also chemically synthesized one kind of fluvastatin (beuvastatin, formerly known as SRI-62320) and another kind of atorvastatin (also known as Lipitor). It is expected that new HMG-CoA reductase inhibitors will continue to appear.
(B) the mechanism of HMG-CoA reductase inhibitors to lower blood lipids
Most of the cholesterol in plasma lipoproteins comes from synthesis in the body and not from food. The pathway of cholesterol synthesis in vivo is shown in Figure 33-2. HMG-CoA reductase converts HMG-CoA to MevilonicAcid, which is a rate-limiting step in the early synthesis of cholesterol in vivo, which regulates cholesterol metabolism in the receptor. The emptying of the cholesterol library in the cell leads to an increase in the activity of the enzyme, which accelerates the synthesis of cholesterol in the body. When the amount of cholesterol in the cell increases, the enzyme activity decreases, and cholesterol in vivo synthesis slows down.
The open acid portion of the chemical structure of HMG-CoA reductase inhibitor is very similar to HMG-CoA, and it has a specific competitive inhibitory effect on the rate limiting enzyme of cholesterol biosynthesis, HMG-CoA reductase. Theoretically, it can inhibit the formation of all methyl divaleric acid metabolites-cholesterol, polyterpene alcohol and coenzyme Q (Figure 33-2). Studies have shown that although it can reduce the production of cholesterol, it has little effect on overall metabolism.
(3) Pharmacokinetics of HMG-CoA reductase inhibitor
So far, only pharmacokinetic reports of such preparations have been published. The pharmacokinetic data of lovastatin are more detailed. It is in the form of an inactive lactone, which is quickly converted into the active? -Hydroxy acid in the liver after taking it. Its main active metabolites, in addition to this? -Hydroxy acid, are 6-hydroxy derivatives and two other unidentified metabolites. The main route of excretion of lovastatin and its metabolites is the small intestine. Whether it is due to non-absorption or re-secretion into the bile after absorption, it is excreted by the intestine. Less than 10% of lovastatin is excreted by the urine. In plasma, these products are bound to proteins. Lovastatin is excreted into the bile by the liver. The liver's ability to excrete depends in part on the concentration of the drug in the plasma.
In animal experiments, a single dose of lovastatin absorbed only 30%. When passing through the liver for the first time, the drug is almost completely taken. It appears that less than 5% of an oral dose enters the systemic circulation. This shows that the main part of the effect of lovastatin is the liver, which may also have a certain effect in the small intestine. Its interaction with other drugs has not been well studied so far. Lovastatin administration in humans does not affect the pharmacokinetics of Antipyrine. This suggests that the drug does not affect the cytochrome P-450 system. In addition, it does not alter the metabolism of other commonly used drugs such as propranolol and digoxin. However, clinical experience suggests that the combination of lovastatin, simvastatin, and pravastatin with cyclamycin (Cyclosporine), gefitizil, or nicotinic acid can make patients susceptible to myopathy, and occasionally even rhabdomyolysis. . Fluvastatin has been used alone or in combination with niacin, and no myopathy has been reported so far.
Clinical application of niacin and its derivatives
(1) Nicotinic Acid (also known as Niacin)
Antihyperlipidemic drugs
Is a B vitamin. When the amount exceeds the dose that acts as a vitamin, it can have a significant effect on regulating blood lipids. The chemical structure of niacin is: niacin is easily absorbed from the gastrointestinal tract, and the blood concentration reaches a peak 30 to 60 minutes after oral administration, which is widely distributed in body tissues and has a half-life of about 45 minutes. Metabolized in the liver. When taken in large doses, the main metabolites are Nicotiuric Acid, N-methylnicotinamide and 2-pyridone derivatives. 2/3 are excreted from the urine in a constant form. The main mechanism of nicotinic acid to regulate blood lipids is to inhibit the formation of cAMP, resulting in a decrease in triglyceride activity, a slowing of lipolysis in adipose tissue, a decrease in the concentration of non-esterified fatty acids (NEFA) in the blood, and a decrease in liver VLDL synthesis, further Reduce IDL and LDL. In addition, nicotinic acid can synthesize nicotinic acid with glycine under the action of coenzyme A (CoA), thereby preventing liver cells from using CoA to synthesize cholesterol. The mechanism by which niacin can increase blood HDL-C levels is unknown.
The efficacy and dosage of niacin to regulate blood lipids are related to the blood lipid levels before taking the drug. The blood lipid levels are abnormal. The dosage should be large and the effect is more obvious. Oral niacin 3-6g / d, TG began to decrease 1 to 4 days after taking the drug, and LDL-C began to decrease 5-7 days. Average decline: TC is 10% -15%, LDL-C is 15% -20%, TG is 20% -80%, and HDL-C increases slightly to moderately. After long-term treatment, the xanthomas disappeared. According to reports insisting on taking nicotinic acid 3g per day for more than 5 years, the average TC decreased by 15% and the TG decreased by 26%. The total mortality rate was not lower than that of the control group, but it could reduce the incidence of re-myocardial infarction in survivors of acute myocardial infarction. %. Niacin can be used for any type of hyperlipidemia except homozygous familial hypercholesterolemia and type I hyperlipoproteinemia.
A serious side effect is the activation of peptic ulcers, which can aggravate ulcers. Can reduce glucose tolerance and thereby make diabetes worse. It can also increase blood uric acid and even cause gout. Occasionally, liver function was impaired, serum transaminase and alkaline phosphatase activities increased, and cholestasis jaundice was even seen. When these reactions occur, the drug should be discontinued in time, and it can be recovered after stopping the drug. Niacin can enhance the vasodilator effect of antihypertensive drugs, and can even cause positional hypotension. Therefore, patients with ulcer disease, diabetes, liver dysfunction and hypertension should use this medicine with caution. Not suitable for pregnant and lactating women. During the medication process, liver function, blood glucose, and uric acid should be reviewed regularly, and the dose should be reduced or discontinued in case of obvious abnormalities.
(2) Acipimox
Also known as trimethoprim and olbetam. It is a new synthetic niacin derivative. Its chemical structure:
In the past ten years or more, foreign countries have made more researches on the pharmacology, clinical efficacy and safety of blood lipid lowering, and there have been reports of clinical application.
The drug is rapidly absorbed after oral administration, and the plasma concentration reaches a peak within 2 hours after the administration, and the half-life is 2 hours. Assimox binds to plasma proteins and is excreted from the urine almost unchanged. It mainly acts on adipose tissue, inhibits the release of non-esterified fatty acids from adipose tissue, and reduces the production of TG, VLDL and LDL. It also accelerates the degradation of VLDL by activating lipoprotein lipase, and increases plasma HDL levels by inhibiting liver lipase. Therefore, its scope of application is similar to that of niacin. It has the following advantages over nicotinic acid: no initial effect and longer half-life; longer duration of anti-lipolytic action, stronger efficacy, no rebound phenomenon of non-esterified fatty acids; can significantly improve glucose tolerance , Can reduce fasting blood glucose by about 15%, does not interact with oral hypoglycemic drugs, so it can be used in patients with diabetes; does not cause changes in uric acid metabolism, can be used in patients with hyperuricemia; very few patients with liver transaminase; Only about 6% of patients with facial flushing and pruritus after taking the medicine were significantly less than those taking niacin. According to foreign data, more than 1,000 cases of hyperlipidemia patients, after 2 years of serving asimox, showed that TC decreased by 25%, TG decreased by 50%, and HDL-C increased by 20%.
It is an ester composed of 1 molecule of inositol and 6 molecules of niacin.
Antihyperlipidemic drugs
After being absorbed from the intestine, the drug is slowly metabolized in the body, gradually hydrolyzed into niacin and inositol, and then functions. It can alleviate and permanently expand peripheral blood vessels, improve lipid metabolism, and have fibrinolytic, thrombolytic and anticoagulant effects. The indications for lowering blood lipids are the same as for niacin.
Beijing Fuwai Cardiovascular Hospital, has conducted a three-month lipid-lowering effect comparison of inositol nicotinate and clofibrate (also known as Guanxinping), and the results have no significant effect on TC. However, both significantly reduced serum TG levels. No significant side effects were seen. Due to the small number of observations, its hypolipidemic effect could not be concluded. In short, most niacin derivatives and their slow-release agents have mild side effects, but their lipid-lowering effect is not as strong as that of niacin.
Fibrates clinical application
(1) Clofibrate
Also known as clobetin, antrum, Guanxinping, CPIB and Atromid-S. Is the earliest application of this class of drugs. Its chemical structure:
The drug has been used clinically in 1962 and has been widely used in its early years. Clobate is well absorbed orally and rapidly hydrolyzes into the living product chlorophenbutyric acid in the body. The concentration of CPIB in blood reached a peak 1.5 to 4 hours after taking the drug, and about 95% bound to plasma proteins. After oral administration, 85% of the drug is excreted from the urine, of which 92% -98% is present in the form of water-soluble glucuronide binding. Clobate passes through the placenta and is excreted from milk.
It is mainly through the inhibition of adenylate cyclase, which reduces the cAMP content in adipocytes, inhibits the hydrolysis of adipose tissue, reduces the non-esterified fatty acid content in the blood, and leads to reduced liver VLDL synthesis and secretion. At the same time, it can increase the activity of lipoprotein lipase and accelerate the catabolism of VLDL and TG. These ultimately reduce the levels of VLDL, TG, LDL-C and TC in the blood. In addition, it can reduce the TC content in blood by inhibiting the synthesis of cholesterol by liver cells and increasing the excretion of cholesterol from the intestine.
Over the years, countries around the world have gained a lot of experience with the large number of applications of clofibrate. The results of large-scale long-term trials by the World Health Organization using the double-blind method have confirmed that not only can chloroform reduce TG, but also TC, and can significantly reduce the incidence and mortality of coronary heart disease. However, it can significantly increase the incidence of gallstones in users, and it can also significantly increase the mortality of non-coronary heart disease, such as gallstones, tumors and other various causes, thus making the medication group higher than the control group. Mortality. As a result, Bate has actually been eliminated.
(2) Fenofibrate
Antihyperlipidemic drugs
Also known as Lipanthyl. Fenofibrate has been reported in clinical trials in 1975 and has been widely used today. Its chemical structure:
After oral administration, the drug is rapidly absorbed from the gastrointestinal tract, and its distribution in vivo conforms to the two-compartment model. After taking the drug, the blood concentration reached a peak 4-7 hours, the phase a half-life was 4.9 hours, and the phase half-life was 26.6 hours. The body is quickly broken down by tissues and plasma enzymes to form free acids that bind to proteins, only 10% of which are invariant. Discharge 80% within 24 hours. About 90% of the metabolites are excreted in urine, and a small part is excreted in feces.
Beijing Fuwai Cardiovascular Hospital had observed the effects of fenofibrate (54 cases) and edroester (52 cases) on lipid regulation for 12 weeks, and the results confirmed that compared with before treatment, fenofibrate It can reduce serum TC, LDL-C, TG levels and TC / HDL-C ratios by 20.3%, 13.8%, 53.1%, and 28.7% respectively, and can increase serum HDL-C levels by 27.8% (P <0.01-0.001 ). Both fenofibrate and edomester significantly reduced serum TC, TG, and increased HDL-C levels, but their effects on TG were more pronounced. As far as the magnitude of the regulation of blood lipids is concerned, fenofibrate is greater than polydextrin, but there is no statistically significant difference.
Probucol Clinical Application
Probucol is also known as probucol. The drug is absorbed less than 10% after oral administration. If taken with food, a higher blood concentration can be obtained. After taking the medicine continuously for 3 to 4 months, the blood concentration gradually increased, and then gradually stabilized. The blood lipid-lowering effect was not closely related to blood drug concentration. Some people think that the drug inhibits the synthesis of ApoB, thereby reducing the production of LD1, and at the same time because it promotes the decomposition of LDL and promotes the cholesterol in the blood to enter the bile and be excreted in the feces. The combination of these effects will ultimately reduce the levels of LDL-C and TC in the blood. And because the drug can inhibit the synthesis of ApoAI, the level of HDL-C in blood is reduced.
The drug regulates the intensity of blood lipid effects, which varies greatly from individual to individual.
After taking probucol, serum 10L-C levels were seen to decline, but it was not seen to promote the progression of atherosclerosis. During the medication, the patient's heel xanthomas and cutaneous xanthomas showed regression. In addition, probucol is a strong antioxidant, which is beneficial to inhibit the formation and development of atherosclerosis.
Panthine
Panthiamine is also known as Pantex. Its molecular structure is a component of CoA.
Antihyperlipidemic drugs
Animal experiments have confirmed that it can promote the normal metabolism of blood lipids, improve fatty liver and alcohol-toxic liver damage, inhibit the formation of lipid peroxides and platelet aggregation, and prevent the deposition of cholesterol on blood vessel walls. After years of clinical application at home and abroad, it was confirmed that oral administration of 0.2 g / time, 3 times / day, TC decreased by 5.2% to 15.2%, TG decreased by 23.6% to 31.7%, and HDL-C increased by 10.0% to 20.5%. Beijing Fuwai Cardiovascular Hospital used a self-controlled and double-blind, randomized placebo-controlled method to evaluate the effect of panthionine on blood lipids. The results show that pantothine reduces TC, TG, and HDL-C with similar magnitudes as those reported in foreign literature. It is certain that pantothine can significantly reduce serum TC and TG levels.
Shows that serum HDL-C levels have increased significantly after taking the drug, but the same changes have also occurred in the placebo. Therefore, the significance of panthionine on HDL-C needs to be further clarified.
Omega-3 fatty acid clinical application
Omega-3 fatty acid means that the last double bond has 3 carbon atoms from the methyl terminal. Omega · 3 fatty acids are mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (HnA). Sea fish oil is the most abundant, including the oil in sea fish meat, which contains a large amount of EPA and DHA. The mechanism by which marine fish oil regulates blood lipids is not fully understood. It may inhibit the synthesis of lipids and lipoproteins in the liver and promote the excretion of cholesterol from feces. In addition, it can dilate the coronary arteries, reduce thrombosis, delay the process of atherosclerosis, and reduce the incidence of coronary heart disease. This is likely to work by affecting prostaglandin metabolism and improving platelet and leukocyte function. Eskimos and Arctic residents who eat large numbers of fish have a low incidence of coronary heart disease.

Precautions for hypolipidemic drugs

If your blood lipid test report shows that cholesterol, triglyceride, low-density lipoprotein, and apolipoprotein day are increased, while high-density lipoprotein and apolipoprotein A are decreased, it indicates that you have arteriosclerosis. And susceptibility to coronary heart disease. At this time you should pay attention to regulating your blood lipid level.
Patients with hyperlipidemia should first take general measures such as controlling diet, increasing exercise, and losing weight. If it does not work, consider medication. Vitamin E should be used with caution in patients with hyperlipidemia.
Antihyperlipidemic drugs
Reasonable selection of lipid-lowering drugs. Phenoxyacetic acids, such as Antomin, Lipin Fat (Fenofibrate), Gefiprozil (Cleansing Fat, Nuo Heng), Benzabetide (Because of lipid reduction), etc. Similar drugs, which can lower low-density lipoprotein cholesterol and triglycerides, but have an effect on raising high-density lipoprotein cholesterol. Hydroxymethylglutaryl coenzyme A reductase preparations (statins), such as lovastatin, meclizine, Xuezhikang (zhibituo), simvastatin (sulbutamine), pravastatin (Plague) and so on. The effect of lowering LDL cholesterol is more obvious than that of phenoxyacetic acids, and the effects of lowering Gan Shan triester and increasing density of lipoprotein cholesterol are not as good as those of phenoxyacetic acids. Polyunsaturated fatty acids, such as fish oil preparations (maidongkang, doxenekang, etc.), linolenic acid, etc., can reduce triglycerides, but the effect of lowering cholesterol is poor. Nicotinic acid, such as nicotinic acid, inositol nicotinate, dongzhiping, pentaerythritol, etc. However, some patients have blushing, palpitations, itchy skin, and gastrointestinal discomfort after use. Elastase, weak lipid-regulating ability, but small side effects, can be used for mild patients. C-receptor blockers such as Telarius can increase high-density lipoprotein, but are prone to orthostatic hypotension. Chinese medicine ginseng, Gynostemma pentaphyllum, Hawthorn, etc. also have a certain lipid-lowering effect. Application principles of lipid-lowering drugs
(3) Many lipid-lowering drugs, especially the lipid-lowering drugs that affect the excretion of cholesterol and bile acids through bile and feces, will make the bile cholesterol in a saturated or supersaturated state, and easily form gallstones.
Cholesterol-lowering drugs have certain damage to the liver. In addition, long-term use of lipid-lowering drugs can cause changes in body lipids, leading to the occurrence of non-cardiovascular diseases. Therefore, in case of adverse reactions, the drug should be stopped in time.
Because the human body needs a certain amount of blood lipids to maintain normal body functions, indicators such as cholesterol, triglycerides, and apolipoproteins that are excessively lower than the normal range are also abnormal.
should stop smoking and avoid alcohol. Because smoking can accelerate the development of arteriosclerosis, one of the mechanisms is that smoking can reduce plasma high-density lipoprotein levels and is not conducive to the elimination of cholesterol, and drinking can increase hyperlipidemia.

Antihyperlipidemic drugs

For the reasonable diet structure of general hyperlipidemia patients, relevant experts summarized it into two sentences, namely "one, two, three, four, five" and "red, yellow, green, white, and black."
The first sentence is "one, two, three, four, five": "one" refers to drinking 1 bag of milk daily, containing 250 mg of calcium, which not only supplements calcium and protein, but also reduces the incidence of hyperlipidemia . "Second" is recommended to use the tea of the traditional Chinese medicine group of Dangwu Tangcha in combination, and long-term drinking can play a very good control effect. "Three" refers to eating 3 high-protein foods each day, each serving can be 50 grams of lean meat, or 1 egg, or 100 grams of chicken and duck meat, or 100 grams of fish and shrimp, or 100 grams of tofu, as early as daily 1 for lunch, lunch, and dinner; "four" means "not sweet and not salty, thick and fine, three to five meals, seventy to eighty percent full", that is, three, four, or five meals per day, each You can eat 70% to 80%. "Five" refers to eating 500 grams of vegetables and fruits daily, generally eating 400 grams of vegetables and 100 grams of fruits daily.
The second sentence is "red, yellow, green, white, and black": "Red" refers to 50-100 ml of red wine that can be consumed daily, which helps raise high-density lipoproteins in the blood and can prevent atherosclerosis . In addition to eating 1-2 tomatoes daily, in addition to reducing blood pressure, the incidence of prostate cancer in men can be reduced by 45%. "Yellow" refers to carrots, sweet potatoes, pumpkins, corn, etc., and one of them should be consumed in an appropriate amount every day. "Green" refers to drinking green tea and eating dark green vegetables. They contain vitamin C, tea polyphenols, and theophylline, which have various functions such as degreasing and lowering blood pressure. "White" refers to oatmeal (or oatmeal), which can be taken in an appropriate amount every day, usually boiled with 50 grams of water for 5 to 10 minutes a day, mixed with milk and used to lower blood fat. "Black" refers to black fungus or shiitake mushrooms. Every day, 10 grams of black fungus or 100 grams of shiitake mushrooms can be used. After foaming, they can be cooked and used in dishes, which can reduce blood lipids and other functions. [3]
Foods that lower cholesterol and bad cholesterol (LDL):
Mandarin fishes contain extremely low saturated fats, especially from cold water fish from the deep sea, which contain a large amount of W-3 fatty acids. According to research by US scientists, people who take W-3 fatty acids (EPA and DHA supplements), Cholesterol, triglyceride content, blood viscosity are reduced, and blood pressure is also reduced.
Consuming a lot of fruits, vegetables, and water-soluble fiber is good for lowering cholesterol. Lightly water-soluble fiber (such as whole wheat bran) prevents constipation, but does not help lower cholesterol. Foods containing water-soluble fiber include beans, dates, grass fruits, figs, dried plums, broccoli, oat bran and so on. Dried plums contain 60% soluble pectin, soy beans and their products with the same effect. Konjac food also contains a large amount of water-soluble fiber.
US researchers have found that eating half a piece of garlic every day (whole whole is better) can help some people lower their cholesterol by 10% and lower blood pressure. The healthful active ingredient in garlic is --- Alliin. Taking 900 mg of odorless garlic capsules daily has the same effect as eating garlic. In addition, onions can also lower cholesterol and blood pressure, and have the effect of lowering blood viscosity. The effect is similar to that of aspirin.
Caffeine increases cholesterol in the body. Therefore, you should pay attention to drinking coffee and tea as much as possible, and ban medication containing caffeine.
The way food is cooked is also important. In cooking animal foods, absolutely avoid frying. The more suitable method is steaming and roasting, so that the fat in the food can drip out.
According to the latest research results submitted by the American Heart Association in Canada, orange juice can increase good cholesterol (HDL). People with high cholesterol drink 3 glasses of orange juice a day. After one month, good cholesterol (HDL) increases by 21%, and at the same time, homocysteine levels decrease, which means that the possibility of heart disease is reduced. Please note that the doctor warns : Elderly high cholesterol patients over 70 years of age, diet therapy is not significant, because for them, nutrition is more important.

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