Antiatherosclerosis drugs

Lipid-regulating drugs  Background  Lipoprotein  Classification of Lipoprotein: CM 、 VLDL 、 IDL 、 LDL 、 HDL 、 Lp(a) CM 、 VLDL 、 IDL 、 LDL 、 HDL 、 Lp(a)  Hyperlipoprotein: VLDL 、 IDL 、 LDL 、 apoB HDL 、 apoA HyperlipoproteinHDL 、 apoA Hyperlipoprotein Antiatherosclerosis :Antiatherosclerosis :  VLDL 、 LDL 、 TC 、 TG 、 apoB  HDL 、 apoA Easy to

HMG-CoA reductase inhibitors(---statins) Drugs: mevastatin, lovastatin and their derivatives Pharmacological effects: Apparently decrease plasma TC and LDL-Cholesterol Mechanism: HMG-CoA mevalonic acid(MVA) hepatic Ch synthesis LDL-R reductase clearance of LDL 、 IDL hepatic apo B-100 synthesis VLDL synthesis

Clinic use: first choice for essential hypercholesterolemia, heterozygous familial hypercholesterolemia 、 Ⅲ -type hyperlipidemia, diabetic and renal hyperlipidemia. Adverse reaction: nearly 10% patients suffer from mild gastrointestional disturdance, insomnia 、 headache and rash. More serious adverse effects are rare but include increased aminotransferase, alkaline phosphatase activity and myositis(rhabdomyolysis), creatine kinase activity.

Bile acid bining resins Drugs :cholestyramine, colestipol Pharmacological effects: TC/LDL-C HDL Mechanism: when taken by mouth, they sequester bile acids in the intestine and prevent their reabsorption and enterohepatic recirculation. The result is decreased absorption of exogenous cholestereol and increased metabolism of endogenous cholesterol into bile acids in the liver. This leads to increased expression of LDL receptors on liver cells, and hence to increased removal of LDL from the blood and a reduced concentration of LDL-cholesterol in plasma.

Clinic use: Ⅱ a-type hyperlipoproteinaemias take effect in 4~7 days, reach maximum effect within 2 weeks Adverse reaction: nausea, abdominal bloating, constipation, malabsorption of vitamins

Nicotinic acid Pharmacological effects:  to decrease VLDL and TG levels in the plasma of patients with a variety of hyperlipidemias.  to inhibit the aggregation of platelet  vasodilation Mechanism of action:  to inhibit the lipolysis of fat  to inhibit the esterification of TG

Nicotinic acid Clinic uses: Ⅱ、Ⅲ、Ⅳ and Ⅴ -type hyperlipidemias. Adverse reactions:  Pruritus, rashes, flush acanthosis  Nausea and abdominal discomfort  Hepatic dysfunction  hyperuricaemia

Drugs: Clofibrate 、 gemfibrozil 、 bezafibrate 、 fenofibrate 、 ciprofibrate Pharmacological effects and mechanisms:  to decrease TG 、 VLDL  Due to its increase of VLDL-TG hydrolyzation and VLDL lipolysis via increase the lipoprotein lipase activity  To increase HDL VLDL-TG HDL-CE  VLDL HDL exchange Fibric acid derivatives: ---brate

Clinic use  to decrease TG 、 VLDL and IDL  for Ⅱ b 、Ⅲ、Ⅳ - hyperlipidemia, especially for familial Ⅲ -hyperlipidemia.  mild hypercholesterolemia with reduced HDL-cholesterol ADR: gastrointestinal symptoms, skin rashes, decrease in white blood count, hepatic dysfunction

Antioxidant ---probucol Pharmacological effects:  to lower TC, LDL-C and HDL MECHANISM:  to inhibit the oxidative modification of LDL via the combination with lipoprotein for its hyper-lipophilic property

Polyunsaturated fatty acids---fish oil EPA and DHA  to decrease TG, VLDL,LDL-C  to increase HDL-C Potentially important effects:  Inhibition of platelet function  Prolongation of bleeding time  Decrease of blood mucosity  Prevention of atherosclerosis

Endothelium protective drugs Drugs: polysaccharide sulfate Mechanisms of action:  to prevent the conglutination of white cell and platelet  to inhibit the proliferation of vascular smooth muscle