Antiatherosclerosis drugs

Lipid-regulating drugs Background Background LipoproteinLipoproteinClassification of Lipoprotein:Classification of Lipoprotein:

CMCM 、、 VLDLVLDL 、、 IDLIDL 、、 LDLLDL 、、 HDLHDL 、、 Lp(a)Lp(a)Hyperlipoprotein:Hyperlipoprotein: VLDLVLDL 、、 IDLIDL 、、 LDLLDL 、、 apoBapoB• HDL HDL 、、 apoAapoA Hyperlipoprotein Hyperlipoprotein• Antiatherosclerosis :Antiatherosclerosis : VLDLVLDL 、 、 LDL LDL 、、 TCTC 、、 TG TG 、 、 apoBapoB HDL HDL 、、 apoAapoA

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HMG-CoA reductase HMG-CoA reductase inhibitors(---inhibitors(---statinsstatins))

• 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:

Ⅱa-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

exchangeexchange

Fibric acid derivatives: ---brate

• Clinic use to decrease TG 、 VLDL and IDL for Ⅱb 、Ⅲ、Ⅳ - hyperlipidemia,

especially for familial -hyperlipidemia.Ⅲ mild hypercholesterolemia with reduced H

DL-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