Antihyperlipoproteinemic Drugs

Antihyperlipoproteinemic Drugs / Mechanism of Action / Indications / AE / CI / Other
Niacin (Nicotinic Acid) / -Water soluble vitamin that inhibits lipolysis in adipose tissue and so lowers free FA in circulations, which is necessary for VLDL and so LDL synthesis. So, both TAG (in VLDL) and cholesterol (in VLDL and LDL goes down.
-Increases tissue plasminogens and lowers plasma fibrinoges / -Tx. of type IIb and type IV hyperlipidemia
-Raise plasma HDL levels (most effective) / -Intense cutaneous flush which can be decreased by taking aspirin prior to taking niacine
-Pruritus
-Nausea
-Abdominal pain
-Hyperuricemia & gout
-Hepatotoxicity
-Impaired glucose tolerance
-Activation of peptic ulcer / Should be avoided in pregnancy b/c of teratogenic effects / Shows decreased mortality
Fibrates: Gemfibrozil &
Clofibrate / -Decrease plasma TAG by increasing lipoprotein lipase activity and so hydrolyzing TAG in VLDL and Chylomicrons
-Moderate increase in HDL
-Inhibits cholesterol synthesis in liver and increases biliary excretion of cholesterol so decreased plasma cholesterol
-Lowers plasma fibrinogen levels / -Tx. Of type III, type IV and type V hyperlipidemia
-Decreased MI incidence had been seen w/ this drug / -Mild GI disturbance
-Gall stone formation b/c of increased biliary cholesterol excretion
-Myositis, muscle weakness and tenderness, myalgia
-Claudications
-Thrombosis (??)
-Decreased libido / Should not be used in pt. w/ hepatic and kidney dysfunction and should be avoided in pt. w/ pre-existing gall bladder disease / Lowers coumarin clearance and so increases its anticoagulant effects, so should lower the coumarin dose when taking this drug
Bile acid binding resins:
Cholestyramine
Colestipol / -Binds to (-)vely charged bile acids and bile salts and increases their excretion in feces and so decreases bile acid return to liver, so liver uses cholesterol to make more bile acid and bile salt so the intracellular cholesterol goes down and so LDL receptors go up, which increases uptake of circulating LDL and so plasma cholesterol goes down. / -DOC in tx. of type IIa and type IIb hyperlipidemia. (it has little effects in pt. who are homozygous of type IIa hyperlipidemia that is they have no functional LDL receptors)
-Cholestyramine relieves pruritus caused by bile acid accumulation in pt. w/ biliary obstruction / -Constipation, bloating
-Flatulence
-Nausea
-Abdominal pain
-Impaired absorption of fat soluble vitamins (vit. A, D, E and K)
-Reduced absorption of folic acid and ascorbic acid
-Interfere w/ intestinal absorption of other drugs / Should be taken w/ meals
HMG CoA Reductase Inhibitors:
Lovastatin
Simvastatin
Pravastatin
Fluvastatin / -Inhibits HMG CoA Reductase, which is necessary for cholesterol synthesis. So, intracellular cholesterol goes down. As a result, LDL receptors goes up and uptake of circulating LDL by cell goes up lowering plasma cholesterol
-HDL may go up in some pt.
-Small decrease in TAG / -Tx. of all kinds of hyperlipidemias
-Less effects in pt. homozygous type IIa hyperlipidemia / -Fewer AEs
-Increased liver enzymes
-Myopathy
-Rhabdomyolysis
-GI disturbance
-Headache
-Increases coumarin levels / CI in pregnancy and nursing mothers, and shouldn’t be used in children and teenagers
Probucol / -Macrophages ingest oxidized LDL and become foam cells, which then accumulates in vessels and forms atherosclerotic plaque, so probucol inhibits oxidation of LDL and so slows development of atherosclerosis / -limited use in type IIa and type IIb hyperlipidiemia b/c it also decreases HDL which is a risk factor for atherosclerosis
-claimed to reduce fq of new angioplasty / -Mild GI Disturbance
-Prolongation of QT interval / CI in pt who have abnormally long QT interval / -Accumulates in adipose tissue for months
- Should be taken w/ food

Combination Drug Therapy:

-Type II hyperlipidemias can be treated with combination of Niacin and Bile acid binding agent such as cholestyramine.

-The combination of HMG CoA Reductase inhibitors and bile acid binding agents can be used to lower LDL cholesterol.

-Triple drug combination is possible but increases risk of kidney failure

Types of Hyperlipidemias

Type of Hyperlipidemia / Problem / Treatment
Type I: Familial Hyperchylomicronemia / Increased chylomicrons and so increased TAG / No drug therapy
Low fat diet
Type IIA: Familial Hypercholesterolemia / Blocked degradation of LDL so, elevated LDL w/ normal VLDL (increased plasma cholesterol) / Bile acid binding resins
HMG CoA Reductase inhibitors
Niacin (in homozygous)
Low saturated fat and low cholesterol diet
Type IIB: Familial Combined (Mixed) Hyperlipidemia / Increased VLDL and LDL, so increased plasma TAG and cholesterol / Niacin
Bile acid binding resins
HMG CoA Reductase inhibitors
Low saturated fat and low cholesterol diet
Type III: Familial Dysbetalipoproteinemia / Increased IDL so increased TAG and cholesterol / Fibric Acid
HMG CoA Reductase inhibitors
Diet modification
Type IV: Familial Hypertriglyceridemia / Increased VLDL and so increased TAG / Fibric Acid
Niacin
Diet modification
Type V: Familial Mixed Hypertriglyceridemia / Increased VLDL and Chylomicrons, so elevated cholesterol but greatly increased TAG / Fibric Acid
Niacin
HMG CoA Reductase inhibitors
Diet modification