Competitive inhibitors of HMG-CoA reductase (1st committed step in sterol synthesis)

↑ LDL receptors = ↑ LDL catabolism and liver’s extraction of LDL precursors (VLDL) from the blood = ↓ plasma LDL

Myositis, rhabdomyolysis

Hepatic toxicity (malaise,

anorexia, decreases in LDL)due to ↑ of aminotransferase activity

Atherosclerosis vascular disease, acute coronary syndromes

Inhibits VLDL secretion, in turn ↓ LDL production. ↑ VLDL clearance via the LDL pathway reduces triglycerides.

↓ HDL catabolism (= ↑HDL). 

↓ lipoprotein(a)

Gastric irritation, cutaneous flushing, low incidence of hepatic toxicity, may ↓ glucose tolerance

Low HDL, elevated VLDL, LDL, Lp(a)

Rx: hypercholesterolemia

(normalizes LDL), severe

mixed lipemia

Agonist for peroxisome proliferator-activated receptor-alpha (PPAR-α) = ↑ transcription of lipoprotein lipase (LPL)

↓VLDL secretion, , ↑HDL

↑ oxidation of fatty acids

Myopathy, hepatic dysfunction

Gallstones due to ↑ in cholesterol content of bile

Hypertriglyceridemia, low HDL

Agonist for peroxisome proliferator-activated receptor-alpha (PPAR-α) = ↑ transcription of lipoprotein lipase (LPL)

↓VLDL secretion, , ↑HDL

↑ oxidation of fatty acids

Myopathy, hepatic dysfunction

Gallstones due to ↑ in cholesterol content of bile

Hypertriglyceridemia, low HDL

Binds to bile acids in the gut preventing reabsorption.  ↑ Bile acid excretion => ↑ cholesterol conversion to bile acids.

Upregulates LDL receptors.  ↑LDL & IDL uptake from plasma.

Constipation/bloating, steatorrhea,

malabsorption (vitamin K, folic

acid, charged drugs)

Elevated LDL, digitalis toxicity, pruritis

Binds to bile acids in the gut preventing reabsorption.  ↑ Bile acid excretion => ↑ cholesterol conversion to bile acids.

Upregulates LDL receptors.  ↑LDL & IDL uptake from plasma.

Constipation/bloating, steatorrhea,

malabsorption (vitamin K, folic

acid, charged drugs)

Elevated LDL, digitalis toxicity, pruritis

Selective inhibitor of intestinal absorption of cholesterol and phytosterols.  Blocks sterol transporter NPC1L1 in intestine brush border inhibiting reabsorption of cholesterol excreted in bile

Low incidence of hepatic dysfunction, myositis

Elevated LDL, phytosterolemia

Inhibits cholesterol (re)absorption

Malabsorption of fat-soluble

vitamins

Rx: ↑ LDL, ↑ cholesterol

inhibits gastric and pancreatic lipases => triglycerides are not hydrolyzed into absorbable free FAs, and are excreted undigested

Malabsorption of fat-soluble

vitamins, steatorrhea, flatulence

Rx: weight loss

Indigestible fat substitute in food

8 FA chains attached to sucrose

Malabsorption of fat-soluble

vitamins, diarrhea

Lower or eliminate fat content of high-fat foods