Lipid Drugs Flashcards
what do the exogenous and endogenous pathways do?
exogenous = LDL, endogenous = foam cells
cell regulation of cholesterol metabolism
binding of apoB100 to LDL receptors promotes LDL absorption. Lipoprotein goes on to be hydrolyzed into amino acids and cholesterol. Cholesterol decreases HMG CoA reductase, activates ACAT (cholesterol storage enzyme), inhibits further uptake of cholesterol by stopping LDL receptor transcription
reverse transport
HDL secreted by liver and intestines. picks up cholesterol from peripheral tissues. carries the cholesterol to the liver or other tissues.
diet as a therapeutic strategy
only treatment necessary for many patients. attain normal body weight and minimize plasma lipids. diet should be low in cholesterol, low in total fats, low in saturated fats.
why is HDL anti-atherogenic?
reverse cholesterol transport, protects against endothelial dysfunction, inhibits oxidation of atherogenic proteins.
nicotinic acid (niacin)
B complex vitamin. need high doses. Raises HDL 30%, lowers triglycerides 40%, lowers LDL 25%. many adverse side effects: hepatotox, hyperglycemia, hyperuricemia, flushing, pruritis, dyspepsia, rashes. Not used due to side effects. Acts by decreasing hormone-sensitive lipase and increasing apoA1.
fibric acid derivatives (fibrates)
cause a marked reduction in VLDL, small effect on LDL, 10% increase in HDL. effects are mediated by binding to PPARa. Primary effect is to stumulate lipoprotein lipase synth, which clears TG-rich lipoproteins. Can cause rhabdo, dont use with statins
bile acid sequestrants (resins)
anion-exchange resins that bind bile acids in the intestines. not absorbed. bind bile acids and are secreted in poop. decreases LDL 20%, but increases TG 5%. safe but interferes with absorption of fat soluble vitamins, cardiac glycosides, coumarin anticoagulants. you get rid of bile salts so it causes body to take up cholesterol to make more bile salts
HMG-CoA reductase inhibitors (statins)
most effective, best tolerated. reduce LDL 20-55%, VLDL 25%, increase HDL 10%. rare hepatotoxicity and myopathy. Can counter osteoporosis, and cardioprotective.
ezetimibe (zetia)
new. inhibits both dietary and biliary cholesterol absorption in the intestine by blocking a sterol transporter on the enterocyte. reduces amount of cholesterol delivered to the liver. Lowers LDL by 18%, synergistic with statins. Few side effects, but no studies done yet
PCSK9 inhibitors
PCSK9 is an endopeptidase that targets LDL receptors for degradation. Inhibition of this allows more LDL receptors and you can remove more LDL from the blood. two out now are Alirocumab and evolucumab.
