antihyperlipidemias 57/58 Flashcards
Ezetimibe (Zetia)
Cholesterol Absorption Inhibitor
oral 1x day
inhibits a specific protein-mediated transport system on or within the brush border membrane of the intestinal wall cell
less delivery of cholesterol to liver via exogenous pathway, liver may compensate by taking up more LDL via up regulating LDL receptors
slight increase HDL
use: lower LDL type hyperlipoproteinemias, used with diet, statins
Converted to an active glucuronide metabolite in the small intestinal wall cells and in the liver where recycled back into the intestinal lumen via biliary system. This enterohepatic recirculation presents more active metabolite
excreted in feces
Cholestyramine (Questran)
Bile Acid Binding Resin
Colestipol (Colestid)
Bile Acid Binding Resin
Colesevelam (WelChol)
Bile Acid Binding Resin
*less SEs
Lovastatin (Mevacor)
HMG-CoA Reductase Inhibitor
prodrug which requires activation
Pravastatin (Pravachol)
HMG-CoA Reductase Inhibitor
active as ingested
Simvastatin (Zocor)
HMG-CoA Reductase Inhibitor
prodrug which requires activation
Atorvastatin (Lipitor)
HMG-CoA Reductase Inhibitor
active as ingested
now “combined” with the calcium channel blocker amlodipine (Caduet) to treat both high cholesterol and high blood pressure
Rosuvastatin (Crestor)
HMG-CoA Reductase Inhibitor
active as ingested
Gemfibrozil (Lopid)
Fibric Acid Analogue (Fibrate)
Enterohepatic recycling
Fenofibrate (Tricor, Triglide)
Fibric Acid Analogue (Fibrate)
prodrug
also ↑ hepatic LDL receptors via PPAR-α, thus ↓ plasma LDL levels more than gemfibrozil
Niacin (Niacor, Niaspan)
LOWERS LDL, RAISES HDL
inhibits intracellular (hormone-sensitive) lipase activity in adipocytes-->inhibits intracellular lipolysis in fat cells-->reduces the major source of fatty acids for hepatic triglyceride biosynthesis-->reduces plasma VLDL by indirectly inhibiting VLDL synthesis in the liver -leads to lower IDL & LDL
enhances the activity of the extracellular lipoprotein lipase–>increases VLDL catabolism
↓ levels of lipoprotein(a) (an unusual, small, highly atherogenic form of LDL)
↓clearance of HDL- apolipoprotein A-1–>considerably ↑ plasma HDL (most effective drug for this)
*tx for all primary forms of hyperlipidemias and isolated HDL deficiency
cheap! oral admin, short duration, some sustained release
-Metabolized to nicotinamide, the vitamin, which has no lipid lowering activity
Omega-3-Acid Ethyl Esters (Lovaza)
Highly purified concentrated preparation of ethyl esters of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids
other formulations (not listed in handout): Icosapent Ethyl (Vascepa) Omega-3-Carboxylic Acids (Epanova)
Mipomersen (Kynamro)
Lomitapide (Juxtapid)
newer, adjuncts to diet and other drugs in patients with HOMOZYGOUS familial hypercholesterolemia
decrease VLDL and LDL by inhibiting formation of apolipoprotein B-containing lipoproteins in GI and liver
Mipomersen: oligonucleotide type inhibitor, given subQ
Lomitapide: microsomal triglyceride transfer protein (MTP) type inhibitor, taken orally
SEs: serious liver toxicity (restricted availability thru REMS)
Alirocumab (Praluent) and Evolocumab (Repatha)
very new drugs, used for pts with atherosclerosis who require additional lowering of LDL cholesterol
“Statin-intolerant” patients
given subQ
SEs: non-specific GI, metabolic and neurocognitive reactions currently under FDA concern
many concern with increase in cholesterol:
atherosclerosis, a condition which can lead to ischemic coronary heart disease (CHD) with MI (Figure 1), and to CVAs
Some types of hyperlipidemias are also associated with an increased risk of pancreatitis and xanthomas in skin and tendons.
4 main risk factors for atherosclerosis: T2 DM smoking HTN hyperlipidemia
lipoproteins
central core of lipids (triglycerides and cholesterol esters) encased in a coat of phospholipids, free cholesterol and apoproteins (also called apolipoproteins)
chylomicrons do not contribute to atherosclerosis bc ??
they are too big
When plasma LDL rises ??
the rate of such oxidation and nonspecific uptake increases leading to atherosclerotic lesions
HDL
tiny, almost completely made up of cholesterol
exogenous pathway
cholesterol and triglycerides derived from the GIT (EXOgenous) are transported as chylomicrons to muscle and adipose tissue
LPL (EC) breaks down TAGs in chylomicrons–>FFAs–>taken up by fat cells–>TAGs
or–>skel musc for energy
taken up by liver–>bile made–>excreted in GIT for digestion aid
OR liver can make own VLDL (endogenous pathway begins)
**HMG-CoA reductase in liver is rate-limiting
VLDL from liver–>
(LPL)–>IDL–>LDL
can be taken up by liver via LDL receptor
or extra hepatic tissue take up LDL to make new cell membranes, hormones, etc via LDL receptors