Anti Hyperlipidemia Flashcards
EPA, DHA, Lovaza class
omega 3 fatty acids
EPA, DHA, Lovaza description/mechanism
With long term use, they can increase HDL
Decrease TAG synthesis and increase fatty acid oxidation in the liver
Adverse-> may increase total LDL as they decrease TAG
Ezetimibe class
Cholesterol Absorption Inhibitors
Ezetimibe description
Inhibits absorption of cholesterol -> increase synthesis
Decrease LDL; Increase HDL
-Complementary actions to statins
Ezetimibe mechanism
Inhibits intestinal transport protein which takes up cholesterol from the lumen, decrease absorption -> decrease chylomicrons -> upregulation of LDL-r and increased clearance
Ezetimibe adverse
Impaired hepatic function (reversible)
Myositis
Increases cholesterol synthesis
Cholestyramine, Colestipol, Colesevelam class
Bile acid binding resins
Cholestyramine, Colestipol, Colesevelam description
H2O insoluble
Charged, high MW -> NOT absorbed or metabolized
Completely excreted in the feces
Cholestyramine, Colestipol, Colesevelam mechanism
Binds the anionic bile acids in the intestine -> prevents reabsorption -> increased produciton in the liver -> decreased production in the liver -> decreased intracellular cholesterol -> upregulate LDL-r -> increased plasma clearance of LDL
Modest increase in HDL
Cholestyramine, Colestipol, Colesevelam indication
only useful in patients with isolated high LDL
Use in combination with statins or niacin
DOC for pregnant women (category B) and children
Cholestyramine, Colestipol, Colesevelam adverse
GI (bloating, cramps, nausea, constipation)
Colesevelam has less AE
Contraindicated with increased TAGs -> may increase TAGs and VLDL
Non specific binding -> may decrease absorption of some drugs and fat soluble vitamins
Gemfibrozil, Fenofibrate class
Fibrate derivatives
Gemfibrozil, Fenofibrate description
Decrease TAG
Modest decrease of VLDL
Increase HDL
Gemfibrozil, Fenofibrate mechanism
Activates PPAR-alpha (peroxisome proliferator activated receptor) which is expressed in the liver and brown adipose tissue
In combined disease: increase LDL with a decrease in TAG
Gemfibrozil, Fenofibrate indication
Hypertriglyceridemia
Dysbetalipoproteinemia
Gemfibrozil, Fenofibrate adverse
Mild GI disturbance
Myositis (patients with renal insufficiency)
Rhabdomyolysis
Cholelithiasis due to increased cholesterol excretion
Niacin (nicotinic acid) description
Increase HDL
Decrease VLDL, LDL and La(a)
Only one that decreases Lp(a)
Niacin (nicotinic acid) mechanism
Activates Gi -> decreases cAMP -> decreases PKA -> Inhibits HSL: decreased plasma FFA sent to liver -> decreases TAG synthesis -> decreases VLDL production/release
Activates LPL -> increase uptake of LDL, Decrease HDL catabolism
Decrease fibrinogen, increase t-PA -> reverses endothelial dysfunction
Niacin (nicotinic acid) indication
Adjuvant therapy with statins
Niacin (nicotinic acid) adverse
Intense cutaneous flush: PG-mediated so it can be blocked by prior administration of aspirin
Pruritis, rash, dry skin
Acanthosis nigricans
Hepatotoxicity (increased serum tansaminase levels)
Insulin resistance -> severe hyperglycemia
Increase uric acid -> gout
Rosuvastatin, Atorvastatin, Simvastatin, Fluvastatin, Lovastatin, Pravastatin class
HMG-CoA reductase inhibitor “Statins”
Statins description
Analogs of HMG Pleiotropic effects: Increased endothelial function Decreased platelet aggregation Decreased Inflammation Decreased plasma CRP Decreased LDL
Statin mechanism
Competitive inhibition of HMG-CoA reductase (rate limiting step in cholesterol synthesis) -> decrease synthesis and intracellular depletion -> upregulation of LDL-r -> increase clearance of LDL from blood
Inhibit cholesterol synthesis and increase absorption
Statin indication
DOC for LDL reduction
Decrease CV mortality
Not as good of an effect for patients homozygous for FH due to lack of functional LDL-r
Best when used in combination with resins, niacin, or ezetimibe
