Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
36 Cards in this Set
- Front
- Back
Define Hyperlipidemia
|
- elevation of plasma cholesterol and/or TAG's or a low HDL level
|
|
Hyperlipidemia and Cardiovascular disease
|
- elevated levels of LDL or decreased HDL levels --> inc risk of cardiovascular mortality
- hypertriglyceridemia = another risk factor |
|
Type I - Familial Hyperchylomicronemia
|
- increased chylomicrons
- etiology = deficiency in LPL or apoCII - rare |
|
Type IIA - Familial hypercholesterolemia
|
- increased LDL
- etiology = decreased or no functional LDL receptor expression |
|
Type IIB - Familial combined hyperlipidemia
|
- increased LDL and VLDL
- etiology = overproduction of VLDL by the liver - relatively common |
|
Type III - Familial dysbetalipoproteinemia
|
- increased IDL
- etiology = abnormal apoE |
|
Type IV - Familial hypertriglyceridemia
|
- increased VLDL
- etiology = overproduction and/or impaired catabolism of VLDL - relatively common |
|
Type V = Familial mixed hypertriglyceridemia
|
- increased chylomicrons and VLDL
- etiology = increased prod or decreased clearance of VLDL and chylomicrons |
|
Secondary Hyperlipidemia
|
- most common in adults
- due to a sedentary lifestly w/ excessive dietary intake of saturated fat, cholesterol, and trans fatty acids |
|
Antihyperlipidemic Drugs
|
- HMG-CoA reductase inhibitors
- Niacin - Bile acid-binding resins - Fibrates - Cholesterol absorption inhibitors |
|
HMG-CoA Reductase Inhibitors (Statins)
|
- Atorvastatin - potent
- Fluvastatin - Lovastatin - Pravastatin - Rosuvastatin - potent - Simvastatin |
|
HMG-CoA Reductase Inhibitors (Statins) - MOA
|
- Statins are competitive inhibitors of HMG-CoA reductase, the enzyme that catalyzes the first committed step of cholesterol biosynthesis
- Statins deplete intracellular supply of cholesterol --> up-regulation of LDL receptors --> increased clearance of LDL from blood |
|
HMG-CoA Reductase Inhibitors (Statins) - Uses
|
- DOC for LDL reduction in all types of hyperlipidemias (reduce CV mortality)
- other: improve endothelial fxn, decrease platelet agg, reduce inflammation, dec plasma levels of CRP |
|
HMG-CoA Reductase Inhibitors (Statins) - Contraindications
|
- Homozygotes for familial hypercholesterolemia lack functional LDL receptors and so benefit less from tx w/ statins
- Contraindicated in pregnancy |
|
HMG-CoA Reductase Inhibitors (Statins) - AE
|
- Elevation of aminotransferases
- Myopathy and rhabdomyolysis (rare) - Creatine kinase levels should be determined regularly - Rhabdomyolysis may cause myoglobinuria --> renal injury |
|
Niacin (Nicotinic acid)
|
Most effective agent for increasing HDL and only agent that may reduce Lipoprotein A
|
|
Niacin - MOA
|
- inhibits adenylyl cyclase in adipocytes --> inhibition of adipocyte hormone-sensitive lipase --> decreased plasma free fatty acid transport to the liver --> decreased hepatic TAG synthesis
- decreases hepatic VLDL production and release (b/c of dec hepatic TAG synthesis) - increases LPL activity (promotes clearance of chylomicrons, VLDL, and TAG) - decreases catabolic rate of HDL (so increases HDL) |
|
Niacin - AE
|
- intense cutaneous flush
- admin of aspirin prior to niacin decreases the flush (which is PG mediated) - acanthosis nigricans**, pruritis, rashes, and dry skin - most serious = hepatotoxicity (elevated serum transaminases) and hyperglycemia - niacin-induced insulin resistance can cause severe hyperglycemia in pts w/ diabetes mellitus - niacin elevates uric acid levels and can precipitate gout |
|
Fibrates
|
- Gemfibrozil
- Fenofibrate - Fibrates lower VLDL levels and increase HDL levels |
|
Fibrates - MOA
|
- activate peroxisome proliferator-activated receptor-alpha (PPAR-alpha)
- PPAR-alpha receptors are expressed primarily in liver and brown adipose tissue and activation of these receptors --> decrease in plasma TAG levels and increase in plasma HDL - decrease in plasma TAG is caused by inc muscle expression of LPL, decreased hepatic expression of apoCIII, and inc hepatic oxidation of fatty acids |
|
Fibrates - Uses
|
- hypertryglyceridemiaa in which VLDL predominate
- dybetalipoproteinemia |
|
Fibrates - AE
|
- mild GI disturbances
- myositis; pts w/ renal insufficiency may be at risk; rhabdomyolysis rarely occurs - lithiasis; fibrates increase biliary cholesterol excretion, so may cause gallstones |
|
Bile acid-binding resins
|
- Cholestyramine
- Colestipol - Colesevelam |
|
Bile acid-binding resins - Uses
|
- hyperlipidemias involving isolated increases in LDL
- DOC for pregnant women and children - neither absorbed nor metabolized; totally excreted in the feces |
|
Bile acid-binding resins - MOA
|
- bind to anionic bile acids in the intestinal lumen and prevent their reabsorption
- resin-bile acid complex is excreted in the feces, thus preventing bile acids from returning to the liver by the enterohepatic circulation - reduction in bile acid conc --> hepatocytes to increase conversion of cholesterol to bile acids --> intracellular cholesterol decreases --> up-regulation of LDL receptors in the liver --> decreased plasma LDL |
|
Bile acid-binding resins - AE
|
- Colesevelam produces fewer GI adverse effects than cholestyramine or colestipol
- They may increase TAG: contraindicated in hypertriglyceridemia |
|
Cholesterol Absorption Inhibitors
|
Ezetimibe
|
|
Ezetimibe
|
- inhibits intestinal absorption of cholesterol and phytosterols
- primary clinical effect = lower LDL - small increase in HDL and mild decrease in TAG |
|
Cholesterol Absorption Inhibitors - MOA
|
- Ezetimibe inhibits an intestinal transport protein, which takes up cholesterol from the lumen --> 3 things
(i) - cholesterol syn increases (ii) - decrease in incorporation of cholesterol into chylomicrons (iii) - upregulation of LDL receptors, enhancing LDL clearance from plasma |
|
Cholesterol Absorption Inhibitors and Statins
|
Ezetimibe = complementary to statins:
Statins inhibit chol syn and inc chol absorption Ezetimibe inhibits chol absorption and increases cholesterol synthesis |
|
Cholesterol Absorption Inhibitors - AE
|
- low incidence of reversible impaired hepatic function
- small increase in incidence when ezetimibe given w/ a statin - myositis has been reported rarely |
|
Omega-3 Fatty Acids
|
- Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce TAG biosynthesis and increase fatty acid oxidation in the liver
- long-term = increased HDL - omega-3 fatty acids may increase total LDL as they lower TAG levels |
|
Omega-3 Fatty Acids - Drugs
|
Lovaza
- given as an adjunt to pts with very high TAG levels |
|
Antihyperlipidemic Drug Combinations - Uses
|
used when:
- pts unable to reach their LDL goal on a single drug - pts w/ combined hypertriglyceridemia and hypercholesterolemia that cant be controlled w/ a single drug - pts w/ high LDL and low HDL |
|
Antihyperlipidemic Drug Combinations
|
- statins + resin/ezetimibe
- vytorin = simvastatin + ezetimibe - advicor = combination of extended-release niacin + lovastatin - statin-fibrate combinations are associated with an increased incidence of severe myopathy and rhabdomyolysis |
|
Antihyperlipidemic Drugs in Pregnancy
|
Statins - ABSOLUTELY CONTRAINDICATED (Category X)
Fibrates, Niacin, Ezetimibe - Category C Cholestyramine and colestipol - might interfere w/ absorption of nutrients - Category C Colesevelam - Category B (used during preg only if clearly needed) |