Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/36

Click to flip

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)