Hyperlipidimia Flashcards
Progression of events in Classic Angina
- High Cholesterol - no symptoms
- Stable Angina - symptoms w/ exertion
- Unstable Angina - symptoms increase in frequency and occur at rest
- Acute MI - complete occlussion
* Acute HF/Congestive HF/Cardiac Arrhythmias
Classic angina is the consequence of _______…
Atherosclerotic plaque formation in the coronary arteries
What does an atherosclerotic plaque consist of?
- Cholesterol deposits and cell components
2. Platelets (white thrombi) and fibrin “Cap”
What drugs are used to prevent atherosclerosis in coronary arteries?
- Cholesterol-Reducing Drugs
- Antiplatelet drugs
What diseases is high cholesterol associated w/?
- Coronary Heart Disease - #1 killer of americans
* High triglyceride levels also increase the risk of CHD - Stroke
Lipoprotein anatomy
Core of nonpolar lipids
Surrounded by protein and polar phospholipids
Carry Cholesterol
Good to bad lipoproteins
HDL = good
VLDL and LDL = bad
Normal Lipids Metabolism (6 steps)
- Chylomicrons
- Lipoprotein lipase
- VLDL + triglycerides in liver to Circulation
- Lipoprotein lipase = IDL -> Liver or LDL
- LDL delivers cholesterol to cells by binding to LDL Receptor
- HDL is synthesized by liver
Hypertryglyceridemia has increased _____ and some risk for ____ and _____.
- VLDL
- CHD
- Pancreatitis
Hypercholesterolemias have increased _____ and high risk for _____.
- LDL
2. CHD
Primary Hyperlipidemias - how are they determined and what are they a result of?
- Genetically Determined
2. Hyperlipoproteinemias
Type IIa hypercholesterolemia - what is it?
Defect in LDL receptors prevents LDL transfer into liver and extrahepatic cells resulting in increased blood cholesterol available to affect the arteries
PRIMARY HYPERLIPIDIMIA
What are seconary hyperlipidiemias?
Secondary to other conditions, such as diabetes, hypothyroidism, increased estrogen… etc…
What is the most common form of hyperlipidia? What are the factors?
Multifactorial
- Genetic
- Lifestyle
- Diet
2 Basic strategies of treating hyperlipidimia
- Decrease amount of lipid entering blood
2. Improve clearance of lipids from the blood
How to decrease amount of lipid entering blood? (3)
- Low fat, low calorie diets (1st line of defense)
- Drugs that reduce lipoprotein Synthesis
- Drugs that reduce dietary cholesterol absorption
How to improve the clearance of lipid from the blood (3)
- For VLDL - involves the enzyme lipoprotein lipase
- For LDL- involves LDL receptors: the less cholesterol in the liver, the more LDL receeptors will be synthesized
- More LDL Receptors = More effecient removal of LDL from the blood
What drugs are used to treat hypertriglyceridemia? (2)
- Niacin
2. Fibric Acid Derivatives
What drugs are used to treat hypercholesolemia? (5)
- Bile-acid binding sequestrants
- Statins
- Ezetimibe
- Niacin
- Combo therapy
What is the primary carrier of triglycerides?
VLDL
What is the most effective drug at increasing HDL and moderately decreasing LDL?
Niacin
What are the SE of Niacin?
Harmless flushing reaction, pruritis
What drug is a fibric acid deriviative? What does it do?
Gemfibrozil - most effective drug at reducing VLDL (50%) but minimal effects on LDL and HDL - only for hypertriglyceridemia
What are 2 mechanisms that drugs can target to reduce hyperlipidimia: triglycerides?
- Inhibit VLDL synth in liver (fish oils also do this)
2. Stimulate breakdown of VLDL by lipoprotein lipase in the blood
What are the differences between Niacin and FA derivatives in terms of LDL levels?
- Lipoprotein lipase increases LDL
Niacin produces a net decrease in LDL
FA Derivatives have no net effect on LDL
What drug is a bile acid sequestrant?
Colesevelam
What does colesevelam do?
Reduce LDL (cholesterol), increase HDL Prevents bile acid re-absorption, causes greater conversion of cholesterol to bile acids and lower liver cholesterol levels
SE of colesevelam?
GI (nausea, bloating), reduced absorption of folic acid
What are statin drugs?
HMG-CoA reductase inhibitors
What is a Statin Drug?
Atorvastatin (lipitor)
What is HMG-CoA redudctase do?
Liver enzyme that synthesizes cholesterol
What happens to LDL when cholesterol synthesis is reduced?
LDL receptors are upregulated, resulting in increased removal of LDL from the blood
How well does atorvastatin work?
Decrease cardiac events by up to 60% and stroke up to 70%
Modest increases in HDL and decreases in VLDL (less than niacin though)
What drug is taken orally before bed?
Atorvastatin
What is the efficiacy of statins at Low, Medium, and High doses?
Low: pravastatin, lovastatin
Medium: simvastatin, pitavastatin
High: atorvastatin rosuvastatin
SE of Statins
Usually safe w/ mild GI SE
- Low liver tox
- Memory loss
- Diabetes risk
- Potential teratogens
- Myopathy
* interacts w/ grapefruit juice
What drug can produce myopathy with a risk for Rhabdo?
Statins
What are the symptoms of a myopathy?
- Muscle pain
- Muscle atrophy
- Fatigue
- Dark urine
- Elevated blood creatine kinase lvls
What is rhabdomyolysis?
Skeletal muscle cell lysis and release of muscle contents into the circulation, potentially resulting in kidney failure and death
Is risk of myopathy and rhabdo related to efficacy?
No: lovastatin and simvastatin have higher risk than a atorvastatin/rosuvastatin
*CYP inhibitors increase risk
What is the newest approved anti-cholestrol drug? What does it do?
Ezetimibe
- Inhibits intestinal absorption of dietary cholesterol
- Reduces LDL elvels
- GI SE
What is Vytorin and what was it a part of?
Ezetimibe and simvastatin
Part of Enhance study
What is the enhance study?
Vytorin produced greater reduction in LDL than simvastatin alone
No difference in coronary atherosclerotic plaque formation
Implications of enhance study?
- Vytorin is no more protective vs CHD than statin monotherapy; questions efficacy of ezetimibe
- Suggests effectiveness of statsin versus CHD may not only involve reductions in LDL, potential anti-inflammatory effects
What is niaspan and what study was it a part of?
Niaspan = extended release niacin
Government study examining benefit of adding niaspan to statin
Results of AIM high study
- Niaspan failed to educe risk for Heart Attack vs placebo
- Risk for stroke was slightly INCREASED
- Benefit of increasing HDL and reducing LDL for prevention of HD and Stroke now in question
What does PCSK9 do?
Breaks down LDL receptors, deceasing number of receptors that get recycled
- variants of gene are associated w/ significant alterations in circulating LDL levels
- Several PCSK9 inhibitors are in development
What is Praluent?
First FDA approved PCSK9 Inihibitor
What does praluent do? When is it prescribed? How is it used?
Antibody that binds and inhibits PCSK9
Approved for cases where statins and diet are insufficient
Injected subcutaneously
ACC and AHA guidelines for statin treatment
- Individuals Diagnosed w/ CHD (history of HA, angina, stroke, IA, PAD)
- LDL > 190mg/dL
- Diabetics 40-75y/o w/o clnical ASCVD and LDL 189mg/DL who have estimated HD risk > 7.5% and 40-75 y/o
