Term
| Name a few of the modifiable risk factors for development of athersclerosis |
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Definition
| smoking, physical inactivity, obesity, hypertension, DM, increased CRP, increased coagulation factors |
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Term
| How do ACE inhibitors and NO synthesis agonists prevent atherosclerosis? |
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Definition
| They improve endothelial function |
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Term
| How does Vit C and E, estrogens, and folic acid supplements prevent atherosclerosis? |
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Definition
| They are all antioxidants which in turn reduce the inflammatory process of atherosclerosis |
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Term
| What is the apoprotein unique to chylomicrons? |
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Definition
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Term
| What apoproteins do chylomicrons acquire in circulation? what are their uses? |
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Definition
acquire Apo-C and Apo-E from HDL.
ApoC promotes interaction of chylomicrons w/ LPL on endothelium, adipose, cardiac, and skeletal muscle tissue.
ApoE mediates the removal of the chylomicron remnant by the liver. |
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Term
| VLDL apoproteins and functions |
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Definition
| VLDLs are synthsized by the liver tpo deliver cholesterol to the tissues. packaged w/ ApoB100 and acquire ApoC and ApoE from circulating HDL's. ApoC mediated interaction w/ LPL. ApoE mediates uptake of the remaining IDL into liver. |
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Term
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Definition
IDLs are VLDLs that have lost most of their triglycerides and cholesterol. They may be uptaken by the liver via ApoE or have their ApoE and ApoC removed to form LDLs.
Remember that this will leave the newly formed LDL w/ ApoB100. |
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Term
| What is the main pathway by which LDL is removed from circulation? |
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Definition
LDL uptake is done via the liver LDL receptor that recognizes ApoB100.
Expression of the LDL receptor is controlled by the levels of intracellular cholesterol. |
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Term
| What occurs with lipoproteins under conditions of cholesterol excess? |
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Definition
| prepheral cells synthsize transporters of CH to ApoA1 proteins (immature HDL. The CH is then esterified by LCAT and handed to an apoB containing lipoprotein for delivery back to the liver. |
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Term
| Under what conditions will hepatic liver cells display high levels of LDL receptors? |
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Definition
| When the intracellular concentration of cholesterol is low. This will lead to a decrease in circulating LDL levels. |
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Term
Type IIa hyperlipoprotenemia is caused by what and what will the blood results show?
Treatment and atherosclerosis risk? |
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Definition
caused by a defect in the liver LDL receptor -> increased plasma cholesterol.
Note: Triglycerides not affected
treat w/ statins and are at high risk for atherosclerosis. |
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Term
| Type IIb hyperlipoprotenemia will show what on lab results? |
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Definition
high CH and TGs.
treat w/ statins, fibrates, and nicotinic acid. High risk of developing atherosclerosis |
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Term
Type I hyperlipoproteinemia will show what on blood work?
Treatment and atherosclerosis risk? |
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Definition
see slightly elevated CH w/ marked elevation of TGs.
no change in risk of atherosclerosis and no treatment necessary |
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Term
| What are the acceptable levels of LDL, HDL and total cholesterol in the blood? |
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Definition
Total: less than 200. 240 is borderline high risk
LDL: less than 130, 160 is borderline high risk
HDO: 60 or more. 35 or less is borderline high risk. |
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Term
| IF a pt has 3 known risk factors for atherolsclerosis, what should their LDL be? |
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Definition
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Term
| If a pt has CHD, what should be the target LDL level? |
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Definition
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Term
| If a pt has CHD and other risk factors, what should their LDL be? |
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Definition
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Term
| HMG-CoA reductase inhibitors are also knows as what class of drugs? Name 3 examples |
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Definition
statins.
Simvastatin (zocor) - prodrug
Atorvastatin (lipitor) - long lasting
Rosuvastatin (crestor) - long lasting |
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Term
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Definition
inhibition of HMG-CoA reductase -> decreased synthesis of CH -> low intracellur CH -> increased expression of LDL receptors -> lower plasma LDL.
Low intracellular LDL decreases synthesis and release of VLDL |
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Term
| overall effect of statins? |
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Definition
significatn reduced LDL, small reduction in TGs and small increase in HDL
Longer lasting statins the better. |
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Term
Name a statin that can cross the BBB?
What do they cause if they cross? |
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Definition
simvastatin (zocor)
Lovastatin
Thus, these can cause insomnia |
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Term
| Special considerations for adminstering statins? |
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Definition
over 90% protein bound in plasma so careful if pt is on warfarin or digoxin.
Short acting (simvastatin) should be taken at night b/c CH synthesis is highest midnight - 2 am. |
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Term
| Name the cardioprotective effects of statins |
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Definition
Improves endothelial function via increasing NO synthesis
Stabilizes plaques
reduces CRP
Reduces LDL oxidation
Reduces platelet aggregation |
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Term
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Definition
Raised concentrations of liver enzymes indicating liver toxicity (monitor frequently)
Myalgia (may lead to myopathy)
GI disturbances
Insomnia
Rash
Category X |
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Term
| Risks of combining statins w/ fibrates or Niacin? |
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Definition
| Increased risk of myopathy if max doses are exceeded. |
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Term
| Under what conditions would you prefer to combine statins w/ fibrates? |
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Definition
| pt w/ high TG and high LDL. |
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Term
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Definition
| Gemfibrozil (lopid) Fenofibrate (lofibra) |
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Term
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Definition
Stimulate LPL
Peroxisome-proliferator associated receptor agonist (PPARa agonist) ->: causes increased LPL transcription, decrease VLDL release by liver, increased LDL uptake by liver, increased ApoA1 and AII which increases plasma HDL |
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Term
| Fibrate effect on lipid profile? |
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Definition
decreased TGs and VLDL
moderate reduction of LDL and increase in HDL |
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Term
| Disorder in which fibrates are the drug of choice? |
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Definition
| Type III hypertriglyceridemia |
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Term
| Pharmacokinetics of statins? route of administration? half life? excretion? |
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Definition
absorbed orally and widely distributed
half life 1-20 hrs
Primarily excreted via glucoronidation and renally. (monitor creatinine levels) |
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Term
| Side effects of fibrates? |
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Definition
statin side effects plus
GI symptoms
Pruritis
Rash
Lithiasis (formation of gallstones) if pt is taking clofibrate. |
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Term
| Contraindications to fibrates |
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Definition
| renal impairment clofibrate (ok if pt has no gallbladder) Category X drug |
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Term
| Name 3 bile acid sequestrants and 1 cholesterol transporter blocker |
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Definition
Colestyramine
Colestipol
Colesevelam
Zetia |
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Term
| when is it appropriate to use a bile acid sequestrant? |
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Definition
| only in combination w/ other drugs in treatment of severe dyslipidemias |
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Term
| Bile acid sequestrant MOA |
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Definition
decrease absorption of dietary CH leading to increased excretion of bile acids and salts in feces
causes increased synthesis of bile acids in liver which decreases hepatic CH levels -> increased LDL expression -> decreased plasma LDL
HDL not affected
Transient increase in TGs (not seen if pt is on combination therapy w/ statins or fibrates) |
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Term
| Side effects of bile acid sequestrants |
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Definition
low toxicity
GI disturbances -> bloating, dyspepsia
decreased absorption of fat soluble vitamins (K) -> reduced coagulation and leads to bleeding gums |
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Term
| What drugs will not be absorbed if the pt is on a bile acid sequestrant? |
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Definition
| fat solube drugs such as chlorathiazide, warfarin, and digoxin |
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Term
| Name a cholesterol uptake inhibitor |
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Definition
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Term
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Definition
| inhibits CH uptake by blocking CH transporter, NPCILI, in duodenum |
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Term
Indications for use of ezitemibe
When would you use it as a monotherapy? |
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Definition
adjunct w/ diet and statins in order to prevent the reflex increase in uptake of CH from the gut w/ statins.
Monotherapy use in pts who cannot tolerate statins |
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Term
| Side effects of ezitemibe (zetia) |
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Definition
diarrhea, abdominal pain, headache, rash, angioedema
Enters breast milk -> contraindicated in nursing mothers |
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Term
| Advantage of ezetimibe over BAS |
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Definition
| higher potency and does not affect fat soluble vitamin/drug absorption |
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Term
| Vytorin is the combination of what two drugs? |
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Definition
Zetia and zocor
ezetimibe and simvastatin |
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Term
| MOA of niacin (nicotinic acid) |
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Definition
| poorly understood. Inhibits hormone sensitive lipase and reduces formation/transport of FFA to liver and decreases TG synthesis |
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Term
| Effects of Niacin on lipids |
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Definition
| Decreases TG and VLDL production -> decreased plasma TG and VLDL and LDL. Increases HDL significantly |
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Term
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Definition
flushing and pruritis is common
palpitations
GI disturbances (dyspepsia)
Hepatotoxicity
impaired glucose tolerance
precipitates gout
causes birth defects |
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Term
| contraindications in niacin use |
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Definition
diabetics
pregnancy
gout pts |
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