Lipids

Front 1

Risk Factors for Coronary Heart Disease (CHD)
 Elevated LDL-C  Reduced HDL-C  Cigarette smoking  Hypertension  Obesity  Type 2 diabetes mellitus  Advanced age
◦ > 45 y/o males; > 55 y/o females
 Family history of premature CHD

Back 1

High HDL; low LDL -> good for CHD risk

Low HDL; high HDL -> more risk

Front 2

1. Oxidized LDL accumulation in macrophages leads to what type of cell formation?
2. 1 are a major constituent of what?
3. molecule that removes cholesterol from cells and transports it to the liver where it is eliminated

Back 2

1. Foam cell - excessive death of these can destabilize atherosclerotic lesions
2. Atherosclerotic lesion
3. HDL - low levels is an independent risk facotr for atherosclerosis and CVD

Front 3

give optimal total cholesterol, HDL, LDL and triglycerides
2. Rx approaches to hyperlipidemia?

Back 3

Total < 200, HDL 40->60, LDL <100, Tri < 150
2. Lifestyle modification, antilipemic drugs

Front 4

1. Dietary fats are absorbed from small intestine and packaged into waht?
2. What converts TGs in chylomicrons to FFAs for use in m. and storage in adipose tissue?
3. chylomicron remnants in blood are removed by what?
4. What does the liver use some cholesterol to make which is excreted into teh intestine?

Back 4

1. Chylomicrons
-- HDL contributes to apoC & apoE
2. Lipoprotein Lipase
3. liver
4. Bile acids

Front 5

1. What 2 things are packaged into VLDL in liver?
2. Lipoprotein lipase does what to VLDL?
3. What does CETP do?
4. how much of IDL is cleared in the liver?

Back 5

1. Triglycerides and Cholesterol
2. forms FFAs for muscle and adipose tissue
3. exchanges apoC and apoE and cholesterol from HDL for TGs from VLDL
4. 1/2

Front 6

1. What happens to 1/2 of IDL that is not cleared by the liver?
2. Clearance of LDL from plasma is mediated by what?

Back 6

1. it is formed into LDL by LPL and HL
2. binding to LDL receptors in liver followed by exoctytosis

Front 7

Fibric acid derivatives,cholesterol absorption inhibitor statin, bile acid sequestrants, fish oil, red yeast rice, niacin: MA:
1. Inhibits HMG- CoA
2. Activates nuclear transcription factor peroxisome proliferator actiavate receptor - alpha
3. activates a GPCR on adipocytes; decreases delivery of FFAs to the liver
4. blocks NPCILI which stops absorption of dietary and biliary cholesterol
5. binds to bile acids in the intestine -> bile stays in stool;; can't be reabsorbed

Back 7

1. Statin - Reduce LDL 18-55% & TG 7-30%, Raise HDL 5-15%
2. Fibric acid
3. Niacin -> increases HDL syn.
4. cholesterol absorption inhibitor
5. Bile acid sequestrants

Front 8

1. Inhibition of HMG-Coa does what?
2. Protein that upregulates expression of LDL R gene?
3. Cause of myopathic syndromes in statins?
Statin Therapeutic effects: reduce coronary events, CHD mortality, coronary procedures, stroke mortality

Back 8

1. decreases the production of cholesterol at an early step. The decrease in cholesterol leads to upregulation of genes that encode the LDL receptor, more LDL R, greater LDL intake in hepatocyte
2. SREBP
3. Decreased synthesis of coenzyme Q10 (ubiquinone) - a role in m. cell enrgy; accumulation of plant sterols, odd fatty acid oxidation,

Front 9

Statins BE:
Improve endothelial fxn (^ NO production), decrease platelet aggregation, reduce inflammation, plaque stabilization
AE: myopathic: myalsgia, Myositis get CK, Rhabdomyolysis (can be life threatening, MGB in blood, renal failure)

Back 9

Myopathic syndrome begins in weeks or months after start of Rx;;;

Front 10

1. 3 major AE of Statins?
2. What do you do to monitor myopathic syndromes?
3. When are statins C/I?
Pravastatin, fluvastatin, rosuvastatin are least effected by other drugs

Back 10

1. Myopathic syndromes (rhabodmylolysis), Hepatic issue (^ ALT, AST, serum billirubin) & Neural (neuropathy; memory loss)
2. Serum creatine Kinase -> if 3-10x ULN reduce dose or DC
3. Liver disease (monitor aminotransferase up to 3x ULN); Pregnancy; Combo w/ drugs that compete/inhibit CYP3A4

Front 11

1. Gemfibrozil, fenofibrate and fenofibric acid are part of what class of drugs?
2. Activation of PPAR alpha does what?
3. effective in lowering LDL levels?
TE: reduce prorgession of coronary lesions, reduce major events

Back 11

1. Fibric acid derivatives (fibrates
2. increases synthesis of apoA-I and apoA-II which leads to ^ plasma HDL; && drop TG synthesis
3. not very, but good decrease of TG

AE: GI disturbances; cholelithiiasis, hepatitis, myositis

Front 12

1. Contraindications of Fibric acid derivatives?
2. CI of statin drugs
3. CI of niacin
4. Bile acid sequestrants

Back 12

1. Severe renal or hepatic disease; may inhibit metabolism of other drugs. esp gemfibrozil
2. Liver disease (monitor aminotransferase up to 3x ULN); Pregnancy; Combo w/ drugs that compete/inhibit CYP3A4
3. liver disease, severe gout, peptic ulcer
4. Complete biliary obstruction, hypertriglycerides

Front 13

1. What is a water soluble discovered in 1937 (B3)
2. What is a key componeent of HDL syn?

Benefits: reduces major events; mb reduces mortality

Back 13

1. Niacin
2. apoA-I -> whose clearance is decreased by niacin via acting on the adipose GPCR
AE: Flushing (PGD and PGE mb), hyperglycemia, hyperuricemia (gout), upper GI distress, hepatotoxciity

Front 14

1. Ezetimibe is an e.g. of what?
2. Transporter that takes up cholesterol from micelles?
3. Fxn of ABCG5G8
4. Fxn of ACAT

Back 14

1. Cholesterol absorption inhibitor
2. NPCILI
3. Pumps cholesterol back into lumen
4. converts cholesterol to cholesterol esters

Front 15

1. Drug that decreases delivery of cholesterol from intestine to liver & amount of cholesterol stored in liver
AE of it: abdominal pain, diarrhea, arthralgia, myalgia, rhabomyolysis, hepatitis, allergic rxn

Back 15

1. Ezetimibe -> decreases plasma LDL, VLDL and upregulates LDL receptor

Front 16

1. Cholestyramine resin, colestipol & Colesevelam are e.g. of what?
2. How does liver respond to the above drugs?
3. What impact might these drugs have on TG?
AE: constipation, hrt burn, nausea, eructation, flatulence, bloating

Back 16

1. bile acid sequestrants
2. it converts more cholesterol into new bile acids to replace the old ones; drop in hepatic cholesterol increases LDL receptor expression, LDL is removed from the plasma
3. May increase

Front 17

1. What is a long-chain highly unsaturated omega-3 fatty acid present in cold water fish and oils/nuts?
2. What does this do?
3. How does it work? - no risk of rhabdomyolysis
4g/day; alternative to fibrates (if AE to fibrates)

Back 17

1. Fish oil
2. Decrease fasting TGs; increase HDL
3. Regulates SREBP and PPAR alpha to reduce hepatic TG productio and ^ triglyceride clearance

Front 18

1. What is the active ingredient of red yeast rice?
2. What does 1 do?
3. Drug class it is very similar to?

AE: active ingredient variew w/ strain of rice and from product to produce, not regulated by FDA, can cause myalgia and myopathy

Back 18

1. Monacolin -- contains various plant sterols, isoflavones and monounsaturated fatty acids
2. inhibit HMG CoA reductase -- same active ingredient as lovastatin
3. statin

Front 19

Bile acid sequestrants, Niacin, Statin, Gemfibrozil, Fenobibrate, Etezimibe, fish oil
1. Biggest ^ in HDL
2. Biggest drop in TG
3. biggest drop in LDL

Back 19

1. Niacin -> good for all lipoproteins/lipids -> increase HDL, decrease LDL & TG
2. Fibrate drugs & fish oil, may increase HDL
3. Statins - also lower TGs & other cardioprotective effects

Front 20

Drugs
1. More effective than other drugs in lowering LDL-C◦ Also lower TG’s ◦ Plus other beneficial cardioprotective effects
2. Lower TG’s 20-50% ◦ May increase HDL-C ◦ LDL-C may be lowered but may also be increased following reduction of high TG’s
3. ◦ Favorably affects all lipoproteins and lipids ◦ Increases HLD-C by 15-35% ◦ Decreases TG’s by 20-35% ◦ Decreases LDL-C 5-25%

Back 20

1. Statin - HMG-CoA reductase inhibitor
2. Fibric acid derivatives
3. Niacin

Risk: age, gender, smoking, TC, LDL/HDL ratio

Front 21

Drugs:
1. ◦ Reduces LDL-C ~ 18% ◦ Not much effect on TG’s or HDL-C ◦ Often combined with a statin  Statins prevent compensatory increase in hepatic cholesterol synthesis
2. ◦ Can lower LDL-C by up to 20% ◦ May or may not increase HDL-C ◦ May increase TG’s in PTX with hypertriglyceridemia

Back 21

1. Cholesterol absorption inhibitor Ezetimibe
2. Bile acid sequestrants

either < 100 mg/dL or > 30-40% of starting level for LDL:::: statins reduce CV risk by 20-30%

Front 22

ATP III recommendations for CHD
1st: initiate LDL Rx after 3 mo of lifestyle tharpy; w/ statins or bile acid sequestrant or niacin; return in 6wk
2nd: intensify LDL therapy if goal not achieve: w/ higher dose of statin or statin + bile acid or nicotinic acid; return in 6 wk

Back 22

High TG Rx w/ wt reduction/exercise, fish oils to replace some TG in diet, fibrates, Niacin

try to get HDL up: wt reduciton, physical activity, smoking cessation, Niacin