Cholesterol lowering drugs- Dr. Maloney
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| Three sources of cholesterol for the liver | Diet (absorbed by small intestine), De novo synthesis, lipoproteins that are reabsorbed
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| Rate limiting enzyme in cholesterol synthesis | HMG CoA reductase
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| HMG CoA reductase inhibitors | -Statins
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| Mechanism of action for HMG CoA reductase inhibitors | Upregulated LDL receptors which removes LDLs from circulation
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| Trigs that are decreased by drugs are found in the ____ mainly on ______ | Blood, VLDLs
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| How do statins reduce triglycerides | Decrease VLDL sythesis(Less cholesterol for VLDL synthesis) and increase clearance of IDLs (Upregulation of LDL receptors)
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| Statin end results on LDL, TG, and HDL | LDL- Large decrease, TG- Modest decrease, HDL- Modest increase
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| The greatest LDL lowering effect is seen with statins at which dose | Starting dose
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| Statins effect on C reactive protein | Decrease causing a decreased inflammation
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| The only class of drugs to demonstrate clear improvements in overall mortality in primary and secondary prevention | statins
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| Short life Statins and when to take them | Take them at night- Lovastatin, Simvastatin, Fluvastatin, Pravastatin (Love Sims for Pop)
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| Why taken statins at night? | Hepatic cholesterol synthesis is maximal between 12-2am
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| Statin side effects | GI symptoms, Elevation of hepatic transaminases, Myalgia,, Myositis (increase creatine kinase levels!), Rhabdomyolysis
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| Statin Drug interactions | Fibrates (especially gemfibrozil), Niacin, CYP3A4 inhibitors
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| Statin Contraindications | Active hepatic disease and pregnancy/lactation
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| What is cholesterol used for in the liver? | Lipoproteins and Bile
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| Bile Acid Binding Resins | Cholestyramine, Colestipol, Colesevelam,
C(h)OLE-
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| Mechanism of action for Bile Acid binding resins | Prevents bile acid recirculation which increases cholesterol requirement in the liver to make more bile which in turn upregulated LDL receptors
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| Can you combine a statin and a bile acid binding resin? | YEP!
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| Bile acid binding resin end results on LDLs, TGs, and HDLs | LDL- Modest decrease, TGs- possible increase, HDL- small increase
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| Why take a BABresin before a meal | Eating stimulates bile acid release
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| BABresin adverse reactions | Constipation, Impaired absorption of anionic drugs, Impaired absorption of fat soluble vitamins (A, D and K)
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| When should you take other drugs in relation to taking a BABresin | 1 hour before of 4 hours after
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| Cholesterol Absorption Inhibitors | Ezetimibe
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| Which transmembrane protein is essential for the transport of free cholesterol from the gut lumen into the enterocyte | Niemann-Pick C1-like1 protein (NPC1L1)
Who the fuck names these things?!
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| Method of action of Ezetimibe | Inhibits NPC1L1 to decrease cholesterol absorption by the gut which upregulates LDL receptors
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| Ezetimibe affect on Chylomicrons | Less chylomicrons are produced because there is less cholesterol
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| Which drugs upregulate LDL receptors | Bile acid binding resins, HMG CoA reducatse inhibitors, Cholesterol absorption inhibitor
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| Cholesterol Absorption Inhibitor End results on LDL, TG and HDL | LDL- Modest decrease, TG- Small decrease, HDL- Small increase
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| Cholesterol absorption inhibitors adverse reactions | GI upset
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| If trigs are above 500, what is your first line treatment | Gemfibrozil to reduce risk of pancreatitis
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| Which drugs are good at lowering trigs | Fibric acid derivatives, Niacin, Omega 3 fatty acids
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| Niacin mechanism of action | Inhibits DGAT2 which decreases TG synthesis in the liver which in turn decreases VLDL production
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| Fibric acid derivatives mechanism of action | Activates PPARalpha which increases expression of LPL to increase the catabolism of VLDLs to IDLs/LDLs. It also increases fatty acid oxidation which decreases TG and hence VLDLs
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| Would you give a Fibrate to a hypertriglyceridemia patient? | No because it can increase LDLs in that case
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| With high trig levels, you get what effect on LDLs | Small and dense (BAD!)
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| When trigs are reduced with niacin or fibrate, what is the effect on LDLs | You get a decreases productin of small, dense LDLs
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| If you are less large VLDLs (because of lowering trigs), what happens to the activity of CETP | Reduced
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| People with high trigs have high CETP levels which does what to HDL levels | Decreases because they are less stable and more easily cleared
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| Niacin and Fibrate effect on TG and HDLs | TG- large decrease, HDLs- large increase
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| Niacin side effects | Flushing (can be prevented with aspirin) and GI irritation
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| Niacin side effects | Abnormal liver function tests, hepatotoxicity, hyperglycemia, hyperuricemia
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| Niacin contraindications | GOUT, Diabetes, Ulcers, Chronic liver disease
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