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Cholesterol PharmMal

Cholesterol lowering drugs- Dr. Maloney

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