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Cholesterol PharmMal
Cholesterol lowering drugs- Dr. Maloney
| Question | Answer |
|---|---|
| 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
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