Term
| what is the purpose of hypolipidemics? |
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Definition
| to treat hyperlipoproteinemias that cause atherosclerosis/CAD, increase the risk of mortality to heart disease and stroke, and treat hypertriglyceridemia that can cause acute pancreatitis |
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Term
| what is the first step in determining treatment of pts with hypolipidemics? |
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Definition
| assessment of risk status, presence of CAD/family hx, diabetes, HTN, smoker, age, and sex |
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Term
| what are the major lipids, how are they transported? what are apoproteins? |
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Definition
| cholesterol and triglycerides - which are transported as lipoproteins. apoproteins are surface proteins on lipoproteins that interact with tissue membrane receptors such as apoB100 for LDLs |
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Term
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Definition
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Term
| which lipoprotein do the bile acid resins bind to? |
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Definition
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Term
| how do VLDLs become LDLs? |
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Definition
| through the action of lipoprotein lipase |
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Term
| what is the main function of HDLs? |
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Definition
| to remove cholesterol from the arteries and tissues as well as inhibit oxidation of atherogenic LPs |
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Term
| how is risk associated with LP(a) determined? |
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Definition
| genetically, and it is a risk factor for CAD |
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Term
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Definition
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Term
| what is the general metabolism of cholesterol of hepatic origin? |
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Definition
| cholesterol is packed into golgi vesicles either from incoming lipoproteins or from the body's own production (via HMG-CoA reductase, which makes mevalonic acid - a cholesterol precursor). the liver sends out VLDLs which are degraded to LDLs by LPL, which give some of their apoproteins to HDL |
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Term
| what is normal in terms of LDL levels? |
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Definition
| <150 mg/dl (<100 if vascular disease) |
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Term
| how can LDL levels be calculated? |
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Definition
| LDL = total cholesterol - HDL - TG/5 |
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Term
| if the LDL/HDL ratio is above ______ then the pt is considered at risk for CAD |
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Definition
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Term
| what is the method of action for bile acid-binding resins? |
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Definition
| by ion exchange with bile acids, these prevent GI bile acid reabsorption back to the liver - preventing fats and cholesterols from being absorbed by the small intestine in the micelles that bile salts form |
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Term
| what is the result of using bile acid-binding resins? |
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Definition
| there is a compensatory increase in liver bile acid synthesis - liver LDL receptors are increased to take up/remove LDL cholesterol from the plasma - this is a beneficial effect |
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Term
| are bile acid-binding resins used in combination with any other drugs? |
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Definition
| yes, bile acid-binding resins are considered second line drugs and are often used in combination for synergistic effects w/statins, niacin, and fibrates |
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Term
| what are the three bile acid-binding resins that we need to know? |
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Definition
| cholestyramine, colestipol, and colesevelam (which has lower adverse affects - doesn't interact w/other drugs) |
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Term
| can bile acid-binding resins increased HDLs? |
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Definition
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Term
| what are ADRs for bile acid-binding resins? |
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Definition
| GI, nausea, bloating, belching, gas, heartburn, constipation, impaired absorption of fat sol. vitamins, impair absorption of drugs (esp acidic compounds, anticoagulants, diuretics, digitalis, and some statins **except colesevelam**), and it **may increase VLDL-triglyceride levels in pts with elevated TGs, due to increased liver TG synthesis |
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Term
| what is the M/A for HMG-CoA reductase inhibitors (STATINS)? |
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Definition
| HMG-CoA reductase inhibitors are competitive inihibitors of HMG-CoA reductase (they bear a strong structural similarity to mevalonate) in their rate limiting step - which significantly reduces endogenous liver cholesterol synthesis |
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Term
| what is the effect of HMG-CoA reductase inhibitors (STATINS) on LDL and LDL receptors? |
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Definition
| plasma LDL is decreased b/c HMG-CoA reductase inhibitors force an increase in LDL receptors, which then increases the intake of plasma LDL |
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Term
| when is the best time for HMG-CoA reductase inhibitor (STATIN) administration? |
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Definition
| in the evening due to the diurnal pattern of cholesterol synthesis *except for pravastatin, whose absorption is increased with food* |
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Term
| what is the synergistic effect of combining statins and bile acid binding resins? |
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Definition
| endogenous cholesterol production is blocked and bile acids are not retained, each individually lowering the cholesterol level and both contributing to increased LDL receptors which increase the level of plasma LDL being taken up |
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Term
| what are the statins (HMG-CoA reductase inhibitors) we should know? |
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Definition
| rosuvastatin, atorvastatin, simvastatin, lovastatin, and pravastatin |
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Term
| do statins decrease TGs? increase HDLs? how do they affect vascular disease? |
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Definition
| statins decrease TGs, increase HDLs, and inhibit platelet aggregation/decrease inflammatory markers/increase fibrinolysis/and **increase endothelial function - eNOS upregulation/activity (increase vasodilation) |
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Term
| what are the ADRs associated with statins? |
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Definition
| increased liver *AST, *ALT, CPK (creatine phosphokinase). hepatitis, myopathy, (increased myoglobin can lead to renal failure) myositis w/flu-like symptoms, rhabdomyolysis, rash, pruritus, dryness, carcinogenicity, teratogenicity, interactions with DMMS inhibitors/inducers - and contraindicated w/liver disease, alcoholism, after sx, and severe trauma |
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Term
| what is the M/A for ezetimibe? |
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Definition
| ezetimibe inhibits jejunal enterocyte uptake of cholesterol by decreasing incorporation into chyolmicrons |
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Term
| how does ezetimibe affect TGs and HDL? |
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Definition
|
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Term
| can ezetimibe be administered with statins? |
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Definition
| yes, usually simivistatin |
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Term
| what is the effect of niacin administration? |
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Definition
| niacin/nicotinic acid/vit B3 inhibits adipose lipolysis (inhibiting intracellular lipase which releases FAs from triacylglycerol in the fat stores), decreases FA and thus supply to the liver - which decreases VLDL/LDL synth and increases HDL. **it also lowers Lp(a) |
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Term
| what ADRs are associated with niacin? how is this combated? |
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Definition
| intense cutaneous vasodilation/vasomotor flushing/pruritis - prostaglandin activated, therefore preemptive ASA dose 30 min before can help prevent. AST and ALT hepatic transaminase enzymes can also be elevated, there is some risk of hepatitis/hepatic necrosis, and hyperglycemia/glucose intolerance, and **hyperuricemia/gout |
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Term
| can niacin be combined with other hypolipemics? |
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Definition
| yes, niacin is combined with lovastatin, which further decreases LDL and increases HDL |
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Term
| what are contraindications/precautions for niacin? |
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Definition
| pts w/diabetes, peptic ulcers, liver disease, pregnancy, and **gout |
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Term
| what is the mechanism of action for fibric acid derivatives? |
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Definition
| fibric acid derivatives can activate nuclear receptors in liver/muscle that **increase lipoprotien lipase, increasing FA oxidation, which decreases TG synthesis and VLDL production and increases HDL (due to increase in apoAI/II) |
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Term
| what drug is considered first line for hypertriglyceridemia? |
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Definition
| fibric acid derivatives such as gemfibrozil |
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Term
| what are ADRs associated with fibric acid derivatives such as gemfibrozil? |
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Definition
| GI disturbances, cholecystitis, **gallstones, increased liver enzymes/hepatitis, myositis/myopathy and caution when used with statins ** except rosuvastatin for hyperlipoproteinemia** also - rash/allergy risk |
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Term
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Definition
| a newer fibric acid derivative also approved for hypertriglyceridemia that decreases TG/VLDL synthesis, but decreases LDL more favorably than gemfibrozil. it increases HDLs 10-20% |
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Term
| what are ADRs for fenofibrate? |
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Definition
| same as gemfibrozil, but lower incidence of myopathy and GI effects |
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Term
| what is a potential ADR for administration of bile acid binding resins and pts w/hypertriglyceremia? |
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Definition
| bile acid binding resins can raise TG and VLDL cholesterol concentrations |
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Term
| what is a specific ADR for the statins? |
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Definition
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Term
| what is the major increased risk of gemfibrozil administration? |
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Definition
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