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68 Cards in this Set
- Front
- Back
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what is a lipoprotein
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a lipid-protein complex that transports lipids in the blood
Principal classes include HDL, LDL, VLDL, and chylomicrons |
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what is hyperlipidemia and what are two examples
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general term for elevated concentrations of lipids in the plasma. Ex include hypertriglyceridemia and hypercholesterolemia
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transport exogenous, dietary cholesterol and triglycerides from small intestine to tissues after meals
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chylomicron
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transports triglycerides from the liver to adipose and muscle tissue
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VLDL
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formed in circulation when VLDL are degraded; transports cholesterol to extrahepatic tissues
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LDL
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intermediate lipoprotein formed during VLDL degradation to LDL
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IDL
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promotes the transport of cholesterol from extrahepatic tissue to the liver for excretion in the bile
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HDL
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what are factors tha increase LDL
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cholesterol, saturated and trans fats
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what are factors that increase TGs
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total fat, alcohol, and excess calories
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what are the dietary recommendations to decrease hyperlipidemia
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Total calories from fat: 20-25% of daily intake
Saturated fats: less than 8% of daily intake Cholesterol: less than 200 mg/day Serum cholesterol reductions can range from 10-20% |
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increased intake of omega 3 PUFAs has been shown to:
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modify membrane function, inhibit thrombus formation, decrease inflammation, lower plasma triglycerides, and alter the electrical activity of the myocardium
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eating fatty fish may be beneficial for who
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healthy people- but no evidence that fish oil supplimetn prevent cv disease in gen pop
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what is the rate limiting step in cholest synth
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HMG coa reduction to mevalonate by HMG COA recutase
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what is the MOA of statins
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inhibit HMG COA reductase
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where are Lovastatin and simvastatin hydolyzed and activated
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in the GI tract
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all statins are metabolized by __ except for pravastatin
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CYP450
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do statins undergo extensive first pass metab
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yes
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where is the primary action of statin
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on the liver
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what happens as a result of HMG COA reductase inhibition
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depletion of intracell supply of cholest, which causes the cell to increase the number of specific cell surface LDL receptos that can bind and internalize circulating LDL
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what are the therapeutic benefits of statins
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plaque stabilization, improvement of coronary endothelial function, inhibition of platelet thrombus formation, and anti-inflammatory effects
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what are the most potent statins and least potent
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most are: atorvastatin and rosuvastatic
least: fluvastatin |
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what is the overall therapeutic use of statin
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lowing plasma cholest in all types of hyperlipidemias
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what can statins be used in combo with
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resins, naicin, ezetimibe
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what are the best tolerated medicines for hyperlipidemia
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statins
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what are the liver side effects of statins
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elevations of serum aminotransferase activity (up to three times normal in patients with underlying liver disease or a history of alcohol abuse)
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what are the side effects of statins on muscle
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increase in creatine kinase activity; rhabdomyolysis; myopathy
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who are statins contraindicated in
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women who are pregnant, lactating, or likely to become pregnant
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avoid use of statins with what other agents
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that inhibit or compete with CYP450 enzymes (except for pravastatin)
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what is the most effective agent for increasing HDL levels
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niacin
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when is niacin commonly used
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combio with a bile acid sequestrant (resin) or statin in the treatment of heterozygous familial hypercholesterolemia, other forms of hypercholesterolemia, and some cases of nephrosis, and mixed lipemia that is incompletely responsive to diet
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Niacin is converted to ____and incorporated into nicotinamide adenine dinucleotide (NAD+)
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nicotinamide
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does niacin have inc first pass metab
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yes
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Nicotinic acid is a component of two coenzymes necessary for
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tissue respiration, lipid metabolism, and glycogenolysis
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what is the MOA of niacin
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inhibits the lipolysis of triglycerides in adipose tissue (the primary producer of circulating free fatty acids)
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what ab niacin can reverse some of the endothelial cell dysfunction causing thrombsis assoc with hypercholest and atherosclerosis
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fibringoen levels are reduced
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what are side effects of niacin
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Intense cutaneous flush accompanied by an uncomfortable feeling of warmth is the most common,Pruritus, rashes, dry skin or mucous membranes
Acanthosis nigricans – hyperplasia of the spinous layer of the skin with dark pigmentation (insulin resistance) |
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who is niacin contraindicated in
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pt with hepatic dz or active peptic ulcer
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what nuclear transcription factor receptor are fibric acid derivatives agonists of
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PPARalpha
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how long is half life of fenofibrate
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20 hr
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what is half life of gemfibrozil
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1.5 hr
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fibric acid derviatives induce expression of __ __ which causes lipolysis of triglycerides and decresaes in plasma conc
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lipoprotein lipase
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fibric acid causes vldl to __ LDL to __ and HDL to __
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dec
dec inc |
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what are the uses for fibric acid deriatives
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Hypertriglyceridemias where VLDL predominate
Dysbetalipoproteinemia Hypertriglyceridemia that results from treatment with viral protease inhibitors (e.g., saquinavir, indinavir, or nelfinavir for HIV therapy) |
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what are side effects of Fibrates
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GI disturbances are most common
Lithiasis; gallstones (cholelithiasis) Myositis, myopathy, rhabdomyolysis (avoid concurrent use with statins) |
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what are the contraindications of fibrates
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inc axn of coumarin and indanedione anticoagulants
Avoid in pts with hepatic or renal prob, not safe in pregnant or lactating women, Incr the risk of cholest gallstones due to an increase of bile cholest content caution in pt with biliary tract disease or those at high risk |
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what is MOA of bile acid sequestrants
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bind to negatively charged bile acids and increase their excretion up to 10 fold
- they are not metabolized or absorbed |
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increased excretion of bile acids enhance the conversion of __ to __ in the liver
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bile acids to cholest- the decline in hepatic cholest- causes inc expression of LDL surface recptos and lowers LDL levels
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what are uses of bile acid sequestrants
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Primary hypercholesterolemia
Type IIa and IIb hyperlipidemias Relief of pruritus in patients who have bile salt accumulation |
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what are side effects of bile acid sequestrants
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GI are the most common
Impaired absorption of fat-soluble vitamins (A, D, E, K) and numerous drugs (digoxin, warfarin, fluvastatin, aspirin, thiazides) Use caution in patients with diverticulitis, preexisting bowel disease |
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what is the MOA of ezetimibe
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selectively inhibits intestinal absorption of cholesterol and phytosterols (plant sterols); thought to inhibit the transport protein NPC1L1
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what can ezetimibe be used in combo with
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statins or fibrates
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ezetimiibe is Glucuronidated in the _- __ to an active compound
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intestinal ep
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what is the half life of ezetimibe
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22 hrs
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what is ezetimiibe used to treat
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Primary hypercholesterolemia
Homozygous familial hypercholesterolemia Mixed hyperlipidemia |
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avoid use of ezetimibe with__ due to absorption inhibition
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resin
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what are some examples of good anti hyperlipemic drug combos
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Niacin and bile acid sequestrants
Niacin and statins Statins and fibrates Statins and ezetimibe (Vytorin) |
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who will always need drug tx for hyperlipidemia- when will they start
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Patients with familial hypercholesterolemia or familial combined hyperlipidemia will always require drug therapy (children may initiate therapy with a resin or statin after 7-8 years of age (myelination of central nervous system is complete) based on LDL level, other risk factors, and family history)
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what statin is almost competely absorbed
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fluvastatin
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what is the half life of atorvastatin
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14 hrs
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vii) Lovastatin, simvastatin, and atorvastatin are metabolized primarily by ___; fluvastatin and rosuvastatin are metabolized primarily by ___; pravastatin is metabolized via other pathways such as sulfation
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CYP34A
CYP2C( |
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what drug interactions can happen with statins to cause myopathy
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cyclosporine, itraconazole, erythromycin, gemfibrozil, or niacin
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what is the approx half life of niacin
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60 min- which means 2-3x day dose
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how are fibrates excreted
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as glucuronide conjugates
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what class of drugs is ezetimiibe
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cholest absorption inhibitos
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what transport protein is ezetimibe thought to inibit
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NPC 1L!
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when are four instances when drug combo therapy is prob going to need to be used
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i) When VLDL levels are significantly increased during treatment of hypercholesterolemia with a resin
ii) When LDL and VLDL levels are both elevated initially iii) When LDL or VLDL levels are not normalized with a single agent iv) When an elevated level of Lp(a) or an HDL deficiency coexists with other hyperlipidemias |
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(6) Currently, drug treatment of hypercholesterolemia should aim at achieving LDL levels below ___ in high-risk patients;
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100 mg/dl
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for patients who cannot achieve these goals with a safe dose of a statin alone, adding____ is still a reasonable option
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ezetimibe (or niacin or a bile acid sequestrant
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