Treatment of Hyperlipidemias Flashcards
high molecular weight complexs of specific proteins and lipids, that transport triglycerides and cholesterol in the blood
lipoproteins
hyperlipidemias can lead to acute ______ (if triglycerides >1,000) and atherosclerosis
pancreatitis
- 4 major group of lipoproteins: chylomicrons, VLDL, LDL, HDL
- in general, ____ dense lipoproteins contain more triglyceride
larger, less dense
chylomicrons synthesized in the ______ transport dietary lipids into circulation, 20% of body’s cholesterol comes from food
enterocyte
VLDL synthesized in _______ transports fatty acids and cholesterol to peripheral tissues, account for 80% of body’s cholesterol
hepatocytes
VLDL is converted to ______ by further removal of ________ mediated by hepatic lipase, then catabolized in hepatocytes by receptor mediate endocytosis
LDL
triglycerides
_____ is responsible for transfer of cholesterol and apoliporporteins to the liver
HDL
elevated _____ is a major risk factor for atherosclerosis, any that is not taken up by hepatic receptors migrate into vascular intima
LDL
____ synthesized by liver and intestine decreased amt of cholesterol available for tissue deposition by removing it from macrophages and promoting its return to the liver
HDL
- high triglycerides (200-500)
- familial of unknown genetic cause
- fibrates are drug of choice
- rarly have familial lipoprotein lipase deficiency or apoCII deficiency
primary hypertriglyceridemia
- high cholesterol (260-500) with normal triglycerides
- familial: defects in LDL receptor, elevated cholesterol from birth, responds well to statins
- familial defective apoB100: decreased aff to LDL receptor
- polygenic
primary hypercholesterolemia
- complex lipid profile: elevated total cholesterol, LDL, triglycerides, reduced HDL
- familial combined: obesity, glucose intolerance, HTN, require statins
- dysbetalipoproteinemia: defect in apoE, increased chylomicrons and IDL like particles, treat with niacin and fibrates
mixed hyperlipidemia
decision to treat cholesterol levels is based on?
risk of CV disease
-statins are what drug class?
HMG-CoA reductase inhibitors
nicotinic acid, vitamin B3 are what class?
niacins
gemfibrozil and fenofibrate?
fibric acid derivatives
colestipol, cholestyramine, colesevelam?
bile acid binding resins
ezetimibe?
intestinal sterol absorption inhibitor
- statins inhibit HMGCoA reductase to reduce hepatic formation of cholesterol and increase _________ in hepatocytes to lower plasma LDL
- decrease plasma triglycerides and increase HDL cholesterol
- prodrugs: ?
- active: atorvastatin, fluvastatin, rosuvastatin, and pravastatin
- GI absorption is almost complete for fluvastatin
- all have high _____ metabolism and mostly excreted in ______
LDL receptors
lovastatin, simvastatin
first pass hepatic
bile
statins are first line therapy for elevated _____ levels, significantly reduce mortality from MI and in CVD patients at high risk, best given at night when _______ occurs, contraindicated in pregnancy
LDL
cholesterol synthesis
- statin toxicity indicated by elevations in serum _______
- macrolides, cyclosporine, ketoconazole, fibrates, grapefruit juice, phenytoin, rifampin, amiodarone inhibit or compete for CYP enzymes
aminotransaminase
______ not metabolized by P450, preferred in combo with other drugs
pravastatin
statins: increased ________ activity indicates skeletal muscle toxicity occurring as rhabdomyolysis
creatine kinase
_____ may enhance the myopathic effect of statins
gemfibrozil
- water soluble vitamin converted to amide, incorporated into NAD and excreted in urine
- decreases lipase activity in adipose tissues, reduce FFA flux to liver, decrease synthesis of triglycerides and VLDL, lower plasma LDL and triglycerides
- drug of choice for patients with elevated LDL and lowered HDL
- toxicity: cutaneous flushing, due to PGs, reduced w/ aspiring, increased uric acid and fasting glucose
niacin (B3, nicotinic acid)
- ligands for PPAR-alpha in hepatocytes
- decrease plasma triglycerides, VLDL, LDL, increase plasma HDL
- used for treatment of hypertriglyceridemia and dysbetalipoproteinemia
- skin rash, hypokalemia, decrease in WBC
- avoid in renal or hepatic dysfunction, risk of myopathy with statins, risk for cholesterol gallstones
fibric acid derivatives - gemfibrozil and fenofibrate
- found in fish oils
- activate PPARalpha
- profound reduction of triglycerides
omega 3 fatty acids
- large cationic exchange resins, insoluble in water
- bind bile acids and increase excretion
- 7a-hydroxylase upregulated, for synthesis of bile acids from cholesterol
- increased bile acid synthesis = reduced amt of heptic cholesterol
- increases LDL receptors, enhances removal from circulation
- lowers plasma LDL and elevates plasma HDL
bile acid binding resins: colestipol, cholestyramine, colesevelam
- used for primary hypercholesterolemia
- might increase VLDL
- digoxin toxicity
- possibly decreased absorption of fat soluble vitamins, bloating and constipation
bile acid binding resins
- inhibits intestinal absorption of cholesterol and phytosterols
- reduces plasma LDL and minimal increase in HDL
- for treatment of primary hypercholesterolemia
- low incidence of reversible hepatic impairment
eztimibe
drug combos when:
- VLDL levels increasing during ____ therapy of hypercholesterolemia
- VLDL and LDL both elevated, or not normalized by single drug
- ____ deficiency with other hyperlipidemias
resin
HDL
