Treatment of Hyperlipidemias

Question 1

high molecular weight complexs of specific proteins and lipids, that transport triglycerides and cholesterol in the blood

Answer 1

lipoproteins

Question 2

hyperlipidemias can lead to acute ______ (if triglycerides >1,000) and atherosclerosis

Answer 2

pancreatitis

Question 3

• 4 major group of lipoproteins: chylomicrons, VLDL, LDL, HDL
• in general, ____ dense lipoproteins contain more triglyceride

Answer 3

larger, less dense

Question 4

chylomicrons synthesized in the ______ transport dietary lipids into circulation, 20% of body’s cholesterol comes from food

Answer 4

enterocyte

Question 5

VLDL synthesized in _______ transports fatty acids and cholesterol to peripheral tissues, account for 80% of body’s cholesterol

Answer 5

hepatocytes

Question 6

VLDL is converted to ______ by further removal of ________ mediated by hepatic lipase, then catabolized in hepatocytes by receptor mediate endocytosis

Answer 6

LDL

triglycerides

Question 7

_____ is responsible for transfer of cholesterol and apoliporporteins to the liver

Answer 7

HDL

Question 8

elevated _____ is a major risk factor for atherosclerosis, any that is not taken up by hepatic receptors migrate into vascular intima

Answer 8

LDL

Question 9

____ 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

Answer 9

HDL

Question 10

• high triglycerides (200-500)
• familial of unknown genetic cause
• fibrates are drug of choice
• rarly have familial lipoprotein lipase deficiency or apoCII deficiency

Answer 10

primary hypertriglyceridemia

Question 11

• 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

Answer 11

primary hypercholesterolemia

Question 12

• 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

Answer 12

mixed hyperlipidemia

Question 13

decision to treat cholesterol levels is based on?

Answer 13

risk of CV disease

Question 14

-statins are what drug class?

Answer 14

HMG-CoA reductase inhibitors

Question 15

nicotinic acid, vitamin B3 are what class?

Answer 15

niacins

Question 16

gemfibrozil and fenofibrate?

Answer 16

fibric acid derivatives

Question 17

colestipol, cholestyramine, colesevelam?

Answer 17

bile acid binding resins

Question 18

ezetimibe?

Answer 18

intestinal sterol absorption inhibitor

Question 19

• 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 ______

Answer 19

LDL receptors

lovastatin, simvastatin

first pass hepatic

bile

Question 20

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

Answer 20

LDL

cholesterol synthesis

Question 21

• statin toxicity indicated by elevations in serum _______
• macrolides, cyclosporine, ketoconazole, fibrates, grapefruit juice, phenytoin, rifampin, amiodarone inhibit or compete for CYP enzymes

Answer 21

aminotransaminase

Question 22

______ not metabolized by P450, preferred in combo with other drugs

Answer 22

pravastatin

Question 23

statins: increased ________ activity indicates skeletal muscle toxicity occurring as rhabdomyolysis

Answer 23

creatine kinase

Question 24

_____ may enhance the myopathic effect of statins

Answer 24

gemfibrozil

Question 25

• 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

Answer 25

niacin (B3, nicotinic acid)

Question 26

• 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

Answer 26

fibric acid derivatives - gemfibrozil and fenofibrate

Question 27

• found in fish oils
• activate PPARalpha
• profound reduction of triglycerides

Answer 27

omega 3 fatty acids

Question 28

• 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

Answer 28

bile acid binding resins: colestipol, cholestyramine, colesevelam

Question 29

• used for primary hypercholesterolemia
• might increase VLDL
• digoxin toxicity
• possibly decreased absorption of fat soluble vitamins, bloating and constipation

Answer 29

bile acid binding resins

Question 30

• 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

Answer 30

eztimibe

Question 31

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

Answer 31

resin

HDL