Block 3: Hypolipidemics

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What are the two conditions that are the exception to the rule of attempting to control hyperlipoproteinemia by dietary management before using drugs?: familial hypercholesterolemia
and
familial combined hyperlipidemia
What diet is recommended for total fat intake? low saturated fat intake? cholesterol intake?: <30% total fat calories
<7% low saturated fat
<200 mg cholesterol
= 10-20% reduction in serum cholesterol
Name three foods that may reduce LDL?: oat
rice bran
soy (LDL and cholesterol)
___ reduce triglyceride levels ___ increase triglyceride levels: omega-3- fatty acids reduce
omega-6- fatty acids increase
Name two dietary supplements that inhibit HMG-CoA reductase?: Cholestin and Evolve
Name two bile acid binding resins: cholestyramine and colestipol
What is the primary aim of cholestyramine and colestipol?: to lower blood cholesterol - especially LDL
Name two indications for cholestyramine and colestipol: HETEROZYGOUS familial hypercholesterolemia
and
combined hyperlipidemia
What is the primary action of cholestyramine and colestipol?: nonspecifically binds bile acids within the intestinal lumen; inhibits the reabsorption of bile acid
What is the secondary action of chlestyramine and colestipol? (6 steps): 1. cholesterol is the precursor of bile acid -> inhibition of bile reabsorption causes increased channeling of cholesterol to the production of bile acids
->
2. decreased intra-hepatic cholesterol level
-> 3. up-regulation of ApoB and ApoE receptors on hepatocytes
-> 4. INCREASED clearance of lipoproteins LDL, IDL, and maybe VLDL
-> 5. ADVERSE effect of reduced intra-hepatic cholesterol -> increased secondary cholesterol production ->
6. constipation, bloating, gallstones, steatorrhea
Name five drug interactions of cholestyramine and colestipol?: digitalis preparations
thiazide diuretics
beta blockers
warfarin
fat soluble vitamins (esp K)
How do you manage those drug interactions?: take cholestyramine and colestipol with or just before meals
take other drugs 2 hours before the resins or 4 hours after the resins (cholestyramine and colestipol)
cholestyramine and colestipol decreased LDL cholesterol by ... increased HDL cholesterol by... and are often given together with...: decrease LDL 15-30%
increase HDL 3-5%
given with HMG-CoA reductase inhibitors
3-hydroxy-3-methylglutaryl coenzyme A: HMG-CoA
Name two indications for HMG-CoA reductase inhibitors: familial hypercholesterolemia
and
combined hyperlipidemia
HMG-CoA reductase inhibitors are also known as...: statins
What is the primary MOA of a statin?: inhibit HMG-CoA reductase
a key enzyme in cholesterol synthesis in the liver
What is the secondary action of statins? (3 steps plus 1 other effect): inhibit the cholesterol synthesis enzyme -?
1. reduced intrahepatic cholesterol ->
2. 180% upregulation of ApoB and ApoE receptors ->
3. increased clearance of ApoB and ApoE containing lipoproteins (LDL, IDL, VLDL)

and

increase HDL
statins can lower triglyceride levels up to... can lower LDL levels by... can increase HDL levels by...: 25% decreased triglycerides
40% decreased LDL
15% increased HDL
Why are statins given in the evening?: the diurnal pattern of cholesterol biosynthesis
How do you prescribe a statin to a patient with hepatic parenchymal disease and why?: mild hepatotoxicity ->
indicated by increased serum aminotransferase levels ->
therefore give reduced dosage
What finding is increased when a patient on a statin is also on cyclosporin or fibric acid derivatives?: myopathy - reversible upon cessation of therapy
Name four psychiatric symptoms associated with statins?: anxiety
depression
obsessions
delusions
What about statins and pregnant women?: Never give a statin to a pregnant woman!
only give to women of childbearing age when they are highly unlikley to conceive
Do statins have any benefit to healthy middle-aged men and women with near NORMAL levels of blood cholesterol?: can reduce risk of heart attacks and stroke by 30%
Grapefruit juice and verapamil can significantly increase the serum concentraions of which three statins by inhibiting which CYP enzyme?: lovastatin
simvastatin
atorvastatin
CYP3A4
What does grapefruit juice and verapamil do to pravastatin and fluvastatin?: nothing
first statin approved by FDA: lovastatin
lovastatin is an inactive ___ prodrug hydrolyzed in the GI tract to active ___ derivative: lactone prodrug
beta-hydroxyl derivative
__% of lovastatin is absorbed from the GI tract...undergoes extensive first pass elimination and leaves less than ___% of orally administered dose to reach circulation?: 30% absorbed
5% reaches circulation
this statin was approved in 1996 and is given as an active drug...it is readily absorbed and is 2x more potent than lovastatin: atorvastatin
This drug is the most effective in reducing LDL (up to 60%) and triglycerides (up to 30%) it also is the most effective in raising HDL levels: atorvastatin
This drug is similar to atorvastatin, was approved in 2004, and is rumored to have a higher incidence of rhabdomyolysis and renal failure: rosuvastatin
(don't give more than 20 mg/day)
Estrogen replacement therapy increases the HDL cholesterol up to __% and decrease LDL __%: 15%
15%
What is the MOA for estrogen replacement therapy?: unknown
What does ezetimibe do?: cholesterol absorption inhibitor --> acts on brush border of gut wall to prevent cholesterol absorption through villi
What happens when you give ezetimibe with a statin?: lower LDL additional 25%
Name four classes of drugs that predominantly lower cholesterol: 1. bile acid binding resins (cholestyramine and colestipol)
2. HMG-CoA reductase inhibitors (statins)
3. Estrogen replacement therapy
4. cholesterol absorption inhibitor (ezetimibe)
trigylceride levels >400 mg.dl increase the risk of... levels >100 mg/dl increase the risk of...: heart disease
pancreatitis
Name five indications for niacin (nicotinic acid): 1. heterozygous familial hypercholesterolemia
2. mixed lipemia
3. combined hyperlipoproteinemia
4. familial dysbetalipoproteinemia
5. Lp(a)hyperlipoproteinemia
What is the primary MOA of niacin?: direct decrease in hepatic synthesis of VLDL
What is the secondary MOA of niacin? (one plus an extra): decreased VLDL ->
decreased IDL and LDL

increases HDL MORE THAN ANY OTHER DRUG (up to 35%) -> decreasing Lp(a) levels
Name six side effects of niacin?: 1. flushes
2. pruritis
3. rashes
4. hyperuricemia
5. reversible carbohydrate tolerance impairment
6. rare hepatotoxicity
Name two fibric acid derivative drugs?: gemfibrozile and fenofibrate
Name two indications for fibric acid derivatives?: familal hypertriglyceridemia
familial disbetalipoproteinemia
Name three MOAs of fibric acid derivatives?: exact MOAS unknown but...
1. increases lipoprotein lipase activity (VLDL catabolism)
2. decreases VLDL synthesis and excretion by liver
3. increases HDL cholesterol
fibric acid derivatives (gemfibrozel and fenofibrate) decrease triglyceride by __% increase HDL by __% and do what to LDL levels: triglycerides down by 50%
HDL up by 15%
LDL may go up or down
What is the most frequently used fibric acid derivative?: gemfibrozil
gemfibrozil is __ absorbed by GI tract has half life of __ and excreted as ___ through kidneys: readily absorbed
t1/2 = 90 minutes
excreted as glucoronid conjugate through kidneys (therefore avoid in patients with kidney disease)
is gemfibrozil the active carboxylic acid form?: yes
Name five possible but rare side effects of gemfibrozil: rash
GI sx
myalgia
anemia
gallstones
gemfibrozil potentiates the action of which two drugs by displacing them from albumin?: coumadin and indandione anticoagulants
this fibric acid derivative is rarely used because of possible increase in malignancies and has pharmacokinetics and drug interactions are similar to gemfibrozil: clofibrate
this fibric acid derivatives is widely used in Europe was recently approved in the USA and is similar to gemfibrozil: fenofibrate
consumption of large amounts of ___ by Alaskan natives reduced CHD mortality rate?: fish oil containing omega-3 polyunsaturated fatty acids
How does fish oil work?: decreases triglyceride levels by suppression of VLDL production and increases HDL cholesterol
What is the fish consumption advice?: 2 servings per week- especially fatty fish like salmon, tuna, mackerel, herring, and sardines
Name the three classes of drugs that predominantly lower triglyceride: niacin
fibric acid derivatives (gemfibrozil, fenofibrate, clofibrate)
fish oil
an antimicrobial agent of the aminoglycoside family: neomycin
neomycin with __ exerts a highly complementary effect for lowering cholesterol levels?: niacin
Name two indications for neomycin?: familial hypercholesterolemia
familial combined hyperlipidemia
what two combinations are effective in lowering LDL-C: statin and resin (cholestyramine and colestipol)
or
niacin and resin
what combination can be used to lower triglycerides in severe hypertriglyceridemia: gemfibrozil and fish-oil capsules
chylomicronemia manifests as... use ... combo: inc chylomicrons and inc VLDL
use niacin and fibrate
familial hypertriglyceridemia manifests as ... use ... combo: inc chylomicrons and inc VLDL
use niacin and fibrate
familial combined hyperlipoproteinemia manifests as... use ... combo: inc VLDL and inc LDL
use niacin and resin or statin
familial hypercholeterolemia heterozygous manifests ... use ... combo: inc LDL
use niacin, statin and or resin
familial hypercholesterolemia homozygous manifests as ... use ... combo: inc LDL
niacin and atorvastatin
Lp(a) hyperlipoproteinemia manifests as ... use ... combo: inc Lp(a)
use niacin and neomycin

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Number of cards 69