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112 Cards in this Set

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LDL contains high levels of ___ which readily deposits in the subendothelial space of arteries. Chylomicrons & VLDL cannot, although VLDL gives rise to ILD which can.
Cholesterol
high LDL increases the incidence of adverse events associated with coronary artery disease whereas ___ is antiatherogenic by removing free cholesterol generated from the metabolism of chylomicrons & VLDL.
HDL
“STATINS” are __________
HMG CoA REDUCTASE INHIBITORS (HMG = 3-hydroxy-3-methylglutarate) –
Statins inhibit the conversion of HMG CoA to _________, the rate-limiting step in the synthesis of cholesterol. Cholesterol synthesis is, therefore, decreased.
mevalonic acid
Statins are heavily extracted by the _____.
liver
Peripheral levels are very low. Therefore, their effect is predominantly on __________.
hepatocytes
As hepatocyte cholesterol synthesis decreases, the number of LDL receptors __________.
increases
WHAT IS THE CLINICAL SIGNIFICANCE OF THIS?
collects more LDL from blood stream to meet cholesterol needs
Macrophages can also take up LDL that contains acetylated or oxidized ____.
apoB-100
Excessive uptake by macrophages of modified (acetylated or oxidized) LDL transforms macrophages into ______.
FOAM CELLS
WHAT IS THE CLINICAL SIGNIFICANCE OF THIS?
They are athrogenic, just like LDL
STATINS also decrease ___ b/c they also contain apoB-100 which is recognized by LDL receptors and is internalized by hepatocytes.
IDL
The decrease in IDLs CONTRIBUTE TO THE decrease IN PLASMA LDL? WHY?
Yes, cuz IDL can become LDL (is a precursor)
Hepatic synthesis of _____ is also decreased.
apoB-100
WHY IS decrease of Hepatic synthesis of apoB-100 THIS IMPORTANT?
How receptor recognizes LDL & IDL
Cholesterol contains high levels of ___ which readily deposits in the subendothelial space of arteries. Chylomicrons & VLDL cannot, although VLDL gives rise to ILD which can.
LDL
high LDL increases the incidence of adverse events associated with coronary artery disease whereas ___ is antiatherogenic by removing free cholesterol generated from the metabolism of chylomicrons & VLDL.
HDL
“STATINS” are __________
HMG CoA REDUCTASE INHIBITORS (HMG = 3-hydroxy-3-methylglutarate) –
Statins inhibit the conversion of HMG CoA to _________, the rate-limiting step in the synthesis of cholesterol. Cholesterol synthesis is, therefore, decreased.
mevalonic acid
Statins are heavily extracted by the _____.
liver
Peripheral levels are very low. Therefore, their effect is predominantly on __________.
hepatocytes
As hepatocyte cholesterol synthesis decreases, the number of LDL receptors __________.
decreases
WHAT IS THE CLINICAL SIGNIFICANCE OF THIS?
-
Macrophages can also take up LDL that contains acetylated or oxidized ____.
apoB-100
Excessive uptake by macrophages of modified (acetylated or oxidized) LDL transforms macrophages into ______.
FOAM CELLS
WHAT IS THE CLINICAL SIGNIFICANCE OF THIS?
-
STATINS also decrease ___ b/c they also contain apoB-100 which is recognized by LDL receptors and is internalized by hepatocytes.
IDL
The decrease in IDLs CONTRIBUTE TO THE decrease IN PLASMA LDL? WHY?
--
Hepatic synthesis of _____ is also decreased.
apoB-100
WHY IS decrease of Hepatic synthesis of apoB-100 THIS IMPORTANT?
-
VLDL is composed mainly of _________.
triacylglycerol
With statins, triglyceride levels decrease _____ .
10-30%
With statins, HDL levels increase _____.
5-10%
WHY do HDL levels rise.
HDL donates cholesterol exters to other lipoP (i.e. LDL & IDL) ; in the process of doing that it gets modified so that it is no longer a HDL. when we decrease the LDLs to donate to, less HDL is modified.
The increase in HDL removes more free unesterified _______ from extrahepatic tissues which contributes to the decrease in plasma cholesterol.
cholesterol
All STATINS are therapeutically ____.
equal
Significant effects occur in ___ wks with maximal effects in ___ wks.
1-2
4-6
Recommend giving statins as a single daily dose at _____ .
bedtime
WHY?
Has to do with when most cholesterol synthesis takes place – in the evening
Statins are used for a wide variety of __________
hypercholesterolemia
STATINS have anti-inflammatory activity as assessed by ____________ levels which are ↑ during systemic inflammation, a part of the atherosclerotic process.
C REACTIVE PROTEIN
High levels of C REACTIVE PROTEIN are associated with _____ survival rates
lower
MECHANISM
Statins inhibit various oxidation pathways (anti-oxidant). CRP is an end product of oxidation & inflammation. Statins have an anti-inflamatory effect reduces risk of CV dz.
STATINS are in PREGNANCY CATEGORY X: which means:
Documented fetal abnormalities in animals or humans or evidence of fetal risk in humans. Risk outweighs benefits.
-ProRx
-Metabolized by cyp 3A4. avoid grapefruit juice. Macrolides ( erythromycin, clorithromicin, azythromicin, derithromycin), itroconasole( conazoles are anti fungals) increase risk of rabdomyolisis.
LOVASTATIN (Mevacor)
SIMVASTATIN (Zocor)
proRx
low protein binding results in short half life (2hrs)
PRAVASTATIN (Pravachol)
FLUVASTATIN (Lescol)
-
longest acting.
ATORVASTATIN (Lipitor)
atorvastatin + amlodipine =
CADUET
WHAT IS AMLODIPINE?
Ca++ channel blocker (CCB), treat arrhytmia’s and HTN
decreases LDLc 46-55%
ROSUVASTATIN (Crestor) -
All STATINS decrease LDL decrease 25% (rosuvastatin more). For a greater effect, higher doses of _____ or _____ are recommended.
LOVASTATIN
SIMVASTATIN
WHY NOT USE HIGHER DOSES OF THE OTHER RXS?
prodrug activated in the liver where it is used
One of the SIDE EFFECTS of Statins is an ______ in plasma transaminases > 3 times the upper limit of normal. Incidence: 1-2%.
increase
Significance of increase in plasma transaminases is ______ damage?
liver
Another SIDE EFFECTS of Statins is _________– transient increase in CK-MM. Muscle tenderness, pain, weakness.
MYOPATHY
_______ dysfunction increases risk of rhabdomyolysis.
Renal
Also with Statins there have been reports of a _____ like syndrome
lupus
OTHER POTENTIAL USES of these two statins is to decrease the Risk of Alzheimer’s & dementias & depression.
(pravastatin & lovastatin but not simvastatin)
statins can also ↓ ____ in patients w/ or w/o decreasing cholesterol.
BP
statins may also ↓ the risk of ____.
glaucoma
Risk of myopathy increases in patients on ______,______ , _______, ________, & _______. Can take together if you decrease the dose of the statin.
cyclosporine
erythromycin
itraconazole
gemfibrozil
nicotinic acid
lovastatin & simvastatin potentiate _______ actions through an unknown mechanism, resulting in increased prothrombin time (PT).
coumarin's
BILE ACID SEQUESTRANTS are used Mostly for Types ___ & ____ hyperlipidemias.
IIa
IIb
BILE ACID SEQUESTRANTS, have Little effect on patients ________ for type IIa. These patients do not have ___ receptors.
homozygous
LDL
BILE ACID SEQUESTRANTS MECHANISM:
Not absorbed systemically, action is totally in the gut—Anion exhange resin- exchange Cl- for bile acids, not absorbed so is excreted-> increased excretion of bile acids.
WHY IS THIS IMPORTANT?
Bile acids contain large amount of cholesterol
WHAT DOES THIS DO TO THE LEVELS OF HEPATOCYTE CHOLESTEROL?
Goes down—set in motion all the events previously discussed—sucks up LDL from plasma , LDL receptors go up in liver- so liver grabs the LDL when it sees apo B100
HOW WILL HEPATOCYTES REPLACE THE BILE ACIDS?
Make more; needs more cholesterol from plasma, LDL receptors increase on hepatocytes-
FROM WHERE WILL HEPATOCYTES GET CHOLESTEROL?
-plasma
WHAT HAPPENS TO THE # OF LDL RECEPTORS? WHY?
-
Increase, low chol levels in hepatocytes, genes transcribe LDL receptors, so grabs apo 100 on LDL, to break down and make more bile acids.
BILE ACID SEQUESTRANTS result in a ____ drop in LDL in 1st wk with maximal effects in ~ 2 wks. HDL rises only _____.
10-35%
~5%
powder to mix in H20 or juice
CHOLESTYRAMINE (Questran)
granules & tablets
CHOLESTIPOL (Colestid)
tablets
COLESEVELAM (Welchol
SIDE EFFECTS of BILE ACID SEQUESTRANTS
Not absorbed. No significant systemic effects
WHAT KIND OF SIDE EFFECTS WOULD YOU EXPECT?
-GI ( remains in gut)—bloating, cramps, constipation
Constipation can persist resulting in _______
impaction
BILE ACID SEQUESTRANTS, can bind _______ charged compounds e.g. thyroxine, digoxin, anticoagulants, thiazides, furosemide, propranolol, tetracyclines, gemfibrozil, pravastatin, fluvastatin, ASA, phenobarbital
negatively
BILE ACID SEQUESTRANTS can decrease Absorption of ___ soluble vitamins (A,D,E,K)
fat
_______ and ______ absorption are also decreased.
Vitamin C
folic acid
TAKE ALL OTHER RXS ___ HR BEFORE OR ___ HRS AFTER TAKING A RESIN
ONE
4
NICOTINIC ACID = ____
NIACIN
NIACIN USES are TYPES __,__,__,__ hyperlipidemias
II, III, IV, V
NICOTINIC ACID MECHANISM
inhibits hormone sensitive lipase (HSL) that normally mobilizes the stored fats. Decrease mobilization of peripheral fat stores
Inhibition of hormone sensitive lipase (HSL) decreases the delivery of FFAs to the liver which decreases the synthesis of ____ & ____. Lower levels of VLDL -> lower levels of LDL. HDL is increased (mechanism unclear).
VLDL
TGs
** NIACIN is the only Rx that will decrease ______
Lp(a)
50% of patients on niacin experience vasodilation -> intense ______ & ______ involving face & upper body.
flushing
pruritus
vasodialation might be accompanied by _______, due to baroreptor response to decrease in BP
palpitations
Taking _____ 30 minutes before or _______ 1 x/day has prevented these symptoms in some patients.
ASA
IBUPROFEN
Niacin can also cause _____ abnormalities --chronic high doses or sustained release preps can increase serum transaminases (AST/ALT).
Hepatic
Niacin can also cause an increase in plasma glucose – caution if patient is ______
diabetic
Niacin can also cause an increase in uric acid levels -> can increase risk of _____ attack
gout
Niacin is also ssociated with abdominal ________
malignancy
Niacin is contraindicated if pt has a Hx of ________ - can precipitate an attack.
peptic ulcers
When used with a STATIN, niacin can increase the risk of _______
rhabdomyolysis
FORMULATIONS of niacin are available ____. Higher doses of some may a require prescription.
OTC
This formulation is absorbed over 1-2 hrs. Given t.i.d.. High incidence of flushing, GI side effects and increase blood sugar.
Immediate release
This formulation is absorbed over 12+ hrs. Given 1x/day. Less flushing but increase risk of hepatotoxicity
Sustained release
This formulation is absorbed over 8-12 hrs. Given 1x/day. Less flushing and GI side effects w/o increase risk of hepatotoxicity.
Extended release
when giving niacin always get BASELINE ______, _____ , _______& ______
LIVER FUNCTION TESTS
GLUCOSE
URIC ACID
LIPID LEVELS
NIACIN + LOVASTATIN=
ADVICOR
In FIBRIC ACID DERIVATIVES the MECHANISM is to activate _________ that increases transcription of ___ & decreases transcription of apoC-III, an inhibitor of LPL.
peroxisome proliferator-activated receptor α (PPARα)

LPL
FIBRIC ACID DERIVATIVES ↑ LPL activity -> increase hydrolysis of ____ -> decrease in VLDL.
TGs
FIBRIC ACID DERIVATIVES ↑ HDL by increasing transcription of genes coding for apo ___ & ___ which are major apoproteins in HDL.
AI
AII
FIBRIC ACID DERIVATIVES also decrease levels of plasma _______ causing a decrease in platelet aggregation. This "might" have beneficial effects on the CV system. The mechanism for this effect is unclear.
fibrinogen
This FIBRIC ACID DERIVATIVE is for Types IV & V. It decreases LDL, VLDL & TGs
FENOFIBRATE (Tricor)
This FIBRIC ACID DERIVATIVE is Preferred for Type III (familial dysbetalipoproteinemia) in which there is a mutant apoE causing an increase in IDL which, in turn, increases TG & cholesterol.
GEMFIBROZIL (Lopid)
SIDE EFFECTS of FIBRIC ACID DERIVATIVEs are that a ______-______ SYNDROME can occur
MYOSITIS-FLULIKE
This CHOLESTEROL ABSORPTION INHIBITOR, Inhibits absorption of LDL and some TGs. CAUTION: Possible allergic reaction in the form of a rash or angioedema.
EZETIMIBE (Zetia)
EZETIMIBE + SIMVASTATIN =
VYTORIN