Drugs To Treat Hyperlipidemias

Front 1

Atherosclerotic plaques ____ vessels and lead to ____, a blot clot occluding a major artery.

Back 1

constrict, thrombosis

Front 2

Atherosclerotic plaques cause ____ and _____

Back 2

strokes, heart attacks (myocardial infarction)

Front 3

Arterial damage leads to an aggregation of platelets and macrophages filled with oxidized lipids (foam cells), including ____.

Back 3

cholesterol

Front 4

Cholesterol is a _____ component of all animal cells.

Back 4

polar

Front 5

Cholesterol is synthesized from _____, 2 carbon fragment, primarily in the ____.

Back 5

acetylCoA, liver

Front 6

Derivatives of cholesterol are used to aid digestion of fats secreted in ____.

Back 6

bile

Front 7

Cholesterol is a precursor to ___ synthesis

Back 7

steroid

Front 8

Most lipid transport in the blood is via carriers called _____

Back 8

lipoproteins

Front 9

The outer surface of lipoproteins is largely a monolayer of _____ mixed with an apolipoprotein

Back 9

triglycerides

Front 10

The inner layers of lipoproteins are mixtures of lipids including cholesteryl ____ (nonpolar.)

Back 10

esters

Front 11

As density of particles increases, fat content ____, while protein content _____.

Back 11

decreases, increases

Front 12

Smaller particles are ____ dense.

Back 12

more

Front 13

____ determine which receptors the particles interact with.

Back 13

apolipoproteins

Front 14

Fats from GI are packaged into large ____ particles. These distribute to tissues and have fatty acids removed by lipoprotein _____ (enzyme) via interaction with apolipoprotein C. Remnants go to liver.

Back 14

chylomicron, lipase

Front 15

VLDL remnants (IDLs) are depleted of ___ and picked up by the liver or converted into LDL particles.

Back 15

Triglycerides

Front 16

LDL have primarily Apo _____.

Back 16

B-100

Front 17

Cholesterol in liver can be converted into bile acids and secreted into GI tract. 90% is _____ and transported back to liver.

Back 17

reabsorbed

Front 18

Calculation of LDL

Back 18

TC=LDL+HDL+VLDL+IDL+CHYLOS

if fasting & no type III dyslipidemia, IDL and Chylos approximately 0
TC=LDL+HDL+VLDL

VLDL~Trig/5 if Trig<450

Front 19

Primary goal of drug therapy

Back 19

lower LDL-cholesterol

Front 20

Secondary goal of drug therapy

Back 20

increase HDL or lower trigs

*No evidence hat secondary goals impact risk of CV events clinically

Front 21

Statins

Back 21

Remarkably effective

Upto 60% reduction in LDL

10% increase in HDL

Slight decline in trigs & C-reactive protein

Front 22

Bile acid sequestrants

Back 22

20% decrease in LDL

Front 23

Fibric acids

Back 23

20% decrease in LDL

20% increase in HDL

50% reduction in trigs/VLDL (additive w/ statins)

Front 24

Niacin

Back 24

40% decline in VLDL/trigs

25% decline in LDL

30% increase in HDL (additive w/ statins)

Front 25

Cholesterol absorption inhibitor (ezetimibe)

Back 25

20% reduction LDL and total cholesterol

No effects on trigs/HDL

Additive w/ statins

Front 26

How statins work....

Back 26

block HMG-CoA reductase (RLS in cholesterol synthesis of liver)

decrease liver intracellular cholesterol, increased LDL-R expression & uptake of LDL cholesterol from circulation

Pleiotropic effects (highest doses): increase eNOS, decrease inflammation & C-reactive protein, decrease platelet aggregation & oxidation

Front 27

Statins reduce hepatic cholesterol synthesis, _____ intracellular cholesterol, which stimulates upregulation of LDL-R and increases the uptake of non-HDL particles from systemic circulation.

Back 27

lowering

Front 28

The ____ statin dose produces most of the LDL-C lowering.

Back 28

initial

Front 29

Statins-common side effects

Back 29

headache; myalgia; fatigue; GI intolerance; flu-like symptoms

*may also cause: increase in liver enzymes & myopathy

Front 30

Cautiously using statins in patients w/ impaired renal failure, using the lowest effective dose, cautiously combining statins with fibrates, avoiding drug interactions and careful monitoring of symptoms are all used in reduction of ______.

Back 30

myopathy

Front 31

Most statins are taken at ____ as most cholesterol synthesis is nocturnal.

Back 31

bedtime

Front 32

Blood must be monitored for ___ and ___. Toxicity is usually _____.

Back 32

liver toxicity, creatine kinase

reversible

Front 33

Several statins are metabolized by _______ (hint: cytochrome)

Back 33

CYP450 3A4

Front 34

______ inhibits degradation and increase blood concentration of drugs.

Back 34

grapefruit juice

Front 35

Fibric acid derivatives activate a transcription factor called _____.

Back 35

PPAR-alpha

Front 36

PPAR-alpha leads to elevations of lipoprotein lipase, which cleaves ____ from chylomicrons and VLDL particles.

Back 36

triglycerides

Front 37

What are the 2 fibric acid derivatives we should know?

Back 37

gemfibrozil, fenofibrate

Front 38

There is a ____ rate of transfer of cholesterol from HDL to VLDL and chylomicrons, leading to _____ HDL-cholesterol.

Back 38

reduced, increased

Front 39

Need to monitor combined use w/ statins due to _____. Increases gall stones.

Back 39

myotoxicity

Front 40

Large insoluble ion-exchange resins (hint: drug class)

Back 40

bile acid sequestrants

Front 41

Bile acid sequestrants exchange ____ for negatively charged bile acids and escorts them out thru the stool.

Back 41

Cl-

Front 42

True/false: Bile acid sequestrants must be taken on an empty stomach.

Back 42

False

Must be taken with meals--up to 20g/day (GRAMS/DAY!!)

Front 43

Other drugs must be given either more than ___ hour(s) before or more than ___ hour(s) after.

Back 43

1, 4

Front 44

Side effects of bile acid sequestrants

Back 44

GI problems; bloating; constipation; absorbs vitamins

Front 45

Which 3 drugs are the bile acid sequestrants we need to know?

Back 45

Cholestyramine

colestipol

colesevelam

Front 46

Bile acid sequestrants mechanism of action...

Back 46

prevents/inhibits reabsorption of bile acids

Front 47

Bile Acid sequestrants...(either increase or decrease)

____ Bile acid excretion
____ Cholesterol 7-alpha hydroxylase
____ Conversion of cholesterol to bile acids
____ bile acid secretion
____ LDL-Rs
____ VLDL & LDL Removal

Back 47

INCREASES ALL

Front 48

Net effect of Bile Acid Sequestrants

Back 48

decrease LDL-C

Front 49

Nicotinic Acid mechanism of action (either increase or decrease)

IN LIVER
___Mobilization of FFAs
___ TG synthesis
___VLDL Secretion
IN SYSTEMIC CIRCULATION
___Serum VLDL results in reduced lipolysis to LDL
___Serum LDL
___HDL

Back 49

decreased
decreased
decreased

decreased
decreased
increased

Front 50

Nicotinic acid decreases hepatic production of VLDL and of ____.

Back 50

Apo B

Front 51

Niacin=Nicotinic acid=Vit ____

Back 51

B3

Front 52

Niacin use can cause _____. Dissipates with use. Can be treated with aspirin.

Back 52

Flushing

Front 53

Niacin ______ insulin resistance and uric acid formation which can exacerbate diabetes and gout.

Back 53

increase

*also increases jaundice & liver dysfunction

Front 54

AIM-High (___+____) examined benefit of elevating HDL when LDL low. Halted early due to LACK of efficacy.

Back 54

Niacin + Statin

Front 55

Major benefit of Niacin + statin vs. statin alone is...

Back 55

improved HDL & trigs

Front 56

Cholesterol Absorption Inhibitor (hint: drug name)

Back 56

ezetimibe

Front 57

Ezetimibe mechanism of action

Back 57

blocks uptake of cholesterol from GI (jejunum) to liver; increase liver LDL-Rs; Reduces circulating LDL

Front 58

If higher statin doses are not well tolerated and lipid goals are not met, consider _____ therapy.

Back 58

combination

Front 59

Statins + bile acid resins or ezetimibe

Back 59

decrease LDL-C by 50% but no additional reduction in CHD risk

Front 60

Fibrates, niacins, omega-3-fatty acids...

Back 60

decrease trigs & non-HDL-C

increase HDL-C

Front 61

Combination therapy make increase risk for ______.

Back 61

drug interactions

Front 62

Fish oil (omega 3s) may decrease trigs in conjunction with other therapies. Rx version is _____ (hint: drug name). AMR101 in Anchor and Marine trials effectively lowers elevated trigs.

Back 62

Lovaza

Front 63

Red Yeast Rice Extract may be effective in patients intolerant of _____.

Back 63

statins

Front 64

Block cholesterol synthesis in liver; compensatory increase in LDL-R reducing circulatory LDL

What drug class am I?

Back 64

Statins

Front 65

Activate PPAR-alpha leading to increased lipoprotein lipase and reduced circulating trigs

What drug class am I?

Back 65

Fibric acids

Front 66

Binds bile acids in gut increasing excretion; leads liver to increase LDL-R to obtain more cholesterol for synthesizing increased amounts of bile acids.

What drug class am I?

Back 66

Bile Acid sequestrants

Front 67

Reduces VLDL production by liver & Apo-B100 thereby reducing LDL in circulation

What drug class am i?

Back 67

Niacin

Front 68

Block uptake from GI tract to liver; increase liver LDL-Rs; reduces circulation LDL

What drug class am I?

Back 68

Absorption Inhibitors