Cv Pharm Lipid Lowering Agents

Front 1

what is rate limiting step of de novo cholesterol synthesis

Back 1

HMG CoA reductase

Front 2

HMG CoA reductase inhibitors - suffix and common ones

Back 2

lovastatin
pravastatin
simbastatin
atorvastatin

Front 3

MOA of HMG CoA reductase inh

Back 3

block synthesis of cholesterols in liver
leads to upregulation of LDL receptors on liver
more LDLs extracted from blood
LARGE reducion in LDL

Front 4

effect of statins on LDL, HDL, and TGs

Back 4

Large decrease in LDL
modest increase in HDL
modest reduction of TGs

Front 5

when is best effect of statin seen?
and what does increasing to dose do?

Back 5

best effect seen at start of statin
doubling the dose reduces LDL by about 6%

Front 6

How are statins metabolized?

Back 6

cytochrome p450 3A
cytochrome p450 2c9
some by non cytochrome p450

Front 7

why should statins be taken at night?

Back 7

liver's cholesterol synthesis is most active at this point

Front 8

side effects of statins

Back 8

GI-diarrhea, constipation, excess flatus
Elecation of hepatic transaminases --> pregresion to hepatotoxicity is rare
Myalgia
Myopathy
Rhabdo!!!!!!!! very rare

Front 9

sequelae of rhabo

Back 9

hypovolemia - h20 into cells
hyperkalemia - cell destruction lets k out
metabolic acidosis
acute renal failure
DIC - disseminated inravascular coag.

Front 10

what drug interactions should we watch out for when giving statins

Back 10

fibrate (GEMFIBROZIL***)
niacin - rare
******cyp3a4 inhibitors - cyclosporine, erythromycin, grapefruit juice --> will increase concentration of statin****

Front 11

absolute contraindications for statins

Back 11

pregnancy and lactation
active hepatic disease

Front 12

list the bile acid binding resins - 3

Back 12

cholestyramine
colestipol
colesevelam

Front 13

MOA for bile acid binding resins

Back 13

resins bind bile acids so they cannot be resorbed into gut and are excreted -
increases the demand for bile acid synthesis
upregulated LDL receptor to get more cholesterol to make bile acids and removes from blood

Front 14

how would u increase the efficacy of BABR

Back 14

combine with statin

Front 15

Effect of BABR

Back 15

decrease LDL by 15-30 percent
INCREASE in TGs - this is transient, but can be sustained with previous hyperTGs

Front 16

would you use cholestyramine for hypertriglyceridemia?

Back 16

no , they increase TGs

Front 17

problem with BABR

Back 17

increase TGs
poor compliance

Front 18

difference in dosing of hyperlipidemia drugs

Back 18

take statin at night
take BABRs before meals

Front 19

Side effects of BABRs

Back 19

GI- constipation, nausea, heartburn, bloating
***impaired absorption of anionic drugs
Impaired absorption of vitmins A, D, and K - take drugs before meals

Front 20

What is the only cholesterol absorption inhibitor?

Back 20

ezetimibe

Front 21

MOA - ezetimibe

receptor?

Back 21

bocks the NPC1L1 receptor on gut lumen.
cholesterol cannot get in and does not get incorporated into chylomicrons

Front 22

effect of Cholesterol absorption inhibitors on lipids

Back 22

Decrease LDL 15-20 %
Decrease TG6%
increase HDL 4-9%

Front 23

effect of statins on lipid levels

Back 23

decrease LDL 18-55%
decrease TG 7-30% modest
increase HDL 5-15%modest

Front 24

side effets of Cholesterol ab inh

Back 24

GI upset, not too bad

Front 25

Niacin - vitamin MOA at high levels

2 possible

Back 25

g couple receptor to inhibits HSL (hormone sensitive lipase) key enzyme for TG hydrolysis with subsequent FA mobilization in adipose tissue. Basically keeps FA in adipose
OR
inhibits DGAT2 which stops the final step in liver TG synthesis --> leads to the degradataion of ApoB because it needs TGs to form VLDL

Front 26

best clinical use for niacin

how to dose

Back 26

hyperTGemia
mixed hyperlipidemia
hypercholestorolemia

Titrate dose over weeks

Front 27

what happens if we combine Niacin to statin

Back 27

Larger decrease in TGs
and LDL may go down further and larger increase in HDL

Front 28

effect of niacin on Lipids

Back 28

decrease LDL 5-25%
decrease TG 20-50%
increase HDL 15-35%
decrease LpA by 15-35%

Front 29

what happens if we combine niacin with cholestyramine

Back 29

LDL way down TG down HDL way up

Front 30

Niacin side effects

IMPORTANT ONES

Back 30

GI - NVD
niacin can stiulate histamine release!!!!! - gastric acid - ulcers*******
Flushing - PG mediated dilation of skin capillaries - block with nsaids
hepatotoxity- more comon with sustained release products , rare
hyperglycemia - DIABETES - elevation of fasting glucose, increase insulin resistance
hyperuricemia - inhibits tubular secretion of uric acid BAD FOR GOUT

Front 31

why does niacin cause flushing

Back 31

increases prostaglandin production

Front 32

contraindications for niacin

Back 32

chronic liver disease
acive peptic ulcer
gout
high doses in type2 diabetes

Front 33

list the fibric acid derivs

Back 33

gemfibrozil
fenofibrate
fenofibric acid

Front 34

fibric acid derivative MOA

end result?

Back 34

activate a transcription factor that increases VLDL clearance

End result - Less small, dense LDL particles and more large buoyand LDL particles

Front 35

effect of Fibric acid derivatives on lipids

Back 35

decrease TG 20-50%
increase HDL 10-35 %
variable change in LDL - may lower may raise in hyperTGemics

Front 36

maine clnical use for fibric acid derivs

Back 36

hyperTGemia

Front 37

Side effects of fibric acid derivs

Back 37

GI - Naus diarrhea
GALL STONE FORMATION!!
MYOPATHY AND RHABDO - mainly in combo with statin
most common with gemfibrozil