Anti-Hyperlipidemia Agents

Front 1

mechanism of statins

Back 1

HMG-CoA reductase inhibitors
this lowerrs the amount of cholesterol synthesized, also increases the amount of LDL receptors expressed by hepatocytes
degradation of LDL receptors also reduced
VLDL and IDL removal increased
HDL may increase

Front 2

which drugs have the most decrease in TG?

Back 2

nicotinic acid
fibric acids

Front 3

which statin has the longest t1/2

Back 3

atorvastatin

Front 4

which statins are metabolized by CYP3A4?

Back 4

atorvastatin
lovastatin
simvastatin

Front 5

which statins are metabolized by CYP2C9?

Back 5

fluvastatin
rosuvastatin

Front 6

which statin is not metabolized by CYP?

Back 6

pravastatin

Front 7

contraindications for statins

Back 7

nursing/pregnancy
children, only if they have homozygous FH or some heterozygotes

Front 8

when should statins be given?

Back 8

in evening if single dose (increased cholesterol biosynthesis at 2am)
atorvastatin can be taken any time b/c of long t1/2

Front 9

which statins are most efficacious for severe hypercholesterolemia?

Back 9

atorvastatin
rosuvastatin
(these drugs also have the greatest TG lowering capacity of the statins)

Front 10

which statins level off at the high dose range?

which have linear dosings?

Back 10

pravastatin, fluvastatin

lovastatin, simvastatin, atorvastatin

Front 11

adverse effects of statins

Back 11

hepatotoxicity (3x normal liver enzymes, esp if using EtOH)
rhabdomyolysis

Front 12

which lipid lowering drug is recommended for cildren 11-20 yo

Back 12

colestipol
cholestyramine
(resins)

Front 13

which drugs are resins

Back 13

cholestyramine
colestipol
colesevelam

Front 14

MOA of resins

Back 14

resins are highly + charge, binding negatively charged bile acids
they are large, so not absorbed, bound bile acids are excreted in stool
hepatic cholesterol content declines, so LDL receptors are increased --> LDL clearance
BUT, then HMG-CoA reductase gets upregulated, so there is increased LDL synthesis, counteracting the LDL reduction

Front 15

what will improve the action of resins?

Back 15

statin

Front 16

what happens to TG levels in resin administration?

Back 16

it increase TG synth, so contra-indicated in pts with severe hyper-TG

Front 17

administration of resins

Back 17

must be taken with food!

Front 18

what is the interaction btwn resins and digitalis

Back 18

removes dig from GI tract

Front 19

adverse effects of resins

Back 19

constipation
bloating
(both relieved by icreasing dietary fiber)
heartburn/diarrhea (occassional)
malabsorption of vitamin K and folate (rarely)

Front 20

drug interactions with resins

Back 20

only cholestyramine adn colestipol bind other drugs
take other drugs either 1 hr before or 3 hrs after resin

Front 21

MOA of niacin

Back 21

inhibits VLDL secreation
inhibits lipolysis of TG by lipase, reducing FFA transport to liver (decresaes TG synth)
enhanced LPL activatity, promoting clearance of chylomicrons and VLDL TGs

Front 22

therapeutic uses of niacin

Back 22

hyper-TG , hyper-LDL
esp useful in pts with high TG and low HDL

Front 23

toxicity of niacin

Back 23

cutaneous vasodilation adn feeling of warmth
pruritis
acanthosis nigricans (associated with insulin resistance, so contraindicated)
nausea and abdominal discomfort
sustained release --> hepatotoxicity

Front 24

contraindications of niacin

Back 24

severe peptic disease
concurrent use wth statin --> myopathy

Front 25

MOA of fibrates

Back 25

activates PRAR-alpha (a transcription factor)
thos reduces TG by stimulating FA oxidation
this increases LPL
this reduces expression of apoC-III (which inhibits lipolytic processing) --> enhanced clearance of VLDL
this stimulates apoA-I and apoA-II expression (increase HDL levels)
only modest decrease in LDL, and can cause increases as TG levels are reduced

Front 26

which fibrate is transported across placenta

Back 26

gemfibrozil

Front 27

contraindications for fibrates

Back 27

pts with renal failure or hepatic dysfxn
children
pregnancy

Front 28

therapeutic uses for fibrates

Back 28

hyper-TG with predominance of VLDL
Dysbetalipoproteinemia

Front 29

adverse effects of fibrates

Back 29

GI sx
potentiates actions of oral anticoags

Front 30

inhibitor of sterol absorption

Back 30

ezetimibe

Front 31

primary effect of ezetimibe

Back 31

reduction of LDL
minimal increase in HDL

Front 32

mOA of ezetimibe

Back 32

selective inhibition of intestinal absorption of cholesterol and phytosterols
effective in absence fo dietary cholesterol b/c inhibits reabsorption of cholesterol excreted in bile

Front 33

adverse rxn of ezetimibe

Back 33

reversible impaired hepatic fxn
do liver tests before starting drug, then again every 2-4 months

Front 34

reasons for using drug combos

Back 34

VLDL levels are significantly increased during resin tx
LDL and VLDL are elevated initially
LDL or VLDL not normalized with single agent

Front 35

fibrate + resin

Back 35

familial combined hyperlipidemia intolerant to niacin

Front 36

statin + resin

Back 36

FH
may not control VLDL insome pts iwth familial combined hyperlipidemia

Front 37

niacin + resin

Back 37

controls VLDL in familial combined hyperlipidemia
controls VLDL in d/o involving increased VLDL and LDL
effective for heterozygous FH (reversal of CAD)

Front 38

niacin + stsatin

Back 38

more effective than either alone
most effective when treating familial combined hyperlipidemia

Front 39

statin + ezetimibe

Back 39

synergistic in combo
can treat homozygous FH

Front 40

resin + niacin + statin

Back 40

lower effective doses
treats severe d/o involving elevated LDL