Pharm for Hyperlipidemia

Question 1

Zetia (Ezetimibe) COI MOA

Answer 1

Selective inhibition of cholesterol absorption by blocking transport at the brush order of the small intestine.

Question 2

Zetia (Ezetimibe) COI Therapeutic Effects

Answer 2

Decrease of LDL Levels
No effect on absorption of fat soluble vitamins, triglycerides or bile salts
Used alone and diet or in combo w/ statins

Question 3

Zetia (Ezetimibe) COI Adverse Effect and Excretion

Answer 3

Flatulence
Diarrhea
Myalgia
Excreted primarily in feces

Question 4

Orlistat (Xenical, Alli) FAI MOA

Answer 4

Inhibitor of pancreatic lipase and decreases absorption of dietary fat by ~25%
Pancreatic Lipase is released into duodenum to break apart large fatty globules into free Fatty acids

Question 5

Orlistat FAI Therapeutic Effects

Answer 5

Primarily used to treat obesity

additional effect to decrease LDL levels in obese patients

Question 6

Zetia ADME

Answer 6

Absorbed, glucouronidated and reexcreted in the gut. Plasma peak concerntration at 4 to 12 h
Zetia is systemic to a limited degree about 90% protein bound.
T1/2 is equal to 22 hours`

Question 7

Orlistat ADME

Answer 7

poorly absorbed systemically
stays in the gut
Minimal metabolism in the gut epithelium and microflora
Eliminated in feces

Question 8

Bile Acid Binding Resins MOA (Cholestyramine)

Answer 8

Bind bile acids
Bind negatively charged bile acids in the small intestine
Resin/bile acid complex is excreted in feces
Hepatocytes increase conversion of cholesterol to bile acid to compensate for loss
up regulate LDL Receptors to increase uptake of cholesterol and decrease plasma LDL

Question 9

Therapeutic effects of BABS

Answer 9

Moderate decrease in LDL levels, increasing HDL

Large Molecules, insoluble in water, not absorbed or metabolized will be excreted via feces

Question 10

Adverse Effects of BABS

Answer 10

GI effects: flatulence, constipation, diarrhea
Impaired absorption: may decrease fat soluble vitamin absorption
Drug interactions: Decrease absorption of many drugs
(tetracycline,phenobarbital, digoxin, warfarin, pravastatin, fluvastatin, aspirin and thiazides)

Question 11

BABSTherapeautic cautions/ Contraindications

Answer 11

Safe drug
Can be used during pregnancy without causing harm
Biliary stones or complete bilary obstruction: contraindicated if bile acid secretion is impaired

Question 12

BABS ADME

Answer 12

A- not systemically absorbed
D-stays in the gut
M-not metabolized
E- Feces

Question 13

Niacin MOA

Answer 13

at gram doses, Strongly inhibit lipolysis of adipose tissue

utilizes circulating FA as precursors of triglycerol synthesis which is used in synthesis of VLDL and ultimately LDL

Question 14

Therapeutic Effects of Niacin

Answer 14

Lowers plasma levels of both cholesterol and triacylglycerol

The most effective antihyperlipidemic to raise plasma HDL Levels

Question 15

Niacin ADME

Answer 15

Peak plasma Concentrations
niacor~ 30 to 60 min
Niaspan ~ 5 h but varies
Broad systemic distribution
Rapid 1st pass metabolism
excreted mostly in urine and 12% as parent compound

Question 16

Adverse effects of Niacin

Answer 16

Primarly Intense Cutaneous Flush and Pruitis
N/V, abdominal pain
Inhibits tubular secretion of uric acid.
may impair glucose tolerance and caution w/ Diabetics
Hepatotoxicity

Question 17

Fibrates MOA

Answer 17

Increase LPL activity by activating PPARs which is a transcription factor for LPL synthesis.
LPL activity will decrease triacylglycerol levels by hydrolyzing triacylglycerols in chylomicrons and VLDL
Increase HDL levels

Question 18

Therapeutic effects of Fibrates

Answer 18

decrease triglyceride levels and Increase HDL cholesterol levels.
First line therapy to reduce risk of pancreatitis in patients with high plasma triglycerides.

Question 19

Adverse effects of fibrates

Answer 19

Mild GI disturbances 
Predisposition of gall stones 
hepatoxicity 
significant number of malignancy related deaths.
Myositis
Drug interactions
Contraindications

Question 20

Fibrate ADME

Answer 20

A: Lopid ~1 to2 h, Niaspan ~5 but highly variable
D: Broad systemic distribution, plasma bound
M: Rapid 1st pass
E: mostly glucouronidated in urine and less than 2% as parent compound. T1/2= 20 to 22 h

Question 21

Statin MOA

Answer 21

analogs HMG cholesterol precursor, Completley inhibits rate limiting enzyme in the synthesis of cholesterol
Depletion of intracellular cholesterol leads to elevated cellular LDL receptors to increase uptake from ciruclation
decreases cholesterol synthesis and increases catabolism of LDL

Question 22

Therapeutic uses of statins

Answer 22

Reduction of total and LDL cholesterol
first choice
may be useful in patients with or without CVD
Pleiotropic effects ( regression of plaque size increased endothelial function stablize platelets reduction of plasma fibrinogen Decrease inflammatory markers)

Question 23

Statin Adverse effects

Answer 23

Give warnings of myopathy and liver enzyme elevation

Hepatotoxicity is rare and muscle is rare and dose related

Question 24

When statins should be taken?

Answer 24

Atorvastatin and Rosuvastatin can be taken whenever

Simvastatin, lovastatin, fluvastatin, and lovastatin should be taken in the evening

Question 25

Pregnancy and Lipid lowering drugs

Answer 25

either totally or relatively contraindicated because essential role of cholesterol in fetal development
Bile acid resins should be used but do not use statins
woman desiring to become pregnant should stop statins 6 months before contraception