Pharm for Hyperlipidemia Flashcards
Zetia (Ezetimibe) COI MOA
Selective inhibition of cholesterol absorption by blocking transport at the brush order of the small intestine.
Zetia (Ezetimibe) COI Therapeutic Effects
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
Zetia (Ezetimibe) COI Adverse Effect and Excretion
Flatulence
Diarrhea
Myalgia
Excreted primarily in feces
Orlistat (Xenical, Alli) FAI MOA
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
Orlistat FAI Therapeutic Effects
Primarily used to treat obesity
additional effect to decrease LDL levels in obese patients
Zetia ADME
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`
Orlistat ADME
poorly absorbed systemically
stays in the gut
Minimal metabolism in the gut epithelium and microflora
Eliminated in feces
Bile Acid Binding Resins MOA (Cholestyramine)
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
Therapeutic effects of BABS
Moderate decrease in LDL levels, increasing HDL
Large Molecules, insoluble in water, not absorbed or metabolized will be excreted via feces
Adverse Effects of BABS
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)
BABSTherapeautic cautions/ Contraindications
Safe drug
Can be used during pregnancy without causing harm
Biliary stones or complete bilary obstruction: contraindicated if bile acid secretion is impaired
BABS ADME
A- not systemically absorbed
D-stays in the gut
M-not metabolized
E- Feces
Niacin MOA
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
Therapeutic Effects of Niacin
Lowers plasma levels of both cholesterol and triacylglycerol
The most effective antihyperlipidemic to raise plasma HDL Levels
Niacin ADME
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
Adverse effects of Niacin
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
Fibrates MOA
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
Therapeutic effects of Fibrates
decrease triglyceride levels and Increase HDL cholesterol levels.
First line therapy to reduce risk of pancreatitis in patients with high plasma triglycerides.
Adverse effects of fibrates
Mild GI disturbances Predisposition of gall stones hepatoxicity significant number of malignancy related deaths. Myositis Drug interactions Contraindications
Fibrate ADME
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
Statin MOA
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
Therapeutic uses of statins
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)
Statin Adverse effects
Give warnings of myopathy and liver enzyme elevation
Hepatotoxicity is rare and muscle is rare and dose related
When statins should be taken?
Atorvastatin and Rosuvastatin can be taken whenever
Simvastatin, lovastatin, fluvastatin, and lovastatin should be taken in the evening
Pregnancy and Lipid lowering drugs
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
