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Flashcards in Drugs for Lipid Disorders Deck (78)
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1

HMG-CoA reductase inhibitors

-Atorvastatin
-Fluvastatin
-Lovastatin
-Pitavastatin
-Pravastatin
-Rosuvastatin
-Simvastatin

2

Fabric acid derivatives

-fibrates
-fenofibrate
-gemfibrozil

3

Bile acid sequestrants

-resins
-cholestyramine
-cholesevelam
-colestipol

4

Cholestrol absorption inhibitors

-ezetimibe

5

Drug combinations

-simvastatin and ezetimibe
-niacin and lovastatin extended release
-niacin and simvastatin extended release

6

New treatment for homozygous familial hypercholestrolemia

-Lomitapide
-Mipomersen

7

Lipoprotein

-any lipid-protein complex in which lipids are transported in the blood; consist of a spherical hydrophobic core of triglycerides or cholestrol esters surrounded by an amphipathic monolayer of phospholipids, cholestrol, and apolipoprotiens; principal classes include HDL, LDL, VLDL, and chylomicrons

8

Hyperlipoproteinemia

-an excess of lipoproteins in the blood due to a disorder of lipoprotein metabolism (may be acquired or familial condition, or combination)

9

Hyperlipidemia (hyperlipemia)

-elevated concentrations of any or all of the lipids in the plasma (e.g. hypertriglyceridemia, hypercholestrolemia)

10

Chylomicron

-transport exogenous, dietary cholestrol and triglycerides from the small intestine to tissues after meals; synthesized in the intestinal mucosa and carried to the bloodstream, they are degraded to chylomicron remnants in the capillaries of muscle and adipose tissue via cleavage of the majority of their triglycerides by endothelial lipoprotein lipase

11

VLDL

-transports triglycerides from the liver to adipose and muscle tissues
-synthesized by liver
-Made up of endogenous TGs

12

LDL

-transports cholestrol to extrahepatic tissues; formed in circulation when VLDL are degraded first to IDL and then to LDL; taken up and catabolized by both the liver and extra hepatic tissues by specific receptor-mediated endocytosis
-made up of cholestrol esters

13

IDL

-formed in the degradation of VLDL; half are absorbed by the liver and the other half are degraded to form LDL
-made up of endogenous cholestrol esters and TGs

14

HDL

-promotes the transport of cholestrol from extra hepatic tissue to the liver for excretion in the bile
-synthesized by the liver
-Made up of phospholipids, cholestrol esters

15

Lipoprotein lipase (LPL)

-located on the inner surface of the capillary endothelial cells of muscle and adipose tissue
-LPL digests the TGs in the chylomicron producing free fatty acids (used for energy production (muscle) or fat storage (adipocyte)) and glycerol (metabolized in the liver

16

Dietary management of hyperlipoproteinemia

-dietary measures are initiated first unless the patient has evident coronary or peripheral vascular disease, which may require the need for drugs

17

Principal factors that increase LDL

-cholestrol and saturated and trans fats

18

Increase triglycerides

-total fat, alcohol and excess calories

19

General dietary recommendations to control hyperlipoproteinemia

-Limit total calories from fat to 20-25% daily intake
-Limit saturated fats to less than 8% of daily intake
-limit cholestrol to less than 200mg/day
-reductions in serum cholestrol range from 10-20% on the above regimen

20

Omega-3 polyunsaturated fatty acids

-found in fish oils can induce profound reduction of triglycerides in some patients, however there is no evidence from prospective trials that fish oil supplements prevent cardiovascular disease in the general population

21

Patients with familial hypercholestrolemia or familial combined hyperlipidemia will

-always require drug therapy (children may initiate therapy with a resin or statin after 7-8 years of age based on LDL levels, other risk factors and family history)

22

HMG-CoA reductase inhibitors (statins) are

the most effective agents in reducing LDL levels and best tolerated class of lipid lowering agents

23

Statin chemistry

-structural analogs of HMG-CoA, an initial precursor of cholestrol

24

Lovastatin and simvastatin are

inactive prodrugs that must be hydrolyzed in the GI tract to active compounds

25

Statin pharmakokinetics

-oral absorption of the ingested disease varies from 40-75% with the exception of fluvastatin, which is almost completely absorbed
-extensive first pass metabolism by the liver; subsequently, their primary action is on the liver
-Plasma half life 1-3 hours except for atorvastatin (14 hours) and rosuvastatin (19 hours)
-most of absorbed dose is excreted in the bile; 5-20% in the urine

26

Statins metabolized primarily by CYP3A4

-Lovastatin
-Simvastatin
-atorvastatin

27

Statins metabolized primarily by CYP2C9

-fluvastatin
-rosuvastatin

28

Pitavastatin metabolism

-undergoes limited CYP450 biotransformation

29

Pravastatin metabolism

-not metabolized by CYP450

30

Statin MOA

-statins inhibit HMG-CoA reductase, the rate limiting enzyme in cholestrol synthesis
-inhibiting de novo cholestrol synthesis depletes in the intracellular supply of cholestrol, which causes the cell to increase the number of specific cell surface LDL receptors that can bind and internalize circulating LDLs
-Increased expression of surface LDL receptors reduces circulating LDL levels