Drugs for Lipid Disorders

Question 1

Lovastatin, atorvastatin, fluvastatin, pitavastatin, pravastin, siimvastatin and rosuvastatin are all inhibitors of _

Answer 1

HMG-CoA

Question 2

Fenofibrate and gemfibrozil are _

Answer 2

Fibric acid derivatives (fibrates)

Question 3

Cholestyramine, colesevelam and colestipol are _

Answer 3

Bile acid sequestrants (resins)

Question 4

name a cholesterol absorption inhibitor

Answer 4

Ezetimibe (Zetia)

Question 5

What are three drug combination to treat hyperlipidemia?

Answer 5

1. Ezetimibe and Simbastain
2. Niacin and lovastatin
3. Niacin and simvatatin

Question 6

New treatment for homozygous familial hypercholesterolemia include

Answer 6

Lomitpide and mipomersen

Question 7

Cholesterol and saturated and transfat are the main factors that increase serum _

Answer 7

LDL

Question 8

Total fat, alcohol, and exess calories increase serum _

Answer 8

triglycerides

Question 9

Dietary management of hyperlipoproteinemia is always the first option unless a patient has _ in which case drug therapy is the first option.

Answer 9

Familial hypercholesterolemia

Question 10

What class of lipid lower drugs are the most effective in reducing LDL levels and best tolerated class of lipid lowering agents.

Answer 10

HMG-CoA reductase inhibitors (Statins)

Question 11

Statin drugs are analogs of _

Answer 11

HMG-CoA which is an initial precursor of cholesterol.

Question 12

Which statins are prodrugs and thus must be hydrolyzed in the GI to active compounds?

Answer 12

Lovastatin and simvastatin

Question 13

Which statins have the longest half life?

Answer 13

atorvastatin (14hrs) and rosuvastatin (19hrs)

Question 14

Which statin is almost completely absorbed when given orally, while most others varies 40-75%

Answer 14

Fluvastatin

Question 15

Which statins are metabolized by
A. CYP3A4
B. CYP2C9

Answer 15

A. Lova, simva, and atorvastatin

B. Fluva, rosuvastatin

Question 16

Explain the MOA for statins

Answer 16

Inhibits HMG-CoA and thus inhibits de novo synthesis of cholesterol. this in turn causes cell to increase cell surface LDL receptors and internalize LDL and thus reduce circulating LDL’s

Question 17

Which statin has the highest potency?

Answer 17

Atorvastain and rosuvastain

Question 18

What therapeutic benefits does statins have beside lowering LDL

Answer 18

stabilize plaques, improve coronary endothelial function, inhibition of platelet thrombus formation, and anti-inflammatory effects.

Question 19

Why should statins be taken in the evening/night?

Answer 19

Cholesterol synthesis occurs primarily at night

Question 20

What are some contraindications for statins?

Answer 20

• pregnancy/lactating
• liver disease/skeletal muscle myopathy
• avoid use with other agents that inhibit or compete CYP450 enzyme except pravastatin and pitavastatin) such as phenytoin, griseofulvin

Question 21

what are some adverse effects of statins?

Answer 21

Liver: elevates aminotransferase activity
Muscle: elevates creatinine kinase activity; rhabdomyolysis –> renal injury; myopathy esp in combo with cyclosporine, intraconzaole, erythromycin, gemfibrozoil or nicin
- Increases warfarin levels

Question 22

WHat drug class is know to be most effective in increasing HDL levels while lower LDL and VLDL and triglyerides?

Answer 22

Niacin (nicotinic acid, vit B3)

Question 23

What lipid-lowering agent is best known to reduce lipoprotein levels significnatly (up to 40%)

Answer 23

Niacin

Question 24

What is the MOA of niacin drugs?

Answer 24

inhibits lipolysis of triglycerides in adipose tissue and thus reduce circulating free fatty acids, and thus liver produces less VLDL and thus decreases LDL
2. Fibrinogen levels are also reduced and tPA levels are increased which can reverse endothelial dysfunction

Question 25

Niacin is often used in combo with _1_ and is utilized in the treatment of mixed lipemia that is incompletely response to diet

Answer 25

bile acid sequestrant (resin)

Question 26

What adverse effects are associated with Niacin?

Answer 26

Intense cutaneous flush (uncomfortable feeling of warmth - can be helped if aspirin or ibuprofen before niacin dose) - pruritis, rashes, dry skin/mucous membranes, acnthosis nigricans

Question 27

What are some contraindications for niacin?

Answer 27

- liver disease --> hepatoxicity - peptic ulcer - caution in pts with DM (niacin-induced insulin resistance --> hyperglycemia)

Question 28

What is the MOA for gemfibrozil and fenofibrate?

Answer 28

(these are fibric acid derivatives) - Agonists for PPAR-alpha which binds to preroxisome proliferator-response elements (encodes lipoprotein structure and function-->incrase lipoprotein lipase) --> induce lipolysis of triglycerides and ultimately decrease plasma concentration of triglycerides

Question 29

what is the indication for gemfibrozil and fenofibrate?

Answer 29

- management of hypertriglyceridemias where VLDL predominates - dysbetalipoproteinemia - adjunct to HIV therapy

Question 30

what adverse effects are associated with gemfibrozil and fenofibrate?

Answer 30

- GI disturbances (most common) - llithiasis (cuz of increased biliary cholesterol excretion) --> gall stones - myositis (muscle weakness); myopathy

Question 31

fibrates are known to potentiate the actions of _

Answer 31

coumarin and indanedione anticoagulents

Question 32

Fibrates are contraindicated in pts with _

Answer 32

- hepatic or renal dysfunction | - pts with increased risk of gallstones

Question 33

Colestipol, choestryamine and colesevelam are all _1_ which binds to _2_ and increase their excretion, and thus enhances the conversion of cholesterol to bile acids in the liver via _3_ which is normally controlled by negative feedback by bile acids. The decline in hepatic cholesterol stimulates an increase in _4_ receptors which enhances _5_ clearance. But becuase this enhances cholesterol synthesis, these drugs are usually used in combo with _6_

Answer 33

1. bile acid sequestrants (resins) 2. bile acids 3. 7a-hyroxylatation 4. LDL 5. LDL 6. HMG-CoA inhibitors (statins)

Question 34

What are the therapeutic uses of bile acid sequestrants?

Answer 34

- primary hypercholesterolemia - in combo with niacin for tx of Type IIa and Type IIb hyperlipidemias - pruritis - digitalis toxicity

Question 35

What adverse effects are associated with bile acid sequestrant?

Answer 35

- GI issues most common - at high dose impairs (ADEK vitamins absorption) - Cholestryramien andcolestipol impairs absorption of drugs such tetracycline, phenobarbital, digoxin, warfarin, pravastain, fluvastatin, aspirin, thiazide diuretics (

Question 36

Ezetimibe is a _ 1_ that which enters enterohepatic circulation as an active compound and inhibits intestinal absorption of cholesterol and phytosterols and inhibits transport protein NPC1L1

Answer 36

cholesterol absorption inhibitor

Question 37

What is ezetimibe used for?

Answer 37

- various forms of elevated cholesterol diseases such as primary hypercholesterolemia (w/wo statins), homozygous familial hypercholesterolemia (in combi with ator or simvastain), mixed hyperlipidemia (in combo with fenofibrate)

Question 38

what adverse effects/contraindications are associated with ezetimibe?

Answer 38

no significant drug interaction but should be avoid with bile acid sequestrant cuz it inhibits ezetimibe absorption

Question 39

what combination of drugs would have the greatest effect in lowering LDL and TG's?

Answer 39

Statins and Fibrates

Question 40

What combination of drugs would have the greatest effect in lowering LDL and increasing HDL?

Answer 40

Statins and Niacin

Question 41

What combination of drugs would have the greatest effect in lower TG's and increasing HDL?

Answer 41

Nacian and Fibrates

Question 42

What is the MOA for lomitapride?

Answer 42

directly binds to and inhibits microsomal triglyceride transfer protien which is located in the lumen of the ER. MTP inhibition prevenst the assembly of apo-B lipoproteins in enterocytes and hepatocytes --> reduced production of chylomicrons and VLDL and --> reduce LDL-C concentration

Question 43

What is lomitapride FDA approved for?

Answer 43

homozygous familial hypercholesterolemia

Question 44

what is the common adverse effect of lomitap? ride

Answer 44

GI symptoms, increased liver aminotransferase levels, and hepatic fat accumulation

Question 45

What is mipomersen approved for?

Answer 45

homozygous familial hypercholesterolemia

Question 46

what is the MOA of mipomersen?

Answer 46

antisense oligonucleotide that targets apoliporotein B-100 mRNA and disrupts its function which is needed for transport and removal of atherogenic lipids.

Question 47

what adverse effects are associated with mipomersen?

Answer 47

- injection site RXN - flu like symptoms - Headaches - elevated liver enzymes