Drugs For Lipid Disorders-Kruse

Question 1

These statins are metabolized primarily by CYP3A4

Answer 1

Lovastatin, Simvastatin, and Atorvastatin

Question 2

These statins are metabolized primarily by CYP2C9

Answer 2

Fluvastatin and Rosuvastatin

Question 3

This statin is not metabolized by CYP450s

Answer 3

Pravastatin and Pitavastatin

Question 4

What are therapeutic benefits of statins?

Answer 4

Plaque stabilization
Improvement of coronary endothelial function
Inhibition of platelet thrombus formation
Anti-inflamm effects

Question 5

What are the more potent statins?

Answer 5

Atorvastatin=Rosuvastatin > Simvastatin….then the rest

Question 6

When should statins be given?

Answer 6

Evening

Question 7

Describe adverse effects of statins and muscle:

Answer 7

Creatine kinase activity levels may increase
Rhabdomyolysis can occur rarely and lead to renal injury
Myopathy can occur with mono therapy; increased incidence of myopathy occurs in pts also taking cyclosporine, itraconazole, erythromycin, gemfibrozil, or niacin

Question 8

What adverse effect can statins have on warfarin levels?

Answer 8

Increase warfarin levels

Question 9

When are statins contraindicated?

Answer 9

Pregant women, lactating, or likely to become pregnant

Use is not recommended in pts with liver disease or skeletal muscle myopathy

Question 10

This is the most effective agent for increasing HDL levels; lowers LDL and VLDL levels by 10-20% and TG’s by 35-45%

Answer 10

Niacin (nicotinic acid, B3)

Question 11

This is the only lipid-lowering agent that reduces lipoprotein(a) levels significantly

Answer 11

Niacin

Question 12

This agent inhibits the lipolysis of TG’s in adipose tissue (plasma TGs in VLDL and cholesterol in VLDL and LDL decrease

Answer 12

Niacin

Question 13

This anti-hyperlipidemic drug class has the greatest effect on decreasing LDL

Answer 13

Statins

Question 14

This anti-hyperlipidemic drug class has the greatest effect on increasing HDL

Answer 14

Niacin

Question 15

This anti-hyperlipidemic drug class has the greatest effect on lowering TG’s

Answer 15

Fibrates

Question 16

What are expected genetic changes with administration of simvastatin (or statins in general)

Answer 16

Increased expression of LDL receptors

Question 17

What is the MOA of FIbrates?

Answer 17

Agonist for PPARalpha receptor

Question 18

Fibrates (PPARa receptor agonists) induce expression of __ enzyme which leads to lipolysis of TGs and decreases in plasma concentrations

Answer 18

Lipoprotein lipase

Question 19

What are some adverse effects associated with fibrates?

Answer 19

GI disturbances (most common
Lithiasis 
Gallstones
Myositis
Myopathy
Rhabdomyolysis

Question 20

Which cholesterol absorption inhibitor can be prescribed in combo with simvastatin to further decrease LDL levels?

Answer 20

Ezetimibe

Question 21

What is the MOA of Ezetemibe (Cholesterol absorption inhibitor)?

Answer 21

Selectively inhibits intestinal absorption of cholesterol and phytosterols (plant sterols); thought to inhibit the transport protein NPC1L1

Used alone or in combo with a statin or fibrates

Question 22

Assuming a pt is heterozygous for a mutation in lipoprotein lipase, which class of agents used to treat hyperlipidemia would be most effective at treating the pts elevated TG levels?

Answer 22

Fibrates

Question 23

What is the most common side effect of niacin?

Answer 23

Intense cutaneous flush accompanied by an uncomfortable feeling of warmth. Aspirin taken before niacin or once-daily ibuprofen can mitigate the flushing, which is PG-mediated

Can also get acanthosis nigricans

Question 24

Gemfibrozil and fenofibrate are part of this drug class

Answer 24

Fibrates

Question 25

Colestipol, cholestyramine, and colesevelam are part of this drug class

Answer 25

Bile acid sequestrants (resins)

Question 26

What is the MOA of bile acid sequestrants (resins)?

Answer 26

These are + charged compounds that bind to negative charged bile acids (metabolites of cholesterol), increasing their excretion up to 10 fold

Question 27

What are therapeutic uses of bile acid sequestrants (resins)?

Answer 27

Used to tx pts with primary hypercholesterolemia

Monotherapy for tx of Type IIa and Type IIb hyperlipidemia

Used to relieve pruritis in pts who have bile salt accumulation

May be used for digitalis toxicity

Question 28

What are adverse effects of bile acid sequestrants?

Answer 28

GI effects are most common (Colesevelam has fewest GI effects of this class)

At high doses, cholestyramine and colestipol impair reabsorption of fat-soluble vitamins ; these drugs also impair absorption of numberous drugs such as tetracycline, phenobarbital, digoxin, warfarin, pravastatin, fluvastatin, aspirin, and thiazide diuretics

Question 29

What are contraindications for bile acid sequestrants?

Answer 29

Avoid or use with caution in pts with diverticulitis, preexisiting bowel disease, or cholestasis

Question 30

What are therapeutic uses of Ezetimibe?

Answer 30

Tx various causes of elevated cholesterol levels

Homozygous familial hypercholesterolemia (in combo with atorvastatin or simvastatin)

Mixed hyperlipidemia (in combo with fenofibrate)

Question 31

What is the MOA for Lomitapide?

Answer 31

Directly binds to an inhibits microsomal TG transfer protein (MTP) which is located in the lumen of the ER. MTP inhibition prevents assembly of apo-B containing lipoproteins in enterocytes and hepatocytes resulting in reduced production of chylomicrons and VLDL and subsequently reduced plasma LDL-C concentrations

Question 32

This drug was approved in 2012 for tx of homozygous familial hypercholesterolemia by directly binding to and inhibiting microsomal TG transfer protein (MTP)

Answer 32

Lomitapide

Question 33

Statins are __ inhibitors

Answer 33

HMG-CoA reductase