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Cardiovascular Medicine Midterm > Drugs for Lipid Disorders > Flashcards

Drugs for Lipid Disorders Flashcards

1
Q

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

A

HMG-CoA

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2
Q

Fenofibrate and gemfibrozil are _

A

Fibric acid derivatives (fibrates)

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3
Q

Cholestyramine, colesevelam and colestipol are _

A

Bile acid sequestrants (resins)

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4
Q

name a cholesterol absorption inhibitor

A

Ezetimibe (Zetia)

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5
Q

What are three drug combination to treat hyperlipidemia?

A
  1. Ezetimibe and Simbastain
  2. Niacin and lovastatin
  3. Niacin and simvatatin
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6
Q

New treatment for homozygous familial hypercholesterolemia include

A

Lomitpide and mipomersen

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7
Q

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

A

LDL

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8
Q

Total fat, alcohol, and exess calories increase serum _

A

triglycerides

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9
Q

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

A

Familial hypercholesterolemia

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10
Q

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

A

HMG-CoA reductase inhibitors (Statins)

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11
Q

Statin drugs are analogs of _

A

HMG-CoA which is an initial precursor of cholesterol.

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12
Q

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

A

Lovastatin and simvastatin

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13
Q

Which statins have the longest half life?

A

atorvastatin (14hrs) and rosuvastatin (19hrs)

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14
Q

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

A

Fluvastatin

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15
Q

Which statins are metabolized by
A. CYP3A4
B. CYP2C9

A

A. Lova, simva, and atorvastatin

B. Fluva, rosuvastatin

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16
Q

Explain the MOA for statins

A

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

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17
Q

Which statin has the highest potency?

A

Atorvastain and rosuvastain

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18
Q

What therapeutic benefits does statins have beside lowering LDL

A

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

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19
Q

Why should statins be taken in the evening/night?

A

Cholesterol synthesis occurs primarily at night

20
Q

What are some contraindications for statins?

A
  • 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
21
Q

what are some adverse effects of statins?

A

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

22
Q

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

A

Niacin (nicotinic acid, vit B3)

23
Q

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

A

Niacin

24
Q

What is the MOA of niacin drugs?

A

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

25
Q

Niacin is often used in combo with 1 and is utilized in the treatment of mixed lipemia that is incompletely response to diet

A

bile acid sequestrant (resin)

26
Q

What adverse effects are associated with Niacin?

A

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

27
Q

What are some contraindications for niacin?

A
  • liver disease –> hepatoxicity
  • peptic ulcer
  • caution in pts with DM (niacin-induced insulin resistance –> hyperglycemia)
28
Q

What is the MOA for gemfibrozil and fenofibrate?

A

(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

29
Q

what is the indication for gemfibrozil and fenofibrate?

A
  • management of hypertriglyceridemias where VLDL predominates
  • dysbetalipoproteinemia
  • adjunct to HIV therapy
30
Q

what adverse effects are associated with gemfibrozil and fenofibrate?

A
  • GI disturbances (most common)
  • llithiasis (cuz of increased biliary cholesterol excretion) –> gall stones
  • myositis (muscle weakness); myopathy
31
Q

fibrates are known to potentiate the actions of _

A

coumarin and indanedione anticoagulents

32
Q

Fibrates are contraindicated in pts with _

A
  • hepatic or renal dysfunction

- pts with increased risk of gallstones

33
Q

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

A
  1. bile acid sequestrants (resins)
  2. bile acids
  3. 7a-hyroxylatation
  4. LDL
  5. LDL
  6. HMG-CoA inhibitors (statins)
34
Q

What are the therapeutic uses of bile acid sequestrants?

A
  • primary hypercholesterolemia
  • in combo with niacin for tx of Type IIa and Type IIb hyperlipidemias
  • pruritis
  • digitalis toxicity
35
Q

What adverse effects are associated with bile acid sequestrant?

A
  • 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 (
36
Q

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

A

cholesterol absorption inhibitor

37
Q

What is ezetimibe used for?

A
  • 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)
38
Q

what adverse effects/contraindications are associated with ezetimibe?

A

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

39
Q

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

A

Statins and Fibrates

40
Q

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

A

Statins and Niacin

41
Q

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

A

Nacian and Fibrates

42
Q

What is the MOA for lomitapride?

A

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

43
Q

What is lomitapride FDA approved for?

A

homozygous familial hypercholesterolemia

44
Q

what is the common adverse effect of lomitap? ride

A

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

45
Q

What is mipomersen approved for?

A

homozygous familial hypercholesterolemia

46
Q

what is the MOA of mipomersen?

A

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

47
Q

what adverse effects are associated with mipomersen?

A
  • injection site RXN
  • flu like symptoms
  • Headaches
  • elevated liver enzymes

Cardiovascular Medicine Midterm (6 decks)

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