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Adv Pharm 1 > Dyslipidemia > Flashcards

Dyslipidemia Flashcards

1
Q

What are Lipoproteins?

A

Droplets of fats surrounded by a single layer of phospholipid molecules.

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2
Q

What are phospholipids?

A

Molecules of fats what are attached to a phosphorus-containing group

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3
Q

What does Amphipathic mean?

A

Having both polar and non-polar ends.

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4
Q

Why is it important that Lipoproteins are Amphipathic?

A

-The polar ends face outwards and interact with water. The lipoprotein can be carried in the blood rather than rising to the top, like cream on milk
-Non-polar fat is balled up inside the phospholipid layer
-Allows fat to be transported through the blood to the place where it must be stored or metabolized despite being insoluble in blood

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5
Q

How are lipoproteins differentiated?

A

Differentiated based on specific proteins attached to the phospholipid outer layer.
-Apolipoprotein, Apoprotein

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6
Q

What are the two major sequelae associated with increased Lipoproteins? (Blue Box!)

A

-Acute Pancreatitis
-Atherosclerosis

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7
Q

What is the leading cause of death for both men & women in the US? (Blue box!)

A

Atherosclerosis

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8
Q

What are Chylomicrons?

A

-The largest and least dense of the lipoproteins
-Originate in the intestines in intestinal lymphatics and deliver fats and cholesterol from the intestines to the muscles, fat cells, and the liver
-Have a protein component synthesized in the liver, which wraps around diet-derived cholesterol and fats.
-Travel from the intestinal lymphatics to the large veins
-Stick to the inner surface of the tiny capillary blood vessels inside the muscles and the fat storage cells in various parts of the body
-Triglycerides are digested & the cholesterol remains
-Cholesterol remnant travels to the liver for metabolism
-Highest triglyceride content (associated with pancreatitis!!)
-The higher the triglycerides, the lower the density

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9
Q

What are VLDL Lipoproteins?

A

-Composed of protein, fats and cholesterol synthesized in the liver.
-5 different apoproteins
-Converted to IDL and LDL by removal of the apoproteins and the esterification of the cholesterol.
-2nd highest triglyceride count

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10
Q

What is esterification?

A

Converting cholesterol to cholesterol, allowing more to become packed inside (becomes more dense).

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11
Q

What are IDL lipoproteins?

A

Created by the metabolism of VLDL

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12
Q

What are LDL Lipoproteins?

A

-Created by the metabolism of VLDL
-Contains chiefly cholesterol
-Only one apoprotein (ApoB-100).
-More dense than VLDL as it goes through esterification process.
-Known for bulking up artery walls and decreasing ability to dilate. Involved with plaques in arteries.

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13
Q

What are HDL Lipoproteins?

A

-Have the highest protein:lipid ratio (densest)
-“Good Cholesterol”
-Carries cholesterol away from the tissues to the liver
-Lowering blood cholesterol levels
-⬆HDL levels are associated with ⬇ risk of cardiovascular disease

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14
Q

What are ways to increase HDL levels?

A

-Exercise
-Higher estrogen levels
-Alcohol consumption (red wine)
-Weight loss
(technically, smoking cigarettes also does but not recommended)

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15
Q

T/F: With LDLs and Triglycerides, the higher amount the better.

A

False; want these to be low and HDLs to be high.

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16
Q

What are the disorders associated with Primary Hypertriglyceridemias?

A

-Primary Chylomicronemia
-Familial Hypertriglyceridemia (Severe or Moderate)
-Familial Combined Hyperlipoproteinemia
-Familial Dysbetalipoproteinemia

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17
Q

What are the disorders associated with Primary Hypercholesterolemias?

A

-Familial Hypercholesterolemia
-Familial Ligand-Defective Apolipoprotein B-100
-Familial Combined Hyperlipoproteinemia
-Lp(a) Hyperlipoproteinemia

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18
Q

Before primary disorders can be diagnosed, ______ causes must be considered.

A

Secondary

Primary diagnosis is of exclusion - have to rule out other secondary causes.

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19
Q

With secondary causes, the lipoprotein abnormality usually ______ if the underlying disorder can be treated.

A

Resolves

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20
Q

What are the most common secondary causes of hypertriglyceridemia (Hyperlipoproteinemia)?

A

-Diabetes Mellitus
-Alcohol ingestion
-Severe nephrosis
-Estrogens
-Uremia
-Corticosteroid excess
-Myxedema
-Glycogen storage disease
-Hypopituitarism
-Acromegaly
-Immunoglobulin-lipoprotein complex disorders
-Lipodystrophy
-Protease inhibitors

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21
Q

What are the most common secondary causes of hypercholesterolemia (Hyperlipoproteinemia)?

A

-Hypothyroidism
-Early nephrosis
-Resolving Lipemia
-Immunoglobulin-lipoprotein complex disorders
-Anorexia nervosa
-Cholestasis
-Hypopituitarism
-Corticosteroid excess

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22
Q

What are the treatments for Hyperlipoprotein diseases?

A

1) Dietary measures always initiated first. But, issues with compliance.
-Unless they have CAD or PVD, then go straight to pharmacologic intervention in addition to dietary
-Familial issues ALWAYS require drug therapy as well
-Weight has to stabilize for 1 month - don’t want them to go on a crash diet and lose weight fast then gain it all back. Establish healthy eating habits.

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23
Q

What increases LDL?

A

-Cholesterol
-Saturated fats
-Trans fats

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24
Q

What increases triglycerides?

A

-Total fat
-Alcohol
-Excess calories

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25
Q

What increases VLDL?

A

-Sucrose
-Fructose

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26
Q

The conclusion that diet suffices for management can only be made after weight has stabilized for at least _____ month. (Blue Box!)

A

The conclusion that diet suffices for management can only be made after weight has stabilized for at least 1 month.

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27
Q

What populations are c/i with the use of meds for Hyperlipoproteinemia?

A

-C/I in pregnant and lactating women and women looking to conceive.
-Has drug interactions with anticoagulants (monitor and adjust warfarin and indadione anticoagulants)
-Typically not used until after the age of 16, but can be used after age 7/8 if you ensure that the neuro system has had time for complete myelination
-Need robust H&P on these people

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28
Q

The ____ is central to cholesterol metabolism.

A

The Liver is central to cholesterol metabolism.

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29
Q

Hepatic Cholesterol can be synthesized from __________ in a multi-step enzymatic process, whose rate-limiting enzyme, _______, is inhibited by _________.

A

Hepatic cholesterol can be synthesized from acetyl coenzyme A (CoA) in a multi-step enzymatic process, whose rate-limiting enzyme, 3-hydroxy-3- methylglutaryl CoA reductase, is inhibited by Statins such as atorvastatin.

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30
Q

What is the rate-limiting enzyme for hepatic cholesterol?

A

3-hydroxy-3- methylglutaryl CoA reductase (3HMG CoA Reductase)

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31
Q

Hepatic Cholesterol is used in part to synthesize _____ that are destined, with sterols, for secretion in bile.

A

Hepatic cholesterol is used in part to synthesize bile acids that are destined, with sterols, for secretion in bile.

32
Q

The luminal sterol pool in the upper portion of the small intestine comes from both ________ and ________ sterols.

A

The luminal sterol pool in the upper portion of the small intestine comes from both dietary and biliary sterols.

33
Q

Intestinal luminal sterols are transported into enterocytes and repackaged into ______________ for secretion into lymph and, ultimately, ______.

A

Intestinal luminal sterols are transported into enterocytes and repackaged into chylomicrons for secretion into lymph and, ultimately, plasma.

34
Q

T/F: Bile acids advance through the intestinal lumen and facilitate intestinal cholesterol absorption. Unbound bile acids are normally recycled through the terminal ileum into the enterohepatic circulation. Bile acid- binding resins, such as colestipol, prevent this recycling and force more hepatic cholesterol into bile acid synthesis.

A

True

35
Q

To compensate for the depletion of hepatic cholesterol stores induced by all of these drugs, the liver increases expression of _________________________________________________ receptors to extract more cholesterol from the plasma by receptor-mediated endocytosis.

A

To compensate for the depletion of hepatic cholesterol stores induced by all of these drugs, the liver increases expression of cell-surface low- density lipoprotein (LDL) receptors to extract more cholesterol from the plasma by receptor-mediated endocytosis.

36
Q

What are the HMG-CoA Reductase Inhibitors?

A

-The “Statins”
-Structural analogs of HMG-CoA
-Most effective in ⬇LDL
-⬇ Oxidative stress (less imbalance of free radicals)
-⬇ Vascular inflammation
-⬆ Stability of atherosclerotic lesions (prevents thrombotic events)

37
Q

When is statin therapy initiated in acute coronary syndrome? (Blue Box!!)

A

Statin therapy is initiated immediately after acute coronary syndromes regardless of lipid levels

38
Q

What are the examples of the HMG-CoA Reductase Inhibitors that you need to know?

A

-Lovastatin (Mevacor) - parent drug
-Atorvastatin (Lipitor) - most lipophilic
-Simvastatin (Zocor)
-Rosuvastatin (Crestor) - least lipophilic (most lipophobic)

39
Q

Which two drugs are the Reductase Inhibitors that are inactive, lactone prodrugs and also are hydrolyzed in the GI tract?

A

-Lovastatin
-Simvastatin

40
Q

Which two drugs are the Reductase Inhibitors that are Fluorine containing congeners and are active as given?

A

-Atorvastatin
-Rosuvastatin

41
Q

Absorption of the Statins varies from ___% to ____%.

A

Absorption of the Statins varies from 45%-75%

42
Q

How are all Statins metabolized/excreted?

A

-All are metabolized in the liver by CYP3A4 and CYP2C9
-All are excreted mostly in the bile with 5-20% in the urine

43
Q

Which 2 Reductase Inhibitors have half-lives of 1-3 hours?

A

-Lovastatin
-Simvastatin

44
Q

Which Reductase Inhibitor has a half-life of 14 hours?

A

Atorvastatin

45
Q

Which Reductase Inhibitor has a half-life of 19 hours?

A

Rosuvastatin

46
Q

What is the therapeutic use for the Reductase Inhibitors (Statins)?

A

-Used in mono or combination therapy to reduce LDLs
-Can be used in combo with Resins, Niacin, or Ezetimibe

47
Q

When are Reductase Inhibitors (Statins) contraindicated?

A

C/I in pregnant/lactating women or women likely to become pregnant

48
Q

What are the administration facts to know regarding Reductase Inhibitors (Statins)?

A

Administer at night b/c cholesterol production happens at night
-Exceptions: Atorvastatin & Rosuvastatin

Absorption is enhanced by food
-Exception: Pravastatin

49
Q

Why can you administer Atorvastatin and Rosuvastatin anytime?

A

Atorvastatin & Rosuvastatin have longer half-lives, so don’t have to be administered at a certain point in time.

50
Q

What are the toxicity S/Sx associated with the Reductase Inhibitors (Statins)?

A

-Elevated serum aminotransferase activity (up to 3xs normal levels)
-Elevated CK
-Myopathies (!), muscle pain, cramps, weakness, stiffness, spasms
-Metabolized by CYP 450 (other drugs that inhibit or induce will change concentration)
-D/C for serious illness, trauma, or major surgery

51
Q

What is important to know regarding Statins and serum aminotransferase activity?

A

-Can cause Elevated serum aminotransferase activity (up to 3xs normal levels)
-Therapy may be continued if patient asymptomatic
-Malaise, Anorexia, & Precipitous decrease in LDL = D/C Immediately due to liver injury
-Measure baseline➜ 1-2 months ➜ 6-12 months (if stable)

52
Q

What is important to know regarding Statins and CK levels?

A

-Can cause elevated CK
-Minor elevations common
-Marked elevations rare ➜ may progress to myoglobinuria & renal injury, Rhabdomyolysis

53
Q

T/F: If patient experiences myopathy, don’t switch them to another Statin because they won’t help.

A

False: Myopathy doesn’t occur in every statin. If they’re experiencing it, switch them to another Statin.

54
Q

What are the clinical effects of Niacin (Nicotinic Acid) = Vitamin B3?

A

-⬇ LDL, VLDL & Lp(a) levels in most patients
-⬆ HDL levels significantly
-Inhibits VLDL secretion from liver to the blood, decreasing production of LDL, and increasing hepatic clearance of VLDLs, leading to decreased triglycerides.
-Converted in the body to an amide builder for NAD (NAD = Niacinamide Adenine Dinucleotide)
-Excreted in the urine unmodified & as several metabolites

55
Q

What is the most effective agent for increasing HDLs, and the only agent that may reduce Lp(a)? (Blue Box!)

A

Niacin (Nicotinic Acid) AKA Vit B3

56
Q

What are the therapeutic uses for Niacin (Nicotinic Acid) AKA Vit B3?

A

-Mono or combination therapy with Resin or Statin
-Hypercholesterolemia (Heterozygous Familial Hypercholesterolemia)
-Severe mixed lipemia incompletely responsive to diet
-Dysbetalipoproteinemia
-Hypertriglyceridemia

57
Q

What are the toxicity symptoms associated with Niacin (Nicotinic Acid) AKA Vit B3?

A

-Cutaneous vasodilation (flushing)
-Pruritis, rashes & dry skin
-Dry mucous membranes
-Acanthosis Nigricans (brown/black hyperpigmentation of the skin),C/I Niacin use 2/2 insulin resistance
-May ⬆insulin resistance
-Nausea & ABD pain (Alleviated with antacid therapy)
-Potentiate Anti-HTN Agents
-Hyperuricemia (Allopurinol PRN)
-Elevated serum aminotransferase (Rarely associated with true hepatotoxicity)
-Impaired carbohydrate tolerance
-Red cell macrocytosis
-Platelet deficiency (rare)
-Atrial arrhythmias (rare)!!
-Macular Edema!!

58
Q

What is important to know regarding Niacin therapy and Acanthosis Nigricans?

A

-Acanthosis Nigricans: brown/black velvety hyperpigmentation of the skin. Usually in folds: armpits, neck folds
-D/c therapy immediately if developed.
-Prone to happen in pts with insulin resistance

59
Q

The occurrence of which two toxicity symptoms would cause you to d/c Niacin therapy?

A

-Atrial Arrhythmias (rare)
-Macular Edema (monitor vision)

60
Q

What are the two example drugs of the Fibric Acid Derivatives?

A

-Gemfibrozil (Lopid)
-Fenofibrate (Tricor)

Older drugs, not used as often anymore.

61
Q

What is Gemfibrozil (Lopid)?

A

-Protein bound
-Absorption improved with food
-Enterohepatic circulation
-Crosses the placenta (C/I in pregnancy)
-Half-life 1.5 hours
-70% kidney elimination (Unchanged)

62
Q

What is Fenofibrate (Tricor)?

A

-Isopropyl ester that is hydrolyzed in the intestine
-Half-life 20 hours
-60% urine excretion
-25% feces excretion

63
Q

Which of the Fibric Acid Derivatives has a longer half life?

A

Fenofibrate: 20 hrs
Gemfibrozil: 1.5 hrs

64
Q

What is the MOA for the Fibric Acid Derivatives?

A

Function primarily as ligands for the nuclear transcription receptor PPAR-α
-⬆ Oxidation of fatty acids in the liver & striated muscle
-⬆ Lipolysis of lipoprotein triglycerides
-⬇ VLDL, modest reductions in LDL
-Moderate ⬆ in HDL

Tells Liver not to secrete LDLs

65
Q

What are the uses for the Fibric Acid Derivatives?

A

-Hypertriglyceridemias in which VLDL predominates
-Dysbetalipoproteinemia

66
Q

What are the RARE toxicity effects associated with the Fibric Acid Derivatives?

A

-Rashes
-GI symptoms
-Myopathy
-Hypokalemia
-Arrhythmias
-⬆ aminotransferase
-⬆ alkaline phosphatase
-⬇ WBC or HCT (!!!)
-Rhabdomyolysis

67
Q

What are the other toxicity effects associated with Fibric Acid Derivatives?

A

-Potentiate actions of Coumadin and Indanedione Anticoagulants (Adjust doses)
-⬆ Myopathy risk with statins
-Avoid in hepatic/renal dysfunction
-⬆Risk of cholesterol gallstones: Caution in pts with obstructed biliary tract. High risk = women, obese patients and Native Americans

68
Q

Which patients are high risk for gall stones?

A

Women, obese patients, Native Americans

69
Q

What is the use for Bile-Acid Binding Resins?

A

-Used for isolated ⬆ in LDL only
-If ⬆ Triglycerides ➜ ⬆ VLDL

70
Q

What is the MOA of the Bile-Acid Binding Resins?

A

-Bile acids = metabolites of cholesterol
-Bind bile acids in the intestines
-Prevent reabsorption
-Excretion ⬆ 10 x’s
-Feedback loop tells body to break down more cholesterol into bile acids
-Also stops the reuptake of bile acids from the gut to the liver
-Taken BID or TID with meals
-Ex: Colestipol, Cholestyramine, Colesevelam

71
Q

What are the clinical conditions that Bile-Acid Binding Resins are utilized in?

A

-Primary Hypercholesterolemia
-Combined Hyperlipidemia (Must add Niacin)
-Can be combined with other agents to maximize effect
-Helpful in relieving pruritus from cholestasis & bile salt accumulation

72
Q

What are the toxicity S/Sx of Bile-Acid Binding Resins?

A

-Impairs the absorption of other drugs (Give other meds 1 hr before or 2 hrs after)
-Constipation & bloating (C/I in Diverticulitis!!!!)
-Malabsorption of Vit K (Monitor PT in pts taking anticoagulants like Coumadin that are Vit K dependent)

73
Q

What is the MOA of the Inhibitor of Intestinal Sterol Absorption (Ezetimibe)?

A

Selective inhibitor of intestinal absorption of cholesterol and phytosterols.
-Targets the transport protein NPC1L1
-Inhibits the reabsorption of cholesterol excreted in the bile
-⬇LDL with minimal ⬆HDL
-Half-life = 22 hours

74
Q

What are Phytosterols?

A

Saturated plant steroid alcohol. Similar to cholesterol

75
Q

What are the therapeutic uses of the Inhibitor of Intestinal Sterol Absorption (Ezetimibe)?

A

Primary Hypercholesterolemia & Phytosterolemia
-Can be used in combo with Statins.
-Synergistic with Statins

76
Q

What is the toxicity associated with Ezetimibe?

A

Low incidence of reversible hepatic dysfunction.
-If you stop therapy, can reverse liver dysfunction that occurred due to toxicity.

Adv Pharm 1 (28 decks)

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