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Pharmacy 302 > Lipid Lowering Agents > Flashcards

Lipid Lowering Agents Flashcards

1
Q

What is the meaning of the term “dyslipidaemia”? Dyslipidaemia is primarily a disorder of what? What type of disorders are most dyslipidaemias?

A

Disordered lipid levels in the blood
Lipoprotein metabolism
Hyperlipidaemias

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2
Q

What characterizes hyperlipidemia?

A

Elevated plasma cholesterol or triglyceride levels

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3
Q

What are the primary forms of hyperlipidemia?

A

Chylomicronemia
Hypercholesterolemia
Type III Familial Dysbetalipoproteinaemia
Type IV Familial Hypertriglyceridemia
Type V Familial Mixed hyperlipoproteinemia
Combined hyperlipoproteinemia

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4
Q

Which diseases can cause secondary hyperlipidemia?

A

Diabetes mellitus, pancreatitis, renal disease, and hypothyroidism

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5
Q

What are the two classifications of hyperlipidaemias?

A

Primary and secondary

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6
Q

How may dyslipidemias be manifested?

A
  1. Elevation of Total Cholesterol (TC), Low-density Lipoprotein (LDL-C) cholesterol, and Triglyceride (TG) concentrations
  2. Decrease in High-density Lipoprotein (HDL-C) cholesterol concentration
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7
Q

What is the cause of primary hyperlipidaemias?

A

Familial inheritance

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8
Q

What is the clinical presentation of hyperlipidaemias dependent on?

A

Type and severity

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9
Q

What causes secondary hyperlipidaemias?

A

Various other diseases, including medications

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10
Q

What are some clinical manifestations of hyperlipidaemias?

A
  1. Skin manifestations (e.g. xanthomas)
  2. Deposits around the eyelid (xanthelasma)
  3. Corneal arcus
  4. Hepatic steatosis (fatty liver disease)
  5. Atherosclerotic cardiovascular diseases
  6. Carotid artery stenosis
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11
Q

Why do skin manifestations, like xanthomas, occur in hyperlipidaemias?

A

High levels of lipoproteins leak out of vessels

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12
Q

What are fat deposits around the eyelid called?

A

Xanthelasma

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13
Q

What is the deposition of lipids around the cornea called?

A

Corneal arcus

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14
Q

What is the clinical term for fatty liver disease, a potential result of hyperlipidaemias?

A

Hepatic steatosis

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15
Q

What are the most troublesome atherosclerotic cardiovascular diseases?

A

Coronary artery disease, stroke, and peripheral vascular disease

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16
Q

What are the steps of atherosclerotic plaque formation?

A
  1. Infiltration of LDL-C into arterial walls
  2. Entrapment of LDL-C in artery walls
  3. Modification of LDL-C
  4. Uptake of modified LDL-C by macrophages
  5. Foam Cell formation
  6. Fatty streak formation
  7. Conversion to fibrous plaques
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17
Q

What is considered a normal lipid profile for healthy individuals after a 9- to 12-hour fast?

A
  • Total (serum) cholesterol: below 5.0 mmol/L (below 193 mg/dL)
  • Non-HDL cholesterol: below 4.0 mmol/L (below 155 mg/dL)
  • LDL cholesterol: below 3.0 mmol/L (below 116 mg/dL)
  • HDL cholesterol: above 1.0 mmol/L for a man (above 39 mg/dL); above 1.2 mmol/L for a woman (above 46 mg/dL)
  • TC:HDL ratio: Above 6 is considered high risk
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18
Q

What level of TC:HDL ratio is considered high risk?

A

> 6

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19
Q

What dietary modifications are recommended for managing hyperlipidemia?

A
  • Decrease intake of saturated fats/cholesterol
  • Increase proportion of mono (MUFA) and poly-(PUFA) unsaturated fatty acid (olive & vegetable oils)
  • Food supplements: Omega-3-fatty acid, essential fatty acids (linolenic & linoleic acids), antioxidants
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20
Q

How much can dietary modification reduce total cholesterol?

A

10-15%

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21
Q

How does obesity affect lipid levels?

A

↑ TG, ↓ HDL-C & slight ↑ in TC & LDL-C

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22
Q

What BMI and waist circumference are recommended for managing hyperlipidemia?

A

BMI < 23 kg/m2 & waist circumference < 90 cm (male); <80 cm (female)

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23
Q

What rate of weight reduction is recommended per week for hyperlipidemia management?

A

0.5-1.0 kg

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24
Q

How does exercise aid in managing hyperlipidemia?

A
  • Helps to burn excess calories
  • Will help ↑ HDL-C & ↓ TG
  • Aerobic exercise: brisk walking, jogging, cycling, swimming
  • Should be regular & adequate (30-45 min per session 3x / week)
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25
How does cigarette smoking affect HDL-C levels?
Reduces HDL-C level and increases lipid peroxidation
26
What are the main categories of pharmacological management for hyperlipidemia?
1. HMG-CoA reductase inhibitors (Statins) 2. Fibric acid derivatives (Fibrates) 3. Bile acid sequestrants (Resins) 4. Nicotinic acid (niacin) & derivatives (Vitamin B3) 5. Cholesterol absorption inhibitor(2-Azetidiones)
27
What is the mechanism of action of HMG-CoA reductase inhibitors (Statins)?
Competitive inhibitors of HMG CoA reductase
28
What does low intracellular cholesterol stimulate in statin use?
Synthesis of LDL receptors
29
What effect do increased LDL receptors have on LDL?
Promotes uptake of LDL from blood
30
What are the therapeutic uses of HMG-CoA reductase inhibitors (Statins)?
- Lowering plasma cholesterol levels in all types of hyperlipidemias - Potent LDL–lowering agents- LDL-C reduction of 25%-60% - Decrease triglyceride levels and may increase HDL cholesterol levels
31
By how much can Statins reduce LDL-C?
25-60%
32
What are common adverse effects of HMG-CoA reductase inhibitors (Statins)?
Elevated liver enzymes and myopathy
33
What conditions are contraindications for using HMG-CoA reductase inhibitors (Statins)?
Hypersensitivity, active liver disease, pregnancy, lactation
34
What is the mechanism of action for fibric acid derivatives (fibrates)?
Activation of peroxisome proliferator–activated receptors (PPARs)
35
How do fibrates enhance lipoprotein lipase? What affect does Fibrates have on hepatic extraction of free fatty acids?
Increasing VLDL catabolism, fatty acid oxidation, and triglycerides elimination Decrease hepatic extraction of free fatty acids
36
What is the effect of fibrates on HDL-C levels? What is the impact of fenofibrate and gemfibrozil on serum triglycerides? What impact does fenofibrate and gemfibrozil have on LDL? What is the effect of fenofibrate and gemfibrozil on HDL levels?
Increase the level of HDL-C Lower serum triglycerides by 35% Lower LDL by 15% Increase HDL levels
37
What is the therapeutic use of fibrates in treating type III hyperlipidemia?
Treating dysbetalipoproteinaemia
38
What diseases are contraindications for using fibric acid derivatives (fibrates)? What are some adverse effects of fibric acid derivatives (fibrates)?
Active liver disease, renal disease, gallbladder disease Mild GI disturbances, myositis
39
What is the mechanism of action of nicotinic acid (niacin)? What effect does Niacin have on VLDL? What does Niacin get converted into?
Inhibits lipolysis in adipose tissue Inhibits very-low-density lipoprotein (VLDL) synthesis Nicotinamide
40
Why is nicotinic acid (niacin) used in the treatment of familial hyperlipidemias? What is Niacin incorporated into? What are therapeutic uses for Niacin?
Because it lowers both cholesterol and triglycerides NAD+ Used to treat other severe hypercholesterolemias
41
What is the affect of Niacin on LDL? What is the effect of Niacin on HDL? How does Niacin impact triglycerides?
Can reduce LDL by 10% -20% Most effective agent for increasing HDL Lowers triglycerides by 20% -35%
42
What is used in combination with niacin? What are contraindications for using nicotinic acid (niacin)?
What are common adverse effects of nicotinic acid (niacin)?
Statins Hypersensitivity, liver disease, active peptic ulcer Intense cutaneous flush and pruritus
43
What is the mechanism of action of bile acid sequestrants? How does the bile acid sequestrant/bile acid complex get removed from the body?
Lowering Total cholesterol and LDL via bile duct sequestration Excreted in the faeces
44
How does lower bile acid concentration affect hepatocytes?
Increases conversion of cholesterol to bile acids
45
What is the affect of decreased intracellular cholesterol concentrations?
Activates an increased hepatic uptake of LDL particles
46
What affect does bile acid sequestrants have on plasma LDL?
Leading to a fall in plasma LDL
47
For which types of hyperlipidemias are bile acid sequestrants useful?
Type IIA and type IIB
48
What is Cholestyramine also used to treat?
Relieve pruritus
49
What additional benefit does Colesevelam have?
Indicated for T2DM
50
What are common side effects of bile acid sequestrants? What do bile acid sequestrants interfere with the absorption of? What are contraindications for using bile acid sequestrants?
GI disturbances, such as constipation and nausea Fat-soluble vitamins (A, D, E, and K) Biliary/bowel obstruction, serum triglycerides >300-500 mg/dL
51
What is the mechanism of action for Cholesterol Absorption Inhibitors? What transporter is inhibited by Cholesterol Absorption Inhibitors?
Inhibits absorption of dietary and biliary cholesterol Niemann-Pick C1-like 1 (NPC1L1) transporter
52
How does inhibiting cholesterol absorption impact hepatic cholesterol stores? What is the affect of inhibiting cholesterol absorption on clearance of cholesterol?
Causes a reduction of hepatic cholesterol stores Increase in clearance of cholesterol
53
By approximately how much does cholesterol absorption inhibitors lower LDL cholesterol? How is cholesterol absorption inhibitors often used?
15-17% Adjunct to statin therapy
54
Who should not be treated with Ezetimibe?
Patients with moderate to severe hepatic insufficiency
55
What is the role of Omega-3 polyunsaturated fatty acids (PUFAs)?
Predominately used for triglyceride lowering
56
How do Omega-3 fatty acids impact VLDL and triglyceride synthesis? What are the most common side effects of Omega-3 fatty acids? What affect do Omega-3 fatty acids have in patients taking anticoagulants?
Inhibits VLDL and triglyceride synthesis GI effects and a fishy aftertaste Bleeding risk can be increased
57
What is the rate-limiting step in cholesterol synthesis?
HMG CoA reductase
58
What impact do fibrates have on Lipase activity?
Fibrates increases Lipase activity
59
What effect does Niacin have on triglycerides and LDL?
Lowers the triglycerides, LDL-C
60
How do Bile acids sequestrants reduce LDL-C level?
Eliminating bile acids/bile salts
61
What impact does Ezetimibe have on cholesterol absorption?
Inhibits free cholesterol absorptions

Pharmacy 302 (31 decks)

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