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5: Y5 - ESA 5 - Pharmacology > Cholesterol Pharmacology > Flashcards

Cholesterol Pharmacology Flashcards

(53 cards)

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1
Q

What effect does a 10% reduction in cholesterol have on CHD mortality?

A

It reduces it by 15%

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2
Q

What effect does a 10% reduction in cholesterol have in total mortality?

A

11% reduction

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3
Q

What is the primary target to prevent CHD?

A

LDL cholesterol

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4
Q

What does the intensity of cholesterol intervention depend on?

A

Total CV risk

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5
Q

What are the pro-atherogenic effects of oxidated LDL?

A
  • Inhibits macrophage motility
  • Induces T-cell activation and VSMC divison/differentiation
  • Toxic to endothelial cells
  • Enhances platelet aggregation
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6
Q

What are the classes of lipid lowering drugs?

A
  • Statins
  • Cholesterol lipase inhibitors
  • Nicotinic acid
  • Fibrates
  • Resins
  • Omega-3 fatty acids
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7
Q

Give a statin

A

Simvastatin

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8
Q

Give a cholesterol lipase inhibitor

A

Ezetimibe

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9
Q

Give a fibrate?

A

Fenofibrate

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10
Q

Give a resin

A

Colestyramine

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11
Q

Give an omega-3 fatty acid

A

Omacor

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12
Q

What are the actions of statins?

A
  • Inhibits cholesterol synthesis in hepatocytes
  • Increase clearance of IDL and LDL
  • Decreases production of VLDL and LDL
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13
Q

What are the indications for the use of statins?

A
  • CV risk prevention in CVD and diabetes
  • Famlial hypercholesterolaemia
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14
Q

What are the potential adverse drug reactions of statins?

A
  • Increased transaminase levels
  • Myopathy
  • Gastrointestinal complaints
  • Arthralgia
  • Headaches
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15
Q

What % of patients treated with statins develop increased transaminase levels?

A

0.1-2.5%

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16
Q

By how much can statins increase transaminase levels?

A

Can increase >3x the upper normal limit, especially at higher doses

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17
Q

Can increased transaminases due to statin use be reversed?

A

Yes, rapidly reversible

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18
Q

Does increased transaminase levels due to use of statins cause liver disease?

A

No

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19
Q

What myopathies can be caused by statins?

A
  • Diffuse muscle pain
  • CPK > 10x upper normal limit
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20
Q

When are myopathies due to statin use primarily seen?

A

When higher doses of statins are used in combination with cyclosporine, gemfibrozil, and occassionally erythromycin and niacin

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21
Q

What are some secondary benefits of statin treatments?

A
  • Anti-inflammatory
  • Plaque reduction
  • Improved endothelial cell functions
  • Reduced thrombotic risk
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22
Q

When is statin therapy recommended?

Study These Flashcards
A

As part of the management strategy for the primary prevention of CVD for adults who have a 20% or greater risk of developing CVD

23
Q

How should the level of CVD risk a patient has be calculated?

Study These Flashcards
A

Using an appropriate risk calculator, or by a clinical assessment for people whom an appropriate risk calculator is not available

24
Q

What kind of molecules are fibric acid derivatives?

Study These Flashcards
A

Ampipathic carboxylic acids

25
How do fibric acid derivatives act to reduce cholesterol?
They are PPAR-alpha agonists, which increase the production of lipoprotein lipase and so reduce triglyceride production
26
By how much can fibric acid derivatives reduce cholesterol?
10-20%, but variable depending on specific drug
27
What are the effects of fibric acids?
* Increase fatty acid uptake and oxidation * Reduces triglyceride levels * Increases LDL particle size and HDL-C levels * Direct vascular effects
28
What are the indications for fibric acid derivatives?
* Hypertriglyceridema * Combined hyperlipidaemia with low HDL, who do not respond to NA
29
Is fibric acid derivative therapy used alone, or as an adjuct?
It is an adjuctive therapy to diet
30
What is the efficacy of fibric acid derivatives?
* Decreases TG by 25-50% * LDL increases, but variable * Increases HDL 15-25% in hypertriglycaemia
31
What are the side effects of fibric acid derivatives?
* GI upset * Cholelithiasis * Myositis * Abnormal LFTs
32
What are the contraindications for fibric acid derivatives?
* Hepatic or renal dysfunction * Pre-existing gallbladder disease *
33
What is the best agent to raise HDL-C?
Nicotinic acid
34
What is the effect of nicotinic acid?
* Reduces VLDL * Increases HDL *at high doses* ## Footnote *​*
35
How does nicotinic acid have a lipid lowering effect?
By inhibition of lipoprotein (a) synthesis
36
What effect does nicotonic acid have on the incidence of coronary events?
It reduces the incidence
37
What are the adverse effects of nicotinic acid?
* Flushing * Itching * Headache * Hepatotoxicity * GI toxicity * Activation of peptic ulcer * Hyperglycaemia and reduced insulin sensitivity
38
How can the side effects of flushing, itching and headache due to nicotinic acid be reduced?
* Using immediate release Niaspan form * Using in combination with low dose aspirin
39
What form of nicotinic acid causes hepatotoxicity and GI toxicity?
Sustained release
40
What are the contraindications for nicotinic acid?
* Active liver disease * Unexplained LFT elevations * Peptic ulcer disease
41
What is the mechanism of action of ezetimibe?
It selectively inhibits intestinal cholesterol absorption, which; * Decreases intestinal delivery of cholesterol of the liver * Increased expression of hepatic LDL receptors * Decreased cholesterol content of atherogenic particles
42
What do ezetimibe metabolise to?
An active glucuronide metabolite
43
How does ezetimibe and its metabolite circulate?
Enterohepatically
44
What is the result of the enterohepatic circulation of ezetimibe?
It delivers the agent back to the site of action, and limits systemic exposure
45
What are the adverse drug reactions of ezetimibe?
* Headache * Diarrhoea * Abdominal pain
46
What can statins be used in combination with?
* Fibrate * Nicotinic acid * Ezetimibe * Omega-3 FAs
47
What should be considered when thinking about giving a patient combination therapy to reduce cholesterol?
* Benefit * Cost * ADRs
48
What is the advantage of combination fibrate and statin therapy?
It may significantly improve triglyceride, LDL-C and HDL-C levels
49
What is the disadvantage of combination fibrate and statin therapy?
Fibrates plus statins are associated with increased risk of myopathy and rhabdomyolosis
50
What effect might gemfibrozil have on statins?
May impair glucuronidation of statins, *with cervistatin being more susceptible than other statins*
51
Which fibrate seems to have less potential for impairment of statin metabolism?
Fenofibrate
52
What dietary factors may have a positive effect on statin metabolism?
* Plant sterols * Fish oils * Fibre * Vitamin C/E * Alcohol *(HDL)*
53
What dietary factors may have a negative effect on cholesterol metabolism?
* Dietary cholesterol/fat * Alcohol *(TG)*

5: Y5 - ESA 5 - Pharmacology (28 decks)

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