Atherosclerosis & Lipid Lowering Drugs

Question 1

What is Hypercholesterolaemia?

Answer 1

Elevated plasma cholesterol, often leading to Atherosclerosis

Question 2

What is Atherosclerosis?

Answer 2

Focal lesions (plaques) on the inner surface of an artery

Question 3

What can Atherosclerosis lead to?

Answer 3

Ischaemic heart disease (IHD)
Peripheral vascular disease (PVD)
Cerebrovascular disease

Question 4

What are the non modifiable risk factors for Atherosclerosis?

Answer 4

Genetics

Infection (dental)

Question 5

What are the modifiable risk factors for Atherosclerosis?

Answer 5

Hypercholesterolaemia (raised LDL/lowered HDL)
Hypertension
Smoking
Obesity
Hyperglycaemia
Reduced physical activity

Question 6

What is dyslipidaemia?

Answer 6

Abnormal levels of lipids in the blood

Question 7

What drugs are known to induce dyslipidaemia?

Answer 7

Beta-blockers
Thiazides
Corticosteroids
Retinoids
Oral contraceptives
Anti-HIV

Question 8

What are lipoproteins?

Answer 8

A group of soluble proteins that transport lipids in the blood

Question 9

What is the structure of lipoproteins?

Answer 9

Central hydrophobic lipid core

Encased in phospholipid, cholesterol & apolipoproteins

Question 10

What are the four main types of lipoprotein?

Answer 10

HDL - High density lipoprotein
LDL - Low density lipoprotein
VLDL - Very low density lipoprotein
Chylomicrons

Question 11

What are Chylomicrons?

Answer 11

Type of lipoprotein that transport TGs/cholesterol from GI tract to the liver
Free FA released
Cholesterol stores/oxidised

Question 12

What is the function of VLDL?

Answer 12

Transports cholesterol/TGs to tissues –> becomes LDL

Question 13

What is the function of LDL?

Answer 13

Transports cholesterol to liver/tissues, taken up by endocytosis

Question 14

What is the function of HDL?

Answer 14

Transports cholesterol from cell breakdown to VLDL/LDL (in liver)

Question 15

What is the ideal level of cholesterol?

Answer 15

<5.0 mmol/L

High HDL:LDL

Question 16

What are the diagnostic criteria for Hypercholesterolaemia?

Answer 16

TC >6.5 mmol/L

High LDL:HDL

Question 17

What are some diagnostic signs of Hypercholesterolaemia?

Answer 17

Xanthoma (cutaneous fatty deposit)
Xanthomata - nails
Xanthelasma - around eyes

Question 18

What is Atherogenesis?

Answer 18

An inflammatory response to injury leading to the development of atheromatous plaques

Question 19

What are risk factors for damage to the arterial endothelium?

Answer 19

Turbulent flow
Smoking
Hypertension

Question 20

What causes Atherosclerosis?

Answer 20

Damage to the endothelium followed by the inflammatory response

Question 21

What cells make up the inflammatory response in Atherogenesis?

Answer 21

Monocytes/Macrophages

Question 22

What is the main effect of Monocytes/Macrophages in Atherogenesis?

Answer 22

Release of Ox radicals

Question 23

What effect does the release of Ox radicals have on LDL?

Answer 23

Converts it to oxLDL

Question 24

What is oxLDL?

Answer 24

Oxidised LDL
Damages receptor
Cholesterol accumulates underneath endothelium

Question 25

How do fatty streaks form?

Answer 25

Cholesterol rich foam cells forming underneath endothelium

Question 26

What is an atherosclerotic plaque?

Answer 26

Cholesterol rich plaque, calcified w/ connective tissue

Question 27

At what point does narrowing of an artery due to an atherosclerotic plaque lead to symptoms?

Answer 27

70% occlusion

Question 28

What are the three main stages of Atherosclerotic formation?

Answer 28

Damage to blood vessel - inflammation/infiltration Formation of fatty streaks - deposition of foam cells Formation of plaques - calcification of cholesterol deposits

Question 29

What are the causes of symptoms in Atherosclerosis?

Answer 29

Stenosis (70%) - angina | Rupture of plaque - clot formation/platelet aggregation

Question 30

What are the main treatments for Atherosclerosis?

Answer 30

Lifestyle measures/hyperlipidaemia treatments Angioplasty & stenting Antiplatelets/clot-busting drugs

Question 31

How is most cholesterol produced?

Answer 31

In the liver (70%) | Key enzyme - HMG-CoA Reductase

Question 32

How do Statins work?

Answer 32

HMG-CoA Reductase Inhibitors

Question 33

What are the clinically most common Statins?

Answer 33

Simvastatin Atorvastatin Pravastatin Fluvastatin

Question 34

What is the effect of Statins?

Answer 34

Reduced plasma cholesterol (therefore) | Upregulation of hepatic LDL receptors - LDL uptake

Question 35

In what condition are Statins less effective?

Answer 35

Homozygous familial hypercholesterolaemia (cannot make LDL-receptor) ATORVASTATIN

Question 36

What is the most important metabolic factor of Statins?

Answer 36

Hepatoselective - 95% 1st pass metabolism

Question 37

In what conditions are Statins effective?

Answer 37

Types IIa & IIb Hyperlioproteinaemia (LDL & LDL/VLDL) Heterozygous Familial Hypercholesterolaemia

Question 38

Are Statins effective at reducing CV risk?

Answer 38

Yes, even if normal cholesterol - Improve endothelial function - Reduce atherosclerosis - Reduce progression of carotid disease

Question 39

To what patients should Statins be given?

Answer 39

Hypocholesterolaemia Raised LDL Atherosclerosis Patients w/ >10% risk of CVD

Question 40

How should Statins be given?

Answer 40

At night - increased cholesterol synthesis at night | EXCEPT ATORVASTATIN

Question 41

What is the dosing structure of Statins in patients with low risk of CVD?

Answer 41

Low intensity | ie. 20 mg Atorvastatin

Question 42

What is the dosing structure of Statins in patients with high risk/secondary prevention of CVD?

Answer 42

High intensity | ie. 80 mg Atorvastatin

Question 43

When should Statins be avoided?

Answer 43

Use in care with liver disease - serious risk of dysfunction | Monitor function

Question 44

What is the main ADR of Statins?

Answer 44

Myopathy leading to Rhabdomyolysis 1:1000/10,000 Fibrates increase risk PRAVASTATIN

Question 45

Which drugs interact with Simvastatin?

Answer 45

``` Contraindication with Macrolides Interactions -Amlodipine -Verapamil -Diltiazem ```

Question 46

What Statin can be given OTC?

Answer 46

Simvastatin 10 mg

Question 47

Which patients can receive Simvastation OTC?

Answer 47

``` All males >55 Males 45-55/Females >55 with -Family history IHD -Smokers -Overweight -S. Asian ethnicity ```

Question 48

What are Fibrates?

Answer 48

Derivatives of fibric acid used to reduce the levels of TGs

Question 49

How do Fibrates work?

Answer 49

Activate PPAR-a - alters lipoprotein metabolism

Question 50

What are the effects of Fibrates?

Answer 50

Promote breakdown in VLDL Reduce TGs Decrease glucose Reduce IHD (not mortality)

Question 51

What are the adverse effects of Fibrates?

Answer 51

Rhabdomyolysis

Question 52

What is Ezetimibe?

Answer 52

Cholesterol Absorption Inhibitor

Question 53

How do fish oils affect lipid levels?

Answer 53

Contain EPA EPA competes w/ Arachidonic acid for COX Reduce TGs/Increase LDL

Question 54

What effect do supplemental Vitamins have on lipid levels?

Answer 54

No benefits seen with supplementation

Question 55

What is Sitostanol?

Answer 55

A phytosterol that prevents absorption of cholesterol | Reduces LDL 10-15%