Module Six: Lipid Lowering Drugs

Question 1

What are the two types of stroke?

Answer 1

Ischemic Stroke: blockage of blood vessel

Haemorrhagic Stroke: rupturing of blood vessels leading to bleeding and leakage into brain

Question 2

Causes of heart failure?

Answer 2

• Myocardial Infarction
• High Blood Pressure
• Damaged Heart Valve
• Cardiomyopathy

Question 3

Modifiable Risk Factors for CVD

Answer 3

• Smoking
• Obesity
• Poor dietary intake
• High Alcohol consumption
• Lack of excercise
• T2D
• Inflammation
• Hypertension
• Dislipidemia

Question 4

Non-Modifiable Risk Factors for CVD

Answer 4

Personal history of CVD, family history, race, ethnicity, age, gender

Question 5

BMI measurements

Answer 5

Healthy: 20-24.99
Overweight: 25-29.9
Obese: >30

Question 6

Waist circumference

Answer 6

Caucasian
Men: >104cm
Women: >88cm

Question 7

Newer indirect measurements of obesity

Answer 7

Body fat %
Skin fold 
Hydrostatic/underwater weight measuring
Bio electrical impedance analysis 
Dual energy X Ray absopbtiometry

Question 8

Newer direct methods of measuring obesity

Answer 8

Ultrasound
Computed tomography
MRI/ MRS

Question 9

Diagnosis for Diabetes

Answer 9

Oral Glucose Tolerance Test
Impaired fasting glucose if:
Fasting glucose: 6.1-7 mM
Blood glucose after 2 hrs is less than 7.8mM
Impaired glucose tolerance if:
Blood glucose after 2hrs is 7.8-11mM
Diabetic if: glucose >11.1 mM

HbA1C: marker for average glucose conc over previous months
A1c >6.5%; >48mM

Question 10

Recommended lipid levels

Answer 10

Total: <5.5mM
HDL: men: >1.04; women:1.30mM
LDL: <2mM
Triglyceride: <1.7mM

Question 11

Lipoprotein lipid components

Answer 11

Cholesterol
Triglycerides
Phospholipids

Question 12

Lipoprotein protein component

Answer 12

Structural: ApoB-100: major structural protein for LDL; ApoA-I: major structural protein for HDL

Enzyme modulator: ApoC-II: co activator of lipoprotein lipase activity

Receptor Ligands: ApoE and ApoB binds to LDL receptor

Question 13

Patterns of Dislipidemia

Answer 13

Increased total and LDL cholesterol
Increased triglycerides (increased triglycerides and LDL)
Increased triglycerides, decreased HDL cholesterol

Question 14

What enzyme converts cholesterol into cholate?

Answer 14

Cholesterol 7alpha-hydroxylase

Question 15

What are the three pathways of lipid metabolism?

Answer 15

Exogenous
Endogenous
Reverse cholesterol transport pathway

Question 16

Cholesterol uptake into the enter ochre across the luminal membrane occurs via what transporter?

Answer 16

Niemann Pick C1 like protein

Question 17

What are mixed micelles?

Answer 17

Structures that carry cholesterol and triglycerides to the intestinal brush border for absorption

Question 18

What enzyme converts 2 fatty acids and monoglyceride back into triglyceride within the enterocyte?

Answer 18

Acyl Co-enzyme A-diglycerol acyltransferase

Question 19

What packages TG and cholesterol esters to form nascent chylomicrons with ApoB-48

Answer 19

Microsomal transfer protein

Question 20

VDVL formation

Answer 20

Packaged in the endoplasmic reticulum of the hepatocytes
DG converted to TG via DGAT
Acetyl co A to free cholesterol via HMG-CoA reductase
Free cholesterol to cholesteryl ester via ACAT

Question 21

Where are cholesteryl ester and TG packaged?

Answer 21

ApoB100 via microsomal transfer protein

Question 22

Sequence of LDL formation

Answer 22

VLDL to FFA by lipoprotein lipase forms IDL
IDL to FFA by hepatic lipase to LDL
LDL taken up by liver receptors facilitated by apoB100 and ApoE

Question 23

What secretes lipid-free ApoA-I and what does ApoA-I do?

Answer 23

Liver and intestine; recruits cholesterol from macrophages via ABCA1

Question 24

What enzyme converts nascent HDL into mature HDL

Answer 24

Lecithin cholesterol acetyltransferase

Question 25

What is a tracee?

Answer 25

Endogenous molecule Protein - AA e.g. Leucine Lipid moiety - glycerol

Question 26

Tracer?

Answer 26

Same as tracee but labelled | Stable isotope

Question 27

What kinetic parameters do tracer methods identify

Answer 27

Production rate | Fractional catabolic rate

Question 28

What n3 polyunsaturated fatty acids are in fish and fish oil?

Answer 28

Eicoapentaenoic acid | Docosahexaenoic acid

Question 29

Factors to consider with dietary interventions

Answer 29

``` Individual nutrition needs Maintenance of pleasure eating Personal preferences Practicality Cultural preferences Lifestyle match Willingness to change Affordability Adherence ```

Question 30

Examples of Fungus derived statins

Answer 30

Lovastatin Pravastatin Simvastatin

Question 31

Examples of synthetic statins

Answer 31

Fluvastatin Atorvastatin Rosuvastatin

Question 32

Effects of statins

Answer 32

LDL cholesterol lowering HDL raising Plasma TG lowering

Question 33

Other effects of statins

Answer 33

Antioxidant, anti thrombotic, anticoagulation, improve endothelial function, cytoprotection, anti inflammatory

Question 34

Adverse effects of statins

Answer 34

``` Muscle damage and pain Rhabdomyolosis Renal failure Liver damage GI problems Rash and flushing Increased risk of T2D Neurological side effects ```

Question 35

What is the structure of NPC1L1

Answer 35

13 Tm domain Penta-domain Sterol sensing domain

Question 36

Mechanism of action of Ezetimbe

Answer 36

Inhibition of the NPC1L1 transporter - prevents cholesterol absorption at brush border membrane Undergoes glucuronidation in the intestinal wall

Question 37

What are the three subtypes of PPAR agonists?

Answer 37

Greek: a, y sigma/b

Question 38

Mechanism and affects of PPAR agonists

Answer 38

Once activates: forms heterodimer with retinoid X receptor; the complex binds to specific nucleotide sequence response element in promoter region of target gene => activation or repression of gene transcription Lipid metabolism, immune/ inflammation response, proliferation, differentiation

Question 39

PPAR alpha agonist examples and targets

Answer 39

Liver, kidney, heart, muscle and macrophages E.g. Fibrates: fenofibrate, gemfibrozil, bezafibrate

Question 40

Effect of PPAR alpha agonists

Answer 40

``` Lowering plasma TG concentrations lipoprotein lipase up regulation Down regulation of apoC-III Increases ApoA-III Up regulation of APOA-I ```