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PHAR3309 > Module Six: Lipid Lowering Drugs > Flashcards

Module Six: Lipid Lowering Drugs Flashcards

1
Q

What are the two types of stroke?

A

Ischemic Stroke: blockage of blood vessel

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

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2
Q

Causes of heart failure?

A
  • Myocardial Infarction
  • High Blood Pressure
  • Damaged Heart Valve
  • Cardiomyopathy
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3
Q

Modifiable Risk Factors for CVD

A
  • Smoking
  • Obesity
  • Poor dietary intake
  • High Alcohol consumption
  • Lack of excercise
  • T2D
  • Inflammation
  • Hypertension
  • Dislipidemia
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4
Q

Non-Modifiable Risk Factors for CVD

A

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

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5
Q

BMI measurements

A

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

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6
Q

Waist circumference

A

Caucasian
Men: >104cm
Women: >88cm

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7
Q

Newer indirect measurements of obesity

A 
Body fat %
Skin fold 
Hydrostatic/underwater weight measuring
Bio electrical impedance analysis 
Dual energy X Ray absopbtiometry
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8
Q

Newer direct methods of measuring obesity

A

Ultrasound
Computed tomography
MRI/ MRS

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9
Q

Diagnosis for Diabetes

A 
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

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10
Q

Recommended lipid levels

A

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

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11
Q

Lipoprotein lipid components

A

Cholesterol
Triglycerides
Phospholipids

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12
Q

Lipoprotein protein component

A

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

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13
Q

Patterns of Dislipidemia

A

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

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14
Q

What enzyme converts cholesterol into cholate?

A

Cholesterol 7alpha-hydroxylase

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15
Q

What are the three pathways of lipid metabolism?

A

Exogenous
Endogenous
Reverse cholesterol transport pathway

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16
Q

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

A

Niemann Pick C1 like protein

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17
Q

What are mixed micelles?

A

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

18
Q

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

A

Acyl Co-enzyme A-diglycerol acyltransferase

19
Q

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

A

Microsomal transfer protein

20
Q

VDVL formation

A

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

21
Q

Where are cholesteryl ester and TG packaged?

A

ApoB100 via microsomal transfer protein

22
Q

Sequence of LDL formation

A

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

23
Q

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

A

Liver and intestine; recruits cholesterol from macrophages via ABCA1

24
Q

What enzyme converts nascent HDL into mature HDL

A

Lecithin cholesterol acetyltransferase

25
Q

What is a tracee?

A

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

26
Q

Tracer?

A

Same as tracee but labelled

Stable isotope

27
Q

What kinetic parameters do tracer methods identify

A

Production rate

Fractional catabolic rate

28
Q

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

A

Eicoapentaenoic acid

Docosahexaenoic acid

29
Q

Factors to consider with dietary interventions

A 
Individual nutrition needs
Maintenance of pleasure eating
Personal preferences
Practicality 
Cultural preferences 
Lifestyle match
Willingness to change
Affordability 
Adherence
30
Q

Examples of Fungus derived statins

A

Lovastatin
Pravastatin
Simvastatin

31
Q

Examples of synthetic statins

A

Fluvastatin
Atorvastatin
Rosuvastatin

32
Q

Effects of statins

A

LDL cholesterol lowering
HDL raising
Plasma TG lowering

33
Q

Other effects of statins

A

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

34
Q

Adverse effects of statins

A 
Muscle damage and pain
Rhabdomyolosis
Renal failure
Liver damage
GI problems
Rash and flushing 
Increased risk of T2D
Neurological side effects
35
Q

What is the structure of NPC1L1

A

13 Tm domain
Penta-domain
Sterol sensing domain

36
Q

Mechanism of action of Ezetimbe

A

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

37
Q

What are the three subtypes of PPAR agonists?

A

Greek: a, y sigma/b

38
Q

Mechanism and affects of PPAR agonists

A

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

39
Q

PPAR alpha agonist examples and targets

A

Liver, kidney, heart, muscle and macrophages

E.g. Fibrates: fenofibrate, gemfibrozil, bezafibrate

40
Q

Effect of PPAR alpha agonists

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

PHAR3309 (6 decks)

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