Anti-hyperlipidemics

Question 1

Why is cholesterol important?

Answer 1

-Cholesterol is an essential component of cell membranes
-also a precursor to sterols and steroids

Question 2

Why is triglyceride important?

Answer 2

Storage form of fuel to support generation of high energy compounds
- component of structural lipids

Question 3

Lipoproteins

Answer 3

Transport cholesterol and triglyceride into the blood
- the surface is made up of particles that have phospholipid, free cholesterol and protein
- Core made up of triglyceride and cholesterol ester
- Apoproteins on the surface play a crucial role in regulating transport and metabolism

Question 4

Lipoprotein classes
Chylomicrons

Answer 4

Play a role in transporting dietary lipids from the gut to the liver and adipose tissue

Question 5

Lipoprotein classes
VLDL - very low density lipoproteins

Answer 5

This is secreted by the liver into blood as a source of triglycerides

Question 6

Lipoprotein classes
IDL - Intermediate density lipoprotein

Answer 6

Triglyceride depleted VLDLs

Question 7

Lipoprotein classes
LDL - Low density lipoproteins

Answer 7

Main cholesterol form in blood

Question 8

Lipoprotein classes
HDL- High density lipoprotein

Answer 8

Secreted by liver and acquired cholesterol from peripheral tissues and atheromas
(This is the good cholesterol)

Question 9

Important Apolipoproteins

Answer 9

ApoA-I
- Structural in HDL
- Mediates reverse cholesterol transport
ApoB-100
- Structural in VLDL, IDL, LDL
ApoB-48
- Structural in chylomicrons
- Produced in intestine
ApoE
- Ligand for LDL remnant receptor
- reverse cholesterol transport with HDL
ApoCII
- Found in chylomicrons
- Binds to lipoprotein lipase to enhance TG hydrolysis

Question 10

Lipid absorption and transport

Answer 10

Exogenous pathway
- Chylomicrons are synthesized from the fatty acids of dietary triglycerides in the small intestine.
- Chylomicrons are converted to chylomicron remnants by LPL
- Chylomicron remnants then get cleared from the plasma by binding to remnant receptors in the liver (ApoE mediated) (stored in the liver)

Question 11

LPL - lipoprotein lipase

Answer 11

In capillaries of fat, cardiac and skeletal muscle

Question 12

HL - Hepatic lipase

Answer 12

Produced in liver, key in converting IDL to LDL

Question 13

Liver synthesis of cholesterol

Answer 13

De novo synthesis is the major source of cholesterol. Liver synthesis is most critical to total body burden

Question 14

Lipoprotein disorders

Answer 14

Detected by measuring lipid in serum after a 10hr fast
Ratio of total cholesterol to HDL - cholesterol is key in assessing risk of CVD
Ratio >4.5 is associated with increased risk of CVD
Ratio of less than or equal to 3.5 is desirable
ratio of less than 3 may be optimal

Question 15

Hyperlipoproteinimia

Answer 15

Can lead to atherosclerosis - excess accumulation of cholesterol in vascular smooth muscle
- Premature coronary artery disease
- Neurologic disease - stroke

Question 16

Hypertriglyceridemia

Answer 16

Pancreatitis
Xanthomas ( Fats build up under the surface of the skin)

Question 17

Hyperlipidemia
Goals of therapy

Answer 17

Decrease reabsorption of excreted bile acids
Decrease secretion of VLDL from liver
Decrease synthesis of cholesterol
Increase Hydrolysis of lipoprotein triglycerides
Specific for lowering triglycerides

Question 18

Drugs for high cholesterol

Answer 18

Bile acid binding resins
Inhibitors of cholesterol absorption
Inhibitors of cholesterol synthesis
PCSK9 inhibitors
MTTP inhibitors

Question 19

Drugs mainly for high triglycerides

Answer 19

Fibrates
Niacin
Omega 3 fatty acids

Question 20

BIle acid binding resins

Answer 20

Focuses on lowering serum cholesterol
MOA
Bind bile acids to form insoluble complex excreted in feces (inhibit reabsorption of bile acids from intestine)
- Also will up- regulate LDL receptors in liver

Question 21

BILE acid Binding DRUGS

Answer 21

Cholestyramine (Queastran)
Colestipol (colestid)

Question 22

Bile acid binding drugs
therapeutic use and treatment

Answer 22

Treatment of primary hypercholesterolemia (High LDL)
Take before meals
SIDE EFFECTS:
Constipation and bloating (High fiber diets and water helps)