Lipid lowering Drugs.

Question 1

List in order of size the classes of Lipoproteins.

Answer 1

From largest to smallest.

Chylomicrons,
VLDL,
LDL,
HDL.

Question 2

Where are chlomicrons synthesized and what does this indicate about the origin of the triglycerides it carries?

Answer 2

Intestine, dietary origin.

Question 3

By which organ is VLDL secreted?

Answer 3

The liver.

Question 4

What is the function of VLDL?

Answer 4

Transport of triglycerides from the liver to peripheral tissues.

Question 5

List the important enzymes in Cholesterol Metabolism.

Answer 5

LPL - Lipoprotein Lipase,
HMG CoA reductase,
LDL receptors,
LCAT - lecithin cholesterol acyl transferase,
CETP - Cholesteryl ester transfer protein.

Question 6

What is the function of Lipoprotein Lipase?

Answer 6

It clears chylomicrons from the ciirculation and breaks down Triglycerides to FFA and glycerol producing IDL and LDL.

Question 7

Where is Lipoprotein lipase found?

Answer 7

Mainly in the blood.

Question 8

HMG CoA reductase.

Answer 8

Involved in the rate limiting step of cholesterol synthesis where HMG is converted to Mevalonate.

Question 9

How do LDL receptors come in to the picture of lowering levels of lipids in blood?

Answer 9

LDL receptors on tissue bind with LDL and internalizes it. The receptor then returns to the membrane.

Question 10

What is Hyperlipidemia?

Answer 10

Elevation of cholesterol, triglycerides or both.

Question 11

Describe the condition of familial hypercholesterimia.

Answer 11

An autosomal dominant trait with defects in LDL receptors. It is characterized by high levels of serum cholesterol and LDL.

Question 12

Name a few causes of Hyperlipidemia.

Answer 12

Familial,
Polygenic lipid disorders (Diet, physical activity),
Secondary to other disease (Diabetes mellitus, alcoholism, nephrosis, drugs taken for other diseases).

Question 13

What is meant by the term pleitrophic.

Answer 13

They can be described as complementary effects that are not adverse.

Question 14

Explain the underlying principle behind lipid lowering treatment.

Answer 14

First the patients’ current health status will be avaluated and depending on this a management plan will be made. If Diet and life style cannot be managed well, then drug treatment will be prescribed.

Question 15

Name the classes for hypolipidemic drugs (drugs that will lower lipid levels).

Answer 15

Statins, 
Fibrates, 
Cholesterol absorption inhibitors, 
Niacin, 
Fish oil derivatives.

Question 16

Explain how statins work?

Answer 16

Analogues of HMG Co A and so competitively inhibit HMG Co A enzyme.
Promotes expression of LDL receptors in the liver.

Question 17

What effect would increased expression of LDL receptors in the liver have?

Answer 17

Increased clearance of LDL.

Question 18

Other indications for statins?

Answer 18

Given for patients with high risk CHD and to prevent MI and stroke.

Question 19

List some Pleitrophic effects of statins (other than lowering LDL)?

Answer 19

Improved endothelial function, 
Decreased oxidative stress, 
Plaque stabilisation, 
Antithombotic, 
Enhanced fibrinolysis, 
Immune supression.

Question 20

Name two statins which are prodrugs.

Answer 20

Simvastatin and Lovastatin.

Question 21

What should you advice a patient receiving statins which are prodrugs?

Answer 21

Stay away from grape juice. It can inhibit activity of Cytochrome P450 needed for the activation of the prodrug.

Question 22

Contraindications of statins.

Answer 22

Pregnancy as it is teratogenic,

Use with caution with people with liver dysfunction.

Question 23

How do fibrates work?

Answer 23

They bind to nuclear receptors and control (upregulate) LPL which would promote breakdown of triglycerides.

Question 24

List the side effects of Fibrates.

Answer 24

GI disturbance, 
Fatigue, 
Rashes, 
Muscle cramps, 
Gall stones.

Question 25

Name some cholesterol absorption inhibitors and whats the basis for their actions.

Answer 25

Ezetimibe and bile acid binding resins (cholestyramine).

Prevents intestinal reabsorption of the cholesterol in the excreted bile salts.

This also causes the liver to compensate for the loss by producing more bile salts.

Question 26

How do bile acid binding resins work?

Answer 26

They prevent reabsorption and enterohepatic recirculation in the intestine.

Question 27

List another important indication for cholestyramine.

Answer 27

Digitalis toxicity.

Question 28

Side effects of bile acid binding resins.

Answer 28

Nausea, bloating, Constipation and prevents absorption of lipid soluble vitamins.

Can’t eat it also cause it probably sucks.

Question 29

What is Niacin?

Answer 29

Vitamin B3 (nicotinic acid).

Question 30

What does Niacin do, and how does it help with reducing cholesterol?

Answer 30

It inhibits intracellular lipase of adipose tissue which results in reduced supply of FFA to the liver which is required for VLDL, LDL and HDL production.

Question 31

Side effects of Niacin?

Answer 31

GIT disturbance, flushing, itching.

Question 32

What do you mainly give for elevated triglycerides?

Answer 32

Fibrates.