Question

What is the target of drugs used to treat high cholesterol? Please explain the pros and cons of these     drugs. (4 points)

Answer 1

Statins are the class of drugs used to lower cholesterol level.

Their mode of action is via inhibition of HMG-CoA (Hydroxymethylglutaryl coenzyme A) reductase,the rate limiting enzyme in the cholesterol biosynthesis pathway i.e. Mevalonate pathway.

Active component of statins is a modified 3,5- dihydroxyglutaric acid moiety, which is structurally similar to to the endogenous substrate i.e. HMG Co A .Statins competitively block the active site of HMG Co A reductase. Inhibition of this active site prevents substrate access ,hence the conversion of HMG CoA to mevalonic acid.

This reduces hepatic cholesterol synthesis .

PROS-

1.Lowered LDL-They lower the low density lipoprotein cholesterol (LDL c) ,which helps in reducing atherosclerotic cardiovascular diseases.

2.Improvement of endothelial function- They also help stabilize the blood vessel lining ,help to relax the blood vessels which leads to decrease in blood pressure.

3. Anti inlammmatory effect-After endothelium is injuured ,inflammatory cells infilterate the atherosclerotic plaques.Statins inhibit inflammation by reducing production of inflammatory markers.

4.Anti-thrombic effect-Statins impair blood clot formation(when endothelium ruptures and atherosclerosis might occur) by reducing the expression of tissue factors and platelet aggregation.

CONS-

1. Increased risk of myopathy i.e. muscle pain.

2. Diabetes-Might be related to lowering of LDL cholesterol or increasingnumber of LDL receptors which might enable more cholesterol to enter pancreatic cells.