Question

Work from the Brown and Goldstein lab provided insights into cholesterol homeostasis that were used to develop several of the LDL cholesterol-lowering therapies, including statins that remain in use today. However, in some patients, statins were not as effective as expected, suggestive of additional mechanisms regulating the LDL receptor. Investigate other LDL cholesterol-lowering therapies (other than PCSK-9 inhibitors), select 1, and compare and contrast the mechanisms of action between the class of drug you select and statins. Include side effects for both types of drugs and information on their efficacy.

Answer 1

Cholesterol lowering drugs:

Cholesterol:

Cholesterol is a sterol lipid synthesized by the liver and transported in the blood stream to the membranes of all animal cells . It plays a central role in many biochemical processes. As a lipoprotein it coats the walls of the blood vessels , but hypercholostrolemia is often associated with Cardiovascular disease .

Cholesterol lowering drugs are meant to decrease high Cholesterol level in the blood , that is dangerous to the cardiovascular  health, including heart and blood vessels.

Statins are class of drugs that lower the amount of cholesterol in the blood by inhibiting an enzyme involved in its biosynthesis .

Comparison between Statin and Bempedoic acid :

Statin is an effective Cholesterol lowering drug , but in some people it found that Statin is not effective. F.D.A ( food and drug administration US) approved another medicine for lowering the cholesterol level , that is Bempedoic acid.  

* Statins are a class of drugs that used in high cholesterol, to lower the LDL level, and is sold under different brand names such as : examples are

Atrovastatin ( lipitor)

lovastatin ( Mevacor)

Pravastatin ( Pravachol)

Bempedoic acid: It is nonstatin, oral , LDL ( low density lipoprotein) lowering medicine, that available in by the trade name Nexletol.The drug is used in Hypercholostrolemia and Atherosclerosis disease.  

* Mechanism of Action:

Statin: It works by blocking the action of liver enzymes that is responsible for the production of Cholesterol. Statins are called HMG - CoA reductase inhibitors . By inhibiting this enzyme , Statins blocks the pathway for producing cholesterol. Thus reduces the Cholesterol level in the blood.

Bempedoic acid: It works as an ATP citrate lyase inhibitors . It is a prodrug, that will be activated in the liver and is activated by ACSVL1 ( Acyl CoA Synthetase 1) . After getting activated it inhibits the ATP citrate lyase enzyme, that is essential for Cholesterol synthesis.  

* Side effects:

Statin: The common side effects are headache, dizziness, tiredness, GI disturbances such as constipation, diarrhoea, indigestion etc.

Bempedoic acid: The major side effects are muscle spasm, back pain, hyperurecrnia, upper respiratory tract infections and abdominal pain and discomfort.  

* Efficacy:

Statin: It is used not only to lower LDL level effectively, but also prevents from stroke and heart diseases.

Bempedoic acid: is used in hypercholostrolemia and Atherosclerosis. Studies show that it is very effective and safe in lowering the LDL level. Patients , who are not responding to Statin , can effectively use Bempedoic acid to lower their Cholesterol level.