Anti-cholesterol drugs

Question 1

How does statins work ?

Answer 1

They work by inhibiting HMG- CoA reductase enzyme which acts at the rate limiting step of Mevalonic acid pathway responsible for hepatic cholesterol synthesis.

Question 2

What are the positive effects of statins ?

Answer 2

The reduce the risk of stroke, IHD and PVD.

Question 3

What are the main functions of cholesterol ?

Answer 3

• Synthesis of hormones and bile.
• important part of cell membrane.
• critical for the synthesis of vitamin D

Question 4

What are chylomicrons ?

Answer 4

They are the largest and least dense lipoproteins responsible for the transport of cholesterol form the small intestine. The chylomicrons release cholesterol into the lymphatic system which will carry it into the blood and finally into the adipose tissue and liver.

Question 5

What is Mevalonate pathway ?

Answer 5

It is the hepatic metabolic pathway responsible for the synthesis of endogenous cholesterol from mevalonate and the process is regulated by the rate limiting enzyme HMG CoAreductase.

Question 6

What is VLDL ?

Answer 6

It is the lipoprotein responsible for carrying triglycerides from the liver to the rest of the body.

Question 7

what is LDL ?

Answer 7

VLDL after unloading the triglycerides transforms into LDL and carries cholesterol to the rest of the body.

Question 8

What is HDL ?

Answer 8

It is a lipoprotein synthesised by the liver to transport back excessive cholesterol from the rest of the body to the liver.

Question 9

what are the drugs in the statin family ?

Answer 9

Simavastatin, Lovastatin, Pravastatin, Atrovastatin and Rosuvastatin.

Question 10

what are the more potent statins with longer 1/2 life ?

Answer 10

Atrovastatin and Rosuvastatin

Question 11

What is the pharmacodynamics of statins ?

Answer 11

They are similar in structure to HMG-CoA and they bind to HMG-CoA reductase and prevent the HMG-CoA from binding. This significantly reduces cholesterol synthesis.

Question 12

How does statin cause an increase in HDL ?

Answer 12

The hepatic inhibition of cholesterol production will cause increase in the hepatic production of HDL which is responsible for brining cholesterol to liver.

Question 12

How does statin reduce circulating LDL ?

Answer 12

Inhibition of hepatic cholesterol synthesis will up regulate the expression of hepatic LDL receptors which will facilitate hepatic uptake of cholesterol rich LDL from the blood leading to reduction in circulating levels of LDL and to some extent VLDL

Question 12

what is responsible for statin metabolism

Answer 12

CYP50.

Question 13

What are the side effects of statin ?

Answer 13

• GI symptoms and rashes.
• Myalgias and rhabdomyolysis
• Hepatotoxicity
• Teratogenicity

Question 14

How does statin cause Rhabdomyolysis?

Answer 14

statin inhibits mevalonate synthesis which reduces Farnesyl pyrophosphate production which is essential for Coenzyme Q. Co-enzyme Q is a necessary co-factor for the electron transport chain leading to reduced ATP production which affects high energy consuming cells such as the skeletal muscle cells leading to myopathy and rhabdomyolysis.

Question 15

which are the four groups of people who benefit from statin ?

Answer 15

*Individuals with ASCVD
*Individuals with primary elevations of LDL-C > 4.9 mmol/L
*Individuals 40-75 years of age with diabetes and LDL-C 1.8-4.8mmol/L
*Individuals without clinical ASCVD or diabetes 40-75 with an estimated 10-year ASCVD risk of 7.5% or greater

Question 16

What are the drugs that inhibit statin breakdown ?

Answer 16

These are drugs that are metabolized by the CYP3A4 which will inhibit the elimination of statins.
* Macrolide antibiotics
* CCB
*Cyclosporine
* Amiodarone
* consumption of >240 ml of grape juice.
*

Question 17

When should statin therapy stopped due to risk for myopathy ?

Answer 17

If symptoms present or when there is significant increase ( 10x ) in CK.