Statins

Question 1

where do the Statins inhibit the process of cholesterol production

Answer 1

they inhibit the 26 step intracellular cholesterol synthesis at the HMG-CoA reductase step.

Question 2

raised intracellular cholesterol has what regulatory effects on the cell

Answer 2

decreased intracellular cholesterol synthesis as HMG CoA reductase is inhibited.
it also inhibits transcription of the LDLR gene
activates acetylCoA:cholesterolacyltransferase (ACAT), to esterify free cholesterol into cholesteryl ester that can be stored in the cell.

Question 3

what are the indications for atorvostatin

Answer 3

CVD, high CVD 5 year risk, high LDL, high LDL to HDL ratio, familial hyperlipidaemia

Question 4

what is the mechanism of atorvostatin

Answer 4

these are reversible HMG-CoA reductase inhibitors, these decrease intracellular synthesis and also increase LDL receptor production.
the net result is an increase in cellular cholesterol uptake from the bloodstream.

Question 5

why do we see the increase in LDL receptor production

Answer 5

because low levels of cholesterol within the cell result in increased transcription of the gene.

Question 6

what are some of the pleiotropic effects of statins

Answer 6

inhibits uptake of LDL by macrophage to reduce c-reactive protein release by 15 - 47%
Increases endogenous NO release to produce systemic vasodilation
Many other effects associated with this pleiotropic drug class

Question 7

what are some PKs of atorvastatin

Answer 7

active statin metabolites are eliminated via bile after extensive first pass hepatic metabolism and CYP3A4 metabolism.

Question 8

what are some major adverse reactions of statins

Answer 8

Myopathy & Rhabdomyolysis rare but significant (breakdown of muscle fibres resulting in the release of myoglobin into plasma and eventually kidney )
teratogenic effects, elevate hepatic enzymes that act as biomarkers for disease.