Statins: HMG-CoA Reductase Inhibitors

Question 1

Simvastatin / Lovastatin / Atorvastatin
MOA

Answer 1

Specific competitive antagonist that inhibits the rate-limiting enzyme HMG-CoA reductase which reduces hepatic cholesterol synthesis. This up-regulates LDL-receptor synthesis and causes increased clearance of LDL clearance from plasma to the liver. Also produces small decrease of TG and small increase in HDL

Question 2

Simvastatin / Lovastatin / Atorvastatin
Abs/Distrb/Elim

Answer 2

Given orally and undergoes first pass metabolism
Inactive until biotransformation in the liver where it is hydrolyzed

Short-acting statins half life 1-4hrs
- Simvastatin & Lovastatin

Long-acting statins half life 20hrs
- Atorvastatin

Question 3

Simvastatin / Lovastatin / Atorvastatin
Clinical use

Answer 3

Hypercholesterolaemia.
Used to prevent atherosclerosis in patients with high Cholesterol serum levels and to prevent cardiac infarction in patients who already have atherosclerosis

Question 4

Simvastatin / Lovastatin / Atorvastatin
Adverse effects

Answer 4

Usually mild: muscle pain, GIT disturbances, insomnia, rash.
Rarer severe effects: severe myositis (risk increased if given with fibrates)
Use with warfarin can increase INR

Simvastatin, Lovastatin & Atorvastatin are metabolized by CY3A4.
- These statins can accumulate in plasma if used with drugs that inhibit CYP3A4 e.g HIV protease inhibitors