Statins Flashcards
What are statins?
Drug used to prevent coronary heart disease by improving the lipid profile of at risk patients.
Reversibly inhibitors of the hepatic enzyme HMG-CoA reductase.
Name 4 commonly used statins.
- Atorvastatin
- Simvastatin
- Pravastatin
- Rosuvastatin
How do statins work?
They prevent acetyl-CoA from forming Mevalonate, which would normally form cholesterol. SO they lower cholesterol levels.
Also:
- anti-inflam
- improve endothelial cell function
- plaque stability
- prevent thrombus formation
Are statins absorbed well?
Yes orally.
When do statins reach Cmax?
1-2 hours
When are therapeutic effects observed?
Within 1-2 weeks
What are a few dose-response issues with statins?
- plasma concentrations vary widely across individuals but therapeutic efficacy appears weakly related to plasma statin levels
- statins produce sigmoidal curve so dose above IC50 results in minor changes
- side effects increased with increased dose.
Of the 3 main statins, which is hydrophilic and which is lipophilic?
Atorvastatin - lipophilic
Simvastatin - lipophilic
Pravastatin - hydrophilic
Of the 3 main statins, which passively diffuses and which is actively pumped?
Atorvastatin - passive diff
Simvastatin - passive diff
Pravastatin - actively pumped
Of the 3 main statins, which is a prodrug that is metabolised in the liver to the active B-hydroxy FA form?
Simvastatin
Of the 3 main statins, which lowers the risk of myopathies and has a longer half life of 77 hours (yet lower protein binding profile)?
Pravastatin
Of the 3 main statins, which is a more potent lipid-lowering drug of the first generation of statins?
Atorvastatin
Which enzymes are involved in statin metabolism?
CYP3A4 and 2A9.
CYP inhibitors can cause what?
Elevated levels of statin and toxicity.
What is the effect of grapefruit juice on CYP3A4?
It is an inhibitor of the enzyme.
