-Rosuvastatin* -Atorvastatin* -Simvastatin* -Pitavastatin -Pravastatin
-Inhibition of HMG CoA reductase leads to the prevention of mevalonate being converted into cholesterol -Expression of the LDL receptor gene is upregulated and this leads to increased endocytosis of LDL -End result is lower serum LDL
Know the word mevalonate and HMG-CoA reductase*
What percent do statins lower LDL and TGs?
-Decrease LDL by 30-60%
-Decrease TGs 20-40%
Other beneficial effects of statins
-Improve endothelial function
-Reduce plasma viscosity
-Primary prevention & secondary prevention
-Start statins in DM patients at diagnosis (secondary)
-Post AMI (secondary)
When should statins be taken?
-Lovastatin, fluvastatin, and simvastatin* should be taken qhs when most cholesterol synthesis occurs due to shorter half life
-the rest can be taken any time (atorvastatin)
Drug monitoring - statins
-LFTs: At baseline and if there is evidence of liver dysfunction
-FLP: 1-3 months after initiation and then every 3-12 months after that
Drug interactions - statins
-Simvastatin and atorvastatin are major CYP3A4 substrates
-Simvastatin most affected, especially with strong CYP3A4 inhibitors
-Increases myopathy risk 5x -Simvastatin also a Pgp substrate --> Pgp inhibitors may increase myopathy risk as well
what drugs when mixed with a statin can cause additive interactions?
-Niacin + statin = additive myopathy -Fibrates + statin = additivt Hepatotoxicity/myopathy ***Specifically gemfibrozil (blocks hepatic clearance)
What antibiotic should you not mix with a statin?
-Daptomycin!!!!! Increased myopathy risk
What is the most common ADR from statins?
-Myopathy (up to 30%)
-Risk and severity often secondary to drug interactions or higher doses
-Stop drug if CK >10x ULN (rhabdo)
-Eval for Vit D deficiency, thyroid disorder, or PMR
Where do myalgias most commonly occur?
-Big muscles (thighs)
What gene (SNP) puts the patient at high risk for myopathy
Strategies to work through myalgia/myopathy symptoms
1. Eval RF 2. Eval med list for interacting drugs 3. Try CoQ10 4. Lowering dose may help 5. Change statin to low dose rosuvastatin 6. Try alternate day dosing*** 7. Add non-stain drug (Ezetimibe)
Myalgia and exercise
-Go slow and work up to 30 min of exercise/day -Increase duration of activity before intensity
Other HMG-CoA reductase inhibitor ADRs
-Increased conc. of aminotransferase
-DM (usually seen in pts with traditional RF*, don't stop giving a statin when DM is dx)
What statin is a great option for someone with renal impairment?
Cholesterol absorption inhibitor, drug and MOA
-Ezetimibe -Blocks absorption in the small bowel, without affecting triglyceride or fat soluble vitamin absorption
Clinical indications of cholesterol absorption inhibitor
Decrease LDL 20-25%
Cholesterol absorption inhibitor drug interactions
-May increase warfarin effect -Do not mix with fibrates*
Bile acid sequestrants, drug and MOA
-Colesevelam* -MOA: binds bile acids in intestines, grabs cholesterol and drags it through the intestines, get a reflexive TG bump
Clinical use of bile acid sequestrants, when is it contraindicated?
-Decrease LDL up to 20%, can raise TG -DON'T USE if TG's > 300 mg/dL
Bile acid sequestrant ADRs
PCSK9 inhibitors, drugs and MOA
-Alirocumab -Evolocumab -MOA: modulates receptor degradation, prevents the LDL-C clearance from blood, and increased serum LDL
Clinical indication and pearls of PCSK9 inhibitors
-Adjunct to diet/max tolerated statin for pts with familial hypercholesterolemia -Decrease LDL by 60% (very potent) -$$$
ATP-Citrate Lyase inhibitors, drug and MOA
-Bempedoic acid (can add ezetimibe) -Activated by ACSVL1, this is basically like an upstream version of a statin that blocks at its precursor
ACL inhibitors clinical indiciations
Same as PCSK9, adjunct to diet and max tolerated statin therapy in pts with hetero familial hypercholesterolemia or ASCVD who need extra LDL lowering
If you combine Bempedoic acid with a statin, you are at in increased risk of..?
Common ADRs of ACL inhibitors
-Muscle spasms and back/extremity/abd pain
-Tendon rupture******** (also FQ)
Targeting HDL and TG, drug and MOA
-Niacin (extended-release -> least flushing and HTX)
-Inhibits the mobilization of free fatty acids from peripheral adipose tissue to the liver, hence VLDL decreased