Lipid Therapeutics Flashcards
Newer statins
-Rosuvastatin* -Atorvastatin* -Simvastatin* -Pitavastatin -Pravastatin
Statins MOA
-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
- Plaque stabilization
- Reduce inflammation
Statin indications
- 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
- Fasting BS/HgBA1c
- CPK
- 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
SCL01B1
Strategies to work through myalgia/myopathy symptoms
- 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?
Atorvastatin
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
GI intolerance
PCSK9 inhibitors, drugs and MOA
-Alirocumab -Evolocumab -MOA: modulates receptor degradation, prevents the LDL-C clearance from blood, and increased serum LDL
