EXAM #1: DYSLIPIDEMIA II Flashcards
What is the MOA of the statins?
Block conversion of HMG-CoA to mevalonic acid
*Many pleiotropic effects as well
What are the effects of statins on lipid levels?
- Lowered LDL
- Lowered TG
- Increased HDL
*Note a primary therapy to increase HDL
What should you do for a patient with ASCVD?
High intensity statin therapy
What should you do for a patient with primary elevations of LDL-C more than 190 mg/dL?
High intensity therapy
What should you do for a diabetic, 40-75 y/o, with a LDL-C between 70 and 189 mg/dL?
Moderate intensity therapy
What should you do for a patient without DM, but with a 10-year CVD risk greater than 7.5% tat is also between 40 and 75 y/o with a LDL-C between 70 and 189 mg/dL?
Moderate to high intensity therapy
What are the adverse effects associated with statins?
1) Muscle complaints (spectrum of myalgia to rhabdomyolysis)
2) Liver Disease
3) DM/ insulin resistance
What drug is specifically contraindicated with statin therapy because of an increased risk of muscle related adverse effects?
Gemfibrozil
Why do you get muscle related symptoms with statins?
Depletion of CoQ10 in muscle mitochondria in the pathway of cholesterol synthesis
What is myositis?
Muscle inflammation that is tender to the touch
What lab is associated with myositis and myonecrosis?
CK elevation
How should you treat a statin related muscle complaint?
1) R/o complicating condition
2) Treat with CoQ10 supplement
3) STOP and rechallenge with alternate statin
4) Alternate agent
What is statin triggered autoimmune myopathy?
Weakness that resolve and elevated CK from HMG-CoA Reductase autoantibody
What are the non-statin lipid lower therapies?
1) Bile acid sequestrants
2) NIacin
3) Fibric acids
4) Ezetimibe
What is the MOA of the bile acid sequestrants?
- Reduce reabsorption of bile acids/ cholesterol
- More cholesterol needs to be output from liver for basal function
- Cholesterol levels lower
What effects do the bile acid sequestrants have on lipid levels?
- Lower LDL
- Raise HDL
May INCREASE TG
What is the contraindication of bile acid sequestrant administration?
High TG
What effects does Niacin have on lipid levels?
- Lower LDL
- Raises HDL
- May REDUCE LP(a)
What are the contraindications to Niacin?
Liver disease
Gout
Peptic ulcer
Should Niacin be added to statin therapy?
No
What major adverse effect is seen with Niacin
Flushing
What is the primary clinical indication for Fibric Acids?
Hypertriglyceridemia
What is the major effect of the fibric acids on lipid levels?
Lowered TG
What adverse effect is specifically associated with the fibric acids?
Gallstones
Do fibric acids show increased theraputic benefit with coadministration with statins?
No
What is the MOA of Ezetimibe?
Impairs dietary cholesterol absorption
Should Ezetimibe be added to Statin therapy?
YES–increased efficacy when added to statin therapy
What is the major lipid effect of fish oil?
Lowers TGs
What is the function of CETP?
Converts HDL into VLDL and LDL
What was the hypothesized effect of CEPT inhibitors?
CETP inhibitors would increase HDL
Good theory, haven’t worked in clinical trials
What are the two drugs that are uniquely indicated for Familial Hyperlipidemia?
1) Mipomersen
2) Lomitapide
What is the MOA of mipomersen?
Blocks the production of apoB mRNA so that the liver doesn’t make VLDL or LDL
What is the MOA of Lomitapide?
Oral MTP inhibitor, which is needed for Apo B lipoproteins
What is the function of PCSK 9?
Regulates the expression of LDL receptors
What is the MOA of PCSK 9 inhibitors?
- Monoclonal antibody
- Locks LDL and LDLR together
- Destroys LDL and LDLR
