(THER) Hyperlipidemia I and II Flashcards
Define Hyperlipidemia
Abnormal/elevated levels of cholesterol/triglycerides in the blood. Increased LDL or low levels of HDL
Increase in what lipid can lead to pancreatitis?
Triglycerides
What is the relationship between LDL and atherosclerosis?
Increased cholesterol leads to increased LDL, which ultimately enters into the arterial wall. This damage ultimately leads to atherosclerosis because it causes monocytes to enter and to eventually form foam cells.
What is the role of foam cells in atherosclerosis? (2)
- Foam cells secrete proteases and growth factors that promote smooth muscle cell migration and proliferation contributing to atherosclerotic plaque
- Necrotic foam cells release cholesterol and other debris that contributes to the formation of a fatty streak
Protective roles of HDL in atherosclerosis (4)
- Inhibit the oxidation of LDLs
- Inhibit expression of adhesion molecles on the endothelium (monocyte recruitment)
- Inhibit formation of FOAM cells
- REVERSE CHOLESTEROL TRANSPORT
Optimal vs high LDL levels
Optimal:
Very high: > 190 mg/dL
Optimal vs very high Triglyceride levels
Optimal:
Very High: >500 mg/dL
At what point do you treat hypercholesterolemia with drugs? What do you do prior?
Once it hits the point of being “severe”. (LDL > 190; LDL w/diabetes > 70; CVD or risk for it)
What is the initial goal of drug therapy for hypercholesterolemia? What is the initial drug of choice?
Goal: reduce LDL
Drug: STATINs
What is the most prescribed class of drug in the US?
STATINs
Name the STATINs from most potent to least potent (6)
- Rosuvastatin
- Atorvastatin
- Simvastatin
- Pravastatin
- Lovastatin
- Fluvastatin
Indication(s) for STATIN use
High LDL
MOA of STATINs
- Inhibits HMG-CoA Reductase
- Triggers SREBP transcription factor
Both lead to increased LDL-R expression and resulting increased LDL clearance.
Effect of STATINs on serum lipids
Decreased LDL and TG
Increased HDL
What is the main adverse effect associated with STATINs?
Rhabdomyolysis
Otherwise they are generally well tolerated
STATINs are contraindicated in what groups?
Individuals with severe liver disease and pregnant/nursing mothers
Name the (4) Drug interactions associated with STATINs
- CYP3A4 inhibitors (increased adverse effects)
- CYP3A4 inducers (decreased efficacy)
- CYP2C9 inhibitors
- Gemfibrozil (decreased glucoronidation)
Name the Bile Acid binding resins (3)
- Cholestyramine
- Colestipol
- Colesevelam
Indication for Bile Acid binding resins
High LDL
MOA for Bile Acid binding resins
- Binds bile (negative charge) and prevents reabsorption, leading to…
- Increased bile production via chol 7a-hydroxylase, leading to…
- Decreased cholesterol and INCREASED LDLR, leading to…
- increased LDL clearance
Effect of Bile Acid Binding Resins on serum lipids
decreased LDL
Adverse effects of Bile Acid Binding Resins
Can increase TG levels in hypertriglyceridemia
Contraindications for Bile Acid Binding Resins
Contraindicated if TG > 400 mg/dL
Bile Acid Binding Resin Drug Interactions
Cholestyramine/ Colestipol interfere with absorption of a number of drugs (warfarin, digoxin, phenobarbital and tetracycline).
Ezetimibe indication(s)
High LDL
Ezetimibe MOA
Inhibits intestinal absorption of cholesterol (via NPCL1), leading to decreased hepatic cholesterol, and increased LDL-R expression/ LDL clearance.