Molecular Biology: Clinical Significance of Lipoproteins Flashcards
What is PCSK9?
A regulatory protein in LDL-receptor metabolism
What are the pre-2013 guidelines for HDL cholesterol levels that are considered “high risk”?
What are the main drugs/drug types that are used to increase HDL levels?
Where do fibrates, niacin, and CEPT inhibitors fit into this figure, and what do they do?
- All increase HDL
- CETP inhibitors decrease LDL
What are the pre-2013 guidelines for HDL cholesterol levels that are considered “low risk”?
Describe how LDL receptors are activated and what happens once they are activated
- Decreases in cholesterol induces an increase in LDL-receptors
- This causes endocytosis of LDL and thus a decrease in serum LDL.
- LDL will donate cholesterol to cells
What are the pre-2013 guidelines for total cholesterol levels that are considered “Desirable”?
Does the use of Ezetimibe and Simvastatin as combo-therapy cause a decrease in LDL? What about a decrease in cardiovascular disease?
- Does the use of Ezetimibe and Simvastatin as combo-therapy cause a decrease in LDL?
- Yes
- What about a decrease in cardiovascular disease?
- No
What are the general ADRs for statins?
- What is the regulatory step in cholesterol synthase?
- What kind of regulation does this enzyme have?
- How do statins affect this mechanism?
- HMG-CoA Reductase
-
Feedback inhibition
- Cholesterol, the product, will inhibit the enzyme, HMG-CoA Reductase
- Bind to HMG-CoA Reductase as competitive inhibitors, inhibiting cholesterol synthase. The cell then uses the mechanism of increasing LDL receptors to get cholesterol instead of synthesizing it on its own.
- What are the pre-2013 guidelines for LDL cholesterol levels that are considered:
- The goal for people with very high attack of heart disease
- The goal for people with heart disease or diabetes
- The goal for people who are generally healthy
What are the main takeaways from the Framingham Heart Study?
- HDL
- High HDL is good, probably independent of other types of cholesterols
- LDL
- Low LDL levels with high HDL levels has the lowest risk of cardiovascular disease
What statistic is important in remembering the relation to lipid profiles and MIs?
Only 50% of PTs who suffer from an MI have bad lipid profiles
Concerning algorithms for calculating statin use,
- What alarming pattern is seen in older patients?
- What measurement is being considered as an addition to the algorithms?
- Why should the outcome of an algorithm be taken with a grain of salt?
- Healthy old people are recommended to be on statins
- Coronary artery calcium levels
- Many different algorithms. Some may say a PT needs to be on statins and others say they do not need a statin.
What are the pros and cons of PCSK9 inhibitors?
Longterm effects are also unknown
Describe the general mechanism for Familial hypercholesterolemia
What are the main drugs/drug types that are used to lower LDL levels?
What are the most used statins and why?
Top two drugs have the highest half-life and decrease LDL the most compared to others.
What are the Pleiotropic Effects of Statins?
What kind of drugs are the current PCSK9 inhibitors?
What are their names?
What is the Primary vs. Secondary Endpoint for cholesterol clinical trials
- Primary
- Better Cardiovascular Outcomes
- Secondary
- Lower LDL levels
- Concerning the 4 main healthy lifestyle changes that people can make to change their lipid profile for the better:
- What are they?
- Which one does not decrease LDL?
How do PCSK9 inhibitors work?
In the liver…
- Normally PCSK9 is secreted into the ECF, which then binds to the LDL-receptor on the cell surface.
- The receptor is endocytosed by the cell and the PCSK9/LDL-receptor complex forces the LDL-receptor into the lysosome degradation pathway rather than the recycling pathway.
- Binding to PCSK9 by PCSK9-inhibitors, therefore, increases the likelihood that LDL-receptors will be recycled, thus decreasing LDL serum concetrations.
Describe the two general ways that serum levels of LDL is altered
- Cholesterol sources for cells
- Importing LDL into cells
- Synthesizing of cholesterol by cell
- LDL receptors
- Degrading after use
- Recycling after use
What is Familial Hypercholesterolemia?
- Familial hypercholesterolemia is a genetic disorder.
- Caused by one of 2 mechanisms
- The LDL-receptors become are defected in these PTs.
- Caused by one of 2 mechanisms
- *OR**
* The APO B-100 on LDL is defective- The defect makes the body unable to remove LDL cholesterol from the blood, and this serum LDL increases.
- PTs have an increase in risk cardiovascular disease
How does ezetimibe work?
- It Inhibits Uptake of Dietary Cholesterol
- Blocks NPC1L1, which is a gut transporter for dietary cholesterol
