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?
- 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
