Exam 2 - Hyperlipidemia Flashcards
What is the cause of Familial Hypercholesterolemia and what abnormality will you see in levels?
Cause: LDL receptor deficiency
Increased LDL
Lovastatin, Simvastatin, and Atorvastatin belong to what drug group?
HMG-CoA Reductase Inhibitors (Statins)
What is the MOA for HMG-CoA Reductase Inhibitors (Statins)?
Inhibits HMG-CoA reductase, reducing the livers ability to synthesize new cholesterol. The only way it will be able to make new cholesterol then is by increasing its LDL receptors to bring in LDL from the blood and using it, therefore reducing its levels.
What is the DOC in reducing LDL levels?
HMG-CoA Reductase Inhibitors (Statins)
What are uses for Statins?
- Reduce LDL (DOC)
- Reduce triglycerides
- Increase HDL
- Increase plaque stability
- Decrease platelet aggregation
What is significant about Atorvastatin when compared to the other Statins?
Can be given in high dose which is used in high-risk ASCVD patients
Which two Statins are inactive and must be hydrolyzed into their active form?
Lovastatin and Simvastatin
What enzymes metabolize Statins?
P450s, CYP3A4
Which two Statins should be taken in the evening and why?
Lovastatin and Simvastatin should be taken in the evening as peak cholesterol synthesis occurs in the early morning hours and we want to block it
What are some adverse effects of Statins?
- Increases levels of serum aminotransferase (enzyme to measure LFTs)
- This increase in aminotransferase can lead to liver damage in alcoholics and those with liver disease
- Myopathy and/or muscle pain due to muscle damage
- Increases serum creatine kinase activity (hallmark)
- Rhadomyolysis - myoglobinuria
What is a hallmark adverse effect of Statins?
Increased serum creatine kinase activity due to muscle damage
What are contraindications/precautions of Statins?
- Pregnancy
- Active hepatic disease
- P450 inhibitors (grapefruit juice, macrolides, verapamil, ketoconazole, ritonavir will increase plasma concentrations)
- P450 activators (phenytoin, griseofulvin, barbiturates, rifampin will decrease the plasma concentrations)
- Gemfibrozil will inhibit metabolism
What drug class does Cholestyramine belong to?
Bile Acid-Binding Resins
What is the MOA for Cholestyramine?
Binds bile acids and prevents their intestinal reabsorption, leading to decreased serum LDL levels as the liver will have to take up serum LDL to make more bile acids
What are uses of Cholestyramine?
Decrease LDL levels
What is Cholestyramine not effective for?
- No effect in homozygous familial hypercholesterolemia due to no functional LDL receptors
- Not effective in hypertriglyceridemia
What is important to remember when taking Cholestyramine in regards to its pharmacokinetics?
Should be taken with meals as bile production is needed for effect
Why is Cholestyramine safe in pregnancy?
It is not absorbed
What is the most common side effect and is a hallmark of Cholestyramine?
Constipation and bloating
What is a rare side effect of Cholestyramine?
- Gallstones in obese patients
- May cause hypoprothrombinemia due to vitamin K malabsorption
What can Cholestyramine impair the absorption of?
Acid or fat-soluble drugs like digitalis, thiazides, statins, tetracycline, thyroxine, or aspirin
What is the MOA for Niacin?
Inhibits VLDL secretion, leading to reduce levels of plasma VLDL and LDL
What is the most effective agent for increasing levels of HDL? What type of patient is this used for?
Niacin - used in patients who cannot exercise
What are uses of Niacin?
- Decrease VLDL/LDL
- Increase HDL
