1 - Lipid Disorders Flashcards
What causes atherosclerosis?
Elevated plasma cholesterol, primarily derived from LDL’s
What are risk factors for increased LDL?
- Smoking
- Hypertension
- Diabetes mellitus
- Genetics
Why should you control plasma cholesterol?
Can lead to atherosclerosis
Why should you control plasma triglycerides?
Can lead to pancreatitis
What causes pancreatitis?
Elevated triglycerides, primarily chylomicrons and VLDL’s
What does the body do when it needs cholesterol?
Liver synthesized VLDL, which are similar to chylomicrons
What is the function of lipoprotein lipase?
Hydrolyzes chylomicrons, producing free fatty acids
What are some possible sites to decrease cholesterol?
- Decrease dietary intake
- Decrease absorption of cholesterol or reabsorption of bile acids
- Decrease endogenous cholesterol synthesis
- Decrease LDL levels by decreasing VLDL or increasing LDL receptors
What are some non-pharm approaches to decrease cholesterol?
- Increase dietary fiber (100g each day)
- Increase omega-3 fatty acids
What are statins?
HMG-CoA reductase inhibitors
What are some examples of statins?
- Rosuvastatin
- Atorvastatin
- Simvastatin
When are statins the 1st line therapy?
For most px w/ risk of coronary heart disease
What do statins do?
- Decrease LDL levels
- Decrease triglyceride levels
- Decrease cardiac morbidity, mortality, and reduce incidence of stroke
What is important about HMG-CoA reductase?
Rate limiting step of cholesterol synthesis
Statins are best given in the _____
Evening
Are statins safe in pregnancy?
No
What are some adverse effects of statins?
Myalgia, muscle weakness
What is contraindicated w/ statins and why?
- Statins undergo first pass metabolism by CYP 3A4
- Contraindicated w/ CYP 3A4 inhibitors (grapefruit juice) because will increase bioavailability of statin
What a flat dose response for statins mean?
Increasing the dose doesn’t increase effect (majority of statin LDL efficacy is w/ the starting dose)
What drug is a cholesterol absorption inhibitors?
Ezetimibe
What does ezetimibe do?
- Inhibits dietary and biliary cholesterol absorption
- Inhibits cholesterol transport protein NPC1L1
What is a side effect of ezetimibe?
Reflex increase in cholesterol synthesis
Which drugs are bile acid binding resins?
- Cholestyramine
- Colestipol
When are bile acid binding resins used?
- Mild to moderate elevated LDL
- Effective w/ statins or nicotinic acid in high LDL levels
How do bile acid binding resins work?
Binds bile acids in intestinal lumen, preventing reabsorption
What are some adverse effects of bile acid binding resins?
- May increase VLDL levels
- Decrease absorption of fat soluble vitamins
- Nausea, constipation, bloating
- Absorption of drugs altered
Why would statins and ezetimibe be combined?
- Ezetimibie decreases cholesterol uptake in gut, which causes a reflex increase in cholesterol synthesis in liver
- Statins block this increased synthesis
Why would statins and bile acid binding resins be combined? Are they commonly combined?
- Statin inhibits synthesis of cholesterol and bile acid binding resins prevent reabsorption of bile, causing increased excretion
- Together they decrease LDL levels
- Not generally used b/c bile acid binding resins are poorly tolerated
What can cause a px to fail to achieve the LDL-C target?
- Poor adherence
- High baseline LDL-C
- High-cholesterol diet
- High cholesterol absorption
- Variable statin response
- Inability to tolerate statins
What is the newest therapy for px that can’t meet target levels of LDL? What is the name of the drug?
- Target LDL receptor PCSK9 by injecting human monoclonal Ab to PCKS9 to increase LDL receptors on liver
- Drug = evolocumab
What are the problems w/ cholesterol lowering drugs?
- Variation in px sensitivity to HMG-CoA reductase inhibitors
- Evidence that ezetimibe plus simvastatin may be no more beneficial in plaque regression than simvastatin alone
What are the potential ways to decrease plasma triglycerides?
- Decrease dietary triglycerides
- Increase lipoprotein lipase activity
- Decrease VLDL secretion from liver
What is a non-pharm to decrease dietary triglycerides? What is the problem w/ this?
- Dietary fiber (soluble better than insoluble)
- Problem = need large amounts of fiber and long term effect and safety unknown
Which drugs are fibrates?
- Fenofibrate
- Gemfibrozil
- Clofibrate
What do fibrates do?
- Don’t change LDL levels, but decrease incidence of non-fatal MI and stroke
- Primarily decrease triglycerides and may increase HDL
- Increase VLDL clearance and decrease VLDL secretion
What is important to note about clofibrate?
- Increased mortality due to malignant and GI disease
- Only used in extreme unresponsive cases
What are some adverse effects of fibrates?
- Flu-like (muscle cramps, tenderness, weakness)
- Avoid in hepatic or renal dysfunction
What does nicotinic acid do?
- Increases HDL levels at low dose
- Decreases VLDL production via inhibition of fatty acid release from adipose tissue => decreases triglycerides at higher dose
What are some adverse effects of nicotinic acid?
- Poor tolerability
- Skin flushing and pruritus
- Exacerbation of peptic ulcer
