Lipid Lowering Drugs Flashcards
What organ makes cholesterol?
What causes more cholesterol to be made?
Liver makes Cholesterol naturally.
However, it makes more cholesterol when we eat saturated fat.
What enzyme helps make Cholesterol?
Liver uses HMG-Coenzyme A
Which lipoprotein transports triglycerides?
Where does it transport the triglycerides to?
VLDL: contains mostly triglycerides.
VLDLs deliver triglycerides from the liver to the adipose tissue in our muscles (where it is used as fuel).
Which lipoprotein is bad?
Where does it transport cholesterol to?
LDL: bad guys, they contain the majority of cholesterol
LDL deliver cholesterol to non hepatic tissues, and the cells that need to take in cholesterol have LDL receptors (so when the demand for cholesterol increases, the cells increase the # of LDL receptors)
Which lipoprotein is good?
Where does it transport cholesterol to?
HDL: good guys, they also have cholesterol but not as much. Their job is to remove cholesterol, so high HDL is a good thing, and helps decrease CAD risk
Increased levels of triglycerides cause?
Increased levels of triglycerides are linked to Coronary Artery Disease (CAD), and very high levels can cause pancreatitis
Goal of Drug Therapy for Lipid Disorders?
- Biggest strategy is to decrease LDL
2. Specific drugs work better to decrease triglycerides
What are HMG-CoA Reductase Inhibitors?
How effective are they at treating lipid disorders?
Statins are 1st line of therapy for lipid disorders.
Statins DECREASE mortality.
Most effective at lowering LDL and total Cholesterol
Raise HDL
What is the MOA of statins? (3 parts)
MOA:
- Inhibit cholesterol synthesis in the liver (by inhibiting HMG CoA Reductase
- stimulate hepatocytes to produce more LDL receptors
- LDL receptors remove the LDL from the blood
What time of day should statins be given?
Most effective at night.
Cholesterol is made at night, so we give statins at night (for most statins)
By what % do statins lower LDL?
Statins can decrease LDL levels by more than 60%
Range is 25-63% depending on doses of statin
Why do we give people with diabetes statins?
We use statins for Primary and Secondary preventions.
We use them to prevent cardiovascular events in people with diabetes, even when their LDL levels are normal (because they are so effective)
Common side effects of statins (atorvastatin (Lipitor))
headache, rash, memory loss, GI disturbance
Pt’s record states they are allergic to statins, what could have caused this?
(Hint: Rare, but serious side effects of statins (atorvastatin )
Hepatotoxicity (2% of pts):
- Check LFTs before use:
(1. Get baseline LFTs
2. pts should have LFTs checked every 6 mos or 12 mos, and discontinue statin if they have increased LFT) - Contraindicated in liver disease (but statins okay in steatohepatitis)
Myopathy/ Rhabdomyolysis (5-10% of pts):
- muscle aches, tenderness, weakness
- But elevated CK levels: Can lead to Rhabdomyolysis
- Sometimes using Vitamin D, Coenzyme Q, or switching to another statin helps
Increase in incidence of cataracts
Pt education: report any unexplained muscle pain or weaknesses (especially when first starting the drug)**
Things to watch out for when using Atorvastatin (Lipitor)
Common statin SE Hepatitis (check LFT) Myopathy/ Rhabdomyolysis (check CK) Monitor for increased SE when statins combined with other lipid-lowering agents No Grapefruit (CYP3A4 pathway)
Pregnancy category X
CYP3A4 pathway drugs: Erythromycin, Azole, Antifungal, protease inhibitors
What is colesevelam?
How does it lower cholesterol?
Colesevelam is a bile-acid sequesterant
Colesevelam BINDs to bile acids to form complexes that are excreted
So more bile acids need to be made
So liver needs more cholesterol to make bile, so it increases LDL receptors (this lowers cholesterol in body)
Colesevelam is Biologically inert
Colesevelam also improved glucose metabolism
SE of colesevelam
Work only in GI tract
GI side effects
constipation, bloating, indigestion
Administer with food + H20
What is Ezetimibe
- Blocks cholesterol absorption in the small intestine
2. Also blocks cholesterol secreted in bile
Ezetimibe SE?
Side Effects: equal placebo, only works on GI tract
Sometimes used with statin as statin booster: but watch out for liver toxicity
Not used in people with liver disease
Why is Vytorin?
What should you watch out for with this drug?
Vytorin: ezetimibe + simvistatin
Watch out for liver toxicity
Ezetimibe boosts statin
What is Gemfibrozil?
What is it’s MOA?
Fibric Acid Derivatives (Fibrates)
MOA: accelerate the clearance of VLDLs
Most effective for lowering TG levels
Used to treat hypertriglyceridemia
Little or no effect on LDL cholesterol
For a pt who was a high carb diet, with hypertriglyceridemia, what would you recommend?
Gemfibrozil
Gemfibrozil is used for pts with high triglycerides (TG)
Seen in pts with: obesity, sedentary lifestyle, smoking, alcohol, Type II Diabetes, high carb diet
SE of Gemfibrozil?
Side Effects: Rash GI upset Increased risk of gallstones Myopathy Hepatotoxicity
Drug-drug interactions with Gemfibrozil
Warfarin: Increase risk of bleeding
Statins: increased risk of rhabdo
