Flashcards in Antihyperlipidemics Deck (25):
With statin therapy, how long does it usually take to see significant LDL reduction?
about 2 weeks
How long does it take for statin therapy to lower BP?
2 days. This occurs due to the stimulation of eNOS.
What are antihyperlipidemics or hypolipidemics?
drugs used to treat hyperlipoproteinemias that cause atherosclerosis/ coronary artery disease (CAD) and reduce risk of mortality to heart disease and stroke.
Also treat hypertriglyceridemia that may also cause acute pancreatitis when triglycerides (TGs) are markedly elevated.
What are the major lipids?
cholesterol and TGs that are transported via lipoproteins
What are apoproteins?
surface proteins on lipoproteins that interact with tissue membrane receptors to assist transport/ uptake to/from tissues (ex. apoB-100 is a ligand for LDL recepors=BAD)
How are lipoproteins correlated to CAD?
increased LDL and low HDL :(
These are associated with plaques (oxidized LDLs), foam cells, atherosclerosis, calcification, endothelial rupture, thrombosis, and MI.
What is Lp(a)?
atherogenic lipoprotein, genetically determined, related to LDL, and a risk factor for CAD.
What should normal LDL be?
Less than 100 mg/dL (2.59 mmol/L) — Optimal.
What should your LDL be if you have vascular disease?
How do you calculate LDL?
LDL= Total cholesterol - HDL - (TG/5)
What is a normal LDL/HDL ratio?
3 - 3.5. Anything above 3.5= increased risk for CAD.
What are the nonpharmacologic strategies to lowering LDL?
- eliminate smoking
- eliminate excess alcohol
- diet (fish oils, omega-3s)
- lose excess weight
- aerobic exercise
- control diabetes
- control thyroid function
**What are bile acid binding resins?
inhibit bile acid reabsorption from the gut and the result is compensatory increase in liver bile acid sythesis from cholesterol by increasing LDL receptors on the liver to remove LDL-cholesterol form the plasma, thus lowering cholesterol.
Usually second-line drugs, or used in combination with statins, fibrates, or niacin.
What are the 3 bile acid binding resins?
**What are the ADRs of bile acid resins?
- bloating, belching, gas, heartburn, and constipation.
- impairs absorption of fat soluble vitamins (A, D, E, K)
- may INCREASE VLDL-triglyceride levels due to increased liver TG synthesis. :(
**What are statins?
- Competitive inhibitors of HMG CoA reductase. This is the rate limiting step and significantly reduces liver cholesterol synthesis. This decrease in LDL forces the liver cells to up-regulate more LDL receptors and import more LDL from the bloodstream.
- Also have anti-inflammatory effects and increased eNOS activity.
What are the more common statins?
Rosuvastatin, Atorvastatin, Simvastatin
Do statins increase HDL?
**What are the ADRs of statins?
- increased liver alanine and aspartate aminotransferase (LFTs) as well as metabolized via CYP450.
- increased CPK and MYOPATHY
- CONTRAINDICATED in PREGNANCY
**What is ezetimibe?
inhibits jejunal enterocyte uptake of cholesterol. It is usually used with a statin or bile acid resin.
**What is Niacin (vitamin B3)?
- Inhibits intracellular lipase, decreasing free fatty acid supply to liver, decreasing synthesis of VLDL, plasma VLDL, and decrease LDLs, while increasing HDL.
- It also improves endothelial function, enhancing the function of t-PA and decreases fibrinogen; keeps the pipes clean.
- It is sometimes combined with a statin.
**What are the ADRs of Niacin (vitamin B3)?
- intense vasomotor flushing and pruritis.
- increased LFTs (AST and ALT)
- hyperglycemia intolerance and may increase insulin resistance
- hyperuricemia (GOUT)
- peptic ulcers
* Thus don't use in diabetics, those with liver disease, pregnant, or if they have gout.
What are the fibric acid derivates?
- Gemfibrozil= activates nuclear receptor in liver and muscle that increases LPL/ fatty acid oxidation, lowering TGs and it increases HDL (due to increased ApoI/II).
*Considered first line drug for increased TGs.
- Fenofibrate= newer drug that decreases LDL more the gemfibrozil but doesn't increase HDL as much.
What are the ADRs of fibric acid derivatives?
cholecystitis (GALLSTONES), myopathy, and increased liver enzymes.