Saturday, October 2, 2010

pharmacology: antilipidemics

this lecture went into the conventional antilipidemic drugs, indicated when patients have high cholesterol levels (high LDL, low HDL, or high total cholesterol levels). there are five classes of antilipidemic drugs: niacin, fibrates, HMG-CoA reductase inhibitors, bile acid binding resins, and cholesterol absorption blockers. The first category, niacin, is given in the form of Vitamin B3, or alternatively, inositol hexaniacinate (considered safer both in the short and long term). niacin is thought to decrease VLDL production in the liver as well as increase its clearance in the serum.

fibrinates, a class of drugs that are derived from fibric acid, are mainly indicated for high TG levels; their main action is to lower TG levels, while also raising HDL levels. the side effects might include liver damage, gallstones, GI upset, myalgias, and rhabdomyolysis. the main fibrinate is called gembibrate / lopid, and it is contraindicated in patients with preexisting liver or gall bladder problems.

statin drugs are a popular category of antilipidemics that act on the HMG-CoA reductase enzyme, which is the first enzyme in cholesterol synthesis. although statins are effective at lowering cholesterol levels, they are not without side effects, the most common being muscle soreness / weakness, thought to be related to HMG-CoA's involvement in CoQ10 synthesis. a severe side effect is rhabdomyolysis which might lead to acute renal failure in some cases. GI symptoms and erectile dysfunction are two other potential side effects from statins as well. they are contraindicated in patients with liver disease, as well as in pregnancy and lactation, and may interact with fibrinates, anti-fungals, macrolides, protease inhibitors. statins can also be used prophylactically during MI's, strokes, or episodes of unstable angina, especially in DM II patients.

the next class of antilipidemics are bile acid sequestrants, which bind to bile salts and form insoluble complexes which are excreted in the feces. the net effect is cholesterol excretion in the stool and secondarily, lowering of LDL blood levels due to a compensatory upregulation of LDL receptors. questran is an example-- side effects include constipation, bloating, and malabsorption of fat soluble vitamins, folic acid, or other medications.

the last class is cholesterol absorption blockers, which are used in conjunction with statins when their cholesterol lowering actions are insufficient. the main side effect is diarrhea (although myalgias and arthralgias can also occur), requiring patients on these medications to wear dark pants and panty liners when starting these medications. along with bile acid sequestrants, cholesterol absorption blockers are considered category C for pregnancy; underresearched and not recommended.

introduction and niacin...
1. how do change in percentage levels of HDL and LDL affect myocardial infarction risk?
2. what are the five categories of antilipidemics?
3. what does niacin do that is unique among lipid lowering medications?
4. what are the longer term side effects of niacin?
5. two potential MOA's for niacin?
6. what tests might be monitored in patients on niacin?
7. niacin is contraindicated in...
8. what is currently considered the safest form of niacin?

9. what are the actions of fibrinates?
10. side effects?
11. examples of fibrinates?
12. main indication for fibrinates?
13. contraindicated in...

statin drugs...
14. what is the enzyme blocked by statin drugs? what does it do?
15. most common complaints from statin users?
16. severe potential side effect of statins? what might be a complication?
17. what is a potential mechanism for statins' relationship to rhabdomyolysis?
18. side effects besides [question 15]?
19. contraindications for statin drugs?
20. potential drug interactions?
21. examples of statin drugs?
22. besides cholesterol lowering, what else are statin drugs indicated for?
23. what lab test might be run if rhabdomyolysis is suspected in a patient taking lipitor?
24. lipitor contraindicated in...

bile acid sequestrants...
25. general mechanism of action?
26. how do bile acid sequestrants lower LDL levels?
27. often used in conjunction with...
28. example of bile acid sequestrants?
29. side effect of [question 28]?
30. use in pregnancy?

cholesterol absorption inhibitors...
31. example of a CAI?
32. often used in conjunction with what other class? when?
33. side effect of CAI's?
34. use in pregnancy?

1. 1% increase in HDL decreases MI risk 3-4%. 1% decrease in LDL decreases MI risk 2%.
2. niacin, firates, HMG-CoA reductase inhibitors, bile acid binding resins, cholesterol absorption blockers. [never forget his bad cholesterol]
3. lowers alpha-lipoprotein(a) levels.
4. liver damage
retinal damage
rhabdomyolysis [liver, eye, uric, muscle] [See Ur Life Strength vanish]
5. mainly unknown, but may be related to decreased VLDL synthesis in liver and increased VLDL clearance in plasma.
6. liver function and glucose.
7. DM, liver disease, peptic ulcer disease.
8. inositol hexaniacinate.

9. decrease liver's TG production, increase HDL levels.
10. liver damage / gall stone formation
nausea / diarrhea / GI upset
rhabomyolysis / myalgias
[LV/GB, ST/SP, PC/TB] [wood, earth, fire]
11. gemfibrozol / lopid, fenobibrate / lofibra. [stupid gemstone, lofi fennel]
12. elevated TG levels.
13. pre-existing GB/LV disease.

14. HMG-CoA reductase, the enzyme that catalyzes the first step of cholesterol synthesis.
15. muscle soreness and weakness.
16. rhabdomyolysis which might lead to acute renal failure.
17. HMG-CoA is also involved in CoQ10 production, which is an enzyme involved in oxidative phosphorylation-- ultimately interfering with muscle cell function and contributing to their degeneration.
18. abdominal pain / nausea / diarrhea
erectile dysfunction
19. liver disease, pregnancy, lactation.
20. fibrinates, macrolides, oral antifungals, protease inhibitors. [mac pro: filled with fungus fiber]
21. atorvastin / lipitor
fluvastatin / lescol
lovastatin / mevacor
22. prophylaxis during MI's, stroke, unstable angina, especially in DM II patients.
23. CPK levels.
24. pregnant women-- category X.

25. bind cholesterol and form insoluble complexes which are ultimately excreted.
26. a compensatory mechanism increases the number of LDL receptors, thereby removing LDL from blood.
27. niacin.
28. cholestryramine / questran
29. bloating, constipation, malabsorption of fat soluble vitamins, folic acid.
30. category C; not adequately studied, but recommended to avoid use.

31. ezetimibe / zetia.
32. statins, when they aren't working to lower serum cholesterol.
33. diarrhea, myalgias, arthralgias.
34. category C.

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