Niacin

General: H20 soluble B-Vitamin.

Mech: 1) Decr. TG synth. in liver, decr. VLDL. 2) Decr. Adipose lipolysis, decr. FFA transport to liver, decr. TG synth. 3) decr. Hepatic HDL-apoA-1 clearance, incr. HDL-C.

Use: Incr. HDL (best), decr. LDL.

SE: Flushing, pruritis of face, upper trunk. Skin rashes, acanthosis nigricans. Dyspepsia (reactivation of peptic ulcer disease). Hepatotox., hyperglycemia, hyperuricemia.

DON'T: Use in DM, Gout patients.

Gemfibrozil

Class: Fibric Acid Derivative (Fibrate)

MECH: Interact with PPARα, decr. TG by 1) Stimulation of LPL synthesis and 2) Inhibition of apoCIII expression, incr. VLDL clearance. Also incr. HDL by stim. of apoA-I and A-II expression.

USE: Decr. circulating VLDL (decr. TGs), variable LDL-C levels, incr. HDL. Used for hypertryglyceridemic pts.

AE: Well-tolerated. GI, flu-like myositis. Bile stones (in older class).

INTXN: Incr. action of oral anticoags.

Fenofibrate

Class: Fibric Acid Derivative (Fibrate)

MECH: Interact with PPARα, decr. TG by 1) Stimulation of LPL synthesis and 2) Inhibition of apoCIII expression, incr. VLDL clearance. Also incr. HDL by stim. of apoA-I and A-II expression.

USE: Decr. circulating VLDL (decr. TGs), variable LDL-C levels, incr. HDL. Used for hypertryglyceridemic pts.

AE: Well-tolerated. GI, flu-like myositis. Bile stones (in older class).

INTXN: Incr. action of oral anticoags.

Ciprofibrate

Class: Fibric Acid Derivative (Fibrate)

MECH: Interact with PPARα, decr. TG by 1) Stimulation of LPL synthesis and 2) Inhibition of apoCIII expression, incr. VLDL clearance. Also incr. HDL by stim. of apoA-I and A-II expression.

USE: Decr. circulating VLDL (decr. TGs), variable LDL-C levels, incr. HDL. Used for hypertryglyceridemic pts.

AE: Well-tolerated. GI, flu-like myositis. Bile stones (in older class).

INTXN: Incr. action of oral anticoags.

Bezafibrate

Class: Fibric Acid Derivative (Fibrate)

MECH: Interact with PPARα, decr. TG by 1) Stimulation of LPL synthesis and 2) Inhibition of apoCIII expression, incr. VLDL clearance. Also incr. HDL by stim. of apoA-I and A-II expression.

USE: Decr. circulating VLDL (decr. TGs), variable LDL-C levels, incr. HDL. Used for hypertryglyceridemic pts.

AE: Well-tolerated. GI, flu-like myositis. Bile stones (in older class).

INTXN: Incr. action of oral anticoags.

Cholestyramine

Class: Bile Acid Sequestrant

MECH: "Binding resins" highly pos. charged (yet hydrophobic) which bind neg. charged bile acids and excrete in stool. Leads to incr. hep. LDL receptors, incr. LDL clearance.

USE: Decr. LDL-C levels, slight incr. HDL & TG. Safe-can be given to kids.

AE: Bloating, dyspepsia, constipation.

INTXN: Resins bind drugs (cardiac glycosides, coumarin anticoags) & ADEK--interfere with absorption.

Colestipol

Class: Bile Acid Sequestrant

MECH: "Binding resins" highly pos. charged (yet hydrophobic) which bind neg. charged bile acids and excrete in stool. Leads to incr. hep. LDL receptors, incr. LDL clearance.

USE: Decr. LDL-C levels, slight incr. HDL & TG. Safe-can be given to kids.

AE: Bloating, dyspepsia, constipation.

INTXN: Resins bind drugs (cardiac glycosides, coumarin anticoags) & ADEK--interfere with absorption.

Colesevelam

Class: Bile Acid Sequestrant

MECH: "Binding resins" highly pos. charged (yet hydrophobic) which bind neg. charged bile acids and excrete in stool. Leads to incr. hep. LDL receptors, incr. LDL clearance.

USE: Decr. LDL-C levels (25%), slight incr. HDL & TG. Safe-can be given to kids.

AE: Bloating, dyspepsia, constipation.

INTXN: Resins bind drugs (cardiac glycosides, coumarin anticoags) & ADEK--interfere with absorption.

Lovastatin

General: Lactone prodrug. Contraindicated in pregnant or nursing women. Take @ night.

MECH: HMG-CoA reductase competitive inhibitor--rate limiting in Chol. biosynth (HMG CoA -->Mevalonate). Low LDL in hepatocyte causes incr. SREBP transcription factor for LDL-R. Incr. Chol. clearance fr. blood, decr. hep. VLDL prod. (incr. TG).

KINETICS: 1-4 hour ½ life in older statins.

USE: Decr. LDL-C (20-55%), decr. TG (25%), incr. HDL (5-10%). Lowers CHF events, stroke, total mortality.

AE: Myopathy and rhabdo.

INTXN: Don't give with fibrate or niacin because of myopathy (unless at 25% max dose).

Simvastatin (Zocor)

General: Lactone prodrug. Contraindicated in pregnant or nursing women. Take @ night.

MECH: HMG-CoA reductase competitive inhibitor--rate limiting in Chol. biosynth (HMG CoA -->Mevalonate). Low LDL in hepatocyte causes incr. SREBP transcription factor for LDL-R. Incr. Chol. clearance fr. blood, decr. hep. VLDL prod. (decr. TG).

KINETICS: 1-4 hour ½ life in older statins.

USE: Decr. LDL-C (20-55%), decr. TG (25%), decr. HDL (5-10%). Lowers CHF events, stroke, total mortality.

AE: Myopathy and rhabdo.

INTXN: Don't give with fibrate or niacin because of myopathy (unless at 25% max dose).

Mevastatin

General: Contraindicated in pregnant or nursing women. Take @ night.

MECH: HMG-CoA reductase competitive inhibitor--rate limiting in Chol. biosynth (HMG CoA -->Mevalonate). Low LDL in hepatocyte causes incr. SREBP transcription factor for LDL-R. Incr. Chol. clearance fr. blood, decr. hep. VLDL prod. (decr. TG).

KINETICS: 1-4 hour ½ life in older statins.

USE: Decr. LDL-C (20-55%), decr. TG (25%), incr. HDL (5-10%). Lowers CHF events, stroke, total mortality.

AE: Myopathy and rhabdo.

INTXN: Don't give with fibrate or niacin because of myopathy (unless at 25% max dose).

Pravastatin

General: Contraindicated in pregnant or nursing women. Take @ night.

MECH: HMG-CoA reductase competitive inhibitor--rate limiting in Chol. biosynth (HMG CoA -->Mevalonate). Low LDL in hepatocyte causes incr. SREBP transcription factor for LDL-R. Incr. Chol. clearance fr. blood, decr. hep. VLDL prod. (decr. TG).

KINETICS: 1-4 hour ½ life in older statins.

USE: Decr. LDL-C (20-55%), decr. TG (25%), incr. HDL (5-10%). Lowers CHF events, stroke, total mortality.

AE: Myopathy and rhabdo.

INTXN: Don't give with fibrate or niacin because of myopathy (unless at 25% max dose).

Fluvastatin

General: Contraindicated in pregnant or nursing women. Take @ night.

MECH: HMG-CoA reductase competitive inhibitor--rate limiting in Chol. biosynth (HMG CoA -->Mevalonate). Low LDL in hepatocyte causes incr. SREBP transcription factor for LDL-R. Decr. Chol. clearance fr. blood, decr. hep. VLDL prod. (decr. TG).

KINETICS: 1-4 hour ½ life in older statins.

USE: Decr. LDL-C (20-55%), decr. TG (25%), incr. HDL (5-10%). Lowers CHF events, stroke, total mortality.

AE: Myopathy and rhabdo.

INTXN: Don't give with fibrate or niacin because of myopathy (unless at 25% max dose).

Atorvastatin (Lipitor)

General: Contraindicated in pregnant or nursing women.

MECH: HMG-CoA reductase competitive inhibitor--rate limiting in Chol. biosynth (HMG CoA -->Mevalonate). Low LDL in hepatocyte causes incr. SREBP transcription factor for LDL-R. Incr. Chol. clearance fr. blood, decr. hep. VLDL prod. (decr. TG).

KINETICS: Long ½ life, once/day.

USE: Decr. LDL-C (20-55%), decr. TG (25%), incr. HDL (5-10%). Lowers CHF events, stroke, total mortality.

AE: Myopathy and rhabdo.

INTXN: Don't give with fibrate or niacin because of myopathy (unless at 25% max dose).

Rosuvastatin (Crestor)

General: Contraindicated in pregnant or nursing women.

MECH: HMG-CoA reductase competitive inhibitor--rate limiting in Chol. biosynth (HMG CoA -->Mevalonate). Low LDL in hepatocyte causes incr. SREBP transcription factor for LDL-R. Incr. Chol. clearance fr. blood, decr. hep. VLDL prod. (decr. TG).

KINETICS: Long ½ life, once/day.

USE: Decr. LDL-C (20-55%), decr. TG (25%), incr. HDL (5-10%). Lowers CHF events, stroke, total mortality.

AE: Myopathy and rhabdo.

INTXN: Don't give with fibrate or niacin because of myopathy (unless at 25% max dose).

Ezetimibe (Zetia)

MECH: Inhibits biliary AND dietary chol. absorption in jejunum. Decr. chol. content of chylomicrons--remnants are atherogenic. 

USE: Decr. LDL-C (15-20%). Used with statins ---> 60% LDL reduction.

AE: None observed!

Advicor

Vytorin