Antihyperlipidemics Flashcards
HMG-CoA Reductase Inhibitors
Fluvastatin (weakest), Pravastatin (safest)
- not metab by liver P450, Lovastatin, Simvastatin
Atorvastatin, Rosuvastatin (most potent)
Fluvastatin, Pravastatin, Lovastatin, Simvastatin
Atorvastatin, Rosuvastatin
- HMG-CoA Reductase Inhibitors
- Mechanism: ↓cholesterol synthesis → activates SREBP2 signaling cascade→ ↑production of LDL receptors @liver → ↑clearance of LDL from plasma → ↓LDL
- no reduction in Lp(a)
- all except pravastatin metabolized by liver P450
- ↓LDL 18-55%; ↑HDL 5-15%; ↓TG 7-30%
- AE: Generally well tolerated so are the primary method for LDL-C reduction!
- Rare: myopathy and/or rhabdomyolysis (combine with niacin used for high cholesterol and triglycerides)
- Hepatotoxicity: altered liver function shown by ↑ plasma levels of ALT and AST
- contraindicated: liver disease; certain drugs → ie Cyclosporine/Erythromycin ie P450 inhibitors)
Bile Acid Sequestrants
CHOLESTYRAMINE, Cholestipol, Colesevelam
CHOLESTYRAMINE
-Bile Acid Sequestrant
-Mechanism: cationic resins that bind bile acids in intestine → ↓reabsorption → ↓bile acids in liver → ↑production of bile acids from cholesterol → ↑demand for cholesterol → ↑hepatic LDL receptors → ↑clearance of LDL from plasma
- no reduction in Lp(a)
- not well absorbed → frequent dosing (problematic)
-↓LDL 15-30%; ↑ HDL 3-5%; may increase TG (↑5-30%) or no change
-AE: Not well tolerated GI
- constipation, bloating, abdominal pain, dyspepsia
- prevents absorption of fat soluble vitamins & drugs
Contraindications: patients with hypertriglyceridemia or in combination with agents that reduce TG
-take before a meal – since they bind other lipid-soluble compounds, patients taking thiazides, warfarin, thyroxine or digitoxin should not take these meds 1-4 hours before taking BAS’s
-interfere with vitamin K; increases risk of excessive bleeding in patients on warfarin
Cholestipol
-Bile Acid Sequestrant
-Mechanism: cationic resins that bind bile acids in intestine → ↓reabsorption → ↓bile acids in liver → ↑production of bile acids from cholesterol → ↑demand for cholesterol → ↑hepatic LDL receptors → ↑clearance of LDL from plasma
- no reduction in Lp(a)
- not well absorbed → frequent dosing (problematic)
-↓LDL 15-30%; ↑ HDL 3-5%; may increase TG (↑5-30%) or no change
-AE: Not well tolerated GI
- constipation, bloating, abdominal pain, dyspepsia
- prevents absorption of fat soluble vitamins & drugs
Contraindications: patients with hypertriglyceridemia or in combination with agents that reduce TG
-take before a meal – since they bind other lipid-soluble compounds, patients taking thiazides, warfarin, thyroxine or digitoxin should not take these meds 1-4 hours before taking BAS’s
-interfere with vitamin K; increases risk of excessive bleeding in patients on warfarin
Colesevelam
-Bile Acid Sequestrant
-Mechanism: cationic resins that bind bile acids in intestine → ↓reabsorption → ↓bile acids in liver → ↑production of bile acids from cholesterol → ↑demand for cholesterol → ↑hepatic LDL receptors → ↑clearance of LDL from plasma
- no reduction in Lp(a)
- not well absorbed → frequent dosing (problematic)
-↓LDL 15-30%; ↑ HDL 3-5%; may increase TG (↑5-30%) or no change
-AE: Not well tolerated GI
- constipation, bloating, abdominal pain, dyspepsia
- prevents absorption of fat soluble vitamins & drugs
Contraindications: patients with hypertriglyceridemia or in combination with agents that reduce TG
-take before a meal – since they bind other lipid-soluble compounds, patients taking thiazides, warfarin, thyroxine or digitoxin should not take these meds 1-4 hours before taking BAS’s
-interfere with vitamin K; increases risk of excessive bleeding in patients on warfarin
Cholesterol Transport Inhibitor
Ezetimibe
Ezetimibe
- Cholesterol Transport Inhibitor
- Mechanism: ↓absorption of cholesterol by the small intestine which ↓delivery of chol to the liver and ↓LDL
- works well w/ statins; effects are additive
- ↓ LDL 20%; ↑ HDL1%; ↓ TG 10%
- AE: Well tolerated, minimal AE
- GI discomfort
Nicotinic Acid
Niacin (vit B3)
Extended-Release Niacin
- better for ↓LDL/TG
Niacin
-Nicotinic Acid
-↓adipose hormone-sensitive lipase activity, so less substrate for hepatic syn of lipoprotein lipids
- ↑HDL (↓HDL removal)
- ↓TG/VLDL production (↓ffa mobilization) → ↓LDL
- ↓LP(a)
- Titrate from low to high dose
- used frequently w/ statins (to ↑HDL)
-↓ LDL 5-25%; ↑ HDL 15-35%; ↓ TG 20-50%
-AE: -cutaneous flushing and itchying (use w/ aspirin)
-↑risk of hepatotoxicity, hyperuricemia, impaired insulin sensitivity and potentiation of statin-induce myopathy
Contraindications: absolute: chronic liver disease, severe gout. Relative: diabetes, hyperuricemia, peptic ulcer disease
Fibric Acids Derivatives
Gemfibrozil, Fenofibrate
Gemfibrozil
-Fibric Acids Derivative + PPAR-alpha→ fibrates active PPFAR-alpha (a nuclear receptor that dimerizes with the retinoid X receptor) to activate transcription of genes. Net effect ↓TG and ↑HDL
↑LP lipase activity → ↑VLDL catabolism
- may ↓platelet reactivity, aggregation, ↓[fibrinogen]
- may ↑LDL (VLDL → LDL), esp. @diabetes
-↓ LDL 5-20% (may ↑patients with ↑TG); ↑ HDL 10-20%; ↓ TG 20-50%
-AE: dyspepsia, gallstones, myopathy, GI issues
-often used with statins so potentiates statins’ effects
-can lead to hepatotoxicity (Fenofibrate) and increased free warfarin levels (and resulting increased anticoagulation activity)
-contraindications: renal failure, liver disease
Fenofibrate
-Fibric Acids Derivative + PPAR-alpha→ fibrates active PPFAR-alpha (a nuclear receptor that dimerizes with the retinoid X receptor) to activate transcription of genes. Net effect ↓TG and ↑HDL
↑LP lipase activity → ↑VLDL catabolism
- may ↓platelet reactivity, aggregation, ↓[fibrinogen]
- may ↑LDL (VLDL → LDL), esp. @diabetes
-↓ LDL 15-30% (but may increase) ; ↑ HDL ↑0-40%; ↓ TG 40-60%
-AE: dyspepsia, gallstones, myopathy, GI issues
-often used with statins so potentiates statins’ effects
-can lead to hepatotoxicity (Fenofibrate) and increased free warfarin levels (and resulting increased anticoagulation activity)
-contraindications: renal failure, liver disease
Omega-3 Fatty Acids
Lovaza
Lovaza
-Omega-3 Fatty Acid
eg eicosapentoic acid, docsahexanoic acid): ↓TG @[high] w/o ↑LDL
-mechanism probably involves regulation of TF’s like PPFARalpha and SREBP-1c to reduce TG synthesis and increase FA oxidation
