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Introduction
  •  lipid loweringTypes of lipid-lowering drugs:
    • HMG-CoA reductase inhibitors
    • bile acid resins (sequestrants)
    • fibrates
    • selective cholesterol-absorption inhibitor (ezetimibe)
HMG-CoA Reductase Inhibitors
  • Examples
    • "statins" - lovastatin, fluvastatin, pravastatin, simvastatin, rosuvastatin, and atorvastatin
  • Mechanism
    • inhibition of cholesterol synthesis
      • HMG-CoA reductase is the rate-limiting step of cholesterol synthesis 
      • causes ↑ in LDL-receptor synthesis
    Change in LDL
    Change in HDL
    Change in triglycerides
    ↓↓↓
  • Toxicity
    • myalgia/myopathy (monitor serum CK)
    • rhabdomyolysis
    • teratogenic
    • hepatotoxic (↑ LFTs)
    • inhibitors of P450 can ↑ serum concentration
Bile Acid Sequestrants
  • Examples
    • cholestyramine, colestipol, and colesevelam
      • remember: act in the colon (col)
  • Mechanism 
    • bind bile acids in the intestine to prevent reabsorption and recycling
      • forces liver to consume cholesterol in the process of making more bile salts
      • causes ↑ in LDL-receptor synthesis
      • contraindicated in patients with hypertriglycerademia
    Change in LDL
    Change in HDL
    Change in triglycerides
    ↓↓
    slightly ↑
    slightly 
  • Toxicity
    • GI disturbances
    • ↓ absorption of fat soluble vitamins and drugs
Niacin
  • Mechanism
    • ↓ lipolysis in adipose tissue
    • ↓ hepatic VLDL synthesis/secretion into circulation
    Change in LDL
    Change in HDL
    Change in triglycerides
    ↓↓
    ↑↑
  • Toxicity
    • flushed face
      • Thought to be caused by prostaglandin and histamine release 
      • ↓ by aspirin 
      • tolerance develops over long-term use
    • hyperglycemia
    • acanthosis nigricans
    • hyperuricemia
      • worsens gout
    • pruritis
Fibrates
  • Examples
    • gemfibrozil and fenofibrate
  • Mechanism
    • activate lipoprotein lipase via activation of PPAR-α
      • results in ↑ TG clearance
    Change in LDL
    Change in HDL
    Change in triglycerides
     ↓
    ↓↓↓
  • Toxicity 
    • myopathy
      • ↑ risk when combined with statins
    • gallstones
      • 7-alpha hydroxylase inhibition increases cholesterol content in the bile
    • can ↑ LDL so not often used as monotherapy
Ezetimibe
  • Mechanism
    • blocks cholesterol reabsorption at small intestine brush border via inhibiting NPC1L1 in the gut lumen.
    Change in LDL
    Change in HDL
    Change in triglycerides
    ↓↓
    -
    -
  • Toxicity
    • hepatotoxic
      • ↑ risk when combined with statins
 

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