questions 4

Lipid Lowering Drugs

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Topic updated on 06/16/17 8:46am

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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Qbank (2 Questions)

TAG
(M1.CV.49) A 53-year-old man with a history of hypertension, hyperlipidemia, and obesity presents to you in clinic for a yearly physical. His current medication regimen includes a beta blocker, angiotensin converting enzyme inhibitor, and a statin. You review his recent lab work and note that despite being on a maximum statin dose, his LDL cholesterol remains elevated. You decide to prescribe another medication to improve his lipid profile. One month later, you receive a telephone call from your patient; he complains of turning bright red and feeling "scorching hot" every time he takes his medications. You decide to prescribe the which of the following medications to alleviate his symptoms: Topic Review Topic

1. Diphenhydramine
2. Aspirin
3. Coenzyme Q10
4. Hydroxyzine
5. Acetaminophen

PREFERRED RESPONSE ▶
TAG
(M1.CV.178) A 60-year-old female patient with a history of hypertension presents to an outpatient office for regular check-up and is found to have hypertriglyceridemia. Her physician prescribes high-dose niacin and recommends taking the medication along with low-dose aspirin. The side effect the physician is trying to avoid is thought to be mediated by what mechanism? Topic Review Topic

1. Bile deposition in the dermis
2. Immune complex formation
3. Release of prostaglandins
4. Mast cell degranulation
5. T cell activation

PREFERRED RESPONSE ▶
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