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Cards (31)

  • Primary prevention
    Statin treatment: Offer atorvastatin 20 mg for the primary prevention of cardiovascular disease to people who have a 10% or greater 10-year risk of developing cardiovascular disease
  • Primary prevention for people 85 years or older

    Consider atorvastatin 20 mg as statins may be of benefit in reducing the risk of non-fatal myocardial infarction
  • Dyslipidaemia
    Primary: combination of dietary and genetic factors, familial hypercholesterolaemia (FH) high risk of CHD
    Secondary: consequence of other conditions, e.g. diabetes mellitus, alcoholism, renal disease
  • Non-Pharmacological treatment of Dyslipidaemia
    • Cardioprotective diet
    • Weight loss
    • Physical activity
    • Reduce alcohol consumption
    • Smoking cessation
  • Pharmacological treatment of Dyslipidaemia
    • Anti-hyperlipidaemic drugs
  • Lipid Lowering Drugs
    • HMG-CoA reductase inhibitors
    • Fibrates
    • Cholesterol absorption inhibitors
    Ezetimibe
    Bile-acid binding resins
    Omega Fatty Acids
    Nicotinic acid
  • Statins: HMG CoA Reductase Inhibitors
    Simvastatin, Pravastatin, Lovastatin, Atorvastatin, Rosuvastatin, Fluvastatin
  • Statins: HMG CoA Reductase Inhibitors
    • Short-acting, Oral, night, Well absorbed, Liver Cytochrome P450 metabolism - not rosuvastatin, CYP3A4 - site of drug interactions, glucuronidation, Simvastatin and lovastatin given in inactive form
  • Statins: HMG CoA Reductase Inhibitors

    Blocks HMG CoA Reductase enzyme: rate limiting step in cholesterol synthesis, blocks convertion HMG CoA to mevalonic acid
    Short acting, Specific, reversible inhibitors: simvastatin, lovastatin
    Longer lasting inhibitors: atrovastatin
    Blocks Cholesterol synthesis: upregulates LDL receptor synthesis, increases LDL clearance by liver
  • Clinical use of Statins: HMG CoA Reductase Inhibitors
    Primary Hyperlipidaemia (e.g. FH): Reduce LDL by 30%, Raise HDL by 20%
    Secondary Hypercholesterolemia: DM, Secondary prevention of MI & stroke
  • Adverse Effects of Statins: HMG CoA Reductase Inhibitors
    Well tolerated but may have muscle pain, GI disturbance, insomnia, rash, Rarely myositis and angio-oedema
  • Scandinavian Simvastatin Survival Study (4S's) - reduced relative risk, Serum LDL reduced by 35%, Death reduced by 30%, Death by CHD reduced by 42%
  • Effects of Statins: HMG CoA Reductase Inhibitors
    • Endothelial function improves, Improved vascularisation of ischaemic tissue, Atherosclerotic plaque stabilisation, Reduces vascular inflammatory response, Reduced platelet activation, Enhanced fibrinolysis, Antithrombotic
  • Fibrates
    Gemfibrozil, Fenofibrate, Bezafibrate
  • Mechanism of Action of Fibrates

    Agonist at peroxisome proliferator-activated receptor (PPAR-alpha) nuclear receptor that regulates lipid metabolism, Increase synthesis of lipoprotein lipase by adipose tissue, Stimulates fatty acid oxidation in the liver, Increases expression of apoA-I and apoA5, Increases hepatic LDL uptake
  • Effects of Fibrates

    Marked reduction circulating VLDL and TG, Modest reduction in LDL (10%), Increase LDL uptake by liver
  • Clinical use of Fibrates
    Hypertriglyceridemia, Mixed hyperlipidaemia (raised TG plus cholesterol), TG levels reduced by 20-30%, cholesterol reduced by 10-15% associated rise in HDL
  • Pharmacokinetics of Fibrates
    • Well-absorbed from the gastrointestinal tract, High degree of binding to albumin, Metabolised by the cytochrome P450 (CYP3A4) - potential drug interactions, Primarily excreted via the kidneys
  • Adverse effects of Fibrates

    Rash, GI disturbance common, Rhabdomyolysis (unusual) causing renal failure, Clofibrate may cause gall stones
  • Cholesterol Absorption Inhibitors: Ezetimibe

    Mechanism of Action: Inhibits intestinal absorption of cholesterol by interfering with Neimann-Pick C1-Like 1 (NPC1L1) transport protein, Decreases LDL and VLDL
  • Pharmacokinetics of Ezetimibe
    • Administered orally, Absorbed into intestinal epithelial cells (site of action), Extensively metabolized (>80%) into active metabolite, Enterohepatic recycling slows elimination, t1/2 ~ 22 hours
  • Clinical use of Ezetimibe
    Treatment of hyperlipidaemia in combination with statins
  • Adverse Effects of Ezetimibe

    Mild: Diarrhoea, abdominal pain, headache, Rash and angioedema, Secreted into breast milk, contraindicated in breastfeeding
  • Cholesterol Absorption Inhibitors: Colestipol, Cholestyramine

    Mechanism of Action: Binds bile acid (BA) in gut, prevents reabsorption, diverting hepatic cholesterol to BA synthesis, upregulates LDL receptors increasing LDL removal from the blood
  • Pharmacokinetics of Colestipol, Cholestyramine
    Administered by mouth (stays in the GIT)
  • Clinical use of Colestipol, Cholestyramine
    Primary hypercholesterolemia when statin is contraindicated, Pruritus associated with biliary obstruction, Bile acid diarrhoea
  • Adverse effects of Colestipol, Cholestyramine
    Constipation, bloating, Malabsorption of vitamin K, folic acid, ascorbic acid, Disrupts absorption of digitalis, thiazides, warfarin, iron
  • Mechanism of Action of Nicotinic Acid (Niacin)

    Liver: Reduces VLDL synthesis, Reduces VLDL and LDL
    Adipose tissue: Reduces hormone-sensitive lipase activity, Reduces TG
    Reduces catabolic rate for HDL: increases HDL
    Increase clearance of VLDL by activating lipoprotein lipase
  • Pharmacokinetics of Nicotinic Acid (Niacin)
    Readily absorbed in GIT following oral administration, Metabolised in the liver, Excreted via kidneys
  • Clinical use of Nicotinic Acid (Niacin)

    Hypercholesterolemia, Hypertriglyceridemia with low levels of HDL
  • Adverse effects of Nicotinic Acid (Niacin)
    Cutaneous flushing (common), Associated with pruritus & palpitation, Reduced with pre-treatment of aspirin or other NSAIDs, Dose-dependent nausea and abdominal discomfort, Moderate elevation of liver enzymes to severe hepatotoxicity, Hyperuricemia in 20% of the patient