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
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
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
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
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)
Cutaneousflushing (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