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43 Cards in this Set
- Front
- Back
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What are the six major risk factors for coronary artery disease?
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1) age (over 45 for men and 55 for women) and gender (male)
2) family history 3) cigarette smoking 4) hypertension 5) low HDL 6) Obesity |
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Name the three bile acid sequestrants
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1) Colestyramine
2) Colestipol 3) Colesevelam |
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Describe the mechanism of action of bile acid sequestrants
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They bind to bile acids and increase bile acid excretion and decreased cholesterol absorption; this decreases hepatic cholesterol content and causes the upregulation of LDL receptors
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What are the adverse reactions associated bile acid sequestrants?
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1) upper and lower GI side effects (bloating, gas, constipation) but LESS so with colesevelam, which is not a resin
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What are the effects of bile acid sequestrants on lipoproteins?
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1) decrease of LDL 15-30%
2) Increase of HDL 0-8% 3) INCREASE of TG 0-30% |
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Describe the drug interactions associated with bile acid sequestrants
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1) impair absorption of warfarin and digoxin
2) impair absorption of fat soluble vitamins |
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In what patients are the use of bile acid sequestrants contraindicated?
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Patients with high triglycerides (>400mg/dL)
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Describe the mechanism of action of the statins
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They are competitive inhibitors of HMG-CoA reductase and therefore decrease the liver synthesis of cholestrol, which increases the LDL receptor production and plasma LDL clearance
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Describe the reduction in LDL with various doses of statins
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The largest reduction occurs with the first dose of the drug, and each doubling can only produce between 5-7% reduction
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Are all statins equally efficacious?
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No, Rosuvastatin (Crestor) is the most efficacious
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Describe the effect of statins on the various lipoproteins
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1) LDL decreased by 25-50% (depending on med)
2) HDL increased by 5-15% 3) TG lowered by 7-30% |
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Besides their effect on lipoproteins, what other beneficial property do statins have?
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They have been shown to decrease C-reactive protein (CRP), which has been associated with increased risk of ischemic heart disease and plaque instability
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What drugs are commonly added to statin therapy?
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Bile acid sequestrants
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What drugs have been shown to slow the progression and even regression of coronary artery atherosclerosis?
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statins
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Describe adverse reactions associated with statins
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1) myopathy (myalgias, myositis, rarely rabdomyolysis)
2) elevation of liver enzymes |
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Describe drug interactions associated with statins
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Lovastatin and simvastatin are metabolized by CYP3A4, so all drugs that inhibit or induce these enzymes will affect drug levels;
Use with fibrates (gemfibrozil) and nicotinic acid may increase the risk of myopathy |
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What are the contraindications of statin use?
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Active or chronic liver disease, pregnancy, and breast feeding
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What is the mechanism of action of ezetimibe?
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It is an inhibitor of the Niemann-Pick C1-like protein, which transports sterols from the lumen of the gut into the enterocyte; this leads to decreased delivery of intestinal cholesterol to the liver and upregulation of the LDL receptor
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What drugs are often given with ezetimibe?
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Statins; co-administration of these drugs provides additional improvement over that seen with a statin alone
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For what illness is ezetimibe the only medication approved?
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Homozygous sitosterolemia (phytosterolemia)
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What are the adverse effects of ezetimibe?
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diarrhea, depression, myalgia
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What are some important precautions to note with ezetimibe?
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1) myalgia-rhabdomyolysis when given with a statin
2) elevated liver enzymes when given with a statin 3) increased plasma concentrations in geriatrics 4) not to be used in pregnant and nursing mothers 5) contraindicated in combination with statins in patients with liver disease |
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Describe the mechanism of nicotinic acid (niacin) at lowering lipids
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Niacin decreases lipolysis in adipose
It activates an inhibitory receptor (Gi) of adenylate cyclase on adipose, downregulating the pathway that leads to hormone sensitive lipase activation; this causes an overall decreased amount of free-fatty acids delivered to the liver, resulting in a decrease in TG and VLDL |
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What is the major adverse reaction of niacin and why does it occur?
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It causes flushing in the face and upper body. It may itch or tingle. A nicotinic acid receptor on Langerhans cells of the skin induces arachadonic acid pathway, leading to PGDE2 production which causes the flushing
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What are other adverse effects of niacin besides the flushing?
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Increased insulin resistance, hyperglycemia, hyperuricemia, hepatotoxicity, heartburn, headache, GI symptoms
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In what patients is niacin contraindicated?
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Active liver disease, peptic ulcer disease, gout, and diabetes
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What are the dugs of the fibric acid derivative class?
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1) fenofibrate
2) gemfibrozil 3) fenofibric acid 4) clofibrate |
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Describe the mechanism of action of the fibric acid derivatives
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They activate the nuclear transcription factor PPARalpha, which lead to modulation of lipid metabolism gene expression
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On what metabolic pathways does fenofibrate act?
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1) promotes beta oxidation in liver and muscle (reduces FFA)
2) reduces acetyl CoA carboxylase and fatty acid synthase activity (decreases FFA synthesis) 3) increases lipolysis by activating lipoprotein lipase |
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What are the effects of fenofibrate on lipoprotein particles?
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1) increases LDL clearance
2) reduces small dense LDL 3) increases binding affinity of less dense LDL for receptors 4) increases Apo AI and ApoII synthesis (increases HDL) 5) reduces cholesterol ester transport protein (increases HDL) |
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In what ways are fibrates different from statins?
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1) MORE efficacious at lowering TG and raising HDL than statins
2) LESS efficacious at lowering LDL than statins 3) adding a statin to a fibrate does not result in additional increases of HDL, but will result in additional lowering of TG |
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What are the major uses of fibrates?
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Hypertriglyceridemia, decreased HDL
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Describe the adverse interactions associated with the various fibrates
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Myalgias - especially gemfibrozil + statins
Elevated liver enzymes clofibrate - gallstones |
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Describe drug interactions of the fibrates
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Gemfibrozil and statins show an increased risk of myalgia and inhibits CYP2C8 as well as glucuronidation of statins
Increased concentration of antidiabetics Fenofibrate prolonges warfarin INR |
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What are the two omega-3 polyunsaturated fatty acids and for what are the used?
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Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) primarily lower the TG levels (40-50%) but can increase the LDL levels
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What is the effect of EPA and DHA on LDL?
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It increases the LDL but the size changes to larger, more buoyant particles that are less atherogenic
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What should be used to treat a patient with very high triglycerides levels and no cholesterol derangements?
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Omega-3 PUFAs
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What are some adverse side effects of omega-3 PUFAs?
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Worsening glycemic control in diabetics, platelet aggregation inhibition
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What is orlistat and for what is it used?
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It is an inhibitor of gastric and pancreatic lipases used as a weight loss agent
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How does orlistat work?
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It inhibits gastric and pancreatic lipases, which prohibits dietary TG absorption and ultimately lowers weight
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What are the adverse side effects of orlistat?
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Gastrointestinal events such as flatus with discharge, oily stool, ect.
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What are some drug interactions associated with orlistat?
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It decreases plasma levels of cyclosporine, and may inhibit absorption of fat soluble vitamins
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Which class of drugs is best at increasing HDL ?
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Nicotinic acid
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