Lipid Lowering Agents PDF

LIPID LOWERING AGENTS ✓ Drugs lower serum levels of cholesterol and various lipids. ✓ These include bile acid sequestrants, HMG-CoA reductase inhibitors, and a cholesterol absorption inhibitor.  BILE ACID SEQUESTRANTS ✓ Used to decrease plasma cholesterol levels. ✓ Three bile acid...

LIPID LOWERING AGENTS ✓ Drugs lower serum levels of cholesterol and various lipids. ✓ These include bile acid sequestrants, HMG-CoA reductase inhibitors, and a cholesterol absorption inhibitor.  BILE ACID SEQUESTRANTS ✓ Used to decrease plasma cholesterol levels. ✓ Three bile acid sequestrants currently in use are Cholestyramine (Questran), Colestipol (Colestid), and Colesevelam (WelChol).  THERAPEUTIC ACTIONS ✓ Binds with bile acids in the intestine to form an insoluble complex that is then excreted in the feces. ✓ Bile acids contain high levels of cholesterol. ✓ As a result, the liver must use cholesterol to make more bile acids. ✓ The hepatic intracellular cholesterol level falls, leading to an increased absorption of cholesterol containing LDL segments from circulation to replenish the cell’s cholesterol. ✓ The serum levels of cholesterol and LDL decrease as the circulating cholesterol is used to provide the cholesterol that the liver needs to make bile acids. ✓ These drugs are used to reduce serum cholesterol in patients with primary hypercholesterolemia (manifested by high cholesterol and high LDLs) as an adjunct to diet and exercise. ✓ Cholestyramine is also used to treat pruritus associated with partial biliary obstruction.  PHARMACOKINETICS ✓ Bile acid sequestrants are not absorbed systemically. ✓ They act while in the intestine and are excreted directly in the feces. ✓ Their action is limited to their effects while they are present in the intestine. ✓ Cholestyramine is a powder that must be mixed with liquids and taken up to six times a day. ✓ Colestipol is available in both powder and tablet form and is taken only four times a day. ✓ Colesevelam is available in tablet form and is taken once or twice a day.  CONTRAINDICATIONS ✓ Complete biliary obstruction, abnormal intestinal function, and pregnancy or lactation because the potential decrease in the absorption of fat and fat-soluble vitamins could have a detrimental effect on the fetus or neonate.  ADVERSE EFFECTS ✓ Headache, anxiety, fatigue, and drowsiness, which could be related to changes in serum cholesterol levels. ✓ Nausea, constipation that may progress to fecal impaction, and aggravation of hemorrhoids. ✓ Increased bleeding times related to a decreased absorption of vitamin K and consequent decreased production of clotting factors. ✓ Vitamin A and D deficiencies related to decreased absorption of fat-soluble vitamins; rash; and muscle aches and pains. DRUG- DRUG INTERACTIONS ✓ Malabsorption of fat-soluble vitamins occurs when they are combined with these drugs. ✓ These drugs decrease or delay the absorption of thiazide diuretics, digoxin, warfarin, thyroid hormones, and corticosteroids. ✓ Any of these drugs should be taken 1 hour before or 4 to 6 hours after the bile acid sequestrant. HMG-CoA REDUCTASE INHIBITORS ✓ Atorvastatin (Lipitor) ✓ Fluvastatin (Lescol ✓ Lovastatin (Mevacor) ✓ Pitavastatin (LIvalo) ✓ Pravastatin (Pravachol) ✓ Rosuvastatin (Crestor) ✓ Simvastatin (Zocor)  THERAPEUTIC ACTIONS ✓ The early rate-limiting step in the synthesis of cellular cholesterol involves the enzyme HMG-CoA reductase. ✓ If this enzyme is blocked, serum cholesterol and LDL levels decrease because more LDLs are absorbed by the cells for processing into cholesterol. ✓ This medications block HMG-CoA reductase from completing the synthesis of cholesterol. ✓ They are chemical modifications of compounds produced by fungi. ✓ Indicated as adjuncts with diet and exercise for the treatment of increased cholesterol and LDL levels that are unresponsive to dietary restrictions alone. ✓ Pravastatin, lovastatin and simvastatin are indicated for patients with documented CAD to slow progression of the disease. ✓ These three agents and atorvastatin are used to prevent a first myocardial infarction (MI) in patients who have multiple risk factors for developing CAD.  PHARMACOKINETICS ✓ The peak effect of these drugs is usually seen within 2 to 4 weeks. ✓ These drugs are most effective when taken at night when the liver is processing the most lipids.  CONTRAINDICATIONS ✓ Statins also are contraindicated in patients with active liver disease or a history of alcoholic liver disease. ✓ Labeled as pregnancy category X. ✓Atorvastatin levels are not affected by renal disease, but patients with renal impairment who are taking other statins require close monitoring.  ADVERSE EFFECTS ✓ Flatulence, abdominal pain, cramps, nausea, vomiting, and constipation, headache, dizziness, blurred vision, insomnia, fatigue, and cataract development and may reflect changes in the cell membrane and synthesis of cholesterol. ✓ Rosuvastatin is associated with rhabdomyolysis, a breakdown of muscles. DRUG- DRUG INTERACTIONS ✓ Rhabdomyolysis increases if combined with erythromycin, cyclosporine, gemfibrozil, niacin, or antifungal drugs. ✓ Increased serum levels and toxicity can occur if taken with digoxin or warfarin. ✓ Monitor serum digoxin levels and/or clotting times. ✓ Increased estrogen levels if taken with oral contraceptives. ✓ Serum levels and the risk of toxicity increase if these drugs are combined with grapefruit juice. CHOLESTEROL ABSORPTION INHIBITORS ✓ Ezetimibe works in the brush border of the small intestine to decrease the absorption of dietary cholesterol from the small intestine. ✓ Less dietary cholesterol is delivered to the liver, and the liver increases the clearance of cholesterol from the serum to make up for the drop in dietary cholesterol, causing the total serum cholesterol level to drop.  PHARMACOKINETICS ✓ Ezetimibe is absorbed well after oral administration, reaching peak levels in 4 to 6 hours. ✓ It is metabolized in the liver and the small intestine, with a half-life of 22 hours.  CONTRAINDICATIONS ✓ If it is used in combination with a statin, it should not be used during pregnancy or lactation or with severe liver disease because of the known effects of statins, including possible liver problems and renal failure.  ADVERSE EFFECTS ✓ Mild abdominal pain and diarrhea, headache, dizziness, fatigue, upper respiratory tract infection (URI), back pain, and muscle aches and pains.  DRUG- DRUG INTERACTIONS ✓ Elevated serum levels increases if it is given with cholestyramine, fenofibrate, gemfibrozil, or antacids. ✓ It should be taken at least 2 hours before or 4 hours after the other drugs. ✓ Toxicity increases if combined with cyclosporine; if combined with fibrate, the risk of cholethiasis increases. ✓ Warfarin levels increase in a patient who is also taking ezetimibe.  FIBRATES ✓ Stimulate the breakdown of lipoproteins from the tissues and their removal from the plasma. ✓ They lead to a decrease in lipoprotein and triglyceride synthesis and secretion. ✓ Peak effects are usually seen within 4 weeks, and the patient’s serum lipid levels should be reevaluated at that time. ✓ Fenofibrate (TriCor) inhibits triglyceride synthesis in the liver, resulting in reduction of LDL levels; increases uric acid secretion; and may stimulate triglyceride breakdown. ✓ It is used for adults with very high triglyceride levels who are not responsive to strict dietary measures and who are at risk for pancreatitis. ✓ Gemfibrozil (Lopid) inhibits peripheral breakdown of lipids, reduces production of triglycerides and LDLs, and increases HDL concentrations. ✓ Associated with GI and muscle discomfort. ✓ Not be combined with statins due to an increased risk of rhabdomyolysis. ✓ Fenofibric acid (Trilipix), a peroxisome proliferator receptor alpha activator. ✓ Increases breakdown of lipids, elimination of triglyceride-rich particles from the plasma, and reduction in the production of an enzyme that naturally inhibits lipid breakdown. ✓ Patients complaining of gallstone-type pain should be screened carefully. ✓ Caution must be used with warfarin anticoagulants; increased bleeding can occur. ✓ Vitamin B3, known as niacin (Niaspan) or nicotinic acid, inhibits the release of free fatty acids from adipose tissue, increases the rate of triglyceride removal from plasma, and generally reduces LDL and triglyceride levels and increases HDL levels. ✓ It may also decrease the levels of apoproteins needed to form chylomicrons. ✓ Associated with intense cutaneous flushing, nausea and abdominal pain. ✓ Increases serum levels of uric acid and may predispose patients to the development of gout. ✓ It is given at bedtime to make maximum use of night time cholesterol synthesis, and it must be given 4 to 6 hours after the bile sequestrant to ensure absorption. ✓Rimonabant is an endocannabinoid blocker that has been used as a weight loss agent. ✓ It reduces weight and abdominal adiposity and improve lipid profiles while increasing insulin sensitivity and reducing the pro inflammatory and prothrombotic markers. ✓ Research is being done on the effects of blocking the endocannabinoid system, resulting in weight loss, improved lipid profi les, and decreased proinfl ammatory and prothrombotic states. ✓ Questions have not been answered about the safety or effectiveness of drugs that block this system.