Medication

Question 1

Drugs that inhibit cholesterol absorption

Answer 1

Bile Acid- Binding Resins and cholesterol absorption inhibitors

Question 2

Bile acid binding resins: MOA

Answer 2

bind to the bile acids prevention reabsorption thereby the availability of cholesterol and triglycerides in the liver; bile acids are the source of 75% of cholesterol in the intestine.

Question 3

Bile acid binding resins: Warning

Answer 3

Use cautiously in pts with hypertriglyceridemia because of the upregulation of cholesterol and triglyceride synthesis.

Question 4

Bile acid binding resins: Colesevelam

Answer 4

lowers glycated hemoglobin and fasting plasma glucose; is approved as add-on tx for glycemic ctrl in select patients with type 2 diabetes

Question 5

Cholesterol Absorption Inhibitors: MOA

Answer 5

block the intestinal absorption of cholesterol of dietary and biliary origin as well as plant sterols do (plant sterols aka phytosterols are available via plants)

Question 6

Cholesterol Absorption Inhibitors: Ezetimibe

Answer 6

Inhibits cholesterol absorption which increases expression of hepatic LDL receptors and enhances clearance of LDL from circulation; reduces LDL by 15-20%; it is indicated as adjunctive tx to diet for reduction of cholesterol, LDL, and ApoB in those with PH; is synergistic with statins can lower LDL by additional 25% than statins alone.

Question 7

Effects

Answer 7

Reduces cholesterol absorption by 50%; unlike bile acid binding resins it does not prevent absorption of triglycerides or fat-soluble vitamins.

Question 8

Vytorin

Answer 8

Is a combo drug made of ezetimibe and simvastatin

Question 9

Cholesterol Absorption Inhibitors: AE

Answer 9

URI, sinusitis, diarrhea, arthralgia; pain in an extremity

Question 10

Drug Interactions

Answer 10

Cyclosporine, cholestyramine and fibrates; use of ezetimibe with a statin is CA in pts with active liver disease or unexplained persistent elevated transaminases as well as pregnant/nursing women

Question 11

Fibrates: MOA

Answer 11

Activation of lipoprotein lipase which lowers triglycerides and VLDL; inhibition of Apo C-III synthesis in the liver, preventing the inhibitory action of Apo C-III on lipoprotein lipase activity; and stimulation of Apo A-I and Apo A-II expression which increases HDL levels

Question 12

Fibrates: Pharmacology

Answer 12

The removal of triglycerides from chylomicrons alters the size and composition of LDL from small, dense particles to large, buoyant and less atherogenic particles that have a greater affinity for LDL receptors and are rapidly cleared from the plasma

Question 13

Fibrates: Types

Answer 13

Fenofibrates, gemfibrozil, and bezafibrate

Question 14

Fibrates: Effectiveness

Answer 14

Decrease triglyceride levels by 20-50%, increase HDL 10-20% and lower LDL by 5-15%

Question 15

Fibrates: Indications for use

Answer 15

Treatment of hypertriglyceridemia and dysbetalipoproteinemia and in individuals with moderately elevated triglyceride levels (150-400), as sign often associated with metabolic syndrome. Prevention of pancreatitis in patients with severely high triglyceride levels (>1,000)

Question 16

Fibrates: Adverse Effects

Answer 16

GI: N/D, dyspepsia, and abdominal pain. Skin rash, myalgias, headache and impotence

Question 17

Fibrates: Drug Interactions

Answer 17

Myositis occurs in up to 5% of patients taking a fibrate who are also being treated with statins. when combined with statins, fenofibrate is the preferred drug because it has less risk of rhabdomyolysis compared with gemfibrozil. Fibrates potentiate the effects of oral anticoagulants as they compete for their binding sites to albumin. fibrates also increase cholesterol excretion onto the bile, leading to a risk of cholelithiasis. D/C fibrate if gallstones occur

Question 18

Statins: MOA

Answer 18

the most effective and the most prescribed class of lipid-lowerin drugs

Question 19

Statins: MOA

Answer 19

Selectively inhibit HMG CoA to mevalonate, the rate-limiting step in cholesterol synthesis in the liver. Inhibition of HMG CoA reductase leads to increased expression of the hepatic LDL receptor and increased clearance of LDL from the circulation

Question 20

Statins: Types and effectiveness

Answer 20

Rosuvastatin, atorvastatin, and simvastatin have the highest drug efficacy. Others - lovastatin, pravastatin, fluvastatin.

Question 21

Statin: effects

Answer 21

Selective inhibition of hepatic HMG-CoA reductase initiates a cascade of events that results in decreases synthesis of cholesterol; decreased liver release of VLDL; and activation of the transcription factor SREBP2, which upregulates the LDL receptor and consequently increases the clearance of plasma LDL. As 60-70% of serum cholesterol is synthesized in the liver by HMG-CoA reductase, inhibition of the enzyme drastically lowers circulating LDL

Question 22

Statins: Additional pleiotropic effects

Answer 22

Modulation of endothelial function, decrease in vascular inflammation, neuroprotection, and immunomodulation by inhibition of major histocompatibility complex II expression, which is upregulated in patients with myocarditis, MS and rheumatoid arthritis. Statins have been linked to a reduction in he risk of developing Alzheimer disease

Question 23

Statins: choice of therapy

Answer 23

initial dosaage should be based on LDL percentage reduction (table 5)

Question 24

Statins: combination therapy

Answer 24

The combination of simvastatin with ezetimibe lowers LDL by an additional 18-20%; Administration of statins with bile acid-binding resin produces 20% to 30% greater reduction

Question 25

Statins: warnings

Answer 25

Stains are well absorbed through eh GI system and are metabolized by the liver by cytochrome P450. metabolites are eliminated through the bile and excreted in the feces and, to a lesser extent, the kidneys. These drugs should not be used in patients with active liver disease and should be used cautiously at lower does in patients with kidney disease

Question 26

Statins: Adverse effects

Answer 26

Dizziness, diarrhea, N/V and abdominal cramps. Associated with hepatotoxicity and elevated transaminases in 1-2% of patients. Rarely causes liver injury. Myopathy (muscle pain, weakness and grossly elevated creatine kinases levels - > 10xs the upper limit of normal) See Table 6 for management of side effects

Question 27

Statins: Drug Interactions

Answer 27

Drugs that inhibit their metabolism and increases their bioavailability such as CYP2CP inhibitors (azole antifungals, erythromycin, protease inhibitors, amiodarone, grapefruit) and CYP2C9 inhibitors (NSAIDs, phenytoin, warfarin); as well as drugs that potentiate stat's therapeutic and AE (fibrates, niacin). These interactions increase statin toxicity

Question 28

Statins: clinical use

Answer 28

Lower LDL by 20-55%. Are also effective in the treatment of hypertriglyceridemias when levels are > 250, although fibrates remain the drug of choice for that use. When elevation of HDL is required, niacin remains the drug of choice, although combo tx may be considered in pts who also have elevated LDL

Question 29

Clinical pearls

Answer 29

Co-administration of statins and niacin, fibrates or ezetimibe increases the lipid lowering benefit but also increases risk of AR; if a fibrate is necessary it is safer to use fenofibrate

Question 30

Nicotinic Acid Derivatives: MOA

Answer 30

Niacin, aka nicotinic acid or vitamin B3, is a water-soluble vitamin. it is available in normal or extended-release formulation as well as in conjunction with lovastatin (Advicor)

Question 31

Niacin: Dosage

Answer 31

1,500-3,000 mg/day is required to gain lipid lowering effects; normal vitamin dose in 50 mg/day

Question 32

Niacin: Recommended Use

Answer 32

Specific Clinical Situations: (1) Triglycerides > 500 mg/dL, (2) a patient who is not able to achieve desired responses, or (3) is intolerant to other therapies. Not recommended by AHA/ACC guidelines

Question 33

Fish Oil Derivatives

Answer 33

Omega 3 polyunsaturated fatty acids are essential fatty acids because our bodies are unable to synthesize them

Question 34

Types of Fish Oil

Answer 34

Eicosapentaenoic (EPA), Docosahexaenoic acid (DHA) are derived from linolenic acid (ALA) and dietary supplementation is the only physiologically reelvenet source

Question 35

Sources of EPA and DHA

Answer 35

fatty fish (salmon, mackerel, sardines, trout, herring), other seafood sources, walnuts, canola, flaxseed and linseed oil

Question 36

Function of EPA and DHA

Answer 36

reduce the synthesis and secretion of VLDL and increase triglyceride removal from VLDL and chylomicrons through the upregulation of lipoprotein lipase

Question 37

Other benefits of Omega 3

Answer 37

anti-arrhythmic, antihypertensive, anti-atherogenic, and antithrombotic

Question 38

Effectiveness of Omega 3

Answer 38

primary and secondary prevention of CHD, reduce the risk of sudden cardiac mortality, and overall mortality; lower triglycerides. Can be used alone or in conjunction with medications

Question 39

Supplements

Answer 39

may also contain unwanted cholesterol or fats or toxins or oxidized fatty acids

Question 40

Prescriptions

Answer 40

900 mg of ethyl esters of Omega-3 (500mg EPA and 400 mg DHA) ; (2) 1,000 mg of omega 3 in free fatty acid form (contains 500-600 mg EPA, 150-250 mg DHA, and 150-320 of other omega 3. Dosage is 4g either once daily or 2 g BID; (3) icosapent ethyl as an adjunct for adults with triglycerides > 150, CVD and/or DM, and at least 2 other risk factors

Question 41

DHA and EPA

Answer 41

may be considered for trigykcerise levels > 1,000 and may be used alone or in conjuction with HMG-CoA

Question 42

Warnings: contamination and toxicty

Answer 42

There is a risk of mercury and other contaminants but in 2009, the FDA posted a warning regarding the ethyl ester formulations reporting anaphylactic or severe allergic rxs, and hemorrhagic diathesis

Question 43

Adverse effects

Answer 43

Minor GI: fish burps, eructation, diarrhea

Question 44

Drug Interactions

Answer 44

Anticoagulants: it has been recommended that bleeding times during 1st 3-6 months be monitored