Medication Flashcards
Drugs that inhibit cholesterol absorption
Bile Acid- Binding Resins and cholesterol absorption inhibitors
Bile acid binding resins: MOA
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.
Bile acid binding resins: Warning
Use cautiously in pts with hypertriglyceridemia because of the upregulation of cholesterol and triglyceride synthesis.
Bile acid binding resins: Colesevelam
lowers glycated hemoglobin and fasting plasma glucose; is approved as add-on tx for glycemic ctrl in select patients with type 2 diabetes
Cholesterol Absorption Inhibitors: MOA
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)
Cholesterol Absorption Inhibitors: Ezetimibe
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.
Effects
Reduces cholesterol absorption by 50%; unlike bile acid binding resins it does not prevent absorption of triglycerides or fat-soluble vitamins.
Vytorin
Is a combo drug made of ezetimibe and simvastatin
Cholesterol Absorption Inhibitors: AE
URI, sinusitis, diarrhea, arthralgia; pain in an extremity
Drug Interactions
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
Fibrates: MOA
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
Fibrates: Pharmacology
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
Fibrates: Types
Fenofibrates, gemfibrozil, and bezafibrate
Fibrates: Effectiveness
Decrease triglyceride levels by 20-50%, increase HDL 10-20% and lower LDL by 5-15%
Fibrates: Indications for use
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)
Fibrates: Adverse Effects
GI: N/D, dyspepsia, and abdominal pain. Skin rash, myalgias, headache and impotence
Fibrates: Drug Interactions
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
Statins: MOA
the most effective and the most prescribed class of lipid-lowerin drugs
Statins: MOA
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
Statins: Types and effectiveness
Rosuvastatin, atorvastatin, and simvastatin have the highest drug efficacy. Others - lovastatin, pravastatin, fluvastatin.
Statin: effects
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
Statins: Additional pleiotropic effects
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
Statins: choice of therapy
initial dosaage should be based on LDL percentage reduction (table 5)
Statins: combination therapy
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
Statins: warnings
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
Statins: Adverse effects
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
Statins: Drug Interactions
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
Statins: clinical use
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
Clinical pearls
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
Nicotinic Acid Derivatives: MOA
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)
Niacin: Dosage
1,500-3,000 mg/day is required to gain lipid lowering effects; normal vitamin dose in 50 mg/day
Niacin: Recommended Use
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
Fish Oil Derivatives
Omega 3 polyunsaturated fatty acids are essential fatty acids because our bodies are unable to synthesize them
Types of Fish Oil
Eicosapentaenoic (EPA), Docosahexaenoic acid (DHA) are derived from linolenic acid (ALA) and dietary supplementation is the only physiologically reelvenet source
Sources of EPA and DHA
fatty fish (salmon, mackerel, sardines, trout, herring), other seafood sources, walnuts, canola, flaxseed and linseed oil
Function of EPA and DHA
reduce the synthesis and secretion of VLDL and increase triglyceride removal from VLDL and chylomicrons through the upregulation of lipoprotein lipase
Other benefits of Omega 3
anti-arrhythmic, antihypertensive, anti-atherogenic, and antithrombotic
Effectiveness of Omega 3
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
Supplements
may also contain unwanted cholesterol or fats or toxins or oxidized fatty acids
Prescriptions
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
DHA and EPA
may be considered for trigykcerise levels > 1,000 and may be used alone or in conjuction with HMG-CoA
Warnings: contamination and toxicty
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
Adverse effects
Minor GI: fish burps, eructation, diarrhea
Drug Interactions
Anticoagulants: it has been recommended that bleeding times during 1st 3-6 months be monitored
