DYSLIPIDEMIA PHARMACOLOGY NURS 203 General Pharmacology Danita - - PowerPoint PPT Presentation
University of Hawaii Hilo Pre - Nursing Program DYSLIPIDEMIA PHARMACOLOGY NURS 203 General Pharmacology Danita Narciso Pharm D 1 LEARNING OBJECTIVES Know normal cholesterol levels Understand what the role of LDL, HDL, and TGs
University of Hawai‘i Hilo Pre- Nursing Program NURS 203 – General Pharmacology Danita Narciso Pharm D
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Know normal cholesterol levels Understand what the role of LDL, HDL, and TGs are in the body
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Cholesterol: A waxy fat-like substance that is found in all cells of the body
Important in the synthesis of many endogenous substances. Normal serum total cholesterol <200 mg/dL The Good HDL & The Triglycerides The Bad LDL
the liver to prepare it for excretion from the body
the cells of the body
a build up in arteries
mg/dL
used immediately, stored in fat cells
mg/dL
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There are no symptoms of high cholesterol
Lipid panel should be part of a regular check-up Elevated lipid panel increases risk of coronary heart disease (CHD)
Cardiovascular Disease Risk Factors
men, >65 for women)
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Chylomicron
transport cholesterol from the diet/GI tract to the liver
lipoprotein lipase VLDL
formed in the liver from endogenous cholesterol
lipoprotein lipase and hepatic lipase remove
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LDL
cholesterol
lingering LDL HDL
periphery to liver where it is metabolized and excreted
apolipoproteins, help with binding to appropriate targets
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Cholesterol
TOO MUCH CHOLESTEROL
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wall of the artery
(including LDL)
cholesterol molecules
site for immunologic cells to “clean up”
cholesterol molecules
begin to grow and turn to plaque
lumen of the vessel
around the outside of the plaque (stable vs unstable)
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31.7% US adults has high LDL What is considered high LDL? 1 in 3 of those adults actually has the condition under control. Less than half are receiving treatment. TOO MUCH CHOLESTEROL TOO MUCH CHOLESTEROL
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Reduce the amount of dietary cholesterol Increase the clearance of cholesterol from the body
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Reduce cholesterol absorption
1. Low fat/calorie diet and exercise 2. Low fat/calorie diet and exercise WITH drugs that reduce lipoprotein synthesis 3. Low fat/calorie diet and exercise WITH drugs that inhibit cholesterol absorption
Increase cholesterol clearance
1. Exercise 2. Low fat/calorie diet and exercise WITH lipoprotein lipase support 3. Low fat/calorie diet and exercise WITH cholesterol receptor support
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Effects on . Class LDL – C HDL – C TG Common ADRs HMG – CoA reductase inhibitors (statins) ↓18% - 55% ↑5% - 15% ↓7% - 30% Myopathy Increased LFTs Niacin/nicotinic acid ↓2% - 25% ↑15% - 35% ↓20% - 50% Flushing, hyperglycemia, hyperuricemia/gout, upper GI upset, hepatotoxicity Fibric acids ↓15% - 30% ↑10% - 20% ↓20% - 50% Dyspepsia, gallstones, myopathy, unexplained non- CHD deaths in WHO study Bile acid sequestrants (resins) ↓15% - 30% ↑3% - 5% No change Gastrointestinal distress, constipation, decreased absorption of other drugs Azetidinones (usually as adjuncts, limited data as monotherapy) ↓16% - 20% ↑1% - 4% ↓5% - 6% Gastrointestinal distress, headache, joint pain Please see page 639 of your text for full reference.
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MOA
inhibitor
in the liver Base hits!!!
Other Effects
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Uses: Indicated for hypercholesterolemia – works on each type of cholesterol, greatest on LDL Statin selection: All work equally well. Have varying potencies. Statin selection
Insurance coverage Cost Adverse effect profile
Dosing: Taken orally prior to bed Heavy first pass metabolism LAS – Lovastatin, atorvastatin, simvastatin (CYP 3A4) GPACMAN/PSPORCS Fluvastatin and rosuvastatin (CYP2C9) Amiodarone & verapamil increase the risk for myopathy
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Adverse Drug Reactions: Teratogenic (pregnant, lactating, or might become pregnant – no statin), not to be used in children under 16, liver toxicity (0.5%), rhabdomyolysis
RHABDO
kinase Monitoring
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Works great on triglycerides. Reduces VLDL which carries mostly TG ↓20% - 50% Works pretty good on HDL. Best medication we have for increasing HDL ↑15% - 35%
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Uses: Hypertriglyceridemia, mixed hyperlipidemia, familial hypercholesterolemia Dosing: Start low and go slow. Titrate. The titration schedule is different if niacin is being combined with other lipid lowering agents:
In combo with a BAR – 500 mg once orally at bedtime, increase in 500 mg intervals every four week, mas of 2000 mg /day 250 mg immediate release daily, titrate every 4-7 days until at 1.5 -2 g daily in divided doses, if not adequate cholesterol lowering titrate every 2-4 weeks to 3 g daily in divided doses Extended release niacin is not to be substituted with equal doses of immediate release niacin WHY WHY WHY??????
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Flushing Increased secretion of gastric acid
CI in peptic ulcer
Reduced glucose tolerance
CI in insulin resistance
Hepatotoxicity Hyperuricemia
Lipid panel LFTs Blood glucose Prothrombin time Signs and symptoms of jaundice Muscle pain
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Gemfibrozil & fenofibrate Uses: Hypertriglyceridemia MOA: Targets the PPAR alpha receptor located on the liver, kidney, heart, skeletal muscle, and adipose tissue. Binding of this receptor leads to an increase in LPL – leads to an increase in fat breakdown. PPAR alpha also activates proteins that take up those cholesterol fragments and package them for disposal or enable them to be used by other cells ADRs: Increased LDL, weight gain, gallstones, myositis CI: Lovastatin & simvastatin co-administration Pregnancy & lactation: Used with extreme caution in pregnancy and not recommended for lactation Monitor: Lipid panel, LFTs, and CBC
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Colestipol, cholestryramine, colesevelam (naming scheme – begin with col or chol) Use: Primarily used to reduce LDL cholesterol MOA: Bind to bile acids in the intestine to prevent reabsorption. Liver uses cholesterol to make more bile acids and upregulates cholesterol receptors to collect more cholesterol from the blood for this process. ADRs: Constipation, bloating, dry skin, abdominal cramping Drug interactions: Decrease the absorption of fat soluble vitamins, folic acid, iron, digoxin, thiazide diuretics, warfarin, thyroxine, etc…. Pregnancy safe – not absorbed Monitor: Lipid panel, drug levels if administered with medication that can have absorption altered
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Ezetimibe Uses: Works well as an adjunct medication to statin therapy. Not used as monotherapy. MOA: Selective inhibitor of intestinal cholesterol reabsorption and reduced re- absorption of cholesterol secreted in the bile ADRs: Increased incidence of rhabdo (by itself for with statins), headache, GI upset Monitor: Lipid panel, CK??
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