-
Hyperlipidemia
- -Elevated blood levels of lipoproteins ( cholesterol, triglycerides, phospholipids)
- -Lipoprotein abnormalities: greater than or less than 1 of the following: Elevated total cholesterol (TC),Elevated low-density lipoprotein (LDL) bad ones, Elevated triglycerides (TG) should not be elevated, Reduced high-density lipoprotein (HDL) you want high, greater than 68
- -National guidline- The National Education Program (NCEP) Adult Treatment Panel III (ATP III)
-
Hyperlipidemia
- -CHD risk directly correlates with TC & LDL levels in continuous fashion
- - > 50% of American adults: TC greater or less than 200 mg/dL
- -Lipid lowering therapy reduces risk of cardiovascular/cerebrovascular even related death
- -LDL level are significant predictor of morbidity/mortality
-
Coronary Heart Disease
-The risk of CHD in patients with cholesterol levels of 300mg/dL is three to four time greater than that in patients with levels less than 200mg/dL
-
Background & Pathophysiology
- -Cholesterol: essential for cell membrane formation & hormone synthesis
- -Lipids not present in free form in plasma; circulate as lipoproteins
-
Triglycerides & Cholesterol
- -Two primary forms of lipids in the blood
- -Water-insoluble fats that must be bound to apolipoproteins, specialized lipid-carrying proteins
- -Lipoproteins is the combination of triglyceride or cholesterol with apolipoprotein
- -3 major plasma lipoproteins
-
Lipoproteins
-Very-low-density lipoprotein (VLDL) <-BAD - Carries ~10 to 15% of total serum cholesterol; carried in circulation as TG; VLDL= TG/5, produced by the liver, Transports endogenous lipids to the cells
-Low-density lipoprotein (HDL) GOOD - Carries 20 to 30% of total serum cholesterol; reverse transportation of cholesterol, responsible for "recycling" of cholesterol, also known as "good cholesterol
-
Lipoprotein Classification
-
Background & Pathphysiology
- -VLDL secreted from the liver - converted to IDL then LDL
- -Plasma LDL taken up by receptors on liver, adrenal, & peripheral cells
- -LDL internalized & degraded by these cells
- -Increased intracellular cholesterol level inhibits HMG-CoA reductase & decreases LDL receptor synthesis
- -Decreases in LDL receptors: plasma LDL not as readily taken up & broken down by cells
- -LDL also excreted in bile
-
-
Background & Pathophysiology
- -Oxidized LDL in artery walls provokes inflammatory response
- -Monocytes recruited & transformed into macrophages- results in cholesterol laden foam cell accumulation
- -Foam cells: beginning of arterial fatty streak
- -If processes continue: angina, stroke,MI,peripheral artery disease, arrhythmias, death
-
LIPID GOALS
-LDL- < 100 optimal, 100-129 near optimal, 130-159 borderline high, 160-189 high, greater than or less than 190 very high
-Triglycerides- < 150 normal, 150-199 borderline high, 200-499 high, greater or less than 500 very high
-HDL - MEN greater or less than 40, women greater or less than 50
-Total cholesterol- <200 desirable, 200-239 borderline high, greater than or less than 240 high
-
RISK FACTORS
- -Men: 45 yrs
- -Women: 55 yrs or premature menopause without estrogen replacement therapy
- -Family history of premature CHD (definite myocardial infarction or sudden death before age 55 yrs in father or other male first-degree relative, or before age 65 yrs in mother or other female first degree relative)
- -Ciggarette smoking
- -Hypertension (140/90 mm hg or taking antihypertensive medication)
- -Low HDL cholesterol ( <40 mg/dL) b
-
Goals and Cutpoints
-
-
-
Risk- Category
| LDL- Goal (mg/
dL) | Initiate TLC (LDL:- mg/dL)
| Consider- Drug Therapy (LDL: mg/dL)
| High- risk: CHD or CHD risk equivalents (10-year risk >20%)
| <100-
(optional- goal: <70)
| 100 | 100 (<100- mg/dL;
consider- drug options)
| Moderately- high risk: 2+ risk factors (10-year risk >10%–20%)
| <130 | 130 | 130 (100–129:- consider drug options)
| Moderate- risk: 2+ risk factors (10-year risk <10%)
| <130 | 130 | 160 | Lower- risk: 0–1 risk factor
| <160 | 160 | 190 (160–189:- LDL-lowering drug optional)
|
-
Antilipemics
- -HMG-CoA reuctase inhibitors (HMGs, or statins)
- -Bile acid sequestrants
- -Niacin ( nocotinic acid)
- -Fibric acid derivatives
-
Antilipemics: HMG-CoA Reductase Inhibitors (HMGs, or statins)
Most potent LDL reducers
- -rosuvastatin (Crestor)
- -atorvastatin (Lipitor)
- -simvastatin (Zocor)
- -lovastatin (Mevacor)
- -pravastatin (Pravachol)
- -fluvastatin (Lescol)
-
Statins (cont'd)
Mechanism of action
- -Inhibit HMG-CoA reductase, which is used by the liver to produce cholesterol
- -Lower the rate of cholesterol production
-
Statins: Indications
-First-line drug therapy for hypercholesterolemia - Reduce LDL levels by 18% to 55%, Increase HDL levels by 5% to 15%, Reduce triglycerides by 7% to 30%
-
Statins: side effects
-Mild, transient GI disturbances, rash, headache, myopathy (muscle pain), Elevations in liver enzymes or liver disease*, Rhabdomyolysis*- muscle breaks down
-
Bile Acid Sequestrants
- -Also caled bile acid-binding resins and ion-exchange resins
- -cholestyramine (Questran)
- -colestipol hydrochloride (Colestid)
-
Bile Acid Sequestrants: Mechanisms of action
- -Prevent resorption of bile acids from small intestine
- -Bile acids are necessary for absorption of cholesterol
-
Bile Acid Sequestrants: Indications
- -Hypercholesterolemia
- -Relief of pruritus associated with partial biliary obstruction (cholestyramine)
-
Bile Acid Sequestrants: Side effects
- -Constipation
- -Heartburn, nausea, belching, bloating- These adverse effects tend to dissapear over time
-
Niacin ( Nicotinic Acid)
- -Vitamin B3
- -Lipid lowering properties require much higher doses than when used as a vitamin
- -Effective, inexpensive, often used in combination with other lipid-lowering agents.
-
Niacin: Mechanism of action
- -Thought to increase activity of lipase, which breaks down lipids.
- -Reduces the metabolism or catabolism of cholesterol and triglycerides
-
Niacin: Indications
- -Effective in loweing triglyceride, total serum cholesterol, and LDL levels
- -Increases HDL levels
-
Niacin:Side effects
- -Flushing
- -Pruritus
- -GI distress
- -Hyperuricemia (gout)
- -Hepatotoxicity
-
Fibric Acid Derivatives
- -clofibrate
- -gemfibrozil (Lopid)
- -fenofibrate (Tricor)
- *used if triglycerides are high
-
Fibric Acid Derivatives: Mechanism of action
- -Believed to work by activiting lipase, which breaks down cholesterol- lower release of free fatty acid from adipose tissue, inhibit synthesis of triglycerides in the liver, higher the secretion of cholesterol in the bile
- -DRUG EFFECTS
- -Decrease the triglyceride levels
- -Increase HDL by as much as 25%
-
Fibric Acid Derivatives: Side Effects
- -Abdominal discomfort
- -Diarrhea
- -Nausea
- -Blurred vision
- - Increased risk of gallstones
- -Pronlonged prothrombin time
- -Liver studies may show increased function
-
Omega 3 fatty acids
- -Diests rich in omega 3 fatty acids from oily fish decrease TC, TG, increase HDL & decrease CV events
- -RX fish oil: Lovaza- lowers TG 14-30%, raises HDL ~10%
- -FDA approved as dietary adjunct for very high TG levels (>500mg/dL)
- -Thrombocytopenia, bleeding disorders: potential complication of high doses
-
Omega 3 fatty acids
- -Greater than or less than 3 grams PO daily generally recognized as safe
- -Until further research is done on nutraceuticals it is recommended that patients get dietary EPA & DHA- eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)
- -2 to 4 g of EPA & DHA may be used for very high TG
- -Adverse effects: GI disturbances, fishy aftertaste, increased bleeding risk, worsening glycemic control, increased LDL, abnormal LFTs
-
Drug
|
Mechanism
of Action
|
Effects
on Lipids
|
Effects
on Lipoproteins
|
Comment
|
Cholestyramine,
colestipol, colesevelam
|
↑ LDL
catabolism
↓ Cholesterol
absorption
|
↓Cholesterol
|
↓ LDL
↓ VLDL
|
Problem
with compliance; binds many coadministered acidic drugs
|
Niacin
|
↓ LDL
and VLDL synthesis
|
↓ Triglyceride
↓Cholesterol
|
↓ VLDL
↓ LDL
↑ HDL
|
Problems
with patient acceptance; good in combination with bile acid resins; ER niacin
causes less flushing and is less hepatotoxic than SR form
|
Gemfibrozil,
fenofibrate, clofibrate
|
↑ VLDL
clearance
↓ VLDL
synthesis
|
↓ Triglyceride
↓Cholesterol
|
↓ VLDL
↓ LDL
↑ HDL
|
Clofibrate
causes cholesterol gallstones; modest LDL lowering; raises HDL; gemfibrozil
inhibits glucuronidation
of simvastatin, lovastatin, atorvastatin
|
Lovastatin,
pravastatin, simvastatin, fluvastatin, atorvastatin, rosuvastatin
|
↑ LDL
catabolism; inhibit LDL synthesis
|
↓Cholesterol
|
↓ LDL
|
Highly
effective in heterozygous familial hypercholesterolemia and in
combination with other agents
|
Ezetimibe
|
Blocks
cholesterol absorption across the intestinal border
|
↓Cholesterol
|
↓ LDL
|
Few
adverse effects; effects additive to other drugs; ENHANCE trial – no change
in carotid intima media thickness
(CIMT) compared to simvastatin monotherapy
in patients with familial hypercholesterolemia
|
Omega
3 Fatty Acids
|
inhibit
VLDL and triglyceride synthesis in the liver
|
↓ Triglyceride
|
↑ LDL
↑ HDL
|
May
be administered orally with or without food. Administration with food may
decrease stomach upset
|
-
Class
|
Effect
|
Side
Effects
|
CI
|
Statins
|
LDL
↓18-55%
HDL↑
5-15%
TG ↓ 7-30%
|
Myopathy
↑
LFTs
|
Active/chronic
liver
dx
|
Bile
acid
sequestrant
|
LDL
↓15-30%
HDL↑
3-5%
TG ßà
|
GI
distress
Constipation
↓Absorption
|
TG > 400
|
Nicotinic
acid
|
LDL
↓5-25%
HDL↑15-35%
TG ↓20-50
|
Flushing
↑
BG
Gout
Hepatotoxicity
|
Chronic
liver dx
Severe
gout
|
Fibric
acid
|
LDL
↓5-20%
HDL↑10-20%
TG ↓20-50%
|
Dyspepsia
Gallstones
Myopathy
|
Severe
renal dx
Severe
hepatic dx
|
Omega
3 Fatty Acids
|
LDL
↑10-44.5%
HDL↑ 9%
TG ↓25-50%
|
↑
LDL
Fishy
Taste
Abnormal
LFTs
↑
Bleed risks
|
Fish hypersensitivity
|
-
Nursing Implications
- -Before beginning therapy, obtain a thorough health and medication history
- -Assess dietary patterns, exercise level, weight, height, VS, tobacco and alcohol use, family history
- -Asses for contraindications, conditions that require caustious use, and drug interactions
- -Contraindications include biliary obstruction, liver dysfunction, active liver disease
- -Obtain baseline liver function studies
- -Patients on long term therapy with sequestrants may need fat-soluble vitamins (A,D,E,K)
- -Take with meals to decrease GI upset
- -Patient must be counseled concerning diet and nutrition on an ongoing basis
- -Instruct on proper procedure for taking medications
- -Powder forms must be taken with a liquid, mixed thoroughly but not stirred, and NEVER taken dry
- -Other medications should be taken 1 hr before or 4 to 6 hrs after meals to avoid interference with absorption
- -Clofibrate often causes constipation; instruct patients to increase fiber and fluid intake to offset effect
- -Instruct patients to report persistant GI upset, constipation, abnormal or unusual bleeding, and yellow discoloration of the skin
- -Monitor for side effects, including increased lives enzyme studies
- -Monitor for therapeutic effects- Reduced cholesterol and trglyceride levels
- -To minimize side effects of niacin, start on low initial dose and gradually increase it, and take with meals
- -Small doses of aspirin or NSAIDs may be taken 30 mins before niacin to minimize cutaneous flushing
- -Inform patients that these agents may take several weeks to show effectiveness
|
|
