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CHAPTER 31- ANTICOAGULANTS,THROMBOLYTICS and BLOOD COMPONENTS
I. Anticoagulants (drugs that retard clotting)---prevent intravascular thrombosis (clotting) by
decreasing the ability of the blood to coagulate
A. primarily prophylactic
1. prevent fibrin deposits
2. prevent extension of a thrombus
3. prevent thromboembolic complications
B. risk factors predisposing to thromboembolism
1. immobility (stroke, bedridden)
2. obesity
3. trauma/surgery of lower extremities/pelvis /hip/abdomen
4. malignancy
5. oral contraceptive use
6. artificial heart valves
7. heart disease (atrial fib, acute MI)
8. history of deep vein thrombosis (DVT) or pulmonary embolism (PE)
C. thrombus---aggregation of platelets, fibrin, clotting factors and cellular elements of the blood
that attach to a blood vessel wall (a blood clot)
D. embolus---part of a thrombis that breaks off, travels through the blood stream and lodges in a
different area of the body---very dangerous---can cause pulmonary embolism,
stroke and death
E. indications for anticoagulant therapy
1. prevent blood clotting during heart/vascular surgery
2. during hemodialysis
3. prevent blood clotting during blood transfusions
4. prevent/treat DVT / PE
5. prevent stroke (a. fib pt)
II. IV anticoagulants
A. heparin---source=bovine lung or mucosal lining of pig intestines
---rapidly acting anticoagulant
---does not dissolve existing clots, but will prevent extension of existing clots
1. mechanism of action
a. (main)---inhibition of Factor Xa and IIa (thrombin) in clotting pathway
---binds to antithrombin III (naturally occurring anti-clotting factor in plasma)
factors given on
combination of these two accelerates the anticoagulant effect of AT III
pg 618
attaches to and irreversibly inactivates thrombin, and Factors IX, Xa, XIa, XIIa
table 30-1
---by inhibiting Factor Xa---prevents conversion of prothrombin to thrombin
therefore inhibiting the formation of fibrin from fibrinogen
b. inhibits platelet function
c. also increases vascular permeability
2. administration---IV or SC (avoid IM)
3. usual dose (adults)--- SC=10,000 – 20,000 units
IV=10,000 bolus, then approx. 1000units/hr (5,000-10,000 units q 4-6 hours)
(watch strengths 100, 1000, and 10,000 units/ml also 2,500 and 25,000 units/ml)
4. lab test used to monitor therapy-APTT (also ACT)
a. test that reflects alterations in the intrinsic pathway of clotting cascade
b. reflects the time required for a fibrin clot to form after Ca++ and an activating agent
are added to a patients plasma
c. usual goal=1.5 – 2.5 times normal control level
d. take APPT 6 hours after loading dose or dose increase then daily thereafter
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5. antidote for severe heparin overdoses
a. protamine sulfate (very weak anticoagulant alone)
b. neutralizes heparin by forming an inactive protamine-heparin complex
c. dose=1mg/100 units heparin given (if within 30 minutes of overdose)
d. must administer slowly, no faster than 1mg/min to avoid resp distress and hypotension
6. side effects
a. thrombocytopenia (decreased platelets)
b. bleeding (~16% of patients have some type of bleeding)
c. watch for---epistaxis (nose bleeding), ↑ecchymosis (bruising), bright red blood in stool,
black/tarry stools, hemoptysis (coughing up blood), tingling of hands/feet, hematuria
(blood in urine), abrupt decrease in hemoglobin/hematocrit
III. Low molecular weight heparins (LMWH)---longer half-life therefore can be given QD-BID
-less or no lab monitoring needed
-slightly fewer bleeding complications
1. indications
a. approved---hip, knee or abdominal surgery (prevent DVT), some unstable MI patients
b. not FDA approved---treat DVT / PE
2. mechanism of action---inactivates Factor Xa (remember heparin affects Xa and IIa)
3. administration---SC in abdomen QD-BID
4. side effects---redness, bruising or itching at injection site, thrombocytopenia, bleeding
5. lab used to monitor---plasma anti-Xa activity (routine monitoring not usually needed)
6. treatment of overdose---protamine sulfate
7. medications---*enoxaparin (Lovenox), ardeparin (Normiflo), dalteparin (Fragmin)
IV. Oral anticoagulant drugs
A. warfarin (Coumadin)---d.o.c. for long term anticoagulant therapy
1. mechanism of action---interferes with liver synthesis of vit K dependent blood clotting
factors synthesis of Factors II, VII, IX, X is inhibited
2. indications---patient is usually switched to warfarin after 2-3 days of heparin therapy
(rapidly anticoagulated with heparin, maintained with Coumadin)
a. treatment of DVT
b. prevention of recurrent venous thromboembolism
c. prevention of thromboembolism in pts with artificial heart vales or chronic atrial fib
3. pharmacokinetic---absorbed well in GI tract, distribution-highly protein bound,
metabolized in liver, excreted by kidneys
4. side effects---alopecia, anorexia, abdominal cramps, N / V / D, hemorrhage/bleeding,
skin necrosis, purple toe syndrome (pain and purple color in toes)
5. food interaction---watch amount of vit K containing foods (brussel sprouts, broccoli,
cabbage, lettuce, spinach)
stay consistent with ingestion
↓ effectiveness
6. drug interactions---MANY!!! herbals, ASA, alcohol
7. contraindicated in pregnancy
8. dosage---10-15mg for 2-4 days , then 2-10mg daily (determined by lab PT values)
9. overdose treatment---vit K adm.---phytonadione (Mephyton-oral)( Aquamephyton-inj)
10. labs---INR (international normalized ratio)---usual goal 1.5-3.5 dependant on diagnosis
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V. Thrombolytic drugs---treat thromboembolic disorders
A. unlike anticoagulants, thrombolytic drugs dissolve clots via endogenous fibrinolytic system
B. used in treatment of acute pulmonary thromboembolism and acute DVT, acute coronary arterial
thrombosis assoc with acute MI, acute ischemic stroke
C. prototype---streptokinase (Streptase)
D. when bleeding occurs it is usually severe and difficult to control
VI. Antiplatelet therapy---used for stroke prevention
A. acetyl salicylic acid (aspirin, ASA)
1. irreversibly inhibits platelet aggregation by inhibiting cyclooxygenase
2. doses range 81-325mg QD (debatable maybe as low as 325mg once weekly)
3. side effects---gastric distress, GI bleeding (especially in elderly or prior history), bleeding
B. anagrelide (Agrylin)
C. cilostazol (Pletal)
1. inhibits cAMP levels, vasodilation, and inhibition of platelet aggregation
2. indications---intermittent claudication
3. side effects---headache, pharyngitis, D / N, peripheral edema
4. dose---100mg BID ½ hour before meals
D. clopidogrel (Plavix)
1. inhibits adenosine diphosphate
2. 50-100 times more potent than Ticlid
3. doesn’t cause neutropenia
4. can be used in place of Ticlid
5. dose---75mg QD
E. dipyridamole (Persantine) or dipyridamole + ASA (Aggrenox)
1. dose---75-100mg QID
200mg/25mg BID
2. side effects---headaches, dizziness, abdominal upset, rash
C. ticlopidine (Tic1id)
1. mechanism of action---inhibition of platelet-fibrinogen binding
2. dose---250mg BID
3. side effects---neutropenia (need lab draws)
4. alternative to ASA in patients who can’t tolerate ASA or in whom ASA has failed
VII. Hemostatic drugs---hasten clot formation to reduce bleeding
A. aminocaproic acid (Amicar)
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Chapter 32- ANTIHYPERLIPIDEMIC DRUGS
I. Overview
A. hyperlipidemia---metabolic disorder characterized by high concentrations of cholesterol
(lipids) and triglycerides
B. artherosclerosis---disorder characterized by lipid deposits in the lining of the large and
medium sized arteries, which produces degenerative changes to the artery and
block blood flow
1. end results--a. HTN
b. coronary heart disease which may result in angina, heart failure, myocardial infarction
stroke (CVA), peripheral arterial occlusive disease (gangrene, and
amputations), renal insufficiency
-CHD affects 12.2 million Americans
-1.1 million Americans have an MI every year---40% will die
-by decreasing lipid levels development and/or progression of artherosclerosis
C. lipoproteins---lipid compounds bound to plasma proteins (albumin, globulin) which act as carriers
1. types of lipoproteins---classified mostly according to densities
a. chylomicrons---transport cholesterol and fatty acids from the diet and GI tract to the liver
-largest and least dense
85-95% triglycerides
3-5% cholesterol
b. very low density lipoproteins (VLDL)---eventually converted to LDL
-30-65% triglycerides
20-30% cholesterol
c. low density lipoproteins (LDL)---contain the major portion of cholesterol in the blood
-60-70% of total blood cholesterol
-most harmful lipoprotein (bad cholesterol)
-↑LDL levels suggest ↑ risk for developing atherosclerosis
d. high density lipoproteins (HDL)---smallest and most dense
-function=to pick up cholesterol from peripheral cells and carry them to the liver for
metabolism and excretion (gets rid of cholesterol)
“good cholesterol”
-prevents the accumulation of lipids in arteries
-the higher the HDL levels, the lower the risk for developing cardiovascular disease
D. cholesterol levels determined by---heredity, age, dietary intake, physical activity
1. secondary causes of increased cholesterol levels---poorly controlled diabetes,
hypothyroidism, kidney or liver disease, alcoholism
E. recommendations and guidelines
1. serum total cholesterol should be measured in all adults >20 years of age every 5 years, if
level is elavated do lipoprotein analysis (total chol., LDL, HDL, triglycerides)
HDL chol + triglycerides
LDL chol.= total cholesterol - (
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)
(must have trigly level < 400 for this calculation to be valid)
2. guidelines for cholesterol levels—pg 653 table 32-4
3. risk factors for CHD---diabetes
- smoking
-HTN (lack of treatment)
-family history of premature CHD
-men >45 yrs women >55 yrs
-postmenopausal women without hormone replacement (HRT reduces risk by 50%)
-low HDL (<35mg/dl), if HDL>60mg/dl can subtract a risk factor)
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4. setting cholesterol patient specific goals
Risk Category
-less than 2 risk factors and no coronary heart disease
-2 or more risk factors and no coronary heart disease
-coronary heart disease (prior heart attack, angioplasty
or bypass surgery)
or diabetes
Goal for LDL chol.
<160
<130
<100
F. medications causing adverse effects on lipid profiles---beta blockers, corticosteroids,
diuretics (mostly thiazides), oral contraceptives
II. Non-pharmacologic management of hyperlipidemia (lifestyle modifications)
A. smoking cessation
B. corticosteroids
C. weight loss
D. dietary therapy
1. step I---no more than 30% total calories from fat
---cholesterol intake <300mg/day,
---saturated fat up to 10% of total calories
2. step II---cholesterol intake <200mg/day
---saturated fat <7% of total calories
III. Pharmacologic management
A. bile acid sequestrants (anion exchange resins)---used for mild-moderate ↑chol or in conjunction
1. cholesterol is a major precursor to bile acids, which are secreted from the gall bladder and liver
into the small intestine---anion exchange resins bind bile acids in the intestine,
preventing their absorption and are eliminated in the feces
a. to compensate the liver increases conversion of cholesterol to bile acids therefore
decreasing serum cholesterol
b. may cause an increase in triglycerides
c. not absorbed in the body therefore okay for pregnant women and children
2. administration---powders
a. sprinkle powder on the surface of 2 ounces of non-carbonated liquid, allow to sit for 2
min. then stir---to prevent lumpiness add another 2-4 ounces of liquid then stir again
(it does not dissolve)
drink immediately
3. side effects---decreased by gradually increasing the dose, most GI related N/V, heartburn,
abdominal pain, belching, bloating, constipation
4. drug interactions
a. interferes with the absorption of other medications if administered at the same time therefore
admin other meds 1hour before or 4-6 hours after
-meds to watch---warfarin, thiazide diuretics, propranolol, tetracycline, penicillin, thyroid,
digoxin
b. interferes with absorption of fat soluble vitamins (ADEK)therefore possible decrease of vit K
absorption→hypoprothrombinemia→excessive bleeding
-patients should report and S/S of bleeding (bruising, nose or gum bleeding, tarry stools)
to health care provider
5. medications---cholestyramine (Questran)
colestipol (Colestid)
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B. nicotinic acid derivatives
1. effects on lipids---↓LDL-20%, ↓VLDL, ↑HDL-15%, ↓triglycerides 30-40%
2. side effects---diarrhea, pruritis, hepatotoxicity (especially in sustained release forms &
>2000mg/day), headache, hyperglycemia, hyperuricemia (avoid in gout pt)
aggravation of peptic ulcer disease, flushing of face and neck due to vasodilation
(mediated by prostaglandins)
-flushing may be reduced by taking 325mg ASA 30 min before niacin,
-also avoid taking with hot liquids
-take at end of meals (reduces GI upset)
3. medications---niacin (Niaspan ER, Nicobid)
C. fibric acid derivatives
1. effects on lipids---↓VLDL, ↓LDL, ↑HDL, ↓↓triglycerides (up to 50%)
2. d.o.c. in hypertriglyceridemia
3. side effects---skin rash, abdominal/stomach pain, N /V /D, muscle pain/cramps, increased risk of
gallstones, potentiate effect of anticoagulant, itching
4. medications---gemfibrozil (Lopid), fenofibrate (Tricor)
D. HMG-CoA reductase inhibitors (statins)
1. competitively inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase)
the enzyme that catalyzes cholesterol biosynthesis
2. most effective drug to lower LDL levels
3. reduce the incidence of CHD by 25-60% and reduce the risk of death by 30%
4. reduce the risk for angina, CVA and decreases the need for coronary artery bypass
5. actions on lipids---↑HDL, ↓VLDL, ↓trig, ↓↓LDL
6. side effects (uncommon)---GI upset, hepatitis (need liver function test every 3-6 months)
muscle aches, risk of rhabdomyolysis (muscle necrosis that can lead to acute renal
failure) and myopathy (increased when used with fibric acid derivatives, niacin,
erythromycin, antifungals)
7. contraindicated in pregnancy
8. rate of endogenous cholesterol synthesis is higher at night, therefore theoretically statins work best
if given in the evening
9. medications---atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor),
pravastatin (Pravachol), simvastatin (Zocor)
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