CHAPTER 40
LECTURE 10
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Drugs for Circulatory
Disorders
Circulatory Disorders
Drugs used are to maintain, preserve or restore circulation
Anticoagulants & antiplatelets (antithrombotics), thrombolytics, antilipemics,
peripheral vasodilatiors
Anticoagulants - prevent formation of clots that inhibit circulation
Antiplatelets - prevent platelet aggregation
Thrombolytics (clot busters) - attack/dissolve formed clots
Antilipemics - decrease bld. lipid concentration
Peripheral vasodilators - promote dilation of vessels narrowed by vasospasm
Circulatory Disorders
Thrombus Formation
Clot is a Thrombus formed in an arterial or venous vessel
thrombophlebitis - Both inflammation and clots are present
Some thrombus can be superficial but it’s the DVT that’s a concern  embolism to
lungs.
Circulatory Disorders
Thrombus Formation
• Venous Formation - Usually from slow bld flow
- Can occur rapidly Stagnation of the blood flow initiate the coagulation cascade
production of fibrinenmeshes RBC’s & platelets to form the thrombus. Venous
thrombus has a long tail that can break off to produce an embolus. These travel to
faraway sites then lodge  in lung (capillary level)  inadequate O2 & CO2
exchange occur (ie. pulmonary embolism & cerebral embolism)
• Oral & parenteral anticoagulants (Heparin/Warfarin) primarily act by preventing
venous thrombosis
• Antiplatelet drugs primarily act by preventing arterial thrombosis
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Circulatory Disorders
Thrombus Formation
Hemostasis is the normal homeostatic process of blood clotting.
Clotting proteins normally circulate in an inactive state & must be activated to form a
fibrin clot. When there is a trigger - inc. bld viscosity from bed rest & stasis - the
clotting cascade is activated.
Bld vessel injured  platelets adhering to site of injury  release of ADP a platelet
plug - is ex. of Intrinsic clotting path.
Tissue injury (outside bld vessels) = extrinsic pathway activated
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Circulatory
Thrombus Formation
Circulatory Disorders
Anticoagulants
Inhibit clot formation - Do NOT dissolve clots already formed, but prophylactically
prevent new clots
Used in clients w/ venous/arterial disorders that put them at inc. risk of clot formation
Venous = DVT & Pulmonary embolism
Arterial = Coronary thrombosis (MI), artificial heart valves, CVA
Circulatory Disorders
Heparin
A natural substance in the liver that prevents clot formation.
Primary use is to prevent venous thrombosis that can lead to pulmonary embolism
(PE) or stroke
Combines w/ antithrombin III  inactivates thrombin and other clotting factors then
the conversion of fibrinogen to fibrin doesn’t occur so the clot is prevented
Poorly absorbed through GI mucosa - given SQ & IV
Prolongs clotting time - partial thromboplastin time (PTT) & activated partial
thromboplastin time (aPTT) - both bld tests are monitored during therapy
Circulatory Disorders
Heparin
• Use - DVT, PE, & CVA, Rx of clients w/ heart valve prosthesis, during CV surgery,
post op, during hemodialysis
* Low doses = prophylactically to prevent DVT
* Full doses = treats a thromboembolism & promotes neutralization of activated clotting
factors = prevents extension of thrombi & formation of emboli
* If started shortly after formation of a thrombus - heparin will also prevent it from
developing into an insoluble stable thrombus = reduced tissue damage
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Circulatory Disorders
Heparin
SE - Decreased platelet count = thrombocytopenia
Hemorrhage - give protamine sulfate IV (an anticoagulant antagonist)
DI - Inc. effects w/ ASA, NSAIDs, thrombolytics
Dec. effect w/ NTG
Circulatory - LMWH
Circulatory Disorders
LMWHs
• Use - Prevention of DVT after hip & knee replacement surgery & abd. surgery
• Can be administered at home
• Administered SQ BID
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Available in prefilled syringes w/ attached needles
Usually given in the abdomen
Average Rx is 7 to 14 days
Bleeding less likely to occur
DI - caution client not to take antiplatelet drugs (ASA) during therapy
Circulatory Disorders
Warfarin (Coumadin)
• Action - Inhibits activity of vit. K required for the activation of clotting factors II, VII,
IX, & X. Blocking these factors prevents clot formation
• Use - prophylactically to prevent venous thrombosis, A. fib., PE, coronary occlusion,
thrombophlebitis
• Prolongs clotting time & is monitored by the lab bld. tests prothrombin time (PT) &
International normalized ratio (INR) - usually before administering the next dose until
therapeutic levels are reached. INR is 1.3 - 2.0 therapeutic levels on coumadin = 2.0 3.0
CIRCULATORY DISORDERS
Warfarin (Coumadin)
• Has a long t1/2 & duration of action - drug accumulation poss. and can cause internal
bldg.
- Observe for: petechiae, ecchymosis, tarry stools, hematemesis. Monitor menstrual
flow
- Teach client importance of bld tests & to look out for signs of bleeding
• DI - LOTS!!! consult a physician before taking any over the counter medications
• Vit. K (phytonadione) = antagonist of Warfarin. Used for OD/ uncontrolled bleeding
Circulatory Disorders
Antiplatelet Drugs
Aspirin, Dipyridamole (Persantine), Ticlopidine (Ticlid)
abciximab (ReoPro), tirofiban (Aggrastat)
• Action: To prevent thrombosis in the arteries by suppressing platelet aggregation via
diff. methods
• Use: Prevention of MI/stroke for clients w/ family hx
- prevention of a repeat MI, stroke in clients having TIA’s
• Persantine & Ticlid = similar to ASA but more expensive
• ReoPro & Aggrastat = mainly for acute coronary syndromes. Route = IV
Circulatory Disorders
Thormbolytics
• Thromboembolism - Occlusion of an artery or vein caused by a thrombus or embolus results in ischemia that causes necrosis of the tissue distal to the obstructed area.
- it takes about 1 to 2 weeks for the blood clot to disintegrate by natural fibrinolytic
mechanisms
- if new thrombus dissolved quicker damage minimized & bld flow restored faster 
purpose of therapy
• Thrombolytics promote fibrinolytic mechanism (convert plasminogen to plasmin &
destroys the fibrin in the clot) - administering a thrombolytic drug = clot disintegrates
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Circulatory Disorders
Thrombolytics
Use = Acute MI - w/ in 4 hrs to dissolve clot & unblock artery, so decrease necrosis to
myocardium & hospital stay is decreased.
Other uses: Pulmonary embolism, DVT, Noncoronary arterial occlusion
Streptokinase, Urokinase, Tissue plasminogen activator (t-PA), anisoylated
plasminogen streptokinase activator complex (APSAC)
Streptokinase & Urokinase are enzymes that act to convert plasminogen to plasmin
t-PA and APSAC activate plasminogen by acting specifically on clot.
Circulatory - Thrombolytics
Circulatory Disorders
Antilipemics
• Used to Lower bld. lipid levels
• Cholesterol, triglycerides & phospholipids transported in the body bound to protein in
various amounts - chylomicrons, very low-density lipoproteins (VLDL), low-density
lipoproteins (LDL), high-density lipoproteins (HDL) - more protein & less lipid
(removes chol. from bld. stream & deliver it to the liver)
• VLDL & LDL contribute to atheroslerotic plaque in bld vessels - composed of mainly
cholesterol & triglycerides
Circulatory Disorders
Antilipemics
• Nonpharmacologic = before drugs to dec. BP
- Reduce saturated fats & chol intake in the diet
- Exercise
- Body wt. reduction
- Eliminate smoking
• If drug therapy needs to be initiated, clients still need to make lifestyle changes
• Compliance an issue
Circulatory Disorders
Antilipemics
• Cholestyramine (Questran) - Powder form, Colestipol (Colestid) - a newer resin both lower chol.
• Clofibrate (Atromid-S), gemfibrozil (Lopid) - fibric acid derivatives effective in
reducing triglyceride & VLDL levels.
- Highly protein bound. do not take w/ anticoagulants - compete
- Clofibrate - many side effects - dysrhythmias, angina
• Nicotinic acid or niacin (vit B2) - reduces VLDL & LDL - effective in dec. chol
levels, Many SE’s
Circulatory Disorders
Antilipemics
• Statin drugs inhibit enzyme HMG CoA reductase in chol biosynthesis ( HMG CoA
reductase inhibitors) = Dec. the concentration of chol & dec. LDL & sl. inc. in HDL
• atorvastatin calcium (Lipitor), cerivastatin (Baycol), fluvastatin (Lescol),
lovastatin (Mevacor) - SE = GI disturbances, headaches, muscle cramps & tiredness (all complaints early in
tx.)
- monitor serum liver enzymes
- Annual Eye exams d/t poss cataract formation
- Useful in coronary artery disease (CAD) &
mortality rate
Circulatory - Antilipemics
Circulatory Disorders
Peripheral Vasodilators
• Peripheral Vasodilators - Increase bld flow to extremities
• Peripheral vascular disease is a problem in the elderly
- Numbness & coolness of extremities, intermittent claudication (pain/weakness of limb
when walking - symptoms absent at rest), poss. leg ulcers
- Primary cause is hyperlipemia from atherosclerosis & arteriosclerosis - arteries
become occluded
Circulatory Disorders
Peripheral Vasodilators
• Peripheral vasodilators more effective for disorders resulting from vasospasm
(Raynaud’s disease) than from vessel occlusion or arteriosclerosis
• Vasodilators have diff. actions but all promote vasodilation
• Isoxsuprine (Vasodilan) - Beta-2 adrenergic agonist - causes vasodilation on arteries
w/in skeletal muscles, bronchodilation may also occur
- SE = lightheadedness, dizziness, orthostatic hypotension, tachycardia, GI distress
Circulatory Disorders
Peripheral Vasodilators
• Pentoxifylline (Trental) - an antihemorrheologic agent - improves microcirculation &
tissue perfusion
inc. in tissue O2. Not a vasodilator, but dilates rigid
arteriosclerotic bld vessels - arterioles, capillaries & venules
- Use = clients w/ intermittent claudication
- Take w/ food
- Avoid smoking d/t nicotine increases vasoconstriction