CHAPTER 40LECTURE 10

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 DisordersThrombus 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

Circulatory DisordersThrombus 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

CirculatoryThrombus Formation

Circulatory DisordersAnticoagulants

•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 DisordersHeparin

•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 DisordersHeparin

•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

Circulatory DisordersHeparin

•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 DisordersLMWHs

•Use - Prevention of DVT after hip & knee replacement surgery & abd. surgery

•Can be administered at home

•Administered SQ BID

•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 DisordersWarfarin (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 DISORDERSWarfarin (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 DisordersAntiplatelet 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 DisordersThormbolytics

•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

Circulatory DisordersThrombolytics

•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 DisordersAntilipemics

•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 DisordersAntilipemics

•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 DisordersAntilipemics

•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 DisordersAntilipemics

•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 DisordersPeripheral 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 DisordersPeripheral 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 DisordersPeripheral 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