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PowerPoint Presentation - LECTUR

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									  CHAPTER 40
  LECTURE 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 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


•Arterial formation - begins w/ platelet adhesion to
arterial vessel wall  Adenosine diphosphate (ADP)
released from platelets  more platelet aggregation 
Bld. flow inhibited  fibrin, platelets & RBC’s surround
clot  build up of size structure  occludes bld
vessels  tissue ischemia
• The result of Arterial Thrombus is localized tissue
injury from lack of perfusion
                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 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
                 Circulatory
             Thrombus Formation
Risk Factors for Deep Vein Thrombophlebitis and
Thromboembolism
• Three factors increasing risk 1) Stasis of venous flow,
2) damage of the endothelium(inner lining of vein), and
3) hypercoagulability of the blood.
• Hx. of thrombophlebitis, abdominal & pelvic surgery, Obesity,
neoplasms (lung), CHF, Advanced age, A-fib, vasospasm, Prolonged
immobility (bed-rest, long trip spinal cord injury, FX. hip), CVA MI
PG, post partum, Estrogen TX (oral contraceptives), IV therapy,
trauma, Sepsis, Venous cannulation, Drug abuse, Cigarette smoking
Excessive vit E intake Hypercoagulable states (Polycythemia, severe
anemias, Dehydration or malnutrition), Antithrombin III deficiency
            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
          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
•Low Molecular Weight Heparins (LMWHs) -
recently introduced to prevent venous
thromboembolism
•Binds to Antithrombin III which inhibits the
synthesis of factor Xa & formation of thrombin
- enoxaparin (Lovenox) & dalteparin sodium
(Fragmin)
 - more stable dose, lower risk of bleeding, freq. lab
monitoring not required
              Circulatory Disorders
                         LMWHs
• 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 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)
• INR is replacing the PT  INR more accurate. Need higher
levels for prosthetic heart valves, cardiac valvular disease and
recurrent emboli.
• PT not consistent lab to lab or reagents used.
• PT is 1.5 – 2 times the reference value to be therapeutic
• Regular monitoring is required for the duration of drug therapy
•Warfarin is well absorbed through the G.I. tract. Food decreases.
             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
                                    The Clotting Cascade
Intrinsic Clotting Pathway                                       Extrinsic Clotting Pathway

 Blood or collagen contact                                          Tissue trauma


   XII            XIIa (H)                                          Tissue factor


             XI               XIa (H)
                                                                   (W) VII  VIIa

                     (W) IX             IXa (H)


                                CA++              PF 3


                                                  VIII (W)


 Common Pathway               (W) X               Xa (H)




                                                  (Next slide)
Common Pathway                      Xa (H)


                       Ca++                         PF 3


                                                    V (W)

                                                      (H) (F)
                  (W) Prothrombin                    Thrombin


                     Ca++

                                                                 CA++
     Fibrinogen                Fibrin (soluble)


                                              (H)
                                             XIIIa              XIII



                               Fibrin (insoluble)
    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
               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
•All 5 drugs induce fibrinolysis (fibrin breakdown)
•Side effects: hemorrhage, allergic reactions (anaphylaxis) &
vascular collapse-more with Streptokinase
•Onset and peak are immediate and rapid, duration can be 12h.
•t-PA most expensive - $2500/tx, short t1/2 (5-7 min.) not
associated with anaphylaxis.
•Aminocaproic acid (Amicar) an antithrombolytic used to stop
bleeding by inhibiting plasminogen activation. Used to stop
bleeding from heart surgery, trauma & abruptio placenta.
             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
•If therapy withdrawn, cholesterol levels return to pretreatment
levels  lifetime commitment
•Lovastatin is absorbed with food. High 1st hepatic pass -50%
•Onset and peak occurs in hours , but takes several days to have
a therapeutic effect. Duration is up to 3 weeks.
•NI Monitor blood lipid levels, liver functions, if GI upset
occurs have client take with sufficient water or with meals.
•Desired Lab Values = CHOL <200; triglyceride <150; LDL <
130; HDL > 60
            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
                          MATH
The order for medication is 12 mg. The medication you have
is labeled 5 mg per ml. How much do you give?

12mg X 1 ml.              = 2.4 ml
5 mg

You have a vial labeled 40 mg/mL. You need to give 0.1 g.
How much should you give.

Convert 0.1g to mg.    = 100mg

 100 mg X 1 mL        =     2.5 mL
 40 mg
                          MATH
You have an order to give 250 mcg. A dosage of 0.2 mg. per
2 ml. is what’s available.

Convert 0.2 mg. to mcg.    = 200 mcg.

 250 mcg X    2 ml. = 5 X 2 ml. =        10    = 2.5 ml.
 200 mcg              4                  4

								
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