CHAPTER 40 LECTURE 10

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CHAPTER 40LECTURE 10

• Drugs for Circulatory
• Disorders

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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

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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 its the DVT
  thats a concern ? embolism to lungs.

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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 RBCs 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

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Circulatory DisordersThrombus Formation

• Venous Formation - Usually from slow bld flow
• - Can occur rapidly Stagnation of the blood
  flow initiate the coagulation cascade? production
  of fibrin?enmeshes RBCs 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 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

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CirculatoryThrombus 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

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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

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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 doesnt 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

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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

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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

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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

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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

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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

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CIRCULATORY DISORDERSWarfarin (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.

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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

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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)
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Common Pathway
Xa (H)
Ca
PF 3
V (W)
(H) (F)
(W) Prothrombin
Thrombin
Ca
CA
Fibrinogen
Fibrin (soluble)
(H)
XIIIa
XIII
Fibrin (insoluble)
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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 TIAs
• Persantine Ticlid similar to ASA but more
  expensive
• ReoPro Aggrastat mainly for acute coronary
  syndromes. Route IV

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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

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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.

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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.

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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

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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

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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 SEs

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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

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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 lt200 triglyceride
  lt150 LDL lt 130 HDL gt 60

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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

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Circulatory DisordersPeripheral Vasodilators

• Peripheral vasodilators more effective for
  disorders resulting from vasospasm (Raynauds
  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

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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

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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. 5 mg
2.4 ml
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
40 mg
2.5 mL
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MATH
You have an order to give 250 mcg. A dosage of
0.2 mg. per 2 ml. is whats available.
Convert 0.2 mg. to mcg.
200 mcg.
10 4
250 mcg X 2 ml. 200 mcg
5 X 2 ml. 4
2.5
ml.