PHARMACOLOGY

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PHARMACOLOGY

• Hematologic drugs

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OBJECTIVES

• Identify the classes of drugs used to treat
  hematologic disorders.
• Identify the uses and varying actions of these
  drugs.
• Identify how these drugs are absorbed,
  distributed, metabolized, and excreted.
• Identify drug interactions and adverse reactions
  to these drugs.

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DRUGS AND THE HEMATOLOGIC SYSTEM

• The hematologic system includes plasma, red blood
  cells, white blood cells, and platelets.
• The types of drugs used to treat hematologic
  disorders include
• Hematinic drugs
• Anticoagulant drugs
• Thrombolytic drugs

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HEMATINIC DRUGS

• Provide essential building blocks for RBC
  production by increasing hemoglobin that is
  necessary for oxygen transportation.
• The following drugs are used to treat microcytic
  and macrocytic anemia iron, vitamin B12, and
  folic acid.
• Epoetin alfa is used to treat normocytic anemia.

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IRON

• Used to treat iron-deficiency anemia which is the
  most common form of anemia.
• Iron preparations include ferrous fumarate,
  ferrous gluconate, ferrous sulfate, and iron
  dextran.

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IRON

• Pharmacokinetics
• Absorbed in the small intestine.
• The amount of iron absorbed depends partially on
  the body stores of iron.
• Enteric-coated preparations decrease absorption.
• Lymph system absorbs IM injections.

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IRON

• Transported by blood and bound to transferrin
  stored in liver, spleen, and bone marrow
  two-thirds is contained in hemoglobin.
• Excreted in urine, stool, sweat, and intestinal
  cell sloughing secreted in breast milk.

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IRON

• Pharmacodynamics
• Most important role is the production of
  hemoglobin.
• Pharmacotherapeutics
• Used to prevent or treat iron deficiency anemia.
• Given to children 6 months to 2 years old and
  pregnant women.

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IRON

• Treatment lasts 6 months.
• Drug interactions
• Absorption is reduced by antacids, coffee, tea,
  milk, and eggs.
• Adverse reactions
• Most common is gastric irritation.
• Also darkens stool.

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VITAMIN B12

• Used to treat pernicious anemia.
• Common B12 preparations include
• Cyanocobalamin
• Hydroxocobalamin

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VITAMIN B12

• Pharmacokinetics
• Administered orally or parenterally.
• When a person has a deficiency of intrinsic
  factor, which is secreted by the gastric mucosa
  and is needed for vitamin B12 absorption, vitamin
  B12 deficiency pernicious anemia develops.
• These people require vitamin B12 injections.

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VITAMIN B12

• Stored in the liver excreted in the urine.
• Pharmacodynamics
• Essential for cell growth and replication and for
  the maintenance of myelin throughout the nervous
  system.

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VITAMIN B12

• Pharmacotherapeutics
• Used to treat pernicious anemia, which is a
  megaloblastic anemia characterized by decreased
  gastric production of hydrochloric acid and the
  deficiency of the intrinsic factor (normally
  secreted by the parietal cells of the gastric
  mucosa and is essential for vitamin B12
  absorption).

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VITAMIN B12

• Drug interactions
• Alcohol may decrease the absorption of oral
  cyanocobalamin.
• Adverse reactions
• No dose-related adverse reactions.

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FOLIC ACID

• Given to treat folic acid deficiency.
• Preparations include folic acid and leucovorin
  calcium.
• Pharmacokinetics
• Absorbed rapidly in the intestine distributed to
  all body tissues metabolized in the liver
  excreted in the urine and stool secreted in
  breast milk.

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FOLIC ACID

• Pharmacodynamics
• An essential component for normal RBC production
  and growth.
• A deficiency results in pernicious anemia and low
  serum and RBC folate levels.

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FOLIC ACID

• Pharmacotherapeutics
• Used to treat folic acid deficiency.
• Patients requiring preventive folic acid therapy
  include pregnant women and patients undergoing
  treatment for liver disease, hemolytic anemia,
  alcohol abuse, skin disease, or renal failure.

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FOLIC ACID

• Drug interactions
• In large doses may counteract the effects of
  anticonvulsants potentially leading to seizures.
• Adverse reactions
• Erythema, itching, and rash.

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EPOETIN ALFA

• Stimulates RBC production.
• Pharmacokinetics
• Administered SC or IV distribution, metabolism,
  and excretion are still unknown.

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EPOETIN ALFA

• Pharmacodynamics
• Boosts the production of erythropoietin, which
  stimulates RBC production in the bone marrow
  (normally produced in the kidneys in response to
  hypoxia and anemia).
• Patients with decreased erythropoietin develop
  chronic normocytic anemia requiring epoetin alfa
  administration.

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EPOETIN ALFA

• Pharmacotherapeutics
• Used to treat patients with
• Normocytic anemia caused by chronic renal
  failure.
• Anemia associated with zidovudine therapy in
  patients with HIV infection.
• Certain types of anemia decreasing the need for
  transfusions.

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EPOETIN ALFA

• Drug interactions
• No known drug interactions.
• Adverse reactions
• Hypertension

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ANTICOAGULANT DRUGS

• Used to reduce the ability of the blood to clot.
• Major categories of anticoagulants include
• Heparin
• Oral anticoagulants
• Antiplatelet drugs

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HEPARIN

• Prepared commercially from animal tissue.
• Used to prevent clot formation but cannot
  dissolve already formed clots.
• Used to prevent deep vein thrombosis in surgical
  patients.

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HEPARIN

• Pharmacokinetics
• Administered parenterally distribution is
  immediate IV not given IM metabolized in the
  liver excreted in the urine.
• Pharmacodynamics
• Prevents the formation of new thrombi.

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HEPARIN

• Pharmacotherapeutics
• Used to prevent the formation of new clots or the
  extension of existing clots in the following
  situations
• Venous thromboemboli
• Disseminated intravascular coagulation
• Atrial fibrillation
• Acute MI

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HEPARIN

• Also used to prevent clotting during use of the
  cardiopulmonary bypass machine and hemodialysis
  machine, and during orthopedic surgery.
• Drug interactions
• Increases the effects of oral anticoagulants -
  monitor PT and INR.
• Risk of bleeding increases when taken with NSAIDS
  and aspirin.

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HEPARIN

• Nicotine may inactivate heparin.
• Adverse reactions
• Bleeding - may be reversed with the
  administration of protamine sulfate.

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ORAL ANTICOAGULANTS

• The major oral anticoagulants used in the US are
  the coumarin compounds warfarin sodium (Coumadin)
  and Dicumarol.

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ORAL ANTICOAGULANTS

• Pharmacokinetics
• Warfarin is absorbed rapidly and completely
  Dicumarol is absorbed more slowly and
  erratically bound to plasma albumin metabolized
  in the liver excreted in the urine.

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ORAL ANTICOAGULANTS

• Pharmacodynamics
• Alter the ability of the liver to synthesize
  vitamin K-dependent clotting factors.
• Pharmacotherapeutics
• Used to treat thromboembolism and prevent DVT.
• Also prescribed for patients with diseased or
  prosthetic heart valves.

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ORAL ANTICOAGULANTS

• Drug interactions
• A diet high in vitamin K reduces the
  effectiveness of oral anticoagulants.
• Chronic alcohol abuse increases the risk of
  clotting acute alcohol intoxication increases
  the risk of bleeding.
• Many drugs may increase the risk of bleeding or
  clotting.

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ORAL ANTICOAGULANTS

• Adverse reactions
• Bleeding - may be reversed with the
  administration of phytonadione (vitamin K1).

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ANTIPLATELET DRUGS

• Used to prevent arterial thromboembolism in
  patients at risk for MI, stroke, and
  arteriosclerosis.
• Examples of antiplatelet drugs include
• Aspirin
• Dipyridamole (Persantine)
• Sulfinpyrazone
• Ticlopidine

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ANTIPLATELET DRUGS

• Pharmacokinetics
• Taken orally absorbed very quickly.
• Pharmacodynamics
• Interfere with platelet activity in different
  drug-specific and dose-related ways.

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ANTIPLATELET DRUGS

• Pharmacotherapeutics
• Used in patients with a previous MI or unstable
  angina TIAs post-cardiac valve replacement
  post-bypass surgery.
• Drug interactions
• Aspirin taken with heparin, oral anticoagulants,
  and dipyridamole increases bleeding risk.

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ANTIPLATELET DRUGS

• Adverse reactions
• Hypersensitivity reactions - anaphylaxis.

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THROMBOLYTIC DRUGS

• Used to dissolve a preexisting clot or thrombus
  in an acute situation.
• Some of these drugs currently being used include
• Alteplase
• Anistreplase
• Streptokinase

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THROMBOLYTIC DRUGS

• Pharmacokinetics
• After IV or intracoronary administration are
  distributed immediately quickly activate
  plasminogen (a precursor to plasmin which
  dissolves fibrin clots).
• Pharmacodynamics
• Convert plasminogen into plasmin which lyses
  thrombi, fibrinogen, and other plasma proteins.

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THROMBOLYTIC DRUGS

• Pharmacotherapeutics
• Used to treat certain thromboembolic disorders.
• The drug of choice to break down newly formed
  thrombi.
• Alteplase is used to treat acute MI, PE, and
  acute ischemic stroke.

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THROMBOLYTIC DRUGS

• Anistreplase is used to treat acute MI.
• Streptokinase is used to treat acute MI, PE, DVT,
  arterial thrombosis, and arterial embolism.
• Drug interactions
• Interact with anticoagulants, antiplatelets, and
  NSAIDS increasing bleeding risk.

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THROMBOLYTIC DRUGS

• Adverse reactions
• Bleeding and allergic response.