2. 2© Paradigm Publishing, Inc. Chapter 13 The Blood and Drug Therapy

3. Chapter 13 Topics Anatomy and Physiology of the Blood Anemia Stroke Clotting Disorders Herbal and Alternative Therapies 3© Paradigm Publishing, Inc.

4. Anatomy and Physiology of the Blood Blood Functions General  Supplies the cells of the body with oxygen and nutrients  Carries hormones and enzymes to control body functions  Helps to regulate body temperature Specific to pharmacokinetics  Absorbs drug and carries drug molecules as either dissolved substances or bound to proteins (albumin)  Distributes drug to organs and tissues © Paradigm Publishing, Inc.4

5. Anatomy and Physiology of the Blood Blood Composition Cells or formed elements (45%)  Erythrocytes, leukocytes, platelets Plasma (55%)  Water, proteins, and other substances © Paradigm Publishing, Inc.5

6. Anatomy and Physiology of the Blood © Paradigm Publishing, Inc.6 Blood Composition (continued)

7. Anatomy and Physiology of the Blood Blood Cells Three types of cells  RBCS or erythrocytes  Are produced in bone marrow (erythropoiesis)  Are formed by iron, folate, and vitamin B 12  Contain iron and hemoglobin to which oxygen and carbon dioxide bind during transport  WBCs or leukocytes  Fight disease (central to the immune system)  Platelets or thrombocytes  Help the blood clot during injury © Paradigm Publishing, Inc.7

8. Anatomy and Physiology of the Blood © Paradigm Publishing, Inc.8 Platelets and Blood Clot Formation Tissue damage triggers platelets to accumulate and activates clotting factors to start coagulation

9. Anatomy and Physiology of the Blood Coagulation Cascade Process  Involves a series of reactions that attract thrombin and fibrin (coagulation proteins)  Results in a functional blood clot Components  Includes two pathways, extrinsic and intrinsic, that converge with the use of clotting factor X, thrombin, and fibrin to form a common pathway  Malfunctions or abnormalities in pathways result in coagulation problems © Paradigm Publishing, Inc.9

10. Anatomy and Physiology of the Blood © Paradigm Publishing, Inc.10 Coagulation Cascade (continued)

11. Anatomy and Physiology of the Blood Effects of Clotting Disorders Blood Loss  May be life-threatening and require transfusion Blood Typing  Allows the matching of donor blood to a recipient for transfusion  Is determined by specific antigen proteins on the surface of RBCs  Includes Types O, A, B, and AB  Type O: universal donor  Type AB: universal recipient © Paradigm Publishing, Inc.11

12. Anemia About Anemia Lack of normal, healthy RBCs containing functional hemoglobin in the blood Symptoms: rapid heartbeat, lightheadedness, and breathlessness Symptoms (chronic): fatigue, weakness, headache, vertigo, faintness, sensitivity to cold, pallor, loss of skin tone Most Common Cause: inadequate production of RBCs Three Types of Anemia: hemolytic, iron-deficiency, and pernicious © Paradigm Publishing, Inc.12

13. Anemia © Paradigm Publishing, Inc.13

14. Anemia Drugs for Anemia Diagnosis based on laboratory markers Hgb and HCT  Blood values measure Hgb and oxygen-carrying capacity in the blood  Anemia is suspected if values are low Therapy determined by type and cause  For nutrient deficiency, replace nutrient  For altered hematopoiesis, administer erythropoietin Multiple causes of anemia make treatment complicated © Paradigm Publishing, Inc.14

15. Anemia Iron and Other Supplements Iron, folate, and vitamin B 12 are used as supplements for anemia caused by nutrient deficiency (see Table 13.1) Indications (iron): iron-deficiency anemia; anemia from CKD (in combination with hematopoietic agents) Indication (folic acid, low doses): prenatal supplement for fetal brain and spinal development Indication (folic acid, high doses): anemia due to alcoholism Indications (vitamin B 12 ): pernicious anemia; prevent neuropathy and certain types of dementia © Paradigm Publishing, Inc.15

16. Anemia Iron and Other Supplements (continued) Side Effects (iron, common): constipation, stomach upset, urine discoloration, dark stools Side Effects (vitamin B 12, common): itching, diarrhea, headache, anxiety Caution (oral iron): enteric coated; do not crush or chew Caution (oral iron): most oral iron supplements are OTC  Poison risk to children; iron overdose can be fatal Caution: do not take with antacids, other acid-reducing drugs, tetracycline, fluoroquinolones Caution (iron dextran): severe allergic reaction © Paradigm Publishing, Inc.16

17. Anemia Hematopoietic Agents: Erythropoietin and Darbepoetin Indications: anemia associated with CKD Indications (other): cancer chemotherapy causing bone marrow suppression which affects blood cell production Always use with iron supplements; these agents deplete iron stores as RBC production increases Mechanism of Action: supplements the body’s normal production of erythropoietin  Stimulates blood cell production in the bone marrow © Paradigm Publishing, Inc.17

18. Anemia Hematopoietic Agents: Erythropoietin and Darbepoetin (continued) Routes: IV, SC injection Side Effects (common): headache, fatigue, fever, muscle/joint pain, swelling, diarrhea, nausea, vomiting Side Effects (other): high blood pressure, clotting, rapid heartbeat Caution: monitor with CBC, Hgb, HCT lab tests; technician may retrieve results; Hgb should be below 12 g/dL Storage and Handling: refrigerate, do not shake or dilute; protect darbepoetin from light © Paradigm Publishing, Inc.18

19. Your Turn Question 1: Both RBCs and platelets are components of blood. How are their functions different? Answer: RBCs carry oxygen and carbon dioxide to and from body cells. Platelets help the blood clot during injury by clumping together and sticking to surrounding tissue. Question 2 What is the purpose of taking iron supplements with erythropoietin? Answer: Hematopoietic agents such as erythropoietin deplete iron stores as RBC production increases. 19© Paradigm Publishing, Inc.

20. Stroke About Stroke An interruption in oxygen supply to the brain (the brain requires constant supply of oxygenated blood) Without oxygen, takes minutes to lose consciousness and for tissue damage to occur  The brain cannot regenerate; cell death is permanent Two types of stroke: ischemic and hemorrhagic © Paradigm Publishing, Inc.20

21. Stroke Ischemic Stroke Results from an obstruction of blood flow to the brain by a blood clot or cholesterol plaque Brief and temporary blockage known as a TIA  Often a precursor (forewarning) of stroke Risk Factors: high cholesterol, cardiac arrhythmia, coronary artery disease, prosthetic heart valve, diabetes, hypercoagulable states, obesity, and physical inactivity © Paradigm Publishing, Inc.21

22. Stroke Hemorrhagic Stroke Results from a rupture in a blood vessel that supplies an area of the brain  Blood vessels in brain are weakened by certain conditions and form aneurysms that easily burst Risk Factors: high blood pressure, cigarette smoking, and excessive alcohol intake © Paradigm Publishing, Inc.22

23. Stroke Treatment of Stroke Most drug therapy for stroke is aimed at prevention rather than treatment after the fact  Risk of stroke is difficult to predict Many times, anticoagulation therapy starts only after someone has had a stroke or a TIA Low-dose aspirin therapy is used for patients who have multiple risk factors with no history of stroke © Paradigm Publishing, Inc.23

24. Clotting Disorders About Clotting Disorders Involves both hypercoagulation (overproduction of blood clots) and hemophilia (inability to produce blood clots) Commonly caused by genetics; may also be the result of certain risk factors Two types of clots: DVT (forms in an extremity such as the lower leg) and PE (forms in the lungs) Embolus (a piece of a clot) can dislodge and travel to the heart, brain, or lungs; creates life-threatening emergency Treatment (DVT, PE): often lasts 3-6 months to prevent emboli as the body dissolves the clot © Paradigm Publishing, Inc.24

25. Clotting Disorders Drugs for Stroke and Clotting Disorders Prevention and treatment of unwanted clots includes anticoagulants, antiplatelet agents, thrombolytics Specific lab tests used to monitor patients during therapy  PTT measures function of the intrinsic pathway of coagulation cascade; monitors heparin therapy  PT measures function of the extrinsic pathway of coagulation cascade; monitors warfarin therapy  INR gives a reference for the extrinsic pathway of coagulation cascade; monitors warfarin therapy Technicians may gather lab results, administer fingerstick © Paradigm Publishing, Inc.25

26. Clotting Disorders Anticoagulant Agents Indication: halt growth of emboli and stop them from forming as the body reabsorbs the clot on its own Treatment (early): usually starts with IV heparin to keep the clot from growing Treatment (later): LMWH via self-injection; oral warfarin therapy begins upon patient discharge from hospital Indication (warfarin): long-term anticoagulation; requires 5 + days for onset, so heparin or an LMWH co-administered Indication (heparin): immediate, short-term IV anticoagulation treatment of blood clots © Paradigm Publishing, Inc.26

27. Clotting Disorders Anticoagulant Agents: Heparin Routes: continuous IV infusion, SC injection Indication: blood clots; only anticoagulant used during pregnancy because it does not cross placental barrier Indications (other): flushes IV lines to keep them open; is given SC for prevention of blood clots in high-risk patients Mechanism of Action: inhibits clotting factors and inactivates thrombin and factor Xa in coagulation cascade  Also affects the platelets’ ability to clump together © Paradigm Publishing, Inc.27

28. Clotting Disorders Anticoagulant Agents: LMWHs Mechanism of Action: inhibit clotting factors and inactivate factor Xa in coagulation cascade Route: SC self-injection; given once or twice a day Indication: bridge therapy from IV heparin to oral warfarin Anticoagulant Agents: Fondaparinux Mechanism of Action: inhibits factor Xa Route: SC self-injection; given once a day Anticoagulant Agents: Direct Thrombin Inhibitors Inhibit thrombin directly; given as continuous infusions © Paradigm Publishing, Inc.28

29. Clotting Disorders Anticoagulant Agents: Warfarin Indications: heart valve disease, artificial heart valve placement, prior stroke, atrial fibrillation, DVT, PE, MI, other heart conditions Mechanism of Action: inhibits the production of vitamin K–dependent clotting factors in the liver Routes: oral, IV Common Doses: individualized to each patient; frequent lab testing is necessary © Paradigm Publishing, Inc.29

30. Clotting Disorders Anticoagulant Agents: Common Side Effects Heparin: bruising, bleeding, thrombocytopenia (low platelet count) LMWHs: bruising, bleeding, fever, thrombocytopenia, pain at injection site Fondaparinux : nausea, fever, anemia, bleeding, thrombocytopenia Direct thrombin inhibitors: nausea, headache, back pain, bleeding Warfarin: bleeding, hair loss, skin lesions, purple/blue toe syndrome © Paradigm Publishing, Inc.30

31. Clotting Disorders Anticoagulant Agents: Cautions Heparin: do not inject IM LMWHs, fondaparinux, and direct thrombin inhibitors: do not use in some cases of severe kidney problems Warfarin: many drug interactions (do not take with aspirin or NSAIDs); be consistent with intake of dietary vitamin K and the time of day when daily doses are taken All anticoagulants: considered high-risk medications; require close monitoring of patient and lab values to avoid life-threatening underdosing or overdosing errors © Paradigm Publishing, Inc. 31

32. Clotting Disorders Anticoagulation Antagonists Indication (vitamin K): reverses warfarin effects when signs of bleeding are present Indication (protamine): reverses heparin effects when hemorrhage or high risk of hemorrhage is present Side Effects (vitamin K, common): flushing, changes in taste, dizziness, sweating, rapid pulse, difficulty breathing Cautions (vitamin K): use SC whenever possible; give IM or IV very slowly (rapid administration can be fatal)  Mix in preservative-free normal saline or dextrose 5% in water (D 5 W) © Paradigm Publishing, Inc.32

33. Clotting Disorders Antiplatelet Agents Indication: decrease the risk of stroke, DVT, and clotting associated with cardiovascular blockage  Usually given after a stroke, DVT, or heart attack to prevent further clotting Indications (low-dose aspirin, 81 mg to 325 mg a day): prevent clots associated with stroke and heart attack; can be used during a heart attack to keep clots from completely occluding blood vessels in the heart Routes: all are oral; dipyridamole is also IV; aspirin is also rectal © Paradigm Publishing, Inc.33

34. Clotting Disorders Antiplatelet Agents (continued) Side Effects (aspirin, common): bleeding, stomach upset, headache, dizziness, and rash  Side effects of clopidogrel and ticlopidine similar to aspirin Side Effects: do not take antiplatelet agents if have or are at risk for bleeding disorders, or have a history of ulcers Cautions: contraindicated in patients with bleeding disorders or a history of ulcers; avoid taking with NSAIDs Consideration: work best when taken with food © Paradigm Publishing, Inc.34

35. Clotting Disorders Thrombolytic Agents Indications: massive MI, stroke, PE (limited to life- threatening situations due to high risk of severe bleeding)  Used when immediate return of blood flow is crucial Mechanism of Action: break up clots that have already formed; many dissolve and shrink blood clots Side Effects: bleeding, bruising, decreased heart rate and blood pressure, arrhythmias, fever, allergic reactions Route: IV in inpatient setting Cautions (reteplase): protect from light; refrigerate Caution (tenecteplase): mix with sterile water only © Paradigm Publishing, Inc.35

36. Clotting Disorders Hemophilia Agents Drugs replace specific missing clotting factors  This allows the coagulation cascade to function and restores normal coagulation These injectable hemophilia agents include factors VIIa, VIII, IX, and Von Willebrand factor Technicians will not prepare or dispense agents unless they work in a specialty pharmacy; few pharmacies stock them Agents are costly; they are monitored by prescribers and insurance providers © Paradigm Publishing, Inc.36

37. Your Turn Question 1: A patient is being treated for a blood clot. She was initially given IV heparin, and then a LMWH product. What drug therapy is likely to happen next? Answer: She likely will begin oral warfarin therapy but must overlap for at least five days with either heparin or LMWH. Once the warfarin is at therapeutic range, she can take the drug alone. Question 2: What are two restrictions of antiplatelet agents? Answer: Patients should not take these agents if they have bleeding, are at risk for bleeding, or have a history of ulcers. In addition, they should not take antiplatelet agents with NSAIDs. 37© Paradigm Publishing, Inc.

38. Herbal and Alternative Therapies Few herbal or natural products are taken for blood disorders Vitamin C is sometimes prescribed along with iron to boost absorption Numerous herbal products interact with anticoagulants (warfarin) and antiplatelet agents (aspirin and ticlopidine)  To avoid drug interactions, technicians should  take complete medical histories of patients on blood clotting medications  remind patients to inform healthcare providers when they take herbal or natural products © Paradigm Publishing, Inc.38

39. Summary Drug therapy for anemia includes iron, folic acid, and vitamin B 12 supplementation as well as hematopoietic agents Costly missing clotting factors are used for hemophilia Blood clots can cause stroke, heart attack, PE, and DVT Anticoagulants and antiplatelet drug therapies are often used to prevent and treat blood clots Thrombolytic drugs can be used in certain situations to break down clots that have formed; costly and many risks 39© Paradigm Publishing, Inc.