1. Introduction to Clinical Pharmacology Chapter 37 Anticoagulant and Thrombolytic Drugs

2. When a blood vessel is injured, a series of events occur to form a clot and stop the bleeding. This process is called hemostasis. It involves a complex process also called the coagulation cascade.

3. Hemostasis and Thrombosis
Hemostasis: complex process by which fibrin forms and blood clots
Thrombosis: formation of a blood clot
Thrombus: blood clot
Embolus: thrombus that detaches from a blood vessel wall and travels through the bloodstream
Pulmonary embolism: goes to the lung and obstructs a pulmonary vessel
Myocardial infarction occurs if the embolus detaches and occludes a vessel supplying blood to the heart

4. Oral and Parenteral Anticoagulants
Anticoagulants: prevent the formation and extension of a thrombus
Warfarin: oral anticoagulant
Fractionated and unfractionated heparin
Low–molecular-weight heparins (LMWHs)
Produce stable responses when administered at recommended dosages; bleeding less likely to occur

5. Oral and Parenteral Anticoagulants: Actions
Warfarin: interferes with the manufacturing of vitamin K–dependent clotting factors by the liver;depletes prothrombin
Heparin(mixture of high and low weight drugs):
Inhibits formation of fibrin clots
Inhibits conversion of fibrinogen to fibrin
Inactivates factors necessary for clotting of blood
LMWHs: inhibit clotting reactions by binding to antithrombin III ;inhibits the formation of a thrombus
These drugs have no effect on clots that have already formed and aid only in preventing the formation of new blood clots.

6. Oral and Parenteral Anticoagulants: Uses #1
Used for prevention and treatment of deep venous thrombosis (DVT), atrial fibrillation with embolization, pulmonary emboli
Used for adjuvant treatment of myocardial Infarction
Used to prevent thrombus formation after valve replacement surgery, postoperative DVT and PE, clotting in arterial and heart surgery, repeat cerebral thrombosis

7. Oral and Parenteral Anticoagulants: Uses #2
Used to treat:
Coronary occlusion, acute MI, peripheral arterial embolism
Used for diagnosis and treatment of:
Disseminated intravascular coagulation
Used for maintaining patency of IV catheters

8. Oral and Parenteral Anticoagulants: Adverse Reactions
Bleeding
Nausea, vomiting, abdominal cramping, diarrhea
Alopecia
Rash or urticaria
Hepatitis, jaundice, thrombocytopenia, blood dyscrasias

9. Oral and Parenteral Anticoagulants: Contraindications
Contraindicated in patients:
With known hypersensitivity to drugs, active bleeding, hemorrhagic disease, tuberculosis, leukemia, uncontrolled hypertension, gastrointestinal (GI) ulcers, recent surgery of the eye or central nervous system (CNS), aneurysms, severe renal or hepatic disease
During lactation

10. Oral and Parenteral Anticoagulants: Precautions
Used cautiously in patients with:
Fever, heart failure, diarrhea, diabetes, malignancy, hypertension, renal or hepatic disease, psychoses, depression
Potential site for bleeding or hemorrhage
Women of childbearing age: use a reliable contraceptive to prevent pregnancy

11. Oral and Parenteral Anticoagulants: Interactions #1
Interactant drug
Effect of interaction
Aspirin, acetaminophen, NSAIDs, chloral hydrate
Increased risk for bleeding
Penicillin, aminoglycosides, isoniazid, tetracyclines, cephalosporins

12. Oral and Parenteral Anticoagulants: Interactions #2
Interactant drug
Effect of interaction
Beta blockers, loop diuretics
Increased risk for bleeding
Disulfiram, cimetidine
Oral contraceptives, barbiturates, diuretics, vitamin K
Decreased effectiveness of the anticoagulant

13. Antiplatelet Drugs: Actions and Uses
Anticoagulant drugs prevent thrombosis in the venous system, and the antiplatelet drugs are used to prevent thrombus formation in the arterial system.
Aspirin: prohibits aggregation of platelets for lifetime of platelet
ADP blockers: alter cell membrane, preventing aggregation
Glycoprotein receptor blockers: prevent enzyme production; inhibit platelet aggregation
Antiplatelet drug therapy: treats acute coronary syndrome, myocardial infarction, stroke, and intermittent claudication

14. Antiplatelet Drugs: Adverse Reactions
Common adverse reactions:
Heart palpitations
Bleeding
Dizziness and headache
Nausea, diarrhea, constipation, dyspepsia

15. Antiplatelet Drugs: Contraindications and Precautions
Contraindicated in patients:
With known hypersensitivity to the drug, congestive heart failure, active bleeding, thrombotic thrombocytopenic purpura
During pregnancy and lactation
Used cautiously in:
Elderly patients, pancytopenic patients, those with renal and hepatic impairment

16. Antiplatelet Drugs: Interactions
Interactant drug
Effect of interaction
Aspirin and NSAIDs
Increased risk for bleeding
Macrolide antibiotics
Increased effectiveness of anti-infective
Digoxin
Decreased digoxin serum levels
Phenytoin
Increased phenytoin serum levels

17. Thrombolytic Drugs: Actions
Break down fibrin clots by converting plasminogen to plasmin
Plasmin: enzyme that breaks down fibrin of blood clot
Reopens blood vessels after occlusion and prevents tissue necrosis
Because thrombolytic drugs dissolve all clots encountered (both occlusive and those repairing vessel leaks), bleeding is a great concern when using these agents.
Before these drugs are used, their potential benefits must be weighed carefully against the potential dangers of bleeding.

18. Thrombolytic Drugs: Uses
Used to treat:
Acute myocardial infarction by lysis of blood clots in coronary arteries
Blood clots causing pulmonary emboli and DVT
Suspected occlusions in central venous catheters

19. Thrombolytic Drugs: Adverse Reactions
Bleeding
Internal bleeding: GI tract, genitourinary tract, brain
External bleeding: broken skin, such as venipuncture sites and recent surgical wounds
Allergic reactions

20. Thrombolytic Drugs: Contraindications and Precautions
Contraindicated in patients:
With known hypersensitivity, active bleeding, history of stroke or aneurysm, recent intracranial surgery
Used cautiously in patients:
Who have recently undergone major surgery
With hypertension, diabetic retinopathy, any condition in which bleeding is a significant possibility
Currently receiving oral anticoagulants

21. Thrombolytic Drugs: Interactions
Increased risk for bleeding when coadministered with medications that prevent blood clots or with an anticoagulant

22. Nursing Process: Assessment #1
Preadministration assessment:
Obtain drug history and vital signs
Examine extremity for color and skin temperature
Check for pedal pulses, noting rate and strength of pulses
Note areas of redness or tenderness and ask patient to describe current symptoms
Obtain complete blood count

23. Nursing Process: Assessment #2
Ongoing assessment:
Assess patient for signs of bleeding and hemorrhage
Monitor for intracranial bleeding by assessing level of consciousness
Monitor PT/INR results
Monitor for any indication of hypersensitivity reaction

24. Patients receiving warfarin require daily adjustment of the dose,based on the daily PT/INR results
If the INR ratio exceeds 3, the primary health care provider is notified before the drug is given.
After the INR has stabilized, it is monitored every 4 to 6 weeks.
The dosage of heparin is adjusted according to daily aPTT monitoring. A therapeutic dosage is attained when the aPTT is 1.5 to 2.5 times the normal.
The LMWHs have little or no effect on the aPTT values.
Periodic platelet counts, hematocrit, and tests for occult blood in the stool should be performed throughout the course of heparin therapy.
Blood coagulation tests for those receiving heparin by continuous IV infusion are taken at periodic intervals (usually every 4 hours)

25. Nursing Process: Diagnosis
Risk for Injury related to excessive bleeding due to drug therapy
Individual Effective Self-Health Management related to inability to communicate drug use if incapacitated
Anxiety related to fear of atypical bleeding during thrombolytic drug therapy

26. Nursing Process: Planning
Expected outcome
Optimal response to therapy
Support of patient needs related to management of adverse reactions
Understanding of postdischarge drug regimen

27. Nursing Process: Implementation #1
Promoting an optimal response to therapy
Oral administration of anticoagulants:
Check prothrombin flow sheet; review PT/INR results
For rapid anticoagulation: Loading dose of heparin, followed by maintenance dose of warfarin based on PT or INR

28. Nursing Process: Implementation #2
Promoting an optimal response to therapy (cont.)
Parenteral administration of anticoagulants:
Administration of heparin: intermittent IV, continuous IV infusion, or subcutaneous route
Inspect needle site for signs of inflammation, pain, and tenderness along pathway of vein
Closely monitor blood coagulation tests, complete blood count, platelets, and stool analysis

29. Nursing Process: Implementation #3
Administration of thrombolytics:
Assess patient for bleeding until therapy is completed; vital signs
Administer opioid analgesic for pain management
Drugs used to maintain IV patency:
Inspect needle site
Avoid using excessive pressure when the drug is injected into the catheter

30. Nursing Process: Implementation #4
Monitoring and managing patient needs:
Risk for injury
Check for signs of bleeding: drop in blood pressure, rise in pulse rate, urine, stool; visually check nasogastric suction; check toothbrush, gums after oral care

31. Nursing Process: Implementation #5
Monitoring and managing patient needs: (cont.)
Individual effective self-health management:
Educate about food and drug interactions
Instruct patient to wear medical identification to indicate receiving anticoagulant or antiplatelet therapy

32. Nursing Process: Implementation #6
Monitoring and managing patient needs (cont.)
Anxiety:
Reassure patient and communicate with family member
Assess for signs of bleeding and hemorrhage
Monitor vital signs and for signs of allergic reactions

33. Nursing Process: Implementation #7
Managing anticoagulant overdosage:
Oral anticoagulants
Monitor for symptoms of warfarin overdosage:
Blood in stool; petechiae
Oozing from superficial injuries
Excessive menstrual bleeding
If bleeding occurs, or the INR exceeds 3, the primary health care provider may either discontinue the anticoagulant therapy for a few days or order vitamin K(phytonadione), an oral anticoagulant antagonist, which should be readily available when a patient is receiving warfarin.

34. Nursing Process: Implementation #8
Managing anticoagulant overdosage (cont.)
Parenteral anticoagulants:
After administration of heparin: monitor blood pressure and pulse rate
Observe new evidence of bleeding until blood coagulation tests are within normal limits
Discontinuation of the drug is sufficient to correct overdosage, because the duration of action of heparin is brief. However, if hemorrhaging is severe, the primary health care provider may order protamine, the specific heparin antagonist or antidote.
Protamine is also used to treat overdosage of the LMWHs.
Blood transfusions or fresh frozen plasma may be ordered

35. Nursing Process: Implementation #9
Educating the patient and family:
Provide full explanation of the drug regimen, possible adverse reactions, and signs of bleeding tendencies
Explain the importance of monitoring PT or INR
Explain the importance of avoiding taking drugs or changing brands of anticoagulants without informing primary health care provider

36. Nursing Process: Implementation #10
Educating the patient and family (cont.)
Advise the patient to inform dentist or primary health care provider of therapy with this drug before any treatment
Explain the importance of taking the drug at the same time each day
Instruct the patient to avoid alcohol unless approved by primary health care provider
Provide dietary information-Be aware of foods high in vitamin K, such as leafy green vegetables, beans, broccoli, cabbage, cauliflower, cheese, fish, and yogurt

37. Nursing Process: Implementation #11
Educating the patient and family (cont.)
Explain the necessity of contacting the primary health care provider immediately if evidence of bleeding occurs
Explain importance for women of childbearing age to use reliable contraceptive to prevent pregnancy
Explain importance of wearing or carrying medical identification

38. Nursing Process: Evaluation
Therapeutic drug effect is achieved
Adverse reactions are identified, reported, and managed successfully
Patient demonstrates understanding of drug regimen
Patient verbalizes importance of complying with prescribed therapeutic regimen
Patient lists or describes early signs of bleeding

39. Question #1 Is the following statement true or false?
Hemostasis is the process of clotting; this is beneficial when injury tears a vessel.

40. Answer to Question #1 True
Hemostasis is the process of clotting; this is beneficial when injury tears a vessel.

41. Question #2 Is the following statement true or false?
A thrombus is a clot that forms in a vessel and impedes blood flow.

42. Answer to Question #2 True
A thrombus is a clot that forms in a vessel and impedes blood flow.

43. Question #3 Is the following statement true or false?
Anticoagulants do reverse damage already done by a clot.

44. Answer to Question #3 False
These drugs do not affect existing clots, nor do they reverse damage already done by a clot. These drugs are used to prevent further clot development.