1. Cardiac Drugs Heather Gates RN, BSN

2. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 The Pumping Action of the Heart Determines Systolic and Diastolic Blood Pressure

3. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Figure 15.1 Blood pressure changes throughout the circulation

4. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Ventricles of Heart Contract to Eject Blood Pressure in arteries increases Systolic pressure

5. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Ventricles of Heart Relax thus Blood Is Not Ejected Pressure in arteries falls Diastolic pressure

6. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Figure 15.2 (a) Systolic pressure occurs when the heart ejects blood, creating high pressure in the arteries. (b) Diastolic pressure occurs when the heart relaxes, resulting in less pressure in the arteries.

7. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Primary Factors Responsible for Blood Pressure Cardiac output Peripheral resistance Blood volume

8. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Figure 15.3 Primary factors affecting blood pressure

9. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Cardiac Output - Volume of Blood Pumped Per Minute The higher the cardiac output, the higher the blood pressure

10. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Peripheral Resistance - Friction of the Blood as it Flows Across the Walls of Arteries Arteries constrict thus resistance increases thus blood pressure increases

11. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Blood Volume - Total Amount of Blood in the Vascular System Increase in blood volume resulting in more force on arterial walls thus blood pressure increases

12. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Classification of Hypertension in Adults Normal - SBP < 120 and DBP < 80 Prehypertension - SBP 120–139 or DBP 80–89 Stage I hypertension - SBP 140–159 or DBP 90–99 Stage II hypertension - SBP > 160 or DBP >100

13. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Methods for Controlling Borderline Hypertension without Drugs Implement a medically supervised, safe weight-reduction plan if 20% over normal weight Stop using tobacco Limit salt (sodium) intake and eat foods rich in potassium and magnesium

14. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Methods for Controlling Borderline Hypertension without Drugs (cont’d) Limit alcohol consumption Implement a medically supervised aerobic exercise plan Reduce sources of stress and learn to implement coping strategies

15. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 “Stepped Care” Principles - Pertaining to Antihypertension Drugs Use two drugs from different classes to control hypertension Allows lower doses of each drug Lower doses produce fewer side effects Better patient compliance

16. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Diuretics Are Often Drugs of First Choice for Reducing Mild to Moderate Hypertension Example - hydrochlorothiazide (HydroDIURIL), furosemide (Lasix) Mechanism of action - increase the amount of urine produced by the kidneys which increases excretion of water and electrolytes (Na, Ca, CL, K) which decreases blood volume which decreases BP Primary use - mild to moderate hypertension Important side effects - electrolyte imbalances (especially loss of K)

17. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Calcium Channel Blockers Have Emerged as Primary Drugs in the Treatment of Hypertension Examples - renin-angiotensin pathway modifier- nifedipine (Procardia, Aldalat), ACE inhibitor- verapamil (Calan) Mechanism of action - block calcium channels in plasma membrane which causes vasodilation of arteriole which decreases BP Primary use - angina, hypertension Important side effects - headache, dizziness, flushing

18. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Renin-Angiotensin Pathway Modifiers Block the Renin- Angiotensin Pathway and Decrease Blood Pressure Examples - enalapril (Vasotec), irbesartan (Avapro) Mechanism of action - ACE inhibitors - block angiotensin-converting enzyme (ACE) that blocks formation of angiotensin II resulting in vasodilation and decrease reabsorption of sodium by kidneys resulting in more urine excreted resulting in decreased blood volume which decrease BP

19. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Renin-Angiotensin Pathway Modifiers Block the Renin- Angiotensin Pathway and Decrease Blood Pressure (cont’d) Angiotensinreceptor blockers - block angiotensin receptors in arteriolar smooth muscle and adrenal glands leading to arteriolar dilation and increase renal sodium excretion which decreases BP Primary uses - hypertension Important side effects - ACE inhibitors - persistent cough, hypotension; angiotensin receptor blockers - hypotension

20. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Alpha- and Beta-Adrenergic Blockers Are Commonly Used to Treat Hypertension Example - doxazosin (Cardura) Mechanisms of action - blockade of alpha-receptors, selective blockade of beta 1 receptors, nonselective blockade of beta 1 and beta 2 receptors or stimulation of alpha 2 -receptors in the brain stem which block effects of the sympathetic division leading to vasodilation which decreases blood pressure Primary use - hypertension Important side effects - orthostatic hypotension, dizziness, nausea, bradycardia, dry mouth

21. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Direct-Acting Vasodilators Act on Arteriolar Smooth Muscle to Lower Blood Pressure Example - hydralazine (Apresoline) Mechanism of action - direct relaxation of arteriolar smooth muscle leading to vasodilation which decreases BP Primary use - severe hypertension, hypertensive crisis Important side effects - reflex tachycardia, sodium and fluid retention

22. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Disorders Associated with Heart Failure Mitral stenosis Myocardial infarction Chronic hypertension Coronary artery disease Diabetes

23. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Classic Symptoms Associated with Heart Failure Skin cyanotic and clammy Anxiety/restlessness Upright posture/leaning forward Persistent cough Rapid breathing Fast heart rate Edema of lower limbs

24. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Figure 16.2 Signs and symptoms of the patient with heart failure

25. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Left-Sided Heart Failure - Decrease Cardiac Output Skin cyanotic and clammy, which leads to decreased oxygen supply Anxiety/restlessness leads to decreased oxygen to the brain Upright posture/leaning forward/persistent cough leads to blood backing into the lungs Rapid breathing leads to decreased oxygen to the body

26. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Right-Sided Heart Failure - Decrease Blood to Lungs Edema of lower limbs leads to blood backing up in venous circulation Fast heart rate leads to the body not getting enough oxygen

27. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 First-Choice Drugs - ACE Inhibitors and Diuretics Given first Reduce most symptoms of mild to moderate heart failure Fewer side effects

28. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Second-Choice Drugs - Phosphodiesterase inhibitors, vasodilators, and beta- adrenergic blockers Used in severe heart failure First-choice drugs not effective

29. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Nonpharmacological Methods for Controlling Heart Failure Stop using tobacco Limit salt (sodium) intake and eat foods rich in potassium and magnesium Limit alcohol consumption Implement a medically supervised exercise plan Learn and use effective ways to deal with stress Reduce weight to an optimum level Limit caffeine consumption

30. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Cardiac Glycosides Increase the Force of Myocardial Contraction Example - digoxin (Lanoxin) Mechanism of action - 1) positive inotropic effect: more blood ejected per beat leads to increased cardiac output in order to meet, the metabolic demands of tissues; 2) slow electrical conduction through the heart, which creates fewer beats per minute and decreases heart rate

31. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Cardiac Glycosides Increase the Force of Myocardial Contraction (cont’d) Primary use - heart failure Important adverse effects - loss of appetite, vomiting, diarrhea, headache, drowsiness, confusion, blurred vision, excessive bradycardia

32. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 ACE Inhibitors Have Become First-Line Drugs for Heart Failure Example - lisinopril (Prinivil) Mechanism of action - blocks ACE enzyme, which lowers blood pressure, increases cardiac output, decreases preload and reduces peripheral edema; increased excretion of sodium and water leads to decreased blood volume primary use - heart failure and hypertension Important adverse effects - elevated potassium levels, cough, taste disturbances, hypotension

33. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Diuretics Relieve Symptoms of Heart Failure by Reducing Blood Volume Example - furosemide (Lasix) Mechanism of action - prevents reabsorption of sodium by the nephron of the kidney, which increases excretion of sodium and water; decreases blood volume, edema, and congestion; lowers blood pressure, and reduces workload on heart. Cardiac output then increases Primary use - acute heart failure Important adverse effects - electrolyte imbalances

34. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Phosphodiesterase Inhibitors Are Used for Short-Term Therapy of Advanced Heart Failure Example - milrinone (Primacor) Mechanism of action - blocks phosphodiesterase enzyme, which increases the amount of calcium available for myocardial contraction, which then increases force of contraction and vasodilation Primary use - short-term support of advanced heart failure Important adverse effects - ventricular dysrhythmia

35. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Vasodilators Reduce Symptoms of Heart Failure by Decreasing Cardiac Oxygen Demands Example - Isosorbide (Isordil) Mechanism of action - relaxes vascular smooth muscle, which leads to vasodilation, which decreases cardiac workload and increases cardiac output Primary use - cannot tolerate ACE inhibitors, angina pectoris, hypertension Important adverse effects - headache, hypotension, reflex tachycardia

36. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Beta-Adrenergic Blockers Are Used in Combination with Other Drugs to Slow the Progression of Heart Failure and to Prolong Patient Survival Example - carvedilol (Coreg) Mechanism of action - blocks beta 1, beta 2, and alpha 1 receptors, which decreases heart rate and blood pressure, decreases afterload, and reduces the workload on the heart

37. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Beta-Adrenergic Blockers Are Used in Combination with Other Drugs to Slow the Progression of Heart Failure and to Prolong Patient Survival (cont’d) Primary use - slow progression of heart failure and increased exercise tolerance when combined with other heart failure drugs Important adverse effects - worsen heart failure

38. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Natriuretic Peptides Are the First New Drugs to Treat Heart Failure in More than 10 Years Example - nesiritide (Natrecor) Mechanism of action - acts on kidney, which increases excretion of sodium and water, thereby lowering blood pressure; also causes vasodilation, which reduces preload Primary use - severe heart failure Important adverse effects - severe hypotension

39. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Figure 16.3 Mechanisms of action of drugs used for heart failure

40. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Hyperlipidemia - Excess Amounts of Lipids in the Blood Major risk factor for cardiovascular disease Hypercholesterolemia Saturated fats

41. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Cholesterol Metabolism Increased blood cholesterol equals increased risk of cardiovascular disease Plaque buildup occurs in the vessel walls

42. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Lipoproteins Cholesterol not soluble in the blood Inner core of lipid, outer core of protein Water soluble and travels freely in the blood

43. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Three Most Common Lipoproteins, Based on Weight or Density: Low-density lipoproteins (LDL) High-density lipoproteins (HDL) Very low-density lipoproteins (VLDL)

44. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Low-density Lipoproteins (LDL) Highest amount of cholesterol Created in liver Build plasma membranes and produce steroids Stored in tissues Contribute to plaque deposits and CHD Aka bad cholesterol

45. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 High-Density Lipoproteins (HDL) Picks up cholesterol Returns it to the liver Becomes part of bile and excreted in feces Aka good cholesterol

46. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Very Low-Density Lipoproteins (VLDL) Triglyceride carrier Converted to LDL in blood High levels are associated with pancreatitis

47. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 National Cholesterol Education Program (NCEP) Recommendations for Therapeutic Lifestyle Changes Increase physical activity Maintain optimum weight Maintain a healthy diet Reduce dietary saturated fats and cholesterol Increase soluble fiber in diet

48. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Other Lifestyle Changes Include Tobacco cessation Control of hypertension Stress reduction Limiting high sugar foods Increasing Omega-3 fatty acids in the diet Avoiding transfatty acids in the diet

49. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 HMG CoA Reductase Inhibitors (Statins) Drugs of first choice in reducing blood lipid levels Reduce LDL, triglyceride, and VLDL levels Raise HDL levels (good cholesterol)

50. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Inhibit HMG CoA Reductase Critical enzyme in cholesterol synthesis Liver produces less cholesterol More LDL receptors More LDL removed from blood Blood levels of LDL and cholesterol reduced

51. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Effect Not Permanent Take statins for the rest of life Or until controlled by lifestyle changes

52. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Administration Give all statins orally Give in the evening Monitor for muscle injury

53. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Drug Profile - HMG-CoA Reductase Inhibitor (Statin) Atorvastatin (Lipitor) Actions Adverse effects and interactions

54. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Newer Approaches to Treating Hyperlipidemia Ezetimibe (Zetia) Fixed-dose combination therapy

55. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Ezetimibe Blocks absorption of dietary cholesterol LDL and triglycerides are reduced Slight increase in HDL Well tolerated by patients

56. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Fixed-Dose Combination Therapy Allows for lower doses of each agent Potentially fewer side effects Better patient compliance Synergistic effect

57. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 New Trend in Treatment of CHD Combine an antihypertensive with an antihyperlipidemic Targeted at the many patients with both hypertension and elevated cholesterol

58. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Figure 20.4 Mechanisms of action of lipid-lowering drugs

59. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Hemostasis - Process of Stopping the Flow of Blood Internally and externally Prevent bleeding from wounds which could lead to shock or even death

60. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Three Basic Steps to Hemostasis Injured vessel constricts to slow blood flow Platelets adhere to injured area and aggregate, plugging damaged vessel Coagulation cascade occurs thus forming insoluble fibrin strands which slows blood flow more

61. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Coagulation Cascade - Series of Complex Steps Injured cells release prothrombin activator Prothrombin activator changes prothrombin to thrombin Thrombin changes fibrinogen to fibrin Fibrin forms an insoluble web over injured area which stops blood flow

62. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Coagulation-Modifier Drugs Anticoagulants Thrombolytics Hemostatics

63. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Anticoagulants - Prevent the Formation of Clots Inhibiting specific clotting factors in the coagulation cascade Diminishing the clotting action of platelets Both ways increase the time to form clots

64. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Thrombolytics Dissolve life-threatening clots

65. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Hemostatics Promote formation of clots Inhibit removal of fibrin

66. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Anticoagulants Prevent the Formation and Enlargement of Clots Examples - heparin (Heplock), warfarin (Coumadin) Mechanism of action - inhibit specific clotting factors which interfere with coagulation cascade in order to prevent formation or enlargement of clot Primary use - thromboembolic disease; prevent formation of clots in veins Adverse effects - abnormal bleeding

67. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Antiplatelet Agents Prolong Bleeding Time by Interfering with Platelet Aggregation Example - ticlopidine (Ticlid) Mechanism of actions Aspirin: inhibits thromboxane2, which prevents aggregation of platelets ADP receptor blockers: interfere with platelet plasma membrane, which prevents platelet aggregation Glycoprotein IIb/IIIa inhibitors: glycoprotein IIb/IIIa enzyme inhibited which prevents platelet aggregation

68. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Antiplatelet Agents Prolong Bleeding Time by Interfering with Platelet Aggregation (cont’d) Primary uses - prevent clot formation in arteries Adverse effects - abnormal bleeding; reduce number of neutrophils

69. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Thrombolytics Are Used to Dissolve Existing Clots Example - alteplase (Activase) Mechanism of action - convert plasminogen to plasmin which causes fibrin to degrade, then preexisting clot dissolves Primary uses - acute MI, pulmonary embolism, acute ischemic CVA, DVT, arterial thrombosis, coronary thrombosis, clear thrombi in arteriovenous cannulas and blocked IV catheters Adverse effects - abnormal bleeding; contraindicated in patients with active bleeding or recent trauma

70. Core Concepts in Pharmacology, 2e By Norman Holland and Michael Patrick Adams © 2007 Pearson Education, Inc. Pearson Prentice Hall Upper Saddle River, NJ 07458 Hemostatics Are Used to Promote the Formation of Clot Example - aminocaproic (Amicar) Mechanism of action - prevent fibrin from dissolving, which enhances stability of the clot Primary use - prevent and treat excessive bleeding from surgical sites Adverse effects - none listed