1. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concepts in PharmacologyCHAPTER Third Edition Drugs for Bacterial Infections 25

2. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Directory Classroom Response System Lecture Note Presentation

3. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Question 1 The patient is taking amoxicillin (Amoxil). Which of the following statements by the patient demonstrates that he or she needs additional instruction?

4. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Question 1 Choices 1.“I will take this medication until it is gone.” 2.“I will call my doctor if I develop a fever or a rash.” 3.“Before I take my medication, I will avoid orange juice.” 4.“I will take the medication until I feel better.”

5. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Question 1 Answer 1.“I will take this medication until it is gone.” 2.“I will call my doctor if I develop a fever or a rash.” 3.“Before I take my medication, I will avoid orange juice.” 4.“I will take the medication until I feel better.”

6. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Question 2 The patient on tetracyclines should be instructed:

7. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Question 2 Choices 1.To take it with food or milk 2.That it is safe for pregnancy 3.To take it 1–2 hours before or after meals 4.That it has no adverse effects

8. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Question 2 Answer 1.To take it with food or milk 2.That it is safe for pregnancy 3.To take it 1–2 hours before or after meals 4.That it has no adverse effects

9. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Question 3 The patient has a urinary tract infection. The nurse anticipates which of the following medications being ordered?

10. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Question 3 Choices 1.Sulfacetamide (Cetamide) 2.Sulfadiazine (Microsulfon) 3.Trimethoprim-sulfamethoxazole (Septra) 4.Vancomycin (Vancocin)

11. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Question 3 Answer 1.Sulfacetamide (Cetamide) 2.Sulfadiazine (Microsulfon) 3.Trimethoprim-sulfamethoxazole (Septra) 4.Vancomycin (Vancocin)

12. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Question 4 The patient asks why he must take two medications for his tuberculosis. The nurse’s best response would be:

13. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Question 4 Choices 1.“You have TB throughout your body. It will take additional medications to cure you.” 2.“You will need to speak with your physician.” 3.“Taking multiple drugs increases the chances that therapy will be successful.” 4.“With multiple drugs, we can decrease the time you need to take the medications.”

14. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Question 4 Answer 1.“You have TB throughout your body. It will take additional medications to cure you.” 2.“You will need to speak with your physician.” 3.“Taking multiple drugs increases the chances that therapy will be successful.” 4.“With multiple drugs, we can decrease the time you need to take the medications.”

15. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Learning Outcomes 1.Distinguish between the terms pathogenicity and virulence. 2.Explain how bacteria are described and classified. 3.Compare and contrast the terms bacteriostatic and bacteriocidal.

16. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Learning Outcomes 4.Using a specific example, explain how resistance can develop to an anti- infective drug. 5.Explain the importance of culture and sensitivity testing to anti-infective chemotherapy.

17. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Learning Outcomes 6.Identify the mechanism of development and symptoms of superinfections caused by anti-infective therapy. 7.For each of the classes in the Drug Snapshot, identify representative drugs, explain the mechanisms of drug action, primary actions, and important adverse effects.

18. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Learning Outcomes 8.Explain how the pharmacotherapy of tuberculosis differs from that of other infections.

19. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.1 Pathogens are organisms that cause disease by invading tissues or secreting toxins.

20. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Figure 25.1 Types of pathogenic organisms: (a) bacterium; (b) virus; (c) protozoan pathogens; (d) multicellular parasites; (e) fungi Source: Reprinted by permission of Pearson Education, Inc., Upper Saddle River, NJ

21. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Figure 25.1 (continued) Types of pathogenic organisms: (a) bacterium; (b) virus; (c) protozoan pathogens; (d) multicellular parasites; (e) fungi Source: Reprinted by permission of Pearson Education, Inc., Upper Saddle River, NJ

22. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams

23. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Table 25.1 (continued) Common Bacterial Pathogens

24. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.2 Anti-infective drugs are classified by their chemical structures or by their mechanisms of action.

25. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams

26. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.3 Anti-infective drugs act by selectively targeting a pathogen’s metabolism or life cycle.

27. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Primary Goal of Antimicrobial Therapy Assist the body’s defenses in eliminating a pathogen. Bacteriocidal Drugs kill bacteria Bacteriostatic slow their growth,allowing the body’s natural defenses to eliminate the microorganisms.

28. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Figure 25.2 Mechanisms of action of antimicrobial drugs

29. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.4 Acquired resistance is a major clinical problem that is worsened by improper use of anti-infectives.

30. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Figure 25.3 Acquired resistance

31. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Nosocomial Infection Acquired in a hospital or other health care setting, Often resistant to common antibiotics Two particularly serious resistant infections methicillin-resistant Staphylococcus aureus (MRSA) vancomycin-resistant enterococci (VRE).

32. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Prevention Principles from CDC Prevent infections whenever possible. It is always easier to prevent an infection, than to treat one. This includes teaching the patient the importance of getting immunizations

33. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Prevention Principles from CDC Restrict the use of antibiotics to those conditions deemed medically necessary. Antibiotics should only be prescribed when there is a clear rationale for their use.

34. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Prevention Principles from CDC Advise the patient to take antiinfectives for the full length of therapy, even if symptoms disappear before the regimen is finished. Prematurely stopping antibiotic therapy allows some pathogens to survive, thus promoting the development of resistant strains.

35. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Prevention Principles from CDC Prevent transmission of the pathogen by using proper infection control procedures. This includes the use of standard precautions and teaching patients methods of proper hygiene for preventing transmission in the home and community settings.

36. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.5 Careful selection of the correct antibiotic is essential for effective pharmacotherapy and to limit adverse effects.

37. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Culture and Sensitivity Testing The organism is grown and the effective antibiotics are identified Should be identified before anti-infective therapy is begun. Treatment needs to begin sooner

38. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Culture and Sensitivity Testing Broad-spectrum antibiotic - one that is effective against a wide variety of different microbial species. Narrow-spectrum antibiotic - one that is effective against a smaller group of microbes or only the isolated species.

39. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.6 The penicillins are one of the oldest and safest groups of anti-infectives.

40. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Action of Penicillins Kill bacteria by disrupting their cell walls Chemical structure of penicillin that is responsible for its antibacterial activity is called the beta-lactam ring.

41. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Action of Penicillins Resistance –Some bacteria secrete an enzyme, called beta-lactamase or penicillinase, which splits the beta-lactam ring. –This structural change allows these bacteria to become resistant to the effects of most penicillins.

42. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Figure 25.4 Action of penicillinase

43. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Modifications Chemical modifications to the natural penicillin molecule produced drugs advantages. Penicillinase-resistant penicillins Broad spectrum penicillins Extended-spectrum penicillins

44. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams

45. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Concept Review 25.1 Why does antibiotic resistance become more of a problem when antibiotics are prescribed too often?

46. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.7 The cephalosporins are similar in structure and function to the penicillins and are one of the most widely prescribed anti-infective classes.

47. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Cephalosporins Contain a beta-lactam ring Bacteriocidal, inhibit bacterial cell wall synthesis. Primary therapeutic use –Gram-negative infections –Patients who cannot tolerate the less- expensive penicillins. Cross allergy with penicillins

48. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Classified by Their “Generation.” First-generation drugs contain a beta- lactam ring, and bacteria producing beta- lactamase will normally be resistant to these agents. Second-generation cephalosporins are more potent and more resistant to beta- lactamase, and exhibit a broader spectrum than the first-generation drugs

49. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Classified by Their “Generation.” Third-generation cephalosporins generally have a longer duration of action, an even broader spectrum, and are resistant to beta-lactamases. Fourth-generation drugs are more effective against organisms that have developed resistance to earlier cephalosporins.

50. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams

51. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Table 25.4 (continued) Selected Cephalosporins

52. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.8 The tetracyclines have broad spectrums but are drugs of choice for few diseases.

53. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Tetracyclines Bacteriostatic effect by inhibiting bacterial protein synthesis Effective against a wide range of gram- negative and gram-positive organisms and have one of the broadest spectrums of any class of antibiotics.

54. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Tetracyclines Patient Teaching –Urged not to drink milk with these medications because tetracyclines bind ions such as calcium and iron, thereby decreasing the drug’s absorption by as much as 50%. –Avoid direct exposure to sunlight because tetracyclines can cause photosensitivity

55. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Tetracyclines Patients younger than 9 years are not given tetracyclines because these drugs may cause permanent yellow-brown teeth discoloration in young children.

56. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams

57. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.9 The macrolides are safe alternatives to penicillin for many infections.

58. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Macrolide Antibiotics Inhibit bacterial protein synthesis and may be either bacteriocidal or bacteriostatic Safe alternatives to penicillin

59. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams

60. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Concept Review 25.2 If penicillins are inexpensive, why might a physician prescribe a more expensive cephalosporin or macrolide antibiotic?

61. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.10 The aminoglycosides are narrow-spectrum drugs that have the potential to cause serious toxicity.

62. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Aminoglycosides Treatment of a number of aerobic gram- negative bacteria, mycobacteria, and some protozoan Bacteriocidal inhibit bacterial protein synthesis.

63. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Aminoglycosides Ototoxicity –Damage to the inner ear, causes hearing impairment, dizziness, loss of balance, persistent headache, and ringing in the ears Nephrotoxicity –Kidney damage, recognized by abnormal urinary function tests, such as elevated serum creatinine or blood urea nitrogen (BUN).

64. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams

65. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.11 Fluoroquinolones have wide clinical applications because of their broad spectrum of activity and relative safety.

66. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Fluoroquinolones Gram-negative pathogens Newer ones are significantly more effective against gram-positive microbes. Bacteriocidal Inhibit bacterial DNA synthesis.

67. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams

68. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.12 Sulfonamides are traditional drugs of choice for urinary tract infections.

69. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams

70. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.13 A number of additional anti-infectives have distinct mechanisms of action and specific indications.

71. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams

72. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Table 25.10 (continued) Miscellaneous Anti-infectives

73. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Core Concept 25.14 The pharmacotherapy of tuberculosis requires special dosing regimens and schedules.

74. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams

75. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Drug Therapy of Tuberculosis Differs from that of most other infections –Therapy for 6-12 months Mycobacteria have a cell wall that is resistant to penetration by anti-infective drugs –2-4 antibiotics needed concurrently

76. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Drug Therapy of Tuberculosis Mycobacteria grow slowly Resistance is common –Drugs are used extensively for preventing the disease in addition to treating it.

77. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Example Treatment Regime Initial phase: 2 months of daily therapy with isoniazid, rifampin (Rifadin, Rimactane), pyrazinamide (PZA) and ethambutol (Myambutol). If laboratory test results show that the strain is sensitive to the first three drugs, ethambutol is dropped from the regimen.

78. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Example Treatment Regime Continuation phase: 4 months of therapy with isoniazid and rifampin, 2 to 3 times per week.

79. Copyright ©2011 by Pearson Education, Inc. All rights reserved. Core Concepts in Pharmacology, Third Edition Holland Adams Concept Review 25.3 How does drug therapy of tuberculosis differ from that of conventional anti- infective chemotherapy? What are the rationales for these differences?