1. CHEMOTHERAPY  Antimicrobial chemotherapy  Antiviral chemotherapy  Antiparasitic Drugs  Cancer Chemotherapy

2. CHEMOTHERAPY  Concepts easy to understand.  Many distinct diseases so less prototype drugs.

3. ANTIBIOTICS  General Principles  Mechanism of Action  Pharmacokinetics/Therapeutic Uses  Adverse effects

4. STUDY AIDS  Objectives  Summary tables

5. STUDY AIDS  Review questions on web: http://info.unmc.edu/scholarchemo1/ AntiBio/AntibioTestframe.htm

6. STUDY AIDS   http://dev1.unmc.edu/JeopardyGame/A ntibiotics.htm http://dev1.unmc.edu/JeopardyGame/A ntibiotics.htm   http://dev1.unmc.edu/JeopardyGame/A ntibioticsDouble.htm http://dev1.unmc.edu/JeopardyGame/A ntibioticsDouble.htm

7. ANTIMICROBIAL CHEMOTHERAPY  Selective Toxicity

8. CHEMOTHERAPY  Allows the normal host- defense mechanisms to gain control.

9. Chemotherapy of Infectious Disease Goal-Assist the body in getting rid of the infecting organism Goal-Assist the body in getting rid of the infecting organism

10. CLASSIFICATION OF CHEMOTHERAPEUTIC AGENTS

11. Time Number of bacteria Control Bacteriostatic agent Bactericidal agent

12. BACTERIOSTATIC DRUGS  Sulfonamides  Erythromycin  Tetracyclines

13. BACTERICIDAL DRUGS  Trimethoprim +Sulfamethoxazole  Aminoglycosides  β-lactams

14. T Antimetabolites Cell Wall Synthesis Inhibit Protein Synthesis Nucleic acid synthesis XXXX Cell membrane Permeability

15. Range of Microorganisms inhibited  Narrow Spectrum  Broad Spectrum  Extended Spectrum

16. SOURCE OF DRUG  Antibiotics-natural substances produced by microorganisms.  Synthetics  Semisynthetics

17. CHOICE OF THE ANTIBIOTIC  First determine etiology of the infection.

18. CHOICE OF THE ANTIBIOTIC  Sensitivity pattern of the infecting organism must be determined.  Successful therapy depends on achieving inhibitory or bactericidal concentrations at the site of infection with minimal toxicity. Consider pharmacokinetics and host factors. Consider pharmacokinetics and host factors.

19. CHOICE OF THE ANTIBIOTIC  Sensitivity pattern of the infecting organism must be determined. Consider pharmacokinetics and host factors. Consider pharmacokinetics and host factors.

20. PHARMACOKINETIC FACTORS  Location of Infection.  Route of Administration.  Pattern of excretion, metabolism, and degree of protein binding.

21. HOST FACTORS  Host defense (Immunocompetence).  Local factors.  Age.  Genetic factors.  Drug Allergy.

22. HOST FACTORS  Renal disease and liver disease.  AIDS  Pregnancy.

23. USES OF ANTIBIOTICS  Empirical antimicrobial therapy- before the pathogen is known.  Infections with known etiology.

24. MISUSES OF ANTIBIOTICS  Treatment of nonresponsive infections.  Therapy of fever of unknown origin  Fever of short duration  Fever persisting for 2 or more weeks.

25. MISUSES OF ANTIBIOTICS  Dosing errors  Wrong frequency  Excessive or subtherapeutic doses

26. MISUSES OF ANTIBIOTICS  Inappropriate reliance on chemotherapy alone (e.g. abscesses).

27. MISUSES OF ANTIBIOTICS  Lack of adequate bacteriological information. Absence of supporting dataAbsence of supporting data Agents selected by habitAgents selected by habit Doses are routine, rather than individualizedDoses are routine, rather than individualized

28. COMBINATION CHEMOTHERAPY  Separate but simultaneous administration.

29. Combination Chemotherapy- Advantages  Treatment of polymicrobial infections.  Prevent or delay resistance.  Synergy.

30. Combination Chemotherapy- Advantages  Severe infections of unknown etiology-empirical therapy.

31. DISADVANTAGES  Increased risk of toxicity.  Increased likelihood of superinfections.  Increased cost.  Antagonism of an antibacterial effect.

32. FIXED DOSE COMBINATIONS  Ratio and dose of antibiotics are determined based on in vitro studies.  Encourages inadequate treatment.

33. PROPHYLAXIS OF INFECTION  This should be used only in circumstances in which efficacy has been demonstrated and the benefits outweigh the risks.

34. PROPHYLAXIS OF INFECTION  Effective when a single drug is used to prevent infection from a specific microorganism.  In patients undergoing organ transplantation or receiving cancer chemotherapy.

35. PROPHYLAXIS OF INFECTION  Primary and 2ndary prevention of opportunistic infections in AIDS patients when CD4 counts are below certain threshholds.

36. PROPHYLAXIS OF INFECTION  Patients with valvular or other structural lesions of the heart who are undergoing dental, surgical or other procedures that produce a high incidence of bacteremia.

37. PROPHYLAXIS OF INFECTION  To prevent wound infections after various surgical procedures.

38. Complications of Antimicrobial Therapy  Drug Resistance  Superinfections  Toxicity

39. DRUG RESISTANCE  Involves a stable genetic change in the bacteria.

40. DRUG RESISTANCE  Mutation and selection with passage vertically.  Horizontal transfer from a donor cell by transduction, transformation or conjugation.

41. MUTATION-SELECTION  Occurs in many different genes.  Random events that confer a survival advantage when a drug is present.

42. CHROMOSOMAL MUTATIONS  Antibiotics are acting as selecting agents.

43. + Antibiotic

45. Resistant Population

46. HORIZONTAL GENE TRANSFER  Mobile genetic elements (plasmids, transposable elements, integrons, gene cassettes).  Transduction  Transformation

47. CONJUGATION Direct cell to cell contact through a sex pilus or bridge Direct cell to cell contact through a sex pilus or bridge Very important for the spread of resistance because multiple resistance genes can be transferred simultaneously. Very important for the spread of resistance because multiple resistance genes can be transferred simultaneously.

50. Enzyme Inactivation Altered Permeability Mod. of target site and reduced affinity

51. CROSS-RESISTANCE e.g. sulfonamides, penicillins

52. PREVENTION OR DELAY OF RESISTANCE  Judicious (appropriate) or careful use of antibiotics  Adequate Dosage  Combination Chemotherapy

56. SUPERINFECTIONS  A new infection appearing during the chemotherapy of a primary one.  Caused by removing inhibitory influence of the normal flora.

57. + Antibiotic (Broad spectrum)

58. Resistant pathogen

59. Secondary infection from resistant organisms

60. TREATMENT OF THE SUPERINFECTION  Stop present therapy.  Culture infected area.  Treat against the offending microorganism.

61. TOXICITY  Hypersensitivity  Direct Toxicity- GI