1. Fungal Basics and Antifungals Slackers Facts by Mike Ori

2. Disclaimer The information represents my understanding only so errors and omissions are probably rampant. It has not been vetted or reviewed by faculty. The source is our class notes. The document can mostly be used forward and backward. I tried to mark questionable stuff with (?). If you want it to look pretty, steal some crayons and go to town. Finally… If you’re a gunner, buck up and do your own work.

3. What are the two forms a fungus can take?

4. Yeast Mould

5. What is a hypha

6. A fungal filament (Sherris)

7. What is a mould

8. An intertwining network of hyphae

9. What is a yeast

10. A smooth colony of fungi that resembles a bacterial colony. Hyphal forms are not present.

11. What is a conidia

12. Asexual fungal reproductive spore-like bodies

13. What are spores

14. Sexually produced reproductive elements.

15. What is the characteristic of all dimorphic fungi?

16. They change from yeast to moulds depending on the environmental conditions.

17. What is the ploidy of the average fungi?

18. Haploid

19. When is a fungi diploid

20. During the sexual state which usually occurs during times of stress.

21. What are the common forms of asexual reproduction

22. Budding Fragmentation Sporulation

23. What is the imperfect state

24. The haploid/asexual state

25. What is the sexual/diploid state referred to as?

26. Perfect

27. What is an anamorph

28. The asexual morphology

29. What is the sexual morphology referred to as?

30. Teleomorph

31. Where do most medically important fungi reside

32. The environment

33. What fungi is part of the normal flora

34. Candida

35. What organic compounds are associated with fungi?

36. High organic nitrogen

37. Which fungi is likely to cause an allergic reaction

38. Apergillis

39. Why are fungi more difficult to treat then bacteria? (i.e. why are there fewer drugs)

40. Fungi are eukaryotic and hence are more closely related to mammalian cells. This substantially increases the risk of toxicity from antifungals.

41. What unique cellular compounds are found in fungi?

42. Ergosterol (instead of cholesterol?) (plasma membrane) Chitin (cell wall) Glucans (cell wall) Mannoproteins (cell wall)

43. What is the principal target for antifungals?

44. Principally ergosterol (polyene) and its synthesis (azoles). Other unique compounds are also targeted but these are the big hitters.

45. List the common polyene antifungals

46. Amphotericin B Nystatin (Oral)

47. What is the mechanism of action of polyene antimicrobials?

48. Interacts with ergosterol to form pores in the plasma membrane that allow electrolytes (K+) to leak from the cell.

49. What is amphotericin’s solubility

50. It is insoluble

51. What preparations of amphotericin are available?

52. IV Preparations that increase its solubility. 1. Sodium deoxycholate suspension 2. Lipid formulations

53. What are the kinetics of amphotericin B?

54. It accumulates in and is released by the peripheral tissues. Its T ½ is therefore variable.

55. What is Amphotericin’s principal systemic toxicity

56. Sodium deoxycholate suspensions are nephrotoxic. Lipid preparations are less nephrotoxic.

57. What symptoms might your patient experience during Amphotericin infusion?

58. Fever Chills Phlebitis (DVT) Arrhythmia

59. What polyene would you prescribe for thrush?

60. Nystatin (swish and swallow)

61. What is the mechanism of action of azoles?

62. Interfere with the synthesis of ergosterol.

63. What are the two classes of azoles?

64. Imidazoles – two nitrogens Triazoles – three nitrogens

65. Which class of azoles is most commonly used

66. Triazoles

67. Describe the kinetics and bioavailability of azoles

68. Varies depending on the individual compound. Physically larger compounds have lower bioavailability.

69. Describe the azoles impact on the cytochrome system

70. Both metabolized by and an inhibitor of the cytochrome p450 system particularly of CYP3A4.

71. List the azoles and their class

72. DrugClass KetoconazoleImidazole FluconazoleTriazole ItraconazoleTriazole PosaconazoleTriazole VoriconazoleTriazole

73. Whats Russian for someone who’s a jerk?

74. Whatanazole

75. Azole resistance basis

76. Ca dependent efflux pumps

77. Azole target fungi

78. Dimorphic fungi Candida Cryptococcus

79. Echinocandin mechanism

80. Block the formation of B-1,3-glucan

81. What are the target fungi for echinocandins

82. Candida Aspergillus Ineffective against dimorphic fungi

83. List the echinocandins

84. Caspofungin Micafungin Anidulofungin

85. Terbinafine mechanism

86. Inhibits squalene epoxidase, an ergosterol precursor

87. Terbinafine target fungi

88. Dermatophytes

89. Flucytosine mechanism

90. Deamination to the uracil analog 5-fluorouracil thus interfering with RNA synthesis. 5-FU also inhibits thymidylate synthase to interfere with DNA synthesis.

91. Flucytosine resistance caveats

92. Resistance rapidly emerges so it must be used in combination

93. Flucytosine target fungi

94. Candida Crytococcus

95. Flucytosine toxicity

96. Metabolite (5-FU) is a uracil analog that is toxic to human cells and damages rapidly dividing cells. NOTE: 5-FU is a cancer chemotherapeutic.

97. Griseofulvin mechanism

98. Interferes with microtubule formation by binding tubulin.

99. Nikkomycin Z mechanism and notes

100. Inhibits chitin synthesis. Orphaned drug. (Seems prime for a social question.) Phase I/II trial underway for coccidiodal pneumonia.