Antifungals Flashcards
(77 cards)
1
Q
What is the MOA of echinocandins?
A
inhibit synthesis of 1,3-ß-D-glucan, an essential component of the fungal cell wall that is not in mammalian cells (inhibits CELL WALL synthesis)
2
Q
What is the MOA of polyene anti fungal agents?
A
bind to ergosterol in fungal membranes, which increases permeability
3
Q
What is the MOA of imidazole & Triazole antifungals?
A
inhibits the synthesis of ergosterol, an essential component of the fungal cytoplasmic membrane by inhibiting fungal CYP450s enzymes and fungal 14-alpha-demethylase
4
Q
What is the MOA of allylamines?
A
inhibits squalene epoxidase and therefore inhibits synthesis of ergosterol in fungal cell membrane
5
Q
What is the MOA of Griseofulvin?
A
inhibits fungal mitosis by binding to microtubules, the structures the form the mitotic spindle; this only affects fungi that are actively growing
6
Q
What is the MOA of Flucytosine?
A
pretends to be a necessary building block of 5-FU, which inhibits DNA & RNA synthesis of fungi
7
Q
[SATA] Which of the following can be administered parenterally? A. Echocandins B. Fluconazole C. Amphotericin B D. Clotrimazole
A
A, B, C
8
Q
[SATA] Which of the following are used systemically for more invasive fungal infections? A. Nystatin B. Amphotericin B C. Ketoconazole D. Flucytosine
A
B, C, D
9
Q
Which class of azole antifungals are mostly administered topically?
A
Imidazoles
10
Q
Which imidazole anti fungal is administered orally?
A
Ketoconazole
11
Q
Which triazole antifungal is only administered topically? A. Voriconazole B. Posaconazole C. Terconazole D. Itraconazole
A
C. Terconazole
12
Q
Which antifungal should you discontinue if the patient has symptoms of HF? A. Voriconazole B. Posaconazole C. Terconazole D. Itraconazole
A
D. Itraconazole
13
Q
[SATA] Which antifungals treat oropharyngeal candidiasis (oral thrush)? A. Fluconazole B. Posaconazole C. Luliconazole D. Caspofungin
A
A, B
14
Q
[SATA] Which of the following treats vaginal fungal infections? A. Butoconazole B. Clotrimazole C. Miconazole D. Tioconazole
A
A, B, C, D
15
Q
[SATA] Which of the following treats vaginal fungal infections? A. Fluconazole B. Posaconazole C. Terconazole D. Irtraconazole
A
A, C
16
Q
Which hepatic enzymes does ketoconazole inhibit?
A
Inhibits CYP2C9, 2C19, 3A4
17
Q
Which enzymes does Fluconazole inhibit?
A
Inhibits CYP2C9, 2C19, 3A4
18
Q
Is fluconazole a CYP substrate?
A
NO
19
Q
What do allylamines mostly treat?
A
nail bed infections
20
Q
What is added to griseofulvin to increase solubility?
A
PEG
21
Q
Which anti fungal can cause bone marrow suppression?
A
flucytosine
22
Q
What are some ADRs of flucytosine?
A
Bone Marrow Suppression
Renal Function Impairment
Photosensitivity
Nephrotoxic
23
Q
Which antifungals cause infusion reactions?
A
Echinocandins Amphotericin B (Polyene Antifungal)
24
Q
How is the infusion reaction mediated in echinocandins?
A
histamine
25
How is the infusion reaction mediated in amphotericin B?
release of pro inflammatory cytokines
26
Which antifungals are hepatotoxic?
echinocandins
| most azole antifungals (especially ketoconazole)
27
Which antifungals are nephrotoxic?
Amphotericin B
Amphotericin B Lipid based
Flucytosine
28
When are azole antifungals fungistatic?
at low concentrations
29
When are azole antifungals fungicidal?
at high concentrations
30
Describe the benefit of the lipid formulation of amphotericin.
LOWER toxicity:
•Lower incidence of infusion reaction
•except amphotec
•Lower incidence of nephrotoxicity
LOWER Cmax (except AmBisome)
31
Which type of antifungals inhibits human CYP450s?
Azole Antifungals
32
Drug concerns for azole antifungals:
```
• QT prolongation may occur
• Most are CYP substrates
o Not fluconazole (renally cleared)
• Some are enzyme inhibitors
• For some, oral absorption is affected by gastric pH
• Most are hepatotoxic
```
33
How long should you separate azole antifungals from antacids?
2 hours
34
When should you give an H2 antagonist or PPI when on an azole antifungal?
Take H2 Antagonist or PPI 1-2 hours BEFORE azole antifungal
35
Posaconazole inhibits which hepatic enzyme?
3A4
36
Itraconazole inhibits which hepatic enzyme?
3A4
37
Miconazole inhibits which hepatic enzyme?
2C19
38
```
2. [SATA] Which of the following antifungals are administered systemically to treat more invasive opportunistic fungal infections generally seen in immunocompromised patients?
A. Nystatin
B. Polymyxin B
C. Amphotericin B
D. Fluconazole
E. Ketoconazole
F. Flucytosine
```
C, E, F
39
```
3. [SATA] Which of the following antifungals are administered locally to treat less serious fungal infections?
A. Nystatin
B. Polymyxin B
C. Luliconazole
D. Fluconazole
E. Miconazole
F. Echinocandins
```
A, C, E
40
```
4. Which of the following antifungals are NOT administered parenterally?
A. Echinocandins
B. Fluconazole
C. Amphotericin B Lipid based
D. Terconazole
E. Posaconazole
```
A, B
41
```
5. [SATA] Which antifungals cause infusion reactions?
A. Echinocandins
B. Fluconazole
C. Amphotericin B
D. Terconazole
```
A, C
42
6. True or false. The infusion reaction caused by Echinocandins is mediated by release of proinflammatory cytokines.
False
43
7. Which antifungals are hepatotoxic?
• Echinocandins
• Most azole antifungals
o Ketoconazole
44
8. Which antifungals are nephrotoxic?
* Amphotericin B
* Amphotericin B Lipid Based (less likely)
* Flucytosine
45
9. Azole antifungals are ______________ at low conc. & ________________ at high conc.
fungistatic, fungicidal
46
10. Describe the benefit of the lipid formulation of amphotericin
Decreases systemic toxicity
47
12. List the azole antifungals that are systemically administered.
Imidazole: ketoconazole
Triazole: fluconazole, Itraconazole, posaconazole, terconazole, voriconazole
48
13. What is the primary indication of Butoconazole, Clotrimazole, Miconazole, Tioconazole, and Terconazole?
vaginal fungal infections
49
15. What is the primary indication of Luliconazole and Itraconazole?
Nail bed infections
50
16. What is the primary indication of fluconazole?
o Treat oropharyngeal candidiasis (oral thrush)
| o Treats vaginal candidiasis
51
17. What are two indications for posaconazole?
o Treat oropharyngeal candidiasis (oral thrush)
| o Treats prophylaxis of invasive fungal infections
52
18. True or false? Triazole antifungals are mostly systemic and treat more serious infections.
True
53
19. What is the effect of hepatic enzyme inhibition on azole antifungals?
o Increases blood levels
o Increases risk of toxicity
o Decreases clearance
54
20. What classes of drugs have a drug interaction with azole antifungals, which can reduce the oral absorption of azole antifungals? Which azole antifungals are affected?
Azole antifungals require acidic gastric environment to dissolve (except fluconazole) therefore, H2 Antagonists, Proton Pump Inhibitors and Antacids interact with the oral absorption of azole antifungals by decreasing its effect. If you must administer both drugs, be sure to separate administration of antacids by 2 hours or to administer the azole antifungal 1-2 hours prior to H2 antagonist or PPI.
55
23. Which antifungal suppresses bone marrow? What is the consequence of this suppression?
Flucytosine
56
25. List the 3 echocandins.
Andidulafungin (Eraxis), Caspofungin, Micafungin (Mycamine)
57
26. Are Echocandins parenteral? Oral?
parenteral
58
27. What are the ADRs of echinocandins?
hepatotoxic, infusion reaction (mediated by histamine)
59
28. What are the 3 polyene antifungals?
Amphotericin B, Amphotericin B lipid based, Nystatin
60
29. When are polyene antifungals used? Which one treats serious infections? Which one treats everyday infections? Route of administration?
Systemically treats serious invasive fungal infections
| Topically treats less serious fungal infections
61
30. What aspect of the human physiology do polyene antifungals affect that results in toxicity?
Has toxicity b/c it also binds to cholesterol in human cells
62
31. What are the ADRs of Amphotericin B?
Infusion reaction
High incidence of phlebitis
Nephrotoxic
63
32. How can you treat/reduce symptoms of the infusion reaction due to Amphotericin B?
o May reduce symptoms if you pretreat with Benadryl + ASA or Tylenol
o Can treat rigors by giving meperidine or dantrolene
o Give hydrocortisone for fever and chills
64
33. How can you treat/reduce symptoms of nephrotoxicity due to Amphotericin B?
minimize with 1L saline infusions
65
34. What should you monitor in pts on Amphotericin B?
Scr & K+
66
35. Compare and contrast Amphotericin B to Amphotericin B Lipid Based.
• LOWER toxicity
o Lower incidence of infusion reaction
• except amphotec
o Lower incidence of nephrotoxicity
• LOWER Cmax (except AmBisome)
• MORE expensive (20-50x more expensive)
67
36. What aspect of the human physiology do Azole antifungals affect that can result in toxicity?
Also inhibits human CYP450s
68
37. [SATA] Which of the following are drug concerns of azole antifungals?
A. some are CYP substrates and/or inhibitors
B. Possibility of QT prolongation
C. Some are affected by gastric pH
D. Nephrotoxicity
A, B, C,
| most are hepatotoxic, not nephrotoxic
69
38. Counsel a patient on when to effectively take an azole antifungal with a PPI.
Administer 1-2 hours prior to H2 antagonist or PPI
70
```
39. Which of the following does NOT inhibit CYP3A4?
A. Fluconazole
B. Posaconazole
C. Voriconazole
D. Tioconazole
```
D. Tioconazole
71
```
40. Which of the following does NOT inhibit CYP2C9?
A. Ketoconazole
B. Posaconazole
C. Fluconazole
D. Voriconazole
```
B. Posaconazole
72
```
41. [SATA] Which of the following inhibit CYP2C19?
A. Ketoconazole
B. Posaconazole
C. Fluconazole
D. Voriconazole
```
A, C, D
73
42. What are the ADRs of ketoconazole?
ADRS:
• Liver injury (hepatotoxicity)
• Adrenal insufficiency
• Drug interactions (heart problems)
74
43. Terbinafine, Butenafine, Naftifine are examples of ______________________.
Allylamines
75
44. What does the class of drugs in #43 primarily treat?
Nail infections
76
45. What does griseofulvin treat? Why does it take so long to work?
Treats ringworm infections and nail infections
| It takes a long time to work b/c it has to be deposited in cells of sin, hair and nails (long duration of therapy)
77
46. What are the ADRs of Flucytosine?
ADRs:
• Closely monitor hematologic renal and hepatic status of all pts
o Bone marrow suppression
oRenal function impairment
• Use with extreme caution in pts with renal impairment
• Photosensitivity
• Nephrotoxic
