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Flashcards in Antifungal drugs Deck (50):
1

Cutaneous mycoses - types

1. tinea capitis (dermatophytoses)
2. tinea corporis (dermatophytoses)
3. tinea cruris (dermatophytoses)
4. tinea pedis (dermatophytoses)
5. tinea unguium (dermatophytoses)
6. Tinea versicolor

2

fungal cell - erogsterol synthesis - pathway and enzymes

Squalene --> Squalene epoxide (Squalene epoxidase)(LANOSTEROL SYNTHESIS)
Squalene epoxide --> Lanosterol
Lanosterol --> Ergosterol (14-α-demethylase)
ertosterol --> cell membrane

3

fungal cell - cell ergosterol synthesis - pathway and enzymes - lanosterol synthesis

Squalene --> Squalene epoxide (Squalene epoxidase) --> Lanosterol

4

fungal cell - ergosterol synthesis - pathway and enzymes - Ergosterol synthesis

Lanosterol --> Ergosterol (14-α-demethylase)

5

drugs that interrupt cell ergosterol synthesis pathway in fungus (and enzymes affected)

1. Terbinafine block Squalene epoxidase (Lanosterol synthesis)
2. Azoles blocks 14-α-deamethylase (Cytochrome P-450 that converts lanesterol to ergosterol) (Ergosterol syntehsis)

6

Antifungul drugs - group according to action (not the names of the drugs)

1. Lanosterol synthesis inhibitor
2. Ergosterol synthesis inhibitor
3. Cell wall synthesis inhibitor
4. Nucleic acid synthesis inhibitor
5. Membrane pores formers
6. Griseofulvin

7

Membrane pores formers - drugs

polyenes
1. Amphotericin B
2. Nystatin

8

Membrane pores formers - drugs - and mechasnim of action

1. Amphotericin B 2. Nystatin
Binds to ergosterol (unique to fungi) --> membranes pores that allow leakage of electrolytes

9

Membrane pores former drugs - harmless for host cell - why

Because ergosterol is UNIQUE TO FUNGI

10

Amphotericin B - clinical use

1. SERIOUS SYSTEMIC MYCOTIC INFECTIONS : Histoplasmosis, Blastomycosis, Coccidioidomycosis, Mucor, Candida, Cryptococcus
2. Naegleria Fowleri
3. Leismania Donovani

11

Amphotericin B - meningitis

- with/without flucytosine for cryptococcal meningitis
- Intrathecally for fungal meningitis

12

Amphotericin B - administrate with (and why)

supplement K+ and Mg2+ because of altered renal tubule permeability

13

Amphotericin B - toxicity

1. fever/chills (shake and bake)
2. Hypotenesion
3. nephrotoxicity
4. arrhythmias
5. anemia
6. IV phlebitis

14

Amphotericin B - solution of toxicity

1. Hydration decreases nephrotoxicity
2. Liposomal amphotericin --> decreased toxicity

15

Nystatin - clinical use

TOPICAL USE ONLY (TOO TOXIC FOR SYSTEMIC USE)
1. oral candidiasis (swish and swallow)
2. topical for diaper rash or vaginal candidiasis

16

Antifungul drugs - Nucleic acid synthesis inhibitor

Flucytosine

17

Flucytosine - mechanism of action

Inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine deaminase --> inhibits thymidylate synthetase

18

Flucytosine - clinical use

Systemic fungal infections (esp meningitis caused by Cryptococcus) in combination with amphotericin B

19

Flucytosine - toxicity

Bone marrow suppression

20

Antifungul drugs - Ergosterol synthesis inhibitor - drugs

-AZOLE
clotrimazole, fluconazole, intraconazole, ketoconazole, miconazole, voriconazole

21

azoles - mechanism of action

inhibit fungal stero (ergosterol) synthesis by inhibiting the cytochrome P-450 enzyme that converts lanosterol to ergosterol (14-α-demethylase)

22

azoles - clinical use

Local and less serious systemic mycoses:
-Fluconazole: chronic suppression of cryptococcal meningitis in AIDS patients, all types of candidal infections, LOCAL systemic mycoses
- Intraconazole: (LOCAL systemic mycoses) Blastomyces, Coccidioides, Histoplasma
- Clotrimazole, miconazole: topical fungal infection

23

Fluconazole - clinical use

- chronic suppression of cryptococcal meningitis in AIDS patients,
- all types of candidal infections
- LOCAL systemic mycoses

24

Intraconazole - clinical use

(LOCAL systemic mycoses) Blastomyces, Coccidioides, Histoplasma

25

Clotrimazole, miconazole - clinical use

topical fungal infection

26

Azoles - toxicity

1. testosterone synthesis inhibition --> gynecomastia (esp ketoconazole)
2. liver dysfunction (inhibits P450)

27

fungus - Lanosterol synthesis inhibitor - drugs

Terbinafine

28

Terbinafine - mechanism of action

inhibits the fungal enzyme squalene epoxidase (Lanosterol synthesis inhibitor)

29

Terbinafine - clinical use

Dermathophytes (esp onychomycoses)

30

Terbinafine - toxicity

1. GI upset
2. headaches
3. hepatotoxicity
4. Taste disturbance

31

Antifungul drugs - Cell wall synthesis inhibitor - drugs

Echinocandins --> 1. Anidulafungin 2. caspofungin
3. micafungin

32

Echinocandins - drugs

1. Anidulafungin
2. caspofungin
3. micafungin

33

Echinocandins - drugs and mechanism of action

Echinocandins --> 1. Anidulafungin 2. caspofungin
3. micafungin
inhibit cell wall synthesis by inhibiting synthesis of β-glucan

34

Echinocandins - inhibit cell wall synthesis by inhibiting synthesis of

β-glucan

35

Echinocandins - clinical use

1. invasive aspergilosis
2. Candida

36

Echinocandins - drugs and toxicity

Echinocandins --> 1. Anidulafungin 2. caspofungin
3. micafungin
GI upset, flushing (by histamine release)

37

Griseofulvin - mechanism of action

interferes with microtubule formation --> disrupts mitosis
DEPOSITIS IN KERATIN-CONTAINING TISSUES (EG. NAILS)

38

Griseofulvin - clinical use

1. oral treatment of superficial infections
2. inhibits growth of dermatophytes (tinea, ringworm)

39

Griseofulvin - toxicity

1. teratogenic 2. carcinogenic 3. confusion 4. headaches 5. increased cytochrome P-450 and warfarin metabolism

40

Tinea versicolor - treatment

1. topical and/oral antifungul medication
2. selenium sulfate

41

Candida ablicans - treatment

topical azole for vagina
nystatin, fluconazole or caspofungin for oral/esophageal
caspofungin, fluconazole or amphotericin B for systemic

42

Mucormycosis treatment

1. surgical debridement
2. amphotericin B

43

Pneumocystis jirevecii - Treatment/prophylaxis/start prophylaxis when

1. TMP-SMX
2. Pentamidine
3. dapsone (only prophylaxis)
4. atovaquone
CD4 cound drops under 2 hundred cells/mm3 in HIV patients

44

Sporothrix schenckii - treatment

intraconazole or potassium iodide

45

terbinafine - toxicity

1. GI upset
2. headaches
3. hepatotoxicity
4. Taste disturbance

46

Echinocandins - drugs and toxicity

Echinocandins --> 1. Anidulafungin 2. caspofungin
3. micafungin
GI upset, flushing (by histamine release)

47

griseofulvin - toxicity

1. teratogenic 2. carcinogenic 3. confusion 4. headaches 5. increased cytochrome P-450 and warfarin metabolism

48

invasive aspergilosis - treatment

echinocandins

49

antifungal drugs - P450

Griseofulvin --> induces
Azoles --> inhibits

50

antimycobacterial drgus - P450

Rifampin --> induces
isoniazid --> inhibits