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Flashcards in AntiFungals Deck (51)
1

General on Fungi

Fungi are generally resistant to antibacterial drugs
Most antifungal drugs are relatively toxic
Only a few substances are effective against pathogenic fungi
Many fungal infections occur in poorly vascularized or avascular skin, nails, hair; treatment presents problems in adequate distribution and retention of therapeutic agents

2

A. Systemic
1. Seen in what type of pts
2. Geographically localized — you see:
3. May be life-threatening

Debilitated or immuno-compromised pts
Blastomyces, Histoplasma, Coccidioides, Sporothrix

3

Supericial fungal infections:
Dermatophytic — (3 of them)
Mucous membranes — (1)

Trichophyton, Microsporum, Epidermophyton

candida

4

Effective (broad-spectrum agent) for most serious systemic mycoses - effective against Candida, Histoplasma, Cryptococcus, Coccidioides, Rhodotorula,
Blastomyces, Paracoccidioides, Sporothrix, Cladosporium, Phialophora,
Torulopsis

Amphotericin B

5

Amphotericin B has variable effectiveness on

Aspergillus, Mucor, Rhizopus, Fusarium

6

Amphotericin B is_______ at serum levels; only drug available for many infections

Fungistatic

7

Amphotericin B only use for proven or highly suspected systemic infections becauase:

Due to side effects

8

Prevent relapses of Histoplasma or Cryptococcus in AIDS patients

Amphotericin B

9

lipophilic;
binds ergosterol = membrane instability

Amphoterecin B

10

Mech of Amphotericin B

lipophilic... binds ergosterol in cell mmebrane of fungus = creates instability

11

Amphotericin B is very_______; binds________ in fungal membranes producing membrane instability/leakage; fungi that lack, or have decreased levels of, ergosterol are resistant

lipophilic
ergosterol

12

Amphotericin route of administration

IV for 6-12 weeks
or intrathecal or oral

13

Absorption of Amphotericin
(what about GI and CSF)

Not good through GI thus effective for GI fungual infection
no CSF penetration

14

Daily dose and ________ is important for renal toxicity of Amphotericin

Total Cumulative Dose

15

Toxicity of amphotericin B:
is Bad for your BBBBUN

(high BUN) Amphotericine B is Bad for your BBBBBUn
- 90% will show nonpermanent nephrotoxicity;
- Hypotension, hypokalemia, tachypnea

16

(high BUN)
- 90% will show nonpermanent nephrotoxicity;
- Hypotension, hypokalemia, tachypnea

Caused by amphotericin B

17

On Amphotericin B, 90% will show nonpermanent nephrotoxicity; enhances toxicity of other renally
excreted drugs (e.g. flucytosine); l

lowers GFR (reversible/permanent renal damage)
-dt total drug dose, monitor BUN

18

Reversible hypochromic, normocytic anemia Thrombophlebitis can occur with IV administration

anemias caused by Amphotericin B

19

Serious infections due to Candida, Cryptococcus, Torulopsis, chromomycosis septicemia, endocarditis, meningitis, urinary and pulmonary infections

Flucytosine

20

Flucytosine is used for:

Used in conjunction (synergistic) with amphotericin

21

Mechanism of Flucytosine:

fungi contain a cytosine deaminase not found in humans which converts 5- FC to 5-FU — metabolites of 5-FU then block nucleic acid synthesis

22

Resistance to Flucytosine

mutants which lack cytosine deaminase

23

cytosine deaminase not found in humans which converts 5- FC to 5-FU — metabolites of 5-FU then block nucleic acid synthesis;

Mech of flucytosine

24

Administration of Flucytosine

Oral capsules,
Give with Amp B to lower dose of Amph B needed

25

Metabolism of Flucytosine

Metabolism / excretion: 90% excreted unchanged in urine

26

Side Effects of Flucytosine

Leukopenia, thrombocytopenia (potentially fatal) and fucks with liver
BE CAREFUL for someone with bone marrow depression or renal insufficient

27

List of imidazoles and triazoles for serious fungal infections

fluconazole
itraconazole
voriconazole

28

Mechanism of action of imidazoles and triazoles

inhibit sterol 14α-sterol demethylase (a fungal cytochrome P450);
this blocks lanosterol to ergosterol;
usually fungistatic

29

Imidazoles and triazoles mechanism:
inhibits _________ which is a cytochrome P450 to bock converstion of lanosterol to ergosterol

14α-sterol demethylase

30

Imdiazole/triazole used for
• Cryptococcus meningitis
• some Candida (oropharyngeal, esophageal, vaginal, and systemic)
• some Candida albicans and glabrata are resistant
• Candida krusei is intrinsically resistant
• Coccidioides meningiti

Fluconazole

31

Fluconazole use

• Cryptococcus meningitis
• some Candida (oropharyngeal, esophageal, vaginal, and systemic)
• some Candida albicans and glabrata are resistant
• Candida krusei is intrinsically resistant
• Coccidioides meningitis

32

• Blastomyces (pulmonary and extrapulmonary)
• Histoplasma (pulmonary and disseminated, non-meningeal)
• Candida, esophageal and oropharyngeal
• refractory Aspergillus

Itraconazole

33

Itraconazole used to tx

• Blastomyces (pulmonary and extrapulmonary)
• Histoplasma (pulmonary and disseminated, non-meningeal)
• Candida, esophageal and oropharyngeal
• refractory Aspergillus

34

invasive Aspergillus (fungicidal), Fusarium, Scedosporium
for Candida at several sites; extended Candida spectrum includes
glabrata and krusei

Voriconazole

35

Voriconazole used for

invasive Aspergillus (fungicidal), Fusarium, Scedosporium
Candida at several sites; extended Candida spectrum includes
glabrata and krusei

36

Administration of the imdiazole/triazoles

oral or IV (oral common for fluconazole)

37

which imdiazoles/triazoles penetrate the CSF

fluconazole

38

Elimination of fluconazole

• fluconazole excreted unchanged in urine

39

Elimiations of itraconazole and voriconazole

metabolized by the liver

40

Some side effects common to fluconazole, itraconazole, voriconazole

hepatotoxicity, usually mild, but some fatalities (fluconazole has lowest incidence)
- Discontinue if signs of liver dysfunction appear
- Inhibits metabolism of several drugs

41

Which imdiazole has the lowest hepatotoxic side effect

fluconazole

42

contraindicated with several drugs that inhibit CYP3A4 (cisapride, quinidine, oral midazolam, triazolam, lovastatin, others)

itraconazole

43

Itraconazoles specific sides

contraindicated with several drugs that inhibit CYP3A4 (cisapride, quinidine, oral midazolam, triazolam, lovastatin, others)

44

visual disturbances, photosensitive rash; contraindicated with St. John's
Wort (a P450 inducer)

voriconazole

45

Voriconazole causes what side effects

visual disturbances, photosensitive rash; contraindicated w/ st.johns

46

Uses for invasive Aspergillus in patients intolerant of/refractory to other drugs
Candida, esophageal and systemic (peritoneal, pleural, blood)

Caspofungin

47

Capsofungin is used for

invasive aspergillus in pts that can't use other drugs or Candida, esophageal and systemic

48

inhibits fungal cell wall synthesis
non-competitively blocking synthesis of β(1,3)-D-glucan; eventually results in cell lysis

Caspofungin

49

Mechanism of Capsofungin

inhibits fungal cell wall synthesis by non-competitively blocking synthesis of β(1,3)-D-
glucan

50

Toxicity: well tolderated
- phlebitis at injection site
- Pulmonary edema

Capsofungin

51

Toxicity of Capsofungin

IG well tolerated, fever and nausea/vomitting and rash, phlebitis at injection site and pulmonary edema