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Block 3 Pharm > AntiFungals > Flashcards

AntiFungals Flashcards

1
Q

General on Fungi

A

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

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2
Q

A. Systemic

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

Debilitated or immuno-compromised pts

Blastomyces, Histoplasma, Coccidioides, Sporothrix

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3
Q

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

A

Trichophyton, Microsporum, Epidermophyton

candida

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4
Q

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

A

Amphotericin B

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5
Q

Amphotericin B has variable effectiveness on

A

Aspergillus, Mucor, Rhizopus, Fusarium

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6
Q

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

A

Fungistatic

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7
Q

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

A

Due to side effects

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8
Q

Prevent relapses of Histoplasma or Cryptococcus in AIDS patients

A

Amphotericin B

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9
Q

lipophilic;

binds ergosterol = membrane instability

A

Amphoterecin B

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10
Q

Mech of Amphotericin B

A

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

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11
Q

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

A

lipophilic

ergosterol

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12
Q

Amphotericin route of administration

A

IV for 6-12 weeks

or intrathecal or oral

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13
Q

Absorption of Amphotericin

what about GI and CSF

A

Not good through GI thus effective for GI fungual infection

no CSF penetration

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14
Q

Daily dose and ________ is important for renal toxicity of Amphotericin

A

Total Cumulative Dose

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15
Q

Toxicity of amphotericin B:

is Bad for your BBBBUN

A

(high BUN) Amphotericine B is Bad for your BBBBBUn

  • 90% will show nonpermanent nephrotoxicity;
  • Hypotension, hypokalemia, tachypnea
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16
Q

(high BUN)

  • 90% will show nonpermanent nephrotoxicity;
  • Hypotension, hypokalemia, tachypnea
A

Caused by amphotericin B

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17
Q 
On Amphotericin B, 90% will show nonpermanent nephrotoxicity; enhances toxicity of other renally
excreted drugs (e.g. flucytosine); l
A 
lowers GFR (reversible/permanent renal damage)
-dt total drug dose, monitor BUN
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18
Q

Reversible hypochromic, normocytic anemia Thrombophlebitis can occur with IV administration

A

anemias caused by Amphotericin B

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19
Q

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

A

Flucytosine

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20
Q

Flucytosine is used for:

A

Used in conjunction (synergistic) with amphotericin

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21
Q

Mechanism of Flucytosine:

A

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
Q

Resistance to Flucytosine

A

mutants which lack cytosine deaminase

23
Q

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

A

Mech of flucytosine

24
Q

Administration of Flucytosine

A

Oral capsules,

Give with Amp B to lower dose of Amph B needed

25
Q

Metabolism of Flucytosine

A

Metabolism / excretion: 90% excreted unchanged in urine

26
Q

Side Effects of Flucytosine

A

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

27
Q

List of imidazoles and triazoles for serious fungal infections

A

fluconazole
itraconazole
voriconazole

28
Q

Mechanism of action of imidazoles and triazoles

A

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

29
Q

Imidazoles and triazoles mechanism:

inhibits _________ which is a cytochrome P450 to bock converstion of lanosterol to ergosterol

A

14α-sterol demethylase

30
Q

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

A

Fluconazole

31
Q

Fluconazole use

A
  • Cryptococcus meningitis
  • some Candida (oropharyngeal, esophageal, vaginal, and systemic)
  • some Candida albicans and glabrata are resistant
  • Candida krusei is intrinsically resistant
  • Coccidioides meningitis
32
Q
  • Blastomyces (pulmonary and extrapulmonary)
  • Histoplasma (pulmonary and disseminated, non-meningeal)
  • Candida, esophageal and oropharyngeal
  • refractory Aspergillus
A

Itraconazole

33
Q

Itraconazole used to tx

A
  • Blastomyces (pulmonary and extrapulmonary)
  • Histoplasma (pulmonary and disseminated, non-meningeal)
  • Candida, esophageal and oropharyngeal
  • refractory Aspergillus
34
Q

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

A

Voriconazole

35
Q

Voriconazole used for

A

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

36
Q

Administration of the imdiazole/triazoles

A

oral or IV (oral common for fluconazole)

37
Q

which imdiazoles/triazoles penetrate the CSF

A

fluconazole

38
Q

Elimination of fluconazole

A

• fluconazole excreted unchanged in urine

39
Q

Elimiations of itraconazole and voriconazole

A

metabolized by the liver

40
Q

Some side effects common to fluconazole, itraconazole, voriconazole

A

hepatotoxicity, usually mild, but some fatalities (fluconazole has lowest incidence)

  • Discontinue if signs of liver dysfunction appear
  • Inhibits metabolism of several drugs
41
Q

Which imdiazole has the lowest hepatotoxic side effect

A

fluconazole

42
Q

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

A

itraconazole

43
Q

Itraconazoles specific sides

A

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

44
Q

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

A

voriconazole

45
Q

Voriconazole causes what side effects

A

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

46
Q

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

A

Caspofungin

47
Q

Capsofungin is used for

A

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

48
Q

inhibits fungal cell wall synthesis

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

A

Caspofungin

49
Q

Mechanism of Capsofungin

A

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

50
Q

Toxicity: well tolderated

  • phlebitis at injection site
  • Pulmonary edema
A

Capsofungin

51
Q

Toxicity of Capsofungin

A

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

Block 3 Pharm (19 decks)

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