AntiFungals Flashcards
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
A. Systemic
- Seen in what type of pts
- Geographically localized — you see:
- May be life-threatening
Debilitated or immuno-compromised pts
Blastomyces, Histoplasma, Coccidioides, Sporothrix
Supericial fungal infections:
Dermatophytic — (3 of them)
Mucous membranes — (1)
Trichophyton, Microsporum, Epidermophyton
candida
Effective (broad-spectrum agent) for most serious systemic mycoses - effective against Candida, Histoplasma, Cryptococcus, Coccidioides, Rhodotorula,
Blastomyces, Paracoccidioides, Sporothrix, Cladosporium, Phialophora,
Torulopsis
Amphotericin B
Amphotericin B has variable effectiveness on
Aspergillus, Mucor, Rhizopus, Fusarium
Amphotericin B is_______ at serum levels; only drug available for many infections
Fungistatic
Amphotericin B only use for proven or highly suspected systemic infections becauase:
Due to side effects
Prevent relapses of Histoplasma or Cryptococcus in AIDS patients
Amphotericin B
lipophilic;
binds ergosterol = membrane instability
Amphoterecin B
Mech of Amphotericin B
lipophilic… binds ergosterol in cell mmebrane of fungus = creates instability
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
Amphotericin route of administration
IV for 6-12 weeks
or intrathecal or oral
Absorption of Amphotericin
what about GI and CSF
Not good through GI thus effective for GI fungual infection
no CSF penetration
Daily dose and ________ is important for renal toxicity of Amphotericin
Total Cumulative Dose
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
(high BUN)
- 90% will show nonpermanent nephrotoxicity;
- Hypotension, hypokalemia, tachypnea
Caused by amphotericin B
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
Reversible hypochromic, normocytic anemia Thrombophlebitis can occur with IV administration
anemias caused by Amphotericin B
Serious infections due to Candida, Cryptococcus, Torulopsis, chromomycosis septicemia, endocarditis, meningitis, urinary and pulmonary infections
Flucytosine
Flucytosine is used for:
Used in conjunction (synergistic) with amphotericin
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
Resistance to Flucytosine
mutants which lack cytosine deaminase
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
Administration of Flucytosine
Oral capsules,
Give with Amp B to lower dose of Amph B needed
