Antifungal drugs Flashcards
(31 cards)
What anti fungal drug is effective for most serious systemic mycoses?
Amphotericin B*
MOA of Amphotericin B*
lipophilic; binds ergosterol in fungal membranes, producing membrane instability/leakage
Is Amphotericin B* absorbed in the GI tract?
NO; oral administration only effective on fungi in GI lumen
What is important for renal toxicity
Daily dose, total cumulative dose
Explain the toxicity of Amphotericin B*
- Fever, nausea, vomiting, headache, chills
- Hypotension, hypokalemia, tachypnea
- 90% will show nonpermanent nephrotoxicity; permanent renal damage can occur, which is related to total drug dose
- Reversible hyopochromic, normocytic anemia
What is used for serious infections due to Candida, Cryptococcus?
Flucytosine*
What is Flucytosine* use with
amphotericin* (synergistic)
MOA of Flucytosine*
contain a cytosine deaminase that converts 5-FC to 5-FU, and 5-FU then block nucleic acid synthesis(???)
Toxicity of Flucytosine*
- Nausea, vomiting, diarrhea, enterocolitis
- Leukopenia, thrombocytopenia
- Reversible elevated hepatic enzymes
- Extreme caution w/ patients w/ renal insufficiency or bone marrow depression
What are the imidazole and triazoles used for serious fungal infections
fluconazole*
itraconazole*
voriconazole*
MOA of imidazoles and triazoles
inhibit sterol 14alpha-sterol demethylase (a fungal cytochrome P450); this blocks the conversion of lanosterol to ergosterol, which deprives the membranes of ergosterol
What is fluconazole* used for
Cryptococcus meningitis, some Candida
What is itraconazole* used for
Blastomyces, Histoplasma, Candida (esophogeal and oropharyngeal)
What is Voriconazole* used for
invasive Aspergillus, Fusarium, Scedosproium
Level of CNS penetration of the imidazoles and triazoles
- fluconazole* – excelent
- itraconazole* – none
- voriconazole – thought to be some
Elimination of imidazoles and triazoles
- fluconazole* – excreted unchanged in urine
- itraconazole, vorivonazole – metabolized by liver
General side effect of imidazoles and triazoles
- Nausea, vomiting, rash, diarrhea, headache
- hepatotoxicity (fluconazole* – lowest incidence)
- discontinue if signs of liver dysfunction appear
- inhibits metabolism of several drugs
Specific side effect of itraconazole*
contraindicated w/ several drugs that inhibit CYP3A4
Specific side effect of voriconazole*
visual disturbances
What is Caspofungin* used for
Treatment of invasive Aspergillus in patients intolerant of/refractory to other drugs and also Candida
MOA of Caspofungin*
inhibits fungal cell wall synthesis by non-competitively blocking synthesis of beta(1,3)-D-glucan
Toxicity of Caspofungin*
- fever, nausea/vomiting
2. phlebitis at injection site
What drugs are used for the treatment of superficial candida infections
Fluconazole, Miconazole, Clotrimazole, Itraconazole, Nystatin*, Amphotericin B
Toxicity of Clotrimazole*
In oral form, may cause abnormal liver function tests
