Antifungal Drugs Flashcards
Polyene antibiotics
Amphotericin B
Natamycin
Nystatin
Polyene antibiotics - MoA
Binds to ergosterol in cell membrane, increasing membrane permeability and leakage of cell contents
Amphotericin B - Clinical use
Systemic and subcutaneous mycoses
Superficial infections
Cryptococcal meningitis Candidiasis Coccidioidomycosis Aspergillosis Blastomycosis Histoplasmosis Mucormycosis Protozoa: leishmaniasis and amebic encephalitis
Amphotericin B - Adverse effects
Most toxic antibiotic today
Renal toxicity in 80%, it reduces the GFR and contributes to development of hypokalemia and hypomagnesemia
Azotemia (Accumulation of creatinine and urea in blood)
Acute liver failure Cardiac arrhythmias (Ventricular fibrillation)
Hematopoietic disorders (anemia, leukopenia, thrombocytopenia)
Amphotericin B - Contraindications
Contraindicated for patients with renal impairment (should use lipid formulations for these patients)
Amphotericin B - Special considerations
Electrolytes should be monitored weekly during treatment
Amphotericin B - Interactions
Cyclosporine, antineoplasics, thiazides, corticosteroids: increased hypokalemia
Natamycin - Clinical use
Superficial mycoses of skin & mucous membranes
Aspergillus
Candida
Fusarium
Penicillum
Opthalmic suspension for the treatment of fungal blepharitis, conjunctivitis, or keratitis
Nystatin - Clinical use
Superficial mycoses of skin & mucous membranes
Candida (mucocutaneous, intestinal, vaginal)
Diazole derivatives
Clotrimazole
Econazole
Ketoconazole
Diazole derivatives - MoA
Inhibits ergosterol synthesis
Clotrimazole - Clinical use
Candidia infection in mouth, throat, vagina, vulva
M. furfur infection in skin (tinea versicolor)
Dermatophyte infections (tinea pedis and tinea cruris) due to epidermophyton, microsporum, trichophyton sp.
Econazole - Clinical use
Candidia and dermatophyte infections of skin
Ketoconazole - Clinical use
Seborrheic dermatitis
Inoperable cushing syndrome
Once-daily dose for chronic mucocutanous candidiasis
Diazole derivatives - Adverse effects
Systemic administration can cause: Skin rash Elevated liver enzyme levels Hepatic injury Hematopoietic toxicity GI distress
Azole derivatives - Interactions
Inhibits CYP3A4: inhibited metabolism of HMG-CoA reductase inhibitors, benzodiazepines, quinidine, warfarin
Triazole derivatives
Fluconazole Itraconazole Posaconazole Voriconazole Isavuconazonium Efinaconazole
Triazole derivative - MoA
Inhibition of ergosterol synthesis
Triazole derivates - Adverse effects
Systemic administration can cause: Skin rash Elevated liver enzyme levels Hepatic injury Hematopoietic toxicity GI distress
Fluconazole - Clinical use
Prevention of cryptococcal meninitis in patients with AIDS, and a follow-up therapy in patients successfully treated with amphotericin B to prevent relapse
Coccidioidal meningitis
Mucocutaneous (oropharyngeal and esophageal) and disseminated candidiasis such as endocardial candidiasis
UTIs by Candida
Vaginal candidiasis (single dose) Inoperable cushing syndrome
Fluconazole - Contraindications
Contraindicated during first trimester of pregnancy because of increased risk of birth defects
Fluconazole - Special considerations
Only one that penetrates CSF well enough and for this reason, only fluconazole is used in the prophylaxis and treatment of fungal meningitis
Itraconazole - Clinical use
Blastomycosis Histoplasmosis Onychomycosis (fungal infections of the nails) Candidiasis Coccidioidomycosis Psuedallesheriasis Sporotrichosis
Which drug is contraindicated for treatment of onychomyscosis in patients with ventricular dysfunction?
Itraconazole
Posaconazole - Clinical use
Enhanced act against Aspergillus and Candidia
Mucormycosis
Fusarium and zygomycetes such as Rhizopus and Mucor species
Voriconazole - Clinical use
Enhanced act against Aspergillus and Candidia
Esophageal and invasive candidiasis
Cryptococcus, Fusarium, Coccidioides, Pseudallescheria
Voriconazole - Adverse effects
Visual disturbances such as altered perception of light, abnormally colored vision (chromatopsia), and photophobia
Elevated serum levels of hepatic enzymes (enzymes should be monitored during treatment)
Isavuconazonium - Clinical use
Enhanced activity against Aspergillus and Candida
Fusarium and zygomycetes such as Rhizopus and Mucor species
Efinaconazole - Clinical use
Topical treatment of onychomycosis
Allylamines
Naftifine
Terbinafine
Allylamines - MoA
Inhibition of ergosterol synthesis
Allylamines - Clinical use
Superficial dermatophyte infections.
Fungostatic for Candidia
Onychomycosis (Terbinafine)
Echinocandin drugs
Caspofungin
Micafungin
Anidulafungin
Echinocandin drugs - MoA
Inhibits fungal cell wall synthesis (noncompetitive inhibition of beta-1-3 glucan synthaze)
Caspofungin - Clinical use
Candida, Aspergillus
Candida strains resistant to azole compounds
Esophageal, oropharyngeal, and invasive candidiasis
Micafungin, Anidulafungin - Clinical use
Prophylaxis and treatment of candidiasis and invasive aspergillosis
Fluorinated pyrimidine analogue
Flucytosine
Flucytosine - MoA
Is incorporated into fungal RNA, interfering protein synthesis
Flucytosine - Clinical use
Severe fungal infection in combination with amphotericin B
Candida, Cryptococcus
Endocarditis, pneumonia, meningitis, septicemia
Flucytosine - Adverse effects
Hematologic toxicity
Cardiac arrest
Flucytosine - Special considerations
Resistance to flucytosine is quickly developed, administered with amphotericin B
Fungistatic antibiotic
Griseofluvin
Griseofluvin - MoA
Disrupts microtubules function and mitosis in dermatophytes
Griseofluvin - Clinical use
Dermatophytes including Epidermophyton, Microsporum, Trichophyton
Tinea capitis
Griseofluvin - Adverse effects
Dizziness, headache, insomnia, GI bleeding, hepatitis, skin rash, leukopenia
Griseofluvin - Interactions
Absorption is increased with high-fat meal
Induces CYP3A4: reducing plasma concentrations of warfarin, oral contraceptives, barbiturates.
Pyridine compound
Ciclopirox
Ciclopirox - Clinical use
Skin infections by C. albicans, M. furfur
Tinea versicolor by M. furfur
Onychomycosis
Thiocarbamate drug
Tolnaftate
Tolnaftate - Clinical use
Tinea versicolor and mild dermatophyte infections of the skin
Polyene antibiotics - Administration
Topical: All of them
Oral: Nystatin
IV, intrathecal or intraventricular: Amphotericin B
Azole derivatives - Administration
Oral: All except Clotrimazole and Econazole
Topical: Clotrimazole, Econazole and Ketoconazole
IV: Fluconazole, Posaconazole, Voriconazole
Allylamine drugs - Administration
Topical: Both
Oral: Terbinafine
Other Antifungal drugs - Administration
IV: Caspofungin
Topical: Ciclopirox, Tolnaftate
Oral: Flucytosine, Griseofulvin
Which drugs are used for cushing syndrome?
Ketoconazole
Fluconazole
Which drugs are used for the treatment of onychomycosis?
Itraconazole
Terbinafine
Efinaconazole
Ciclopirox
