Antifungal Agents Flashcards
Amphotericin B: mechanism of action
- binds ergosterol in fungal cell membrane
- forms pores–> cell content leakage
- fungicidal
Amphotericin B: pharmacokinetics
- IV/topical
- renal excretion
Amphotericin B: clinical uses
- broad spectrum, including opportunistic and systemic
- drug of choice in all life-threatening fungal infections
Amphotericin B: adverse reactions
- very toxic <–less selective toxicity b/c binds to cholesterol components in mammals
- nephrotoxicity
- infusion-related toxicity=chills, fever, vomiting, rigor, hypotension
- anemia
Nyastatin: mechanism of action
-binds ergosterol in fungal cells
Nyastatin: pharmacokinetics
- topical only
- no absorption from GI
Nyastatin: clinical uses
-topical treatment of Candidal infections of skin, mucous, membranes
Nyastatin: adverse reactions
-mild GI upset
Types of Echinocandins
- Capsofungin 2. Micafungin
Capsofungin: mechanism of action
- inhibits synthesis of Beta (1,3)-D-glucan (=component of fungal cell walls)
- disrupts cell wall assembly
- high selective toxicity
Capsofungin: pharmacokinetics
- IV
- hepatic metabolism
- dosage reduction w/hepatic insufficiency
- dosage increase w/co-tx w/CYP450 inducers
Capsofungin: clinical uses
-invasive aspergillosis in pts intolerant to other therapies
Capsofungin: adverse reactions
- histamine-mediated possible
- fever, nausea/vomiting, headache, phlebitis
Types of Triazoles
- Fluconazole
- Itraconazole
- Terconazole (topical only)
Triazoles: mechanism of action
- highly selective inhibitor of fungal cytochrome P450 (14alpha-demethylase)
- reduces normal sterol synthesis
- fungistatic
Triazoles: pharmacokinetics
- oral
- can enter CNS
- renal excretion
- long half-life=daily dosing
Triazoles: clinical uses
- fluconazole: vaginal candidiasis, oropharyngeal and esophageal candidiasis
- itraconazole: aspergillosis, histoplasmosis, sporotrichosis
- viraconazole: invasive aspergillosis
Triazoles: adverse reactions
- overall well tolerated
- GI distress
- some drug interactions similar to imidazoles
Types of Imidazoles
- ketoconazole (systemically and topically)
- clotrimazole (topical only)
- miconazole (topical only)
Imidazoles: mechanism of action
- inhibits P450 enzyme (14alpha-demethylase) -_> decreased levels of ergosterol
- disruption of membrane synthesis –> altered membrane permeability
- fungicidal
Imidazoles: pharmacokinetics
- ketconazole=oral and IV
- clotri/micon=topical only
- hepatic metabolism
- excreted in breast milk
Imidazoles: clinical uses
- keto: chronic mucocuatneous candidiasis and systemic fungal infections
- oral and vaginal cadidiasis (mico/clotri)
Imidazoles: adverse reactions
- ketoconazole systemically:
- nausea, vomiting, anorexia. hepatotoxicity.
- avoid in pregnancy
- can inhibit mammalian testosterone synthesis
- ketoconazole=strong inhibitor of CYP3A4 drug metabolism
- rifampin decreases ketocon effect by inducing metabolism
Terbinafine: mechanism of action
- ihibits squalene oxidase –> interferes w/ergosterol synthesis
- fungicidal
Terbinafine: pharmacokinetics
-oral and topical
Terbinafine: clinical uses
- oral=toe/finger nail infections
- topical=athletes foot
Terbinafine: adverse reactions
- GI upset
- interferes w/CYP450 metabolism
Flucytosine: mechanism of action
- converted in fungal cell to 5-fluorouracil –> interferes w/DNA synthesis
- high selective toxicity
- fungicidal
Flucytosine: pharmacokinetics
- oral
- renal excretion
Flucytosine: clinical uses
- effective, but rarely given alone; usually Ampho B + Flucytosine
- serious infections of cryptococcosis, candidiasis, chromoblastomycosis
Flucytosine: adverse reactions
- nausea, vomiting, skin rashes
- prolonged tx=bone marrow depression, abnormal liver fxn, hair loss
Griseofulvin: mechanism of action
- binds microtubules –> inhibits fungal mitosis and processing of cell wall components
- fungistatic
Griseofulvin: pharmacokinetics
- oral
- fecal excretion
Griseofulvin: clinical uses
- severe dermatophytosis @ skin, hair, or nails
- infrequently used, often replaced by shorter course therapy
Griseofulvin: adverse reactions
- hypersenstivity
- headache, GI distress
Pentamidine: mechanism of action
-inhibits protein/nucleic acid synthesis
Pentamidine: pharmacokinetics
- IV/IM
- inhalation for fungal pneumonia
Pentamidine: clinical uses
- effective against wide variety of protozoa
- treats P. jirovici (carinii) pneumonia in AIDS patients
Pentamidine: adverse reactions
- leukopenia, hypoglycemia, hypotension
- nephro/hepatotoxicity
