Anti-fungal agents Flashcards
Amphotericin B, Echinocandins, Azole
-primary drugs used in systemic infections
Amphoterin B –> highly effective but quite toxic
Echinocandins –> non-toxic, only parenteral form
Azole –> non-toxic, oral and parenteral form
Polyenes
-names
Amphotericin B
Nystatin
Amphotericin B (5)
- binds to ergosterol and alters the permeability of the cell by forming amphotericin B- associated pores in the cell membrane
- Fungicidal
- broadest spectrum
- useful for nearly all life-threatening fungi infections
- used as the initial induction regimen to rapidly reduce fungal burden and then replaced by one of the newer azole drugs
Amphotericin B
- pharmacokinetics
- unwanted effects
- poorly absorbed
- oral effective only on fungi in the lumen of the tract
- systemic infections
- slow hepatic metabolism
- only very small amount crosses blood brain barrier
- infusion related reactions (recommended slow infusion rate)
- renal damage
Nystatin
- pharmacokinetics
- indications
- unwanted effects
- same mechanism of action as amphotericin
- oral; not absorbed
- GI (mouth, throat, pharynx), mucous membranes fungus infections (Candidiasis)
- GI effects
Echinocandins
- name
- mechanism of action
- pharmacokinetics
- Caspofungin
- inhibit synthesis of 1,3 beta glucan (glucose polymer) –> necessary for maintaining the structure of fungal cell walls
- IV
- eliminated largely via hepatic metabolism
Caspofungin
- indications
- unwanted effects
-candidiasis and invasive aspergillosis that are refractory to amphotericin
- fever
- injection related reactions
- GI effects
Azole
- names
- mechanism of action
- Imidazole: Ketoconazole
- Triazoles: Itraconazole, Voriconazole, Fluconazole
- broad spectrum
- inhibit fungal cytochrome P450 enzymes (inhibits also liver cytochrome enzymes)
Azole
- pharmacokinetics
- unwanted effects
- oral, iv, topical
- liver toxicity, GI side effects, allergic reactions
Ketoconazole
- indications
- unwanted effects
- drug interactions
- systemic fungal infections
- inhibitions of adrenocortical steroid and testosterone synthesis from cholesterol (gynecomastia, menstrual irregularities, infertility)
- many drug interactions - because it inhibits CYP450 which could increase the concentration of other drugs
- Rifampin by inducting CYP450 –> decrease concentrations of ketoconazole
Indications of:
- Fluconazole
- Voriconazole
- Itraconazole
- high concentration in the cerebrospinal and ocular fluids –> meningitis
- invasive aspergillosis
- skin and nail infections
Ketoconazole shouldn’t be used with which drug?
Amphotericin B
Fluorinated pyrimidines
- name
- mechanism of action
- indications
- unwanted effects
-Flucytosine
- block DNA synthesis
- fungicidal
- severe Candidiasis and Cryptococcal meningitis
- GI side effects, liver dysfunction, bone marrow depression
Which drug should not be used alone because resistance emerges rapidly?
Flucytosine should be used together with Amphotericin
Griseofulvin
- mechanism of action
- pharmacokinetics
- indications
- disrupt dermatophytes microtubule function, may inhibit synthesis of nucleic acids
- fungistatic
- oral
- distributed to the stratum corneum (outermost layer of the epidermis), where it binds to keratin
-dermatophytosis of the skin and hair
