35)Antifungal drugs Flashcards
Fungal infections
Superficial infection
- Dermatophytes
- Candidiasis
Systemic infection
- Histoplasmosis
- Cryptococcosis
- Coccidioidomycosis
Classification
Antifungals damaging permeability of cell membrane
- Imidazole’s ⇢ Clotrimazole, Ketoconazole, Miconazole
- Triazoles ⇢ Systemic ⇢ Fluconazole + Itraconazole
- Allylamines ⇢ Terbinafine
- Polyene antibiotics ⇢ Amphotericin B, Nystatin (most important of oral candidiasis)
Antifungals inhibiting chitin synthesis in cell wall
- Caspofungin + Micofungin
Antifungals inhibiting synthesis of nucleic acids
- Flucytosine
Antifungals that inhibit mitosis
- Griseofulvin
Pharmacodynamics - Group 1
Azoles
- inhibit synthesis of ergosterol ⇢ fungal cell membranes damages - fungistatic
Allylamines
- Interfere w/ergosterol biosynthesis ⇢ inhibit squalene epoxidase
Polyene antibiotics
- Interact w/ergosterol in fungal membrane ⇢ form pores ⇢ disrupt membrane permeability
Pharmacodynamics - Group 2, 3 + 4
Group 2
- Inhibit synthesis of 1-3 B-glucan ⇢ fungal cells lose integrity + lyse
Group 3
- Interferes w/nucleic acid synthesis ⇢ inhibits thymidylate
Group 4
- Binds to microtubules responsible for mitotic spindle formation
Pharmacokinetics of azoles
Oral, topical + IV administration
Azoles ⇢ inhibitors of P450 + prone to DDI
Ketoconazole
- Well absorbed from GI tract
- Widely distributed throughout fluids + tissues ⇢ only reaches CNS w/ ⇡ doses
Fluconazole
- More soluble than ketoconazole
- Orally + IV
- Reaches CSF by crossing BBB
- Drug of choice for fungal meningitidis
Itraconazole
- Oral only
- Doesn’t cross BBB
- Does not inhibit steroid synthesis
Allylamines - Terbinafine
Treats fungal infections of nails
Amphotericin B ⇢ prepared in liposomes w/artificial lipids ⇢ ⇣ Nephrotoxicity
- Nephrotoxicity ⇢ due to vasoconstriction of afferent renal arteries
- Leads to destruction of renal tubular cells + disruption of tubular basement membrane
Flucytosine
Well absorbed by oral route
Penetrates CNS
- Used in combo w/amphotericin in severe candida infections of CNS
Excreted via GF
Mycostatin
- Poorly absorbed from GI tract
- Administered P.O for treatment of oral candidiasis
Clinical uses in dentistry
Amphotericin B widely used:
- Neutropenic patients w/ candida albicans
- AIDS patients w/ cryptococcal menilites/ disseminated histoplasmosis
Nystatin
- Candida infections of skin, mucous membrane + GI tract
- Used topically for thrush
Azoles
- Treat mucocutaneous candidiasis + deep mycosis
Adverse effects
GI problems
Hepatotoxicity
Inhibition of P450
Headaches
Nephrotoxicity
Adverse effects pt 2
Echinocandis ⇢ histamine release ⇢ facial flushing, rash + fever
Azoles:
- Anorexia
- nausea
- vomiting
- allergic skin rash
- endocrine effects
- Liver toxicity
