Anti-fungal & Anti-parasitic Drugs; Algae Flashcards
Anti-fungal Targets:
- Ergosterol synthesis
- Cell wall synthesis
- Cell division
- Nucleic acid synthesis
3 Classes of Drugs Targeting Ergosterol:
- Polyenes
- Azoles
- Allylamines
Polyenes
- Amphotericin B
- Nystatin
Amphotericin B
Produced by Streptomyces nodosus
Binds ergosterol
- Increases cell membrane permeability
- Causes cell lysis
Systemic fungal infections
- IV over long periods
Adverse side effects (very toxic):
1. Renal toxicity (monitor kidney function)
2. Chills/fever
3. Inflammation of vein (phlebitis)
Less toxic lipid formulations also given
Nystatin
Binds ergosterol
- Increases cell membrane permeability
- Causes cell lysis
Used to treat:
1. Oral & esophageal infections
(oral, esophageal, gastric candidiasis)
2. Vaginal candidiasis (topical)
NOT used systemically
Azoles
Chemically synthesized drugs
Inhibit cytochrome P450 14a-demethylase (P45014DM)
- Enzyme in sterol biosynthesis pathway (lanosterol –> ergosterol)
- Depletion of ergosterol
- Increased membrane permeability
Azole Drugs
Imidazoles:
1. Ketoconazole
2. Mixonazole & Clotrimazole
Triazoles (less toxic):
1. Fluconazole
2. Itraconazole
3. Posaconzale
OTC:
1. Ketoconazole
2. Clotrimazole
3. Miconazole
Ketoconazole
(Imidazole)
Chronic mucocutaneous candidiasis
Adverse side effects:
1. Nausea
2. Vomiting
3. Hepatotoxicity
4. Inhibition of testosterone
Miconazole & Clotrimazole
(Imidazole)
Topical fungal infections
- Cutaneous candidiasis
- Tinea versicolor
- Dermatophytosis
(tinea pedis, tinea corporis, etc.)
Fluconazole
(Triazole)
Cutaneous & vaginal candidiasis (Diflucan - pink pill)
Systemic candidiasis & cryptomeningitis
Most commonly used
Itraconazole
(Triazole)
Broad-spectrum anti-fungal
Spectrum of activity includes:
1. Chromoblastomycosis
2. Histoplasmosis
3. Coccidioidomycosis
4. Blastomycosis
Posaconzale
(Triazole)
Excellent activity against:
Candida & Aspergillus
OTC Azoles
Superficial skin infections or vaginal candidiasis
- Ketoconazole
- Clotrimazole
- Miconazole
Allylamines
Inhibition of squalene epoxidase
- Essential step in ergosterol synthesis
(squalene –> lanosterol –> ergosterol)
Dermatophyte infections
(superficial skin infections)
- Chronic tinea pedis
- Tinea corporis
- Naftitine (topical)
- Terbinafine (topical & oral)
Echinocandins
Capsofungin
Target cell wall synthesis
- Inhibits beta-1,3 glucan synthesis
(inhibits secretion of subunits)
- Depletion of cell wall component
(falls apart)
Candida & Aspergillus infections
Griseofulvin
Produced by Penicillium species
Targets cell division
- Disrupts spindle formation
- Prevents mitosis
Taken orally for months
- Becomes concentrated in dead keratinized layers of skin
- Inhibits growth (fungus takes up)
Ringworm of skin, nails, hair
- Trichophyton spp.
- Epiderophyton spp.
- Microsporum spp.
NOT effective against:
- Superficial candidiasis
- Tinea versicolor
Flucytosine
Targets nucleic acid synthesis
- Replaces uracil with 5-fluorouracil in fungal RNA (chain inhibitor)
- Inhibits protein synthesis (transcription)
Candidiasis & cryptococcosis
- Used synergistically with Amphotericin B
Anti-protozoan Drugs
- Intestinal/urogenital protozoa
- Anti-malarial drugs
- Trypanosomiasis & Leishmaniasis
- African Sleeping Sickness
- Chaga’s Disease