1. By Dr.Mohamed Abd AlMoneim Attia
Antifungal drugs By
Dr.Mohamed Abd AlMoneim Attia

2. Fungal Infections
Develop due to a loss of mechanical barriers (i.e. burns, major surgery) or immunodeficiency (chemotherapy, organ transplant, AIDS)
fungal infections may be superficial or systemic
Fungi possess different ribosomes, cell wall components, and discrete nuclear membrane

3. Bacteria Fungi Nucleus no yes Ribosomes 70S 80S
Cell Wall Peptidoglycan Chitin
Membrane No sterols Ergosterol

4. Fungal Pathogens Systemic Infections Opportunistic pathogens
Candida albicans
Cryptococcus neoformans
Aspergillus
Pneumocystis carinii

5. Fungal Pathogens Systemic Infections Blastomyces dermatitidis
Histoplasma capsulatum
Parracoccidiodes brasiliensis

6. Fungal Pathogens
Superficial Infections
Dermatophytes
Candida albicans

7. Antifungal drugs Drugs for systemic infections
Polyene Antibiotics
Imidazole Antifungal Drugs
Flucytosine
Drugs for superficial infections
Polyenes, Imidazoles and
Griseofulvin
Naftifine

8. Polyene Antibiotics Polyenes bind to sterols - selectivity is poor.
Clinical Uses
Amphotericin B: systemic fungal infections
Nystatin: topical treatment of skin, oral and intestinal Candida infections
Candicidin: topical treatment of vaginal candidiasis.
Adverse Reactions (systemic use)
Fever, gastrointestinal distress, cardiotoxicity, hemolytic anemia, leukopenia, hepatotoxicity, nephrotoxicity.

9. Ketoconazole Mechanisms of action (we think)
blocks synthesis of ergosterol

10. Ketoconazole Clinical Uses - Adverse Reactions
Systemic and mucocutaneous infections.
Prevention of Candida infection in immune suppressed patients.
Adverse Reactions
Mild side effects: GI distress and pruritus
Serious side effects:
Hepatic toxicity - The drug must be discontinued if hepatitis occurs.
Gynecomastia - inhibition of testosterone synthesis

11. Other Imidazole Antifungals
Miconazole- topical treatment of dermatophyte infections and treatment of vaginal candidiasis.
Clotrimazole - topical treatment of cutaneous and vaginal infections.
Triazole Antifungals
Itraconazole - wider spectrum of activity than ketoconazole and fewer adverse effects. Drug of choice for several systemic infections.
Fluconazole - Cryptococcus (HIV+)

12. Flucytosine Clinical Uses (limited): Adverse Reactions:
Combined with amphotericin B - systemic Cryptococcus and Candida infections.
Adverse Reactions:
Bone marrow depression - leukopenia and thrombocytopenia
Gastrointestinal distress
Reversible hepatotoxicity

13. Griseofulvin G G G G
Centrosome
Microtubules
Nucleus

14. Griseofulvin
Binds to keratin and reaches high concentrations in the keratinized cells of the skin and the hair.
Clinical Uses:
Dermatophytes - Trichophyton, Epidermophyton and Microsporum.
Adverse Reactions:
Temporary headache is common.
Nervous system - mental confusion, fatigue, visual impairment.
Gastrointestinal distress

15. Mucocutaneous Antifungals
Griseofulvin
enters fungal cells by an energy-dependent process
interacts with the microtubules within the fungus to disrupt the mitotic spindle and inhibit mitosis
resistance due to lack of energy-dependent uptake system
toxicities include allergic syndrome and hepatitis

16. Naftifine Broad spectrum, fungicidal Clinical Uses:
inhibits squalene epoxidase
causes buildup of intracellular squalene
decreases ergosterol synthesis
Clinical Uses:
Dermatophytes (tinea cruris & tinea corporis), Candida.
Can cause local irritation.

17. Thank you