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Antifungal chemotherapy
1. INSTITUTE OF HEALTH TECHNOLOGY, DHAKA
Department of Laboratory Medicine
BSc in Health Technology (Laboratory)- 1st Year
MYCOLOGY
Lecture No. 8 (Antifungal Chemotherapy)
By
Sk. MIZANUR RAHMAN
Lecturer, Mycology
MS in Biotechnology & Genetic Engineering (UODA)
MS in Microbiology (SU)
2. Antifungal Chemotherapy
The treatment of disease by the use of chemical substances,
especially the treatment of fungal diseases by cytotoxic and
other drugs.
3. Chemotherapy Types
1. Prophylactic – Anti-fungal agents at, or near,
the time of chemotherapy.
Posaconazole now approved.
2. Empirical – Start therapy when patient at risk,
i.e., fever and/or infiltrate without response to
anti-bacterials.
3. Pre-emptive –When there is some additional
evidence of fungal infection (serology, isolate,
etc.)
4. Antifungal agents targeted towards:
Inhibition of fungal cell wall synthesis – caspofungin is a
-glucan synthesis inhibitor; several more compounds are
under investigation
Inhibition of fungal cell membrane synthesis – ergosterol
is the target (cell membranes of fungi and mammals
contain different sterols): polyenes, azoles, triazoles,
alkylamines
Inhibition of cell division – microtubule effects:
griseofulvin; DNA: flucytosine.
Biochemical Targets for Antifungal Chemotherapy
9. What are the targets for antifungal therapy?
Cell membrane
Fungi use principally ergosterol
instead of cholesterol
Cell Wall
Unlike mammalian cells, fungi have a
cell wall
DNA Synthesis
Some compounds may be selectively
activated by fungi, arresting DNA
synthesis.
Atlas of fungal Infections, Richard Diamond Ed. 1999
Introduction to Medical Mycology. Merck and Co. 2001
12. Cell Wall Active Antifungals
Cell membrane
• Polyene antibiotics
• Azole antifungals
DNA/RNA synthesis
• Pyrimidine analogues
- Flucytosine
Cell wall
• Echinocandins
-Caspofungin acetate (Cancidas)
Atlas of fungal Infections, Richard Diamond Ed. 1999
Introduction to Medical Mycology. Merck and Co. 2001
13.
14.
15.
16. Azoles
• Azoles
• Causes Inhibition of C-
14 α demethylase, (an
enzyme required for
the synthesis of
ergosterol) by binding
to cytochrome P450
Imidazoles Triazoles
17. Allyamines
• Inhibits squalene
epoxidase, an enzyme
essential for synthesis
of ergosterol
• Drug acculmulates in
nails, skin and fat
• Very useful for nail
infections
18. Polyenes
• Amphotericin, nystatin
• Antifungal activity by
binding to membrane
sterols such as
ergosterol and they
increase membrane
permeability and
leads to cell death
19. Amphotericin
• Numerous forms
• Pastilles, Parenteral forms: amphotericin B,
deoxycholate form, colloidal form, Liposomal form
• Toxicity: Dose dependent reduction in GFR, by direct
vasoconstritive effect on afferent renal arterioles,
destruction of renal tubular cells and basement
membrane and loss of functioning units
• Also nausea .vomiting, phlebitis and ACUTE
REACTION: fever,chills,tachyapnea
20. Pyrimidines
• Fluorine analogue of a
normal cell constituent
cytosine
• Demination results in 5-
fluorouracil, to 5-
flurodeoxyuridylic acid
monophosphate, a non-
competitive inhibitor of
thymidylate synthetase
• Used particularly in
crytococcal meningitis-
74% of serum levels
21. Benzofurans
• Griseofulvin
• Inhibits nucleic acid synthesis, macrotubule
formation and chitin formation
• Active against ringworm, not candidia or tinea
versicolor
22. Lipopeptides
• Echinocandins, derivatives of pneumocandin
BO
• Inhibition of ß 1 ,3 glucans in the fungal wall
• Active candida, aspergillosis and pneumocystis
carinii
