1. Antifungal drugs Lec 18 30 -1-2017 Dr. Naza M. Ali

3. Antifungal Drugs Fungal infections are generally resistant to
Unlike bacteria, fungi are eukaryotic.
Fungal infections are generally resistant to
antibiotics used in the treatment of bacterial
infections, and conversely, bacteria are resistant to
antifungal agents.
Infectious diseases caused by fungi are called mycoses, they are often chronic in nature.

4. Mycoses divided into: Cutaneous mycoses:
Infection are superficial and only involve the
(skin, hair, nails).
Subcutaneous mycoses:
Fungi that grow in soil and on vegetation and
are introduced into subcutaneous tissue
through trauma.

5. Systemic mycoses:
Infections result from inhalation of the spores
of dimorphic fungi that have their saprophytic
mold forms in the soil.
are most difficult to treat which are often life
threatening.

6. Mechanism of drug acting on fungi
Alter cell membrane permeability
2. Block nucleic acid synthesis
3. Disrupt microtubule functions

7. Drugs for subcutaneous and systemic fungal infections
1. Amphoteracin B 2. Flucytosine 5-FC 3. Azole antifungal agents: -Ketoconazole -Fluconazole -Itraconazole -Voriconazole -Posaconazole (new)

8. 4. Echinocandins -Caspofungin - Micafungin

9. Amphoteracin B
Is a naturally occurring polyene macrolide antibiotic produced by Streptomyces nodosus.
Is the drug of choice for the treatment of life-threatening systemic mycoses.
Conventional amphotericin (amphotericin B deoxycholate, the nonlipid formulation)
has undergone several formulation improvements to reduce the incidence of side effects( nephrotoxicity).

10. The drug is used in combination with flucytosine to achieve more rapid sterilization of the CSF.
Amphotericin B is either fungicidal or fungistatic,
depending on organism and concentration of the drug.
It is often used for initial induction regiments before follow up treatment with an azole.

11. It has widest antifungal agents spectrum than any
agents and the drug of choice for systemic most
infections caused by
Aspergillus, Blastomyces, Candida albicans,
Cryptococcus, Histoplasma and Mucor.
it is usually given by slow IV infusion.
In case of fungal meningitis( by intrathecal route).
Local administration in treatment of mycotic corneal ulcer

13. Mechansim of action of Amphoteracin B
Is a polyene macrolide related to nystatin
polyenes are molecules with both hydrophilic &
lipophilic characteristics.
Several amphotericin B molecules bind to ergosterol
in the plasma membranes of fungal cells, and cause
the formation of artificial pores (channels).
The pores disrupt membrane function, allowing
electrolytes and small molecules to leak from the cell,
resulting in cell death.

15. Resistance:
Fungal resistance, is associated with decreased ergosterol content of the fungal membrane.

16. Pharmacokinetics:
Amphotericin B is used by slow, (IV) infusion
Is insoluble in water, and injectable preparations require the addition of sodium deoxycholate, which produces a soluble colloidal dispersion.
The more dangerous intrathecal route is chosen for the treatment of meningitis.

19. Amphotericin B has also been formulated with a
variety of artificial lipids that form liposomes.
Amphotericin B is extensively bound to plasma protein.
Inflammation favors penetration into various body fluids.

20. Adverse effects
Amphotericin B has a low therapeutic index
A total adult daily dose should not exceed
1.5 mg/kg
Small test doses are usually administered to avoid
anaphylaxis or convulsions

21. Fever & chills:
These occur most commonly 1-3 hours after
starting IV, but they usually subside with repeated
administration of the drug.
Premedication with an antipyretic or a corticosteroid
helps to prevent problem.

22. Azotemia (elevated blood urea)
2. Renal impairment:
Azotemia (elevated blood urea)
adequate hydration can decrease its severity.
3. Hypotension:
A shock-like fall in blood pressure
4. Anemia
5. Neurologic effects