Download Antifungal drugs Lec 15-16 15-12

Antifungal drugs
Lec 18
30 -1-2017
Dr. Naza M. Ali
Antifungal Drugs

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.
Mycoses divided into:
1. Cutaneous mycoses:
Infection are superficial and only involve the
(skin, hair, nails).
2. Subcutaneous mycoses:
Fungi that grow in soil and on vegetation and
are introduced into subcutaneous tissue
through trauma.
3. 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.
Mechanism of drug acting on fungi
1. Alter cell membrane permeability
2. Block nucleic acid synthesis
3. Disrupt microtubule functions
Drugs for subcutaneous
and systemic fungal infections
1. Amphoteracin B
2. Flucytosine 5-FC
3. Azole antifungal agents:
-Ketoconazole
-Fluconazole
-Itraconazole
-Voriconazole
-Posaconazole (new)
4. Echinocandins
-Caspofungin
- Micafungin
Amphoteracin B
• Is a naturally occurring polyene macrolide antibiotic
produced by Streptomyces nodosus.
• Is the drug of choice for the treatment of lifethreatening systemic mycoses.
• Conventional amphotericin (amphotericin B
deoxycholate, the nonlipid formulation)
• has undergone several formulation improvements to
reduce the incidence of side effects( nephrotoxicity).
• 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.
• 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
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.
Resistance:
• Fungal resistance, is associated with decreased
ergosterol content of the fungal membrane.
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.
• 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.
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
1. 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.
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