antifungl drugs

fungi are eukaryotic, with rigid cell walls composed largely of chitin rather than peptidoglycan (a characteristic component of most bacterial cell walls).
the fungal cell membrane contains ergosterol rather than the cholesterol found in mammalian membranes.
Fungal infections are generally resistant to antibiotics, and, conversely, bacteria are resistant to antifungal agentsInfectious diseases caused by fungi are called mycoses, and they are often chronic in nature.
Mycotic infections may be superficial and involve only the skin (cutaneous mycoses extending into the epidermis).
others may penetrate the skin, causing subcutaneous
( systemic infectionsa
Amphotericin B
naturally antifungal produced by Streptomyces nodosus. In spite of its toxic potential, it remains the choice for treatment of life-threatening mycoses.Amphotericin B binds to ergosterol in the plasma membranes of sensitive fungal cells , it forms pores (channels) The pores disrupt membrane function, allowing electrolytes (k+) and small molecules to leak from the cell, resulting in cell death.

fever and chill ( start within 1-3 hrs after iv infusion prevented by corticosteroid
or an antipyretic )
2. Renal imperment which is reversible (because the drug has low Theraputic index).
3. hypotension (shock like state )
4. thermbophilibits (treated by heparin).
Note: Amphotericin B is administered by slow, intravenous (IV) infusion.
azole group:
Two groups:
Imidazoles are given topically for cutaneous infections.
Triazoles are given systemically for the treatment or prophylaxis of cutaneous and systemic fungal infections.
Mechanism of action:
Blocking of ergosterol biosynthesis that disrupts membrane structure and function which inhibits fungal cell growth.

Fluconazole :
It is commonly used as a single-dose treatment for vulvovaginal candidiasis.
2.Voriconazole
has replaced amphotericin B as the drug of choice for invasive aspergillosis.
It is also used for treatment of invasive candidiasis.Itraconazole has a negative inotropic effect and should be avoided in patients with evidence of ventricular dysfunction, such as heart failure.
Echinocandins class (new)
mechanism of action :
interfere with the synthesis of the fungal cell wall by
inhibiting the synthesis of ?(1,3) glucan, leading to lysis and cell death.
The echinocandins have potent activity against Aspergillus and most Candida species, including those species resistant to azoles. However, they have minimal activity against other fungi.
S.E histamine-like reaction (flushing) when infused too rapidly.
Terbinafine
These agents act by inhibiting squalene epoxidase, so blocking the biosynthesis of ergosterol, an essential component of the fungal cell membrane. Accumulation of toxic amounts of squalene results in:
increased membrane permeability
death of the fungal cell
Griseofulvin
M.O.A: causes disruption of the mitotic spindle and inhibition of fungal mitosis.
USES: The drug concentrates in skin, hair, nails, and adipose tissue.so used for dermatophytosis of skin ,nail and scalp.
contraindicated in pregnancy .
Nystatin is structure, chemistry, mechanism of action like amphotericin B.
It of choice for treatment of oropharyngeal candidiasis (thrush), intravaginally for vulvovaginal candidiasis, or topically for cutaneous candidiasis.
The drug is negligibly absorbed from the G.I.T. and it is not used parenterally due to systemic toxicity (acute infusion-related adverse effects and nephrotoxicity
Ciclopirox
MOA: inhibits the transport of essential elements in the fungal cell, disrupting the synthesis of DNA, RNA, and proteins.
Ciclopirox shampoo is used for treatment of seborrheic dermatitis.
Tinea pedis, tinea corporis, tinea cruris, and tinea versicolor treated with cream, gel, or suspension