ANTIFUNGAL DRUGS

                                                          ANTIFUNGAL DRUGS


 These are the drugs uses to treat systemic and tropical fungal infections. Most of the fungal infections are iatrogenic in nature .
Classification :
1)Polyene antibiotics : Amphotericin B,Nystatin B
2)Antimetabolite: Griseofulvin
3)Azoles:
a)Imidazoles : Oral- Ketoconazole                    
                          Topical- Miconazole
 b)Triazoles : Oral- Fluconazole, Itraconazole ,Viriconazole.

4)Allylamines : Fluconazole,Itraconazole.

5)Others:Tolnaftate, Undecylenoic acid.

  

 INDIVIDUAL DRUGS:

Amphotericin B: It is obtained from Streptomyces Nodous.

• MOA:

It has high affinity for ergosterol present in the fungal cell membranes.

Amphotericin B binds to it and form  micropores.

So amino acids start leaking out.

Causes cell death.

•      Spectrum of activity:

AMB  is active against a wide range of yeasts and fungi.
Like Candida albicans, Histoplasma, Capsulatum, Torulopsis,Rhodotorula,Aspergillus,Sporothrix etc...
It is fungicidal at high and  static at low concentration.
It is also active on various species of Leishmania, a protozoa.

•    Pharmacokinetics:

*It is not orally absorbed
*It can be given orally for intestinal Candidiasis without systemic toxicity.
*Adminstered I.V. As a suspended made with the help of deoxycholate,it get widely distributed in the body but penetration in CSF is poor.
*T1/2 is 15days.
*Metabolism in the liver.
*Excretion in both urine and bile.

•    Adverse Effects:

Thrombophlebitis 

Nephrotoxicity

Azotemia

Reduced g.f.r.

Acidosis

Hypokalameia

CNS toxicity

Anaemia

•    Uses

*Treatment of systemic mycosis 

*Treatment of Leishmaniasis.

Griseofulvin : It is obtained from S.noursei.

MOA: It interfere with mitosis and causes abnormal metaphase configuration.

The daughter nuclei fail to move apart.

Thus cell division is attested at metaphase.

Treatment of systemic mycosis 

Treatment of Leishmaniasis.

Griseofulvin : It is obtained from S.noursei.

MOA: It interfere with mitosis and causes abnormal metaphase configuration.

The daughter nuclei fail to move apart.

Thus cell division is attested at metaphase.

Treatment of systemic mycosis 

Treatment of Leishmaniasis.

Griseofulvin : It is obtained from S.noursei.

MOA: It interfere with mitosis and causes abnormal metaphase configuration.

The daughter nuclei fail to move apart.

Thus cell division is attested at metaphase.

Chemical structure:

•    Adverse Effects

Pheripheral neuritis
Transient leukemia
Albuminuria
Photoallergy

•    Uses:

Dermatophytosis
Localized tinea infection

Imidazoles and Triazoles

These are presently the most extensively used antifungal drugs.

• MOA : They inhibit the fungal cytochrome P450 enzyme lanosterol 14-demthylase.

Which is required for the conversion of lanosterol to ergosterol.

This results in membrane abnormalities in the fungus

.

• Spectrum of activity: 

they act on Dermatophtes,Candida albicans,Nocardia,

• Adverse Effect

Inhibits CYP3A4 there by raising the blood levels of drugs like warfarin, terfenadine.

• Uses :  

systemic and topical infections.
Dermatophytosis.
Monilial vaginitis.
Kala azar.

Flucytosine

• MOA :

It is taken up by fungal cells and then converted into 5-FU.

5-FU then gets converted into 5 flurodeoxyuridylic acis which inhibit thymidylate synthetase .

This is required for the synthesis of thymidylic acid which is a component of DNA.

Spactrum of activity: it mainly act against Cryptococcus neoformans, candida, Torula, Aspergillus, Chrome blast once.

Chemical  structure

•  Adverse Effect: 

Leukopenia

Thrombocytopenia

Bone marrow depression

Alopecia

Hepatotoxicity

• Uses: 

Chromoblastomycosis.