ANTIFUNGAL TREATMENTS-PART-I

ANTIFUNGAL AGENTS

Fungal infections are generally classified into two categories such as systemic and superficial. Although drugs are also classified accordingly but can be used both the classes interchangeably.

Interestingly the organism pneumocystis carinii which causes life-threatening pneumonia in AIDS patients has been recently demonstrated to be a fungus and not a protozoan.

Fungi are eukaryotic organisms like animals, plants, and algae and their cell structures are well defined and complexed with many compartments known as the organelles. Eukaryotes differ from prokaryotes like bacteria by having a well-defined nucleus which in turn contains the defined nucleolus which in turn envelopes the inner contents, the chromosomes which in turn embedded with the DNA. These defined structures were not present in bacterial cells which is prokaryotic.

Fungal cells are rigid contains chitin a fiber polysaccharide forms like a thick transparent membrane structured cell wall.

Mycoses-Treatments:-

A superficial disease caused by fungi. It can be systemic too.

1.Amphotericin-B

This is a polyene macrolide antibiotic.

This is the drug of choice for treating mycoses.

Chemically it is a long aliphatic chained polyenes contains 200 polyenes in a chain with an open ring at the end contains the active carboxylic acid(-COOH) group. This is the primary chain and the secondary chain which contains the second active amino group attached to a glucosamine glycocidal ring. Refer to the above structure. 

Mechanism of Action:-

The mechanism of action is very interesting. The fungal cell contains ergosterol, a sterol which is specific to fungal cell similar to cholesterol a sterol content of human body cells.

Amphotericin-B binds with ergosterol and damages the fungal cell wall which is ruptured and leaked out the content and the cell dies.

Fortunately amphotericin will no-bind with cholesterol and hence it will not cause any harm to human cells.

Amphotericin-B has no CNS effects as it cannot into the blood-brain barrier.

Antifungal Spectrum

Amphotericin-B is effective against,

1.Candida

2.Histoplasma capsulatum

3.Cryptococcus neoformans

4.Blastomyces dermatitidis

5.Aspergillus

6.Coccidioides immitis

I.V.route is common

Intrathecal is preferred in fungal meningitis.

Amphotericin-B is not absorbed orally well.

Metabolized in the liver and excreted in bile via stools.

A small part is excreted in the urine.

Side Effects

Kidney failure.

Hypotension

Fever and chills

Hypochromic normocytic anemia.

2.Flucytosine

A synthetic pyrimidine antimetabolite.Structurally similar to 5-fluorouracil an anticancer drug.

Use

1. Primarily it can be used alone to treat subcutaneous chromomycoses.

2. In al other mycotic treatments it can be used with amphotericin-B.

Mechanism

Interestingly it is converted by the fungal cell into toxic 5-fluorouracil which impairs the DNA synthesis of thev fungus. Humen cells are not affected as they would not convert this drug into 5-fluorouracil.

Antifungal spectrum

1.Candida

2.Cryptococcus neoformans

3.Aspergillus

4.Chromomycoses

Can be given orally

It is well distributed in all tissue compartment including CSF(cerebrospinal fluid) and excreted in the urine.

Side Effects

1.Bonemarrow depression-reversible

2.Elevated liver enzymes

3.Enterocolitis.