Fungal Treatment

Igri Septian Risky

I11109018

Mechanism of Antifungal Drug

Amphotericin
mixture of antifungal substances derived from
cultures of Streptomyces. Structurally, these
are very large ('macrolide') molecules
belonging to the polyene group of antifungal
agents

Amphotericin
the site of amphotericin action is the fungal
cell membranes, where it interferes with
permeability and with transport functions.
The hydrophilic core of the molecule creates a
transmembrane ion channel, causing gross
disturbances in ion balance including the loss
of intracellular K+.

Unwanted effect
The commonest and most serious unwanted
effect of amphotericin is renal toxicity. Some
degree of reduction of renal function occurs in
more than 80% of patients receiving the drug;
although this generally recovers after
treatment is stopped, some impairment of
glomerular filtration may remain.

Nystatin
Nystatin is a polyene macrolide antibiotic
similar in struxture to amphotericin with the
same mechanism of action
its use is mainly limited to Candida infections
of the skin, mucous membranes and the
gastrointestinal tract.
Unwanted effects may include nausea,
vomiting and diarrhoea

Griseovulvin
antifungal agent isolated from cultures of
Penicillium griseofulvum. It causes a
fungistatic action by interacting with fungal
microtubules and interfering with mitosis.

Pharmacokinetic aspect
Griseofulvin is given orally. It is poorly soluble in
water, and absorption varies with the type of
preparation, in particular with particle size. Peak
plasma concentrations are reached in about 5
hours. It is taken up selectively by newly formed
skin and concentrated in the keratin. The plasma
half-life is 24 hours, but it is retained in the skin
for much longer. It potently induces cytochrome
P450 enzymes and causes several clinically
important drug interactions.

Unwanted effect
Unwanted effects with griseofulfin use are
infrequent, but the drug can cause
gastrointestinal upsets, headache and
photosensitivity. Allergic reactions (rashes,
fever) may also occur. The drug should not be
given to pregnant women.

Echinocandin
Fungal cells lose integrity and lysis quickly
followsEchinocandins comprise a ring of six
amino acids linked to a lipophilic side-chain.
The echinocandins inhibit the synthesis of 1,3-glucan, a glucose polymer that is necessary
for maintaining the structure of fungal cell
walls. In the absence of this polymer

Azole regiment
The azoles inhibit the fungal cytochrome P450
3A enzyme, lanosine 14-demethylase, which
is responsible for converting lanosterol to
ergosterol, the main sterol in the fungal cell
membrane. The resulting depletion of
ergosterol alters the fluidity of the membrane,
and this interferes with the action of
membrane-associated enzymes.

Flucytosine
Flucytosine is converted to the antimetabolite
5-fluorouracil in fungal but not human cells. 5Fluorouracil inhibits thymidylate synthetase
and thus DNA synthesis

Terbinafine
terbinafine have effect inhibiting the enzyme
squalene epoxidase, which is involved in the
synthesis of ergosterol from squalene in the
fungal cell wall. The accumulation of squalene
within the cell is toxic to the organism