Fungi is:
Eukaryotic – a true nucleus
Do not contain chlorophyll
Have cell walls
Produce filamentous structures
Produce spores
Contain ergosterol
The Term mycosis (plural: mycoses) refers
to conditions in which fungi pass the
resistance barriers of the human or animal
body and establish infections.
Classification of Mycoses:

Mycoses are classified according to the tissue

levels initially colonized:
1. Superficial mycoses - limited to the
outermost layers of the skin and hair.
2. Cutaneous mycoses - extend deeper into
the epidermis, as well as invasive hair and
nail diseases. These diseases are restricted
to the keratinized layers of the skin, hair,
and nails. The organisms that cause these
diseases are called dermatophytes.
Classification of Mycoses:

3. Subcutaneous mycoses - involve the

dermis, subcutaneous tissues, muscle, and
fascia. These infections are chronic and can
be initiated by piercing trauma to the skin,
which allows the fungi to enter.
4. Systemic mycoses due to primary
pathogens - originate primarily in the lungs
and may spread to many organ systems.
Treatment
Unlike bacteria, both fungi and humans are
eukaryotes. Thus fungal and human cells are
similar at the molecular level. This means it is
more difficult to find a target for an antifungal
drug to attack that does not also exist in the
infected organism.
Antifungal drugs are used to treat mycoses.
Depending on the nature of the infection, a
topical or systemic agent may be used.
Photochemotherapy or photopheresis is a
technique used at major medical centers for
the treatment of mycosis
Amphtericin B & Nystatin
 Amphtericin B

Uses and spectrum:

Amphotericin B for injection (IV) administered primarily to
patients with progressive, potentially life-threatening fungal
infections such as:
 Aspergillosis
 cryptococcosis (torulosis)
 systemic candidiasis
 coccidioido-mycosis
 histoplasmosis

Its spectrum is the broadest of all antifungals.

Amphtericin B

Contraindication:
This product is contraindicated in those patients
who have shown hypersensitivity to
Amphotericin B or any other component in the
formulation.
Amphtericin B

Pharmacokinetic:
Poorly absorbed from GIT.
Start with small initial dose then gradually increase it.
An elimination half-life approximately 15 days.
Amphotericin B circulating in plasma is highly bound
(>90%) to plasma proteins.
Amphotericin B is excreted very slowly (over weeks
to months) by the kidneys.
After treatment is discontinued, the drug can be
detected in the urine for at least seven weeks.
Side effects:
acuteAmphtericin
reaction: B
 fever, shaking chills, hypotension, anorexia, nausea,
vomiting, headache, dyspnea, tachypnea
 NYSTATIN
mechanism:
Same as amphotericinB
Uses: intestinal candida or trush(oral candida).
Drug of choice for vaginal & cutaneous candidiasis.

Administered in vaginal tablets or topically.

SIDE EFFECTS:
Nystatin is well tolerated even with prolonged therapy.
Oral irritation and sensitization have been reported.

Gastrointestinal: Diarrhea ,nausea, vomiting,

gastrointestinal upset/disturbances.

Dermatologic: Rash, including urticaria has been

reported rarely.

Other: Tachycardia, bronchospasm, facial swelling.

Pharmacokinetics:
Gastrointestinal absorption of nystatin is insignificant
(poorly absorbed).
Most orally administered nystatin is passed unchanged in
the stool.
In patients with renal insufficiency significant plasma
concentrations of nystatin may occur.
 azoles
Ketoconazole

Mechanism of action: impairs synthesis of the

principle sterol of the fungal plasma
membrane.
Pharmacokinetics: the drug is oraly active in
the acidic PH require for dissolution absorption
decreased by food, anti acids, high protein
bound and less CNS level.
Clinical uses:
Paracoccidiodes, thrush(pharyngeal candida) also used for
the treatment of chronic mucocutaneus
candidiasis,dermatophytes.
side effects: nausea,diarrhea,headache,rash,fatal hepatic
necrosis,gynecomestia.
 fluconazole
Mechanism: inhibits fungal enzyme cytochrome
p450 damages plasma membraneby inhibiting sterol
demethylation.
Phramacokinetics: PO/IV the drug exhibit long half
life excellent penetration of CSF,eye,urine and
hepatic metabolism.
Uses:
aspiragillosis,histoplasmosis,blastomy
cosis,coccidiomycosis,
(minengitis)sporotricosis
opportunistic cryptococcis,vaginitis
esophagitis and candidal infections.
Side effects:
nause,headache,rash,
vomiting,diarrhea.
 Itraconazole

Mechanism: same as fluconazole

Pharmacokinetics:
Given orally require acidic
environment for absorption
accumulates over time long half life
poor CSF the drug undergoes
hepatic metabolism
Uses:
asparagillosis,histoplasmosis,blast
omycosis coccidiomycosis, local
tinea or candidal infections better
than ketaconazole for asparagilus
Side effects:
nausea edema hepatitis no
gynecomestia
clotrimazole:
pharmacokinetics:
Topical
uses:
candida dermatophyte infection
Miconazole:
Pharmacokinetics:
Topical and vaginal suppositories
Uses: vanginal candidiasis and severe
fungal infections.
Side effects: phlebitis nausea vomiting
fever and rash.
 Voriconazole

A broad spectrum antifungal agent

Given orally or IV
High oral bioavailability
Penetrates tissues well including CSF
Inhibit P450
Used for the treatment of invasive aspergillosis &
serious infections.
Reversible visual disturbances
Mechanism: inhibits squalence epoxidase the critical enzyme that
converts squalence to ergosterol in fungi.
terbinafine
Pharmacokinetics: given orally the drug has long half life with good
penetration in all tissues.
Uses: nail infections due to tricho phyton species.
Side effects: neutropnea skin reactions and opthalmic
 flucytosine
MOA
Activated by fungal deaminase cytosine to FU.
5-FU also forms 5-Fd_UMP which inhibits thymidylate
synthase which interfers DNA synthesis
Resistance:
Resistance rapidly develops if used alone.
Used with amphotericinBin severe candidal infections
and cryptococcal infectionenters CSF
Side effects: bone marrow toxicity
Griseofulvin
Active only against dematophytes(orally nt topically)
Distributes where keratin is present

Terbinafine
Active only against dermatophytes by inhibiting
squalene opoxidase which decreases ergosterol
P.Kinetics taken topically for topical infections and
oral for systemic infections
Side effects:
GI distress,rash,headache,hepatotoxicity
 Echinocandins
Caspofungin, is the first approved member of the
echinocandins class of
antifungal drugs. Echinocandins interfere with the
synthesis of the fungal cell wall by inhibiting the
synthesis of
Beta 1,3-D-glucan, leading to lysis and cell death. This
drug's spectrum is limited to Aspergillus and Candida
species.