Unit 3: Mycology
149
Lecture 6 - Antifungal Chemotherapy
Compared with antibacterial agents, relatively few antimicrobics are
available for treatment of fungal mfection, in addition to that mere are
limitations in use of antibiotic such as profound side effects, a
narrow antifungal spectrum, poor penetration of certain tissues and
the selection of resistant fungi.
New azoles (has significantly highest antifungal activity and lowest
toxicity to the host). Fortunately most of fungal infections are self-
limiting and require no treatment .superficial mycosis are often
treated but topical therapy can be used ,thus limited toxicity to the
host .The remain small group of deep or systemic mycosis that are
uncontrolled by the host immune system require prolonged use of
relatively toxic antifungals.
Amphotericin B
The major polyeneantibiotic, Amphtericin B is the most effective
drugs for systemic mycoses, it has a broad spectrum.
Mechanism of action
Amphotericin B binds the ergosterol component of the fungal cell
membrane and alters the selection of the permeability of this
membrane, mammalian cell lack ergosterol and are relatively
resistant to this drug.
Indication
In Gryptococcosis, candidiasis, Histoplasmosis & sporotrichosis.
Amphtericin B is used in combination with flucytocin to treat
Cryptococcosis.
Is fluorinated derivative of cytocin, it penetrate well into all tissue, it
is oral antifungal component
Azoles
The azoles groups of antifungal agents consist of the
imidazol (eg.Ketoconazol
9
Clotrimazol or Miconazol) or
Triazol (eg. Fluconazol, itraconazol, orVoriconazole
Xmidazzol (Miconazol or Clotrimazol) are used topically while others
are used orally or IV.
Clotrimazol and Miconazol
Are available for topical and intravaginal (suppositories or
creams) applications.they are useful in mild case of
dermatophytosis (Tineapedis,Tineacruris ,Tineacorporis)
Tineaversicolor and cutaneous candidiasis vulvovaginal candidiasis
can be treated with suppositories Or creams.
Clotrimazol is effective against oral or esophageal thrush in
immunocomromized patients.
Fluconazol
is given either orally or IV Fluconazol has an
excellent activity against both Candida Spp. and Cneoformans and
oropharyngeal candidiasis in AIDS patients and candedemia in
^immunocompetentpatients.this drug is the best in this group in
penetration of the CNS hence, can be used as maintenance therapy for
Cryptococcal or Cooccidioidal meningitis,
Itraconazol
is now the agent of first choice for
Histoplasmosis, Paracoccidioidomycosis and Aspergillosisalso
effective in Sporotichosis ^Cryptococcosis and Onychomycosis in
immunocompetent and AIDS patientsltraconazol or fluconazol or
terbinafen may be used intermittently in case of long term therapy
of Tineaunguium.
Vericonazol
which can be given either orally or IV and active
against Aspergillosis or Pseudallescheriasis. Side effect
Adverse effect of
Ketoconazol include transient elevation of liver enzymeSjnausea
,irreversiblegynecomastia, decreaselipido and oligospermia in males
and menstrual irregularity.it is the most toxic agent in this group.
Clotrimazol and Miconazol side effect include burn, itching and/or
skin irritation.
Adverse effect of Itraconazol consisting of GIT disturbences,
vestibular disturbences,odema or skin irritation.
Vericonazol causes irreversible visual impairment in about 30% of
patients.
Griseofolvin
Griseofulvin is an antifungal antibiotics produce by Spp. of
pencillium.Griseofulvin is an oral agent poorly absorbed and
concentrate on the stratum corneunvt is inhibit hyphal growth.
Side effect Headache, GIT disturbances ^photosensitivity,
drowsiness and hepatotoxicity.
Indication: Useful for treatment of Dermatophyte infection of the
skin, hail and nail,OraI therapy for weeks or months are required.
Nystatin
It is a polyene antibiotics produced by StreptomyceSjStructurally
related to Amphotericin B»it is not absorbed by GIT, it is too toxic
for parentraladministration.
It is used locally to treat oral or vulvovaginalcandidiasis ,also
suppress esophageal candidiasis and gastrointestinal overgrowth
with no side effect. Other fungal agent
Echinocandins
Echinocandins are a new class of antifungal agents»their mode of
action by disturbing cell wall integrity, the recently licensed drug
Caspofungin has shown efficacy against invasive Aspergilosis and
Systemic candidiasis, Two newly approved
ecynocandms»micafunginand antdulafungJn,have similar activity
Unit 3: Mycology
150
against Spp. of Candida and Aspergillus, also used for
esophageal candidiasis.
Terbinafine
Is an allylamin drug, it is block ergosterol synthesis
Indications: is given orally for treating Dermatophytic infections
of nails and hair.
Side effects are not common but include GI disturbancesj,
headache, and loss of sense of taste.
Tolnaftate and naftiftne
Are topical antifungasl agents used in treatment of many
dermatophyticinfections and Tineaversicolor, available as
creams, powders and sprays Selenium sulfide
Selenium sulfide shampoo effective against Malazzesiafurfur. the
causative agents of Tineaversicolor, Undecylenic acid
Is available in several formulations for treatment of Tineacruris and
Tineapedis.
Hypersensitivity to fungi
Throughout life, the respiratory tract is exposed to airborne conidia
and spores of many saprophytic fungi. These particles often possess
potent surface antigens capable of stimulating strong allergic
reactions. These hypersensitivity responses do not require growth
of inducing fungi.
Depending on the site of deposition of the allergen, a patient may
exhibit rhmitis,bronchialasthma,alveolitis or pneumonitis .A topic
persons are more susceptible.
The diagnosis can be determined by skin testing with fungal
extracts-Management may include avoidance of the offending
allergens, treatment with corticosteroids or attempts to desensitize
patients.
Indoor air exposure to large number of fungal spores has led to the
recognition of a condition described as sick building syndrome
whereby moisture in construction materials such as wood allow
contaminating mold to flourish this resulting in debilitating cases
of systemic allergic or toxic reactions.