2. Introduction
Definition :-
Anti fungal medication is also known as an antimycotic medication , is a fungicide
or fungistatic used to treat and prevent mycosis such as ring worm , candidiasis,
serious systemic infections such as cryptococcal meningitis and others
Most of the fungi that are now known to cause infections ,usually in live associate
with humans as commensals without harming the host
Fungal infections are more frequent than bacterial infections
More complex than bacteria
They have different ribosomes & posses rigid outer cell wall which contains
polysaccharides
Inner to the cell wall lies the cell membrane which consists of ergo sterol
3. Four main characteristics of fungi are
*Eukaryotic (nuclei & mitochondria)
*Heterotrophs (depend on other organisms)
*Multicellular
*They cannot move on their own
Fungi are classified as yeast and moulds
Yeast like pathogens are
*Histoplasmosis
*Candida
*Coccidioidomycosis
*Blastomycosis
*Cryptococcosis
Moulds like pathogens are
*Aspergillosis
*Dermatophytes
*Mucormicosis
4. *
*Classified as superficial and deep mycosis (systemic)
Superficial
*Mainly effect on skin, hair, nails, mucous membranes .
*Most common in dermatophytoses
*Encouraged by hot & humid conditions
*They are classified according to the body site
Tinea barbae
Tinea capitis (Scalp)
Tinea corporis (Body)
Tinea manuum (Head)
Tinea pedis (Foot)
Tinea unguium (Nails)
7. Many topical antifungals have been available since the antiseptic era.
Two important antibiotics viz. amphotericin B—to deal with systemic mycosis, and
griseofulvin—to supplement attack on dermatophyte were introduced around 1960.
Antifungal property of flucytosine was noted in 1970, but it could serve only as a
companion drug to amphotericin.
The development of imidazoles in the mid 1970s and triazoles in 1980s has been an
advancement.
Terbinafine is a novel antifungal.
A group of potent semisynthetic antifungal antibiotics, the Echinocandins are the
latest addition.
8. Classification of Anti Fungal drugs
1. Antibiotics
A. Polyenes: Amphotericin B (AMB), Nystatin, Hamycin
B. Echinocandins:Caspofungin, Micafungin, Anidulafungin
C. Heterocyclic benzofuran: Griseofulvin
2. Antimetabolite :-
Flucytosine (5-FC)
3. Azoles
A. Imidazoles Topical : Clotrimazole, Econazole, Miconazole, Oxiconazole
. Systemic:Ketoconazole
B. Triazoles: Fluconazole, (systemic) Itraconazole, Voriconazole, Posaconazole
4. Allylamine: - Terbinafine
5. Other topical agents: - Tolnaftate, Undecylenic acid, Benzoic acid, Quiniodochlor, .
. Ciclopirox olamine, Butenafine, Sod. thiosulfate.
9. *
Amphotericin B:
It is a Polyene macrolide antibiotic obtained from Streptomyces nodosus
Mechanism of action :-
Binds to ergosterol present in the fungal cell memberane and forms pores in
memberane , through which macromolecules Na ⁺, k ⁺,Mg ² ⁺,H ⁺leak out which
ultimately results in the death of susceptible death of fungi
Affinity towards ergosterol is due to presence of both lipophilic and hydrophilic
groups
Antifungal spectrum :-
Broad spectrum antifungal agent
Fungicidal at higher concentrations & fungi static at lower concentrations
Found to be effective against yeast and fungi namely aspergillus species,
blastomyces dermatitis, candida albicans
Pharmacokinetics:
i.v route , prolonged half life of drug is 15days
More than 60% of drug metabolized in liver & eliminated through urine & bile
10. Adverse effects: -
Acute toxicity : chills, fever, dyspnoea, nausea, vomiting & pain
Long term toxicity in anemia, neurotoxicity , renal toxicity .
Uses :
systemic therapy :
Drug choice in the treatment of Blastomycosis ,candidiasis, Histoplasmosis etc.
Topical therapy :
Cutaneous candidiasis , mycotic corneal ulcers and keratitis can be treated
11. Heterocyclic benzofuran
Griseofulvin :
It is fungistatic agent obtained from pencillium griseofulvum
Mechanism of action: -
Binds to polymerised microtubules and disrupts the mitotic spindle fibers which
eventually leads to the arrest of mitotic division at metaphase
Dermatophytes primarily attack the keratinous tissue . Griseofulvin binds to newly
synthesized keratin of skin ,nails, hair and makes it resistant to dermatophyte attack.
Pharmacokinetics :-
oral, plasma half life of the drug is 24hrs
Adverse effects:-
Head ache is most common manifestation
12. Dose: 125–250 mg QID with meals; duration depends on the site of infection
(turnover rate of keratin).
Scalp 4 weeks Palm,
Soles 6 to 8 weeks
Finger nails 6 to 8 months
Toe nails 10 to 12 months
Uses :
Ring worm infections
13. Antimetabolites
The analogues which compitatively inhibit the action of metabolites
Flucytosine :-
Halogenated analogue of cytocine , it structurally resembles 5-fluorourasil
Mechanism of action :-
Inhibit the synthesis of DNA & RNA of fungus
Flucytosine enters in to fungal cells with the help of cystone permease enzyme ,and it
gets converted in to 5-fluorouracil 5-flurodeoxyuridine monophosphate
inhibit
thymidylate synthetase enzyme
Which is required for the formation of thymidilic acid an important component of
DNA thus DNA synthesis is inhibited
Pharmacokinetics :-
orally absorbed , t½ of the drug is 3-6 hrs. eliminated to kidneys through G.F
Adverse effects:-
Causes G.I disturbances , liver damage , bone marrow depression
14. These are systemic anti fungal agents they are having fungistatic and fungicidal action
depending on the concentration of the drug
They are chemically 5membered ring structure with nitrogen group
Mechanism of action of azoles:-
Inhibit ergosterol synthesis in the fungal cell memberane
Ergosterol a sterol component of cell memberane of fungi responsible for rigidity of
cell memberane
Azole binds to cytochrome p450 dependent 14-α demethylase enzyme responsible for
synthesis of ergosterol from lanosterol & inhibit the action.
Imidazoles
Ketoconazole:-
1st azole is used orally for systemic infections
pharmacokinetics
orally ,absorbed from GIT , metabolized in liver & t½ of drug is 1.5-6hrs.
Adverse effects :
Nausea and vomting are common side effects
15. Contraindicated :-
In pregnant women and nursing women
Uses :-
» Dermatophytosis can be treated
» Controls and terminates the non CNS blastomycosis , oropharyngeal candidasis etc.
» Systemic mycosis can be treated
Triazoles :-
They are largely replaced azoles becoz of
Better absorption and distribution
High efficacy
Prolonged duration of action
Fewer drug interactions
Wider spectrum of activity
16. Fluconazole :-
Soluble in water and more beneficial compared to imidazoline agents
Pharmacokinetics:-
Distributed in body tissues & t½ of some drugs is 25-30 hrs. elimnated throgh urine
Adverse effects :-
Nausea, vomiting , headache, abdominal pain, and rashes
Uses :-
Mucocutaneous , oropharyngeal (150mg/day 2 weeks), vulvovaginal (150 mg orally ,
single dose)
Fungal keratitis
It is also effective againt blastomycosis, histoplasmosis , & sporotrichosis .
17. Allylamines
Terbinafine:-
Fungicidal agent which acts effectively against dermatophytes & candida species
Mechanism of action:-
squalene lanosterol ergosterol
squalene 14-demethylase
epoxide
Pharmacokinetics:-
Orally well absorbed , t½ of drug is 11-16hrs.
Adverse effects
1. Gastric disturbances, skin rashes , altered levels of liver enzymes,
hematological disorders.and hepatic impairment.
2. Dry ness, itching , skin rashes are common side effects
Uses:
Control onychomycosis of toe nail
Treating pityriasis vasicolour
To treat Tinea infections
