Antifungal agents

Systemic & Topical

Some are fungistatic,

while others are fungicidal
 Fungi- Cell wall- Chitin
- Cell membrane- ergosterol - resembles cholesterol
 Fungal infections are called as Mycoses.

 Fungal infections are opportunistic.

 More common in D.M, Cancer, AIDS, Pregnancy & pt’s

receiving immunosuppressant's.

 Fungal infections may be systemic or superficial.

 These drugs are used for superficial & deep fungal
infections.
 Fungal infection require prolonged therapy.
Fungal infections & causative organisms.

Superficial mycosis Deep mycosis

Dermatophytes Aspergillus
-Epidermophyton Blastomyces
-Trichophyton
- Microsporum Cryptococcus
Coccidioides
Candida Candida
Malassezia furfur Histoplasma
Mucormycosis
Sporotrichosis
 Classification-
1. Antibiotics :-
Amphotericin -B, Nystatin, Hamycin, Natamycin, Griseofulvin.
2) Antimetabolite:- Flucytosine (5-FC).
3) Azoles:-
a) Imidazoles (Topical) : Clotrimazole, Econazole, Miconazole &
Oxiconazole. (Systemic)- Ketoconazole.
b) Triazoles (Systemic) : Fluconazole, Itraconazole & Voriconazole.
4) Allylamine:- Terbinafine
5) Other topical agents- Tolnaftate, Benzoic acid, Quinoidochlor,
Ciclopirox, Butenafine & Sod. Thiosulfate.
 M.O.A of

Squalene
Terbinafine
AMB-
 Streptomyces nodosus.
 Polyene antibiotic with many double bonds.
 Its has broad spectrum antifungal.
P.K
 Poorly absorbed from GIT
 Effective only in intestine but not systemic fungal inf’s.
 Highly bound to sterols & lipoproteins-long acting.
 Peak antifungal activity at alkaline PH.
 T1/2 -15days, Fungistatic/ cidal.
M.O.A of Polyenes:-

Binds to ergosterol in fungal cell membrane

Form pores in the membrane

Permeability of membrane increases

Leakage of intracellular contents of the fungi

Death of the fungi

A/E’s:-
 A/C reactions-Fever, chills, muscle spasm, V, dyspnea,
hypotension on IV infusion..
 Thrombophlebitis, nephrotoxicity, anaemia, neurotoxicity &
bone marrow depression.
Uses :-
 DOC in Aspergilosis, Mucromycosis, Cryptococcosis,
Sporotrichois Histoplasmosis, Blastomycosis,
Coccidioidmycosis & Paracoccidioidmycosis.
 Candida cystitis

 Orally for fungal gut wall infections.

 Topical- Candidiasis.

 Kala azar & Leishmaniasis as a alternative.

Nystatin-
 Streptomyces noursei.
 Polyene & MAO is similar to AMB.
 Too toxic for systemic & used topically.
 Locally in superficial candidiasis.
 Vaginal candidiasis, Oral thrush- corticosteroid induced
candidiasis.

 Oral ,corneal, cutaneous & conjunctival candidiasis

A/E’s:-systemic toxicity & bad taste.
Hamycin- Similar to Nystatin.
 Topically for cutaneous candidiasis & otomycosis.
Griseofulvin- fungistatic
 Penicillium griseofulvum.
 Ineffective topically & give through orally for superficial
dermatophytosis.
 Micronisation & fatty meals improves B.A.
 T1/2 is 24hrs & duration of Rx varies from 3wks to 1yr.
Uses:-
 Rx dermatophytosis - drug gets actively conc.
 Long term therapy to attain fungal resistant keratin.
 Tinea capitis, pedis, barbae & corporis.
 Griseofulvin
M.O.A

binds to micro tubular Ptn's in nucleus

Disrupts the mitotic spindles

inhibits fungal mitosis Binds to newly synthesised

keratin making them resistant to
fungal invasions.
Duration of the Rx with griseofulvin –
T. Capitis - Scalp & Hair - 4-6wks
T. Cruris - Groin - 3wks
T. Corporis - Body - 3-4 wks
T. Unguium - Nails/ Fingers - 6-9months
- Toe - 12months.
T.pedis - foot - 4-8wks.
T.pedis
Fungal memgitis

Oral candidiasis

T.barbae
Flucytosine- Prodrug
 Structurally analogue of 5-FU (anti neoplastic drug).
 Effective against Cryptococcus neoformans & some strains
of Candida.
 Used with AMB in cryptoccocal meningitis & systemic
candidiasis.
 Used alone- develops resistance.
A/E’s- Bone marrow depression, GIT disturbances.
Flucytosine
Enters in to fungi
5-fluorouracil

Inhibits thymidylate synthase enzyme

Interferes with DNA synthesis

 AZOLES
Squalene
 Azoles are newer synthetic
antifungal agents that are effective Squalene epoxidase

orally & less toxic.

Lanosterol
Imidazoles

Less selective & Short acting M.O.A

Triazoles Cyt-p450 dependent 14α demethylase

More selective & longer acting

Ergosterol

Antifungal Spectrum- Dermatophytes, Candida, Deep mycosis

Cryptococcocal, Histoplasmosis, Nocardia, G+ve and anaerobic bacteria.
Ketoconazole-
 Well absorbed orally in acidic PH.

 B.A- antacids, H2, PPI & food, grape juice.

 A/E’s- N,V, headache, allergic reactions, Hepatotoxicity.

 X synthesis of adrenal & gonadal steroids – Gynaecomastia,

infertility, decreased libido, azoospermia, menstrual
irregularities & HTN.

Uses:- Mucocutanoeus candidiasis, Dermatophytosis &

Cushing’s syndrome
Clotrimazole & Miconazole-
 Used in topically in dermatophytic infections &
mucocutanoeus candidiasis.
 Miconazole penetrates skin layer & remains for 3-4days.
 It has better efficacy.
 Clotrimazole troche – oral thrush.
Prep-
 Clotrimazole- lotion, cream, vaginal pessary-100mg given
at bed time for 7days or 200mg daily for 3 days or 500mg as
S.D.
 Miconazole- 2-4% ointment, gel, cream, lotion & vaginal
suppository ( 100-200mg).
Fluconazole-
 Attains good conc. in CSF.
 Useful in fungal meningitis.
 Available oral & IV use.
Uses-
 Cryptoccocal meningitis after initial Rx AMB.
 DOC in coccididal meningitis.
 Systemic & Mucocutanoeus candidiasis.
 Tinea infections
 High cost makes it less preferable.
Itraconazole-
 Most potent azole.
 orally absorption is by food &gastric fluid & T1/2-36 hrs.
 Available for both oral & IV use.
A/E’s- headache, dizziness, GIT upset, allergy. Hepatitis &
hypokalemia.
Uses-
 DOC in most of systemic mycosis.
 Onychomycosis, Candidiasis & Dermatophytosis.

 Econazole, Terconazole, Ticonazole, Butaconazole,

Oxiconazole & Sulconazole- Topical use as creams/lotions
for dermatophytosis & mucocutaneous candidiasis.
Terbinafine- synthetic
 Effective in Dermatophytes & Candida
 Orally effective & is a fungicidal.
 Gets concentrated in keratin like griseofulvin.
 It X an enzyme involved in fungal ergosterol synthesis.
 Used in dermatophytosis, Pityriasis, Onychomycosis &
candidiasis.
 Preferred in Onychomycosis 250mg OD for 12wks-
superior to azole & griseofulvin.
M.O.A-
Squalene
fungicidal

Terbinafine Squalene 2,3-epoxidase

Lanosterol

Azoles

Ergosterol

AMB

Integrity & Function of fungal cell membrane

Pneumocandins ( echinocandins)-
 X fungal cell wall formation resulting break/ruptures.

e.g., Caspofungin & Micafungin.

 Useful in candidiasis & Aspergillosis.

Topical agents-

 Salicylic acid, benzoic acid, Tolnaftate & Ciclopirox

olamine used for dermatophytosis & Pityriasis versicolor.
 Selenium sulfide- Tinea versicolor caused by Malassezia
fur.
 Available as a shampoo.
Anthelmintics
Scabies
Pediculosis
 Drugs used in Amoebiasis
Leishmaniasis & Trypanosomiasis
Anti-amoebic drugs
• Amoebiasis caused by the protozoan common Entamobea
histolytica is a tropical disease common in developing
countries.
• spreads by faecal contamination of food & water.
• I0 affects colon and 20 sites are liver, lungs & brain.
• A/c amoebiasis is characterized by bloody mucoid stools &
abdominal pain.
• Chr. Amoebiasis is as anorexia, abd.pain, intermittent
diarrhea & constipation.
• Cyst passers/ carriers are from free symptoms.
Thank u