ANTIFUNGAL

1
 Fungi

are eukaryotes
VIJAy

 Fungal

infections Mycoses

 Less

frequent than bacterial & Virus but
common.

 Anyon...
FUNGI MAY BE CLASSIFIED AS YEAST OR MOULDS.
Yeast like pathogenic
 Histoplasmosis


Coccidioidomycosis

Blastomycosis
 ...
Oropharyngeal
 Vaginal candidiasis
 Sporotrichosis (Granulomatus of skin & Lymph abscess)
 Pityrosporum orbiculare - h...


Fungal infections classified as Superficial & Deep
mycosis (Systemic)



Superficial affecting skin, hair, nails, muco...


Systemic fungal infections: Affect deeper tissues
and organs.


Systemic candidiasis (RTI)



Meningitis, endocarditi...


Fungal cell structure and function is essential for
understanding the pharmacology of antifungal agents.



Four targe...
Fungal Cell Wall contain β- 1,3-D-glucan
 Depletion of glucan  Leads to death


Capsofungin

8
Altering membrane permeability

AMPHOTERICIN-B

Leading to cell death.

9
MEMBRANE SYNTHESIS


Ergosterol is the predominant sterol in many pathogenic
fungi.
Squalene
Terbinafine
squalene 2,3 epo...


Inhibits DNA synthesis by blocking the functions of
a key enzyme in DNA replication- thymidylate
synthetase.



Fungal...
12
CLASSIFICATION BASED ON MECHANISM OF ACTION
Inhibitor of cell wall
synthesis:


Caspofungin

Drugs altering membrane
synt...
Drugs altering membrane permeability


Amphotericin-B

Nystatin

Hamycin

Amphotercin:


First drug introduced in 1950s
...


MOA:

Lipophilc end

Hydrophilc end
Creates ion channel

15

Leading to cell death.
PK:


Poor absorbed from GIT- effective against intestinal fungal
infection



For systemic - IV slow infusion



Peak ...
Antifungal spectrum & uses:


After advent of azoles groups, the use of AMB declined.



Still it is DOC for


Treatmen...
Dose: 0.5 mg/kg/day
 Adverse events:




Acute reaction (infusion related events, chills, fever,
headache, nausea, vomi...


3 new formulations available


AMB Lipid complex (ABLC): 35% AMB incorporated in
ribbon like particles of dimyristoyl ...
 Special

features of these formulations:



Milder acute reaction



Dec. infusion associated side effects



Can be ...


Nystatin:



Similar to AMB in antifungal properties



high systemic toxicity so used locally only
Poorly absorbed f...


Drugs altering membrane synthesis
Azoles: 1970



Broad spectrum



Fungistatic / Fungicidal



Most commonly used
...


Triazoles : Three nitrogen in structure 1980





Fluconazole, itraconazole, voriconazole, Terconazole
Topical for s...
Acetyl CoA

Squalene

Allylamine
Drugs (Terbinafine)

Squalene
monooxygenase
Squalene-2,3 oxide

Lanosterol

Azoles

14-α-...


Miconazole & clotrimazole:
Topical use
 Cream, gel, spray, lotion ,solution , pessary








Dermatophyte infecti...
Ketoconazole:
First orally effective broad spectrum antifungal
 Effective against


Dermatophytosis
 Deep mycosis
 Can...


Dose : 200 mg OD or BD



Adverse events:


Nausea , vomiting , anorexia



Headache , paresthesia, alopecia



Red...


Drug interactions: Inhibits CYP450 enzyme


H2 receptor blockers



↑ Sr conc of cisapride, terfenadine, astemizole, ...


Use: Restricted use, most serious mycoses


Dermatophytosis: conc in stratum corneum



Monilial vaginitis : 5-7 days...
RESISTANCE

May develop by altered
demethylase or
by enhanced removal from
the fungal cell.


30
Fluconazole:


Newer water soluble triazole



Oral, IV as well as topical



Broad spectrum antifungal activity


Can...


Pharmacokinetics:


94% oral bioavailability



Not affected by food or gastric pH



Primarily excreted unchanged i...


Drug Interactions:


Effects hepatic drug metabolism to lesser extent than
Ketoconazole





H2 blockers & PPI do no...


Disseminated candidiasis, cryptococcal, coccidiodal
meningitis & other systemic fungal infections:


200-400 mg / day ...
Itraconazole:





Broadest spectrum of activity also against aspergillus
Fungistatic

Pharmacokinetics:


50-60% bioa...


Adverse events:



Dizziness, pruritis , headache, hypokalemia, hypotension



Increase plasma transaminase





G...


Uses:


DOC for paracoccidomycosis & chromoblastomycosis



DOC for histoplasmosis & blastomycosis in AIDS patients

...
Voriconazole:



High oral bioavailability, low protein binding



Good CSF penetration



Metabolized by CYP2C19



...
Dose : 200 mg BD
 Adverse events:




Transient visual changes like blurred vision , altered color

perception & photop...
Cell wall synthesis inhibitor: Capsofungin


Introduced in 2000s.



Echinocandins



MOA: Inhibits- β-(1,3)-D-glucan

...


Active against wide variety of fungi.



Effective treatment for Aspergillus infection and

Candidiasis (Esophageal, i...
5 Flucytosine




Prodrug, pyrimidine analogue, anti metabolite

Mechanism of action
Converted to 5 FU by FUNGAL CYTOSIN...
5-flucytosine permease 5-flucytosine
(outside)
(inside)
Cytosine
deaminase

5-fluorouracil

5dUMP
(inhibits
thymidylate
sy...


Uses: in combination with AMB in cryptococcal meningitis



,



Advantages of combination:
Entry of 5 FC
 Reduced t...
SYSTEMIC ALLY FOR TOPICAL INFECTIONS


Terbinafine:
Orally & topically effective drug against candida &
dermatophytes
 F...
Adverse events:
 Nausea , vomiting , Diarrhoea
 Taste disturbances
 Rarely hepatic dysfunction
 Topical: erythema , it...
Griseofulvin :


Systemic administration for topical infections



Fatty meal inc. BV



T1/2- 24hrs





Obtained f...


Uses:-



Dematophytosis caused by Microsporum



Trichophyton, Epidermatophyton



Duration of therapy depend open ...
OTHER DRUGS
 Ciclopirox

olamine - may block amino acid
transport - penetrates well - useful for Candida
and dermatophyte...
Disease

1st choice drugs

2nd choice drugs

Candiasis
oral/vaginal/cutaneous
disseminated

FLU/NYS/CLO
AMB/VOR

ITR
FLU

...
Topical
Ketoconazole
Miconazole
Clotrimazole
Terbinafine
Nystatin

VIJAy

Systemic
administration
Griseofulvin
Ketoconazol...
SPECTRUM OF ACTION

AMB

5FC

KTZ

FLU

ITR

Aspergillus

--

--

--

Y

Blastomycosis

--

Y

Y

Y

cryptococcus

Y

--

...
TOPICAL AZOLES
 Clotrimazole

 Terconazole

 Miconazole

 Sulconazole

 Econazole

 Tioconazole

 Oxiconazole

 Bu...


Nystatin:

Candidiasis only



Griseofulvin: Dermatophytosis only



Terbinafine : Dermatophytosis & candidiasis



...
Some important characteristics:


Broad spectrum: AMB, KTZ, FLU, ITR



Resistance: 5 FC



Nephrotoxic/ Anemia: AMB

...


Grisofulvin K M C

VIJAy

For SYSTEMIC

F I T Nystatin

For Topical
56
TH

VIJAy

57
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  • Sporotrichosis; chronic granulomatous infection usually of skin and lymph node marked by formation of abscesses, caused by fungal sporothrixPityrosporum : a genous of lipophilic yeast present in normal skin
  • Endocarditis: inflammation or infection of heart valvesmucormycosis: caused by mucoraceae. Afinity towards blood vessels cause thrombosis Blastomycosis: caused by inhalation of blastomyces. It produce inflammation lesion of skin
  • Antibiotic
  • Kalaazaar: infections caused by Leishmania an intracellular protozovan fever, splenic enlargement
  • Nephrotoxicity renal tubulaes acidosis,Anemia dec. erythropoietin production from damaged renal tubules.Azotemia inc. ureates levels in blood
  • At high doses it acts as fungicidal
  • ELEVATES SERUM TRANSAMINES
  • Azoles dec. ergosterol production , so no use of AMB
  • Hypotension due to odema formation
  • 16. antifungal

    1. 1. ANTIFUNGAL 1
    2. 2.  Fungi are eukaryotes VIJAy  Fungal infections Mycoses  Less frequent than bacterial & Virus but common.  Anyone can succumb to fungal infection but more at risk in older people, diabetics, pregnant women and burn wound. 2
    3. 3. FUNGI MAY BE CLASSIFIED AS YEAST OR MOULDS. Yeast like pathogenic  Histoplasmosis  Coccidioidomycosis Blastomycosis  Cryptococcosis  Candida  Mould group of pathogenic  Aspergillosis  Dermatophytes  Mucormicosis  Candida Spp. and Pneumocyst carinii are not pathogenic  pathogenic in immuno compromised patients OPPORTUNISTIC INFECTION. 3
    4. 4. Oropharyngeal  Vaginal candidiasis  Sporotrichosis (Granulomatus of skin & Lymph abscess)  Pityrosporum orbiculare - hyperpigmetnation  4
    5. 5.  Fungal infections classified as Superficial & Deep mycosis (Systemic)  Superficial affecting skin, hair, nails, mucous membranes.  Most common: Dermatophytoses Encouraged by hot (Hygiene)and humid environment  Dermatophytoses classified according to body site • Tinea barbae • Tenia capitis(Scalp) • Tinea corporis(Body) • Tinea manuum(Hand) • Tinea pedis(Foot) • Tinea unguium(Nails)  5
    6. 6.  Systemic fungal infections: Affect deeper tissues and organs.  Systemic candidiasis (RTI)  Meningitis, endocarditis  Rhinocerebral mucormycosis (Thrombosis)  Pulmonary aspergillosis  Blastomycosis (lesion of skin)  Histoplasmosis (cough , fever, multiple pneumonic infiltrates)  Coccidioidomycosis  Pneumocystis carinii pneumonia 6
    7. 7.  Fungal cell structure and function is essential for understanding the pharmacology of antifungal agents.  Four targets in fungal pathogens:  Fungal Cell Wall  Fungal Cell Membrane  DNA/RNA Synthesis  Inhibition of fungal mitosis 7
    8. 8. Fungal Cell Wall contain β- 1,3-D-glucan  Depletion of glucan  Leads to death  Capsofungin 8
    9. 9. Altering membrane permeability AMPHOTERICIN-B Leading to cell death. 9
    10. 10. MEMBRANE SYNTHESIS  Ergosterol is the predominant sterol in many pathogenic fungi. Squalene Terbinafine squalene 2,3 epoxide Lanosterol Azoles 14-demethylase Ergosterol 10
    11. 11.  Inhibits DNA synthesis by blocking the functions of a key enzyme in DNA replication- thymidylate synthetase.  Fungal cell mitosis by disrupting mitotic spindle formation-a critical step in cellular division. 11
    12. 12. 12
    13. 13. CLASSIFICATION BASED ON MECHANISM OF ACTION Inhibitor of cell wall synthesis:  Caspofungin Drugs altering membrane synthesis  Inhibition of ergosterol Drugs altering membrane permeability Trimidazoles  Fluconazle,  Itraconazole,  Voriconazole Imidazoles  Ketoconazole,  Miconazole,  Clotrimazole. Amphotericin-B,  Nystatin,  Hamycin  Inhibit nucleic acid Synthesis  5 Flucytosine Disruption of mitotic spindle  Griseofulvin  Inhibition of ergosterol+ lanosterol  Terbinafine 13
    14. 14. Drugs altering membrane permeability  Amphotericin-B Nystatin Hamycin Amphotercin:  First drug introduced in 1950s  Obtained from Strepomyces nodosus  Systemic Antifungal drug  Polyene group- Multi lactone ring with conjugated double bond .  One end – Hydroxyl group (OH)–polar (Hydrophilc)  Other end – Hydrocarbon group-non polar (Lipophilic) 14
    15. 15.  MOA: Lipophilc end Hydrophilc end Creates ion channel 15 Leading to cell death.
    16. 16. PK:  Poor absorbed from GIT- effective against intestinal fungal infection  For systemic - IV slow infusion  Peak antifungal activity at pH 6.0-7.5.  High con- Fungicidal, low- fungi static  90% plasma protein binding  T1/2- 15days ( binds with sterol)  It is insoluble in water  colloidal suspension with sodium 16 desoxycholate(1:1)
    17. 17. Antifungal spectrum & uses:  After advent of azoles groups, the use of AMB declined.  Still it is DOC for  Treatment of Invasive aspergillosis in immune compromised patients  Mucormycosis  Rapidly progressing histoplasmosis, blastomycosis, meningeal cocciodomycosis(intrathecal) Topical use:- 3% cream for oropharngeal candidiasis,  Reserve drug for resistant case of KALA AZAR. Leishmania . Splenic enlargement  17
    18. 18. Dose: 0.5 mg/kg/day  Adverse events:   Acute reaction (infusion related events, chills, fever, headache, nausea, vomiting)  Long term toxicity: nephrotoxicity(>4g), anemia (D. Ery)  azotemia, hypokalemia  CNS toxicity : intrathecal administration-seizures, headache, vomiting, nerve palsies   Hepatotoxicity rarely DI:Flucytosine –synergetic action inc. permeability FC  Aminoglycoside inc. renal toxicity.  18
    19. 19.  3 new formulations available  AMB Lipid complex (ABLC): 35% AMB incorporated in ribbon like particles of dimyristoyl phospholipids  AMB colloidal dispersion (ABCD): Disc shaped particles containing 50% each of AMB & cholesteryl ester in aqueos dispersion  Liposomal AMB (Small Unilamellar Vesicles) : 10% AMB incorporated in SUV made up of lecithin 19
    20. 20.  Special features of these formulations:  Milder acute reaction  Dec. infusion associated side effects  Can be used in intolerance to conventional preparations  Lower nephrotoxicity & anemia  Deliver AMB to reticular endothlial cell of liver spleen so useful in leshmania & immuno compromised 20
    21. 21.  Nystatin:  Similar to AMB in antifungal properties  high systemic toxicity so used locally only Poorly absorbed from mucus membrane  Available as ointment, cream, powder, tablet   Uses:5 lac U in intestinal moniliasis TDS  1 lac U in vaginitis (1mg=2000U)  Can be used in oral, cutaneous, conjunctival candidiasis  Adverse events: Gastrointestinal disturbances with oral tablets  21
    22. 22.  Drugs altering membrane synthesis Azoles: 1970   Broad spectrum  Fungistatic / Fungicidal  Most commonly used   Synthetic anti fungals Classified as imidazoles & triazoles Imidazoles: Two nitrogen in structure Topical: Econazole, Miconazole, Clotrimazole  Systemic : ketoconazole   Newer : Butaconazole, Oxiconazole, Sulconazole 22
    23. 23.  Triazoles : Three nitrogen in structure 1980    Fluconazole, itraconazole, voriconazole, Terconazole Topical for superficial infections Both these groups are  Structurally related compounds  Have same mechanism of action  Have similar antifungal spectrum 23
    24. 24. Acetyl CoA Squalene Allylamine Drugs (Terbinafine) Squalene monooxygenase Squalene-2,3 oxide Lanosterol Azoles 14-α-demethylase (ergosterol)
    25. 25.  Miconazole & clotrimazole: Topical use  Cream, gel, spray, lotion ,solution , pessary     Dermatophyte infections ( pedis, cruris, corporis, versicolor) Candida: oral pharyngeal, vaginal, cutaneous Adverse events:  Local irritation , itching or burning  Miconazole shows higher incidence of vaginal irritation & pelvic cramps  No systemic side effects 25
    26. 26. Ketoconazole: First orally effective broad spectrum antifungal  Effective against  Dermatophytosis  Deep mycosis  Candidiasis   Pharmacokinetics:  Effective orally  Requires acidic environment for absorption  High protein binding  Readily distributed, not to BBB  Metabolized in liver, excreted in bile t1/2 = 8-10 hrs 26
    27. 27.  Dose : 200 mg OD or BD  Adverse events:  Nausea , vomiting , anorexia  Headache , paresthesia, alopecia  Reduces steroid, testosterone & estrogen synthesis  Thus can cause gynaecomastia,  oligospermia, loss of libido & impotence in males.  Menstrual irregularities & amenorrhoea in females  Elevation of liver enzymes  Hypersensitivity reaction like skin rashes 27
    28. 28.  Drug interactions: Inhibits CYP450 enzyme  H2 receptor blockers  ↑ Sr conc of cisapride, terfenadine, astemizole, quinidine  Phenytoin toxicity  Sulfonylureas: hypoglycemia  Cyclosporine: nephrotoxicity  Warfarin: bleeding  Rifampicin, phenytoin ↑ metabolism of ketoconazole  Should not combine with AMB 28
    29. 29.  Use: Restricted use, most serious mycoses  Dermatophytosis: conc in stratum corneum  Monilial vaginitis : 5-7 days  Systemic mycosis: blastomycosis, histoplasmosis, Coccidioidomycosis  Less efficacious than AMB & produces slower response  Efficacy low in immunocompromized and meningitis  Lower toxicity than AMB higher than triazoles  So triazoles have replaced it in systemic mycosis  High dose used in cushings syndrome  Topical: T.pedis, cruris, corporis, versicolor 29
    30. 30. RESISTANCE May develop by altered demethylase or by enhanced removal from the fungal cell.  30
    31. 31. Fluconazole:  Newer water soluble triazole  Oral, IV as well as topical  Broad spectrum antifungal activity  Candida, cryptococcosis, coccidioidomycosis  Dermatophytosis  Blastomycosis  Histoplasmosis  Sporotrichosis 31
    32. 32.  Pharmacokinetics:  94% oral bioavailability  Not affected by food or gastric pH  Primarily excreted unchanged in urine t1/2 = 25 -30 hrs  Poor protein binding (10-12%)  Widely distributed crosses BBB   T ½ -27-32hrs Adverse events:  GIT upset  Headache, alopecia, skin rashes, hepatic necrosis  Teratogenic effect  CYP450 Enzyme inhibiting property less  No anti androgenic & other endocrine effects 32
    33. 33.  Drug Interactions:  Effects hepatic drug metabolism to lesser extent than Ketoconazole   H2 blockers & PPI do not effect its absorption Uses:  Candida:    150 mg oral dose  cure vaginal candidiasis with few relapse Oral candidiasis  2 weeks treatment required Tinea infections & cutaneous candidiasis:  150 mg weekly  4 weeks, tinea unguim  12 months 33
    34. 34.  Disseminated candidiasis, cryptococcal, coccidiodal meningitis & other systemic fungal infections:  200-400 mg / day 4- 12 weeks or longer  3 days oral  Candida UTI (100-800mg OD)  Meningitis preferred drug  Eye drops for fungal keratitis 34
    35. 35. Itraconazole:    Broadest spectrum of activity also against aspergillus Fungistatic Pharmacokinetics:  50-60% bioavailability, absorption is variable, enhanced by food & gastric acidity  High protein binding 99 %  Well distributed accumulates in vaginal mucosa, skin, nails but CNS penetration is poor  Metabolized in liver CYP3A4 excreted in feces t1/2= 30- 64hr 35
    36. 36.  Adverse events:   Dizziness, pruritis , headache, hypokalemia, hypotension  Increase plasma transaminase   GI Intolerance Rarely Hepatotoxicity Drug interactions:  Oral absorption decreased by antacids, H2 blockers  Rifampicin, phenytoin induce metabolism  Potentiates effect of hypnotic drugs  Inhibits CYP3A4 drug interaction profile similar to ketoconazole 36
    37. 37.  Uses:  DOC for paracoccidomycosis & chromoblastomycosis  DOC for histoplasmosis & blastomycosis in AIDS patients  Esophageal, oropharyngeal vaginal candidiasis   Dermatophytosis: less effective than fluconazole   Not superior to fluconazole : 200 mg OD X 3 days 100- 200 mg OD X 15 days Onychomycosis : 200 mg / day for 3 months  Intermittent pulse regime 200 BD once weekly for 3 months equally effective  Aspergillosis: 200 mg OD/ BD with meals for 3 months or more 37
    38. 38. Voriconazole:   High oral bioavailability, low protein binding  Good CSF penetration  Metabolized by CYP2C19  Doesn’t require gastric acidity for absorption   II generation triazole T1/2-6 hrs Uses:  DOC for invasive aspergillosis  Most useful for esophageal candidiasis  First line for moulds like fusarium  Useful in resistant candidal infections 38
    39. 39. Dose : 200 mg BD  Adverse events:   Transient visual changes like blurred vision , altered color perception & photophobia  Rashes in 5 -6 %  Elevated hepatic enzymes  Prolongation of QT 39
    40. 40. Cell wall synthesis inhibitor: Capsofungin  Introduced in 2000s.  Echinocandins  MOA: Inhibits- β-(1,3)-D-glucan  T½-9-11hrs.  P.B- albumin 97%  Excreted through urine(41%) and feces (35%)  Dose: IV infusion (intial 70mg slowly then 50mg/day) 40 »Contd.,
    41. 41.  Active against wide variety of fungi.  Effective treatment for Aspergillus infection and Candidiasis (Esophageal, intra abdominal peritontis).  ADR: Sensation of warmth, flushing, rashes.  DI:- Cyclosporine hepatotoxicity. 41
    42. 42. 5 Flucytosine   Prodrug, pyrimidine analogue, anti metabolite Mechanism of action Converted to 5 FU by FUNGAL CYTOSINE DEAMINASE  5FU  5FUTP RNA DEFECTIVE  5FU 5dUMP Inhibit Thymidylate synthesis  , Human cells cant convert it to 5FU  Adverse events:   Bone marrow toxicity , GIT , Alopecia, skin rashes, itching , rarely hepatitis
    43. 43. 5-flucytosine permease 5-flucytosine (outside) (inside) Cytosine deaminase 5-fluorouracil 5dUMP (inhibits thymidylate synthase) RNA Phosphoribosyl transferase 5-FUMP
    44. 44.  Uses: in combination with AMB in cryptococcal meningitis  ,  Advantages of combination: Entry of 5 FC  Reduced toxicity  Rapid culture conversion  Reduced duration of therapy & resistance 
    45. 45. SYSTEMIC ALLY FOR TOPICAL INFECTIONS  Terbinafine: Orally & topically effective drug against candida & dermatophytes  Fungicidal : shorter courses of therapy required & low relapse rates  Mechanism of action:  Inhibition of Lanosterol + Ergosterol production  Pharmacokinetics:       Well absorbed orally 75% Highly keratophilic & lipophilic High protein bound , poor BBB permeability Metabolized in liver excreted in urine & feces t1/2- 15 days Negligible effect on CYP450
    46. 46. Adverse events:  Nausea , vomiting , Diarrhoea  Taste disturbances  Rarely hepatic dysfunction  Topical: erythema , itching , dryness , urticaria, rashes Uses:  Dermatophytosis: topically/ orally 2- 6 weeks  Onychomycosis: first line drug 3- 12 months  Candidiasis: less effective 2- 4 weeks therapy may be used as alternative 250 mg OD
    47. 47. Griseofulvin :  Systemic administration for topical infections  Fatty meal inc. BV  T1/2- 24hrs   Obtained from Pencillium griseofulvum   Fungistatic Drug binds to keratin in stratum corneum of the skin Mechanism of action:- Interact with polymerised microtubles causing disruptions of mitotic spindle and arrest mitosis metaphase 47
    48. 48.  Uses:-  Dematophytosis caused by Microsporum  Trichophyton, Epidermatophyton  Duration of therapy depend open the body area  TINEA CORPORIS – 2-4 WEEKS    TINEA CAPITIS -4-6WEEKS TINEA PEDIS – 4-8 WEEKS Dose- 500-1000mg/day/in 2doses 48
    49. 49. OTHER DRUGS  Ciclopirox olamine - may block amino acid transport - penetrates well - useful for Candida and dermatophytes  Haloprogin - useful for dermatophytes and Candida, may cause burning  Tolnaftate - useful for dermatophytes - inhibits synthesis of macromolecules  Undecylenic  KI acid - dermatophytes - taken orally for cutaneous sporotrichosis may cause a rash and irritation of salivary and lacrimal glands
    50. 50. Disease 1st choice drugs 2nd choice drugs Candiasis oral/vaginal/cutaneous disseminated FLU/NYS/CLO AMB/VOR ITR FLU Cryptococcosis AMB+/- 5-FC FLU Histoplasmosis ITR/AMB FLU Coccidioidomycosis AMB/FLU ITR/KTZ Blastomycosis ITR/AMB KTZ/FLU Sporotrichosis AMB ITR Paracoccidioidomycosis ITR AMB Aspergillosis AMB/VORI ITR Mucormycosis AMB - Chromomycosis ITR VIJAY KTZ/5-FC 50
    51. 51. Topical Ketoconazole Miconazole Clotrimazole Terbinafine Nystatin VIJAy Systemic administration Griseofulvin Ketoconazole Fluconazole Itraconazole Terbinafine 51
    52. 52. SPECTRUM OF ACTION AMB 5FC KTZ FLU ITR Aspergillus -- -- -- Y Blastomycosis -- Y Y Y cryptococcus Y -- Y Y Coccidiodo -- Y Y Y candida Y Y Y Y Histoplasma -- Y Y Y Mucor -- -- -- -- Sporotrichosis -- -- Y Y chromoblast dermatophyte 52 Fusarium
    53. 53. TOPICAL AZOLES  Clotrimazole  Terconazole  Miconazole  Sulconazole  Econazole  Tioconazole  Oxiconazole  Butoconazole  Sertaconazole
    54. 54.  Nystatin: Candidiasis only  Griseofulvin: Dermatophytosis only  Terbinafine : Dermatophytosis & candidiasis  Caspofungin: Aspergillosis & candidiasis 54
    55. 55. Some important characteristics:  Broad spectrum: AMB, KTZ, FLU, ITR  Resistance: 5 FC  Nephrotoxic/ Anemia: AMB  LEUCOPENIA: 5 FC  GIT upset: All  Over all toxicity: highest for AMB lowest for fluconazole, itraconazole 55
    56. 56.  Grisofulvin K M C VIJAy For SYSTEMIC F I T Nystatin For Topical 56
    57. 57. TH VIJAy 57
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