This document provides a classification and overview of pathogenic fungi and antifungal drugs. It begins by classifying fungi into yeasts, yeast-like fungi, molds, and dimorphic fungi. It then categorizes fungal infections as superficial, cutaneous, subcutaneous, or systemic/opportunistic. The document further discusses the classification, mechanisms of action, pharmacokinetics, uses, and adverse effects of various antifungal drug classes including polyenes, azoles, allylamines, echinocandins, and others. It provides details on specific drugs like amphotericin B, nystatin, ketoconazole, fluconazole, itraconazole,

1. Dr. Vikram Sharma, MD
MAMC

2. Eukaryote

4. 1. Yeasts – Crypyptococcus neoformans
2. Yeast –like fungi- Candida albicans
3. Moulds – Dermatophytes
(Trichophyton, Epidermophyton, Microsporum)
4. Dimorphic fungi- (Filament - 25◦; Soil / Yeast - 37◦; Host)
Blastomyces dermatitidis, Histoplasma
capsulatum, Coccidioides immitis, Sporothrix
Pathogenic Fungi Classification

6. Fungal infections (Mycoses)
SUPERFICIAL - Black Piedra
CUTANEOUS - Tinea
SUBCUTANEOUS - Sporotrix
SYSTEMIC-
Blastomycosis, Histoplasmosis, Coccidioidomycosis,
Cryptococcosis
OPPORTUNISTIC –
Mucormycosis, Aspergillosis,
Candidiasis

7. Classification based on MOA
1. Acting on fungal cell wall :
Echinocandins
2. Acting on fungal cell membrane : Polyenes,
Azoles & Allylamine
3. Inhibition of nucleic acid synthesis: 5-Flucytosine.

8. 4. Acting on mitotic spindle: Griseofulvin
5. Topical: Cicloprix, Tolnaftate,
Haloprogin,Butenafine, Undecylenic acid, Topical
Azoles, Clotrimazole, Nystatin

9. DRUGS
i)Polyenes: Amphotericin, Nystatin, Natamycin
ii)Azoles:
A) Imidazoles - Ketoconazole, Butaxonazole,
Clotrimazole, Econazole, Miconazole
Oxiconazole, Sulconazole
B) Triazoles – Fluconazole Itraconazole Tioconazole

10. DRUGS
iii) Allyamines: Terbinafine, Naftifine, Butenafine
(iv) Echinocandins: Caspofungin, Micafungin,
Anidulafungin

11. Mechanism of Action

12. Echinocandins

13. Polyenes

14. Amphotericin B
Binds ergosterol in fungal cell membrane
Form pores in cell membrane
Cell contents leak out
Cell death

15. Squalene
Ergosterol
14--demethylase
Squalene Epoxidase
Lanosterol
Fungal cell membrane
Azoles & Allylamines
Allylamines
Azoles

16. 5-Flucytosine

17. Griseofulvin
Binds to polymerised microtubules
Disrupt Mitotic Spindles
Inhibit Mitosis

19. ECHINOCANDINS

20. Echinocandins
 Spectrum: Candida (Broad -spectrum activity against all
Candida species); Aspergillus
(NOT active againt Cryptococcus)
 High PPB
 Metabolites are eliminated by kidneys & GIT
 Available only as i/v formulations
 Adv.- Relatively low toxicity among the safest

21. Caspofungin
o FDA approved in 2001
o Dose – Single loading dose 70mg followed by
daily dose of 50mg iv over 1 hr
o Use -
 Invasive forms of candidiasis
 Invasive aspergillosis

22. Micafungin
FDA approved in 2005
 Candida esophagitis (150 mg/day)
 Candidemia (100mg/day)
 Prophylaxis of fungal infections in those
receiving stem cell transplant (50mg/day)
 D/I: Micafungin -↑ the levels of
nifedipine,cyclosporine and sirolimus

23. Anidulafungin
FDA approved in 2006
 Candida esophagitis (100mg 1st day followed by 50mg/day)
 Candidemia (200mg 1st day followed by 100mg/day)

24. Adverse Effects
 Flushing , phlebitis (Anidulafungin)
 Increase in liver enz, GI disturbances
(Caspofungin)

25. Lactone ring
Lipophilic part
 Amphotericin B:
 Streptomyces Nodosus
 Amphoteric
Hydrophilic part

26. Mechanism Of Resistance
 Replacement of ergosterol by other
sterols in fungal plasma membrane.

27. Pharmacokinetics
 Poorly absorbed orally
 Insoluble in water so colloidal
suspension prepared with sodium
deoxycholate(1:1 complex)
 t ½ = 15 days

28. Lipid formulations of AMB
Amphotericin B Lipid Complex(ABLC)
(ABLC; Abelcet®)
Amphotericin B Colloidal Dispersion(ABCD)
® ®)
Liposomal Amphotericin B
(L-AMB; Ambisome®)

29. part l
r ipi DMPC, PG
J Liposome Res 1993; 3:
451
AMB Lipid
complex
(ABLC)

30. AMB
Colloidal
Dispersion
(ABCD)

31. Hospital Practice 1992; 30: 53
Liposomal AMB
(Small unilamellar vesicles)

32. Antifungal spectrum
- Aspergillus
Broadest
spectrum
- Blastomyces
- Candida albicans
- Cryptococcus neoformans
- Coccidioides immitis
- Histoplasma capsulatum
- Mucor

33.  Systemic mycotic infections
• Invasive aspergillosis
• Rapidly progressive Blastomycosis &
Coccidiomycosis
• Mucormycosis
• Disseminated rapidly progressing
Histoplasmosis
• Cryptococcus neoformans (intra-
thecal)
Uses

34. Liposomes in the therapy of infectious
diseases and cancer 1989: 105
Antiprotozoal spectrum
• Mucocutaneous Leishmania
• Naegleria fowleri

35. Liposomes in the therapy of infectious
diseases and cancer 1989: 105
Release from
macrophage
Macrophage
Endocytosis
Liposome Lysosome
Fusion
Liposome
degradation
Endocytic
vesicle
Release in blood
compartment
Reserve drugs
for resistant
kala azar

36. Adverse events (Amphoterrible !!!)
o Acute reaction (infusion related)
o Long term toxicity
 Nephrotoxicity (Renal Tubular
necrosis, ↓ K+/Mg2+,Azotaemia; Irreversible)
 CNS toxicity (Arachanoiditis, Seizures)
 Anaemia (Hypochromic Microcytic)
o Hepatotoxicity (Jaundice,rarely)

37. Measures to Avoid Nephrotoxicity
 Prior hydration with 1L N.S.
 Avoid Concomitant Diuretics
 Liposomal AMB

38. Topical Uses
 Intestinal Monoliasis (Orally)
 Vaginitis
 Otomycosis (3 % drops)
 Mycotic infections of the bladder (bladder irrigation)
 Mycotic corneal ulcers & keratitis

39. Nystatin
 S. noursei
 Toxic; Locally
Uses:
 Intestinal moniliasis
 Vaginitis
 Prevention of oral candidiasis
 Oral, cutaneous, conjunctival candidiasis

40. Hamycin
 S. Pimprina
Topical use
 Thrush, cutaneous candidiasis,
trichomonas & monilial vaginitis,
otomycosis by aspergillus

41. Natamycin
Broad spectrum
Used topically
Fusarium solani keratitis, Trichomonas
& Monilial vaginitis

42. AZOLES

43. Azoles
 Synthetic (Imidazoles; Triazoles)
 Broad spectrum
 Fungistatic or fungicidal depending on conc.
of drug
 Also block fungal respiratory chain?

44. Imidazoles:
 Two nitrogen in structure
 Topical: Econazole, Miconazole,
Clotrimazole, Butaconazole, Oxiconazole,
Sulconazole
 Systemic: Ketoconazole

45. Triazoles
o Three nitrogen in structure
o Topical: Terconazole
o Systemic: Fluconazole, Itraconazole, Voriconazole

46. SYSTEMIC TOPICAL
 Ketoconazole
 Fluconazole
 Itraconazole
 Voriconazole
 Clotrimazole
 Miconazole
 Econazole
 Oxiconazole
 Sertaconazole
 Terconazole
 Sulconazole
 Tioconazole
 Butaconazole

47. Imidazoles

48. Miconazole & Clotrimazole
 Topical use:
 Miconazole - 2% ; Clotrimazole - 1%
 Uses:
 Dermatophyte infections
 Candida: oral pharyngeal, vaginal,
cutaneous
 Adverse events:
 Local irritation

49.  First orally effective broad spectrum antifungal
 Acidic environment favours absorption
Antacids, H2 blocker ↓ absorption
 CSF penetration is less Ineffective for fungal
meningitis
 Elimination thru Bile Ineffective for fungal
cystitis
Ketoconazole

50. Ketoconazole and Steroid hormone
synthesis
o Inhibit cholesterol side-chain cleavage
enzyme
 17α-hydroxylase - which converts cholesterol
to pregnenolone
 17,20-lyase ,which convert pregnenolone into
androgens
 11β-hydoxylase, which converts 11- deoxycortisol
to cortisol.

51. Ketoconazole
 ADRs:
 ↓ Steroid, Testosterone & Estrogen synthesis
o Males: Gynaecomastia, oligospermia ,
loss of libido & impotence
o Females: Menstrual irregularities
& amenorrhoea

52. Drug Interactions

53. Dangerous interaction with
terfenadine, astemizole and
cisapridePolymorphic ventricular
tachycardia (Torsades De Pointes)
Drug Interactions

54. Uses
Monilial vaginitis
Systemic mycosis
Topical: T.pedis/cruris/corporis/
versicolor

55. Non-antifungal Uses of Ketoconazole
 Prostate cancer
 Precocious puberty
 Cushing syndrome
 Hirsuitism

56. Triazoles

57. Fluconazole
 Broad spectrum:
 Candida, Cryptococcosis,
Coccidiodomycosis
 Dermatophytosis
 Blastomycosis
 Histoplasmosis
 Sporotrichosis
 Oral; IV;Topical
 Not effective against Aspergillosis & Mucormycosis

58. Pharmacokinetic Advantages of Fluconazole
 Notaffected by food or gastric pH
 Crosses BBB → Fungal meningitis
 Least effect on heaptic microsomal enzyme
Fewer D/I
 Noanti-androgenic & other endocrine effects

59. Uses of Fluconazole
 Candida:
 Vaginal candidiasis (150 mg oral dose)
 Oral candidiasis (2 weeks treatment required)
 Tinea infections & Cutaneous candidiasis:
o 150 mg weekly for 4 weeks
o Tinea unguim : 12 months[
 Systemic fungal infections
 Meningitis: preferred drug
 Fungal keratitis (eye drops)

60. Itraconazole
Broad spectrum of activity
including Aspergillus.
Does not inhibit steroid hormone
synthesis and no serious
hepatoxicity.

61. Pharmacokinetics of Itraconazole
 Absorption enhanced by food & gastric acidity
(D/I: Oral absorption ↓ by Antacids, H2 blockers)
 Accumulates in vaginal mucosa, skin, nails
 CNS penetration is poor

62. Uses of Itraconazole
 (DOC)Paracoccidomycosis,Chromoblastomycosis,
Histoplasmosis & Blastomycosis.
 Candidiasis - Oesophageal, Oropharyngeal, Vaginal
 Dermatophytosis
 Onychomycosis
 Aspergillosis

63. Adverse events of Itraconazole
 Hypokalaemia
 Increase plasma transaminase
 Hypertension, Edema
 Headache, nausea, epigastric distress

65. Voriconazole
o High Oral Bioavailability
o Good CSF penetration
o Doesn’trequire gastric acidity for absorption
o Extensive Hepatic Metabolism (2C19)
o Enzyme Inhibitor

66. Uses of Voriconazole
 DOC for Invasive Aspergillosis
 Most useful for Esophageal Candidiasis
 First line for moulds like Fusarium
 Resistant Candida infections

67. ADRs of Voriconazole
 Transient visual changes like blurred vision ,
altered color perception & photophobia
 QT Prolongation
 Rashes (5-6%)

68. Posaconazole
 Broadest spectrum azole
 Liquid oral formulation
 Fatty meal ↑ absorption
 Dose : 800 mg/day
 Potent Inhibitor of CYP3A4

69. Uses of Posaconazole
Prophylaxis of invasive candidiasis
Salvage therapy for invasive
aspergillosis
Mucormycosis & Zygomycosis
(only activeazole !!!)

70. Ravuconazole
Phase II clinical trial
Spectrum: Candida, Aspergillus,
Dermatophytes
Oral

71. Water
solubility
Absorption Halflife (hr) Elimination ROA
Ketoconazole low variable 7-10 Hepatic Oral
Itraconazole low variable 24-42 Hepatic Oral/IV
Fluconazole high high 22-31 Renal Oral/IV
Voriconazole high high 6 Hepatic Oral/IV
Posaconazole low high 25 Hepatic Oral

72. Allyamines

73. Terbinafine
 Orally & topically effective
 Fungicidal
 Pharmacokinetics:
 Well absorbed orally
 Highly keratophilic & lipophilic (very slow release
of drug from skin, nails & adipose tissue)
 Poor BBB permeability
 t1/2 - 15 days

74. Terbinafine
 Adverse events:
 Taste disturbances
 Rarely hepatic dysfunction (symptomatic
hepatobiliary dysfunction)
 Uses:
 Dermatophytosis
 Onychomycosis
 Candidiasis

75. 5-Flucytosine
 Narrow spectrum
 Prodrug; pyrimidine analog
 Adverse events: (Fluotoxin)
 Bone marrow toxicity, alopecia, reversible
hepatomegaly
 Uses: In combination with AMB for cryptococcal
meningitis

76. Advantages of
combination:
 Entry of 5 FC
 Reduced toxicity
 Rapid culture
conversion
 Reduced duration of
therapy
 Decreased
resistance

77. Griseofulvin
 Penicillium griseofulvum
 Fungistatic
 Systemic drug for superficial fungal
infections (topically binds to newly synthesized keratin in stratum
corneum of skin, hair & nails)
 Active against dermatophytes
(Dermatophytes concentrate it actively hence selective toxicity)

78. Pharmacokinetics
o Increased absorption by fatty food &
Micronisation
o Accumulates in keratinized tissue
o t1/2 - 24 hrs
o CytP450 INDUCER !!!

79.  Adverse events:
 Headache most common
 CNS symptoms: confusion, fatigue, vertigo
 Peripheral neuritis
 Photoallergy
 Transient leukopenia, albuminuria
Griseofulvin

80.  Uses:
o Systemically only for dermatophytosis, ineffective
topically.
o Duration of treatment depends on site, thickness
of keratin & turnover of keratin.
o Treatment must be continued till infected
tissue is completely replaced by normal
skin,hair, nail.
o Dose: 125-250 mg QID

81. Duration of treatment
•
•
•
•
Body skin -- 3 weeks
Palm, soles -- 4-6 weeks
Finger nails -- 4-6months
Toe nails -- 8-12 months

82.  Interactions:
 Warfarin, OCP Failure
 Phenobarbitone
 Disulfiram-like reaction
Griseofulvin

83. Topical Agents
for Dermatophytes

84.  Ciclopirox olamine:
 Tinea infections, pitryasis versicolor
, dermal candidiasis, vaginal
candidiasis
 Penetrates superficial layers
 Tolnaftate:
 Tinea infections
 Not effective in hyperkeratinized lesions
 Salicylic acid aids its effect by keratolysis

85.  Undecylenic acid: 5% (Tineafax)
 Generally combined with zinc (20%)
 Used in Tinea cruris & nappy rash
 Sodium thiosulfate: (Karpin lotion)
 Reducing agent known as hypo
 Effective in Pitryasis versicolor only 20%
solution for 3-4 weeks

86.  Benzoic acid:
 Used in combination with salicylic acid
 Whitfields ointment: (benzoic acid 6% + salicyclic acid 3%)
 Salicyclic acid due to its keratolytic action helps to
remove infected tissue & promotes penetration of
benzoic acid in fungal infected lesion
 Adverse events: irritation & burning
sensation
(Ring cutter ointment)

87.  Haloprogin
 Dermatophytosis (Mainly T. pedis)
 Quinidiochlor
 Luminal amoebicide
 Weak antifungal & antibacterial
 External application: dermatophytosis, mycosis
barbae, pitryasis versicolor

88.  Selenium sulfide: T. versicolor
 Potassium iodide

89. THANK YOU
ALL
vikramsharma161@gmail.com
8826012309
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