This document discusses various types of fungi that can cause infections and the antifungal drugs used to treat them. It notes that fungi have more complex cell structures than bacteria. Common fungal infections mentioned include candidiasis, which can occur in the mouth, vagina, and other areas. The main classes of antifungal drugs covered are azoles, polyenes, allylamines, echinocandins, and antimetabolites. Their mechanisms of action target components of fungal cell membranes like ergosterol to disrupt function. Specific drugs discussed are amphotericin B, nystatin, griseofulvin, flucytosine, fluconazole, terbinaf

1. Aasifa Shaikh
Mpharmacology, Sem 2
18SSRMPH023

2. Fungi are eukaryotic cells and therefore represent a more
complex and evolved organism.
Since 1970s, there has been a steady increase in the
incidence of serious secondary systemic fungal infections.

4. Candida albicans
Due to antibiotic therapy, antineoplastics, or
immunosuppressants
May result in overgrowth and systemic infections
In mouth
Oral candidiasis or thrush
Newborn infants and immunocompromised patients

5. Vaginal candidiasis:
• Yeast infection
• Pregnancy, diabetes mellitus, oral contraceptives

6. Also called antimycotic drugs
1) Superficial fungal infections - skin or mucous
membrane
Examples: clotrimazole, miconazole, nystatin
2) Systemic fungal infectons - lungs or central nervous
system
Examples: amphotericin B, fluconazole, ketoconazole,
itraconazole

7. 1 ANTIBIOTICS
a) Polyene: Amphotericin, nystatin, hamycin
b) Hetrocyclic benzofuran: griseofulvin
2 ANTIMETABOLITE : Flucytosine
3 AZOLES
a) Imidazoles: Ketoconazole, clotrimazole,
oxiconazole, miconazole
b) Triazoles: Fluconazole, itraconazole,
voriconazole,

8. 4 Allylamines – Terbinafine, butenafine
5 Echinocandins – Caspofungin, anidulafungin,
micafungi
6 Other topical agents – Tolnaftate, Undecyclinic acid,
benzoic acid
7 Antiprotozoal - Atovaquone (Mepron)

10. SITES OF ACTION OF COMMON ANTIFUNGAL DRUGS

11. ANTI FUNGAL DRUGS
MECHANISAM

12. Several amphotericin B
molecules bind to ergosterol in
the plasma membranes of
sensitive fungal cells.
There, they form pores
(channels) that require
hydrophobic interactions
between the lipophilic
segment of the polyene
antibiotic and the sterol.
The pores disrupt membrane
function, allowing electrolytes
(particularly potassium) and
small molecules to leak from
the cell, resulting in cell
death.
Mechanism of action of
Polyenes

13. Available Forms of amphotericin B
Lozenges: 10mg
Oral Suspension: 100mg/mL
Powder for injection: 50mg
Tablets: 100mg
IV: 0.25-1.0 mg in 20ml of D5W infused over 20-30
min

14. Available Forms of nystatin
Lozenges:200,000 units
Oral suspension:100,000 units/mL
Powder: 50,150, or 500 million units; 1,2 0r 5 billions
units
Tablets: 500,000 units
Vaginal Suppositories: 100,000 units

16. One of early antibiotics from penicillium griseofulvum
 Fungistatic, systemic drug for superficial fungal
infections
 Active against most dermatophytes

17.  Griseofulvin interacts with polymerized
microtubules and disrupts the mitotic
spindles thus arresting fungal mitosis
 It is only fungistatic, and it causes a
number of significant drug interactions.
 Griseofulvin accumulates in newly
synthesized, keratin-containing tissue,
where it causes disruption of the mitotic
spindle and inhibition of fungal mitosis .
 Duration of therapy is dependent on the
rate of replacement of healthy skin or
nails.

18. Induction of
hepatic
cytochrome P450
activity by
griseofulvin

20. Prodrug, pyrimidine analog, antimetabolite
Adverse events: • Bone marrow toxicity , GIT , Alopecia,
skin rashes, itching , rarely hepatitis
Uses: in combination with AMB in cryptococcal meningitis
– Narrow spectrum of action
Note: [Amphotericin B increases cell permeability,
allowing more 5-FC to penetrate the cell. Thus, 5-FC and
amphotericin B are synergistic.]

21. Flucytosine enters fungal cells
via a cytosine-specific
permeaseâ an enzyme not
found in mammalian cells.
Flucytosine is then converted
by a series of steps to 5-
fluorodeoxyuridine 5'-
monophosphate.
This false nucleotide inhibits
thymidylate synthase, thus
depriving the organism of
thymidylic acid an essential
DNA component.

23. Azoles are predominantly fungistatic.
They inhibit C-14 α-demethylase (a
cytochrome P450 enzyme), thus
blocking the demethylation of
lanosterol to ergosterol the principal
sterol of fungal membranes.
This inhibition disrupts membrane
structure and function and, thereby,
inhibits fungal cell growth.

24.  Available Forms of fluconazole
Injection: 200mg/mL,400 mg/200 mL
Powder for oral suspension: 10mg/mL, 40mg/ mL
Tablets: 50mg,100mg150mg,200 mg
Route and Dose:
PO/IV: 200mg x 1 d; maint: 100mg/d for 2 wk
PO/IV: 3-6 mg/kg/d

26. Terbinafine inhibits fungal squalene
epoxidase, thereby decreasing the
synthesis of ergosterol .
This plus the accumulation of toxic
amounts of squalene result in the
death of the fungal cell.
[Note: Significantly higher
concentrations of terbinafine are
needed to inhibit human squalene
epoxidase, an enzyme required for
the cholesterol synthetic pathway.]
.MECHANISM OF TERBINAFINE

28. Available Forms: –
Capsules: 250mg, 500mg
USE AND CONTRAINDICATIONS:
Use with amphotericin B may increase therapeutic action
as well as toxicity.
Fungal resistance occurs if the drug is given alone.

29. Semisynthetic antifungal
MOA: Inhibits B (1,3) D glucan an essential component of
fungal cell wall
Uses: Treatment of invasive aspergillosis & candidiasis
(esophageal, intraperitoneal)
Dose: IV 70 mg slowly then 50 mg daily infusion

30. Available Forms:
Suspension: 750 mg/5 mL
Route and Dose:
PO: 750mg b.i.d. with food x 21d

31. Thank you