Pharmacology- anti-fungal drugs.Classification and details on polyenes, echinocandins, griseofulvin, azoles, terbinafine, and topical azoles. Their uses, side effects, adverse effects are mentioned with the mechanism of action.

2. Structure of fungal cell
Classification of antifungal drugs
Flucytosine
Polyenes - Amphotericin B
Allyl amines
Griseofulvin
Azoles
Echinocandins
Topical antifungal drugs

4. Polyenes
• Amphotericin B
• Nystatin
Heterocyclic
benzofuran
• Griseofulvin
(fungistatic)
Flucocytosine
(antimetabolite)
Echinocandins
• Capsofungin
• Micafungin
• Anidulafungin
Terbinafine(allyl
amine)

5. Imidazoles
• Ketoconazole
• Clotrimazole
• Econazole
• Miconazole
• Oxiconazole
Triazoles
• Fluconazole
• Itraconazole
• Voriconazole
• Posaconazole
AZOLES

7. Adverse effects
Toxicity of 5-FC is lower
than that of AMB
Consists of dose dependent
bone marrow depression
Gastrointestinal disturbances
(enteritis and diarrhoea)
Liver dysfunction- mild and
irreversible
Uses
Not employed as sole
therapy
Rapid development of
resistance limits its utility in
deep mycosis
Used in meningeal,
nonmeningeal
cryptococcosis with AMB
to produce a synergistic
action

8. Mechanism of action
Binds to ergosterol
Pore formation
Cell contents leak out
Death of fungus(fungicidal)

9. Fungicidal drug
Effective against
most of the fungal
infections(broad
spectrum)
But given in very
serious
conditions only
Given Intravenous(5%
dextrose) (not effective
orally)

10. Poorly absorbed orally
(exp: intestinal candidiasis)
Administered I.V. as a suspension
made with help of deoxycholate.
t1/2 = 15 days
60% metabolized in liver

12. • Chills, fever, headache, pain all over, nausea,
dyspnea(release of IL & TNF)
Acute reaction
• Nephrotoxicity:Azotemia
• Hypokalemia, acidosis, anemia
Long term toxicity
• nerve palsies, headache
CNS toxicity
Hepatotoxicity rarely

13. Infusion related reaction (most common)
Nephrotoxicity (renal tubular acidosis with
hypokalemia)
Bone marrow suppression
hypotension

16. Inhibition of Sq.
epoxide
Accumulation
of squalene
• Toxic to
fungal cells
Death of fungal
cells (fungicidal)
Fungicidal drugs
given orally as well as topical preparations
These drugs accumulate in keratin rich areas

17. Nausea, vomiting
Taste disturbances
Rarely hepatic dysfunction
Topical: erythema, itching,
dryness, rashes, urticaria
Uses
Used in fungal infections
(dermatophytosis infection)
Tinea pedis/cruris corporis
• 1% cream twice daily
Onychomycosis, tinea
capitis
• 250mg OD
Less effective in cutaneous
and mucosal candidiasis

18. Acts on mitotic
spindle
Oral, static drug
High affinity for
keratin – Max.
conc. in stratum
corneum of skin

19. PK- Fatty foods increase the absorption
• Efficacy of oral contraceptives may be lost
Interaction: It induces CYP450 enzymes and hastens
warfarin metabolism
• DOSE : 125-250 mg QID with meals
DOC- Only for dermatophytosis
Avoided in patient taking disulfiram
S/E- Hepatotoxic, neutropenia

23. Ketoconazole
• Microsomal enzyme
inhibition
• Causes gynecomastia
• Causes adrenal
suppression
• DOC- dermatophytosis
• Hepatotoxic
• 200mg OD

24. DRUG INTERACTIONS

25. Itraconazole (DOC)
• Aspergilosis 200mg OD/BD
used for 3 month
• Dermatophytosis 100-
200mg OD 7-15 days
• Onychomycosis 200mg/day
for 3 months
• Histoplasmosis, Sporothrix,
Blastomyces,ABPA
(prednisolone+)
• S/E- increase
Mineralocorticoids,
hypokalemia
Voriconazole (DOC)
• Invasive Aspergillosis,
scedosporium, trichosporon
• DOSE- 200mg oral BD taken
1 hr before or 1 hr after meal
• Begin i.v. infusion with 6mg/kg
12 hourly infused over 2 hrs
twice followed by 3-4mg/kg 12
hourly
• S/E- periostitis, hallucinator,
visual abnormalities

26. Posaconazole (DOC)
• Mucormycosis300 mg BD- 1
days
• 300 mg O.D.- 2nd day onwards
• Prophylaxis of invasive
aspergillosis
• Prevent fungal infections in
GVHD and induction
chemotherapy in leukemia
Fluconazole
• Maximum oral bioavailability
• Max CNS penetration
• DOC- Candida(SSTIs) and
cryptococcus
• Single 150 mg oral dose cure
vaginal candidiasis with few
relapses
• S/E- Alopecia

27. Ivasuconazole (I.V. / oral)

29. Tolnaftate
• Tinea cruris, corporis,1-3
weeks treatment
• Not effective in hyper
keratinized lesions
• Salicylic acid aids its effect by
keratolysis
Ciclopirox olamine
• Tinea infections, pityriasis
versicolour, dermal candidiasis
• Penetrates superficial layer
• Acts by inhibiting membrane
uptake of precursors of
macromolecules needed for
fungal growth