lecture by Dr/ Ahmad Nofal about antifungal treatment

2. By
M.D.

3. Fungi are eukaryotic, heterotrophic (not
self sustaining) organisms that live as
saprobes or parasites.
They are complex organisms in
comparison to bacteria.
Fungal infections are also called as
mycoses.

4. Classification
Superficial
1-Dermatophytes
2-Candida
3-TVC
Deep:
1-Candiadiasis
2-Aspergillosis
3-Histoplasmosis
4-Coccidiomycosis

5. Ideal Antifungal
1-Potent activity against different fungal
pathogens
2-Flexibility to oral and parenteral route
3-Favourable pharmacokinetics
4-Few adverse effects
5-Low cost

6. What are the targets for antifungal
therapy?
Cell membrane
Fungi use principally
ergosterol instead of
cholesterol
Cell Wall
Unlike mammalian
cells, fungi have a
cell wall
DNA Synthesis
Some compounds may be
selectively activated by
fungi, arresting DNA
synthesis

7. Site of action
At the nuclear level
1-Flucytosine
2-Griseofulvin
At the cell membrane level
1-polyenes
2-Imidazoles
3-Triazoles
4-Allylamines

8. Squaline epoxidase
14-alpha sterol demthylase

11. Effect Mechanism Antifungals Involved Suggested clinical
management
Decreased serum
concentration of azole
Antacids
H2 Receptor
antagonism
Proton Pump
Inhibitors
Sulcrafate
Didanosine (oral)
Decreased
dissolution/absorption
of solid dosage form
Ketoconazole,
itraconazole
(capsules),
Use solution
formulation of
itraconazole or other
azole if indicated (i.e.
voriconazole)
Avoid taking antacids
within 2 hours of oral
azole therapy
Increased metabolism
of azole
Isoniazid
Rifampin
Phenytoin
Carbamazepine
Phenobarbital
Barbiturates
Induction of
mammalian
cytochrome-P450
mediated metabolism of
azole
Ketoconazole,
itraconazole,
Griseofulvin
fluconazole,
voriconazole,
posaconazole
Avoid concomitant use
of these agents if
possible. May require
switch to amphotericin
B formulation or
echinocandin
Drug interactions

12. Increased serum
concentration of co-
administered drug or
metabolite
Oral hypoglycemics
warfarin
Cyclosporin
Phenytoin
Carbamezepine
Triazolam,
midazolam
Diltiazem
Lovastatin
Isoniazid
Rifampin
Quinidine
Busulfan
Vincristine
Cyclophosphamide
Digoxin
Loratidine
Inhibition of
cytochrome P450,
P-gp, or both
Ketoconazole,
itraconazole,
voriconazole >
fluconazole (usual
doses)
Avoid concomitant
use if possible.
Severity of possible
interaction is drug-
dependent. Consult
prescribing
information of each
drug to address
interaction severity
Drug interactions

13. Griseofulvin: OCP, warfarin, cyclosporin
Fluconazole: OCP
Itraconazole: OCP
Lamisil: Non
Decreased level of other drugs

15. Clinical uses
TVC:
Topical: lotion, cream, shampoo
Systemic: Curative and prophylactic

16. Clinical uses
Tinea Capitis
Topical: lotion, cream, shampoo
Systemic: Curative and prophylactic

20. Griseofulvin versus other antifungals
Trichophyton species: similar efficacy &
much shorter duration of treatment.
Microsporum species: Griseofulvin is
better, but needs longer duration

21. Treatment protocols should therefore
reflect local epidemiology and be based on
the most likely culprit organism. A
prolonged course or a change of agent may
be required in cases of treatment Failures.

22. Treatment failures
-Wrong diagnosis
-Lack of compliance – especially in long TTT
-Suboptimal absorption of drug
-Relative insensitivity of the organism
-Reinfection

23. Clinical uses
Tinea Corporis/cruris/axillaris
Topical: lotion, cream, gel
Systemic: indications and doses

25. Clinical uses
Tinea pedis: Inflammatory & Non
Topical: lotion, cream, gel
Systemic: indications and doses

26. Clinical uses
Onychomycosis
Topical: Amorolfine 5%, ciclopirox
8% & tioconazole 28%
Systemic: indications and doses
Pulse & continous

27. Treatment of onychomycosis

28. Treatment of toe onychomycosis

29. Clinical applications