Anti fungal.. department of pharmacology

Anti fungal.. department of pharmacology

1. ANTI FUNGAL DRUGS Dr S Rajaram

2. Fungal Infections 1. Dermatophytes ( Taenia infection) Epidermophyton,Microsporum , Tricophyton 2. Yeast like candidiasis ( moniliasis )- Candida Albicans . 3. Yeast – Cryptococcus → Meningitis Deep mycosis :- Aspergillosis Coccidioidomycosis Histoplasmosis Blastomycosis Mucormycosis cryptococcosis

3. Factors promote fungal infection- Indiscreminate use of broader spectrum antibiotics Anticancer cytotoxic drugs. HIV Implants – indwelling catheters and drainage tubes Corticosteroids.

4. Classification :- 1.Antibiotics polyene :- Amphotericin B,Nystatin,Hamycin Others- Griseofulvin,Caspofungin 2. Antimetabolites :- Flucytosine , 3. Azoles - Imidazoles :- Ketoconazole Clotrimazole , Econazole , Miconazole – only topical dosage forms.

5. Triazole :- Fluconazole Itraconazole . Others- Terbinafine :- TOPICAL- Tolnaftate , Benzoic &salicylic acid, undecyclenic acid , sod.thiosulfate , Butenafine

6. Amphotericin B, Mechanism of action :- combined with ergosterol in the cell membrane many such molecules arrange in such a way forming pores in the membrane . Essential intracellular elements leak out of the cell . Enhance cell mediated immunity

7. Kinetics :- Effective only by iv route, oral route is only for GIT infection. Does not cross CSF barrier, ADR :- Acute reaction- on i.v infusion – chills, fever, aches, Nausea , vomiting are very common.. Thrombophelebitis . Long term toxicity- Renal impairment Hypokalemia , anaemia

8. Drug interaction :- Caution while nephrotoxic drugs that are given concurrently. eg : Amino glycoside antibiotics, cisplatin , Analgesics. Liposomal formulations Amp.B : Mild acute reaction, low nephrotoxicity Liposomes carry Amp-B to the reticuloendothelial cell. Uses :- Candidiasis,otomycosis, Systemic mycoses , febrile neutropenia , Kala- azar

9. Nystatin :- Polyene , similar to Amp.B . Too toxic for systemic use. Dosage form – Topical /local : Creams, powders, Vaginal tablets, eye ointment. Use : Vaginal, oral, dermal, corneal, conjuntival , candidiasis Orally- monilial diarrhoea

10. Griseofulvin :- orally effective antifungal antibiotics Antifungal spectrum :- Dermatophytes alone are sensitive, Mechanism of action ;- Inhibits mitosis. Prevents fungal invasion of keratin cells , It does not kill dermatophytes - fungistatic . Binds to microtubules & intereferes function

11. Kineties :- Orally absorbed, long half life in the keratin. ADR :-Low toxicity than amph.B CNS- headache, Alcohol intolerance GIT symptoms. Use :- Reserved for extensive dermatophyte infection of the skin, hair follicles, nails. Dosage schedule : Skin, 3-4 weeks, finger nail : 4-6 month, Toe nails 8-12 months.

12. Flucytosine :- Antimetabolite . Inhibit thymidilate synthesis Produces cytotoxic ADR Resistance develops rapidly. Use : Limited to treat Cryptococcus and other meningitis along with Amph.B

13. Imidazoles & Triazoles Actions :- Broad spectrum- Both dermatophytons fungi and deep mycosis respond. Mechanism :- Inhibit fungal cytochrome P450 Impair Ergosterol synthesis in membrane Leakage of essential elements from the cell

14. Ketoconazole :- orally effective broad spectrum antifungal drug. Does not cross CSF – Not effective in meningeal infection. ADR :- Less toxic than Amp.B GI symptoms. CNS : Headache, giddiness, photophobia. Liver - liver enzymes increase, Inihibit synthesis of steroid, Androgen - gynacomastia Menstrual disturbance. Pregnancy – contraindicated.

15. Uses :- Alternative to griseofulvin in dermatophytosis Candidiasis Deep mycosis : it is less toxic than AMB Dose :- 200-400mys daily. Drug interactions :- H2 blockers decrease oral absorption Enzyme inhibitor Rifampicin & phenytion : Efficacy of ketoconazole is reduced .

16. Miconazole :- Used only topically, cure rate 90% Spectrum similar to other azoles. Use :- candidiasis,otomycosis Pilyriasis versicolor Taenia infection,onycomycosis Clotimozole : cure rate- 60% Econozole

17. 5 Triazoles :- Fluconazole :- Fungicidal, more efficacious, Wider range of activity. Effective in immuno compromised patients. Drug interaction -low-less enzyme inhibition Androgen synthesis not affected. Tissue penetration better :- Useful in meningitis .

18. Fluconazole contd …. Long duration of action Contraindicated in pregnancy Route :- Both oral & IV Use :- oropharyngeal candidiasis Disseminated candidiasis , cryptococcal meningitis Taenia,Cuteneous ,vaginal candidiasis -150mgs weekly for 4 weeks. Ophthalmic drops for keratitis . .

19. Itaconazole :- Similar to fluconazole Candidiasis,taenia Histoplasmosis,blastomycosis,sporotrichosis but antacids reduced absorption. Enzyme inhibition Not useful in meningitis – poor penetration Voriconazole – invasive aspergillosis Posaconazole - mucormycosis , aspergillosis

20. Terbinafine :- Fungicidal unlike other drugs Duration of treatment is shortened. Less relapse rate. More effective is dermatophyte infection oral dose 250mg OD for 2-6 weeks. Nail infection 3-12months. Topical preparations for tinea infection . ADR :- GIT symptoms,Rashes,Taste disturbances Liver & Bone marrow may be effected.

21. Topical Antifungal drugs :- Tolnaftate - tinea , Cyclopirox olamine - tinea , candidiasis Undecyclinic acid- tinea Benzoic acid & Salicylic acid → tinea , Hyperkeratinized lesions . Sodiumthiosulfate – Pityriasis versicolor seborrhic dermatitis . butenafine - dermatophytosis

22. Summary- Dermatophytes and Deep mycoses Azoles - Imidazoles , Triazoles Griseofulvin - Dermatophytosis Amphoterecin B -Deep mycoses Local synthetic antifungal- tolnaftate , cyclopirox for Dermatophytoses Topical azoles- candidiasis

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