antifungals use in icu

1. ANTIFUNGALS
DR RIYAS
CRITCAL CARE

2. INTRODDUCTION
• HUMAN FUNGAL INFECTIONS HAVE INCREASED DRAMATICALLY IN RECENT YEARS, OWING
MAINLY TO

3. • FUNGAL INFECTIONS ARE USUALLY MORE DIFFICULT TO TREAT
1. FUNGAL ORGANISMS GROW SLOWLY
2. FUNGAL INFECTIONS OFTEN OCCUR IN TISSUES THAT ARE POORLY PENETRATED BY
ANTIMICROBIAL AGENTS(E.G., DEVITALIZED OR AVASCULAR TISSUES).
• THERAPY OF FUNGALINFECTIONS USUALLY REQUIRES PROLONGED TREATMENT

4. CLASSIFICTION
YEAST (BLASTOMYCES; CANDIDA; HISTOPLASMA; COCCIDIOIDES;
CRYPTOCOCCUS)
FUNGI
MOULDS (ASPERGILLUS SPP; DERMATOPHYTES, MUCOR)
SUPERFICIAL
CLINICALLY
DEEP(SYSTEMIC MYCOSIS)

5. SYSTEMIC (DEEP FUNGAL )
a. SYSTEMIC CANDIDIASIS: RTI WITH PROGRESSIVE DIMUNITION
b. CRYPTOCOCCAL MENINGITIS, ENDOCARDITIS
c. RHINOCEREBRAL MUCORMYCOSIS
d. PULMONARY ASPERGILLOSIS
e. BLASTOMYCOSIS (PNEUMONITIS, WITH DISSEMINATION)
f. HISTOPLASMOSIS(COUGH , FEVER, MULTIPLE PNEUMONIC INFILTRATES)
g. COCCIDIODOMYCOSIS
h. PNEMOCYSTIS CARINII PNEUMONIA

6. CLASSIFICATION

7. CLASSIFICATION OF DRUGS

8. MOA

11. BASED ON STRUCTURE
ALLYLAMINES –
Terbinafine, butenafine
• ECHINOCANDINS –
Caspofungin, anidulafungin,
micafungin
• OTHER TOPICAL AGENTS –
Tolnaftate, Undecyclinic acid,
benzoic acid

12. AMB
• OBTAINED FROM STREPTOMYCES NODOSUS
• AMPHOTERIC IN NATURE

13. MOA

14. PHARMACO KINETICS &DYNAMICS
• HIGHEST CONCENTRATION N LIVER ,SPLEEN BONE MARROW WITH LESS IN
KIDNEY AN LUNG
• CSF =2-3%BLOOD
• ITS FUNGICIDAL AT HIGHER CONC ATATIC AT LOWER CONC

16. ADMINISTRATION &DOSE
• SYSTEMIC MYCOSIS: IV
AVAILABLE AS 50MG VIAL
SUSPENDED IN 10 ML WATER AND THEN DILUTED WITH 500 ML GLUCOSE
0.5MG/KG TO 1 MG/KG
TOTAL DOSE- 3-4 GM OVER 2-3 MONTHS
• • INTESTINAL MONOLIASIS: 50-100 MG QID ORALLY
• • VAGINITIS: TOPICAL
• • OTOMYCOSIS: 3 % DROPS
• • INTRATHECAL: 0.5 MG BD IN FUNGAL MENINGITIS

17. SPECTRUM OF ACIVITY
• ASPERGILLUS
• BLASTOMYCES DERMATITIDIS
• CANDIDA ALBICANS
• CRYPTOCOCCUS NEOFORMANS
• COCCIDIOIDES IMMITIS
• HISTOPLASMA CAPSULATUM
• MUCOR SPP.
• ALSO ACTIVE AGAINST LESHMANIA

18. AVERSE EFFECTS

19. • FEVER AND CHILLS : LASTING 2-5 HRS BECAUSE OF RELEASE OF IL & TNF – CAN
BE TREATED WITH HYDROCORTISONE 0.6MG/KG

20. DIS ADVANTAGES
SIDE EFFECTS OF AMB
Nephrotoxicity
Acute infusion related reactions
Hypopotassemia, anemia, hepatic dysfunction..

21. LIPID FORMULATIIONS OF AMB

24. AZOLES
1. SYNTHETIC ANTIFUNGALS
2. BROAD SPECTRUM
3. FUNGISTATIC OR FUNGICIDAL DEPENDING ON CONC OF DRUG
4. MOST COMMONLY USED
5. CLASSIFIED AS IMIDAZOLES & TRIAZOLES • IMIDAZOLES: TWO NITROGEN IN
STRUCTURE
6. TOPICAL: ECONAZOLE, MICONAZOLE, CLOTRIMAZOLE
7. SYSTEMIC : KETOCONAZOLE
8. NEWER : BUTACONAZOLE, OXICONAZOLE, SULCONAZOLE

26. • TRIAZOLES : THREE NITROGEN IN STRUCTURE
• FLUCONAZOLE, ITRACONAZOLE, VORICONAZOLE
• TERCONAZOLE: TOPICAL FOR SUPERFICIAL INFECTIONS
• BOTH THESE GROUPS ARE
STRUCTURALLY RELATED COMPOUNDS –
HAVE SAME MECHANISM OF ACTION –
HAVE SIMILAR ANTIFUNGAL SPECTRUM

28. KETOCONAZOLE

29. • ADVERSE EFFECTS
• NAUSEA , VOMITING , ANOREXIA • HEADACHE , PARESTHESIA, ALOPECIA •
• ↓ STEROID, TESTOSTERONE & ESTROGEN SYNTHESIS – GYNAECOMASTIA,
OLIGOSPERMIA , LOSS OF LIBIDO & IMPOTENCE IN MALES – MENSTRUAL
IRREGULARITIES & AMENORRHOEA IN FEMALES • ELEVATION OF LIVER ENZYMES
• HYPERSENSITIVITY REACTION - SKIN RASHES, ITCHING
First orally effective broad spectrum antifungal
Effective against • Dermatophytosis, Deep mycosis ,
Candidiasis

30. USES
• DERMATOPHYTOSIS: CONC IN STRATUM CORNEUM
• MONILIAL VAGINITIS : 5-7 DAYS
• SYSTEMIC MYCOSIS: BLASTOMYCOSIS,
• HISTOPLASMOSIS, COCCIDIODOMYCOSIS
• LESS EFFICACY THAN AMB & SLOWER RESPONSE
• ↓EFFICACY IN IMMUNOCOMPROMIZED AND MENINGITIS
• LOWER TOXICITY THAN AMB HIGHER THAN TRIAZOLES
• HIGH DOSE USED IN CUSHINGS SYNDROME
• TOPICAL: T.PEDIS, CRURIS, CORPORIS, VERSICOLOR

31. FLUCONAZOLE
• NEWER WATER SOLUBLE TRIAZOLE
• ORAL, IV AS WELL AS TOPICAL
• BROAD SPECTRUM ANTIFUNGAL ACTIVITY
• CANDIDA, CRYPTOCOCCOSIS, COCCIDIODOMYCOSIS
• DERMATOPHYTOSIS
• BLASTOMYCOSIS
• HISTOPLASMOSIS
• SPOROTRICHOSIS
• NOT EFFECTIVE AGAINST ASPERGILLOSIS & MUCORMYCOSIS

32. FLUCONAZOLE

33. ITRACONAZOLE

34. • DOC FOR PARACOCCIDOMYCOSIS & CHROMOBLASTOMYCOSIS
• DOC FOR HISTOPLASMOSIS & BLASTOMYCOSIS
• ESOPHAGEAL, OROPHARYNGEAL VAGINAL CANDIDIASIS NOT SUPERIOR TO FLUCONAZOLE :
200 MG OD X 3 DAYS
• DERMATOPHYTOSIS: LESS EFFECTIVE THAN FLUCONAZOLE 100- 200 MG OD X 15 DAYS
• ONYCHOMYCOSIS : 200 MG / DAY FOR 3 MONTHS
INTERMITTENT PULSE REGIME 200 BD ONCE A WEEK / MONTH FOR 3MONTHS EQUALLY
EFFECTIVE
• ASPERGILLOSIS: 200 MG OD/ BD WITH MEALS FOR 3 MONTHS

35. VORICONAZOLE

37. ECHINOCANDINS

40. • THANK
YOU