Download - Anti Fungal Drugs[1]
-
8/3/2019 Anti Fungal Drugs[1]
1/60
-
8/3/2019 Anti Fungal Drugs[1]
2/60
Dr Azza Baraka
http://upload.wikimedia.org/wikipedia/commons/9/99/Amanita_phalloides_1.JPG -
8/3/2019 Anti Fungal Drugs[1]
3/60
There is increase in incidence ofopportunistic fungal infection ( dueto wide spread use ofimmunosuppressants andemergence of AIDS) ranging fromtrivial cutaneous infection to
systemic diseases which demandprolonged treatment with toxicagents
-
8/3/2019 Anti Fungal Drugs[1]
4/60
Fungal infections (Mycoses):
Systemic infection
Mucocutaneous(superficial) infection
-
8/3/2019 Anti Fungal Drugs[1]
5/60
Systemic candidiasis
Cryptococcsis
Aspergillosis
Blastomycosis
Histoplasmosis
-
8/3/2019 Anti Fungal Drugs[1]
6/60
-
8/3/2019 Anti Fungal Drugs[1]
7/60
Candidisis (Yeast)
Dermatomycosis
(Molds)
-
8/3/2019 Anti Fungal Drugs[1]
8/60
-
8/3/2019 Anti Fungal Drugs[1]
9/60
-
8/3/2019 Anti Fungal Drugs[1]
10/60
Tinea corporis
http://dermatlas.med.jhmi.edu/derm/IndexDisplay.cfm?ImageID=-664370511 -
8/3/2019 Anti Fungal Drugs[1]
11/60
onchmycosis
-
8/3/2019 Anti Fungal Drugs[1]
12/60
-
8/3/2019 Anti Fungal Drugs[1]
13/60
-
8/3/2019 Anti Fungal Drugs[1]
14/60
Alter membrane permeability:
Azoles Polyenes Allylamines
Disrupt cell wall:Echinocandins(caspofungin).
Block nucleic acid synthesis:
Flucytosine
Disrupt microtubular functions:
Griseofulvin
-
8/3/2019 Anti Fungal Drugs[1]
15/60
-
8/3/2019 Anti Fungal Drugs[1]
16/60
Systemically administered (oral or parenteral)
AFDS for systemic (invasive) fungal infections.
Oral AFDs for mucocutaneous (superficial)
fungal infections.
Topically applied AFDs for mucocutaneous
fungal infections.
-
8/3/2019 Anti Fungal Drugs[1]
17/60
AMPHOTERICIN B
FLUCYTOSINEAZOLES
Echinocandins
-
8/3/2019 Anti Fungal Drugs[1]
18/60
-
8/3/2019 Anti Fungal Drugs[1]
19/60
It has a broad antifungal spectrum.
It is often used as the initial induction
regimen for serious fungal infectionsand then replaced by a less toxic drug.
-
8/3/2019 Anti Fungal Drugs[1]
20/60
D
Na+
Cytoplasmic membrane
Fungal cell
SqualeneLanosterolErgosterol
Fungal celldeath
Amphotericin Binds to ergosterol and form pores
in the membrane
-
8/3/2019 Anti Fungal Drugs[1]
21/60
No
Only ergosterol is affected by this drug
-
8/3/2019 Anti Fungal Drugs[1]
22/60
IV infusion
Poorly absorbed from GIT
Intrathecal for fungal meningitis
-
8/3/2019 Anti Fungal Drugs[1]
23/60
Infusion related
HypotensionAttenuated by :
Slowing infusion ratePremedication with: Antihistamines ,antipyretic
Fever
chills muscle spasmvomiting
-
8/3/2019 Anti Fungal Drugs[1]
24/60
Nephrotoxicity
Anemia : renal erythropoietin formation
-
8/3/2019 Anti Fungal Drugs[1]
25/60
-
8/3/2019 Anti Fungal Drugs[1]
26/60
Fluocytosine is converted to 5-fluorouracil (5-FU)
-
8/3/2019 Anti Fungal Drugs[1]
27/60
Permease
5-FC
5-FC
Deaminase
5-FU
DNA & RNA synthesis
Inhibition
5-FUTP
5-FdUMP
-
8/3/2019 Anti Fungal Drugs[1]
28/60
Narrow spectrum antifungal
-
8/3/2019 Anti Fungal Drugs[1]
29/60
Flucytosine is often used orally incombination with other antifungal
drugs to avoid development ofresistance and for synergistic actions
-
8/3/2019 Anti Fungal Drugs[1]
30/60
YesBecause Mammalian cells have low level of enzymes that
convert Flucytosine to 5-FU
Does resistance occur to FC?
Yes
Decrease activity of fungal enzymes thatconvert Flucytosine to 5-FU
-
8/3/2019 Anti Fungal Drugs[1]
31/60
Orally
-
8/3/2019 Anti Fungal Drugs[1]
32/60
Reversible BMS: anaemia, leucopenia, thrombocytopenia
Alopecia
Elevatedhepaticenzymes
-
8/3/2019 Anti Fungal Drugs[1]
33/60
A-Imidazoles: KetoconazoleB-Triazoles:1st generation: Itraconazole,Fluconazole2nd generation: Voriconazole
2nd generation triazoles differ from 1st
generation triazoles in having an extendedspectrum of activity and being active
against fluconazole-resistant species.
-
8/3/2019 Anti Fungal Drugs[1]
34/60
SqualeneLanosterol
Fungal celldeath
Blocked by azole
P450Ergosterol
Loss of membrane selectivity & loss of important cell contents
-
8/3/2019 Anti Fungal Drugs[1]
35/60
Broad spectrumanti-fungal
-
8/3/2019 Anti Fungal Drugs[1]
36/60
1. Triazoles have a broader antifungal spectrum thanimidazoles.
2. Triazoles achieve better distribution into body fluids.3. Triazoles have greater affinity for fungal compared
with mammalian P450 enzymes so produce lesseffect on human steroid synthesis . Thus their safetyprofile is significantly improved over imidazoles.
4. Triazoles have broad application in therapy of bothsuperficial and systemic fungal infections. Whereas,the use of imidazoles is limited to treating superficialfungal infections.
-
8/3/2019 Anti Fungal Drugs[1]
37/60
Both imidazoles and triazoles might causehepatotoxicity ranging from mild transientelevations in transaminases to clinical hepatitis
and liver failure. These reactions areidiosyncratic, so there is no cross-sensitivitybetween azoles.
Imidazoles might cause endocrinal
disturbances due to inhibition of synthesis ofgonadal and adrenal steroids as a result ofinhibition of human P450.
-
8/3/2019 Anti Fungal Drugs[1]
38/60
The major drawback associated with azole userelates to their metabolism by the hepaticcytochrome P450 (CYP) enzyme system.
Because azoles also inhibit CYP enzymes,plasma levels of any drug metabolized bythese enzymes may be elevated .
The potential for drugdrug interactions isgreatest for itraconazole and voriconazole, butlower for fluconazole, as these azoles are notmetabolized to the same extent by the CYP
system .
-
8/3/2019 Anti Fungal Drugs[1]
39/60
Echinocandins have poor oral absorption so givenIV.
As effective as Amphotricin B but toxicity associatedwith echinocandins is infrequent because their action
is specific to fungal cell walls. They are not metabolized via the cytochrome
P450 enzymes, so there are minimal drugdruginteractions.
Adverse effects include histamine release reactions(irritation at infusion site, headache, rash) and fever.
-
8/3/2019 Anti Fungal Drugs[1]
40/60
1. Azoles2. Griseofulvin3. Terbinafine
-
8/3/2019 Anti Fungal Drugs[1]
41/60
It is an allylamine.
-
8/3/2019 Anti Fungal Drugs[1]
42/60
Squalene Lanosterol Ergosterol
Squalene
epioxidase
Terbinafine
Squalene
-
8/3/2019 Anti Fungal Drugs[1]
43/60
Dermatophyte infection
It accumulates in Keratinized tissues(skin)
>effective thangriseofulvin or azoles
-
8/3/2019 Anti Fungal Drugs[1]
44/60
GIT upsetHeadache
-
8/3/2019 Anti Fungal Drugs[1]
45/60
Treatment of Dermatophyteinfection as tinea infections of theskin. After oral absorption it is takenup selectively by newly formed skinand concentrated in keratin.
Azoles and terbinafine are moreeffective alternatives.
-
8/3/2019 Anti Fungal Drugs[1]
46/60
Oral.
binds to keratinresistant to fungalinfections.
No eradication of infection.
-
8/3/2019 Anti Fungal Drugs[1]
47/60
Fungal cell
Inhibit microtubule functions
Support , transport , division
GG
-
8/3/2019 Anti Fungal Drugs[1]
48/60
1.Allergic reactions2.Hepatoxicity
3.BMS
-
8/3/2019 Anti Fungal Drugs[1]
49/60
Griseofulvin is a P450 inducer.
-
8/3/2019 Anti Fungal Drugs[1]
50/60
NYSTATIN
Topical Amphotericin B
Topical Terbinafine Topical Azoles
-
8/3/2019 Anti Fungal Drugs[1]
51/60
Not absorbed from GIT
It is only used topically andis never administeredparentrally because of its
serious systemic toxicity.
-
8/3/2019 Anti Fungal Drugs[1]
52/60
D
Na+
Cytoplasmic membrane
Fungal cell
SqualeneLanosterolErgosterol
Fungal celldeath
Nystatin Binds to ergosterol and form pores in the
membrane
-
8/3/2019 Anti Fungal Drugs[1]
53/60
Candida albicans
Nystatin
Oropharyngeal thrushVaginal candidiasis
Skin candidal infection
N.B. never systemic.
-
8/3/2019 Anti Fungal Drugs[1]
54/60
1-Mycotic corneal ulcers &keratitis.
2- Fungal arthritis.
3- Candiduria.
-
8/3/2019 Anti Fungal Drugs[1]
55/60
Local irritation,hypersensitivity.
-
8/3/2019 Anti Fungal Drugs[1]
56/60
Topical azoles
Ketoconazole Miconazole Clotrimazole
Candida AlbicansDermatophytes
-
8/3/2019 Anti Fungal Drugs[1]
57/60
ORAL(KETOCONAZOLE, ITRACONAZOLE,FLUCONAZOLE) or PARTENTRAL(ITRACONAZOLE, FLUCONAZOLE) for
systemic infections ORAL(KETOCONAZOLE, ITRACONAZOLE,
FLUCONAZOLE) or Topical(KETOCONZOLE, MICONAZOLE,
CLOTRIMAZOLE) for mucocutaneousinfections
-
8/3/2019 Anti Fungal Drugs[1]
58/60
Terbinafine,
Cream or gel.Local irritation,
erythema, burningsensation.
-
8/3/2019 Anti Fungal Drugs[1]
59/60
DERMATOPHYTESCompounds like benzoic acid
(Whitfield oint.) still can be usedfor mild infections.Topical imidazoles (miconazole)
are usually preferred.If multiple areas (esp. in scalp ornails) or if failed topical; oral
itraconazole or terbinafine.
-
8/3/2019 Anti Fungal Drugs[1]
60/60