ANTI FUNGI
3
T
A
R
G
E
T
K
E
R
J
A
(1) Polien
Binds to ergosterol within the fungal cell
membrane resulting in depolarization of
the membrane and the formation of
pores. The pores permit leakage of
intracellular contents. Exhibits
concentration dependent killing.
Toxic selective
Fungisidal / fungistatic depend on drugs
concentation
Contohnya : Amphotericin B, Nystatin
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Polien
Amphotericin B
Nystatin
Spektrum luas
Spektrum sempit
Pemakaian
jangka panjang
Amphotericin (liposom)
menurunkan toksiksitas,
nephrotoksisitas menurun
Polien-Amphotericin
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Azol-Ketoconazole
Fungicidal & fungistatik
Broad spectrum
Resistance <<<<
Needs acidic environment for absorption
Only available PO
Distributes into epidermis, synovial fluid, saliva, and
lungs. Poor distribution into CSF and eye.
Ex : therapy for Dermofita, Candida albicans,
Aspergillus spp
Dose
200 to 400 mg once daily
Decrease dose for severe liver failure
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TriazolesSpectrum of Activity
Fluconazole
Itraconazole
Voriconazole
Mycosis superfisial
dan sistemik
spektrum luas
(bukan Aspergillus)
Aktif melawan
Aspergillus ,
candidiasis
oropharyngeal dan
esophageal
Tidak hepatotoksik
Jarang hepatotoksik
Tidak menghambat
sintesa steroid
adrenal
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TriazolesSpectrum of Activity
Fluconazole
Itraconazole
Voriconazole
Posaconazole
C. albicans
+++
++
+++
+++
C. glabrata
++
++
C. krusei
--
+++
++
C. tropicalis
+++
++
+++
+++
C. parapsilosis
+++
++
+++
+++
C. lusitanae
++
++
+++
+++
Aspergillus
--
++
+++
+++
Cryptococcus
+++
+++
+++
+++
Coccidioides
+++
+++
+++
+++
Blastomyces
++
+++
++
+++
Histoplasma
+++
++
+++
Fusarium
--
--
++
++
Scedosporium
--
+/-
+/-
Zygomycetes
++
Fluconazole
TriazolesADME
Itraconazole
Voriconazole
Posaconazole
Absorption
IV and PO
Good
bioavailability
PO
Capsule Suspension
Capsules best
absorbed with food.
Suspension best
absorbed on empty
stomach.
IV and PO
90% oral
bioavailability
PO--Absorption
enhanced with
high fat meal
Distribution
Wide.
Good CNS
penetration
Wide.
Good CNS
penetration
Widely
distributed into
tissues
Metabolism
Hepatic/Renal
Hepatic
Elimination
80% excreted
unchanged in the
urine
Excreted in feces
Minimal renal
excretion
Not a substrate
of
or metabolized by
P450, but it is an
Inhibitor of 3A4
Minimal renal
excretion of
parent
compound
66% excreted in
(4) Flucytosine
Narrow spectrum dan mudah
resisten
dalam tubuh jamur diubah
menjadi 5-FU secara spesifik
oleh cytosine deaminase
sintesa RNA jamur terhambat
Efek fungistatik
PO / Infus IV
Terutama untuk Candidiasis
sistemik atau infeksi
Crypthococcus (meningitis
Crypthococcus)
Pada 5% pasien menyebabkan
peningkatan transaminase hepar
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Flucytosine
(5) Griseofulvin
Hambat mitosis jamur
Griseofulvin
terakumulasi pada
keratin yang baru
disintesis
menyebabkan gangguan
gelendong mitosis
Digunakan untuk infeksi
dermathopyta dan
onychomycosis (jamur
kuku)
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(6) Echinocandin
Irreversibly inhibits B-1,3 D glucan synthase, the enzyme
complex that forms glucan polymers in the fungal cell wall.
Glucan polymers are responsible for providing rigidity to
the cell wall. Disruption of B-1,3-D glucan synthesis leads
to reduced cell wall integrity, cell rupture, and cell death.
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Echinocandins
Caspofungin
Micafungin
Anidulafungin
Absorption
Distribution
Metabolism
spontaneous degradation,
hydrolysis and N-acetylation
Elimination
Chemical degradated
Not hepatically
metabolized
Limited urinary excretion. Not dialyzable
Half-life
9-23 hours
11-21 hours
26.5 hours
Dose
70 mg IV on day
1, then 50 mg IV
daily thereafter
Child-Pugh 7-9
70 mg IV on day 1,
then 35 mg IV
daily thereafter
CYP inducers
70 mg IV daily
100 mg IV
once daily
200 mg IV on day 1,
then 100 mg IV
daily thereafter
None
Dose
Adjustment
None
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ANTI VIRAL
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Penggolongan Virus
Virus DNA :
Herpes simplex, Herpes
zooster dan Varicella zooster,
adeno-virus, Human papilomavirus (HPV), Cytomegalo-virus
(CMV), Eipstein Barr. Parvovirus
Virus RNA :
HIV, Hepatitis, Rhinovirus,
Polio, influenza, rotavirus,
rubella, mumps, paramixovirus
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Viral attachment
Cell entry
Transcription
Translation
Viral assembly
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Klasifikasi Antivirus
1.Block viral attachment to cells : -Globulin
2.Block uncoating of virus : Amantadine, Rimantadine
3.Inhibit viral DNA/RNA synthesis :
1) Analog Purin & Pirimidin :
Acyclovir, Valacyclovir, Famciclovir, Penciclovir,
Ganciclovir, Idoxuridine, Cidofovir, Vidarabine, Ribavirine
2) Pyrophosphate anorganic : Foscarnet
3) NRTI (Nucleoside Reverse Transcriptase Inhibitor)
Zidovudine, Didanosine, Zalcitabine, Lamivudine, Stavudine,
Abacavir
4) NNRTI (Non Nucleoside Reverse Transcriptase Inhibitor)
Nevirapine, Efavirenz, Delavirdine
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Nama Obat
Antiherpes virus
dan Varicella
Zoster
Cytomegalo virus
(CMV)
Anti-influenza
Antihepatitis
HIV
Ophthalmic
Trifluridine
Topical Agents
Acyclovir
Docosanol
Penciclovir
Acyclovi
r
Acyclovir acyclovir
triphospate
terminasi rantai DNA.
Acyclovir diubah
menjadi monophospat
oleh herpes virus
thimidine kinase.
Acyclovir-MP DP
TP (oleh enzim sel
virus)
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Acyclovir
Guanosine analog
Topical, oral, and iv
Spectrum: Herpes simplex 1 and 2,
varicella-zoster virus, possibly the
Epstein-Barr Virus
Treatment of choice for visceral,
disseminated, or central nervous system
involvement
Valacyclovir
L-valyl ester prodrug of acyclovir
Rapidly and almost completely converted to
acyclovir
Famciclovir
Cyclic guanine analog
Converted to pencyclovir in the liver and
intestines
Acyclovir Resistance
Defined as MIC > 2-3 mcg/mL
Mostly occurs in immunocompromised host
4-14% (compared to 0.1-0.7% in immunocompetent)
Anti-CMV Agents
Ganciclovir
Valganciclovir
Foscarnet
Cidofovir
Ganciclovir
Competes with deoxyguanosine triphosphate similar to
acyclovir
Unlike acyclovir, ganciclovir contains a 3-hydroxyl
group, allowing for DNA to continue
Oral, intravenous, and intraocular
Spectrum:
CMV (10X potency of acyclovir)
EBV (10X potency of acyclovir)
HSV/VZV (equal to acyclovir)
Human Herpesvirus 6
Influenza Agents
Oseltamivir
Zanamivir
Amantadine
Rimantadine
Oseltamivir
Inhibit viral release
Oral neuraminidase inhibitor
Cleaves terminal sialic acid residues on
glycoconjugates and destroys receptors
Spectrum: Infuenza A and B in both children
and adults, avian influenza, H5N1 disease
Tamiflu
Amantadine &
Rimantadine
ANTI
PROTOZOA
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DAUR HIDUP
AMEBIASIS
INTESTINAL
USUS BESAR
MANUSIA
TERTELAN
MANUSIA
TINJA
SISTA
TROF
TROFOZOIT
MENEMBUS
DD. USUS MSK
ALIRAN DARAH
Metronidazole
termasuk antibiotik,
amoebisid, dan
antiprotozoal
Efektif untuk
eradikasi infeksi
intestinal dan ekstra
intestinal
Digunakan untuk :
Amoebiasis,
Giardiasis,
Trichomoniasis,
infeksi Anaerob ,
Pseudomembranous
enterocolitis, H.
pylori induced
peptic ulcer
Tugas
Satu kelas dibagi menjadi 6 kelompok, membuat makalah
dan ppt yang akan dipresentasikan (cari alternatif hari
lain sebelum UTS) dengan topik :
1. anti hepatitis virus
2. anti HIV / AIDS golongan NRTI (Nucleoside Reverse
Transcriptase Inhibitor)
3. Anti HIV / AIDS golongan NNRTI (Non Nucleoside
Reverse Transcriptase Inhibitor)
4. Anti HIV ./ AIDS golongan protease inhibitor
5. Anti Malaria
6. Anti Toxoplasma
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