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ANTIFUNGALS

KELOMPOK 2

JAJANG JAMALUDIN

KURNIA
WIWIN

AGEN ANTI JAMUR

Senyawa Yang Digunakan Untuk


Pengobatan Penyakit Yang
Disebabkan Oleh Jamur.

MIKOSIS
Superficialis
Dermatofitosis

Non
Dermatofitos
is

Tinea capitis
Tinea barbae
Tinea corporis
( T. imbrikata &
T. favosa )
Tinea manum
Tinea pedis
Tinea kruris
Tinea unguium

Pitiriasis
versikolor
Piedra hitam
Piedra putih
Tinea nigra
palmaris
Otomikosis

Intermediate

Kandidiasis
Aspergillosis

Profunda
Subcutis

Sistemik

Misetoma
Kromomikosis
Sporotrikosis
Fikomikosis subkutan
Rinosporodiosis

Aktinomikosis
Nokardiosis
Histoplasmosis
Kriptokokosis
Koksidioidomikosis
Blastomikosis
Fikomikosis
-sistemik

ANTI JAMUR

INFEKSI SISTEMIK

Infeksi Yang
Disebabkan Oleh
Jamur Disebut
Mikosis.

Description of
the contents

INFEKSI TOPIKAL

ANTI
FUNGALS

Antifungal Agents
Polyene antibiotic
The polyene antibiotics bind with sterols in the fungal
cell membrane, principally ergosterol. This causes
the cell's contents to leak out and the cell dies.
Animal cells contain cholesterol instead of ergosterol
and so they are much less susceptible.
Nystatin
Amphotericin B (may be administered liposomally)

Natamycin
Rimocidin
Filipin
Pimaricin

Nystatin: The first antibiotic against fungi


Like many other antimycotics and antibiotics, nystatin is of
bacterial origin. It was isolated from Streptomyces noursei in
1950 by Elizabeth Lee Hazen and Rachel Fuller Brown, who
were doing research for the Division of Laboratories and
Research of the New York State Department of Health. The soil
sample where they discovered nystatin, was from the garden of
Hazen's friends called Nourses, therefore the strain was called
noursei. Hazen and Brown named nystatin after the New York
State Public Health Department (now known as the
Wadsworth Center) in 1954.
The two scientists donated the royalties from their invention,
over $13 million dollars, to the nonprofit Research Corporation
for the advancement of academic scientific study. Elizabeth Lee
Hazen and Rachel Fuller Brown were inducted into the National
Inventors Hall of Fame in 1994.

Antifungal Agents
Imidazole and triazole
The imidazole and triazole groups of antifungal drugs
inhibit the enzyme cytochrome P450 14-demethylase.
This enzyme converts lanosterol to ergosterol, and is
required in fungal cell membrane synthesis. These drugs
also block steroid synthesis in humans.

Imidazoles:

Miconazole
Ketoconazole
Clotrimazole
Mebendazole
Isoconazole
Sertaconazole
Thiabendazole

Bifonazole
Butoconazole
Econazole
Fenticonazole
Oxiconazole
Sulconazole
Tiaconazole

Antifungal Agents
The triazoles are newer, and are
less toxic and more effective:
Fluconazole
Itraconazole
Ravuconazole
Posaconazole
Voriconazole

Antifungal Agents
Allylamines
Allylamines inhibit the enzyme squalene
epoxidase, another enzyme required for
ergosterol synthesis:
Terbinafine - marketed as Lamisil
Amorolfine
Naftifine
Butenafine

Antifungal Agents
Echinocandin
Echinocandins inhibit the synthesis of glucan
in the cell wall, probably via the enzyme 1,3-
glucan synthase:
Anidulafungin
Caspofungin
Micafungin

Antifungal Agents
Others:
Flucytosine is an antimetabolite.
Griseofulvin binds to polymerized microtubules
and inhibits fungal mitosis; It is derived from the
mold Penicillium griseofulvum.
Fluocinonide
Salicylic Acid (topical)
Tinactin or Tolnaftate
Potassium Iodide

Anti jamur untuk infeksi sistemik


1. AMFOTERISIN B

Bersifat fungistatik
/fungisidal
tergantung dosis &
sensivitivitas jamur

Farmakokinetika
Absorpsi melalui saluran cerna
sedikit.
T 24 - 48 jam.
Kadar mantap dicapai setelah
beberapa bulan.
Dapat melewati plasenta,CSS &
vitreus.
Ekskresi melalui ginjal lambat sekali.

Efek samping
Infus kulit panas, keringatan, sakit
kepala, demam, flebitis ,penurunan
fungsi ginjal > 80% pasien ,dll.
Derajat kerusakan ginjal tergantung
dosis.
Efek toksik ginjal dapat ditekan
dengan pemberian bersama flusitosin.

Indikasi
1. Terapi awal infeksi jamur yang
mengancam kehidupan
2. Koksidiomikosis,Aspergilosis,
kandidiosis dll.
3. Obat terpilih (Drug of choice)
untuk Blastomikosis.

Perhatian
1. Selama pengobatan pasien harus
di rawat di rumah sakit
2. Monitoring ketat urinalisis, darah
dan kimia darah (K,Mg,ureum
dan kreatinin) menjelang tercapai
dosis optimal
3. Bila terjadi insuffisiensi
ginjal,terapi stop

2. FLUSITOSIN
Spektrum sempit
Efektif untuk kriptokokosis,
kandidiasis, Aspergilosis
Bila diberikan bersama
Amfoterisin B bersifat
supraaditif.

Efek samping

Toksisitas < amfoterisin B


Dapat menimbulkan anemia,
leukopenia dan trombositopenia
Tidak bersifat nefrotoksik.
Keamanan pada ibu hamil belum
terbukti.

3. Imidazol & Triazol


Spektrum luas
Terdiri dari : ketokonazol, mikonazol,
fluokonazol , dll.
Banyak digunakan sebagai anti jamur
sistemik.
Vorikonazol relatif baru, tosisitas
lebih rendah.

ANTI JAMUR UNTUK INFEKSI


DERMATOFIT & MUKOKUTAN

1. Griseofulvin
in vitro efektif terhadap berbagai jenis
jamur.
Absorpsi melalui sal cerna kurang baik
Efek samping : Leukopenia & granulo
sitopenia.
Sediaan tablet 125 mg & 500mg

ANTI JAMUR UNTUK INFEKSI


DERMATOFIT & MUKOKUTAN

2. Imidazol & triazol


3. Tolnaftat
4. Nistatin
Mekanisme kerja :
Nistatin + sterol perubahan
permeabilitas membran sel sel
kehilangan berbagai molekul kecil

Nistatin
Merupakan antibiotik polien.
Mekanisme kerja : berikatan dengan
ergosterol pada membran jamur,
permeabilitas meningkat, sel jamur mati.
Indikasi : kandidiasis kulit, selaput lendir,
dan saluran cerna.
Efek samping : jarang ditemukan, mual,
muntah, diare ringan

ANTI JAMUR LAIN


Asam benzoat & as salisilat
(whitfield) 2 : 1
Asam benzoat fungistatik
Asam salisilat keratolitik
Asam undesilenat
Haloprogin

PERTIMBANGAN TERAPI
Infeksi berat gol imidazol
Lesi hiperkeratosis kuku anti
jamur topikal + zat keratolitik
Infeksi jamur dgn tanda
radanghebat anti jamur +
kortikosteroid
Tinea versikolor selenium
sulfid

ANTELMENTIK
Obat untuk memberantas atau mengurangi
infestasi cacing dalam lumen usus atau
jaringan tubuh
Antelmentik lama kurang aman
kurang efektif
Antelmentik baru lebih aman & efektif
rasa tidak mengganggu, sebagian
dapat diberikan oral, dosis tunggal.

Jenis infestasi cacing


Cacing tambang (ankilostomiasis)
Cacing kremi (enterobiasis)
Cacing gelang (askariasis)
Cacing Pita (taeniasis)
Filaria (W bancrofti, B malayi, Loa
loa (filariasis)
dll.

1. Dietilkarbamazin
Obat pilihan pertama untuk
filariasis
Dapat menghilangkan
mikrofilaria
W bacrofti, B malayi, loa loa dari
peredaran darah.

Dietilkarbamazin
Mekanisme kerja :
1.Menurunkan aktivitas otot cacing

paralisis
2.Menyebabkan perubahan pada
permukaan membran mikrofilaria
sehingga mudah dihancurkan.

Efek samping
Relatif aman pada dosis terapi
Pusing,gangguan sal cerna, sakit kepala
dll.
Reaksi alergi karena matinya parasit
dan substansi yang dilepaskan oleh
mikrofilaria yang hancur.

2. Piperazin
Efektif terhadap A. lumbricoides &
E vermicularis
Mekanisme kerja :
Blokade respon otot cacing
terhadap asetil kolin paralisis
Cacing mudah dikeluarkan oleh
peristaltik usus,cacing keluar 1-3
hari setelah pengobatan.

3. Pirantel Pamoat
Untuk : caing kremi, gelang,
tambang.
Mekanisme kerja : depolarisasi otot
cacing dan meningkatkan frekuensi
impuls
Cacing mati dalam keadaan
spastis

Pirantel Pamoat
Absorpsi kurang baik, ekskresi
sebagian besar melalui tinja
Efek non terapi: keluhan saluran cerna,
demam & sakit kepala
Kontra indikasi :
wanita hamil,Usia < 2 tahun
Pemberian bersama piperazin

Pirantel Pamoat
Obat terpilih untuk : askariasis,
ankilostomiasis, enterobiasis &
strongiloidiasis
Sediaan : tablet 125mg, 250 mg
Dosis 10 mg/kgBB, dosis tunggal

Antelmentik

4. Mebendazol
Spektrum paling luas, obat terpilih
untuk enterobiasis & trichuriasis.
Mekanisme kerja :
menyebabkan kerusakan struktur
subseluler & menghambat sekresi
asetilkolinesterase cacing.
Menghambat ambilan glukosa secara
irreversibel.

Antelmentik lain

Levamisol
Niklosamid
Niridazol
Prazikuantel
Ivermektin, dll.

TERAPI PILIHAN
Helminth
Ascaris
lumbricoides

Treatment of Choice
Albendazole, Mebendazole P
pamoat

E. vermicularis
Hookworms
Trichuris trichiura
Filaria

Albendazole, Mebendazole, P
pamoat
Albendazole Mebendazole, P
pamoat
Mebendazole, albendazole
Dietilcarbamazine

Cutaneus larva
migrans

Thiabendazol (topical), ivermectin,


Albendazol

S. stercoralis
ect

Ivermectin, Thiabendazole

Rational Use of Antimalarial


Drugs
1.

Choice of Antimalarial Drugs:


Control symptoms: chloroquine
Cerebral malaria: chloroquine phosphate, quinine bimuriate,
artemisinin injection
Chloroquine-resistant falciparum malaria: quinine, mefloquine,
artemisinin
Dormant hypnozoite stages : pyrimethamine + primaquine
Prophylaxis: pyrimethamine, chloroquine

2.

Combination therapy:

chloroquine + primaquine: symptom stages


pyrimethamine + primaquine: dormant hypnozoite stages
Combination of drugs with different mechanisms: therapeutic
effect, resistance

Drug Classification

Classified by their selective actions on


different phases of the parasite life cycle:
1. Tissue schizonticides( ): eliminate
developing or dormant( ) liver forms.
2. Blood schizonticides: act on erythrocytic parasites.
3. Gametocides( ): kill sexual stages and
prevent transmission to mosquitoes.

No one available agent can reliably effect a


radical cures.

Anti-amebiasis Drugs
Amebiasis is infection with Entamoeba histolytic.
Amebiasis is transmitted through gastrointestinal
tract.
Ameba has two stages of development: cyst(
) and trophozoite( ).
Cysts small intestine little trophozoites (ileocecum)

cysts (colon) asymptomatic intestinal infection,


source of infection
big trophozoites (tissues of intestine) intestinal
amebiasis
extraintestinal infection

CHLOROQUINE
A synthetic 4-aminoquinoline formulated as the
phosphate salt for oral use.
Pharmacokinetics
Rapidly and almost completely absorbed from the
gastrointestinal tract.
Very large apparent volume of distribution of 1001000 L/kg.
Necessitate the use of a loading dose to rapidly
achieve effective serum concentrations.
Slowly released from tissues and metabolized.
Principally excreted in the urine.

Pharmacological Effects
1.

Antimalarial action: highly effective blood schizonticide.


Moderately effective against gametocytes of P vivax, P
ovale, and P malariae but not against those of P falciparum.
not active against liver stage parasites.

2.
3.

Mechanism: plasmodium aggregates chloroquine.


chloroquine incorporated into DNA chain of plasmodium
inhibit proliferation. chloroquine prevents the polymerization(
) of the hemoglobin( ) breakdown product,
heme( ), into hemozoin( ) and thus eliciting
parasite toxicity due to the buildup of free heme. pH
plasmodium protease activity
Resistance: very common among strains of P falciparum and
uncommon but increasing for P vivax. The mechanism of
resisitance to chloroquine is resistant strains excretes drug more
rapidly.

Killing Amibic trophozoites : chloroquine reaches high liver


concentrations.
Immunosuppression action:

Clinical Uses
1. Treatment: nonfalciparum and sensitive
falciparum malaria. Primaquine( )
must be added for the radical cure of P vivax
and P ovale, because chloroquine does not
eliminate dormant liver forms of these
species.
2. Chemoprophylaxis: for without resistant
falciparum malaria in malarious regions.
3. Amebic liver abscess( ): not
effective in the treatment of intestinal or
other extrahepatic amebiasis.

Adverse Effects and Cautions


Usually very well tolerated, even with prolonged use.
Pruritus( ) is common.
Nausea, vomiting, abdominal pain, headache,
anorexia( ), malaise( ), blurring of
vision( ), and urticaria( ) are
uncommon.
Dosing after meals may reduce some adverse effects.
Rare reactions include hemolysis in G6PD-deficient
persons, impaired hearing, confusion, psychosis,
seizures, hypotension, ECG changes.
teratogenesis

Metronidazole
A nitroimidazole( ). The nitro group of
metronidazole is chemically reduced in
anaerobic( ) bacteria and sensitive
protozoans. Reactive reduction products appear
to be responsible for antimicrobial activity.
Pharmacokinetics
Oral metronidazole is readily absorbed and
permeates all tissues by simple diffusion.
Protein binding is low (<20%)
Through blood brain barrier
Metabolizing in liver.
Excreted mainly in the urine.

Pharmacological Effects and Clinical


Uses
1. Anti-amebiasis: kills E histolytic trophozoites
but not cysts. Treatment of all tissue
infections with E histolytic. No effection
against luminal parasites and so must be
used with a luminal amebicide to ensure
eradication of the infection.
2. Anti-trichomoniasis( ):
3. Anti-anaerobic bacteria( ):
4. Anti-giardiasis( ):

Adverse Effects and Cautions


Nausea, headache, dry mouth, a metallic
taste in the mouth.
Infrequent: vomiting, diarrhea, rash, insomnia,
neutropenia,
Rare: severe central nervous system toxicity (
ataxia, encephalopathy( ), seizures)
drug withdrawal
Has a disulfiram( , )like effect, so that nausea and vomiting can
occur if alcohol is ingested during therapy.

GOOD

BYE