1. KELOMPOK 2

4. MIKOSIS
Superficialis Inter- Profunda
Dermatofitosis Non
mediate Subcutis Sistemik
Dermatofitosis
Tinea capitis Pitiriasis Kandidiasis Misetoma Aktinomikosis
Tinea barbae versikolor Aspergillosis Kromomikosis Nokardiosis
Tinea corporis Piedra hitam Sporotrikosis Histoplasmosis
( T. imbrikata & Piedra putih Fikomikosis - Kriptokokosis
T. favosa ) Tinea nigra subkutan Koksidioidomikosis
Tinea manum palmaris Rinosporodiosis Blastomikosis
Tinea pedis Otomikosis Fikomikosis -
Tinea kruris sistemik
Tinea unguium

5. Description of
the contents

6. 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

7. 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.

8. Antifungal Agents
• Imidazole and triazole
The imidazole and triazole groups of antifungal drugs
inhibit the enzyme cytochrome P450 14α-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 Bifonazole
• Ketoconazole Butoconazole
• Clotrimazole Econazole
• Mebendazole Fenticonazole
• Isoconazole Oxiconazole
• Sertaconazole Sulconazole
• Thiabendazole Tiaconazole

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

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

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

12. 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

13. Anti jamur untuk infeksi sistemik
1. AMFOTERISIN B
Bersifat fungistatik
/fungisidal
tergantung dosis &
sensivitivitas jamur

14. Farmakokinetika
• Absorpsi melalui saluran cerna
sedikit.
• T ½ 24 - 48 jam.
• Kadar mantap dicapai setelah
beberapa bulan.
• Dapat melewati plasenta,CSS &
vitreus.
• Ekskresi melalui ginjal lambat sekali.

15. 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.

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

17. 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

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

19. Efek samping
• Toksisitas < amfoterisin B
• Dapat menimbulkan anemia,
• leukopenia dan trombositopenia
• Tidak bersifat nefrotoksik.
• Keamanan pada ibu hamil belum
• terbukti.

20. 3. Imidazol & Triazol
• Spektrum luas
• Terdiri dari : ketokonazol, mikonazol,
fluokonazol , dll.
• Banyak digunakan sebagai anti jamur
sistemik.
• Vorikonazol  relatif baru, tosisitas
• lebih rendah.
•

21. 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

22. 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

23. 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

24. ANTI JAMUR LAIN
• Asam benzoat & as salisilat
(whitfield) 2 : 1
• Asam benzoat  fungistatik
• Asam salisilat  keratolitik
• Asam undesilenat
• Haloprogin

25. 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

26. 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.

27. Jenis infestasi cacing
• Cacing tambang (ankilostomiasis)
• Cacing kremi (enterobiasis)
• Cacing gelang (askariasis)
• Cacing Pita (taeniasis)
• Filaria (W bancrofti, B malayi, Loa
loa (filariasis)
• dll.

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

29. Dietilkarbamazin
Mekanisme kerja :
1.Menurunkan aktivitas otot cacing

paralisis
2.Menyebabkan perubahan pada
permukaan membran mikrofilaria
sehingga mudah dihancurkan.

30. 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.

31. 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.

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

33. 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

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

35. Antelmentik

36. 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.

37. Antelmentik lain
• Levamisol
• Niklosamid
• Niridazol
• Prazikuantel
• Ivermektin, dll.

38. TERAPI PILIHAN
Helminth Treatment of Choice
Ascaris Albendazole, Mebendazole P
lumbricoides pamoat
E. vermicularis Albendazole, Mebendazole, P
Hookworms pamoat
Trichuris trichiura Albendazole Mebendazole, P
Filaria pamoat
Mebendazole, albendazole
Dietilcarbamazine
Cutaneus larva Thiabendazol (topical), ivermectin,
migrans Albendazol
S. stercoralis Ivermectin, Thiabendazole
ect

39. 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↓

40. Drug Classification
• Classified by their selective actions on
different phases of the parasite life cycle:
1. Tissue schizonticides(杀组织裂殖体药): eliminate
developing or dormant(静止) liver forms.
2. Blood schizonticides: act on erythrocytic parasites.
3. Gametocides(杀配子体药): kill sexual stages and
prevent transmission to mosquitoes.
• No one available agent can reliably effect a
radical cures.

41. Anti-amebiasis Drugs
• Amebiasis is infection with Entamoeba histolytic.
• Amebiasis is transmitted through gastrointestinal
tract.
• Ameba has two stages of development: cyst(包
囊) and trophozoite(滋养体).
Cysts → small intestine → little trophozoites (ileocecum)
cysts (colon) —— asymptomatic intestinal infection,
source of infection
big trophozoites (tissues of intestine) —— intestinal
amebiasis
→ extraintestinal infection

42. 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 100-
1000 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.

43. • Pharmacological Effects
1. Antimalarial action: ①highly effective blood schizonticide. ②
Moderately effective against gametocytes of P vivax, P ovale,
and P malariae but not against those of P falciparum. ③ not
active against liver stage parasites.
 Mechanism: ① plasmodium aggregates chloroquine. ②
chloroquine incorporated into DNA chain of plasmodium → inhibit
proliferation. ③ chloroquine prevents the polymerization(聚合作用)
of the hemoglobin(血红蛋白) breakdown product, heme(血红素),
into hemozoin(疟原虫色素) and thus eliciting parasite toxicity due
to the buildup of free heme. ④pH↑→ 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.
2. Killing Amibic trophozoites : chloroquine reaches high liver
concentrations.
3. Immunosuppression action:

44. • Clinical Uses
1. Treatment: nonfalciparum and sensitive
falciparum malaria. Primaquine(伯氨喹)
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(阿米巴肝脓肿): not
effective in the treatment of intestinal or
other extrahepatic amebiasis.

45. • Adverse Effects and Cautions
– Usually very well tolerated, even with prolonged use.
– Pruritus(瘙痒) is common.
– Nausea, vomiting, abdominal pain, headache,
anorexia(食欲缺乏), malaise(不适), blurring of
vision(视力模糊), and urticaria(风疹) 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

46. Metronidazole
• A nitroimidazole(硝基咪唑类). The nitro group of
metronidazole is chemically reduced in
anaerobic(厌氧的) 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.

47. • 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(滴虫病):
3. Anti-anaerobic bacteria(厌氧细菌):
4. Anti-giardiasis(梨形鞭毛虫病):

48. • 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(脑病), seizures)——
drug withdrawal
– Has a disulfiram(双硫仑,乙醛脱氢酶抑制药)-
like effect, so that nausea and vomiting can
occur if alcohol is ingested during therapy.

49. BYE