• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
Antifungals
 

Antifungals

on

  • 2,386 views

 

Statistics

Views

Total Views
2,386
Views on SlideShare
2,368
Embed Views
18

Actions

Likes
0
Downloads
45
Comments
0

1 Embed 18

http://nerskomalihsan.wordpress.com 18

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Antifungals Antifungals Presentation Transcript

    • KELOMPOK 2
    • MIKOSIS Superficialis Inter- ProfundaDermatofitosis 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
    • Description of the contents
    • Antifungal Agents• Polyene antibiotic The polyene antibiotics bind with sterols in the fungal cell membrane, principally ergosterol. This causes the cells 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 Hazens 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 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
    • 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-β 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 sistemik1. AMFOTERISIN B Bersifat fungistatik /fungisidal tergantung dosis & sensivitivitas jamur
    • 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.
    • Efek sampingInfus  kulit panas, keringatan, sakitkepala, demam, flebitis ,penurunanfungsi ginjal > 80% pasien ,dll.Derajat kerusakan ginjal tergantungdosis.Efek toksik ginjal dapat ditekan denganpemberian bersama flusitosin.
    • Indikasi1. Terapi awal infeksi jamur yang mengancam kehidupan2. Koksidiomikosis,Aspergilosis, kandidiosis dll.3. Obat terpilih (Drug of choice) untuk Blastomikosis.
    • Perhatian1. Selama pengobatan pasien harus di rawat di rumah sakit2. Monitoring ketat urinalisis, darah dan kimia darah (K,Mg,ureum dan kreatinin) menjelang tercapai dosis optimal3. 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 & MUKOKUTAN1. 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 & MUKOKUTAN2. Imidazol & triazol3. Tolnaftat4. 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
    • ANTELMENTIKObat untuk memberantas atau mengurangiinfestasi cacing dalam lumen usus ataujaringan tubuhAntelmentik lama  kurang aman kurang efektifAntelmentik 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.
    • DietilkarbamazinMekanisme kerja :1.Menurunkan aktivitas otot cacing  paralisis2.Menyebabkan perubahan pada permukaan membran mikrofilaria sehingga mudah dihancurkan.
    • Efek sampingRelatif aman pada dosis terapiPusing,gangguan sal cerna, sakit kepaladll.Reaksi alergi  karena matinya parasitdan substansi yang dilepaskan olehmikrofilaria 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 Treatment of ChoiceAscaris Albendazole, Mebendazole Plumbricoides pamoatE. vermicularis Albendazole, Mebendazole, PHookworms pamoatTrichuris trichiura Albendazole Mebendazole, PFilaria pamoat Mebendazole, albendazole DietilcarbamazineCutaneus larva Thiabendazol (topical), ivermectin,migrans AlbendazolS. stercoralis Ivermectin, Thiabendazoleect
    • Rational Use of Antimalarial Drugs1. 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, chloroquine2. 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(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.
    • 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
    • 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.
    • • 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:
    • • 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.
    • • 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
    • 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.
    • • 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):
    • • 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.
    • BYE