ANTIFUNGAL Flashcards
Introduction
- Fungi exist in two basic forms: yeasts and moulds.
- Yeasts are solitary forms of fungi that reproduce by budding. When they are left
to grow in colonies, they have a moist, shiny appearance. - Moulds are multicellular fungi that consist of many branching hyphae and can reproduce either by translocation of existing hyphae to a new area, or through
spore formation and spread (hence, one bad apple really does spoil a bunch)
Definisi bagi fungicidal, fungistatic & fungal infection
Fungicidal = Agen yg blh membunuh fungal pathogen
Fungistatic = Agen yg menghalang pembiakan fungal pathogen
Fungal infection = jangkitan kulat / mycosis merupakan penyakit kulit yg
disbbkan oleh kulat
Nyatakan & terangkan jenis2 jangkitan kulat
(1) Superficial (mucocutaneous) :
- Dermatophytes: menyebabkan jangkitan pada kulit, kepala dan kuku.
E.g. tinea capitis (kepala), tinea cruris (paha), tinea pedis (kaki),onychomycosis (kuku)
- Yeast: menyebabkan jangkitan pada moist skin dan mucous membranes.E.g. Candida albicans
menyebabkan jangkitan pada pharyngeal,vaginal & bladder
(2) Systemic = Memberi kesan kepada internal organ apabila fungi memasuki badan melalui paruparu dan merebak ke sistem darah. Biasa
berlaku dalam immunocompromised patient. E.g. cryptococcocosis, aspergillosis (lung)
Definisi fungal nail infections (onychomycosis)
- Infeksi fungal pd kuku merupakan infeksi yg biasa terjadi kuku jari tangan & kaki
yg menyebbkan kuku hilang warna, menebal dan mudah utk patah.
Definisi vaginal candidiasis
- Nama lain bagi vaginal candidiasis ialah vaginal yeast infection, vulvovaginal candidiasis atau candidal vaginitis
- Candidiasis merupakan infeksi yg disbbkan oleh yis Candida yg biasanya hidup dalam bdn sperti dlm mulut, tekak, usus dan vagina
Definisi ringworm
- Ringworm ialah infeksi kulit yg disbbkan oleh fungus. Nama lain bagi ringworm
ialah tinea atau dermatophytosis - Ringworm menyebbkan circular rash yg biasanya kemerahan & gatal
Definisi candida infections of the mouth, throat & esophagus
- Candidiasis dlm mulut / tekak = thrush / oropharyngeal candidiasis
- Candidiasis dlm esophagus = esophageal candidiasis / Candida esophagitis
- Esophageal candidiasis biasanya berlaku dlm kalangan pesakit HIV / AIDS2
Definisi antifungal resistance
- Apb kulat tdk lagi memberi tndk balas pd agen antifungal
- Beberapa jns kulat sprti Candida auris blh mnjadi rintg trhadap ketiga-tiga jenis
agen antifungal
Senaraikan 3 kategori utama berserta cth ubat bagi antifungal drugs
Utk jangkitan mucocutaneous :
(1) Systemic drugs :
- Azole (Fluconazole, Itraconazole, Voriconazole), Griseofulvin, Nyastatin
(2) Topical drugs :
- Azole (Ketoconazole, Miconazole, Clotrimazole, Tioconazole), Nyastatin, Terbinafine
Utk jangkitan sistemik :
- Azole (Fluconazole, Itraconazole, Variconazole), Amphotericin B, Flucytosine, Caspofungin
Nyatakan kelas antifungal beserta cth ubat berdasarkan struktur kimia / MOA
(1) Azole - Ketoconazole, Clotrimazole, Miconazole, Fluconazole, Itraconazole, Posaconazole,
Voriconazole, Isavuconazole
(2) Polyenes - Amphotericin B, Nyastatin
(3) Allylamines - Terbinafine
(4) Echinocandins - Anidulafungin, Caspofungin, Micofungin
(5) Miscellaneous - Flucytosine, Griseofulvin
Azole
MOA :
- Ergosterol merupakan sterol utama dalam sel membrane fungal.
- Azole antifungals merencat enzim 14-alphademethylase.
- Enzim ini penting dalam pertukaran lanosterol kepada ergosterol.
- Kekurangan ergosterol menyebabkan kerosakan pada sel membrane fungal lalu sel
mati.
Adverse Effect :
- Hepatotoxicity
Indications :
- SUPERFICIAL SKIN INFECTIONS = Tinea infection, Hair infection, Onychomycosis,
Mucocutaneous candidiasis
- SYSTEMIC FUNGAL INFECTIONS = Blastomycosis, Systemic candidiasis dan cryptococcal meningitis,
Invasive aspergillosis
Cont. Azole
Side Effects :
- Headache, Dizziness, Hepatoxicity, Pruritus, Thrombocytopenia, GI disturbances
Drug Interactions :
- Amphotericin B
Contraindications :Allergic to Amphotericin, Liver dysfunction, Renal dysfunction
Persediaan : Clotrimazole 1% solution (Canestan) Clotrimazole 1% cream (Canestan) Clotrimazole 200mg/500mg vaginal tablet (Canestan) Miconazole Nitrate 2% cream (Daktarin) Fluconazole 100mg cap Fluconazole 50 mg cap Fluconazole 2mg/ml inj Itraconazole100mg cap Itraconazole10mg/ml oral solution Voriconazole 200mg/vial for in
Polyenes
MOA :
- Polyenes berfungsi dengan berinteraksi dengan ergosterol, sejenis steroid yang
terdapat pada membran kulat.
- Pengikatan ini menyebabkan saluran terbentuk
(Pore) pada membran kulat dan pore ini akan mengakibatkan kehilangan potassium
dan beberapa molekul kecil dari sel kulat. Ini mengakibatkan sel kulat mati.
Amphotericin
Adverse Effects :
- Chills, muscle spasm & fever. nephrotoxicity, Hypokalemia and anemia
Indications :
- Systemic fungal infections caused by Candida albicans
Side Effects :
- headache, nausea, vomitting
Cont. Polyenes
Drug Interactions :
- Digitalis, neuromuscular agents
Contraindications :
- allergic to drug
Cautions :
- renal impairment
Persediaan :
- Amphotericin B eye drops
Nystatin
Adverse Effects :
- Too toxic for parenteral administration, only use oral or topically
Indications :
- Suppressions of local candidal infections
Side Effects :
- nausea, vomitting, diarrhea, rash, local irritation
Contraindications :
- allergic to nystatin
Cautions :
- pregnancy & lactation
Persediaan : Nystatin 100 000 unit/g cream/ ointment (Mycostatin) Nystatin 100 000 unit/ml suspension (Mycostatin)
Allylamines
MOA :
- Allylamines merencat enzim squalene epoxidase dimana enzim ini sepatutnya
mengubah squalene kpd ergosterol
- Perecatan ini mybbkn squalene trkumpul dgn byk dlm sel kulat
- Squalene mrupkn bhn beracun bg sel kulat maka sel kulat akn mati
Indications :
- Dermatophytoses, Onychomycosis
Side Effects :
- Headache, hastrointestinal upset
Contraindication :
Chronic or active liver disease.History of an allergic reaction to oral terbinafine
Cautions :
- elderly patients yang ada masalah hati, jantung dan buah pinggang
Persediaan :
- Terbinafine hydrochloride 1 % Topical Cream
Echinocandins
MOA :
- Echinocandins menganggu sintesis dinding sel dengan menghalang enzim β(1,3)-d-glucan synthase.
- Enzim yang bertanggungjawab dalam sintesis D-glucan iaitu bahan dalam dinding sel kulat.
- Ini menyebabkan sel lysis kerana tekanan osmotic.
Miscellaneous (Flucytosine)
MOA :
- Akan ditukar kepada 5 Fluorouracil yang akan menganggu sintesis RNA dan protein.
- 5- fluorouracil akan dimetabolise kepada 5- fluorodeoxyuridylic acid yang mana akan merencat
thymidylate synthetase iaitu enzim diperlukan dalam sintesis DNA.
- Ini menyebabkan sel kulat mati.
Adverse Effects :
- depression of bone marrow, hair loss
Cont. Miscellaneous (Flucytosine)
Indications :
- treatment of serious infections caused by certain strains of two types of fungi: Candida
and Cryptococcus.
Side effects :
- nausea, vomitting, diarrhea
Drug Interactions :
- Cytarabine & NSAIDs such as ibuprofen or naproxen
Contraindications :
- liver problems, anemia
Persediaan :
Flucytosine 500 mg Tablet
Flucytosine 2.5 g/250 ml Injection
Griseofulvin
MOA :
- Griseofulvin merencat mitosis sel kulat.
- Ia juga mengikat dan mengganggu fungsi mikrotubulus spindle dan sitoplasma dengan
mengikat alpha dan beta tubulin.
- Ini menghalang pembahagian sel anak serta merencat pembiakan sel kulat
Adverse Effects :
- A lupus like syndrome, Hepatotoxicity , Serious skin reaction
Indications :
- Systemic treatment of dermatophytosis
Warning :
- Serious skin reactions warning: This drug can cause skin reactions. These may be serious and life-threatening
Side Effects :
- Headache, Dizziness, Rash, Urticaria, GI disturbances, Photosensitivity, Peripheral neuropathy
Drug Interactions :
- Warfarin, Phenobarbital
Contraindications :
- Allergic to Griseofulvin, Hepatic Failure, SLE, Pregnancy
Persediaan :
- Griseofulvin (Ultramicrosize 125 mg = 250 mg Microsize) Tablet
