EM Sutrisna

Beberapa tahun terakhir, diduga terjadi

peningkatan luar biasa kasus infeksi oleh
jamur, seperti”
- infeksi mukosa mulut,
- bronchia, usus, vagina dan lain-lain oleh
Candida albicans.
Gray Patch
 Papulosquamous
 Erythematous
 Annular
 Scaling
 Crusting
 ‘Ringworm’
 Perubahan pigmen kulit.
◦ Red
◦ Hypo pigmented
◦ Hyperpigmented
 Jrang di wajah, banyak ditubuh,leher
 Pityrosporum orbicularis, M. furfur
◦ Normal flora of skin
 Asymptomatic.
More
apparent in
the summer.
Tinea
Vesicolor
Hyperpigmented
Variety
Looks Like: intertrigo,
erythrasma ….
•Vitiligo
•Pityriasis Alba
•Pityriasis Rosea
•Nummular Eczema
•Psoriasis
•Idiopathic guttate hypomelanosis
White without
scale.
Frequently on face, KOH
neg. Few lesions.

May have fine white

scale.
•Papules or
plaques with
Collarette of scale,
KOH (-), Woods
light neg. HX.
1- Antifungal Antibiotik :
◦ Griseofulvin
◦ Polyene macrolide : Amphotericin- B & Nystatin
2- Synthetic :
◦ Azoles :
 A) Imidazoles : Ketoconazole , Miconazole
 B) Triazoles : Fluconazole , Itraconazole
◦ Flucytosine
◦ Squalene epoxidase inhibitors : e.g.
 Terbinafine & Naftifine.
 Flucytosine
 Squalene epoxidase inhibitors : e.g.
◦ Terbinafine & Naftifine.
Systemic :
 Griseofulvin , Amphotericin- B , Ketoconazole ,
Fluconazole , Terbinafine.
Topical
 In candidiasis :
◦ Imidazoles : Ketoconazole , Miconazole.
◦ Triazoles : Terconazole.
◦ Polyene macrolides : Nystatin , Amphotericin-B
◦ Gentian violet : Has antifungal & antibacterial.
 Squalene epoxidase inhibitors : Terbinafine
&Naftifine.
 Tolnaftate.
 White field ointment : 12% Benzoic acid &
6% Salicylic acid .
 Castellani paint.
 Cell membrane
• Polyene antibiotics
• Azole antifungals

DNA/RNA synthesis
• Pyrimidine analogues
- Flucytosine

Cell wall
• Echinocandins
-Caspofungin acetate (Cancidas)

Atlas of fungal Infections, Richard Diamond Ed. 1999

Introduction to Medical Mycology. Merck and Co. 2001
 Amphotericin A & B merupakan antifungal
antibiotics.
 Amphotericin A tidak digunakan diklinis
 Merupakan natural polyene macrolide
 (polyene = many double bonds )
 (macrolide = containing a large lactone
ring)
 absorbed per orall jelek ,
 effective untuk fungal infection di
gastrointestinal tract.
 For systemic infections given as slow I.V
 Highly bound to plasma protein .
 Poorly crossing BBB.
 Metabolized in liver
 Excreted slowly in urine over a period of
several days.
 Half-life 15 days.
 merupakan “ selective fungicidal”.
 Merusak membrane sel jamur dengan
mengikat ergosterol , merubah
permeability of the cell membrane 
intracellular ions & macromolecules bocor (
cell death ).
Terjadi jika ikatan ergosterol lemah. Hal ini
disebabkan:
 Decreasing the membrane concentration of
ergosterol.
 Or by modyfing the sterol target molecule.
1- Immediate reactions ( Infusion –related toxicity
).
 Fever, muscle spasm, vomiting ,headache,
hypotension.
 Can be avoided by :
◦ A. Slowing the infusion
◦ B. Decreasing the daily dose
◦ C. Premedication with antipyretics, antihistamincs or
corticosteroids.
◦ D. A test dose.
 Most serious is renal toxicity (nearly in all
patients ).
 Hypokalemia
 Hypomagnesaemia
 Impaired liver functions
 Thrombocytopenia
 Anemia
 Has a broad spectrum of activity & fungicidal
action(Candida albicans and Cryptococcus
neoformans; the organisms causing endemic
mycoses, including Histoplasma capsulatum,
Blastomyces dermatitidis, and Coccidioides
immitis; and the pathogenic molds, such as
Aspergillus fumigatus and mucor)
 The drug of choice for life-threatening mycotic
infections.
 For induction regimen for serious fungal infection.
 Also, for chronic therapy & preventive therapy of
relapse.
 In cancer patients with neutropenia who remain
febrile on broad –spectrum antibiotics.
1- Slow I.V.I. For systemic fungal disease.
2- Intrathecal for fungal C.N.S. infections.
 Topical drops & direct subconjunctival
injection for Mycotic corneal ulcers &
keratitis.
3- Local injection into the joint in fungal
arthritis.
4- Bladder irrigation in Candiduria.
 Amphotericin B yg dikemas dalam lipid-
menurunkan pengikata thd human cell
membrane , so menurunkan:
◦ A. Nephrotoxicity
◦ B. Infusion toxicity
◦ Also, more effective
◦ But More expensive
 Efek Segera (infuse efek)
 Efek kumulatif
 . A. INFUSION-RELATED TOXICITY
 These infusion-related reactions are nearly
universal and consist of fever, chills, muscle
spasms, vomiting, headache, and
hypotension. They can be ameliorated by
slowing the infusion rate or decreasing the
daily dose. Premedication with antipyretics,
antihistamines, meperidine, or corticosteroids
can be helpful.
 starting therapy with a test dose of 1 mg
intravenously to gauge the severity of the
reaction.
 B. CUMULATIVE TOXICITY
◦ Nefrotoksik
 Merupakan polyene macrolide ,
 Structure & mechanism sama dengan
amphotericin B.
 Too toxic for systemic use.
 Used only topically.(creams, ointment ,
suppositories & other preparations)
 Preventif dan pengobata superficial
candidiasis of mouth, esophagus, intestinal
tract.
 Vaginal candidiasis
 Can be used in combination with
antibacterial agents & corticosteroids.
 A group of synthetic fungistatic agents
with a broad spectrum of activity .
 They have antibacterial , antiprotozoal
anthelminthic & antifungal activity .
 1-Menghambat cytochrome P450 enzyme
jamur (α-demethylase) menghambat
perubahan lanosterol menjadi ergosterol (
sterol utama membrane sel jamur).
 2- menghambat mitochondrial cytochrome
oxidase accumulation of peroxides that
cause autodigestion of the fungus.
 3- merubah metabolism RNA& DNA.
 Merupakan antibacterial , antiprotozoal,
anthelminthic & antifungal.
 They are fungistatic agents.
 dibagi:
◦ Imidazole group
◦ Triazole group
 Ketoconazole
 Miconazole
 Clotrimazole
◦ Selectivitas kurang
◦ menghambat human gonadal and steroid
synthesis penurunan produksi testosterone &
cortisol
◦ Menghambat sitokromP-450 manusia
 Absorbsi po baik .
 Bioavailabilitas turun jika diberikan bersama
antacids, H2 blockers , proton pump
inhibitors & makanan .
 Dimetabolisme liver & diexcresi di
emepedu (feces ) & urine.
 Does not cross BBB.
 Used topically or systematic (oral route only
) to treat :
1- Oral & vaginal candidiasis.
2- Dermatophytosis.
3- Systemic mycoses & mucocutaneous
candidiasis.
 Nausea, vomiting ,anorexia
 Hepatotoxic
 Inhibits human P 450 enzymes
 Inhibits adrenal & gonadal steroids leading
to :
◦ Menstrual irregularities
◦ Loss of libido
◦ Impotence
◦ Gynaecomastia in males
Kontraindikasi :
 Prgnancy, lactation ,hepatic dysfunction
 Interact with enzyme inhibitors , enzyme
inducers.
 H2 blockers & antacids menurunkan
absorpsinya
 Fluconazole
 Itraconazole
 Voriconazole
◦ sifat :
 Selective
 Resistant thd degradasi
 Menyebabkan sedikit gangguan
indocrine
 Sedikit side effects indokrin
 broad spectrum
 Diberikan orally & IV
 Food meningkatkan absorpsinya
 Di Metabolized di liver  active metabolite
 Highly lipid soluble ,well distributed to
bone, sputum ,adipose tissues.
 Can not cross BBB
 Half-life 30-40 hours
 Used orally in dermatophytosis & vulvo-
vaginal candidiasis.
 IV only in serious infections.
 Effective in AIDS-associated histoplasmosis
 Side effects :
◦ Nausea, vomiting, hypokalemia, hypertension,
edema, inhibits the metabolism of many drugs as
oral anticoagulants.
 Water soluble
 Completely absorbed from GIT
 Excellent bioavailability after oral
administration
 Bioavailability is not affected by food or
gastric PH
 Conc. in plasma is same by oral or IV route
 Has the least effect on hepatic microsomal
enzymes
 Jarang terjadi interaksi obat
 Penetrates well BBB so, it is the drug of
choice of cryptococcal meningitis
 Safely given in patients receiving bone
marrow transplants (reducing fungal
infections)
 Excreted mainly through kidney
 Half-life 25-30 hours
 Candidiasis
◦ is effective in all forms of mucocutaneous
candidiasis)
 Cryptococcus meningitis
 Histoplasmosis, blastomycosis, , ring worm.
 Not effective pada aspergillosis
 Nausea, vomiting, headache, skin rash ,
diarrhea, abdominal pain , reversible
alopecia.
 Hepatic failure may lead to death
 Highly teratogenic ( as other azoles)
 Inhibit P450 cytochrome
 No endocrine side effects
 A broad spectrum antifungal agent
 Given orally or IV
 High oral bioavailability
 Penetrates tissues well including CSF
 Inhibit P450
 Used for the treatment of invasive
aspergillosis & serious infections.
 Reversible visual disturbances
 Synthetic pyrimidine antimetabolite
(cytotoxic drug ) often given in combination
with amphotericin B & itraconazole.
 Systemic fungistatic
 Merubah the fungal cell  5- fluorouracil(
Not in human cell )menghambat
thymidylate synthetase menghambat
sintesis DNA

 ( Amphotericin B increases cell permeability

, allowing more 5-FC to penetrate the cell,
they are synergistic).
 Rapidly & well absorbed orally
 Widely distributed including CSF.
 Mainly excreted unchanged through kidney
 Half-life 3-6 hours
 Severe deep fungal infections as in
meningitis
 Generally given with amphotericin B
 For cryptococcal meningitis in AIDS patients
 Nausea, vomiting , diarrhea, severe
enterocolitis
 Reversible neutropenia, thrombocytopenia,
bone marrow depression
 Alopecia
 Elevation in hepatic enzymes
 (some adverse effects related to 5-Fu
formed by intestinal organisms from5-FC)
 Inhibits the synthesis of fungal cell wall by
inhibiting the synthesis of β(1,3)-D-glucan,
leading to lysis & cell death.
 Given by IV route only
 Highly bound to plasma proteins
 Half-life 9-11 hours
 Slowly metabolized by hydrolysis & N-
acetylation.
 Elimination is nearly equal between the
urinary & fecal routes.
 Effective in aspergillus & candida infections.
 Second line for those who have failed or
cannot tolerate amphotericin B or
itraconazole.
 Adverse effects :
◦ Nausea, vomiting
◦ Flushing( release of histamine from mast cells)
◦ Very expensive
 Fungistatic, has a narrow spectrum
 Given orally (Absorption increases with fatty
meal )
 Half-life 24 hours
 Taken selectively by newly formed skin &
concentrated in the keratin.
 Induces cytochrome P450 enzymes
 Should be given for 2-6weeks for skin &
hair infections to allow replacement of
infected keratin by the resistant structure
 Inhibits fungal mitosis by interfering with
microtubule function
 Used to treat dermatophyte infections ( ring worm
of skin, hair, nails ).
 Highly effective in athlete,s foot.
 Ineffective topically.
 Not effective in subcutaneous or deep mycosis.
 Adverse effects ;
◦ Peripheral neuritis, mental confusion, fatigue, vertigo,GIT
upset,enzyme inducer, blurred vision.
◦ Increases alcohol intoxication.
NDICATIONS ADRs-
 TENIA CAPITIS,  HEADACHE - 15%
CORPORICRURIS  PERIPHERAL
RUBRUM NEUROPATHY
 ATHLETS FOOT  CONFUSION
[EPIDERMOPHYTOS  ANTABUSE
IS] REACTION
 DOSE-10-15  PHOTO
MG/Kg SENSITIVITY
 drug interactions

PATKI 79
 1. Topical azole derivatives
 2. Nystatin& Amphotericin
 3. Terbinafine
 4. Tolnaftate
 5. Naftifine
 6. Griseofulvin
 Dermatophytosis ( ring worm),
 candidiasis, fungal keratitis.
 Tidak effective pada mycoses kuku &
rambut atau subcutaneous mycoses.
 Absorption is less than 0.5% from intact
skin, 3-10% from vagina (its activity
remains for 3 days ).
 Used in dermatophytes , cutaneous
candidiasis & vulvovaginal candidiasis.
 Causes : Erythema, edema, , urticaria & mild
vaginal burning sensation.
 Effective for treatment of onychomycoses.
 Should not be given in patients with
ventricular dysfunction.
 Evaluation of hepatic function is
recommended.
 Effective in most cutaneous mycosis.
 Ineffective against Candida.
 Used in tinea pedis ( cure rate 80% ).
 Used as cream, gel, powder, topical
solution.
 Applied twice daily.
 Broad spectrum fungicidal .
 Available as cream or gel.
 Effective for treatment of tinea cruris.
 Obat pilihan untuk dermatophytes yang
mengacam jiwa (onychomycoses).
 Menghambat fungal squalene
epoxidasemenurunkan synthesis
ergosterol .(Accumulation of squalene
,which is toxic to the organism causing
death of fungal cell).
 Merupaka Fungicidal ,
 Activitasnya terbatas pada candida albicans
& dermatophytes.
 Effective for treatment of onychomycoses
 6 weeks for finger nail infection & 12 weeks
for toe nail infections .
 Well absorbed orally , bioavailability
decreases due to first pass metabolism in
liver.