ANTI FUNGI AGENTS

ARJO SURJANTO
SCHOOL OF NURSERY
BANDUNG POLYTECHNIC OF HEALTH
 INTRODUCTION
A lot of fungi is very resistance to anti bacteria. There is a little
chemicals known could inhibit pathogen fungi in human, and many
of them relative toxic.
Among of available anti fungi, amphotericin B is most difficult
application and many side effect, however it is still most effective for
medication of severe systemic mycosis. Flucithocyn could taken
orally for systemic infection, but some times resistance appear. Anti
fungi of azol group (like ketoconazol, fluconazol, etc) could given
orally for several systematic mycosis. Myconazol, other azol, is
applied effectively for topical (and in certain limitation for systemic)
Azol group inhibits P450 oxydative enzyme in liver and others
they might influence drug metabolism and synthetic of endogen
compound.
Griseofulvin orally might effective for dermaphytosis, but might not
for systemic infection, while nystatin, haloprogin and others only
topically
MEDICINES OF SYSTEMIC INFECTION OF FUNGI (1)
AMPHOTERICIN B
Amphotericin A and B is antifungi antibiotics produced by Streptococcus nodosus, purified in
1956. Amphotericin A is not applied in therapy
Amphotericin B is a amphoter polien macrolide. It microcrystal could applied topically but did
not significant absorbed. For systematical application is used colloidal preparation intra venous
Amphotericin B 0.1 0.8 ug/ml, in vitro, inhibits Histoplasma capsulatum, Cryptococcus
neofarmans, Coccidiodes immitis, Candida albicans, Blastomyces dermatitidis, Sporothrix
schenckii, and other organism caused fungi in human. This medicine is recommended to
meningoencephalistis caused Naegleria
Amphotericin B binds ergosterol of fungi cell membrane cell membrane disorder death of
cell. Bacteria is not sensitive to amphotericyn because bacteria has more less ergosterol than
fungi
Resistance of amphotericin happens because decreasing of ergosterol membrane or structure
modification of membrane binds to medicine not so ggod resistance
Amphotericin B is difficult to absorbed from digestion tract effective for fungi on lumen only.
Intra venous administration of 0.6 mg/kg BW/day produce 0.3 1 ug/ml blood level. It is widely
distibuted, but 2 3% reach cerebrospinalis liquid only. As a consequence, intrathecal
administration is needed for fungi.
Amphotericin B could prepared as liposome granules with average diameter 0.5 3.5 um.
Total cumulative dose of liposome amphotericyn B 75 mg/kg BW is effective for therapy and
none or less causes renal toxicity
In the case of fungi systemic infection, amphotericin B given by slow infuse more than 4 6
hours. Initial dose is 1 5 mg/day, increases day by day 5 mg up to end dose 0.4 0.7 mg/kg
BW per day reached. Therapy is still going on by daily dose not more than 60 mg for 6 12
weeks. Since initial response appearance, the dose should given 2 3 times per weeks (or out
patient)
 MEDICINES OF SYSTEMIC
INFECTION OF FUNGI (2)
In the case of meningitis caused fungi, intrathecal injection of 0.5 mg
amphotericin B should given 3 times a weeks for 10 weeks or more.
Continuous infuse sometimes applied (Ommaya reservoir). Meningitis some
times relapse, but combination amphotericin B flucytocin begin applied for
meningitis caused Candida and Cryptococcus and systemic candidiasis
On cornea ulcus caused fungi, amphotericin B eyedrops of 1 mg/ml might
be dropped every 30. Other application is injection to infected joint of
coxidioidomycosis or sporotrikosis or irigation of vesica urinaria on cystitis
caused Candida
Side effects of intra venous administration are tremble, fever, vomit, and
head pain. The severity of side effect could decreasing by minimize
administration, taken aspirin, phenothiazin, antihistamin, and corticosteroid
or stopping injection for several days.
Quantity of amphotericin B in therapeutical dose usually disturbing kidney
function and liver cells anaemia. Decreasing of glomerulus filtration
speed and tubular function change are happen decrease of creatinin
clearance and increase of potassium clearance. Decrease of blood pressure
and several neurology syndrome some times would present
 MEDICINES OF SYSTEMIC INFECTION
OF FUNGI (3)
FLUCYTOCIN
Flucytocin 5 ug/ml, in vitro, inhibit a lot of strain Candida, Cryptococcus, and
Tarulopsis and several strain Aspergillus and other fungi. Fungi cell should
sensitive, when its cell changes flucytocin to fluorouracyl inhibit
thymidilate synthetase and DNA synthetic.
Combination amphotericin B flucytocin is applied to prevent appearing
resistance either amphotericin B or flucytocin themselves.
Oral dose flucytocin is 150 mg/kg BW/day. This medicine should widely
distributed to serum and tissues, included cerebrospinalis liquid, which
serum concentration reach 50 ug/ml. 20% of flucytocin binds to protein,
while excretion via kidney, and urine concentration reach 10 times serum
concentration. In the case of kidney failure, medicine could deposit until
toxic concentration. However in liver failure, flucytosin had not influence and
eliminated by hemolysis.
Flucytocin is relatively non toxic, but in high concentration of serum and long
medication could cause spinal cord depression, hair losing, abnormality of
liver function. Administration of uracil could minimize hematopoietic toxicity
Side effects of flucytocin are some times vomit, nausea and skin rash
Administration 6 12 g/day in devided dose might prolongation of fugemia,
sepcis and meningitis relapse caused sensitive organism
 MEDICINES OF SYSTEMIC INFECTION
OF FUNGI (4)
CHLOTRIMAZOLE, KETOCONAZOLE, MICONAZOLE, FLUCONAZOLE AND OTHER AZOLE
Azole synthetic antifungi prevent fungi by inhibitation biosynthesis of fungi lipid, especially
ergosterol on cell membrane.
Chlotrimazole 10 mg sweetlet, 5 times a day, could depress candidiasis of mouth cavity. As
cream of 1% topically, effectives for dermatophytosis. It is presented in vaginal tablet for
candidiasis. Chlotrimazole is very toxic in systemic application
Miconazole is used 2% as cream for dermatophytosis and vaginal candidiasis had not response
by nystatin topically. It is also i. v. administration (30mg/kg BW/day) to several severity mycosis
to inhibit relapse. However, mainly side effects are vomit, hyperlipidemia, thrombophlebitis,
hematologic disorder etc some times occur.
Ketoconazole is a first oral imidazole and effective for several systemic mycosis. Daily single
dose is 200 400 mg, administered by meal. It well absorbed and widely distributed, however its
concentration in CNS is low. Daily dose depress candidiasis infection on mouth and vagina in 1
2 weeks and dermatophytosis in 3 8 weeks.
Ketoconazole 200 600 mg a day, effectively depress clinical manifestation of systemic
parakoxidioidomycosis and blastomycosis, and sometimes lung, bone, and skin lesion
hystoplasmosis and koxidioidomycosis. Ketoconazole is drug of choice in severity blastomycosis
On the oral dose of 200 mg a day, the peak concentration is 2 3 ug/ml, standing in 6 hours or
more sometimes could cause toxic effect. There are nausea, vomit, skin rash and increasing
of transaminase serum concentration. Other effect might be seriously arythmia, but it is rarely.
Absorption of ketoconazole disturb when it taken together antacide, cimetidine, or rifampicine.
Oral fluconazole is taken 100 200 mg a day could depress oral and oesophagus candidiasis.
On dose 400 mg a day, fluconazole could depress meningitis caused cryptococcus on AIDS
patient, but sometime ralapse. It might be continued with maintenance dose 200 mg a day for
month by month.
Side effects are vomit, diarhea, rash and some times liver function diturbance
 MEDICINES OF SYSTEMIC INFECTION
OF FUNGI (5)
GRISEOFULVIN
Griseofulvin is a matter isolated from Penicillium griseofulvum on 1939,
and clinically introduced on dermaphytosis medication on 1957.
Griseofulvin inhibits growth of dermatophyt, included Epidermophyton,
Microsporum and Trichophyton in the concentration on 0.5 3 ug/ml
Its mechanism of action is not known, however it estimates that
griseofulvin influenced microtubulus or synthesis of nucleic acid, and
polimerization.
Ultramicrosize griseofulvin is applied in adult 0.3 0.6 g/day per oral
(7.25mg/kg BW/day for children). Medication should take place 3 6
weeks when only hair or skin infected, and 3 6 month if nail infected. It
indicate to severe dermatophytosis on skin, hair or nail, especially
caused by Trichophyton rubrum. Other topical antifungi could applied
together. Griseofulvin could increase warfarin metabolism high dose
of anticoagulant needed. Phenobarbital decreases bioavability
griseofulvin
Allergy reaction like fever, skin rash, leucopenia, and serum sickness
reaction might happen.
A lot of griseofulvin is excreted via faeces, only a part through via urine
 MEDICINES OF TOPICAL
INFECTION OF FUNGI (1)
NYSTATIN
Nystatin is polien macrolide, stable in dry form, but immediately
shatter by water or plasma. It has not effect to bacteria and
protozoa, but inhibit vary of fungi in vitro. In vivo, its act limited on
topical surface where direct contact take place to yeast or fungi.
Its mechanism of action might be participated of binding nystatin
membrane sterol of fungi, especially ergosterol nystatin forms
porous on cell wall
Nystatin is not significant absorbed from skin, mucosa membrane or
digest tract. Excretion is going via faeces. Parentheral
administration is not recommended because of its toxicity
Nystatin might administered topically on skin or mucosa (bucal,
vaginal), in doses form cream, ointment, suppositoria, suspension or
flour to depress local Candida infection. It could taken oral to
depress Candida in intestine lumen.
 MEDICINES OF TOPICAL
INFECTION OF FUNGI (2)
TOLNAFTATE AND NAFTIFIN
Tolnaftate is a local antifungi agent given in cream, flour, or liquid for
dermatophytosis. Clinical efficacy is take place on 1 10 weeks. Topical
administration had not absorption, while toxic and allergic reaction minimize
Naftitin is an alinamine naftalene derivate which inhibit squalene epoxidase enzyme
dan decreasing ergosterol synthesis. Cream of 1% effectives for treatment of Tinea
cruris and Tinea corporis
Other azole (econazole, oxyconazole, sulconazole) are topical azole applied in
candidiasis on mouth, vagina or skin in dose form cream or sweetlet, while
butoconazole, terconazole and thioconazole are applied on vulvovaginal candidiasis.
NATAMICYN
Natamicyn is a polien antifungi agent that active in vary of fungi in vitro. Topical eye
administration in 5% suspension is useful for keratitis caused by Fusarium,
Cephalosporium or other fungi. Natamicyn also effectives for oral or vagina
candidiasis
FATTY ACID AND HALOPROGIN
Undecylinic acid and its salt are applied as topical antifungi on Tinea pedis and Tinea
corporis as a cream or flour
Haloprogin is applied for T corporis topically as cream or liquid of 1%. This medicine
sometimes cause local irritation
 PRESENTATION
MEDICINES FOR SYSTEMIC
INFECTION OF FUNGI
Amphotericin B (Funizone
Intravenous)
Parentheral 50 mg per vial
Fluconazole (Diflucan)
Oral : tablet of 50, 100, 200 mg
Paentheral : 2mg/ml in 200 and 400 ml
infuse
Flucytocin (Ancobon)
Oral : capsule of 250, 500 mg
Itraconazole (Sporanox, Forcanox)
Oral : capsule of 100 mg
Ketoconazole (Nizoral)
Oral : Tablet of 200 mg
Miconazole (Monistat, Daktarin)
Parentheral : 10 mg/ml injection
MEDICINES FOR LOCAL INFECTION
OF FUNGI
Griseofulvin (Biogrisin, Fulcin)
Oral: 1 tablet of 200mg/day, severe 2
tab
Miconazole (Daktarin)
Topical : Cream 2%
Undecylenic acid (Decyline)
Topical: Cram, ointment and flour
Clotrimazole (Kranos, Lotremin)
Topical: cream of 1%
Ketoconazole (Nizoral, Mycoral)
Topical: Cream of 2%