9 - Anti Fungal Drugs_2

7/23/2019 9 - Anti Fungal Drugs_2

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ANTI FUNGAL DRUGSANTI FUNGAL DRUGS

By;By;

Dr. Saeed AhmedDr. Saeed Ahmed

Medical pharmacologyMedical pharmacology

King Sad Uni!er"i#yKing Sad Uni!er"i#y


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Fngi are e$aryo#ic% he#ero#rophic &no# "el'Fngi are e$aryo#ic% he#ero#rophic &no# "el'""#aining( organi"m" #ha# li!e a" "apro)e" or""#aining( organi"m" #ha# li!e a" "apro)e" or

para"i#e".para"i#e".

They are comple* organi"m" in compari"on #oThey are comple* organi"m" in compari"on #o)ac#eria .Th" an#i)ac#erial agen#" are no# e''ec#i!e)ac#eria .Th" an#i)ac#erial agen#" are no# e''ec#i!e

again"# 'ngi.again"# 'ngi.

Fngal in'ec#ion" are al"o called a" myco"e"Fngal in'ec#ion" are al"o called a" myco"e"


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Diference between prokaryotes and eukaryotes


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They ha!e ncle" and +ell de'ined nclearThey ha!e ncle" and +ell de'ined nclearmem)rane% and chromo"ome".mem)rane% and chromo"ome".

#hey ha!e rigid cell +all compo"ed o' chi#in & N ,#hey ha!e rigid cell +all compo"ed o' chi#in & N ,ace#ylglco"amine (ace#ylglco"amine (

+here a" )ac#erial cell +all i" compo"ed o'+here a" )ac#erial cell +all i" compo"ed o'pep#idoglycanpep#idoglycan

'ngal cell mem)rane con#ain" ergo"#erol % hman'ngal cell mem)rane con#ain" ergo"#erol % hmancell me)mrane i" compo"ed o' chole"#erolcell me)mrane i" compo"ed o' chole"#erol


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Fungal infection may be

Fungal infection may be

SUPERFECIALSUPERFECIAL DermatomycosesDermatom

ycosesa''ec#ing "$in% hair or nail".a''ec#ing "$in% hair or nail". Epidermophyton (sin and nails!Epidermophyton (sin and nails!

"richophyton (sin#hair $ nail!"richophyton (sin#hair $ nail! %icrosporum (sin and hair!%icrosporum (sin and hair!

)()( CandidiasisCandidiasis&commonly normal 'lora o' mo#h% "$in% in#e"#ine"&commonly normal 'lora o' mo#h% "$in% in#e"#ine"and !agina( in'ec#ion ca"ed )y gen" candida a''ec#ing "$in% mco"and !agina( in'ec#ion ca"ed )y gen" candida a''ec#ing "$in% mco"mem)rane o' mo#h or G.I.T or 'emale geni#al #rac#mem)rane o' mo#h or G.I.T or 'emale geni#al #rac#

S&S"E%ICS&S"E%IC

-andidia"i" %cryp#ococo"i"% A"pergillo"i"%-andidia"i" %cryp#ococo"i"% A"pergillo"i"%

Bla"#omyco"i"% i"#opla"mo"i"%Bla"#omyco"i"% i"#opla"mo"i"%

-occidioidomyco"i"% /aracoccidioidomyco"i" e#c-occidioidomyco"i"% /aracoccidioidomyco"i" e#c


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'rug Classification'ru

g Classification A! 'rugs that disrupt fungal cell membraneA

! 'rugs that disrupt fungal cell membrane i!i

! PolyenesPolyenes

AmphotericinAmphotericin ystatinystatin

atamycinatamycin

ii! A)olesii! A)olesA! Imida)oleA! Imida)ole

*etocona)ole*etocona)ole

+uta,ona)ole+uta,ona)ole

Clotrima)oleClotrima)oleEcona)oleEcona)ole

%icona)ole%icona)ole

-,icona)ole-,icona)ole

Sulcona)oleSulcona)ole

+! "ria)ole+! "ria)oleFlucona)oleFlucona)ole

Itracona)oleItracona)ole "iocona)ole"iocona)ole

iii! Allylaminesiii! Allylamines"erbinafine"erbinafine

aftifineaftifine

+utenafine+utenafine

.i!.i! Echinocandinscaspofungin#


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Diagram showing mechanism o action o diferent anti ungal durgs


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Drug classifcation cotdDrug classifcation cotd

+!+! 'rugs that inhibits mitosis'rugs that inhibits mitosis

/riseoful.in/riseoful.in

C!C! 'rugs that inhibits 'A synthesis'rugs that inhibits 'A synthesis

flucytosineflucytosine

d!d! %iscellaneous%iscellaneous

0aloprogi

"olnaftate

1hitefield2s ointmentCiclopiro, olamine


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Superficial %ycosisSuperficial %ycosis

a! 'ermatophyte infectiona! 'ermatophyte infection &ring +orm%#inea(.&ring +orm%#inea(.

+en)oic acid+en)oic acidoin#emen# 'or mild in'ec#ion.oin#emen# 'or mild in'ec#ion.

"opical imida)ole"opical imida)ole&li$e micona0ole%clo#rima0ole( i"&li$e micona0ole%clo#rima0ole( i"pre'erred no+ a day"pre'erred no+ a day"

"iocona)ole"iocona)ole'or nail in'ec#ion'or nail in'ec#ion

/riseoful.in/riseoful.in orally 'or e*#en"i!e "calp or nail #ineaorally 'or e*#en"i!e "calp or nail #ineain'ec#ion. in'ec#ion.


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b! Candida infectionb! Candida infection..

Cutaneous infectionCutaneous infection1 )y1 )y

#opical ampho#ericin%clo#rima0ole %econa0ole%#opical ampho#ericin%clo#rima0ole %econa0ole%

micona0ole or ny"#a#inmicona0ole or ny"#a#in

Candidiais of elementary tractCandidiais of elementary tractmucosamucosa

ampho#ericin%'lcona0ole% $e#ocona0ole%ampho#ericin%'lcona0ole% $e#ocona0ole%

micona0ole or ny"#a#in.micona0ole or ny"#a#in.

3aginal candidiasis3aginal candidiasis11-lo#rima0ole%econa0ole%$e#ocona0ole% micona0ole-lo#rima0ole%econa0ole%$e#ocona0ole% micona0oleoror

ny"#a#inny"#a#in


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Systemic MycosisSystemic Mycosis

P-L&EE A"I+I-"ICSP-L&EE A"I+I-"ICS They ac# )y1They ac# )y1

Binding #o "#erol in cell mem)rane.Binding #o "#erol in cell mem)rane.

De'ormi#y in pla"ma mem)rane occr"De'ormi#y in pla"ma mem)rane occr"

In#er'ere" +i#h permea)ili#y and +i#h #ran"por# 'nc#ion"In#er'ere" +i#h permea)ili#y and +i#h #ran"por# 'nc#ion"

Thi" allo+" lea$age o' in#racelllar ion" and en0yme" e"pecially lo"" o'Thi" allo+" lea$age o' in#racelllar ion" and en0yme" e"pecially lo"" o'

in#racelllar $2% ca"ing cell dea#h.in#racelllar $2% ca"ing cell dea#h.

They )ind "elec#i!ely #o ergo"#erol in 'ng" )# no# in mammalian cellThey )ind "elec#i!ely #o ergo"#erol in 'ng" )# no# in mammalian cell+all.+all.


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A%P0-"ERICI4A%P0-"ERICI4

I# i" macrolide an#i)io#ic A large lac#one ring +i#h ml#iple $e#one and hydro*ylI# i" macrolide an#i)io#ic A large lac#one ring +i#h ml#iple $e#one and hydro*ylgrop(grop(

/oorly a)"or)ed orally% "e'l 'or 'ngal in'ec#ion o'/oorly a)"or)ed orally% "e'l 'or 'ngal in'ec#ion o'

ga"#roin#e"#inal #rac#.ga"#roin#e"#inal #rac#.

Locally "ed in corneal lcer"% ar#hri#i" and candidial )ladder irriga#ionLocally "ed in corneal lcer"% ar#hri#i" and candidial )ladder irriga#ion

For "y"#emic in'ec#ion" gi!en a" "lo+ I34 in'"ion.For "y"#emic in'ec#ion" gi!en a" "lo+ I34 in'"ion.

ighly pro#ein )ondighly pro#ein )ond

/ene#ra#ion #hrogh BBB i" poor )# increa"e" in in'lamed meninge"./ene#ra#ion #hrogh BBB i" poor )# increa"e" in in'lamed meninge".

5*cre#ed "lo+ly !ia $idney"% #race" 'ond in rine 'or mon#h" a'#er ce""a#ion o'5*cre#ed "lo+ly !ia $idney"% #race" 'ond in rine 'or mon#h" a'#er ce""a#ion o'drg".drg".

al' li'e 67 day"al' li'e 67 day"


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Mechanism o action o Amphotericin


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Remain" in #he )ody 'or +ee$" a'#er "#opping #heRemain" in #he )ody 'or +ee$" a'#er "#opping #he

drg.drg.

Drg o' choice 'or mo"# "y"#emic in'ec#ion".Drg o' choice 'or mo"# "y"#emic in'ec#ion".

-or"e o' #rea#men# la"#" 896: +ee$".-or"e o' #rea#men# la"#" 896: +ee$".

Do"e .796 mg$gdayDo"e .796 mg$gday


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Ad.erse reactionsAd.erse reactions

Mo"# "erio" i"Mo"# "erio" i" renal #o*ici#yrenal #o*ici#y% +hich occr" in o' pa#ien#"% +hich occr" in o' pa#ien#" There may occr decrea"e in glomerlar 'il#ra#ion% and renalThere may occr decrea"e in glomerlar 'il#ra#ion% and renal

'nc#ion% drop in crea#inine clearance%and lo"" o' po#a""im and'nc#ion% drop in crea#inine clearance%and lo"" o' po#a""im andmagne"im% nephro#o*ci#y may )e po#encia#ed )y "odim deple#ion.magne"im% nephro#o*ci#y may )e po#encia#ed )y "odim deple#ion.

ypo$alaemia in :7> o' pa#ien#"% re?iring po#a""imypo$alaemia in :7> o' pa#ien#"% re?iring po#a""im"pplemen#a#ion."pplemen#a#ion.

ypomagne"aemiaypomagne"aemia AnemiaAnemia

Impaired hepa#ic 'nc#ionImpaired hepa#ic 'nc#ion Throm)ocy#openiaThrom)ocy#openia


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Anaphylac#ic "hoc$Anaphylac#ic "hoc$

Anore*ia% na"ea% !omi#ing% a)dominal% @oin# andAnore*ia% na"ea% !omi#ing% a)dominal% @oin# andm"cle pain% lo"" o' +eigh#% and 'e!er.m"cle pain% lo"" o' +eigh#% and 'e!er.

A"pirin% an#ihi"#amine" &6( an#ieme#ic" may help inA"pirin% an#ihi"#amine" &6( an#ieme#ic" may help in

alle!ia#ing #he "ymp#om".alle!ia#ing #he "ymp#om".

Fe)rile reac#ion" can )e mi#iga#ed )y hydrocor#i"oneFe)rile reac#ion" can )e mi#iga#ed )y hydrocor#i"one:797= mg )e'ore each in'"ion.:797= mg )e'ore each in'"ion.


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Liposomal preparations of amphotericin +4Liposomal preparations of amphotericin +4

To redce #he #o*ici#y o' ampho#ericin B %"e!eral ne+To redce #he #o*ici#y o' ampho#ericin B %"e!eral ne+'ormla#ion" ha!e )een de!eloped in +hich'ormla#ion" ha!e )een de!eloped in +hichampho#ericin B i" pac$aged in a lipid9a""ocia#ed deli!eryampho#ericin B i" pac$aged in a lipid9a""ocia#ed deli!ery

"y"#em% #o a""me #ha# #hey +ill le"" )ind #o mammalian"y"#em% #o a""me #ha# #hey +ill le"" )ind #o mammaliancell. Lipid !ehicle ac# a" a re"er!oir% redcing )inding #ocell. Lipid !ehicle ac# a" a re"er!oir% redcing )inding #ohman cell. In #hi" +ay i# permi#" a larger do"e"% e!enhman cell. In #hi" +ay i# permi#" a larger do"e"% e!en'i!e #ime" more #han colloidal prepara#ion% #hey ha!e'i!e #ime" more #han colloidal prepara#ion% #hey ha!e

)e##er clearance .)e##er clearance .

-linically #hey ha!e more e''icacy % le"" nephro#o*ici#y.-linically #hey ha!e more e''icacy % le"" nephro#o*ici#y.

B# #he"e are !ery e*pan"i!e.B# #he"e are !ery e*pan"i!e.


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Liposomal preparations o Amphotericin


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Comparison between two types o Amphotericin


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&S"A"I&S"A"I

I# i" polyene macrolide%"imilar in "#rc#re #oI# i" polyene macrolide%"imilar in "#rc#re #oampho#ericin and +i#h "ame mechani"m o'ampho#ericin and +i#h "ame mechani"m o'

ac#ionac#ion

Too #o*ic 'or "y"#emic "eToo #o*ic 'or "y"#emic "e

No# a)"or)ed 'rom GIT% "$in or !agina%No# a)"or)ed 'rom GIT% "$in or !agina%#here'ore admini"#ered orally #o#here'ore admini"#ered orally #o


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/re!en# or #rea# "per'icial candidia"i" o' mo#h%/re!en# or #rea# "per'icial candidia"i" o' mo#h%e"ophag" or in#e"#inal #rac#% oral ""pen"ion o'e"ophag" or in#e"#inal #rac#% oral ""pen"ion o'6==%=== U3ml #ime" a day and #a)le#" 7==%=== U are6==%=== U3ml #ime" a day and #a)le#" 7==%=== U are"ed #o decrea"e GIT coloni0a#ion +i#h -andida"ed #o decrea"e GIT coloni0a#ion +i#h -andida

For !aginal candidia"i" in 'orm o' pe""arie" "ed 'orFor !aginal candidia"i" in 'orm o' pe""arie" "ed 'or: +ee$": +ee$"

In -#aneo" in'ec#ion a!aila)le in cream% oin#men#In -#aneo" in'ec#ion a!aila)le in cream% oin#men#

or po+der 'orm and applied :9 #ime" a dayor po+der 'orm and applied :9 #ime" a day

-an )e "ed in com)ina#ion +i#h an#i)ac#erial agen#"-an )e "ed in com)ina#ion +i#h an#i)ac#erial agen#"and cor#ico"#eroid"and cor#ico"#eroid"


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A5-LESA5-LES

a )i!alen# chemical grop compo"ed o' #+o ni#rogen a#om".a )i!alen# chemical grop compo"ed o' #+o ni#rogen a#om". They are an#i)ac#erial% an#ipro#o0oal% an#helmin#hic andThey are an#i)ac#erial% an#ipro#o0oal% an#helmin#hic and

an#i'ngalan#i'ngal44

The"e are grop o' "yn#he#icThe"e are grop o' "yn#he#ic 'ngi"#a#ic'ngi"#a#ic agen#"agen#"

They ha!eThey ha!e)road "pec#rm)road "pec#rmo' ac#i!i#yo' ac#i!i#y Inhi)i# #he 'ngal cy#ochrome /7= AInhi)i# #he 'ngal cy#ochrome /7= Aen0yme % lano"ineen0yme % lano"ine

66

9de"me#hyla"e %+hich i" re"pon"i)le 'or con!er#ing9de"me#hyla"e %+hich i" re"pon"i)le 'or con!er#inglano"#erol #o ergo"#erol% #he main "#erol in #he 'ngal celllano"#erol #o ergo"#erol% #he main "#erol in #he 'ngal cellmem)rane% #hi" al#er" 'lidi#y o' #he mem)rane% #h"mem)rane% #hi" al#er" 'lidi#y o' #he mem)rane% #h"inhi)i#ing #he gro+#h o' 'ngi.inhi)i#ing #he gro+#h o' 'ngi.


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Imida)oles4Imida)oles4 *etocona)ole#*etocona)ole#

micona)ole#micona)ole# clotrima)ole#clotrima)ole# isocona)ole #isocona)ole# "iocona)ole"iocona)ole

TheyThey in#er'ere +i#h 'ngal o*ida#i!e en0yme" #o ca"e le#halin#er'ere +i#h 'ngal o*ida#i!e en0yme" #o ca"e le#halaccmla#ion o' hydrogen pero*ide; #hey redceaccmla#ion o' hydrogen pero*ide; #hey redce#he 'orma#ion#he 'orma#iono' ergo"#erol )y inhi)i#ion o' 'ngal cy#ochrome /7= en0yme%o' ergo"#erol )y inhi)i#ion o' 'ngal cy#ochrome /7= en0yme%+hich )ecome permea)le #o celllar con"#i#en#".+hich )ecome permea)le #o celllar con"#i#en#".

They lac$ "elec#i!i#y%and al"o inhi)i#" hman gonadal andThey lac$ "elec#i!i#y%and al"o inhi)i#" hman gonadal and"#eroid "yn#he"i" leading #o decrea"ed #e"#o"#erone and cor#i"ol"#eroid "yn#he"i" leading #o decrea"ed #e"#o"#erone and cor#i"ol

prodc#ion. I# al"o inhi)i#" cy#ochrome /7= ,dependan#prodc#ion. I# al"o inhi)i#" cy#ochrome /7= ,dependan#hepa#ic drg ,me#a)oli0ing en0yme.hepa#ic drg ,me#a)oli0ing en0yme.


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b!4"ria)oles4b!4"ria)oles4

Flucona)ole#Flucona)ole# itracona)ole#itracona)ole# .oricona)ole.oricona)ole

They damage #he 'ngal cell mem)rane )y inhi)i#ing en0yme de"me#hyla"eThey damage #he 'ngal cell mem)rane )y inhi)i#ing en0yme de"me#hyla"e

They are "elec#i!eThey are "elec#i!e

/ene#ra#e #o -NS/ene#ra#e #o -NS

Re"i"#an# #o degrada#ionRe"i"#an# #o degrada#ion

-a"e le"" endocrine di"#r)ance.-a"e le"" endocrine di"#r)ance.


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*E"-C-A5-LE6*E"-C-A5-LE6

Fir"# a0ole #ha# cold )e gi!en orally #o #rea# "y"#emic 'ngal in'ec#ion".Fir"# a0ole #ha# cold )e gi!en orally #o #rea# "y"#emic 'ngal in'ec#ion".

Cell a)"or)ed orally a" acidic en!ironmen# 'a!or" i#" di""ol#ion.Cell a)"or)ed orally a" acidic en!ironmen# 'a!or" i#" di""ol#ion. nly admini"#ered orallynly admini"#ered orally

Bioa!aila)ili#y i" decrea"ed +i#h 9: )loc$ing drg"% pro#on pmpBioa!aila)ili#y i" decrea"ed +i#h 9: )loc$ing drg"% pro#on pmp

inhi)i#or" and an#acid" and i" impaired +i#h 'ood.inhi)i#or" and an#acid" and i" impaired +i#h 'ood.

cola drin$" impro!e i#" a)"orp#ion in pa#ien#" +i#h achlorhydria.cola drin$" impro!e i#" a)"orp#ion in pa#ien#" +i#h achlorhydria.

A'#er oral admini"#ra#ion o' :==%== and


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Mechanism o action o ketoconazole


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Decrease in the ergosterol in the unagal membrane

By ketoconazle reducesthe ungicidal action o amphotericin


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Me#a)oli0ed e*#en"i!ely in li!er and inac#i!e prodc#" appearMe#a)oli0ed e*#en"i!ely in li!er and inac#i!e prodc#" appear

in #he 'ece".in #he 'ece".

i" )ond #o pla"ma pro#ein". i" )ond #o pla"ma pro#ein".

I# doe" no# en#er -SF.I# doe" no# en#er -SF.

Modera#e hepa#ic dy"'nc#ion ha" no e''ec# on drgModera#e hepa#ic dy"'nc#ion ha" no e''ec# on drgconcen#ra#ion.concen#ra#ion.

Indc#ion o' micro"omal en0yme" )y o#her drg" redce" #heIndc#ion o' micro"omal en0yme" )y o#her drg" redce" #heconcen#ra#ion.concen#ra#ion.


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I# inhi)i#" adrenal and gonadal "#eroid". +hich lead"I# inhi)i#" adrenal and gonadal "#eroid". +hich lead"#o men"#ral irreglari#ie"% lo"" o' li)ido%#o men"#ral irreglari#ie"% lo"" o' li)ido%

impo#ency and gynaecoma"#ia in male".impo#ency and gynaecoma"#ia in male".

I#" e''icacy i" poor in immno"ppre""ed pa#ien#" andI#" e''icacy i" poor in immno"ppre""ed pa#ien#" andin meningi#i".in meningi#i".

ral do"e == mg daily.ral do"e == mg daily.


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It is not useul or ungal inections o !as le"el o parent drug in urine is "ery low


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Side e''ec#"Side e''ec#"11

Do"e dependan# na"ea% anore*ia %!omi#ingDo"e dependan# na"ea% anore*ia %!omi#ing

Li!er #o*ici#y i" rare )# may pro!e 'a#al.Li!er #o*ici#y i" rare )# may pro!e 'a#al.

air lo""air lo""

A" i# inhi)i#" "#eroid )io"yn#he"i"% "e!eralA" i# inhi)i#" "#eroid )io"yn#he"i"% "e!eralendocrinological a)normali#ie" may )e e!iden# a"endocrinological a)normali#ie" may )e e!iden# a"

men"#ral a)normali#ie"% gynecoma"#ia% decrea"edmen"#ral a)normali#ie"% gynecoma"#ia% decrea"edli)ido and impo#ency.li)ido and impo#ency.

Flid re#en#ion and hyper#en"ion.Flid re#en#ion and hyper#en"ion.


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Drg in#erac#ion"Drg in#erac#ion"

cyclo"porin%pheny#oin %cyclo"porin%pheny#oin %66)loc$er" inhi)i# i#")loc$er" inhi)i# i#"me#a)oli"m and hence increa"e #o*ici#y.me#a)oli"m and hence increa"e #o*ici#y.

Car'arin %Ri'ampin increa"e i#" me#a)oli"m andCar'arin %Ri'ampin increa"e i#" me#a)oli"m andhence decrea"e concen#ra#ion.hence decrea"e concen#ra#ion.

::)loc$er" %an#acid" decrea"e i#" a)"orp#ion.)loc$er" %an#acid" decrea"e i#" a)"orp#ion.

-on#raindica#ed in pregnancy-on#raindica#ed in pregnancy


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I"RAC-A5-LEI"RAC-A5-LE

I# i" a "yn#he#ic #ria0oleI# i" a "yn#he#ic #ria0ole

i# i" ne+ drgi# i" ne+ drg

I# lac$" endocrine "ide e''ec#" o' $e#ocona0ole.I# lac$" endocrine "ide e''ec#" o' $e#ocona0ole.

I# ha"I# ha")road "pec#rm)road "pec#rmac#i!ir#yac#i!ir#y

Admini"#ered orally a" +ell a" I34.Admini"#ered orally a" +ell a" I34.

Food increa"e" i#" a)"orp#ionFood increa"e" i#" a)"orp#ion


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Me#a)oli0ed in li!er e*#en"i!ely )y cy#ochrome -/AMe#a)oli0ed in li!er e*#en"i!ely )y cy#ochrome -/A

I# i" highly lipid "ol)le% i# i" +ell di"#ri)#ed #o )one %"p#mI# i" highly lipid "ol)le% i# i" +ell di"#ri)#ed #o )one %"p#mand adipo"e #i""e.and adipo"e #i""e.

ighly )ond #o pla"ma pro#einighly )ond #o pla"ma pro#ein

Do no# pene#ra#e -SFDo no# pene#ra#e -SF ade?a#ely %#here'ore i#" concen#ra#ionade?a#ely %#here'ore i#" concen#ra#ioni" le"" #o #rea# meningeal 'ngal in'ec#ioni" le"" #o #rea# meningeal 'ngal in'ec#ion


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al' li'e i" =9= hor"al' li'e i" =9= hor"

S#eady "#a#e reache" in S#eady "#a#e reache" in day"% "o loading do"e" areday"% "o loading do"e" arerecommended in deep myco"i".recommended in deep myco"i".

Do"e 6== mg #+ice daily +i#h 'ood% ini#ially == mg #hriceDo"e 6== mg #+ice daily +i#h 'ood% ini#ially == mg #hrice

daily a" a loading do"e.daily a" a loading do"e.

In#ra!eno"ly re"er!ed only in "erio" in'ec#ion".:== mg #+iceIn#ra!eno"ly re"er!ed only in "erio" in'ec#ion".:== mg #+icedaily in in'"ion 'or one hor 'or #+o day" 'ollo+ed )y :==daily in in'"ion 'or one hor 'or #+o day" 'ollo+ed )y :==mg daily 'or 6: day".mg daily 'or 6: day".

Side e''ec#"1 na"ea% !omi#ing% hyper#riglyceridemia%Side e''ec#"1 na"ea% !omi#ing% hyper#riglyceridemia%ypo$alaemia% increa"ed amino#ran"'era"e% hepa#o#o*ic#y ra"hypo$alaemia% increa"ed amino#ran"'era"e% hepa#o#o*ic#y ra"hlead" #o drg di"con#ina#ion.lead" #o drg di"con#ina#ion.


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FLUC-A5-LEFLUC-A5-LE

I# i" 'lorina#ed )i"#ria0ole.I# i" 'lorina#ed )i"#ria0ole.

-omple#ely a)"or)ed 'rom GIT-omple#ely a)"or)ed 'rom GIT

5*cellen# )ioa!aila)ili#y )y oral ro#e.5*cellen# )ioa!aila)ili#y )y oral ro#e.

-oncen#ra#ion in pla"ma i" "ame )y oral or I3! ro#e.-oncen#ra#ion in pla"ma i" "ame )y oral or I3! ro#e.

Bioa!aila)ili#y no# al#ered )y 'ood or ga"#ric acidi#yBioa!aila)ili#y no# al#ered )y 'ood or ga"#ric acidi#y

I# ha" lea"# e''ec# on hepa#ic micro"omal en0yme".I# ha" lea"# e''ec# on hepa#ic micro"omal en0yme".

Drg in#erac#ion" are le"" common.Drg in#erac#ion" are le"" common.


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/ea$ pla"ma concen#ra#ion 9Renal e*cre#ion =>

#63: :79= hor".#63: :79= hor".

Di''"e in all )ody 'lid" inclding -SF concen#ra#ion 7=9= >.Di''"e in all )ody 'lid" inclding -SF concen#ra#ion 7=9= >.


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UsesUses

-andidia"i"1 :== mg on 6"# day #hen 6== mg daily 'or : +ee$".-andidia"i"1 :== mg on 6"# day #hen 6== mg daily 'or : +ee$".

-ryp#ococco"i"1 == mg daily 'or < +ee$" in meningi#i".-ryp#ococco"i"1 == mg daily 'or < +ee$" in meningi#i".

In AIDS :== mg 'or li'e.In AIDS :== mg 'or li'e.

-occidial meningi#i" i# i" drg o' choice-occidial meningi#i" i# i" drg o' choice

I# ha" al"o ac#i!i#y again"# hi"#opla"mo"i"% )la"#omyco"i"%I# ha" al"o ac#i!i#y again"# hi"#opla"mo"i"% )la"#omyco"i"%

"piro#richo"i" %and ring +orm )# i#racona0ole i" )e##er in "ame"piro#richo"i" %and ring +orm )# i#racona0ole i" )e##er in "amedo"edo"e

No# e''ec#i!e in a"pergillo"i".No# e''ec#i!e in a"pergillo"i".


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Un7anted effectsUn7anted effects11

na"ea% !omi#ing% headache% "$in ra"h% a)dominalna"ea% !omi#ing% headache% "$in ra"h% a)dominal

pain% diarrhea% re!er"i)le alopeciapain% diarrhea% re!er"i)le alopecia

No endocrine ad!er"e e''ec#".No endocrine ad!er"e e''ec#".

epa#ic 'ailre may lead #o dea#hepa#ic 'ailre may lead #o dea#h

I# i" highly #era#ogenicI# i" highly #era#ogenic


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4oricona0ole4oricona0ole

A ne+ drgA ne+ drg

a!aila)le in i.! and oral 'romla#ion".a!aila)le in i.! and oral 'romla#ion".

recommended do"age i" == mg3 dayrecommended do"age i" == mg3 day

high )iological a!aila)ili#y +hen gi!en orallyhigh )iological a!aila)ili#y +hen gi!en orally

hepa#ic me#a)oli"m predominan#.hepa#ic me#a)oli"m predominan#.

mammalian inhi)i#ion o' /7= le"".mammalian inhi)i#ion o' /7= le"".

re!er"i)le !i"al di"#r)ance"re!er"i)le !i"al di"#r)ance"

i# i" "imilar #o i#racona0ole )# more po#en#.i# i" "imilar #o i#racona0ole )# more po#en#.

FLUC&"-SIEFLUC&"-SIE


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FLUC&"-SIEFLUC&"-SIE

a" "e'l ac#i!i#y again"# -andida and -ryp#ococc".a" "e'l ac#i!i#y again"# -andida and -ryp#ococc".

i# i" "yn#he#ic pyrimidine an#ime#a)oli#e #ha# i" o'#en "ed ini# i" "yn#he#ic pyrimidine an#ime#a)oli#e #ha# i" o'#en "ed incom)ina#ion +i#h ampho#ericin Bcom)ina#ion +i#h ampho#ericin B

i# i"i# i" 'ngi"#a#ic%'ngi"#a#ic%e''ec#i!e in com)ina#ion +i#h i#racona0ole 'or #rea#inge''ec#i!e in com)ina#ion +i#h i#racona0ole 'or #rea#ingchromo)la"#omyco"i" and +i#h ampho#ericin 'or #rea#ingchromo)la"#omyco"i" and +i#h ampho#ericin 'or #rea#ing

cryp#ococo"i".cryp#ococo"i".

%echanism of action%echanism of actionI# i" con!er#ed #o an#ime#a)oli#e 79'lororacil in a 'ngal )# no#I# i" con!er#ed #o an#ime#a)oli#e 79'lororacil in a 'ngal )# no#hman cell. Thi" 79FU inhi)i#" #hymidyla#e "yn#he#a"e en0yme andhman cell. Thi" 79FU inhi)i#" #hymidyla#e "yn#he#a"e en0yme and#h" DNA "yn#he"i". Re"i"#an# m#an#" may occr% "hold ne!er )e#h" DNA "yn#he"i". Re"i"#an# m#an#" may occr% "hold ne!er )e

"ed alone."ed alone.


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Mechanism o action o #lucytosine

dump$%uorodeo&yuridnemonophosphate


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Ph8ineticsPh8inetics

A)"or)ed rapidly and +ell 'rom GITA)"or)ed rapidly and +ell 'rom GIT

Cidely di"#ri)#ed in )ody and pene#ra#e" +ell in#o -SF.Cidely di"#ri)#ed in )ody and pene#ra#e" +ell in#o -SF.

Minimally )ond #o pla"ma pro#einMinimally )ond #o pla"ma pro#ein

/ea$ pla"ma con. reache" E=9


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UsesUses

do"e 6==967= mg 3$g per day di!ided in#o do"e".do"e 6==967= mg 3$g per day di!ided in#o do"e".

Generally "e in com)ina#ion +i#h ampho#ericinGenerally "e in com)ina#ion +i#h ampho#ericin

For cryp#ococcal meningi#i" in AIDS pa#ien#"For cryp#ococcal meningi#i" in AIDS pa#ien#"


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Un7anted effectsUn7anted effects11

re!er"i)le ne#ropenia% #hrom)ocy#openia andre!er"i)le ne#ropenia% #hrom)ocy#openia andocca"ional )one marro+ depre""ion.occa"ional )one marro+ depre""ion.

Na"ea %!omi#ing %diarrhea% "e!ere en#erocoli#i"Na"ea %!omi#ing %diarrhea% "e!ere en#erocoli#i"

epa#ic en0yme ele!a#ion in 7> pa#ien#" i" re!er"i)le.epa#ic en0yme ele!a#ion in 7> pa#ien#" i" re!er"i)le.


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CaspounginCaspoungin

It is echinocandin class o antiungal drugsIt is echinocandin class o antiungal drugs

it intereres with the synthesis o ungal cellit intereres with the synthesis o ungal cell

wall by inhibiting synthesis o D'glycan(wall by inhibiting synthesis o D'glycan( especially useul or aspergillus andespecially useul or aspergillus and

candida(candida(

not acti"e orallynot acti"e orally

)igly bound to serum proteins)igly bound to serum proteins

)as hal lie o *'++ hours)as hal lie o *'++ hours


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slowly metabolized by hydrolysisslowly metabolized by hydrolysis

and ,'acetylation(and ,'acetylation(

eliminated e-ually by urinary andeliminated e-ually by urinary andecal route(ecal route(

Ad"erse efects include nauseaAd"erse efects include nausea

."omiting. %ushing."omiting. %ushing "ery e&pensi"e"ery e&pensi"e


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Anti ungal drugs used orAnti ungal drugs used or

topical ungal inectionstopical ungal inections

Topical anti ungal preparationsTopical anti ungal preparations

+(+( !opical azole deri"ati"es!opical azole deri"ati"es

/(/( Ciclopiro& olamineCiclopiro& olamine0(0( ,ati1ne,ati1ne

2(2( !erbina1ne!erbina1ne

3(3( Butena1neButena1ne4(4( tolnatatetolnatate

5(5( ,ystatin and Amphotericin,ystatin and Amphotericin


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6ral anti ungal agents used6ral anti ungal agents used

or topical inectionsor topical inections

+(+( 7riseoul"in7riseoul"in

/(/( oral azolesoral azoles

0(0( !erbina1ne!erbina1ne


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"-PICAL A"IFU/AL A/E"S"-PICAL A"IFU/AL A/E"S

In "per'icial 'ngal in'ec#ion" #ho"e drg" areIn "per'icial 'ngal in'ec#ion" #ho"e drg" are

pre'erred +hich ge# con'ined #o "#ra#mpre'erred +hich ge# con'ined #o "#ra#m

cornem% "?amo" mco"a% or cornea.cornem% "?amo" mco"a% or cornea.

Sch di"ea"e inclde" derma#ophy#o"i" &ringSch di"ea"e inclde" derma#ophy#o"i" &ring

+orm(% candidia"i" #inea and 'ngal $era#i#i".+orm(% candidia"i" #inea and 'ngal $era#i#i".


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Topical admini"#ra#ion o' an#i'ngal agen#" i" "allyTopical admini"#ra#ion o' an#i'ngal agen#" i" "ally

no# "cce""'l in myco"e" o' #he nail" and hair and ha"no# "cce""'l in myco"e" o' #he nail" and hair and ha"no place in #he #rea#men# o' ")c#aneo" myco"e".no place in #he #rea#men# o' ")c#aneo" myco"e".

The e''icacy o' #opical agen#" in #he "per'icial myco"e"The e''icacy o' #opical agen#" in #he "per'icial myco"e"

depend" no# only on #he #ype o' le"ion and #hedepend" no# only on #he #ype o' le"ion and #hemechani"m o' #he drg ac#ion )# al"o on #he !i"co"i#y%mechani"m o' #he drg ac#ion )# al"o on #he !i"co"i#y%hydropho)ici#y and acidi#y o' #he 'ormla#ion.hydropho)ici#y and acidi#y o' #he 'ormla#ion.

The pre'erred 'ormla#ion 'or c#aneo" applica#ionThe pre'erred 'ormla#ion 'or c#aneo" applica#ion"ally i" a cream or "ol#ion."ally i" a cream or "ol#ion.


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I%I'A5-LE A' "RIA5-LES F-R "-PICALI%I'A5-LE A' "RIA5-LES F-R "-PICAL

infectionsinfections

The"e are "yn#he#ic and "ed )o#h #opically andThe"e are "yn#he#ic and "ed )o#h #opically and

"y"#emically"y"#emically

Selec#ion depend" on co"# and a!aila)ili#ySelec#ion depend" on co"# and a!aila)ili#y

Shold )e applied #+ice a day 'or :9 +ee$".Shold )e applied #+ice a day 'or :9 +ee$".

4aginal cream"% "ppo"i#orie" and #a)le#" 'or !aginal4aginal cream"% "ppo"i#orie" and #a)le#" 'or !aginal

candidia"i" "ed once a day pre'era)ly a# )ed #ime.candidia"i" "ed once a day pre'era)ly a# )ed #ime.


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CL-"RI%A5-LECL-"RI%A5-LE

Absorption less than 8(3 9 rom intact skin. 0'+8 9Absorption less than 8(3 9 rom intact skin. 0'+8 9rom "agina and acti"ity in "agina remains or 0rom "agina and acti"ity in "agina remains or 0days(days(

6ral dose o /88 mg per day gi"e rise to 8(/'6ral dose o /88 mg per day gi"e rise to 8(/'8(03ug:ml concentration(8(03ug:ml concentration(

;tigma. erythema. edema. "esication. pruritus.;tigma. erythema. edema. "esication. pruritus.

urticaria mild "aginal burning sensation may occour(urticaria mild "aginal burning sensation may occour(

Cure dermatophytes(it is efecti"e in 48'Cure dermatophytes(it is efecti"e in 48'+889(cutaneous candidiasis is


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ItraconazoleItraconazole

Itraconazole is efecti"e or treatment oItraconazole is efecti"e or treatment oonychomycosis in a dose o /88 mg dailyonychomycosis in a dose o /88 mg dailyater ood or 0monthsater ood or 0months

;hould not be gi"en in patients with;hould not be gi"en in patients with"entricular dysunction"entricular dysunction

=outine e"aluation o hepatic unction is=outine e"aluation o hepatic unction is

recommended(recommended( should not be used concurrently withshould not be used concurrently with

midazolam. triazolam and )M7'CoA(midazolam. triazolam and )M7'CoA(


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"-LAF"A"E"-LAF"A"E

5''ec#i!e in mo"# c#aneo" myco"i".5''ec#i!e in mo"# c#aneo" myco"i".

I# i" ine''ec#i!e again"# -andida.I# i" ine''ec#i!e again"# -andida.

In #inea pedi" cre ra#e i" arond .In #inea pedi" cre ra#e i" arond .

A!aila)le in 6> con.a" cream%gel%po+der and #opicalA!aila)le in 6> con.a" cream%gel%po+der and #opical

"ol#ion."ol#ion.

Applied locally #+ice a day.Applied locally #+ice a day.


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AF"IFIEAF"IFIE

I# i" )road "pec#rm% 'ngicidal.I# i" )road "pec#rm% 'ngicidal.

A!aila)le a" 6> cream or gelA!aila)le a" 6> cream or gel

5''ec#i!e 'or #ropical #rea#men# o' #inea crri".5''ec#i!e 'or #ropical #rea#men# o' #inea crri".


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"ER+IAFIE"ER+IAFIE

I# i" "yn#he#ic allylamineI# i" "yn#he#ic allylamine i# i" a drg o' choice 'or #rea#ing derma#ophy#e"i# i" a drg o' choice 'or #rea#ing derma#ophy#e"

i# i" )e##er #olera#ed % re?ire" "hor#er dra#ion o' #herapyi# i" )e##er #olera#ed % re?ire" "hor#er dra#ion o' #herapy

i# inhi)i#" 'ngal "e?alene epo*ida"e %decrea"e" "yn#he"i" o'i# inhi)i#" 'ngal "e?alene epo*ida"e %decrea"e" "yn#he"i" o'ergo"#erolergo"#erol

Al"o accmla#ion o' #o*ic amon#" o' "?alene ca"e" cell dea#h.Al"o accmla#ion o' #o*ic amon#" o' "?alene ca"e" cell dea#h.

i# i" 'ngicidal )# ac#i!i#y i" limi#ed #o -.al)ican" andi# i" 'ngicidal )# ac#i!i#y i" limi#ed #o -.al)ican" andderma#ophy#e".derma#ophy#e".


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?i#e e''ec#i!e 'or #he #rea#men# o' onychomyco"i"?i#e e''ec#i!e 'or #he #rea#men# o' onychomyco"i"

:7= mg daily 'or 8+ee$" 'or 'inger nail in'ec#ion and 'or 6::7= mg daily 'or 8+ee$" 'or 'inger nail in'ec#ion and 'or 6:+ee$" in #oe nail in'ec#ion+ee$" in #oe nail in'ec#ion

Cell a)"or)ed orally %)ioa!aila)ili#y decrea"e" de #o 'ir"# pa""Cell a)"or)ed orally %)ioa!aila)ili#y decrea"e" de #o 'ir"# pa""

me#a)oli"m in li!er.me#a)oli"m in li!er.

/ro#ein )inding more #han > in pla"ma./ro#ein )inding more #han > in pla"ma.

Drg accmla#e" in "$in%nail" and 'a#.Drg accmla#e" in "$in%nail" and 'a#.

"e!erely hepa#o#o*ic % li!er 'ailre e!en dea#h."e!erely hepa#o#o*ic % li!er 'ailre e!en dea#h.


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Mechanism o action o terbina1ne


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Ini#ial hal' li'e 6: hr" )# e*#end" #o :==9== hr" %+hichIni#ial hal' li'e 6: hr" )# e*#end" #o :==9== hr" %+hichre'lec#" i# "lo+ relea"e 'rom #he #i""e"re'lec#" i# "lo+ relea"e 'rom #he #i""e"

-an )e 'ond in pla"ma 'or 9 < +ee$" a'#er prolong #herapy.-an )e 'ond in pla"ma 'or 9 < +ee$" a'#er prolong #herapy. -learance i" redced in modera#e and hepa#ic impairmen#.-learance i" redced in modera#e and hepa#ic impairmen#.

No# recommended in a0o#emia or hepa#ic 'ailre.No# recommended in a0o#emia or hepa#ic 'ailre.

Do"e :7= mg 'or mon#h"3'or local in'ec#ion applied #+iceDo"e :7= mg 'or mon#h"3'or local in'ec#ion applied #+ice

dailydaily(( unwanted efects include 7I! disturbance .!aste and "isualunwanted efects include 7I! disturbance .!aste and "isual

disturbance .transient rise in serum li"er enzymes(disturbance .transient rise in serum li"er enzymes( =iampicin decreases it serum and cimetidine increases=iampicin decreases it serum and cimetidine increases


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/RISE-FUL3I/RISE-FUL3I i# ha" largely )een replaced )y #er)ina'ine 'or #rea#men# o'i# ha" largely )een replaced )y #er)ina'ine 'or #rea#men# o'

derma#ophy#ic in'ec#ion" o' #he nail".derma#ophy#ic in'ec#ion" o' #he nail". !ery in"ol)le in +a#er!ery in"ol)le in +a#er I# i" "e'l 'or derma#ophy#e"I# i" "e'l 'or derma#ophy#e"

I# i" 'angi"#a#ic 'or "pecie" o' derma#ophy#e". i# ha" narro+I# i" 'angi"#a#ic 'or "pecie" o' derma#ophy#e". i# ha" narro+"pec#rm."pec#rm.

I"ola#ed 'rom /encillim gri"eo'l!mI"ola#ed 'rom /encillim gri"eo'l!m

I# in#erac#" +i#h micro#)le" and in#er'ere" +i#h mi#o"i".I# in#erac#" +i#h micro#)le" and in#er'ere" +i#h mi#o"i".


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67/73

PharmacoineticsPharmacoinetics

/ea$ pla"ma concen#ra#ion o' 6g3ml in a)o# hor"/ea$ pla"ma concen#ra#ion o' 6g3ml in a)o# hor"

A)"orp#ion increa"e" +i#h 'a##y mealA)"orp#ion increa"e" +i#h 'a##y meal

I# i" ine''ec#i!e #opically.I# i" ine''ec#i!e #opically. Bar)i#ra#e" decrea"e" #he a)"orp#ion 'rom GIT.Bar)i#ra#e" decrea"e" #he a)"orp#ion 'rom GIT. 5*#en"i!ly me#a)oli0ed in li!er.5*#en"i!ly me#a)oli0ed in li!er. Indce -/7=.Indce -/7=. # 63: 6day.# 63: 6day. Drg i" depo"i#ed in $era#in and nail and hair are 6"# #o ge#Drg i" depo"i#ed in $era#in and nail and hair are 6"# #o ge#

rid o' di"ea"e.rid o' di"ea"e.


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UsesUses

Myco#ic di"ea"e" o' "$in% hair &par#iclarly 'orMyco#ic di"ea"e" o' "$in% hair &par#iclarly 'or

"calp( % nail."calp( % nail.

I# i" al"o highly e''ec#i!e in a#hle#eH" 'oo#I# i" al"o highly e''ec#i!e in a#hle#eH" 'oo#


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'ose'ose

7967 mg 3$g 'or children and =.7 96 gram 'or adl#".7967 mg 3$g 'or children and =.7 96 gram 'or adl#".

Trea#men# re?ired i" 6 mon#h 'or "calp and hair ring+orm%Trea#men# re?ired i" 6 mon#h 'or "calp and hair ring+orm%

89 mon#h" 'or 'inger nail"% and a# lea"# 6 year 'or #oe nail"89 mon#h" 'or 'inger nail"% and a# lea"# 6 year 'or #oe nail" 44

No# e''ec#i!e in ")c#aneo" or deep myco"e".No# e''ec#i!e in ")c#aneo" or deep myco"e".


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Un7anted effects4Un7anted effects4

eadacheeadache

/eripheral neri#i" % le#hargy % men#al/eripheral neri#i" % le#hargy % men#al

con'"ion% impairmen# in per'ormance o'con'"ion% impairmen# in per'ormance o'

ro#ine #a"$% 'a#ige% !er#igo %"yncope% )lrredro#ine #a"$% 'a#ige% !er#igo %"yncope% )lrred

!i"ion.!i"ion.

C i f A l f i t ti dComparison of A)oles fungistatic drugs


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Comparison of A)oles fungistatic drugsComparison of A)oles fungistatic drugs

>etoconazole>etoconazole #luconazole#luconazole ItraconazoleItraconazole

"pec#m"pec#m narro+narro+ e*pandede*panded e*pandede*panded

Ro#e o' admini"#ra#ionRo#e o' admini"#ra#ion ralral ral% i.!ral% i.! oraloral

TT 63:63: 8989 == =9==9=

-"' pene#ra#ion-"' pene#ra#ion nono ye"ye" nono

Renal e*cre#ionRenal e*cre#ion nono ye"ye" nono

In#erac#ion +i#h o#herIn#erac#ion +i#h o#her

drg"drg"'re?en#'re?en# cca"ionalcca"ional occa"ionalocca"ional

Inhi)i#ion o'Inhi)i#ion o'

mammalian "#erolmammalian "#erol

"yn#he"i""yn#he"i"

Do"e dependen#Do"e dependen#

inhi)i#ory e''ec#inhi)i#ory e''ec#no inhi)i#ionno inhi)i#ion N inhi)i#ionN inhi)i#ion

ses o an unga rugsses o an un

ga rugs


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g gg gDiseaseDisease Drug usedDrug used

Systemic infectionsSystemic infections

"y"#emic candidia"i""y"#emic candidia"i"

-ryp#ococco"i"& meningi#i"(-ryp#ococco"i"& meningi#i"(

"y"#emic a"pergillo"i""y"#emic a"pergillo"i"

Bla"#omyco"i"Bla"#omyco"i"

i"#opla"mo"i"i"#opla"mo"i"

-occidiomyco"i"-occidiomyco"i"

/aracoccidiomyco"i"/aracoccidiomyco"i"

Mcormyco"i"Mcormyco"i"

Di""emina#ed "por#richo"i"Di""emina#ed "por#richo"i"

Ampho#ericin% 'lcy#ocin% % 'lcona0ole.Ampho#ericin% 'lcy#ocin% % 'lcona0ole.

Ampho#ericin% 'lcy#ocin % 'lcona0ole%Ampho#ericin% 'lcy#ocin % 'lcona0ole%

i#racona0olei#racona0ole

i#racona0ole Ampho#ericin%i#racona0ole Ampho#ericin%

i#racona0ole Ampho#ericin%i#racona0ole Ampho#ericin%

Ampho#ericin% i#racona0ole %'lcona0ole.Ampho#ericin% i#racona0ole %'lcona0ole.

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9 - Anti Fungal Drugs_2

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