ANTI-FUNGAL DRUGS

AGENTS
Subcutaneous and Systemic Anti-fungal Agents
Ampote!icin "
#aspofungin
Flucytosine
Imida$oles% &etocona$ole' It!acona$ole' Flucona$ole' (icona$ole' )o!icona$ole
Nystatin
Te!binafine' Amo!olfine
Topical Anti-fungal Agents
Ampote!icin "' "utenafine' "utocona$ole' G!iseoful*in' #iclopi!o+' #lio,uinol'
#lot!ima$ole' Econa$ole' Gentian *iolet' &etocona$ole' (icona$ole' Naftifine' Nystatin'
-+icona$ole' Sulcona$ole' Te!binafine' Te!cona$ole' Tolnaftate

Antifungal Antibiotics
Ampote!icin "
Nystatin
G!iseoful*in

A(./-TERI#IN "
A polyene antibiotic de!i*ed f!om St!eptomyces nodosus0
"!oad spect!um of acti*ity 1#0 albicans' /0 capsulatum' #0 neofo!mans' #0 immitis'
aspe!gillus2 3 bot fungistatic and fungicidal acti*ity0
(-A% "inds to ste!ols 1e!goste!ol2 in te cell
memb!anes' fo!ming po!es o! cannels 4ic inc!ease memb!ane pe!meability' ma5ing te cell
mo!e susceptible to dest!uction0
(-R% Dec!eased e!goste!ol content of te fungal memb!ane0
Acti*e in g!o4ing and !esting cells3 not igly selecti*e and 4ill inte!fe!e 4it memb!ane
function of mammalian ost cell0
.a!maco5inetic p!ofile%
Gi*en by slo4 I) in6ection' topical' int!atecal 1meningitis2 o! o!al0
/igly #/-N-bound3 e+c!eted *e!y slo4ly t!oug te u!ine0
ADR%
Infusion !eactions% Fe*e!' sa5ing cills' ypotension' ano!e+ia' NA)' eadace' dyspnea'
tacypnea0
-te!s% Renal to+icity 1potentiated by sodium depletion2' elect!olyte impai!ment
1ypo5alemia' ypomagnesemia' ypocalcemia2' no!mocytic no!moc!omic anemia' impai!ed
epatic function' local t!omboplebitis3 int!atecal neu!oto+icity3 topical s5in !as0
Te!apeutic Uses% Acute' se*e!e' systemic fungal infections 1p!ima!y d!ug' D-#20
Local de!matopytic and mucocutaneous infections 1topical20
Fungal infections of te GIT 1o!al20

N7STATIN
Isolated f!om St!eptomyces3 fi!st antimycotic antibiotic0
.olyene antibiotic 4it b!oad spect!um of acti*ity0
(-A% "inds to ste!ols in fungal cell memb!anes' te!eby inc!easing memb!ane
pe!meability and ma5ing te cell mo!e susceptible to dest!uction0
.a!maco5inetic p!ofile%
Gi*en by o!al o! topical !oute0
ADR% Local bu!ning and itcing 1topical20
GI upset 1NA)' dia!!ea2' !enal to+icity0
Te!apeutic Uses% .!e*ention and topical t!eatment of supe!ficial candidal infections of
te s5in and mucous memb!anes 1gums' GIT' !ectum' *agina20

GRISE-FUL)IN
Fungistatic in acti*ity0
(-A% Inibits fungal cell mitosis by being accumulated in te ne4ly-syntesi$ed
5e!atin-containing tissue' tus p!oducing multinucleated defecti*e cells tat bind to te
mic!otubules' te!eby dis!upting mitotic spindle0
.a!maco5inetic p!ofile%
-!ally administe!ed3 t89:% :; ou!s0
Dist!ibutes to g!o4ing nails and s5in' binding to 5e!atin and ma5ing te cells !esistant to
fungal infection0
"iot!ansfo!med in te li*e! to <-metyl-g!iseoful*in3 u!ina!y e+c!0
ADR% /eadace' leta!gy' fatigue' blu!!ed *ision' insomnia' GI upset' epato+icity0
D!ug Inte!actions%
=it anticoagulants !educed effecti*eness of anticoagulants because of enanced
metabolism0
=it ba!bitu!ates enanced metabolism of g!iseoful*in0
=it alcool tacyca!dia and flusing3 potentiation of into+icating effects of alcool0
=it o!al cont!acepti*es ameno!!ea' inc!eased b!ea5t!oug bleeding0
Te!apeutic Use% Fo! tinea infections of te s5in' ai!' nails including atletes foot and
!ing4o!m caused by (ic!ospo!um' Epide!mopyton' and T!icopyton 1o!al20

FLU#7T-SINE
Fluo!inated py!imidine de!i*ati*e fo! candidiasis' c!yptococcosis' and c!omomycosis0
Fungistatic' syne!gistic effect 4it Ampote!icin "0
(-A% #on*e!ted to >-FU in sensiti*e fungi biot!ansfo!med to >-fluo!o-
deo+yu!idylic acid tat inibits tymidylate syntetase' tus dep!i*ing te o!ganism of tymidilic
acid 1essential DNA component2 dis!upts DNA syntesis0
(-R% Dec!eased le*el of te en$ymes in te con*e!sion of flucytosine to >
FU0
.a!maco5inetic p!ofile%
Administe!ed by o!al !oute3 t89:% ?-< ou!s0 E+c!etion% U!ine0
ADR% NA)' dia!!ea' !as' anemia' leu5openia' t!ombocytopenia3 inc!eased li*e! en$ymes'
"UN' @ c!eatinine0
S7STE(I# I(IDAA-LE
&etocona$ole
"!oad antifungal acti*ity3 fungistatic acti*ity0
(-A% Selecti*ely inc!eases fungal cell memb!ane pe!meability by bloc5ing te
demetylation of lanoste!ol to e!goste!ol0 1effecti*e only in g!o4ing cells2
(-R% (utation in te #8;-demetylase gene dec!eased a$ole binding3 fungiBs
ability to pump te a$ole out of te cell0
-!ally gi*en3 !eadily abso!bed unde! acidic p/0
ADR% NA)' dia!!ea' !as' itcing' di$$iness' constipation' fe*e!' cills' and eadace3
gynecomastia and impotence3 epatocellula! to+icity0
Te!apeutic Uses% R+ of systemic and *aginal candidiasis' mucocandidiasis' o!al t!us'
istoplamosis' c!omomycosis0 coccidioidomycosis' de!matopytosis0

-te! A$oles
Flucona$ole
Administe!ed .- o! I)0
(ay p!oduce te!atogenic effects0
D-# fo! #!yptococcus neofo!mans0
It!acona$ole
D-# fo! blastomycosis' aspe!gillosis' spo!ot!icosis' istoplasmosis' and
pa!acoccidioidomycosis0
-!ally administe!ed0
=it te!atogenic capability0
)o!icona$ole
Administe!ed o!ally and effecti*e fo! in*asi*e aspe!gillosis and se!ious infections caused
by Scedospo!ium apiospe!mum and fusa!ium species0
ADR% T!ansient *isual distu!bance0

#aspofungin
Fi!st of te ecinocandins class of antifungal d!ugs0
(-A% Inte!fe!es 4it te syntesis of te fungal cell 4all by inibiting te syntesis
of D- glucan cell lysis and deat0
ADR% Fe*e!' !as' nausea' plebitis' flusing0

S7STE(I# @ T-.I#AL I(IDAA-LE% (icona$ole
Administe!ed bot pa!ente!ally and topically0
Te!apeutic Uses% Fo! R+ of candidal and de!matopytic infections of te s5in and fo!
*aginal candidiasis 1topical20
Fo! se*e!e systemic fungal infections un!esponsi*e o! not tole!ant to Ampote!icin " 1I)20
ADR% Local bu!ning' itcing' and !as 1topical20
NA)' anemia' anapylactoid !eactions' #NS to+icity' yponat!emia' plebitis 1I)20

T-.I#AL I(IDAA-LE
#lot!ima$ole
"!oad antifungal acti*ity0
Te!apeutic Uses% )ul*o*aginal candidiasis 1topical2
-!opa!yngeal candidiasis 1topical o!al2
ADR% E!ytema' bliste!ing' edema' p!u!itus' u!tica!ia0

E#-NAA-LE
De!i*ati*e of micona$ole0
Used fo! te t!eatment of tinea pedis' tinea c!u!is' tinea co!po!is' tinea *e!sicolo!' and
cutaneous candidiasis0
ADR% "u!ning' itcing' !as0
"UT-#-NAA-LE
A$ole c!eam fo! *aginal use and is effecti*e against *aginal infections caused by #andida
albicans and #andida t!opicalis0
(ay cause *ul*o*aginal bu!ning and itcing0

-T/ER T-.I#AL ANTI(7#-TI# AGENTS
Undecylenic acid' alop!ogin0
TER"INAFINE
Fungicidal agent tat acts by selecti*ely inibiting s,ualene epo+idase tat is in*ol*ed in te
syntesis of e!goste!ol f!om s,ualene in te fungal cell 4all accumulation of s,ualene
to+icity to o!ganism0
Gi*en o!ally o! topically fo! fungal infections of te nails0
ADR% GI distu!bances' !ases' p!u!itus' eadace' di$$iness' 6oint and muscle pains'
epatitis0
Related d!ug% Naftifine

A(-R-LFINE
A mo!poline de!i*ati*e tat inte!fe!es 4it fungal ste!ol syntesis0
Gi*en o!ally fo! fungal infections of te nails0

"UTENAFINE
A syntetic ben$ylamine0
(-A
Alte!s fungal memb!ane pe!meability and g!o4t inibition0
Inte!fe!es 4it ste!ol biosyntesis by allo4ing s,ualene to accumulate 4itin te cell0
Te!apeutic Uses
De!matopytoses' including tinea co!po!is' tinea c!u!is' and tinea pedis 18C c!eam20

#I#L-.IR-D
(-A%
Int!acellula! depletion of amino acids and ions necessa!y fo! no!mal cellula! function0
Te!apeutic Uses%
Tinea pedis' tinea c!u!is' tinea co!po!is' tinea *e!sicolo!' cutaneous candidiasis 1topical20

#lio,uinol
A*ailable in ?C ointment fo! tinea pedis and c!u!is0
(ay cause local i!!itation' !as' and sensiti*ity !eactions0
-+icona$ole
A*ailable in 8C c!eam o! lotion fo! tinea c!u!is' co!po!is' mannum' and pedis and tinea
*e!sicolo!0
Sulcona$ole
Imida$ole de!i*ati*e a*ailable in 8C c!eam o! solution and used fo! tinea co!po!is' c!u!is'
pedis' *e!sicolo! and impetigo0
Te!cona$ole
Imida$ole de!i*ati*e a*ailable in *aginal c!eam and supposito!y and used fo! *ul*o*aginal
candidiasis0

ANTI)IRAL DRUGS

STAGES -F )IRUS (ULTI.LI#ATI-N
.ase 8% Adso!ption' penet!ation' and uncoating as te *i!us
ente!s te ost cell and seds its p!otecti*e coating0
.ase :% Syntesis of *i!al components0
.ase ?% Assembly and !elease of te *i!us 4ic can dest!oy o! pe!manently cange te cell0
IN/I"IT-RS -F )IRAL #ELL (ULTI.LI#ATI-N
.ase 8 and pase ? inibito!% Amantadine0
.ase : inibito!s% Acyclo*i!' Ganciclo*i!' )ida!abine' T!ifluo!idine' Ido+u!idine' Riba*i!in'
Aido*udine0

ANTI)IRAL DRUGS
D!ugs fo! Respi!ato!y )i!us Infections
Amantadine' -seltami*i!' Riba*i!in' Rimantadine' Aanami!*i!
D!ugs fo! /epatic )i!al Infections
Adefo*i!' Enteca*i!' Inte!fe!on' Lami*udine
D!ugs fo! /e!pes and #ytomegalo*i!us Infections
Acyclo*i!' #idofo*i!' Famciclo*i!' Fomi*i!sen' Fosca!net' Ganciclo*i!' .enciclo*i!'
)alacyclo*i!' )algancyclo*i!' )ida!abine
D!ugs fo! /I) Infections
Abaca*i!' Amp!ena*i!' Ata$ana*i!' Dela*i!dine' Didanosine' Emt!icitabine' Enfu*i!tide'
Efa*i!en$' Indina*i!' Lami*udine' Lopina*i!' Nelfina*i!' Ne*i!apine' Ritona*i!' Sa,uina*i!'
Sta*udine' Tenofo*i!' Aalcitabine' Aido*udine

T!eatment of Respi!ato!y )i!us Infections
Neu!aminidase Inibito!s% -seltami*i!' Aanami*i!
Sialic acid analogues
(-A% Inibits te neu!aminidase en$yme p!e*enting te !elease of ne4 *i!ions
and tei! sp!ead f!om cell to cell0
(-R% (utation of te neu!aminidase0
-seltami*i!% -!ally acti*e p!od!ug acti*e metabolite in li*e!3 ADR% GI discomfo!t and
nausea0
Aanama*i!% Inalation o! int!anasal administ!ation3 a*oided in se*e!e !eacti*e astma o!
#-.D0
Effecti*e fo! influen$a A and " infections0
Inibito!s of )i!al Uncoating% Amantadine' Rimantadine
Riba*i!in

A(ANTADINE @ RI(ANTADINE
Adamantadine de!i*ati*es0
Syntetic t!icyclic amine 4it a na!!o4 spect!um of acti*ity0
Te!apeutic Uses% T!eatment o! p!opyla+is of influen$a A *i!us and fo! .a!5insonBs
disease0
(-A% - Inibits te adso!ption of *i!al pa!ticles to ost cells' !esulting in delayed
penet!ation of te *i!us into te cell and9o! inibition of uncoating0
- Inibits *i!us assembly0
(-R% #ange in one amino acid of te (: mat!i+ p!otein0
Gi*en o!ally3 t89:% 8:-?< ou!s3 pea5 effects in :-; ou!s0
ADR% Di$$iness' insomnia' and slu!!ed speec3 confusion' ata+ia' sleep diso!de!s' tumo!s'
allucinations3 ano!e+ia' NA)' o!tostatic ypotension3 edema0

RI"A)IRIN
A syntetic nucleoside analog0
(-A% Inte!fe!es 4it guanidine monopospate' te!eby !educing nucleic acid
syntesis0
Te!apeutic Uses% RS) infections' e!pes simple+ infections' influen$a A and "
infections0
ADR% Ras' eadace' fatigue0

TREAT(ENT -F /E.ATI# )IRAL INFE#TI-NS
/epatitis "% R+ 4it inte!fe!on-E F and lami*udine
/epatitis #% R+ 4it inte!fe!on-E F and !iba*i!in
INTERFER-N
Immunomodulato!0
Inducible p!oteins syntesi$ed by mammalian cells and no4 p!oduced by !ecombinant
DNA tecnology0
(-A% Induces' in te !ibosomes of te ost cells' te p!oduction of en$ymes tat
inibit t!anslation of *i!al mRNA into *i!al #/-N stops !ep!oduction of *i!uses0
Gi*en I)3 t89: of :-; ou!s0
Te!apeutic Uses% /epatitis " infection and AIDS-!elated &aposi sa!coma
1E F inte!fe!on2 /epatitis # infection 1a:b inte!fe!on2
ADR% Fe*e!' lassitude' eadace' myalgia' bone ma!!o4 dep!ession' !ases'
alopecia0

-te! D!ugs fo! /epatic )i!al Infections
Lami*udine
#ytosine analog tat inibits bot epatitis " *i!us 1/")2 DNA polyme!ase and uman
immunodeficiency 1/I)2 !e*e!se t!ansc!iptase0
-!al administ!ation 4it t89: of G ou!s0
Adefo*i!
Nucleotide analog tat is pospo!ylated into adefo*i! dipospate and inco!po!ated into
te *i!al DNA te!minates fu!te! syntesis p!e*ents *i!al !eplication0
Enteca*i!
Guanosine analog tat is con*e!ted into enteca*i! t!ipospate 4ic competes fo! *i!al
!e*e!se t!ansc!iptase0

A#7#L-)IR
Acycloguanosine' G-:--/-eto+ymetylguanine0
A nucleoside analog of te py!imidine' guanosine0
(-A% Its t!ipospate 1acyclo GT.2 competiti*ely inibits *i!al DNA polyme!ase and
is also inco!po!ated into *i!al DNA 4e!e it functions as a cain te!minato!' tus p!e*enting te
fu!te! elongation of te DNA molecule and te!efo!e *i!al !eplication0
(-R% #anges in te *i!al genes coding fo! DNA polyme!ase0
Gi*en o!ally' topically' and int!a*enously3 t89: of :0> - ?0> !s0
Related d!ugs% )alaciclo*i! 1p!od!ug of aciclo*i!2
Famciclo*i! 1met0 to penciclo*i! - acti*e2
Te!apeutic Uses% - R+ of mucocutaneous e!pes and genital and disseminated adult
e!pes simple+0
- (gt0 of initial e!pes genitalis and in non-life-t!eatening cutaneous
simple+ *i!us infections in immunocomp!omised p+0
- R+ o! supp!ession of !ecu!!ent episodes of genital e!pes infection
and in *a!icella $oste!0
ADR% (ild pain' t!ansient bu!ning and stinging' p!u!itus' and !as 1ointment23 NA)' eadace'
dia!!ea' di$$iness' ano!e+ia' fatigue' edema' s5in !as' leg pain' adenopaty' so!e t!oat 1o!al23
plebitis' t!ansient ele*ation of se!um c!eatinine' !as 1I)20

GAN#I#L-)IR
A syntetic pu!ine nucleoside analog0
Te!apeutic Use% #ytomegalo*i!us infections 1I)2 and fo! maintenance te!apy in AIDS
patients 1o!al20
(-A% Acti*ated to its t!ipospate fo!m 4ic competes 4it guanosine
t!ipospate fo! inco!po!ation into te *i!al DNA0
Gi*en int!a*enously and o!ally 4it t89: of ; ou!s0
ADR% "one ma!!o4 dep!ession' ca!cinogenicity0
D!ug Inte!actions%
=it .!obenecid inc!eased ganciclo*i! le*el to+icity0
=it Imipenem-#ilastatin gene!ali$ed sei$u!es0
=it Aido*udine and cytoto+ic d!ugs neut!openia0

)IDARA"INE
Adenine a!abinoside0
(-A% Its t!ipospate inibits *i!al DNA polyme!ase' tus !educing DNA syntesis0
Administe!ed topically o! int!a*enously 1slo4 infusion20
T89:% ; ou!s0
Unde!goes deamination to a!abinosyl-ypo+antine0
Te!apeutic Uses% /e!pes simple+ 5e!atitis 1optalmic20 /e!pes simple+ encepalitis'
ote! se*e!e systemic e!pes infections' and *a!icella $oste! 1I)20
ADR% NA)' ano!e+ia' dia!!ea3 dec!eased /gb and /ct' inc!eased SG-T' t!emo!s' di$$iness'
allucinations0

TRIFLURIDINE
T!ifluo!otymidine3 a alogenated tymidine de!i*ati*e used as optalmic solution fo!
e!pes simple+-induced 5e!atocon6uncti*its0
(-A% #on*e!ted to its t!ipospate 4ic inibits DNA polyme!ase0
ADR% Local bu!ning o! stinging0

ID-DURIDINE
/alogenated de!i*ati*e of deo+yu!idine0
(-A% Inibits te !eplication of of DNA *i!uses by its inco!po!ation into te *i!us0
Gi*en topically0
Used fo! te t!eatment of e!pes simple+ 5e!atitis0
ADR% Inflammato!y edema of te eyelids' potopobia' lac!imal duct occlusion' and contact
de!matitis0

F-S#ARNET
T!isodium posponofo!mate e+ayd!ate o! .FA
A syntetic non-nucleoside analog of py!opospate3 gi*en I)0
(-A% Inibits *i!al DNA polyme!ase by binding di!ectly to te py!opospate
binding site0
ADR% Nep!oto+icity3 ype!9ypocalcemia' sei$u!es0

AID-)UDINE
A$idotymidine o! AAT0
Te!apeutic Indication% R+ of AIDS patients 4it .0 ca!inii pneumonia o! ad*anced
AIDS- !elated comple+0
Gi*en o!ally o! by I)3 t89:% 8 ou!0
(-A% Inte!fe!es 4it /I) !eplication by being con*e!ted to t!ipospate and
inibiting te DNA polyme!ase0
(-R% Rapid mutation of te *i!us3 dec!eased acti*ation of te d!ug to its
t!ipospate3 inc!eased *i!us load due to !eduction in immune mecanisms0
ADR% Insomnia' myalgia' nausea' se*e!e eadace' anemia' and neut!openia0

DIDAN-SINE
Dideo+yinosine' ddI0
A syntetic pu!ine analog0
(-A% .ospo!ylated to t!ipospate 4ic acts as a cain te!minato! and inibito!
of te *i!al !e*e!se t!ansc!iptase0
Gi*en o!ally 4it plasma t89: of ?H mins0 and int!acellula! t89: of 8: ou!s0
Used to t!eat AIDS0
ADR% .ain and senso!y loss in te feet3 dose-!elated panc!eatitis0

AAL#ITA"INE
Dideo+ycytidine' dd#0
A syntetic nucleoside analog0
(-A% Inibits te !e*e!se t!ansc!iptase en$yme0
Gi*en o!ally 4it a plasma t89: of :H mins0 and int!acellula! t89: of ? ou!s0
Used in te R+ of AIDS in combination 4it Aido*udine0
ADR% Dose-!elated neu!opaty' GI distu!bances' eadace' mout ulce!s' edema of te lo4e!
limbs' gene!al malaise' panc!eatitis0

NU#LE-SIDE RE)ERSE TRANS#RI.TASE IN/I"IT-RS
Abaca*i!' Adefo*i!' Lami*udine' Sta*udine' Aalcitabine' Didanosine' Aido*udine0
#ompetiti*e inibito!s of !e*e!se t!ansc!iptase cain te!mination 4en inco!po!ated into
te *i!al DNA cain0

N-N-NU#LE-SIDE RE)ERSE TRANS#RI.TASE IN/I"IT-RS
Dela*i!dine' Efa*i!en$' Ne*i!apine
#ompetiti*e inibito!s of !e*e!se t!ansc!iptase cain te!mination 4en inco!po!ated into
te *i!al DNA cain0

.R-TEASE IN/I"IT-RS
Amp!ena*i!' Indina*i!' Nelfina*i!' Ritona*i!' Sa,uina*i!0
#ompetiti*ely inibit te *i!al p!otease en$yme' p!e*enting te en$yme f!om clea*ing te
polyp!otein necessa!y fo! te p!oduction of te infectious *i!ions0

)i!al Fusion Inibito!
Enfu*i!tide
Anti!et!o*i!al d!ug0
A ?< AA peptide tat binds to gp;8' p!e*enting te confo!mational cange of te *i!al
t!ansmemb!ane tat is necessa!y fo! te fusion of te /I) memb!ane 4it tat of te ost cell
Subcutaneous administ!ation0

NATI-NAL GUIDELINES F-R ANTI-/I) TREAT(ENT
=en to begin t!eatment
T!eat any symptomatic patient0
-ffe! t!eatment to asymptomatic patients 4it #D; I>HH o! /I)-RNA J:H'HHH o!
!ecommend obse!*ing patients 4it #D; ?>H->HH and RNA I:H'HHH0
-bse!*e o! t!eat asymptomatic patients 4it #D; J>HH and /I)-RNA I:H'HHH0
.!efe!!ed Regimen
#oose f!om one of te p!otease inibito!s and one of te nucleoside !e*e!se
t!ansc!iptase inibito! combinations 1NRTI2 1$ido*udine K lami*udine' $ido*udine K
didanosine' $ido*udine K $alcitabine' sta*udine K lami*udine2
Alte!nati*e Regimen
#oose : NRTI combinations K 8 non-nucleoside RTI' eite! ne*i!apine o! dela*i!dine0
(onito!ing
(onito! /I)-RNA le*el3 if /I)-RNA does not fall mo!e tan 8H-fold by 4ee5 L' cange d!ug
!egimen and use :-? ne4 agents0
#onside! canging if #D; is falling o! if te!e is clinical dete!io!ation0

ANTI-.R-T-A-AL DRUGS

ANTI-(ALARIAL DRUGS
- DRUG #LASSIFI#ATI-N
- "lood sci$onticides
- D!ugs fo! supp!essi*e o! clinical cu!e0
- Affect te e!yt!ocytic stage of life cycle0
- Supp!ess te symptoms of actual attac5 by dest!oying te sci$onts and me!o$oites in
te e!yt!ocytes0
- #/L-R-MUINE' A(-DIAMUINE' (EFL-MUINE' MUININE' /AL-FANTRINE0
- Tissue sci$onticides
- Effects !adical cu!e by acting on te mala!ial epatic stage0
- Dest!oys gametocytes' tus !educing te sp!ead of infection0
- .RI(AMUINE0
- D!ugs tat affect bot e+o- and e!yt!ocytic fo!ms
- Anti-folate d!ugs o! diydo!folate !eductase inibito!s0
- #/L-R-GUANIDE' .7RI(ET/A(INE' TRI(ET/-.RI(0
- GA(ET-#IDES
- .!e*ent infection in mos,uitoes by dest!oying te gametocytes in te blood0
- .RI(AMUINE' #/L-R-MUINE0
- S.-R-NTI#IDES
- Rende! te gametocytes non-infecti*e in te mos,uito0
- .7RI(ET/A(INE' .R-GUANIL0

- "L--D S#/IA-NTI#IDES
- ;-A(IN-MUIN-LINES% #lo!o,uine' Amodia,uine0
- MUIN-LINE (ET/AN-LS% Muinine' (eflo,uine0
- ./ENANT/RENE (ET/AN-L% /alofant!ine0

#/L-R-MUINE
- (E#/ANIS(S -F A#TI-N
- "loc5s te en$ymatic syntesis of DNA and RNA in umans and p!oto$oal cells fo!ms
a comple+ 4it DNA p!e*ents DNA f!om acting as template fo! te !eplication and
t!ansc!iption to RNA0
- Fo!ms a comple+ 4it fe!!ip!otopo!py!in damage to cell memb!ane lysis of te
pa!asite and R"#0
- (E#/ANIS( -F RESISTAN#E
- Impai!ed mecanism of d!ug t!anspo!t ac!oss te pa!asite cell 4all concent!ation of
d!ug in !esistant sci$onts ne*e! !eaces a le*el sufficient to a!!est nucleic acid syntesis0
./AR(A#-&INETI#S
Fo!mulation% .ospate' yd!oclo!ide0
.."% >H-<>C0
/ig concent!ations in te e!yt!ocytes' li*e!' spleen' 5idneys' lungs' leu5ocytes0
.enet!ates te #NS and c!osses te placenta0
T89:% ?-> days0
./AR(A#-L-GI# EFFE#TS
Antimala!ial effect0
Muinidine-li5e effect on te ea!t dep!esses te ca!diac function0
Distinct anti-inflammato!y capability especially in !eumatoid a!t!itis and c!onic
discoid LE0
T/ERA.EUTI# USES
Acute mala!ial attac5s0
Te!minates fe*e! in :;-;L ou!s0
Te!minates pa!asitemia in ;L-N: ou!s0
#emopopyla+is *s all fo!ms of mala!ia e+cept .0 falcipa!um !esistant to ;-
amino,uinolines0
Amoebiasis' autoimmune diso!de!s as D(ARD0
ADR
(ild% GI complaints 1nausea' epigast!ic dist!ess2' s5in !as' eadace0
/ig dosage% Alopecia' g!aying of te ai!' s5in e!uptions and des,uamations'
5e!atopaty' !etinopaty0
-*e!dosage% )isual distu!bances' ype!e+citability' con*ulsions' A) bloc5' deat0

MUININE
Al5aloid f!om te cincona ba!50
(E#/ANIS( -F A#TI-N
#omple+es 4it double-st!anded DNA to p!e*ent st!and sepa!ation' t!ansc!iption' and
#/-N syntesis0
./AR(A#-L-GI# EFFE#TS
.e!ipe!al *osodilation0
Muinidine-li5e dep!ession of myoca!dial e+citability and conduction *elocity0
Di!ect !ela+ant effect on te smoot muscles se*e!e o! letal ypotension0
Distinct cu!a!e-li5e action0
#ont!action of te p!egnant ute!us0
/ypoglycemia0
./AR(A#-&INETI#S
Administ!ation% .- ' I)' I( 1N-day cou!se20
.."% NH-LHC0
T89:% N-8: ou!s0
/igest concent!ations in te li*e!' lungs' 5idneys' spleen0
(etabolism in te li*e!3 e+c!etion t!oug te u!ine0
T/ERA.EUTI# USES
.a!ente!al t!eatment of se*e!e falcipa!um mala!ia0
-!al R+ of falcipa!um mala!ia !esistant to #lo!o,uine0
.!opyla+is fo! #lo!o,uine-!esistant falcipa!um st!ains0
Relief of nigttime leg c!amps0
Se*e!e babesiosis 4it #lindamycin0
Ad*e!se Reactions
GI% I!!itation NA)' epigast!ic pain0
#inconism% At a d!ug plasma le*el of N-8H Eg9ml0
GI dist!ess' tinnitus' *e!tigo' eadace' blu!!ed *ision0
/ematologic effects
/emolysis' leu5openia' ag!anulocytosis' t!ombocytopenia pu!pu!a' /enoc-Sconlein
pu!pu!a' ypop!ot!ombinemia0
/ypoglycemia' t!omboplebitis' mode!ate-se*e!e ypotension' sei$u!es' *ent!icula!
fib!illation' deat0
Se*e!e to+icity
Fe*e!' s5in e!uptions' GI symptoms' deafness' *isual abno!malities' #NS effects
1syncope' confusion2' ,uinidine-li5e effects0
"lac54ate! fe*e!
#a!acte!i$ed bye+cessi*e int!a*ascula! emolysis follo4ed by emoglobinu!ia' da!5
u!ine' a$otemia' !enal failu!e0
DRUG INTERA#TI-NS
K aluminum-containing antacids delayed abso!ption of Muinine0
K Digo+in dec!eased !enal clea!ance of Digo+in inc!eased se!um concent!ation
of Digo+in0
K =a!fa!in and ote! anticoagulants enanced action of tese anticoagulants0
K #imetidine slo4ed elimination of Muinine0

(EFL-MUINE
Syntetic ;-,uinoline metanol de!i*ati*e cemically !elated to ,uinine0
(E#/ANIS( -F A#TI-N
Inibition of eme polyme!ase 1en$yme tat polyme!i$es to+ic f!ee eme to emo$oin2
pa!asite becomes a!mless0
./AR(A#-&INETI#S
Administe!ed by o!al !oute3 igly p!otein-bound' concent!ated in te R"# and
e+tensi*ely dist!ibuted to te tissues3 t89: of J < days0
./AR(A#-L-GI# EFFE#T
Muinidine-li5e effects on te ea!t ". !eduction and dep!ession of ca!diac function0
T/ERA.EUTI# USES
.!opyla+is and t!eatment of #lo!o,uine-!esistant st!ains of .0 falcipa!um0
AD)ERSE REA#TI-NS
.!opylactic dose%
GI distu!bances' eadace' di$$iness' syncope' e+t!asystoles0
T!ansient leu5ocytosis' t!ombobocytopenia' aminot!ansfe!ase ele*ations0
T!ansient neu!opsyciat!ic e*ents as con*ulsions' dep!ession' and psycosis0
T!eatment dose%
GI distu!bances' fatigue' neu!opsyciat!ic symptoms' p!u!itus' s5in !as' myalgia0
#-NTRAINDI#ATI-NS
/isto!y of epilepsy' psyciat!ic illness' a!!ytmias' ca!diac conduction defects' o!
sensiti*ity to ,uinidine o! !elated d!ugs0
#oncu!!ent use 4it ,uinine' ,uinidine' o! alofant!ine0
.!egnancy0
.e!sons 4ose 4o!5 !e,ui!es fine coo!dination and spatial disc!imination0
=it anti-con*ulsant d!ugs b!ea5t!oug sei$u!es0

/AL-FANTRINE
Acti*e against st!ains of .0 falcipa!um !esistant to clo!o,uine' py!imetamine' o! ,uinine
and te e!yt!ocytic fo!m of .0 *i*a+0
./AR(A#-&INETI#S
Administe!ed .- 4it pea5 plasma concent!ation ;-< ou!s afte! ingestion0
(ain metabolite% N-debutyl-alofant!ine3 e+c!etion% feces0
T89:% ;-> days0
ADR
Abdominal pain' GI distu!bances' eadace' coug' t!ansient !ise in epatic en$ymes'
p!u!itus' syncope' dys!ytmias' emolytic anemia' con*ulsions0

.RI(AMUINE
An L-amino,uinoline d!ug0
(E#/ANIS( -F A#TI-N
Fo!ms ,uinoline-,uinone metabolites 4ic inte!fe!e 4it elect!on t!anspo!t causing
o+idati*e damage to mitocond!ial en$yme system in te pa!asite s4elling and
*acuolation of te mitocod!ia lysis of te pa!asite0
./AR(A#-&INETI#S
Administe!ed .- 0
#oncent!ated in te li*e!' lungs' b!ain' ea!t' and s5eletal muscles0
Rapidly biot!ansfo!med 1li*e!2 to ca!bo+yp!ima,uine0
T89:% ?-> ou!s0
.RI(AMUINE
T/ERA.EUTI# USES
Te!minal p!opyla+is of *i*a+ and o*ale mala!ia0
Radical cu!e of acute *i*a+ and o*ale mala!ia0
Gametocidal action0
.neumocystis ca!inii pneumonia0
AD)ERSE REA#TI-NS
Abdominal discomfo!t' nausea' eadace' canges in *isual accommodation0
Leu5openia' ag!anulocytosis' leu5ocytosis' p!u!itus' a!!ytmias0
.!ima,uine sensiti*ity
Int!a*ascula! emolysis accompanied by te fo!mation of metemoglobin in G<.D-
deficient patients0

ANTIF-LATE DRUGS -R F-LATE (ETA"-LIS( IN/I"IT-RS -R DI/7DR-F-LATE REDU#TASE
IN/I"IT-RS
DRUGS% #lo!oguanide9.!oguanil' .y!imetamine' T!imetop!im
(E#/ANIS( -F A#TI-N
Inibits plasmodial diyd!ofolate !eductase 1D/FR2 !eduction of diyd!ofolic acid
to tet!acyd!ofolic acid 1folinic acid2 is inibited0
./AR(A#-&INETI#S
#lo!oguanide
Slo4ly abso!bed f!om te GIT3 acti*ated by con*e!sion to te t!ia$ine compound3 t89: of
8< ou!s0
.y!imetamine9T!imetop!im
Rapidly abso!bed in te GIT3 tissue concent!ation is ig3 t89: of ; days0
T/ERA.EUTI# USES
.!opyla+is against mala!ia and in #lo!o,uine-!esistant falcipa!um mala!ia
1#lo!oguanide02
T!eatment of #lo!o,uine-!esistant .0 falcipa!um mala!ia 14it sulfone o! sulfonamide20

AD)ERSE REA#TI-NS
Ano!e+ia 1#lo!oguanide20
Folic acid deficiency manifested as bone ma!!o4 dep!ession and megaloblastosis
1.y!imetamine20

ALTERNATI)E ANTI(ALARIAL DRUG% MING/A-SU
A!temisinin
Ses,uite!pene lactone endope!o+ide0
E+t!act f!om a #inese e!bal medicine 1A!temisia amma20
-te! de!i*ati*es% A!tesunate' a!temete!' a!tete!0
./AR(A#-&INETI#S
Administe!ed .- ' I)' I(' !ectal inse!tion0
#on*e!ted into diyd!o,ingaosu o! diyd!oa!temisinin0
T89:% A!temisinin - ; ou!s3 a!tesunate - ;> minutes3 a!temete! - ;-88 ou!s0
#LINI#AL USES
Effecti*e blood sci$onticide against all mala!ial fo!ms and #lo!o,uine-!esistain
falcipa!um mala!ia3 ce!eb!al falcipa!um mala!ia0
AD)ERSE REA#TI-NS
Abdominal pain' dia!!ea3 dep!ession of !eticulocyte ct3 t!ansient ea!t bloc50

-T/ER ALTERNATI)E ANTI(ALARIAL DRUGS
MUINA#RINE
A blood sci$onticide tat supp!esses all types of uman mala!ia3 effects !adical cu!e
of .0 mala!iae and non-!esistant st!ains of falcipa!um mala!ia0
ADR% yello4is discolo!ation of te s5in' psycotic !+ns
Also used in te t!eatment of gia!diasis0
D-D7#7#LINE
A tet!acycline used *s multid!ug !esistant .0 falcipa!um0
Also fo! blood stages of te ote! .lasmodium species0
=it ,uinine fo! acute mala!ia0
ADR% GI symptoms' candidal *aginitis' potosensiti*ity0
DA.S-NE
;';-diaminodipenylsulfone 1DDS2 used in te p!opyla+is of mala!ia usually combined
4it .y!imetamine0

.-TENTIAL NE= ANTI(ALARIAL DRUGS
.7R-NARIDINE
Syntetic sci$onticidal agent de!i*ed f!om mepac!ine3 de*eloped in #ina 0
AT-)AMU-NE
/yd!o+ynapto,uinone fo! .0 ca!inii penumonia0


A(-E"IASIS% E0 istolytica
DRUG #LASSIFI#ATI-N
(i+ed amoebicidal d!ug
Effecti*e against bot luminal and systemic fo!ms0
(ETR-NIDAA-LE0
Luminal amoebicides
Act on te pa!asite in te lumen of te bo4el0
Diclo!oacetamides% DIL-DANIDE FUR-ATE' TE#L-AAN'
ET-FA(IDE0
/alogenated yd!og,uinolines% I-D-MUIN-L' #LI-MUIN-L0
Antibiotics% TETRA#7#LINE' .AR-(-(7#IN0
Systemic amoebicides
Effecti*e against amoebae in te intestine and li*e!0
E(ETINE' DE/7DR-E(ETINE' #/L-R-MUINE0

NITR-I(IDAA-LES% (et!onida$ole' Tinida$ole
(E#/ANIS( -F A#TI-N
Unde!goes !educti*e bioacti*ation of its nit!o g!oup by fe!!edo+in to fo!m !eacti*e
cytoto+ic p!oducts0
./AR(A#-&INETI#S
Administe!ed .- ' I)' !ectal inse!tion0
.ea5 plasma concent!ation 8-? ou!s afte! administ!ation0
T89:% (et!onida$ole - N ou!s3 Tinida$ole - 8:-8; ou!s0
D!ug of coice in se*e!e intestinal 4all disease and in epatic abscess and ote! e+t!a-
intestinal amoebic disease0
#LINI#AL USES% (ild-se*e!e intestinal disease' li*e! abscess' amoeboma' e+t!a-intestinal
infections0
T-DI#IT7% "itte! metallic taste' GI i!!itation' eadace' discolo!ation of te u!ine'
leu5openia' di$$iness' ata+ia0
DRUG INTERA#TI-N% Disulfi!am-li5e !+n 4it etanol and potentiation of
couma!in anticoagulant effect0

DIL-DANIDE FUR-ATE 1Entami$ole 9 Fu!amide2
D!ug of coice in te t!eatment of asymptomatic passe!s of cysts and in te t!eatment of
intestinal amoebiasis0
Di!ect amoebicidal action' affecting te amoeba befo!e encystment0
Administe!ed .- 3 con*e!ted in te gut to dilo+anide-f!ee base 4ic is acti*e0
ADR% Flatulence' d!yness of te mout' nausea' p!u!itus' u!tica!ia0
#I in p!egnant 4omen and cild!en unde! : yea!s old0

E(ETINES% Emetine' Deyd!oemetine
Al5aloid obtained f!om "!a$il !oot0
(E#/ANIS( -F A#TI-N
Inibits p!otein syntesis by bloc5ing !ibosomal mo*ement along te messenge! RNA0
Used as bac5-up d!ugs fo! te t!eatment of se*e!e intestinal o! epatic amoebiasis in
ospitali$ed patients0
Gi*en pa!ente!ally 1I(23 4idely dist!ibuted3 e+c!eted slo4ly by te 5idneys0
T-DI#IT7% .ain' tende!ness' GI dist!ess' muscle 4ea5ness' #) dysfunction
1a!!ytmias and #/F 4it dyspnea and ypotension0
#LINI#AL USES% Amoebic dysente!y' amoebic li*e! abscess'
amoebomas' and e+t!a-intestinal amoebiasis0

/AL-GENATED /7DR-MUIN-LINES% Iodo,uinol' #lio,uinol
-!ally acti*e luminal amoebicides used as alte!nati*e d!ugs fo! mild to se*e!e intestinal
infections0
#LINI#AL USES
Intestinal amoebiasis' T0 *aginalis *aginitis' ote! intestinal pa!asites as "0 coli' G0
lamblia0
AD)ERSE REA#TI-NS
(ild% Dia!!ea' NA)' gast!itis' eadace' malaise0
La!ge doses and p!olonged use% S(-N 1subacute myelo-optic neu!opaty0

-T/ER DRUGS
#/L-R-MUINE
Acti*e against amoebas in te li*e! especially 4en gi*en 4it Emetine0
Used in combination 4it (et!onida$ole and Dilo+anide fu!oate to t!eat and p!e*ent
amoebic li*e! abscesss0
.AR-(-(7#IN 1/umagel2
Aminoglycoside antibiotic used as a :nd-line amoebicide 1luminal type20
Reduces te population of te intestinal flo!a0
ADR% GI dist!ess' dia!!ea' eadace' !ases' a!t!algia0
Fo! mild intestinal disease combine 4it Do+ycycline0
T!eatment fo! t!ypanosomiasis
Af!ican sleeping sic5ness
#aused by T!ypanosoma b!ucei gambiense and T!ypanosoma b!ucei !odiense0
Li*e and g!o4 in te blood in*ade #NS inflammation of te b!ain and spinal
co!d leta!gy and continuous sleep0
Ame!ican sleeping sic5ness
#agasOPQ disease0
#aused by T!ypanosoma c!u$i0
-ccu!s in Sout Ame!ica 0
T!eatment fo! t!ypanosomiasis
(ela!sop!ol
A de!i*ati*e of me!salyl o+ide tat is used fo! te t!eatment of late stage of te
infection 4it #NS in*ol*ement0
(-A% Reacts 4it sulfyd!yl g!oups of *a!ious substances' including te en$ymes
to+ic compounds0
(-R% Dec!eased pe!meability of te d!ug0
Administe!ed by I)3 so!t t 89:3 !apidly o+idi$ed into nonto+ic penta*alent a!senic
compound0
D-# in te R+ of T0 b!ucei !odiense and fo! meningoencepalitis caused by T0 b!ucei
gambiense0
ADR% Encepalopaty3 ype!sensiti*ity !eactions3 GI distu!bances' suc as se*e!e
*omiting and abdominal pain3 emolytic anemia in G-<-.D deficiency0
.entamidine isetionate
Administe!ed I( o! by ae!osol3 no metaboli$ed but e+c!eted *e!y slo4ly into te u!ine3
t89: of > days0
Used to p!e*ent and t!eat te o!ganismOPQs ematologic stage0
Nifu!timo+
Used fo! #agasOPQ disease0
Unde!goes !eduction into int!ecellula! o+ygen !adicals 1supe!o+ide and yd!ogen
pe!o+ide !adicals2 to+ic to o!ganism0
Administe!ed o!ally0
ADR 1elde!ly2% /ype!sensiti*ity !eaction and GI p!oblems3 pe!ipe!al neu!opaty0
Su!amin
Used fo! Af!ican t!ypanosomiasis0
(-A% Inibits many en$ymes in*ol*ed in ene!gy metabolism0
Gi*en I)0
T!eatment fo! ote! p!oto$oal infections
LEIS/(ANIASIS
Sodium stibogluconate
T-D-.LAS(-SIS
.y!imetamine
Sulfadia$ine K .y!imetamine
GIARDIASIS
(et!onida$ole