Antituberculosis Drugs
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Transcript of Antituberculosis Drugs
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BismillahirrohmaanirrohiimBismillahirrohmaanirrohiim
Asyhadu anlaa ilaaha illallohAsyhadu anlaa ilaaha illalloh
wa asyhadu anna Muhammadan rasuulullohwa asyhadu anna Muhammadan rasuululloh
Rodliitu billahi robbaaRodliitu billahi robbaa
wa bil-islaami diinaawa bil-islaami diinaa
wa bi Muhammadin nabiyyaw wa rosuulaawa bi Muhammadin nabiyyaw wa rosuulaa
Robbii zidni ‘ilmaaRobbii zidni ‘ilmaa
warzuqnii fahmaawarzuqnii fahmaa
Aamiin....Aamiin....
Do’a belajar
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CURRICULUM VIA!
URRICULUM VIA!
Wiwik Kusumawati,Wiwik Kusumawati, MDMD, M, Master of Health Scienceaster of Health Science
Lecturer of Pharmacology (199 toLecturer of Pharmacology (199 to nownow!!
Lecturer of Me"ical #"ucation ($%%& toLecturer of Me"ical #"ucation ($%%& to nownow!! 'ice Dean for aca"emic affair ($%%& to $%%!'ice Dean for aca"emic affair ($%%& to $%%!
)oor"inator of Pharmacology De*t (199 to $%%$!)oor"inator of Pharmacology De*t (199 to $%%$!
)oor"inator of Me"ical #"ucation +nit ($%%& to)oor"inator of Me"ical #"ucation +nit ($%%& to
$%1%!$%1%!
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CURRICULUM VIA!
URRICULUM VIA!
PhD )an" of Me"ical #"ucation ofPhD )an" of Me"ical #"ucation of -aculty of-aculty of
Me"icine .a"/ah Ma"a +ni0ersity, ogyakartaMe"icine .a"/ah Ma"a +ni0ersity, ogyakarta
(($%%$%% 2 2 nownow!!
Magister of Health Sciences from -aculty ofMagister of Health Sciences from -aculty ofMe"icine of .a"/ah Ma"a +ni0ersity,Me"icine of .a"/ah Ma"a +ni0ersity,
ogyakarta (199 2 $%%%!ogyakarta (199 2 $%%%!
Me"ical Doctor from -aculty of Me"icine ofMe"ical Doctor from -aculty of Me"icine of
3irlangga +ni0ersity, Sura4aya (1956 2 1991! 3irlangga +ni0ersity, Sura4aya (1956 2 1991!
.eneral Practitioner (P77 "octor! at #n"e,.eneral Practitioner (P77 "octor! at #n"e,
-lores, 877 (199$-lores, 877 (199$ 2 2 1996!1996!
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A"IU !RCUL#$I
"IU !RCUL#$I
$ %RU&$ %RU&$
yy
Wiwik KusumawatiWiwik Kusumawati
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I"R#%UCI#"
"R#%UCI#"
7u4erculosis :nfection7u4erculosis :nfection
??
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I"R#%UCI#"
"R#%UCI#"
Pulmonary tu4erculosisPulmonary tu4erculosis
6 to1%$ million new cases of t4c (WH;!6 to1%$ million new cases of t4c (WH;!
$6 to <6 million tu4erculosis "eath$6 to <6 million tu4erculosis "eath De0elo* an" "e0elo*ing countriesDe0elo* an" "e0elo*ing countries
:mmuno"eficiency 0irus (H:'! infection:mmuno"eficiency 0irus (H:'! infection
+* 5% = t4c *> are H:' *ositi0e+* 5% = t4c *> are H:' *ositi0e <6 million, "ual infection<6 million, "ual infection
?eacti0ation 2 "ormant infection?eacti0ation 2 "ormant infection
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I"R#%UCI#"
"R#%UCI#"
74c infection in :n"onesia@74c infection in :n"onesia@
Po*ulationPo*ulation
Hygiene an" sanitationHygiene an" sanitation
Status of immunityStatus of immunity
Status of economyStatus of economy
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CA$!
A$!
3 3 66& years ol" man& years ol" man 4ring to the hos*ital with4ring to the hos*ital with
cough more than < weeks,cough more than < weeks, fe0er,fe0er, an"an"
"ecreasing of a**etite"ecreasing of a**etite after taking history an"after taking history an"
con"ucting clinical e>amination, the "octor "ocon"ucting clinical e>amination, the "octor "ola4oratory test (s*utum test! La4oratory resultla4oratory test (s*utum test! La4oratory result
re0eale" myco4actterium t4c *ositi0e an" there0eale" myco4actterium t4c *ositi0e an" the
"octor *rescri4e antitu4erculosis "rugs"octor *rescri4e antitu4erculosis "rugs
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'ulmonary
ulmonary
ub(r)ulosis
b(r)ulosis
Prom*t "iagnosis an" effecti0e treatmentProm*t "iagnosis an" effecti0e treatment
.eneral sym*toms.eneral sym*toms
Weight loss, malaise, fe0ersWeight loss, malaise, fe0ers
?es*iratory sym*toms?es*iratory sym*toms
)ough, s*utum an" haemo*tysis)ough, s*utum an" haemo*tysis
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R(sistan)( of M.
(sistan)( of M.
tub(r)ulosisub(r)ulosis
S*ontaneous mutationS*ontaneous mutation
:m*ro*erly *rescri4e" thera*y:m*ro*erly *rescri4e" thera*y
#rratic "rug ingestion#rratic "rug ingestion
:na"eAuate "osage:na"eAuate "osage
:ncom*lete thera*y:ncom*lete thera*y
Lack of com*liance 4y *>Lack of com*liance 4y *>
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R(sistan)( of M.
(sistan)( of M.
tub(r)ulosisub(r)ulosis
MD? B :8H an" ?ifam*icinMD? B :8H an" ?ifam*icin
CD? B -luoroAuinolone 1 in/ectionCD? B -luoroAuinolone 1 in/ection
"rug"rug PrimaryPrimary
Secon"arySecon"ary
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%istribution of 'rimary
istribution of 'rimary
M%R
%R
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%istribution of
istribution of
$()ondary M%R()ondary M%R
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MA*#R 'R# L!M+
A*#R 'R# L!M+
Compliance ?Compliance ?
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%#,$
#,$
D:?#)7L ;S#?'# 7H#?3PD:?#)7L ;S#?'# 7H#?3P
-i0e com*onent of D;7S-i0e com*onent of D;7S
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)L3SS)L3SS ?;+7#?;+7# M3E;? :8D:)37:;8M3E;? :8D:)37:;8
:soniaFi":soniaFi" P;P; PrimaryPrimary
?ifam*in?ifam*in :', P;:', P; PrimaryPrimaryStre*tomycinStre*tomycin :M:M PrimaryPrimary
#tham4utol#tham4utol P;P; PrimaryPrimary
PyraFinami"ePyraFinami"e P;P; Primary )8S orPrimary )8S or
secon"arysecon"ary
)a*reomycin)a*reomycin :M:M Secon"ary or aty*icalSecon"ary or aty*ical
KanamycinKanamycin :M:M Secon"arySecon"ary
)ycloserine)ycloserine P;P; Secon"arySecon"ary#thionami"e#thionami"e P;P; Secon"ary or aty*icalSecon"ary or aty*ical
3minosalicylic aci" 3minosalicylic aci" P;P; Secon"arySecon"ary
)lofaFimine)lofaFimine P;P; 3ty*ical in H:' *> 3ty*ical in H:' *>
?ifa4utin?ifa4utin P;P; 3ty*ical in H:' *> 3ty*ical in H:' *>
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%RU&$
RU&$
:8H G ?ifam*in:8H G ?ifam*in 7u4erculoci"al for 4oth e>tracellular intracellular7u4erculoci"al for 4oth e>tracellular intracellular
organismorganism
Stre*tomycinStre*tomycin 7u4erculoci"al for e>tracellular organism only7u4erculoci"al for e>tracellular organism only
PyraFinami"ePyraFinami"e 7u4erculoci"al for intracellular organism7u4erculoci"al for intracellular organism
#tham4utol, *aminosalicylic aci" G#tham4utol, *aminosalicylic aci" Gethionami"eethionami"e 7u4erculostatic7u4erculostatic
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%RU&$ -I"/
RU&$ -I"/
acterici"al 2 cell wall synthesisacterici"al 2 cell wall synthesis
)om4ination)om4ination
3cti0e infection 3cti0e infection Secon"ary chemo*ro*hyla>isSecon"ary chemo*ro*hyla>is shoul" 4e gi0en with $shoul" 4e gi0en with $
or more effecti0e "rugsor more effecti0e "rugs
Shoul" ne0er 4e use" as a single to treat acti0eShoul" ne0er 4e use" as a single to treat acti0e
t4ct4c Single agent (monothera*y!Single agent (monothera*y!
Primary chemo*ro*hyla>isPrimary chemo*ro*hyla>is
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%RU&$ -I"/
RU&$ -I"/
P;B well an" ra*i"ly a4sor4e"P;B well an" ra*i"ly a4sor4e"
Peak concentration 1 to $ hoursPeak concentration 1 to $ hours
7he "istri4ution is e>tensi0e7he "istri4ution is e>tensi0e
< to 6 mgIkgI"ay 2 $% mgIkgI"ay< to 6 mgIkgI"ay 2 $% mgIkgI"ay Meta4olism 4y acetylation an" hy"ro>ylationMeta4olism 4y acetylation an" hy"ro>ylation
Slow acetylators (Scan"ina0ia, 8orth 3frica! 2Slow acetylators (Scan"ina0ia, 8orth 3frica! 2a"0erse effectsa"0erse effects
?a*i" acetylators (Ea*an, #scimo! 2?a*i" acetylators (Ea*an, #scimo! 2 intermittentintermittentregimenregimen
8o influence 4oth the effect of thera*y an" si"e8o influence 4oth the effect of thera*y an" si"eeffect if :8H gi0en e0ery"ayeffect if :8H gi0en e0ery"ay
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%RU&$ -I"/
RU&$ -I"/
Si"e effectSi"e effect
Peri*heral neuro*athy 2 1% mgI"ay ofPeri*heral neuro*athy 2 1% mgI"ay of
*yri"o>ine*yri"o>ine :n"uce" he*atic in/ury:n"uce" he*atic in/ury
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%RU&$ -Rifam0i)in(/
RU&$ -Rifam0i)in(/
3 firstline 4acterici"al antitu4erculosis 3 firstline 4acterici"al antitu4erculosis
:nhi4its ?83*olymerase:nhi4its ?83*olymerase
)om4ination with *yraFinami"e B J*ersisters)om4ination with *yraFinami"e B J*ersisters
P;, :'P;, :'
P; B well an" com*letely a4sor4tion (em*tyP; B well an" com*letely a4sor4tion (em*ty
stomach!stomach! Peak concentration $ to & hoursPeak concentration $ to & hours
)om4ination with :8H not influence a4sor4tion)om4ination with :8H not influence a4sor4tion
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%RU&$ -Rifam0i)in(/
RU&$ -Rifam0i)in(/
Distri4ution is e>tensi0e, *roteinDistri4ution is e>tensi0e, *rotein
(al4umin! 4in"ing 5%=(al4umin! 4in"ing 5%=
?e"4rown colouration of 4o"y flui"?e"4rown colouration of 4o"y flui" Meta4olism "eacetylation 2 acti0eMeta4olism "eacetylation 2 acti0e
meta4olitemeta4olite
#>cretion B 4iliary an" renal (<%=!#>cretion B 4iliary an" renal (<%=!
?esistant rifam*icine 2 rifa4utine?esistant rifam*icine 2 rifa4utine
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%RU&$ -Rifam0i)in(/
RU&$ -Rifam0i)in(/
Dose &6% 2 %% mgI"ay (a"ult! 1% 2 $% mgIkgDose &6% 2 %% mgI"ay (a"ult! 1% 2 $% mgIkg
WI"ay (chil"ren!WI"ay (chil"ren!
Si"e effectSi"e effect ?ash, fe0er, nausea, 0omiting?ash, fe0er, nausea, 0omiting
-lu like syn"rome-lu like syn"rome
He*atoto>ic 2 he*atitisHe*atoto>ic 2 he*atitis
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%RU&$ -Rifam0i)in(/
RU&$ -Rifam0i)in(/
#nFyme he*atic in"ucer (increase meta4olism#nFyme he*atic in"ucer (increase meta4olism
of oral contrace*tion, corticosteroi",of oral contrace*tion, corticosteroi",
hy*oglycemic agent, 0itamine D!hy*oglycemic agent, 0itamine D!
P3S inhi4its a4sor4tion of rifam*icineP3S inhi4its a4sor4tion of rifam*icine
?ifam*icine :8H (slow acetlators!?ifam*icine :8H (slow acetlators!
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%RU&$ -'yrazinamid(/
RU&$ -'yrazinamid(/
acterici"al to myco4acteria multi*lyingacterici"al to myco4acteria multi*lyingintracellularly at low *H le0elintracellularly at low *H le0el
7he first $ months of a treatment regimen7he first $ months of a treatment regimen
?e"uce later rela*s rates?e"uce later rela*s rates
3 shorter "uration of thera*y 3 shorter "uration of thera*y
P; B well a4sor4e"P; B well a4sor4e"
Penetrates well in )S-Penetrates well in )S- 8ausea, flushing, arthralgia,8ausea, flushing, arthralgia, he*atoto>iche*atoto>ic
reactionsreactions
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$R!'#M1CI"
R!'#M1CI"
3n aminoglycosi"e 3n aminoglycosi"e
#>tracellular 4acteria#>tracellular 4acteria
Single "rug 2 no effecti0eSingle "rug 2 no effecti0e Must 4e gi0en 4y in/ection (:M!Must 4e gi0en 4y in/ection (:M!
Wi"ely "istri4utions 2 "oesnt cross wellWi"ely "istri4utions 2 "oesnt cross well
into )S-into )S- <% = *rotein 4in"ing<% = *rotein 4in"ing
9% = "rugs e>crete" 0ia urine9% = "rugs e>crete" 0ia urine
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$R!'#M1CI"
R!'#M1CI"
DoseDose
$% mgIkg W 2 ma>imally 1 gramI"ay$% mgIkg W 2 ma>imally 1 gramI"ay
Si"e effectSi"e effect 8euroto>ic an" ne*hroto>ic8euroto>ic an" ne*hroto>ic
5 cranial ner0e "amage, 0esti4ular5 cranial ner0e "amage, 0esti4ular
to>icity, rashto>icity, rash )aution)aution
Pregnancy, el"erly, renal "isease, etcPregnancy, el"erly, renal "isease, etc
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!AM U#L
AM U#L
3n essentially 4acteriostatic 3n essentially 4acteriostatic
:nhi4its myco4acterial cell wall synthesis:nhi4its myco4acterial cell wall synthesis
P; B well a4sor4e" (6= to 5% =!P; B well a4sor4e" (6= to 5% =!
Doesnt cross Doesnt cross
#>cretion B unchange" in the urine#>cretion B unchange" in the urine
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!AM U#L
AM U#L
Dose 16 mgIkg WI"ayDose 16 mgIkg WI"ay
Si"e effectSi"e effect
?etro4ul4ar neuritis (4ilateral!?etro4ul4ar neuritis (4ilateral!
?ash, fe0er, :ncreasing 4loo" uric aci",?ash, fe0er, :ncreasing 4loo" uric aci",
etcetc
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I"IIAL R!AM!"
"IIAL R!AM!"
3t least < "rugs 3t least < "rugs
:8H, ?ifam*icin, PyraFinami"e:8H, ?ifam*icin, PyraFinami"e
-or at least 5 weeks 2 sensiti0ity-or at least 5 weeks 2 sensiti0ity
esta4lishe"esta4lishe"
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C#"I"UAI#"
#"I"UAI#"
R!AM!"
R!AM!"
?ifam*icin an" :8H?ifam*icin an" :8H
-urther & months-urther & months
$H?NI&H? 2 months$H?NI&H? 2 months
$#H?IH? 2 9 month$#H?IH? 2 9 month
?ifam*icin not inclu"e" B 15 months?ifam*icin not inclu"e" B 15 months
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M#"I#RI"&
#"I#RI"&
Monitoring a"0erse effect an" efficacy ofMonitoring a"0erse effect an" efficacy of
"rugs"rugs
Monitoring u* to 1 year after a regimenMonitoring u* to 1 year after a regimencom*letelycom*letely
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CA$!
A$!
3 3 &&& years ol"& years ol" woman suffering from t4cwoman suffering from t4c
infection an" also 3 ty*e of he*atitis infectioninfection an" also 3 ty*e of he*atitis infection
Health care *ro0i"er gi0e this *atientHealth care *ro0i"er gi0e this *atient
rifam*icine, :8H, *yraFinami"e asrifam*icine, :8H, *yraFinami"e asantitu4erculosis "rugs for $ months in intensi0eantitu4erculosis "rugs for $ months in intensi0e
*hase*hase
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$'!CI2IC C#"%II#"
'!CI2IC C#"%II#"
7reatment "uring *regnancy7reatment "uring *regnancy :8H, #tham4utol, ?ifam*icin (safely!:8H, #tham4utol, ?ifam*icin (safely!
:8H,:8H, PyrazinamidePyrazinamide, ?ifam*icin (*oorly tolerate"!, ?ifam*icin (*oorly tolerate"!
#thionami"e is contra in"ication#thionami"e is contra in"ication
Stre*tomycin is 4est a0oi"e"Stre*tomycin is 4est a0oi"e"
7reatment in renal "isease7reatment in renal "isease ?ifam*icin (normal "ose!?ifam*icin (normal "ose!
;ther "rugs (re"uce" "ose!;ther "rugs (re"uce" "ose! PyraFinami"e 2 *reci*itate goutPyraFinami"e 2 *reci*itate gout
Stre*tomycin 2 if essentialStre*tomycin 2 if essential
#tham4utol is 4est a0oi"e" in renal failure (.-? 6%#tham4utol is 4est a0oi"e" in renal failure (.-? 6%
mlImin or < LIh!mlImin or < LIh!
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$'!CI2IC C#"%II#"
'!CI2IC C#"%II#"
7reatment in li0er "isease7reatment in li0er "isease
:8H, rifam*icin, ethionami"e an" *yraFinami"e can:8H, rifam*icin, ethionami"e an" *yraFinami"e can
all 4e ha*atoto>icall 4e ha*atoto>ic
#tham4utol, Stre*tomycin, :8H#tham4utol, Stre*tomycin, :8H ?egular li0er function monitoring?egular li0er function monitoring
7reatment in chil"ren7reatment in chil"ren
Stan"ar" initial regimenStan"ar" initial regimen
:8H, rifam*icin an" *yraFinami"e:8H, rifam*icin an" *yraFinami"e
if $ "rugs regimenif $ "rugs regimen (:8H an" rifam*icin!(:8H an" rifam*icin! B 9 monthsB 9 months
#tham4utol is 4est a0oi"e"#tham4utol is 4est a0oi"e"
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R(ff(r(n)(s
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30erys Drug 7reatment & 30erys Drug 7reatment &thth e"itione"ition
(7re0or G 8icholas! B 1%& 2 1%6&(7re0or G 8icholas! B 1%& 2 1%6&
)linical Pharmacology, asic Princi*les)linical Pharmacology, asic Princi*lesin 7hera*eutics (Melmon an" Morellis! Bin 7hera*eutics (Melmon an" Morellis! B
11 2 1$11 2 1$
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$ubhaana3allohumma$ubhaana3allohumma
wabihamdi3awabihamdi3a
asyhadu anlaa illaaha illa antaasyhadu anlaa illaaha illa antaasta4hfiru3a wa atuubu ilai3aasta4hfiru3a wa atuubu ilai3a
Do’a penutup majelis