Antituberculosis Drugs

7/18/2019 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

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%!

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!

A"IU !RCUL#$I

"IU !RCUL#$I

$ %RU&$ %RU&$

Wiwik KusumawatiWiwik Kusumawati

I"R#%UCI#"

"R#%UCI#"

7u4erculosis :nfection7u4erculosis :nfection

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

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

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

'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

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 *>

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

%istribution of 'rimary

istribution of 'rimary

%istribution of

istribution of

$()ondary M%R()ondary M%R

MA*#R 'R# L!M+

A*#R 'R# L!M+

Compliance ?Compliance ?

D:?#)7L ;S#?'# 7H#?3PD:?#)7L ;S#?'# 7H#?3P

-i0e com*onent of D;7S-i0e com*onent of D;7S

)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:' *>

: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

%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

%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

%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

%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

%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

%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

%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!

%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

$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

$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

!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

!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

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"

C#"I"UAI#"

#"I"UAI#"

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

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

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

$'!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!

$'!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"

R(ff(r(n)(s

(ff(r(n)(s

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$11 2 1$

$ubhaana3allohumma$ubhaana3allohumma

wabihamdi3awabihamdi3a

asyhadu anlaa illaaha illa antaasyhadu anlaa illaaha illa antaasta4hfiru3a wa atuubu ilai3aasta4hfiru3a wa atuubu ilai3a

Do’a penutup majelis

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