drug therapy of tb, 2015.ppt
TRANSCRIPT
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DRUG THERAPY OFDRUG THERAPY OF
TUBERCULOSISTUBERCULOSIS
1
Dr. Marlar Myint
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Objectives1. Classif a!tit"be#c"l$"s% a!tit"be#c"l$sis "'s
(. E)*lai! t+e ,ea!i!' $f t+e te#,s -fi#st li!e- a!& -sec$!& li!e- "'s
. Desc#ibe t+e ,ec+a!is,s $f acti$!s/ *+a#,ac$0i!etics a!& a&ve#se effects $f t+e fi#st li!e
a!tit"be#c"l$sis "'s
. List t+e sec$!& li!e a!tit"be#c"l$sis "'s
2. State t+e $bjectives $f a!tit"be#c"l$sis c+e,$t+e#a* a!& t+e #ati$!ale $f 'ivi!' c$,bi!ati$!
c+e,$t+e#a* a!& l$!' &"#ati$! $f t+e#a*
3. State t+e '"i&eli!es f$# a!tit"be#c"l$sis c+e,$t+e#a*
4. O"tli!e t+e sta!&a#& t#eat,e!t #e'i,e! $f a!ti5t"be#c"l$sis t+e#a* #ec$,,e!&e& b 6HO
7. 6+at is DOTS a!& &esc#ibe t+e a&va!ta'es $f DOTS
(
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II Tuberculosis
Ca"sal $#'a!is, 5 Mycobacterium tuberculosis
8AFB9
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Tuberculosis
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:
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D#"'s "se& f$# t+e t#eat,e!t
$f t"be#c"l$sis 8Classificati$!9
1.1. First line drugsFirst line drugs
D#"'s ;it+ +i'+e# efficac a!& #elativel lesse# t$)icit
Is$!iaa!a,ci!/
A,i0aci!/ Et+i$!a,i&e/ Pa#a5a,i!$saliclic aci& 8PAS9/
Ccl$se#i!e// Ca*#e$,ci!/ Li!e
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Isoniazid (INH)
Isonicotinic Acid Hydrazide
St#"ct"#al c$!'e!e# $f *#i&$)i!e 8?ita,i! B29
Bacte#i$static f$# #esti!' bacilli b"t bacte#ici&al f$# #a*i&l
&ivi&i!' ,ic#$$#'a!is,s
Selective f$# ,c$bacte#ia b"t/ $!l M. Kansasii is
s"sce*tible a,$!' at*ical ,c$bacte#ia
Mechanism of actionMechanism of action@ I!+ibits t+e bi$s!t+esis $f ,c$lic aci&/ a c+a#acte#istic
c$!stit"e!t $f t+e ,c$bacte#ial cell ;all
@I!te#fe#es ;it+ cell ;all f$#,ati$! 3
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!ar"aco#inetics o$ INH!ar"aco#inetics o$ INH
@ Rea&il abs$#be& $#all *e!et#ate cells t$ act $! i!t#acell"la#
,c$bacte#ia 8active a'ai!st e)t#a5cell"la# a!& i!t#a5cell"la# bacte#ia9
@ Pea0 *las,a c$!ce!t#ati$! #eac+es at 15( +#s afte# i!'esti$!
@ 6i&el &ist#ib"te& 8*le"#al ascitic fl"i&/ CSF/ ,ac#$*+a'es/ case$"s
t"be#c"l$"s lesi$!9 a!& c#$sses t+e *lace!ta
@ =etab$li
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%i"odal distribution o$ isoniazid !al$&li'es caused by raid and slo
acetylation o$ t!e drug 7
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T!eraeutic uses o$ INHT!eraeutic uses o$ INH
@ T#eat,e!t $f all t*es $f TB 8as t+e ,ai! "' i! a!ti5TB #e'i,e!s
@ C+e,$*#$*+la)is $f TB 8i! c$!tact/ IH $!l9
DoseDose : ,'%0'%&a/ ,a)i,", ,'
Ad'erse *$$ects o$ INHAd'erse *$$ects o$ INH
@ Pe#i*+e#al !e"#$*at+ &"e t$ *#i&$)i!e &eficie!c 8es*. i! sl$; acetlat$#s9
@ He*atitis 8es*. i! el&e#l a!& fast acetlat$#s as ,etab$lites a#e ,$#e t$)ic t$
t+e live#9
@ D#"' +*e#se!sitivit #eacti$!s 5 feve#/ a#t+#itic s,*t$,s/ vasc"litis a!& s0i!
e#"*ti$!s
@ Hae,$ltic a!ae,ia i! G52PD &eficie!t *atie!ts 1
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Is$!ia
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+i$a"in (+i$a"icin)+i$a"in (+i$a"icin)
Rifa,ci!s 5 c$,*le) ,ac#$cclic a!tibi$tics.
Rifa,*i! 5 se,is!t+etic &e#ivative $f #ifa,ci! B
Antimicrobial activity and spectrumAntimicrobial activity and spectrum
Bacte#ici&al a'e!t f$# b$t+ i!t#acell"la# a!& e)t#acell"la#
,c$bacte#ia
Bacte#ici&al ,$st ,ic#$$#'a!is,s s"c+ as E. coli, Proteus,
Pseudomonas, Klebsiella, Chlamydia and Pox virus
Als$ effective a'ai!st Staph.Aureus, Nisseria meningitidis a!& .
in!luen"ae
Resista!ce ,a &evel$* #a*i&l 1(
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Mec!anis" o$ action o$ +i$a"icinMec!anis" o$ action o$ +i$a"icin
I!+ibits DA5&e*e!&e!t RA *$l,e#ase e!
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!ar"aco#inetics o$ +i$a"icin
Well absorbedWell absorbed f#$, GIT b"t i,*ai#e&
b f$$&
@ About 80% protein boundAbout 80% protein bound
@ PeakPeak c$!ce!t#ati$! #eac+es i! (5 +#s
@ Widely distributedWidely distributedi!t$ tiss"e a!& b$&
b$& fl"i&s i!cl"&i!' CSF
@ saliva/ ,ac#$*+a'es/ !e#ves
@ Passes t+e BBB a!& *lace!ta ba##ie#
@ MetabolizedMetabolizedi! t+e live# a!&
@ eli,i!ate& i! bile/ faeces a!& "#i!e1
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T!eraeutic uses o$ +i$a"icin
C+e,$t+e#a* $f t"be#c"l$sis 8as a c$,*$!e!t $f a!ti5TB #e'i,e!s9
P#$*+la)is i! meningococcal a!& . in!luen"ae ,e!i!'itis
Sta*+l$c$ccal e!&$ca#&itis t$'et+e# ;it+ beta lacta, a!tibi$tics
Oste$,elitis ca"se& b sta*+l$c$cc"s t$le#a!t t$ *e!icilli! ;it+ $t+e#
a!tibi$tics
T$ e#a&icate !asal staphylococcal i!fecti$!
T$ t#eat ,e!i!'$c$ccal ca##ie#s
C+e,$t+e#a* f$# le*#$s
Dose -Dose - :52 ,' % &a i! a&"lts/ 1 ,' % 0' i! c+ile!
@ 1:
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Ad'erse e$$ects o$ +i$a"icin
@ O#a!'e c$l$#ati$! $f "#i!e/ s;eat/ tea#s a!&
c$!tact le!s 8si&e effect/ !$t +a#,f"l9
@ He*atitis
@ Fl"5li0e s!$,e ;it+ feve#/ c+ills a!& ,al'ia/ #as+es/
e$si!$*+ilia/ i!te#stitial !e*+#itis/ ac"te t"b"la# !ec#$sis/
t+#$,b$ct$*e!ia/ a!& eve! a!a*+lactic s+$c0
@ P#$tei!"#ia/ CS &ist"#ba!ces
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Drug interactions it! +F
@ nduces dru! metabolizin! enzymesnduces dru! metabolizin! enzymes $f &i'$)i!/ $#alc$!t#ace*tives/ $#al a!tic$a'"la!ts/ a!ti&iabetic a'e!ts/
!a#c$tic a!al'esics/ "i!i&i!e/ *#$*#a!$l$l/ cl$fib#ate/
ve#a*a,il a!& t+e$*+lli!e
,t!er +i$a"ycins
"ifabutin"ifabutin e"all effective/ less #esista!ce/ less e!
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+i$a"in induces cytoc!ro"e -/0 !ic! can decrease t!e !al$&li'es o$
coad"inistered drugs t!at are "etabolized by t!is syste"
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*t!a"butol
Mechanism of actionMechanism of action Bacte#i$static/ i!+ibit a#abi!$sl t#a!sfe#ase
i!v$lve& i! t+e s!t+esis $f a#abi!$'alacta!/ a c$,*$!e!t $f ,c$bacte#ial
cell ;all/ effective a'ai!st !ea#l all st#ai!s $f ,c$bacte#ia
PharmacokineticsPharmacokinetics
@6ell abs$#be& f#$, GIT 849 Pea0 c$!ce!t#ati$! #eac+es i! (5 +#
@6i&el &ist#ib"te&/ ca! c#$ss i!fla,,e& ,e!i!'es a!& *lace!ta
@3: $f "' is e)c#ete& "!c+a!'e& i! "#i!e ;it+i! ( +#s
#linical use $#linical use $ T#eat,e!t $f TB i! c$,bi!ati$! ;it+ $t+e# a!ti5Tb "'s
DoseDose & 1:5(: ,'%0'%&a
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Adverse effects of thambutolAdverse effects of thambutol
@ ?is"al t$)icit &"e t$ $*tic !e"#itis is c$,,$! es*. i! c+ile! #es"lti!'
i! &ec#ease& vis"al ac"it/ c$l$# bli!&!ess/ #eti!al &a,a'e
@ D$se #elate&/ #eve#sible if "' is ;it+a;! $# #e&"cti$! i! &$se
@ C+ile! "!&e# : ea#s a#e c$!t#ai!&icate&
@ Alle#'ic #eacti$!s 5 "' feve#/ #as+es
@ GI "*sets/ +ea&ac+e/ c$!f"si$!
@ H*e#"#icae,ia/ a#t+#al'ia
@ Pe#i*+e#al !e"#itis
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yrazina"ide
St#"ct"#all #elate& $f !ic$ti!a,i&e
Mechanism of actionMechanism of action
Bacte#ici&al a'e!t
P#$5"'/ c$!ve#te& b *#a
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yrazina"ide
PharmacokineticsPharmacokinetics
6ell abs$#be& f#$, GIT/ *e!et#ati!' i!t$ CSF a!& &ist#ib"te&
t+#$"'+$"t t+e b$&
H$lse& t$ *#a
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yrazina"ide and et!a"butol "ay cause urate retention and gouty attac#s
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Streto"ycin
Fi#st li!e "' i! t#eat,e!t $f t"be#c"l$sis
=ai! acti$! is $! t+e e)t#acell"la# $#'a!is,s
Mec!anis" o$ action
@Bacte#ici&al/ sa,e as $t+e# a,i!$'lc$si&es/ i##eve#sibl bi!& t$ S
#ib$s$,al s"b"!it $f #ib$s$,es a!& i!te#fe#e *#$tei! s!t+esis $f bacte#ia
&ses&ses## f$# t#eat,e!t $fJ
T"be#c"l$sis/ T"la#ae,ia/ Pla'"eB#"cell$sis 8c$,bi!e& ;it+ tet#accli!es9/ Bacte#ial e!&$ca#&itis
Dose -Dose - a&"lt 5 .3:51 ' I=/ c+il& 5 ,'%0' I=
(
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Adverse effects of 'treptomycin(Adverse effects of 'treptomycin(
@ )toto*icity)toto*icity5 4t+ c#a!ial !e#ve t$)icit lea&i!' t$ &sf"!cti$! $f
lab#i!t+/ i!abilit t$ ,ai!tai! e"ilib#i", ea#l si'!s $f vestib"la#
t$)icit i!cl"&e ,$ti$! #elate& +ea&ac+e/ &i
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So"e co""on ad'erse side
e$$ects o$ anti&T% drugs
(2
H + * S
eri&
!eral
Neuro&at!y
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,b3ecti'es o$ anti&tuberculosis
t!eray
@ T$ c"#e t+e *atie!t $f TB
@ T$ *#eve!t &eat+ f#$, active TB $# its c$,*licati$!s
@ T$ *#eve!t TB #ela*se
@ T$ &ec#ease TB t#a!s,issi$! t$ $t+e#s
(3
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"ationale of combination chemotherapy in the
treatment of ,
1. T$ *#eve!t ,ic#$bial #esista!ce
(. T$ ac+ieve a!ti,ic#$bial s!e#'is, 8t$ #e&"ce t+e bacte#ial
*$*"lati$! as #a*i&l as *$ssible9
. T$ #e&"ce t+e a&ve#se effects b #e&"ci!' t+e &$se $f eac+ "'
"ationale of !ivin! prolon! duration of treatment"ationale of !ivin! prolon! duration of treatment
1. F$# c$,*lete e#a&icati$! $f i!fecti$! as $#'a!is,s '#$; sl$;l
(. T$ *#eve!t ,ic#$bial #esista!ce
. T$ *#eve!t #ela*se
. T$ *#eve!t t#a!s,issi$! (4
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(7
K
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,ne o$ se'eral reco""ended "ultidrug sc!edules $or t!e treat"ent o$
tuberculosis
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Ma3or c!allenging $actors
@ M. tuberculosis is a! i!t#acell"la# $#'a!is,
@ O#'a!is, '#$;s ve# sl$;l/ c$!se"e!tl
i!fecti$!s a#e c+#$!ic *#$l$!'e& t+e#a* ,a#e"i#e
@ Resista!ce t$ "'s &evel$*s #a*i&l
1
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4uidelines $or anti&T%
c!e"ot!eray
1. C$!si&e#ati$! f$# +ist$# $f *#i$# a!ti5TB t+e#a*
(. $ si!'le "' t+e#a*
. $ &ivi&e& &$sa'e
. T$ a&& at least ( !e; "'s at a ti,e/ if !$t #es*$!& t$
*#evi$"s #e'i,e!
:. T$ 'ive a&e"ate &$sa'e #e'i,e!
2. T$ 'ive a&e"ate &"#ati$! $f t#eat,e!t acc$#&i!' t$
t+e &isease c$!&iti$! 8cate'$#9(
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5ategory I 6e; case
@ s,ea# *$sitive
@ se#i$"sl ill s,ea# !e'ative $#
@ e)t#a*"l,$!a# t"be#c"l$sis 8seve#e9
5ategory II 6Rela*se 8t#eat,e!t fail"#e $f
CatJ I III9 $# #et#eat,e!t $f &efa"lte#s
5ategory III 6e; case 5 s,ea# !e'ative
*"l,$!a# TB/ e)t#a*"l,$!a# TB
5ategory I7 6C+#$!ic case 8fail"#e afte# Cat II9
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H is$!ia
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Standard treat"ent
regi"en o$ 8H,
:
CATInitial
IntensivePhase
ContinuationPhase
Total
I2 HRZE(daily)
4 HR (daily) 6 Months
II
2 HRZES
(daily)
1 HRZE & then
5 HRE(daily) 8 Months
III 2 HRZ (daily) 4 HR (daily) 6 Months
IV To be teated in s!e"iali#ed "entes
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For c!ildren
Initial phaseContinuation
phase
CAT I 2 HRZ 4 H$R$
CAT III 2 HR 2 H$R$
2
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In secial circu"stances
Initial PhaseContinuation
Phase
Intolean"e to H 2RZE %RE
Intolean"e to Z 2HRE %HRe'nan"y 2HRE %HR
Resistan"e toHR
ZES o anothe ine"table a'enttho*'ho*t 12+18 ,th
Resistan"e to all ine"table a'ent - $ o. these 4/Ethiona,ide0 oa"in 3st lineanti+T a'ents
y"loseine and S tho*'ho*t
24 ,onth 3
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De$inition o$ D,TS
Di#ectl Obse#ve& T#eat,e!t/ S+$#t C$"#se
T+e #ey to sto t!e T% eide"ic.
Case &etecti$! t+#$"'+ sutu" "icroscoy is accurate0
si"le and reliable.
.ealth /orkers and trained volunteers
="st ;atc+ t+e *atie!t s;all$; $f eac+ &$se =$!it$# *#$'#ess $f t+e *atie!t "!til c"#e&
'upervision- m"st c$!ti!"e
e'eryday $or t!e $irst 2 "ont!s
4
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Advanta!es of D),'Advanta!es of D),'
@ DOTS doesn9t re:uire !ositalization$# is$lati$!.
Patie!ts ca! #e,ai! i! t+ei# +$,es a!& #et"#! t$
;$#0 i! a fe; ;ee0s.
@ DOTS +el*s t$ re'ent drug resistance;+ic+ is
$fte! fatal a!& "* t$ 1 ti,es ,$#e e)*e!sive t$
t#eat.
@ DOTS ca! *#$&"ce cure rates o$ u to ;D 8(9. I!J Essentials o! Medical Pharmacology. :t+e&iti$!/ Na*ee B#$t+e#s/
=e&ical *"blis+e#s Lt&/ e; De+li.