Drug therapy of TB, 2015.ppt

7/24/2019 Drug therapy of TB, 2015.ppt

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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

12


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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"

14


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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

17


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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.

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Drug therapy of TB, 2015.ppt