Post on 07-Apr-2018
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TB TREATMENTS
DR. DANNY SUWANDI, Ph.D,Sp.FKPharmacology and Therapy
Faculty of MedicineHasanudin University
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
General D escri pt ion
G eneral Description
My cobac t erium t uberculosis
Characteristic:Ver y con t agious
Route of contagious:D ro p le t I nfec t ion
Infected organs:Lung ( mos t ly)
Founder :R ober t K oc h (24/03/1882)
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
C linical S igns & D iagnose
C linical Signs and Diagnose
C linical signs :
Cough Hemoptoe Short of breath Anorexia Malaise Fever Noctural sweating
D iagnose :
Clinical signs Lab : BTA + , ESR increased Radiology : Specific feature
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
Trea t men t C h oice
T reatment Choice
INH
St re pt om y cin
R ifam p icin
Et ambu t ol
Py razinamide
Ofloxacin
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
I ndica t or of S uccesful Th era py
I ndicator of Successful Therapy
I m p roved general condi t ion :Weight gain, diminishing clinical signs.
R adiologie ;Prominent improvement
Bac t eriologie ;BTA within 3 consecutive months
ESR ;Return to normal value
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
C ause of Trea t men tFailure
C auses of Treatment Failure
D rug :
Insufficient dose Unregulated drug consumption Insufficient duration of drug intake
Bac t erial resis t anceD rug in t eru pt ion
P a t ien t :
Inadequate feeding Insufficient rest Unfavorable neighbourhood condition
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
TB E radica t ion P rogram
TB Eradication Program
B C G vaccina t ion
Actively and passively case finding. Health promotion Treatment Evaluation
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
F requenc y of B ac t erial R esis t ance
F requency of Bacterial Resistance
Frequency of bacterial resistance to anti-TB drugs
INH = 1 : 10 6 Basil
St re p = 1 : 10 6 Basil
PAS = 1 : 10 6 Basil
ETB = 1 : 10 4 Basil
RFP = 1 : 10 8 Basil
PZA = 1 : 10 2 Basil
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
P rinci p les of C h oosing D rug C ombina t ion
P rinciples of Choosing Drug Combination
Choosing drug combination based onth e dura t ion of t rea t men t and th e com p osi t ion of combina t ion .
F rom th e ver y beginning of t rea t men t, c h osen drug s h ould be de t ermined .
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
I soniasid
I soniasid
The standard drug to be given for the full durationof all s h or t course regimens because of itsefficac y , h ig h earl y bac t ericidal ac t ivi ty , low t oxici ty and its c h ea p ness .
I sonico t inil h idrazid : INH
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
I soniasid
Tuberculosidal property. Action mechanism lost of acid bearing property
and decrease of lipid synthesis.
G ood oral absorption
Distribution to the whole body tissues includingC avum C aseosa
85 90% excreted in form of acetylisoniasideand isonicotinate acid
Speed of acetilazation depends on genotype;R ecessive H omoz y go t e Au t osome slowacetylator
D ominan t H omoz y go t e H e t eroz y go t equick acetylator
I soniasid
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
I soniasid
Mostly found side effect : Peripheral neuritis treatwith Pyridoxine 100mg/day.
Other side effects : fever, skin disorders, anemia,convulsion, optic neuritis, dry mouth, epigastricpain and tinnitus.
Liver damage es p eciall y for elders ( could be p rogressive ). T ransamine t es t (S GO T) is crusial .
Dose :Adult : 5mg/kg b.w 400 mg /day
Children : 10 20mg/kg b.w
Preferable single dose Prophylactive dose : 300mg /day
I soniasid
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
R ifam p icin
R ifampicin
Absorption : Oral Plasma peak concentration : 1-4 hours Distributed through body fluids, tissues and
organs.
Matabolism through enterohepatic cycledeacetylization
Excreted especially through bile and urine Dose:
Children : 10 20 mg / kg b.wMax. 450 mg / day
Adult : 50 kg : 600mgInterm : 600 900 mg
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
R ifampicin
D rug in t erac t ions
Anti-coagulant hypoprothrom-binaemic effectdecreased
Oral contraceptive ostrogen decreased Corticosteroid effects decreased Oral Anti-diabetic t 1/2 tolbutamid
decreased
Digitalis t 1/2 digoxindecreased
Quinidine Cardiac arrhythmia Methadone withdrawal
R ifam p icin
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
Et ambu t ol
E tambutol
Bac t erios t a t icG ood absorption through digestive system
Excretion through urine and stoal mostly inoriginal form.
Most important side effect is optic neuritisdeteriorated visual accuracy and green colorblindness.
Other side effects : pruritus, digestive disorders,malaise, headache, vertigo, parasthesia andleucopenia.
Uric acid retention. Disorientation and hallucination might occur.
D ose 15 25 mg/kg b . w
Single dose
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
S hort Term TB Treatment
Sh or t T erm TB T rea t men t
For daily consumption of drugs with 4 weeks :INH 400 mg ,R ifam p icin 450 mg ,Et ambu t ol 1000 mg ,Vi t amin B6 10 mg ,
Then consumption of drug twice a week within thefollowing 22 weeks :
INH 700 mg ,R ifam p icin 600 mg ,Vi t amin B6 10 mg .
1
2For daily consumption of drugs within 8 weeks :INH 400 mg ,R ifam p icin 450 mg ,P irazinamid 1500 mg ,Vi t amin B6 10 mg ,
Then consumption of drug twice a week within thefollowing 18 weeks :INH 700 mg ,R ifam p icin 600 mg ,Vi t amin B6 10 mg .
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
S hort Term TB Treatment
Sh or t T erm TB T rea t men t
For daily consumption of drugs within 4 weeks :INH 400 mg ,P irazinamid 1500 mg ,Et ambu t ol 1000 mg ,
Then consumption of drug twice a week within thefollowing 20 weeks :INH 700 mg ,P irazinamid 3000 mg ,Et ambu t ol 2000 mg .
3
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
W HO Recomendation of TB Treatment (1995)
WH O TB T rea t men t 1995
11
B od y weig htbefore
th era py
I n t ensive F aseEver y da y
(2 mon th s )
F ollowing F aseTwice a week
(4 mon th s )
R H Z E R H
< 33 kg 300 200 1000 800 300 50033 50 kg 450 300 1500 800 450 600
> 50 kg 600 400 2000 1200 600 600
C a t egor y
For : New patient with BTA + Patient with BTA severe Ro + Severe extra pulmonary
D escri pt ion : R : Rifampicin, H : Isoniasid, Z : Pirazinamid, E : Etambutol.
2 H R Z E / 4 H3 R3
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
W HO Recomendation of TB Treatment (1995)
WH O TB T rea t men t 1995
22
Bod y weig htbefore
th era py
I n t ensive FaseEver y D a y
(3 mon th s )
F ollowing Fase
Th rice a week(5 mon th s )
R H Z E S*
R H E< 33 kg 300 200 1000 800 500 300 500 800
33 50 kg 450 300 1500 800 750 450 600 1200
> 50 kg 600 400 2000 1200 750 600 700 1600
C a t egor y
For : Repeating patient with BTA + Relapsing patient Failure patient
2 H R Z E S / 5 H3 R3 E3
D escri pt ion : R : Rifampicin, H : Isoniasid, Z : Pirazinamid, E : Etambutol,S : Streptomycin (*)hanya dua bulan saja)
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G eneral DescriptionClinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
W HO Recomendation of TB Treatment (1995)
WH O TB T rea t men t 1995
33Bod y weig ht
before th era py
I n t ensive F aseEver y da y (2 mon th s )
F ollowing Fase3 x a week (2 mon th s )
R H Z R H
< 33 kg 300 200 1000 300 500
33 50 kg 450 300 1500 450 600
> 50 kg 600 400 2000 600 700
C a t egor y
For : Patient with BTA Ro + Patient with extra pulmonary
2 H R Z / 2 H3 R3
D escri pt ion : R : Rifampicin, H : Isoniasid, Z : Pirazinamid.
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General Description
Clinical Signs and Diagnose
Treatment Choice
Indicator of SuccesfulTherapy
Causes of TreatmentFailure
TB Eradication Program
Frequency of BacterialResistance
Principle of Choosing DrugCombination
Isoniasid
Rifampicin
Etambutol
Pirazinamide
Long Term TB TreatmentShort Term TB Treatment
WHO TB Treatment 1995
WHO TB Treatment 1999
Examples of Cheaper DoseRegimens
Conclusion
TBTREATMENTS
C onclusion
C onclusion
Based on the above mentioned datawe could conclude that various drug
combination for TB treatment are
ver y effec t ive .The cause of TB treatment failure
mostly is due to inconsis t en t drug consum pt ion which brings up
resis t ance .
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UPDATIN G YO UR KN O W LED GE
is the key to
SU CC ESSFU L TREATMENT