tb treatments

8/6/2019 TB Treatments

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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


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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





Conclusion

TBTREATMENTS

TB E radica t ion P rogram


B C G vaccina t ion

Actively and passively case finding. Health promotion Treatment Evaluation


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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





Conclusion

TBTREATMENTS



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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Treatment Choice






Isoniasid

Rifampicin

Etambutol

Pirazinamide





Conclusion

TBTREATMENTS



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






Isoniasid

Rifampicin

Etambutol

Pirazinamide





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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tb treatments

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