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Oleh :Annisa Amriani. S, M. Farm, AptAntituberkolosis

Tuberkolosis (TB)Adalah penyakit kronik yang disebabkan oleh berbagaijenis strain Mycobacteria, khususnya Mycobacterium tuberculosis.

TB biasanya menyerang paru-paru (80%), namun dapat juga menyerang organ lainnya.

Pengobatan TB melibatkan banyak antibiotik yg diminum dalam jangka waktu lama

Etiologi

Mycobacterium tuberculosis Merupakan basil gram positif, berbentuk batang, dinding selnya mengandung komplek lipida-glikolipida serta lilin (wax) yang sulit ditembus zat kimia.Umumnya M. tuberculosis menyerang paru dan sebagian kecil organ tubuh lain.

(Depkes RI, 2005)

Gejala

Batuk Kronis DemamBerkeringat di Malam HariKeluhan pada PernapasanAnoreksia (Kurang Nafsu Makan)Berat Badan TurunNyeri di Bagian DadaDahaknya Mengandung Darah

(Tjay, 2002)

Patofisiologi

Patogenesis

Kuman (droplet nuclei)Menempel pada saluran napas atau jaringan paruMekanisme protektif tubuh oleh neutrofil dan makrofagKuman tetap menetap di jaringan paruKuman berkembang biak dalam sitoplasma makrofag dan membentuk sarang primerKuman mati dan keluar dari percabangan trakeobronkial bersama gerakan silia dan sekretnya

DIAGNOSA

Samir, S. 2009. Pediatric Practice Infectious Disease. Philadephia, Pennsylvania. The McGraw-Hill Companies, Inc. All rights reserved.

Samir, S. 2009. Pediatric Practice Infectious Disease. Philadephia, Pennsylvania. The McGraw-Hill Companies, Inc. All rights reserved.

Recommended treatment regimens for each diagnostic category

There is a standard code for anti-TB treatment regimens, which uses an abbreviation for each anti-TB drug, e.g. isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E). A regimen consists of two phases: the initial and continuation phases. The number at the front of each phase represents the duration of that phase in months

Samir, S. 2009. Pediatric Practice Infectious Disease. Philadephia, Pennsylvania. The McGraw-Hill Companies, Inc. All rights reserved.

Reserve or second-line anti-tuberculosis drugsGie, R. P. 2006. Anti-tuberculosis treatment in children. Int J Tuberc Lung Dis, World Health Organization, Geneva, Switzerland.

TERAPI TBTablet OAT - FDCKomposisi / KandunganPemakaian4FDC75 mg INH150 mg Rifampisin400 mg Pirazinamid275 mg EtambutolTahap intensif / awal dan sisipan Harian2FDC150 mg INH150 mg RifampisinTahap lanjutan 3 kali semingguPelengkap paduan kategori-2 : Tablet etambutol @ 400 mgInjeksi (vial) Streptomisin 750 mgAquabidest dan spuit

Tabel V.1 Kandungan OAT FDC

Paduan pengobatan OAT-FDC yang tersedia saat ini di Indonesia terdiri dari:2(HRZE)/4(HR)3 untuk Kategori 1 dan Kategori 32(HRZE)S/1(HRZE)/5(HR)3E3 untuk Kategori 2

TERAPI TBTabel V.1 Dosis Pengobatan kategori1 dan kategori 3 : {2(HRZE)/4(HR)3}

Berat BadanTAHAP INTENSIF(tiap hari selama 2bulan)TAHAP LANJUTAN(3 kali seminggu selama4 bulan)30 37 kg2 tablet 4FDC2 tablet 2FDC38 54 kg3 tablet 4FDC3 tablet 2FDC55 70 kg4 tablet 4FDC4 tablet 2FDC> 70 kg5 tablet 4FDC5 tablet 2FDC

REGIMEN PENGOBATAN

DrugDoseLiteratur doseNotePharmacokinetic Isoniazid1 x 100 mg10-15 mg/kg/d in 1-2 divided doses (max 300 mg/d)100-150 mg. Isoniazid (INH) is a synthetic hydrazine derivative of isonicotinicacid that inhibits the synthesis of mycolic acid, a component of the mycobacterialcell wallAbsorb: GIT,slow wit foodProtein binding: 10-15%Metabolism: heparExcretion: urine, feces, salivaT : 1-6 hRifampicin1 x 100 mg10-20 mg/kg/d as single dose or in divided dose; max 600mg/d100-200 mg. Rifampin is a synthetic rifamycin B derivative that inhibits theaction of DNA-dependent RNA polymerase. It is highly active against mycobac-teria, most Gram-positive bacteria, and some Gram-negative bacteria, most no-tably Neisseria meningitidisAbsorb: GIT, delay/reduce with foodProtein binding: 80%Metabolism: heparExcretion: feces, urineT : 2-5 hPyrazinamid1 x 250 mg15-30 mg/kg/d max 2g/d150-300 mg. Pyrazinamide is a synthetic analogue of niacinamide that is onlyactive against mycobacteria. The mode of action is unknownAbsorb: GITProtein binding: 50%Metabolism: heparExcretion: urineT :9-10 h

DrugDosesLiteratur doseNoteVit B6 (pyridoxine)1 x 10 mg1-2 mg/24hGive as profilaxis for drug induced neuritis (INH)

Isoniazide Absorbsi: in GIT, can be slowed with food Distribution: protein binding 10-15%Metabolism: hepaticT : 1-6 hours, with shorter half-lives in fast acetylatorsExcretion: urine (75-95%), feces, salivaInteraksi: The risk of hepatotoxicity may be increased in patients receiving isoniazid with rifampicin or other potentially hepatotoxic drugsIsoniazid is removed by dialysisLacy,F.C.,Amstrong,L.L.,Goldman,M.P.,Lance,L.L.,2008-2009,Drug Information Handbook 17th Ed .,American Pharmacists AssociationSweetman SC (Ed),2007, Martindale: The Complete Drug Reference. London: Pharmaceutical Press. Electronic version

Rifampicine Absorbtion: in GIT, food may delay or slightly reduce peakDistribution: protein binding 80%Metabolism: in the liver mainly to active 25-O-deacetylrifampicinExcretion: 60-65% in feces, ~30% in urine as unchanged drugT : 2-5 hours, prolong in hepatic impaiement and end-stage renal diseaseInteraction: rifampin may induce the microsomal enzymes in the liver that convert isoniazid to hepatotoxic metabolitesLacy,F.C.,Amstrong,L.L.,Goldman,M.P.,Lance,L.L.,2008-2009,Drug Information Handbook 17th Ed .,American Pharmacists AssociationSweetman SC (Ed),2007, Martindale: The Complete Drug Reference. London:Pharmaceutical Press. Electronic version Medscape, Drug Interaction Checker

Pyrazinamide Absorbtion: in GIT, slightly reduced peak serum concentrations when given with a high-fat mealDistribution: protein binding 50%Metabolism: primarily in the liver by hydrolysis to the major active metabolite pyrazinoic acid, which is subsequently hydroxylated to the major excretory product 5-hydroxypyrazinoic acidExretion: About 70% in the urine as metabolites and about 4% as unchanged drugT : 9-10 hours Interaction: combination with rifampine has been associated with severe and fatal hepatotoxic reactionResistance to pyrazinamide rapidly develops when it is used aloneLacy,F.C.,Amstrong,L.L.,Goldman,M.P.,Lance,L.L.,2008-2009,Drug Information Handbook 17th Ed., American Pharmacists AssociationSweetman SC (Ed),2007, Martindale: The Complete Drug Reference. London: Pharmaceutical Press. Electronic version

Vit B6 (Pyridoxine)To prevent deficiency vitamin caused by drug induced neuritis (ex: isoniazid)Dose Treatment :10-50 mg mg/24 hoursProfilaxis : 1-2 mg/kg/24 hoursPyridoxine 10 mg daily is usually recommended for prophylaxis of peripheral neuritis associated with isoniazid although up to 50 mg daily may be used

McEvoy, G. K. 2008. AHFS Drug Information. America Society of Health-System Pharmacist.

PYRIDOXINE SUPPLEMENTATION DURING ISONIAZID THERAPYDixie E. Snider, Jr., M.D.*Research and Development Branch, Tuberculosis Control Division, Bureau of State Services, Center for Disease Control,Public Heaith Service, Department of Health and Human Services, Atlanta, Georgia 30333

Vitamin Bs (pyridoxine) supplementation during isoniazid (INH) therapy is necessary in some patients to prevent the development of peripheral neuropathy. ln vivo pyridoxine is converted into coenzymes which play an essential role in the metabolism of protein, carbohydrates, fatty acids, and several other substances, including brain amines. INH apparently competitively inhibits the action of pyridoxine in these metabolic functions. The reported frequency of INH-induced neuropathy in various studies is reviewed and population groups at relatively high risk of developing this complication are identified. The routine use of pyridoxine supplementation to prevent peripheral neuropathy in high risk populations is recommended.

Use of Corticosteroids in Treating Infectious DiseasesSteven McGee,; Jan HirschmannDepartment of Medicine, University of Washington,Seattle-Puget Sound Veterans Affairs Health Care System, Seattle.Arch Intern Med. 2008;168(10):1034-1046Pulmonary tuberculosis :In these studies, 4 to 12 weeks of corticosteroid therapy diminished the duration of fever and cough, accelerated radiographic improvement, and promoted weight gain, especially among cachectic patients.In 2 trials, corticosteroids increased clearance of organisms from sputum, but they had no effect in 2 others.

Clinical review: A systematic review of corticosteroid use in infectionsJody Aberdein and Mervyn SingerCritical Care 2006, 10:203 (doi:10.1186/cc3904)Recommendation :Steroids may be considered for patients with pulmonary tuberculosis, particularly those with extensive disease, but not in HIV-positive patients.Grade of evidence II; grade of recommendation C.

Pyridoxine and the Isoniazid-Induced NeuropathyWilliam Mandel, M.D.San Francisco, CaliforniaAnnual Meeting, American College of Chest Physicians, NewYork City, May 29-June 2, 1957.

The isoniazid-induced peripheral neuropathy occurring in adult tuberculous patients results from a deficiency of biologically active pyridoxine. The deficiency is caused by the combination of isoniazid and pyridoxine to form a hydrazone which is excreted in the urine. It can be prevented by administration of pyridoxine whenever isoniazid is given. A 10 mg. dose of pyridoxine for each 100 mg. of isoniazid appears adequate to prevent both clinical and potential subclinical manifestations of pyridoxine deficiency. The administration of pyridoxine does not interfere with the antituberculous action of isoniazid.

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