2. Chronic granulomatous disease. Causative org M.TUBERCULOSIS.
Incidence in India 1.8 million people develop T.Bevery year of
which 0.8 million are infectious. Mode of Transmission Droplet
Infection Contact transmission 3. Droplets are expelled by coughing
or sneezing Tubercle bacilli then spread to other body organs
Tubercle bacilli may become dormant Even if extend beyond the lymph
nodes, TB lesion gethealed and calcified But in immounocomparmised
or undernourished becomeactive 4. Mycobacterium Infections Common
Infection Sites lung (primary site) liverbrain Kidneybone Less o2
tensionSymptoms Low grade fever Night sweats Fatigue Weight loss
Blood streaked productive coughMalaise 5. Other acid fast bacilli
Mycobateria other than M. tuberculosis c/s non tuberculosis/
atypical mycobacteria M.kanasasii- milder but chronic pulmonary
disease M.scrofulaceum cervical lymphadenitis M.avium complex
M.marinum- swimming pool granulommaAnti tubercular agents treat all
forms of mycobacterium 6. Different pools Dormant phase
Multiplication phase Semi dormant phase- R Inside macrophages-Z 7.
Antitubercular Therapy Effectiveness depends upon: Type of
infection Adequate dosing Sufficient duration of treatment Drug
compliance Selection of an effective drug combination 8.
Antitubercular Agents: Mechanism of Action Three Groups Cell wall
synthesis inhibitors cycloserine, ethionamide,isoniazid Protein
wall synthesis inhibitors streptomycin, kanamycin, capreomycin,
rifampin, rifabutin Other mechanisms of action 9. Anti-TB drugs
First line IsoniazidH Rifampin R Pyrazinamide Z Ethambutol E
Streptomycin S High efficacy Low toxicity Easily available Used in
new cases All are given orally except S(i.m.) All are
tuberculocidal exceptE(tuberculostatic) 10. SECOND LINENEWER DRUGS
Thiacetazone Ciprofloxacin PAS Ofloxacin Ethionamide Clarithromycin
Cycloserine Azithromycin Kanamycin rifabutin Amikacin Less
efficaciousmore toxic and expensive Used in resistant cases 11. HOW
DOES INH KILLS M. TUBERCULOSISPRODURG ACTIVATED BY CATALYSE EANZYME
PEROXYDASE (katG) UNABLE TO ENCODE ENOYL - ACP REDUCTASE OF FATTY
ACID SYNTHASE II NO CONVERSION OF UNSATURATED FATTY ACIDS TO
SATURATED FATTY ACIDS NO BIOSYNTHESIS OF MYCOLIC ACIDM.
TUBERCULOSIS CAN NOT SURVIVE 12. Resistance: Mutation in KatG
geneP.K: Dose300mg/day or 600mg 3 times weekly Orally well absorbed
Effective for actively growing org. Distributed in pleural,
peritoneal and synovial fluid CSF -20% in inflammed -100% Does not
binds to serum proteins Metabolised in liver by N-acetyltransferase
Excreted in urine 13. Side effects: Dose depended toxity Peripheral
neuritis: vitamin B6(10-40mg) Induce increase excretion of
pyridoxine Dec peripheral utilization of pyridoxine Hepatotoxicity
Allergic reactionsDI: Aluminium hydroxide dec. absorption PAS-
Inhibits metabolism INH dec metabolism of Phenytoin 14. Mech: It
binds to the b subunit of bacterial DNAdependent RNA polymerase
Bacteriocidal action Good sterilizing and prevent resistance Act
best on slow multiplying bacilli Resistance : rpo B gene 15. P.K:
Well absorbed orally Penetrates all tissues, TB cavities, Placenta
and CSF Excreted through liver in to bile Under go hepatic
circulation Metabolites excreted through faces Potent enzyme
inducer 600mg daily dose before breakfast 16. Side effect:
Hepatitis Red orange colour Urine DI: More interaction it inc.
metabolism of other drugs 17. ETHAMBUTOL : MECHANISM OF ACTION
EXACT MECHANISM : NOT KNOWN PROBABILITIES :ETHAMBUTOL BLOCKS
ARABINOSYL TRANSFERASE (ENCODED BY emb)NO POLYMERIZATION REACTION
OF ARABINOGLYCANINTERFERANCE IN CELL WALL SYSNTHESIS 18. Included
as 4th drug Oral BV -80% Wide distribution Daily dose 800-1000mg or
1600mg thrice a weekSide effects: 25mg for 9 months cause
retrobulbar neuritis impairing visual acuity Dec renal urease
excretion- gouty arthritis 19. Synthetic analogue of nicotinamide
acid ACTIVE IN ACIDIC PH (5.5) Excellent action against
intracellular bacilli Active against old non- replicating bacilli
due to theirlow membrane potential and disruption of membrane
potentil by pyrazinoic acid and acidic pH 20. PZA : MECHANISM OF
ACTION PZA enter through passive diffusion Bac.
PyrazinamidasePyrazinoic acidinhibit myobacterial fatty acid
synthase -IINTERFERANCE IN CELL WALL SYSNTHESIS 21. Well absorbed
Orally Wide distribution Metabolized by liver Excreted through
urine Half life 9-10hrsSide effects: Hepatotoxicity Daily dose
1500mg or 2000mg thrice in week 22. SULPHATE FIRST ANTI TUBERCULAR
DRUG DISCOVERED BY WAKSMAN IN 1943 ISOLATED FROM Streptomyces
griseus IM 1000 MG CONTAINS N - METHYL- L- GLUCOSAMINE CONTAINS
STREPTIDINE BACTERICIDAL ACTIVE AGAINST EXTRACELLULAR BACILLI 23.
Seldom use Cause gastric irritation, peripheral neuritis, optic
neuritis It block mycolic acids Tuberculostatic Acts on
extracellular and intra cellular organism Recommended dose 1g/day
24. It was once used as first line drug Low cost, more efficacy In
combination with INH But now it was used as 2nd line drug
Ototoxicity, hepatotoxicity, life threatening hypersensivity
reaction Tuberculostatic drugs 150mg once daily in combination with
INH 25. It is structural analogue of PABA Bacteriostatic Effect
against only M. Tuberculosis Fir second due to poor compliance
Cause crystalueria Hypersensivity reaction Dose 8-12g/day orally in
3 divided doses 26. Rifabutin is structural analogue of rifampicin
Same mech, resis, spectrum Less enzyme inducer Better activity on
M.avium complex It used alone or combination with PZA in
latenttubercular infectionADR: Neutopenia Skin rashes 27. National
Tuberculosis Progamme 1997 To dec therapeutic failure Patient poor
compliance Directly Observed treatment Strategy (DOTS) Intensive
phase Continuous phase 28. Intensive phase: period of 2-3months
Rapidly kill the bacteria To minimize the chance for devp.
Resistances Bring about sputum conversion Symptomatic relief
Continuous phase: 4-6months Remaining bacilli eliminated Minimize
the chance of relapse 29. Special Terms Fresh case Open case
Defaulter Treatment failure 30. Regime TB categoryIntensive
Contin.. phase phaseTotal durationNew smear +Ve New smear Ve but
serious ill New seriously ill extrapulmonary TB2(HRZE)6II2(HRZES)
5(HRE)Smear +ve retreatment group Treatment failure/relapse+
1(HRZE)3I 4(HR)8II New smear Ve pulmonary TB but not serious ill
Extra pulmonary TB2(HRZ)4(HR)6 31. MDR TB Resistance to both H and
R with or without resistance to other drugs. Incidence of H
resistance = 10-6 Incidence of R resistance =108 Incidence of
resistance to both = 1014 Therapy depends on earlier regime Dosage
Regularity Presence of associated diseases-HIV/AIDS, Diabetes,
Leukaemia 32. MDR: For INH : RMP+ PZA+ ETB for 12mon For RMP:
INH+PZA+ETB for 12months For Both : PZA+ETB+S+ ciprofloxacin for
12-18months Chemoprophylaxis: closed contact to infected patientsor
neonate of TB mother INH 300mg/day (5mg/kg/day children) for
6-12month INH (5mg/kg/day)+RMP(10mg/kg/day) for 6months 33. In
pregnancy All drugs are safe except E In hepatic dysfunction Z is
contraindicated In renal dysfunction S is contraindicated
