This document provides information about tuberculosis (TB) and anti-tubercular drugs. It discusses how TB is caused by Mycobacterium tuberculosis and spreads through droplets from coughing or sneezing. Common symptoms include low-grade fever, night sweats, and cough. First-line drugs to treat TB include isoniazid, rifampin, pyrazinamide, ethambutol, and streptomycin. Second-line drugs are used to treat multi-drug resistant TB. Treatment involves a two month intensive initial phase followed by a four to six month continuation phase to prevent relapse. Directly observed treatment is recommended to ensure patient compliance and treatment success.

1. TUBERCULOSIS
&
ANTI TUBERCULAR DRUGS

2.  Chronic granulomatous disease.
 Causative org M.TUBERCULOSIS.
 Incidence in India 1.8 million people develop T.B
every 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 get
healed and calcified
 But in immounocomparmised or undernourished become
active

4. Mycobacterium Infections
Common Infection Sites
lung (primary site)
liver
brain
Kidney
bone
Less o2 tension
Symptoms
Low grade fever
Night sweats
Fatigue
Weight loss
Blood streaked productive cough
Malaise

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 granulomma
•Anti 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
 Isoniazid
H
 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 except
E(tuberculostatic)

10. SECOND LINE
NEWER DRUGS
 Thiacetazone
 Ciprofloxacin
 PAS
 Ofloxacin
 Ethionamide
 Clarithromycin
 Cycloserine
 Azithromycin
 Kanamycin
 rifabutin
 Amikacin
•Less efficacious
•more toxic and expensive
•Used in resistant cases

11. HOW DOES INH KILLS M. TUBERCULOSIS
PRODURG 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 ACID
M. TUBERCULOSIS CAN NOT SURVIVE

12.  Resistance: Mutation in KatG gene
P.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 reactions
DI:
 Aluminium hydroxide – dec. absorption
 PAS- Inhibits metabolism
 INH dec metabolism of Phenytoin

14.  Mech: It binds to the b subunit of bacterial “DNA
dependent 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 ARABINOGLYCAN
INTERFERANCE IN CELL WALL SYSNTHESIS

18.  Included as 4th drug
 Oral BV -80%
 Wide distribution
 Daily dose 800-1000mg or 1600mg thrice a week
Side 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 their
low membrane potential and disruption of membrane
potentil by pyrazinoic acid and acidic pH

20. PZA : MECHANISM OF ACTION
PZA enter through passive diffusion
Bac. Pyrazinamidase
Pyrazinoic acid
inhibit myobacterial fatty acid synthase -I
INTERFERANCE IN CELL WALL SYSNTHESIS

21.  Well absorbed Orally
 Wide distribution
 Metabolized by liver
 Excreted through urine
 Half life 9-10hrs
Side 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 latent
tubercular infection
ADR: 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 category
Intensive Contin..
phase
phase
Total
duration
New smear +Ve
New smear –Ve but serious ill
New seriously ill
extrapulmonary TB
2(HRZE)
6
II
2(HRZES) 5(HRE)
Smear +ve retreatment group
Treatment failure/relapse
+ 1(HRZE)3
I
4(HR)
8
II
New smear –Ve pulmonary TB
but not serious ill
Extra pulmonary TB
2(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 =10–8
 Incidence of resistance to both = 10–14
 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 patients
or 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