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.
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
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