2. Introduction
o Disease
o Bacteria
Epidemiology
Symptoms
Diagnosis
Classification
Mechanism of Drugs
Treatment
Resistance
Bibliography
2
3. TUBERCULOSIS is an infectious disease caused by
Mycobacteria; Mycobacterium tuberculosis &
Mycobacterium bovis.
MODE OF TRANSMISSION
Inhalation
Ingestion
Inoculation
Transplacental
3
4. Major portion of tubercle bacilli become
intracellular, so it is inaccessible for most
of the antibiotics as they cannot penetrate
easily into the macrophage.
It was once considered to be an incurable
disease but now it is curable by a number
of chemotherapeutic agents.
Macrophage with
Tubercle bacilli
4
5. Gram +ve , aerobic acid fast bacilli.
Resistant to disinfectant , detergent & common
antibiotics.
Capable of intracellular
growth.
Person to person spread
is by aerosol.
Human are the only
natural reservoir.
5
7. Tuberculosis (TB) is one of the top 10 causes of death
worldwide.
In 2017, 10 million people fell ill with TB.
In 2017, an estimated 1 million children became ill with TB
and 230 000 children died of TB (including children with HIV
associated TB).
Multidrug-resistant TB (MDR-TB) remains a public health
crisis and a health security threat. WHO estimates that there
were 558 000 new cases with resistance to rifampicin.
An estimated 54 million lives were saved through TB
diagnosis and treatment between 2000 and 2017.
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10. FIRST line drugs[HRZES]
F Field defects causing drug i.e. Ethambutol [E]
I Isoniazid (INH) [H]
R Rifampicin [R]
S Streptomycin [S]
T Twice a day given drug i.e. Pyrazinamide [Z]
10
11. SECOND line drugs
S Salicylates like Para-amino salicylate
E Ethionamide
C Cycloserine
O Old drug: Thiacetazone
N Newer Drugs: Quinolones e.g. Ciprofloxacin,
Levofloxacin , gatifloxacin and Moxifloxacin
Macrolides e.g. Clarithromycin , Azithromycin
D Drugs rarely used: Aminoglycosides e.g. Capreomycin ,
Kanamycin , Amikacin
Rifabutin
11
12. First line drugs:- kill active bacteria, important in
the early stages of infection.
Second line drugs:- hinder bacterial growth.
- Strengthen treatment in the case of resistant
bacteria.
- Less efficient and generally more toxic than first
line drugs.
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14. 14
The activated form of isoniazid - forms a covalent complex with an
inh-A (Acyl carrier protein -AcpM) and KasA, a ßketoacyl carrier
protein synthetase, which blocks mycolic acid synthesis and kills
the cell.
18. 18
• Interference with the initiation complex of peptide formation.
• Breakup of polysomes into nonfunctional monosomes.
• Misreading of mRNA,
which causes incorporation
of incorrect aminoacids into
the peptide, resulting in a
Non functional or toxic
protein.
19. Drug Bactericidal/
Bacteriostatic
Mechanism of action Side Effects
Isoniazid Bactericidal to rapidly
dividing bacteria and
bacteriostatic to slowly
dividing bacteria
Inhibit Mycolic acid
Synthesis , also inhibits
DNA, RNA & various
oxidative enzymes.
Rash, abnormal liver
function, anaemia,
peripheral neuropathy,
optic neuritis, mild
CNS effects,
gynaecomastia etc
Rifampicin Bactericidal Inhibits bacterial DNA
DEPENDENT
RNA POLYMERASE.
Fever, immune
reactions, GI irritation,
liver damage, can
cause tears and urine
to turn red/orange etc
Streptomycin Bactericidal Inhibit protein synthesis
of mycobacteria in
the ribosome
Damage to the ears,
nausea, rash,
vomiting, Vertigo etc
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20. Drug Bactericidal/
Bacteriostatic
Mechanism of action Side Effects
Ethambutol Bacteriostatic Inhibits polymerisation
of arabinoglycans of
cell wall by inhibiting
arabinosyl transferase.
Decrease in visual acuity,
Colour blindness and
other visual defects, joint
pain, nausea, vomiting,
fever, malaise, headache,
dizziness etc
Fluoro-quinolones Bactericidal Inhibiting DNA gyrase
and topoisomerase IV
resulting in the
inhibition of DNA
replication
Heart problems, swelling
of face and throat,
shortness of breath, rash,
loss of consciousness etc
Pyrazinamide Bacteriostatic,
Bactericidal
Inhibits mycobacterial
fatty acid synthetase 1
enzyme & disrupts
mycolic acid synthesis
needed for cell wall
synthesis.
Joint pain, nausea,
vomiting, rash, malaise,
fever, Photosensitivity etc
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21. GOALS –
Kill dividing bacilli.
Kill persisting bacilli.
Prevent emergence of resistance.
WHO , has recommended DOTS (Directly Observed
Therapy for Short course) wherein the anti-TB drugs
are given under direct supervision of medical
professional 3 days a week.
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23. CATEGORY PATIENT TYPE DURATION OF
TREATMENT
DRUG REGIMEN
CATEGORY 1 New Untreated
SMEAR +VE
Pulmonary T.B
6 MONTHS RIPE For 2
Months , Then RI
For 4 Months.
CATEGORY 2 SMEAR +VE
Re-treatment
Group (Relapse Or
Treatment Failure)
8 MONTHS RIPES For 2
Months; Then RIPE
For 1 Month; Then
RIE For 5 Months.
CATEGORY 3 SMEAR –VE
Pulmonary T.B Or
Less Severe Extra
Pulmonary TB
6 MONTHS RIP For 2 Months
Then RI For 4
Months
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24. Mono-resistant: Resistance to a single drug.
Poly-resistant: Resistance to more than one drug, but
not the combination of isoniazid and rifampicin.
Multidrug-resistant (MDR): Resistance to at least
isoniazid and rifampicin.
Extensively drug-resistant (XDR): MDR plus
resistance to fluoroquinolones and at least 1 of the 3
injectable drugs (amikacin, kanamycin, capreomycin).
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25. Reduced entry of antibiotic into pathogen.
Enhanced export of antibiotic by efflux pumps.
Release of microbial enzymes that destroy the
antibiotics.
Alteration of microbial proteins that transform pro-
drugs to the effective moieties.
Alteration of target proteins.
Development of alternative pathways to those
inhibited by the antibiotics.
25
26. Goodman, L.S., 2011. Goodman and Gilman's the
pharmacological basis of therapeutics (pp. 1245-). New York:
McGraw-Hill.
Tripathi, K.D., 2018. Essentials of medical pharmacology.
(Pp. 815-830) Jaypee Brothers Medical Publishers, New
Delhi.
Garg, G.R. and Gupta, S., 2018. Review of pharmacology. (Pp.
423-426) Jaypee Brothers Medical Publishers (p) Limited.
https://www.who.int/en/news-room/fact-
sheets/detail/tuberculosis
https://www.google.co.in/search?source=hp&ei=HC9XXPC1
B4n4vAS1oKr4BA&q=tuberculosis&oq=tuber&gs_l=psy-
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