Mycobacterium Tuberculosis

Presented By : Saad Raza 2K20/PHAE/81

Assigned By: Sir Mazhar Ul Musatafa
Contents;
• Introduction of Tuberculosis
• Types of Tuberculosis
• Symptoms of Tuberculosis
• Risk factors/causes of Tuberculosis
• Diagnosis of Tuberculosis
• Prevention of Tuberculosis
• Treatment of Tuberculosis
Tuberculosis  (TB)
• Contagious disease move in shape/form of droplets form one person
to an other person.
• Communicable chronic granulomatous disease caused by
Mycobacterium tuberculosis.
• Involve respiratory tract lungs also affect on other organs like G.I.T
• Tuberculosis  (TB) is unlike most bacterial infections in that it usually
doesn't cause symptoms immediately. Even when it starts to make
you sick, symptoms come on very gradually and can often be
confused with other conditions.

• Most commonly, tuberculosis goes through three stages:

1. Primary TB infection
2. Latent TB infection
3. Active TB disease
Primary TB Infection

• Infection with M. tuberculosis begins when a person breathes in

airborne bacteria.

• This is more likely to happen if a person is in close contact with one or

more infected people with active TB who are coughing or sneezing.
Active Tuberculosis Disease
• In active tuberculosis, the bacteria multiply in the body, causing
noticeable symptoms.
• This is also when the disease can spread to others.
• The difference between active and latent TB is the amount of
organisms in the body, according to Dr. Reichman.
Latent TB
• latent TB has no symptoms and is not infectious, a tuberculin skin test
or blood test for TB — called the interferon-gamma release assay, or
IGRA — will be positive, showing that the person has not only been
exposed to tuberculosis, but has a latent (or "occult") infection with
the bacteria that causes tuberculosis.

• Treatment for latent TB involves less medication and a shorter

regimen than treatment of active TB.
Pulmonary tuberculosis (TB)

• Pulmonary tuberculosis (TB) is a serious infection caused by the

bacterium Mycobacterium tuberculosis (MTB) that involves the lungs
but may spread to other organs. TB is a contagious disease that can
infect anyone exposed to MTB.
 Tuberculous pleurisy
• Tuberculous pleurisy usually presents as an acute illness. The most
common presenting symptoms are nonporoductive cough and
pleuritic chest pain. Other symptoms include fever, night sweats,
weight loss, malaise, and dyspnea varying in severity according to the
size of effusion.
Cavitary Tuberculosis
• TB cavity is a pathologic gas-filled space in the lung parenchyma with
a border, or wall, which was caused by infection with a pathogen of
the M. tuberculosis complex.
• Cavitation is a dangerous consequence of pulmonary TB associated
with poor outcomes, treatment relapse, higher transmission rates,
and development of drug resistance. However, in the antibiotic era,
cavities are often identified as the extreme outcome of treatment
failure and are one of the least-studied aspects of TB.
• Cavitary TB carries a poor prognosis
Risk factors and of T.B
• Malnutrition
• Poor economy
• Illiteracy
• Alcoholism
• HIV
• Tobacco use
 Diagnostics methods of T.B
1. Blood test

2. Imagine test
• X-ray
• Sonography

3. Bronchoscopy

4. Sputum analysis

5. Lung biospy
6. Skin test =>    injecting Tuberculin on dermis  skin  0.1 ml => 48-72
hours =>bumpy structure 5mm indicate a T.B
Prevention of T.B
• Stop the spread of T.B

• If you have a latent infection, take all of your medication so it doesn’t become active and contagious.
• If you have active TB, limit your contact with other people. Cover your mouth when you laugh, sneeze, or
cough. Wear a surgical mask when you’re around other people during the first weeks of treatment.

• lIf you’re traveling to a place where TB is common, avoid spending a lot of time in crowded places with sick
people.

2 Get Vaccination to prevent T.B

• BCG

3. Maintain well balance diet to keep immune system strong

4. Don’t smoke or drink.

Treatment of Tuberculosis:
Classification

• First line drugs : Isoniazid, Rifampicin, Pyrazinamide, Streptomyces, Ethambutol

• 2nd line drugs: Flouroquinolones

• Oral Drugs: Ethionamide, Prothianamide, Cycloserine, Rifambutin, Rifampentin,

Salicylic acid.

• Injections: Amikacin, Kanamycin, Capreomycin.

Classified on the basis of Mechanism of
Action:
1) Inhibition of mRNA translation
E.g. Streptomyces
2) RNA Polymerase Inhibitors: Initiate protein synthesis
E.g. Rifampicin/ Rifambutin
3) Gyrase Inhibitors in DNA synthesis
E.g. Flouroquinolones
• +ve supercoiling correct into -ve supercoiling
4) Inhibition of Mycolic acid Synthesis
E.g. Isoniazid (INH), Ethambutol
 Classified on the basis of Mechanism of
Action:

5) Arabingalactone Synthesis Inhibitors

E.g. Ethambutol
6) Inhibition of Bacterial fatty acid synthesis
E.g. Pyrazinamide
7) Inhibit ATP synthesis
E.g. Bedaquinilline(Novel drug)
Isoniazid (INH)
Mechanism of action:
• (Prodrug) Inhibit a Mycolic acid Synthesis.

• INH => Inactive form convert into active form by catalase

peroxidaseMetabolites active ->  Covalent bonding -> Inhibit InhA
gene -> Inhibit Mycolic acid = Cell wall weak
Adverse effects
1. Peripheral neuritis: Tingling, Itching, rashes, Pain feelings at the
ending of nerves.

2. Hepatitis: Associated symptoms like Nausea, vomiting,  G.I.T

discomfort, annorrhea, Jaundic

3. CNS toxicity: Psychosis, seizures

Resistance:
• Overproduction of enzyme
• Mutation in inhA gene + Catalase peroxidase

Interaction:
Albumin hydrooxide, Phenytoin + Diazepam,  Theophylline
Rifampicin
• Mechanism of action:
Rifampicin -> bind with B-subunit of DNA-dependent RNA Polymerase
-> inhibiting protein synthesis -> Cell death (cidal effect)
ADRS
• Hepatoxicity, GIT disturbance, flue like symptoms, CNS (neuropathy),
hypersensitivity

Uses:
• T.B + Atypical microbes, leprosy

• Resistant Staphylococcus infection

• Brucellosis -> 6 weeks

• Combination: Rifampicin + Deoxycyclin

Ethambutol
• Synthetic derivative
• Tuberculostatic -> Inhibit  growing bacteria
• Only used for rapid growing/Multiplying bacteria

M.O.A
• Ethambutol Inhibits arabinosyl-Transferase III enzyme ->Disruption of
transport  of arabinose sugar -> Arabinogalactan biosynthesis impaird
-> Disruption Mycolic acidMultiplyingand Inhibit cell wall synthesis =
weak
ADRS
Optical Neuritis (Dose-dependent)
Visualization, colours, size of image
Peripheral Neuritis
Nausea, vomiting
 Ethionamide
• Prodrug activate by monoxigenase enzyme

M.O.A
• Inhibits the inhA gene -> Inhibit synthesis of Mycolic acid -> weak cell
wall

ADRS:
• Anorexia, Vomiting  Gastric Irritation, CNS depression, restlessness,
Endocrine effects like alopecia, gynocomastia, increase blood glucose
level and hyperthyroidism
Prothianamide
• Related to Ethionamide and same mechanism as Ethionamide 
o Passes C.S.F

ADRS:
GIT disturbance, arthralgia, myalgia gout
Para amino Salicylic Acid:
• Synthetic derivative Related to PABA + Sulphonamide
o Bacteriostatic at  high dose

M.O.A
 Inhibit a folic acid synthesis

Pharmacokinetics:
o Completely absorbed oral route
o Distribution in every cell/ tissue except C.S.F
o Excretion: Glomerular filtration + Tubular secretion
• AIMS of Treatment:

1. To kill dividing bacteria(bacilli)

2. To destroy the persistent

Advantages of Combination therapy

1. Delayed resistance
2. Reduce Toxicity
3. Shortens the treatment (cause)