Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis that primarily affects the lungs. It spreads through droplets in the air from coughing or sneezing. Risk factors include HIV/AIDS, diabetes, and malnutrition. Diagnosis involves chest x-rays, sputum smear and culture tests, tuberculin skin tests, and interferon-gamma release assays. Treatment uses a combination of antibiotics over 6-9 months including isoniazid, rifampin, pyrazinamide, and ethambutol. The WHO recommends the DOTS strategy to directly observe treatment and ensure adherence and cure. Drug-resistant TB requires longer and more toxic treatment regimens.

1. TUBERCULOSIS
Guided By:
Dr.Devang B. Sheth
Department of Pharmacology
B.K mody Govt. pharmacy college
Prepared By:
Krunal A. Goyani
M.Pharm, Sem-I
Enrolment No.-152120803008

2. INDEX
 Introduction
 Epidemiology
 Ethology
 Risk factor
 Transmission
 Pathophysiology
 Symptoms of tuberculosis
 Diagnosis step
 Anti-tubercular drug
 Treatment and management

3. INTRODUCTION
Tuberculosis is granulomatous disease and major health problem in
developing countries.
As per “WHO” Tuberculosis also call “TB” Is An Infectious Bacterial
Disease Caused By Mycobacterium Tuberculosis, Which Most Commonly
Affects The Lungs. It Is Transmitted From Person To Person Via Droplets
From The Throat And Lungs Of People With The Active Respiratory
Disease.
Tuberculosis ancient disease remains a leading infectious killer of mankind.
TB commonly was known as “consumption” because of the pronounced
weight loss that it caused Other common names included “wasting disease”
and the “white plague.”
To Aggravate The Situation Is The Immunocompromised Patient.

4. EPIDEMIOLOGY

5. EPIDEMIOLOGY
Globally In 2013, an estimated 9.0 million people developed TB and 1.5
million died from the disease,360 000 of whom were HIV positive ,480 000
of them being affected by multidrug-resistant (MDR) Mycobacterium
tuberculosis strains. On average, an estimated 43,200 of patients with MDR-
TB had extensively drug resistant TB (XDR-TB).
There were 80 000 deaths from TB among HIV-negative children in the same
year.
TB is slowly declining each year and it is estimated that 37 million lives
were saved between 2000 and 2013 through effective diagnosis and
treatment.

6. EPIDEMIOLOGY

7. EPIDEMIOLOGY
India is the second-most population country in the world one fifth of the
global incident TB cases occur in India annually.
WHO statistics for 2013 giving an estimated incidence figure of 1.96 million
cases of TB for India out of a global incidence of 9 million.
India’s TB control programme is on track as far as reduction in disease
burden is concerned. There is 42% reduction in TB mortality rate by 2012 as
compared to 1990 level. Similarly there is 51% reduction in TB prevalence
rate by 2012 as compared to 1990 level.

8. ETIOLOGY
TB infection caused by tubercle bacilli, which belong genus to
mycobacterium.
Mycobacterium, from the greek “mycos” refers to mycobacteria’s waxy
appearance, which due to highly lipid contain cell wall with slender shape
bacillus.
Ziehl-neelson stain or the fluorochrome stain must be used instead gram
stain.
Main species of mycobacterium cause tuberculosis.
Typical mycobacteria
1. Mycobacterium tuberculosis
2. Mycobacterium hominis
3. Mycobacterium bovine
Atypical mycobacteria
1. Saprophytic mycobacteria
2. Mycobacterium avium

12. RISK FACTOR
A healthy immune system can often successfully fight TB bacteria,
but your body can't mount an effective defence if your resistance is
low. diseases and medications can weaken your immune system,
including :
HIV/AIDS
Diabetes
Chemotherapy
Malnutrition
Advanced age
Alcoholism
Immunosuppressive medications
Immigrant (From area with high TB incidence )

13. TRANSMITTION
Tuberculosis Is Transmitted Mainly By Droplet Infection And Droplet
Nuclei. Generated By Sputum-positive Patient With Pulmonary Tuberculosis.
To Transmit Infection , The Particles Must Be Fresh Enough To Carry A
Viable Organism.

14. PATHOPYSIOLOGY

15. Type of tuberculosis infection
Pulmonary TB :
1. Primary Tuberculosis :
The infection of an individual who has not been previously infected or
immunized is called Primary tuberculosis or Ghon’s complex or
childhood tuberculosis.
Lesions forming after infection is peripheral and accompanied by hilar
which may not be detectable on chest radiography.
2. Secondary Tuberculosis :
The infection that individual who has been previously infected or
sensitized is called secondary or post primary or reinfection or
chronic tuberculosis.

17. SYMPTOMS OF TUBERCULOSIS
coughing Cough with blood Fever
Fatigue Weight loss Chest pain
Chills Night sweats Feel hungerless

18. DIAGNOSTIC STEPS
BACTERIOLOGIC
EVALUATION
HISTORY AND CLINICAL
EXAMINATION
RADIOGRAPHIC
FEATURES

19. “The first rule of TB diagnosis: is to think of TB….”
The physician Include TB in his differential diagnosis when history &
symptoms are consistent with TB diagnosis THEN he will recommended
appropriate diagnostic tests to prove the infection.
1

20. 2
Chest X-ray
Tuberculosis creates cavities visible in x-rays like this
one in the patient's right upper lobe. Abnormalities on chest
radiographs may be suggestive, but are never diagnostic of
TB. However, chest radiographs may be used to rule out.

21. BACTERIOLOGIC
EVALUATION
3

22. Specimen:
Fresh Sputum ,Gastric Washing , Urine, Pleural Fluid , Cerebrospinal
Fluid , Biopsy Material , Blood.
Decontamination & concentration of specimens :
Sputum Specimens (Non Sterile) Should Be :
 Liquefied with N-acetyl-L-cysteine.
 Decontaminated with NaOH.
 Neutralized with buffer.
 Concentrated By Centrifugation.
Specimens processed in this way can be used for acid fast stains and for
culture.

23. Acid Fast Bacilli “AFB”
Smear Test
Specimen examined for acid fast bacilli by staining:
Ziehl-neelson Acid Fast
Staining
Auramine-rhodamine
Staining

24. Acid Fast Bacilli “AFB”
Culture Test
 Löwenstein-Jensen (egg and also contain high concentrations of malachite
green to overcome contamination with other bacteria).
 Middlebrook 7H10 & 7H11 are ( contain defined vitamins, salts, catalase,
glycerol, oleic acid and albumin to neutralize toxic effect of fatty acids).
Acid fast bacilli (AFB) smear microscopy and culture are still the “gold
standards” for the diagnosis of active TB but this conventional methods for
culture required (6-8) weeks for isolation from media.

25. Tuberculin skin Test
Purified Protein Derivative (PPD) :
Is a concentrated filter of broth in which tubercle bacilli have grown
for 6 weeks(old).
 Measuring The Size Of Induration 48-72 Hours.
 Positive If ≥ 10 mm Induration Size.
 Standard Method For Screening & Measuring Of A Person’s Cellular
Response.
1 2

26. Positive Reaction
Person Infected In The Past Or Latent TB Infection.
After BCG Vaccination, But This May Last For Only 3-7 Years .
Persons Are Retested 2 Weeks Later; Their PPD Skin Test “Boosted” By The
Recent Antigen Injection. High Risk Of (Endogenous Infection)

27. Negative Reaction
 Persons Who Have NEVER Been Infected, They Are Not Subject To That
Risk, Though They May Become Infected From An External Source
(Exogenous Infection)

28. γ-Interferon release assays (GIRA)
 Test Rely On The Fact That T-Lymphocytes Will Release γ-interferon
When Exposed To Specific Antigens. These Tests Are Mostly Developed
For The Field Of Tuberculosis Diagnosis, But In Theory, May Be Used In
The Diagnosis Of Other Diseases Which Rely On Cell-mediated
Immunity.

29.  FIRST LINE DRUG
1. Isoniazid (H)
2. Rifampin (R)
3. Pyrazinamide (Z)
4. Ethambutol (E)
5. Streptomycine (S)
 SECOUND LINE DRUG
1. Thiacetazone (Tzn)
2. Paraaminosalicylic acid (PAS)
3. Ethionamide (Etm)
4. Cycloserine (Cys)
5. Kanamycine (Am)
6. Capriomycine (Cpr)
NEWER DRUG
1. Ciprofloxacin
2. Ofloxacine
3. Clarithromycine
4. Azithromycine
5. Rifabutine
6. Bedaquiline(Recently)
ANTI-TUBERCULAR DRUG

30. ANTI-TUBERCULOSIS DRUGS BY GROUP

31. ISONIAZIDE(H)-Pyridine hydrazide.
Mechanism of Action
Action
 Bacteriostatic for resting mycobacteria, bactericidal for proliferating
mycobacteria.

32. Mechanisms of Resistance
 Mutation or deletion of katG gene.
 Mutation in kasA gene.
 Over-expression of the inhA & aphC gene (detoxify organic peroxide)
Dose
 5 mg/kg (300 mg),OD
 Oral / im / iv
Pharmacokinetics
 Oral BA ~ 100%.
 Only ~10% is protein bound
 Metabolised in liver by Arylamine N-acetyltransferase2 (NAT2).
 Excreted in urine as Acetylisoniazid & Isonicotinic acid.
Adverse reaction
 Peripheral neuritis
 Liver damage.
 Optic neuritis, Convulsions, Hypersensitivity reactions

33. RIFAMPICINE(R)-Rifamycine
Action
 Bactericidal for mycobacteria; also effective against most Gram-positive
and many Gram-negative bacteria.
Mechanism of Action
Binds to the β subunit of DNA-dependent RNA polymerase (rpoB) .
Inhibit RNA synthesis
Mechanisms of Resistance
 Mutation at codons site of rpoB gene.
Dose
 10 mg/kg (600 mg),OD
 Oral

35. Pharmacokinetic
Absorption is variable-Oral bioavailability Rifampicin (68%) &
Rifabutin (20%)
Food- ↓Rifampicin absorbtion but no effect on Rifabutin.
High fat diet- ↑Rifapentin absorption.
Half life - Rifampicin→2-5hrs, Rifabutin →32-67hrs, Rifapentine →14-18hrs
Adverse reaction
 Flu like symptoms.
 Thrombocytopenic purpura.
 GIT disturbances &
 Harmless orange tint to saliva, sweat & tears

36. PYRAZINAMIDE(Z)-Nicotinamide analogue
Action
 Bactericidal for actively dividing intracellular mycobacteria.
Main effect occur in first few months.
Mechanism of Action
PYRAZINAMIDE
Enter M.tuberculosis
Pyrazinoic acid (POA+)
Kill the mycobacteria
Pyrazinamidase/Nicotinamidase
Inhibit FAS
Inhibit growth mycobacteria
Go extra-
cellular

38. Mechanisms of Resistance
Point mutation in pncA gene (encodes Pyrazinamidase)
Dose
 1,000 mg (40–55 kg)
 1,500 mg (56–75 kg)
 2,000 mg (76–90 kg)
Abs/Distrb/Elim
Given orally, widely distributed, crosses into the CSF, excreted in urine.
Adverse reaction
 Sideroblastic Anemia.
 Hepatotoxic &
 Joint pains

39. STREPTOMYCINE(S)-aminoglycoside
Action
 Bactericidal for actively dividing intracellular mycobacteria.
Mechanism of Action
Bind 30S ribosomes.
False pair of codon:anticodone
False reading of genetic cord
Inhibit protein synthesis

41. Dose
 1,000 mg (40–55 kg)
Pharmacokinetics
 Very poor oral bioavailability hence given in injectable form.
 Distributed extracellularly mainly.
 Excreted unchanged in urin
Adverse reaction
 Ototoxicity
 Nephrotoxicity
 Neuromuscular blockade- ↓release of Ach by inhibiting fusion of
vesicles with terminal membrane

42. ETHAMBUTOL(E)-Ethylenediamine derivative
Action
 Tuberculostatic drug.
Mechanism of Action
Inhibit Arabinosyl transferase-Ш enzyme
Disrupt the transport of Arabinose sugar
Arbinogalactan biosynthesis impaired
Disruption in mycobacterial cell wall formation

44. Dose
 1,000 mg (40–55 kg)
Mechanisms of Resistance
 Mainly by mutation in codon of embB gene.
 KatG mutation Co-occurance of Ethambutol & Isoniazid resistance.
Pharmacokinetics
 Oral bioavailability ~80%.
 ~10-40% bound to plasma proteins
Adverse reaction
 Optic neuritis
 Colour blindness

45. FLASH CARD OF ANTITUBERCULAR DRUG

46. TRATMENT & MANAGMENT
DOTS (Directly Observed Treatment, Short-Course)
 DOTS is the name given to the tuberculosis control strategy
recommended by the World Health Organization.
 According to WHO, “The most cost-effective way to stop the spread of
TB in communities with a high incidence is by curing it. The best
curative method for TB is known as DOTS.
 DOTS is an interventional strategy developed by Dr. Karel Styblo and
is recommended by the WHO as the strategy that ensures cure of TB.
 A DOT Lay Worker meets with clients to help with TB medication, and
provide support and education. Watching clients swallow each dose of
anti-TB medication.

47. The five elements of DOTS
1. Political will.
2. Case detection through quality-assured bacteriology.
3. Standardized treatment, with supervision and patient support.
4. An effective drug supply and management system. &
5. Systematic monitoring and accountability for every patient
diagnosed.

48. Medication
1. INTENSIVE PHASE ( 2-3 months)
 Under direct supervision of a health worker or trained
person
2. CONTINUATION PHASE (4-6 months)
 A multiblister combipack with drugs for 1 week is given
of which the first dose is taken under supervision

49. H: Isoniazid (300 mg), R: Rifampicin (600 mg), Z: Pyrazinamide (1500 mg),
E: Ethambutol (1000 mg), S: Streptomycin (1000 mg)
1.Patients who weigh 60kg or more receive additional Rifampicin
150mg.
2.Patients who are more than 50 years old receive Streptomycin
500mg.
3.Patients who weigh less than 30kg receive drugs as per Paediatric
weight band boxes according to body weight.
Category Type of Patient Regimen Duration in months
Category I
Color of box:
RED
New Sputum Positive ,
Seriously ill sputum negative,
Seriously ill extra pulmonary,
2 (HRZE)3,
4 (HR)3
6
Category II
Color of box:
BLUE
Sputum Positive relapse,
Sputum Positive failure
Sputum Positive treatment after
default
2 (HRZES)3,
1 (HRZE)3
5 (HRE)3
8

50. ADVANTAGES
The client is supported to successfully complete the full course of
medication
The client is monitored closely for side effects of medications and supported
to work through the side effects appropriately
The client is encouraged and support.
Reduces the possibility of tuberculosis germs becoming resistant to the
medication.

51. DRUG RESISTANT TB
1. Multiple drug resistance TB (MDR-TB)
 An MDR-TB suspect who is sputum culture positive and whose TB
is due to Mycobacterium tuberculosis that are resistant in-vitro to at
least isoniazid and rifampicin.
2. Extensively Drug Resistant TB (XDR–TB)
 is a subset of MDR-TB where the bacilli, in addition to being
resistant to R and H, are also resistant to any fluoroquinolones and
any one of the second-line injectable drugs (namely Kanamycin,
Capreomycin, or Amikacin).

52. TREATMENT
STANDARDISED TREATMENT REGIMEN
For the treatment of MDR-TB cases
6 drugs
- kanamycin - ofloxacin
- ethionamide - pyrazinamide
- ethambutol - cycloserine
for 6-9 months of the Intensive Phase

53. TREATMENT
 CONTINUATION PHASE-
4 drugs
Ofloxacin
Ethionamide
Ethambutol
Cycloserine
for 18 months.

54. DOTS DOTSPLUS
1. Standardised treatment throughout
the duration of treatment
1. Individualised treatment regimens
when mycobacterial culture and
anti-tuberculosis drug sensitivity
reports become available
2. Diagnosis by microscopy 2. Diagnosis by DSC
3. Reliable supply of a limited number
of reliable first-line drugs
3. Provision of a wide-range of
second-line anti-tuberculosis
drugs.
4. Continuous evaluation of patient
notifications, smear results, and
outcome
4. Three monthly culture and anti-
tuberculosis drug susceptibility
testing and more extensive
programmatic reviews
5. Commitment from the local
government
5. Additional support from external
governments and agencies.

55. REFERENCE
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56. THANK YOU