Pharmacotherapeutics of Tuberculosis

1. V.S.Swathi
Assistant Professor
VIPT, Vizag
TUBERCULOSIS

2. Definition
 According to WHO, Tuberculosis is caused by
bacteria called Mycobacterium tuberculosis, that
most often affects the lungs and it is curable and
preventable

3. Epidemiology
 It is one of the top 10 causes of death world wide
 In 2017, 10 million people fell ill with TB, and 1.6
million died from this disease
 In India in 2017, 2.7 million people developed TB
disease and over 4, 00, 000 people died
 India accounts for 27% of global estimated cases,
25% of estimated deaths

4. Types
Active TB
It is illness in which the TB bacteria are rapidly multiplying and invading
different organs of the body
Typical symptoms include:
 Cough
 Phlegm
 Chest pain
 Weakness
 Fever
 Chills and sweating at night
A person with active pulmonary TB disease may spread TB to others by
airborne transmission of infectious particle coughed in to the air

6. Types
Miliary TB
 It is rare form of active disease that occurs when TB bacteria find their
way in to the blood stream
 In this form, the bacteria quickly spread all over the body in tiny
nodules and affect multiple organs at once
 This form is fatal one
Latent TB infection
 Many of those who are infected with TB do not develop overt disease
 Only it will give positive results for tuberculin skin test
 There is a ongoing risk that is latent infection may escalate to active
disease
 Risk increased by taking HIV medication which decreases our immune
response

7. Risk factors
 HIV positive cases
 Injecting drug users
 Solid organ transplantation
 Haematological malignancy
 Chronic renal failure on dialysis treatment
 Receiving anti TNF α treatment

8. Etiology
 Mycobacterium tuberculosis (Common)
 Mycobacterium bovis
 Mycobacterium africanum

9. Pathogenesis
Patients with active pulmonary TB, if they cough and sneeze, then droplet
nuclei containing bacteria generated
↓
Close contact persons inhale these droplets; TB is deposited in terminal
airways (alveoli) and ingested by macrophages
↓
TB spreads to remaining organs
Normal person ↓ ↓ Immunocomprimised patients
Cellular immune
response controls
infection preventing
reactivation
developing TB
Infection not
contained;
Patients are at risk
for developing TB

10. Clinical Presentation
 Cough for 3 weeks/ more productive cough
 Sputum usually mucopurulent
 Haemoptysis is not always feature
 Fever may be associated with night sweats
 Tiredness
 Weight loss
 Anorexia
 Malaise

12. Complications
 Haemoptysis
 Pleural effusion
 Emphysema
 Pnemothorax
 Pyopneumothorax
 Endobronchitis
 Bronchiectasis
 Tuberculosis laryngitis
 Corpulmonale
 Carcinomas
 Tuberculosis enteritis
 Military tuberculosis

13. Diagnosis
 Based on symptoms and risk factors
 Chest radiography
 Microscopy of sputum
 Culture of sputum
 Tuberculin skin test
 Blood based immunological tests
 PCR and DNA fingerprinting

15. Non Pharmacological Treatment
 BCG vaccination
 Oxygen therapy
 Physiotherapy of chest
 Ventilator support
 Surgery in case of carcinoma

16. Treatment Algorithm
1. Respiratory TB
Isoniazid, Rifampicin, Pyrizinamide and Ethambutal
for 2 months
↓
Isoniazid and Rifampicin for 6 months

17. 2. TB of Peripheral Lymphnodes
Isoniazid, Rifampicin, Pyrizinamide and Ethambutal
for 2 months
↓
Isoniazid and Rifampicin for 6 months

18. 3. Meningial TB
Isoniazid, Rifampicin, Pyrizinamide and Ethambutal
for 2 months
↓
Isoniazid and Rifampicin for 8 months
+
 Prednisolone 20-40mg if on Rifampicin otherwise
10-20mg (Adults)
 Prednisolone 1-2mg/ Kg (Children)

19. 4. Bone and Joint TB
Isoniazid, Rifampicin, Pyrizinamide and Ethambutal
for 2 months
↓
Isoniazid and Rifampicin for 6 months
 Occasionally, surgery may be needed to either relieve
spinal cord compression/ correct spinal deformities

20. 5. General/ Miliary/ TB
Isoniazid, Rifampicin, Pyrizinamide and Ethambutal
for 2 months
↓
Isoniazid and Rifampicin for 6 month
 Depending upon complication give individualised
therapy

21. 6. Pericardial TB
Isoniazid, Rifampicin, Pyrizinamide and Ethambutal
for 2 months
↓
Isoniazid and Rifampicin for 8 months
+
 Prednisolone 60mg/day in adult
 Prednisolone 1mg/kg/day in Children

22. 7. Latent TB
 Isonoazid for 6 months/
 Isoniazid +Rifampicin for 3 months
8. Multidrug resistant TB
 Do culture test
 Based on sensitivity of organism give specific
antibiotic

23. 9. TB in Children
 6 months regimen with reduced dose (Ethambutal is
not preferable in children)
10. TB in pregnancy
 6 months regimen with reduced dose (Streptomycin is
not preferable in pregnant women)
 Pyridoxine 10-15mg is needed to prevent adverse
effects of Isoniazid in women

24. 11. Renal disease patients
 Follow 6 months regimen
 Decrease the dose of nephrotoxic drugs such as Ethambutal
and Streptomycin
 Monitor renal function tests
12. Liver disease patients
 Follow 6 months regimen
 Monitor liver function tests
 In case of severe transaminitis, stop the treatment
temporarily until the LFT levels comes to normal

25. 13. HIV patients
 Extend regimen up to 9 months
 Check the interactions with retroviral drugs and adjust
the frequency or dose

26. Drugs used in treatment of Tuberculosis
Drug Category Mode of action Dose Adverse effects
Rifampicin Anti Tubercular drug Inhibits RNA transcription
by inhibiting DNA
dependent RNA polymerase
<50kg-450mg-OD
>50kg-600mg-OD
 GI disturbances
 Hepatitis
 Cutaneous reactions
 Flu like syndrome
Isoniazid Anti Tubercular drug Inhibit cell wall synthesis in
bacteria by inhibiting lipid
and DNA synthesis
300mg-OD  GI disturbances
 Hepatitis
 Cutaneous reactions
 Peripheral Neuropathy
Ethambutal Anti Tubercular drug Inhibit cell wall synthesis in
bacteria
15mg/Kg-OD  Retro tubular neutitis
 Arthralgia
 Hyperurecemia
 LFT changes
 Pruritis
Pyrizinamide Anti Tubercular drug Not Clear <50kg-1.5g-OD
>50kg--2g-OD
 GI disturbances
 Hepatitis
 Cutaneous reactions
 Hyperurecemia
Streptomycin Aminoglycoside Inhibit protein synthesis in
bacteria
<50kg-750mg-OD
>50kg- 1g-OD
 Tinnitis
 Ataxia
 Vertigo
 Renal impairment

27. Amicacin Aminoglycoside Inhibit protein synthesis in
bacteria
15mg/Kg-OD  Tinnitis
 Ataxia
 Vertigo
 Renal impairment
Kanamycin Aminoglycoside Inhibit protein synthesis in
bacteria
15mg/Kg-OD  Tinnitis
 Ataxia
 Vertigo
 Renal impairment
Ofloxacin Fluroquinolone Inhibit protein synthesis in
bacteria
400mg-BD  Abdominal distress
 Headache
 Tremulousness
 Vaginitis
 Fatigue
Ciprofloxacin Fluroquinolone Inhibit protein synthesis in
bacteria
750mg-BD  Abdominal distress
 Headache
 Tremulousness
 Vaginitis
 Fatigue
Azithromycin Macrolide antibiotic Inhibit protein synthesis in
bacteria
500mg-OD  Diarrhea
 Nausea
 Abdominal pain
 Loose stools
 Dyspepsia

28. Important points
 In pulmonary TB, Sputum examination and culture are the most
sensitive markers of treatment success
 Patients taking Rifampicin and Isoniazid should be non-
infectious within 2 weeks
 Isoniazid and Rifampicin should be taken before food to improve
absorption
 If the patient can not able to take oral preparation, then give IV
formulation of Rifampicin and Isoniazid
 If a patient does not become culture negative after treatment, that
indicates drug resistance and non adherence

29.  Good adherence is essential if treatment is to be successful and
checking this is difficult, especially when a patient is unwilling to
cooperate
 BCG vaccine does not protect against infection, but it prevents the
more serious forms of disease such as miliary TB and Meningeal TB
 Common problem with TB treatment include non adherence which
leads to resistance, relapse and failure of current treatment
 Factors affecting adherence to treatment include increase frequency of
drugs, more number of drugs, adverse affects and stopping of treatment
if their symptoms are relieved
 DOT means Directly observed therapy is used to observe whether the
patient taking medication correctly or not by health care professional
and it is used to the patients who are non adherent

31. Resources
 https://www.ncbi.nlm.nih.gov/pubmed/30738187
 https://www.ncbi.nlm.nih.gov/pubmed/30669990
 https://www.ncbi.nlm.nih.gov/pubmed/30382835
 https://www.ncbi.nlm.nih.gov/pubmed/30378646
 https://www.ncbi.nlm.nih.gov/pubmed/30376558