This interesting ppt contains Anti TB drugs topic for II MBBS CBME students Illustrated with pictures and flowcharts..

1. ANTITUBERCULAR
DRUGS
DR.V. Sathyanarayanan M.B.B.S., M.D., ACME
Professor of Pharmacology,
SRM MCH & RC,
INDIA

2. COMPETENCY
ACHIEVMENT
1:44
PH 1.44 Describe the first
line antitubercular drugs,
their mechanism of action,
side effects and doses.
1:45
PH 1.45 Describe the drugs
used in MDR and XDR
tuberculosis

3. OUTLINE
What is tuberculosis ?
Symptoms
First line drugs
Second line drugs
Newer drugs
Treatment of tuberculosis : Goals & General principles
Drug resistant tuberculosis
Management ofADR
Chemoprophylaxis
TB in pregnancy & in AIDS

4. SPECIFIC LEARNING OBJECTIVES
At the end of the session, learners shall be able to
• Classify Antitubercular Drugs correctly.
• Describe the mechanism of action, adverse effects, drug interactions
and therapeutic uses of first line Antitubercular drugs rightly.
• Describe the mechanism of action, adverse effects of Antitubercular
drugs used in MDR and XDR tuberculosis rightly.
• Enumerate the Antitubercular drug regimen with dosage accurately.

5. TUBERCULOSIS
A chronic
granulomatous disease
caused by
mycobacterium
tuberculosis
Major health problem
1/3 of world population
infected
Increased incidence
because of HIV spread
MDR tuberculosis is
emerging

12. SYMPTOMS
Persistent cough more than 3 weeks
Evening rise of temperature
Loss of appetite
Loss of weight

15. ORGANS AFFECTED
• Lungs
• Lymph nodes
• Bone
• Brain

17. AFTER INH (1952)
• Tuberculosis became curable

19. CLASSIFICATION

22. FIRST LINE DRUGS
INH (1952)
Rifampicin
(1962)
Pyrazinamide
Ethambutol
(1961)
Streptomycin
(1947)
Have high
efficacy and
low toxicity
Used routinely

25. SECOND LINE DRUGS
Thiacetazone Ethionamide PAS Kanamycin
Amikacin Capreomycin
Have low
efficacy or high
toxicity or both
Used in special
circumstances
only

26. NEWER DRUGS
Ciprofloxacin ,
Ofloxacin ,
sparfloxacin,
Moxifloxacin
Clarithromycin Azithromycin
Rifabutin Linezolid
Bedaquiline,
Delamanid

28. FIRST-LINE DRUGS

29. ISONIAZID

30. ISONIAZID
( INH )
Rapidly tuberculocidal
Inhibit mycolic acid synthesis in the bacterial cell wall
highly selective forTB bacilli
Given alone produces resistance by mutation
Orally absorbed & penetrates tissues
Metabolized by acetylation
Essential component of antitubercular regimen

31. ISONIAZID – ADR & D/I
Well tolerated by
most.
peripheral neuritis, hepatitis, convulsions,
rash, fever, optic neuritis
D/I – increase
phenytoin, warfarin,
carbamazepine,
diazepam levels
Aluminium
hydroxide inhibits
INH absorption

32. INH –
TOXICITY &
PREVENTION
Hepatotoxicity is seen in
older people and alcoholics,
reversible on stoppage of drug
Pyridoxine given along with INH to prevent
neurotoxicity

33. RIFAMPICIN

34. RIFAMPICIN
Semisynthetic derivative of
Rifamycin B
Binds with beta subunit of
DNA dependent RNA
polymerase of bacteria 
forms drug-enzyme
complex Inhibits mRNA
synthesis  bactericidal
Orally absorbed, food
interferes, has to be taken
in empty stomach
undergo enterohepatic
circulation
Attains high concentrations
in CSF

35. RIFAMPICIN - ADVERSE EFFECTS
hepatitis – dose
related,
reversible
Flu like
syndrome,
abdominal
syndrome,
cutaneous
syndrome,
respiratory
syndrome
Urine, secretions
become orange-
red(harmless )

36. RIFAMPICIN - Other uses
Important 1st line drug
in leprosy
Atypical mycobacterial
infections
2nd choice for MRSA
with doxycycline 1st line
for brucellosis,
prophylaxis of
meningococcal
meningitis, H.influenza
meningitis,
legionella pneumonia
Alternative drug for
anthrax

45. RIFAMPICIN –
DRUG
INTERACTIONS
it is a microsomal enzyme inducer  failure of
OC pills,
decreases levels of
sulfonylureas,
anti HIV drugs,
theophylline

46. RIFAMPICIN - ADVANTAGES
Acts best on
spurters and
persisters
Also act on
semidormant
bacilli
Has good
sterilizing
action
Has resistance
preventing
action
Widely
distributed

47. PYRAZINAMIDE

48. PYRAZINAMIDE
Chemically similar to
INH
Weakly tuberculocidal
More active in acidic
medium
Have good ‘sterilizing’
activity
Inhibit mycolic acid
synthesis
Widely distributed &
penetratesCSF well
ADR – hepatotoxicity,
hyperuricemia, fever,
arthralgia, flushing,
rashes, loss of diabetes
control
C/I – liver disease

49. ETHAMBUTOL

50. ETHAMBUTOL
Tuberculostatic As active as S
Inhibit arabinosyl
transferases and
Interfere with mycolic
acid incorporation into
cell wall
Resistance develop
slowly
ADR – loss of visual
acuity/colour vision due
to optic neuritis, rash,
fever, hyperuricemia
CAUTION – renal
disease
C/I - < 6 years of age

51. STREPTOMYCIN

52. STREPTOMYCIN
1st AntiTubercular drug, supplemental 1st line drug
Less effective than INH, Rifampicin
Acts only on extracellular bacilli
Penetrates tubercular cavities
Does not cross CSF
Resistance develops rapidly when used alone
Has to be given I.M
Has lower margin of safety
ADR - Ototoxicity, nephrotoxicity
Usage has declined ( used for the maximum of 2 months )

56. SECOND-LINE
DRUGS

57. SECOND LINE
DRUGS
• Thiacetazone
• Ethionamide
• PAS
• Kanamycin
• Amikacin
• Capreomycin
• Have low efficacy or high toxicity or both
• Used in special circumstances only

58. THIACETAZONE
Tuberculostatic, low
efficacy drug
Hepatotoxic 
discarded in the west
Low cost
Used with INH to
prevent DRUG
RESISTANCE
ADR – hepatitis, bone
marrow depression,
stevens johnson
syndrome, cerebral
edema
Reserve anti-TB drug
Should not be used in
HIV patients

59. PAS
Related to sulfonamide
Tuberculostatic
Delays resistance
Cause Hypersensitivity reactions,
GI distress
Very high dose ( 10 – 12 grams / day )
 Poor patient acceptability
Rarely used now ( only in resistantTB )

60. OTHER DRUGS
• ETHIONAMIDE – Hepatotoxic, cause allergy, neuritis,
gastric intolerance,CNS toxicity  seldom used 
used only in case of resistance
• CYCLOSERINE – An antibiotic with high CNS toxicity
(sleepiness, headache, tremor, psychosis, suicidal
tendencies, convulsions ) inhibits cell wall synthesis
• KANAMYCIN,AMIKACIN, CAPREOMYCIN – more
toxic antibiotics, reserve drugs in rare cases, given I.M

61. Second-line Anti-TB Drugs
Weaker than
first-line.
Cause adverse
reactions.
Difficult for
patient to
tolerate
Should be
taken for long
periods
Very expensive.
Cure rates are
much lower
than of patients
susceptible to
the first-line
drugs.

63. NEWER DRUGS

64. NEWER DRUGS
• CIPROFLOXACIN,OFLOXACIN, LEVOFLOXACIN,
SPARFLOXACIN, MOXIFLOXACIN – Combination
regimen in MDR tuberculosis, MAC infection in HIV
patients, good tolerability, penetrates cells
• MACROLIDES – CLARITHROMYCIN,AZITHROMYCIN
- MDR tuberculosis, non tubercular mycobacteria
• RIFABUTIN – Related to rifampicin, cross resistance
seen, More active on MAC in AIDS, weak enzyme
inducer
• ADR  cause rash, myalgia, uveitis, granulocytopenia

67. BEDAQUILINE
• Recent diarylquinoline drug
• Act by novel mechanism
• Inhibits mycobacterial ATP synthase  limits energy
production within the mycobacterial cell
• MICs are very low
• No cross resistance
• Well absorbed orally
• Due to redistribution terminal half life is very long ( 160
days )
• Only for MDR-TB
• ADR  NAUSEA, headache, arthralgia, prolongation
of QTc interval, hepatotoxic

72. TREATMENT OF
TUBERCULOSIS

74. THE GOALS OFTREATMENT
Kill dividing bacilli
– to relieve
symptoms and
non-contagious
Kill persisting
bacilli – to prevent
relapse
& to provide cure
Prevent
emergence of
resistance –
to prevent
treatment failure
• to provide adequate
response

75. Antitubercular
Therapy
Effectiveness depends upon:
Type of infection
Adequate dosing
Sufficient duration of treatment
Drug compliance
Selection of an effective drug combination

77. GENERAL
PRINCIPLES
Use Combinations of 2 or more drugs
Combination of INH and R is synergistic which shortens
the duration of therapy
Single daily dose of all 1st line drugs is preferred
Response is fast in the 1st few weeks
Follow DOTS (directly observed treatment short course )

79. SHORT COURSE CHEMOTHERAPY
Initial intensive phase – 2-3 months
Continuation phase – 4-6 months

83. TREATMENT OF
TUBERCULOSIS
INH, rifampicin,pyrazinamide ,
ethambutol – for 2 months
followed by
INH, Rifampicin For 4 months

84. RESISTANT
TUBERCULOSIS

87. MDRTB
(MULTIDRUG
-RESISTANT)
Some die in 4-16 weeks
1 or more 2nd line drugs for 12-24 months
Total of 5-6 drugs are given
Intensive phase ( 6-9 months )
Continuation phase ( 18 months )
H resistance – RZE for 12 months
H+R resistance – ZE+S/Kmc/Am/Cpr + Cipro/Ofl+- Etm

90. EXTENSIVELY DRUG RESISTENTTB
MDR-TB CASES
Resistant to at
least 4 cidal drugs
Virtually
untreatable
Mortality high
Intensive phase
( 6-12 months ) –
7 DRUGS
Continuation
phase( 18 months )
– 6 DRUGS

92. MANAGEMENT
OF SIDE EFFECTS

94. MANAGEMENT
OF ADR
Z – arthralgia ----- NSAIDs
H- peripheral neuritis ------ pyridoxine
E-optic neuritis ---- stop E
R - hemolysis, thrombocytopenia- stop R
H,R,Z – hepatotoxicity ---- stop all drugs till reaction
clears , add S+E or C

95. CHEMOPROPHYLAXIS

96. CHEMOPROPHYLAXIS
H 300mg daily for 6 months
or High dose of INH ( 15mg/kg) +ONCE A
WEEK Rifapentine (10 mg/kg) for 3 months

98. ROLE OF
CORTICOSTEROIDS

99. ROLE OF
CORTICOSTEROIDS
Ordinarily should not be used
Used under chemotherapeutic cover in
MiliaryTB
Hypersensitivity reactions
MeningealTB, renalTB, pleural effusion
Severe forms in AIDS patients
CONTRAINDICATED IN INTESTINAL TB

100. TB IN
PREGNANCY

101. TB IN
PREGNANCY
H,R, Z, E  SAFE
2HRZE +4 HRE
S is contraindicated ( Ototoxic )
To Avoid Z 2HRE +7HR
During lactation baby should be watched, infant has to
be given BCG vaccine + INH prophylaxis,+ Pyridoxine

108. TUBERCULOSIS
IN AIDS
More severe
ADR and drug interactions more common
ATT duration longer
HRZE for 2 months +HRE for 4- 7 months
Pyridoxine to be added
Also receive co-trimoxazole
Rifabutin for Rifampicin

111. MAC INFECTION IN
AIDS
• Clari/azithro + E + Rifabutin + one FQ for 2-6 months
followed by clari /azithro + E/ one FQ for 12 months

114. THEME :“STOPTB IN MY LIFETIME.”

119. THANKYOU