Thank you for the presentation on the pharmacotherapy of tuberculosis and leprosy. I appreciate you taking the time to educate us on these important topics.

1. Presented by-
Mukul Sunil Tambe
M. Pharm Sem. II
Pharmacology
Roll No. 8
*PHARMACOTHERAPY
OF TUBERCULOSIS
AND LEPROSY
Tuesday, October 10, 20171

2. *INTRODUCTION OF TB:
*What is TB?
*TB is a disease caused by infection
with a bacteria called
Mycobacterium tuberculosis.
Tuesday, October 10, 20172

3. *Characteristics of M. tuberculosis
*Slightly curved, rod
shaped bacilli
*0.2 - 0.5 microns in
diameter; 2 - 4 microns in
length
*Acid fast - resists
decolorisation with
acid/alcohol
*Multiplies slowly (every
18 - 24 hrs)
*Thick lipid cell wall
*Can remain dormant
for decades
*Aerobic
*Non-motile
Tuesday, October 10, 20173

4. *How is TB Transmitted?
*Person-to-person
through the air by a
person with TB disease
of the lungs
 Less frequently transmitted by:
• Ingestion of Mycobacterium bovis found in
unpasteurized milk products
• Laboratory accident
Tuesday, October 10, 20174

5. Tuesday, October 10, 20175

6. Chiclls
THINK TB !
Chills
Fatigue
Difficulty
in
Breathing
Anorexia
Loss
of Appetite
Night sweats
Coughing
up Blood
EVEN IF A SKIN TEST IS
NEGATIVE…..
Fever
Tuesday, October 10, 20176

7. *DIAGNOSIS
Radiology (commonly
chest x-rays)
A tuberculin skin test
Blood tests
Microscopic examination
and microbiological culture
of body fluids.
Treatment is difficult and
requires long courses of
multiple antibiotics.
Tuesday, October 10, 20177

8. *TREATMENT OF T.B.
*Divided into Chemoprophylaxis and Treatment of
active disease.
*Careful diagnostic studies must always precede
therapy.
Tuesday, October 10, 20178

9. *CHEMOPROPHYLAXIS
*To prevent clinically active disease in people already
infected.
*Given only to those who will derive the greatest benefit and
the least risk.
*300mg Isoniazidonce daily for 6 to 12 months
Tuesday, October 10, 20179

10. *TREATMENT OF ACTIVE
DISEASE
FIRST line drugs[HRZSE]
• 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]
(All other first line antituberculars are given
once a day) Tuesday, October 10, 201710

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
• Rifabeutin
Tuesday, October 10, 201711

12. *MECHANISM OF ACTION
ETM
STM
Tuesday, October 10, 201712

13. *SIDE EFFECTS
*INH: Iron accumulation in Mitochondria
Neuritis (Peripheral)
Hepatitis
*Ethambutol : Eyes (Decreased Visual activity, Optic neuritis,
Red- Green Discrimination)
*Pyrazinamide: Hyperuricemia (Gout)
*Rifampicin: Red-Orange metabolites
Vitamin B6
Tuesday, October 10, 201713

14. *Recommended Doses Of First line Anti-
Tubercular Drugs For Adults
Tuesday, October 10, 201714

15. *TREATMENT OF T.B.
*Therapy requires at least two
effective drugs concurrently.
*If the treatment is appropriate
improvement is usually seen
within 2 weeks.
*Continue treatment for at least
3-6 months after the sputum
becomes negative.
*Never use 1 drug and never
add a single drug to a failing
regimen.
*Minimum length of therapy is
6-9 months.
*Initiation phase of 2 months.
*Continuation phase of 4-7
months.
*Combining daily therapy with
intermittent therapy.
Tuesday, October 10, 201715

16. DRUG Mechanism of
Action
Adverse effects Drug
Interactions
Cycloserine Inhibition of Alanine
racemerase & D-alanine
ligase
Headache, Irritability,
Depression,
Psychosis,
Convulsions
With Tramadol,
increases risks of
Tremors
PASA Amino salicylic acid is
decarboxylated to produce
CO2 & 3-aminophenol
Cell was synthesis is
disrupted
Hepatitis, Diarrhea,
Haemolysis
Slows the phenytoin
elimination
Ethionamide Inhibits Mycolic acid
synthesis
Dizziness, Loss of
appetite, metallic
taste
Worsens liver damage
along with Rifampin.
Tuesday, October 10, 201716
*SECOND LINE DRUGS:

17. Directly Observed Treatment Short-course (DOTS) strategy is the management
package that ensures effective diagnosis and treatment of infectious cases
On March 24, 1997, the Director-General of the World Health Organization
declared, “the DOTS strategy for TB control represents the most important public
health breakthrough of the decade, in terms of lives which will be saved”
The DOTS strategy consists of increased commitment, effective diagnosis,
standard treatment given under direct observation, secure drug supply and
systematic monitoring and evaluation of all patients started on treatment
DOT means that a trained health care worker or other designated individual
(excluding a family member) provides the prescribed TB drugs and watches the
patient swallow every dose.
Tuesday, October 10, 2017
17
*DIRECTLY OBSERVED
TREATMENT SHORT-COURSE
(DOTS)

18. Tuesday, October 10, 201718
PHARMACOTHERAPY OF
LEPROSY

19. *INTRODUCTION
*Chronic granulomatous infectious disease.
*Caused by Mycobacterium leprae
*Mainly involves the peripheral nerves and skin
*Other organs may involve:
Mucosa of mouth
Upper respiratory tract
Eyes
Bones & Muscles.
Testes etc.
Commonly involves every organ except :
CNS, Ovary and Lungs.

20. Tuesday, October 10, 201720
*

21. *MODE OF TRANSMISSION
*Transmission by inhalation
*Droplet infection (most common)
* Transmission by contact
*Skin to skin contact with infectious cases
*Contact with soil or fomites
*Other Routes
*Insect Vectors e.g. Mosquito, Bedbugs
*Tattooing needles
Breast feeding and Transplacental infection do not occur.

22. *Ridley- Jopling 1966
CLASSFICATION OF LEPROSY
*Divides Leprosy cases into five groups according to their
position on an immunohistological scale.
 Tuberculoid (TT)
 Borderline Tuberculoid (BT)
 Borderline Borderline (BB)
 Borderline Lepromatous (BL)
 Lepromatous (LL)

23. *TUBERCULOID
LEPROSY
*Single or a few lesions
*Asymmetrically distributed on trunk and limbs
*Sharply defined, dry, flat or raised, erythematous or
hypopigmented, and are anesthetic.
*One or two nerves may be enlarged near the skin lesion
*SS for AFB: Negative
*Lepromin test may be strongly positive

24. *Tuberculoid Leprosy

25. *Borderline Tuberculoid
*Four or more lesions, asymmetrically distributed
*Macules or plaques of variable sizes with well or ill-
defined margins & satellite lesions
*Peripheral nerves enlarged asymmetrically
* Sensation: Hypoesthesia (numbness)
*SS for AFB: may or may not be positive.
*Lepromin test may be weakly positive

27. *Borderline Borderline
*Multiple erythematous macules & plaques
*Various sizes and shapes with punched out center and ill
defined slopping outer margin
*Tend to be symmetrical
*Nerves may be asymmetrically enlarged
*Sensation:+/-
*SS for AFB: seen +/-
*Lepromin test-usually negative, may be doubtful

28. *Borderline Borderline

29. *Borderline Lepromatous
*Numerous, symmetrically distributed lesions
*Hypopigmented or erythematous irregularly shaped
maculopapular, infiltrative nodules, or plaques, with smooth
surfaces & ill defined borders, sloping outwards
*Nerves may be symmetrically or asymmetrically enlarged
*Sensation:+/-
*SS for AFB: numerous seen
*Lepromin test -negative

30. *Borderline
Lepromatous

31. *Lepromatous Leprosy
*Numerous macules, plaques, nodules or diffusely
infiltrated lesions, shiny, smooth, symmetrically
distributed on face, trunk and extremities with ill-
defined margin which may be slightly hypopigmented
or erythematous
*Symmetrical nerve enlargement is seen
*Sensation: normal
*SS for AFB: numerous seen
*Lepromin test - negative

32. *Lepromatous
Leprosy

33. *DIAGNOSIS
*HISTORY
*CLINICAL EXAMINATION
*BACTERIOLOGICAL EXAMINATIONS
*FOOT-PAD CULTURE
*HISTAMINE TEST
*BIOPSY
*IMMUNOLOGICAL TEST

34. *TREATMENT
MULTIDRUG CHEMOTHERAPY
In multidrug regimens only bactericidal drugs are
used :
*First line drugs : Rifampicin, Dapsone, Clofazimine,
Ethionamide and Prothionamide.
*Second line drugs : Quinolones, Minocycline,
Clarithromycin.

35. *TREATMENT
MULTIDRUG CHEMOTHERAPY
Important points :
MDT is not contraindicated in patients with HIV
infection.
MDT is safe during pregnancy.
Drugs are excreted in breast milk but no reports of
adverse reaction except for mild discoloration of infants
skin by Clofazimine
Leprosy is exacerbated during pregnancy, it is important
that MDT is continued

36. *TREATMENT
MULTIDRUG CHEMOTHERAPY
Drugs
Rifampicin : Highly bactericidal, a single 1500mg dose
kills 99 percent of viable organisms
Toxic effects includes anorexia, nausea, vomiting,
abdominal discomfort and orange discoloration of body
secretions. It is hepatotoxic.
Dapsone : Weakly bactericidal.
Adverse effects include hemolytic anemia,
methemoglobinemia, agranulocytosis, hepatitis,
neuropathy, psychosis and rarely…

37. *TREATMENT
MULTIDRUG CHEMOTHERAPY
DDS syndrome : Fever, maculopapular rash, enlarged lymph
nodes, hepatitis and dermatitis.
Clofazimine : Was originally synthesized for TB. Less
effective than Dapsone but has added advantage of
preventing lepra reaction. More expensive but less toxic
which includes dark red discoloration of skin, mucus
membranes, sweat and urine.

38. *TREATMENT
MULTIDRUG CHEMOTHERAPY
Ethionamide and Prothionamide :
Highly bactericidal killing 98
percent of viable bacilli in 3 to 4 days. Relatively more
expensive and more toxic.

39. *TREATMENT
MULTIDRUG CHEMOTHERAPY
WHO RECOMMENDED REGIMENS OF
CHEMOTHERAPY :
MULTIBACILLARY LEPROSY
Rifampicin : 600mg once monthly under supervision
Dapsone : 100mg daily self administered
Clofazimine : 300mg once monthly under supervision
50mg daily self-administered
Where Clofazimine is unacceptable due skin coloration it may be
substituted by 250 to 375mg daily dose of Ethionamide or
Prothionamide.
The above regimen needs to taken for 12 months within 18 months

40. *TREATMENT
MULTIDRUG CHEMOTHERAPY
WHO RECOMMENDED REGIMENS OF
CHEMOTHERAPY :
PAUCIBACILLARY LEPROSY :
The above regimen needs to be taken for 6months within 9 months

41. *TREATMENT
MULTIDRUG CHEMOTHERAPY
Treatment regimen for children 10-14 years :
MULTIBACILLARY LEPROSY
 Rifampicin : 450mg once monthly under supervision
 Dapsone : 50mg daily self administered
 Clofazimine : 150mg once monthly under supervision
50mg every other day self-administered
PAUCIBACILLARY LEPROSY
 Rifampicin : 450mg once a month under supervision
 Dapsone : 50mg daily self administered.

42. *IMMUNOPROPHYLAXIS
*Till date there is no effective vaccine against leprosy
*The vaccine undergoing trials are :
BCG –34.1% PROTECTION
BCG+KILLED M.LEPRAE – 64.0%
M.W – 25.7%
ICRC – 65.5%

43. *PREVENTIVE MEASURES
*Measures include care of dry and denervated skin
of palms and soles.
*Treating wounds, ulcers, and cracks in palms &
soles
*Use of protective gloves and footwear
*Prevent joint stiffness in case of paralysis
*Protection of eyes
*Periodic check up for progression of disease.

44. Tuesday, October 10, 201744
*REFERENCES
1.Essentials of medical pharmacology, 5th edition by Tripathi, 2004,
page no.698-708
2.Essentials of Pharmacotherapeutics by FSK Barar, 434-441
3.www.wikepedia.org/wiki/pharmacotherapy_of_tuberculosis
4.www.wikepedia.org/wiki/pharmacotherapy_of_leprosy
5.Pharmacology A Companion Handbook with Illustrations By K
Ravi Shankar and G V N Kiranmayi