Drugs for Tuberculosis and

Leprosy

Lecturer – Sameera Liyanaarachchi

(BSc (Special) University of Sri Jayewardenepura)
Registered Pharmacist (SLMC)
 Tuberculosis
• Tuberculosis (TB) is a potentially serious
infectious disease that mainly affects the
lungs.
• The bacteria that cause tuberculosis are
spread from person to person through tiny
droplets released into the air via coughs and
sneezes.
• In developing countries it is a major health
problem
• ≈ 30% of world population is infected with
Mycobacterium Tuberculosis infection
 Tuberculosis
Mycobacterium tuberculosis

Vaccinations
In countries where tuberculosis is more common, infants often are
vaccinated with bacillus Calmette-Guerin (BCG) vaccine.
The BCG vaccine isn't very effective in adults.
 Mycobacterium Infections
Common infection sites
• Lung (primary site) - Intestines
• Brain - Lymph nodes
• Bone
• Liver
• Kidney

• Aerobic bacillus
• Passed from infected:
– Humans
– Cows (bovine) and birds (avian)
• Much less common
 Mycobacterium Infections
• Tubercle bacilli are conveyed by droplets

• Droplets are expelled by coughing or sneezing,

then gain entry into the body by inhalation

• Tubercle bacilli then spread to other body organs

via blood and lymphatic systems
Tuberculosis - Pathophysiology
• Spread from person to person via
airborne droplets
– Coughing, sneezing, speaking – disperse
organism and can be inhaled
– Not highly infectious – requires close, frequent,
and prolonged exposure
 Tuberculosis – Clinical Manifestations
• Early stages – free of symptoms
– Many cases are found incidentally
• Systemic manifestations:
– Fatigue, anorexia, weight loss, low-grade fevers, night sweats
– Weight loss – occurs late
– Characteristic cough – frequent & produces mucopurulent
sputum
• Some cases: acute high fever, chills, general flulike
symptoms, pleuritic pain, productive cough
• HIV Pt with TB: Fever, cough, weight loss
 Antitubercular Agents
First line drugs:
Isonized
Rifampicin
Ethambutol
Pyrazinamide

• Streptomycin now reserved drug

in first line
 Antitubercular Agents
Second line drugs:

Ethionamide
Amikacin
 Antitubercular Agents
Newer Second Line drugs:
Ciprofloxacin
Ofloxacin
Levofloxacin
Clarithromycin
Azithromycin
 Drugs used in Tuberculosis

1st line drugs 2nd line drugs

high efficacy, low toxicity Low efficacy, high toxicity or both

• Isoniazid (INH) • Ethionamide

• Rifampin • Amikacin
• Pyrazinamide • Fluoroquinolones
• Ethambutol
• Streptomycin
 MOA of 1st line drugs
Isoniazid
Ethambutol
-
Mycolic Acid
-
Arabinogalactan
Peptidoglycan
Cell membrane
- Mitochondria
(ATP)
Pyrazinamide - Rifampin

- Streptomycin

- Cytoplasm

R
I Protein
B
O
S
O
M
e
 Antitubercular Agents
Isoniazid:
Essential component of all anti TB regimen

-It is tuberculocidal , kills fast multiplying

organism & inhibit slow acting organism
-Acts both on intracellular ( present in
macrophages ) & extracellular bacilli
-It is the cheapest AT Agent
 Antitubercular Agents
ADRs -
Well tolerated drug
1.Peripheral neuritis & other neurological
manifestations- parasthesia , numbness,
mental disorientation & rarely convulsion
 Antitubercular Agents
Due to this, Pyridoxine given
prophylactically
-10 mg/day which prevents neurotoxicities
(INH neurotoxicity treated with Pyridoxine-100 mg/ day )
2. Hepatitis – more common in older patients &
alcohlics ( reversible)
3. Rashes , fever , acne & arthralgia .
 Antitubercular Agents
Rifampicin:
-Semisynthetic derivative of Rifamycin B
from Streptomyces
-Bactericidal to M. Tuberculosis & others –
S. aureus Klebsiella
N. meningitidis Pseudomonas
H. influenzae
E. coli
 Antitubercular Agents
Mechanism:
Inhibit DNA dependant RNA Synthesis
(by ↓ bact RNA polymerase)
- No resistance
 Antitubercular Agents
ADR’s
1. Hepatitis – mainly in pts having pre
existing liver disease & dose related-
Jaundice requesting stoppage of drug
2. Respiratory syndrome –breathlessness
shock & collapse .
3. Purpura , Hemolysis , shock , renal
failure
 Antitubercular Agents
D/I
Rifampicin is microsomal enzyme inducer
-↑ several CYP 450 isoezymes
-↑ its own metabolism as well as of others
e.g.-Oral contraceptive Digoxin
Warfarin Theophylline
Steroids Metoprolol
Sulphonyl urea Fluconazole & Ketoconazole
 Antitubercular Agents
Contraceptive failure can occur if given
simultaneously in child bearing age women taking
oral contraceptive
 Antitubercular Agents
Pyrazinamide
Chemically≡ INH
-Weak tuberculocidal and more active in
acidic medium
-More effective in first two months of therapy
 Antitubercular Agents
ADRs :
-Hepatotoxic -dose related
-Arthralgia , hyperuricaemia, flushing ,
rashes , fever & anaemia
Dose – 20-30 mg /kg daily , 1500 mg if > 50 kg
 Antitubercular Agents
Ethambutol :
-Tuberculostatic , clinically active as
Streptomycin
 Antitubercular Agents
-Neurological changes
-Hyper uricaemia is due to interference
with urate excretion
Dose – 15-20 mg/kg , > 50kg -1000mg
 Antitubercular Agents
Streptomycin (S):
--It is protein synthesis inhibitor by
combining
with 30S ribosome
-It is tuberculocidal , but less effective than
INH / Rifampicin
-Acts on extracellular bacilli only ( poor
penetration in the cells )
 Antitubercular Agents

-It penetrates tubercular cavities but does

not cross BBB
- Resistance when used alone
- Popularity ↓ due to lower margin of safety
( because of ototoxicity & nephrotoxicity.)

- Dose- 15 ( 12-18 ) mg/kg

 Relative activity of first line Drugs
• INH: potent bactericidal Combination is synergistic
• Rifampin: potent bactericidal
• Pyrazinamide: Weak bactericidal, active against
intracellular bacilli.
• Ethamutol: bacterisostatic, prevents resistance
development.
• Streptomycin: bactericidal, active against
extracellular rapid growers.
Never use a single drug for chemotherapy
in tuberculosis, a combination of two or
more drugs must be used.
 Antitubercular Agents
Newer drugs :
Ciprofloxacin
Ofloxacin
Levofloxacin
( all are used in TB)
 Antitubercular Therapy
Short course chemotherapy-
Regimen of 6-9 months treatment In 1997 WHO
framed clear cut guidelines for different category
of TB treatment .
All regimen have
initial intensive phase
2 months to rapidly kill the TB bacilli & afford
Symptomatic relief , Smear positive to negative
followed by continuation phase last 4 months
FDC
FDC(Fixed Dosed Combination)
• Anti TB FDCs are usually a combination of two
or more first line anti TB drugs.
• These are rifampicin, isoniazid, pyrazinamide
and ethambutol.
• The reason for using FDCs for TB treatment
comes from the fact that TB always requires
multi drug therapy.
 The potential advantages associated
with the use of FDCs are:
• Reduced risk of emergence of drug
resistant strains
• Less risk of medication errors
• Better patient compliance
• Reduced cost of treatment
• Simplified drug supply management,
shipping & distribution.
• Currently, the WHO Model List of
Essential Drugs includes,
• two-drug formulations (INH + RIF and INH
+ ethambutol),
• three-drug formulations (INH + RIF +
ethambutol and INH + RIF +
pyrazinamide)
• and a four-drug formulation (INH + RIF +
ethambutol + pyrazinamide)
The Mantoux test

The Mantoux test (also known as the Mantoux screening

test, tuberculin sensitivity test) is a tool for screening for tuberculosis
(TB) and for tuberculosis diagnosis.
Leprosy
 Leprosy
• Leprosy is a chronic infectious disease
caused by a bacillus, Mycobacterium
leprae.
• Leprosy is an infectious disease that causes severe,
disfiguring skin sores and nerve damage in the
arms, legs, and skin areas around your body.
• Leprosy has been around since ancient times.
Outbreaks have affected people on every
continent.
 Treatment of Leprosy
-Organism may or may not be found in skin
lesions.
-Lepromine test is positive (diagnostic for
Leprosy)
It evaluate the immune system of the patient
& classify the type of disease.)
-prolonged remission occurs
 Treatment of Leprosy
• Leprosy primarily affect skin , mucous
membranes & nerves
 Treatment of Leprosy
Dapsone - 100 mg
Clofazimine – 300 mg
Rifampicin – 600 mg
Dapsone – 100 mg
 Anti- Leprotic agents
-Fluoroquinolones : Ofloxacin , Pefloxacin,
Gatifloxacin are highly active against
M. leprae ( but not Ciprofloxacin )
-Minocycline: due to high lipophilicity, it is
active against M. leprae. , antibacterial
activity is less than Rifampicin but more
than that of Clarithromycin .
 Anti- Leprotic agents
Clarithromycin:
Only macrolide antibiotic having significant
activity against M. leprae ..
Thank You