S.SEETARAM SWAMY, M.Pharm.,
Dept. of Pharmaceutical Chemistry,
Chilkur Balaji College of Pharmacy.
MODE OF TRANSMISSION AND SYMTOMS
TEST AND DIAGNOSIS
CLASSIFICATION OF ANTI TB DRUGS
Tuberculosis is a chronic granulomatous disease caused by Mycobacterium
tuberculosis, which most commonly affects the lungs.
M. tuberculosis organisms are also called tubercle bacilli.
A major health problem in developing countries.
It is currently estimated that 1/2 of the world's population (3.1 billion) is infected
with Mycobacterium tuberculosis.
Global Emergency Tuberculosis kills 5,000 people a day.
2.3 million die each year.
A. PULMONARY TUBERCULOSIS
B. AVIAN TUBERCULOSIS( MICROBACTERIUM AVIUM ;OF BIRDS)
C. BOVINE TUBERCULOSIS(MYCOBACTERIUM BOVIS ;OF CATTLE)
D. MILIARY TUBERCULOSIS / DISSEMINATED TUBERCULOSIS
Divides every 15-20 hours
Unable to be digested by microphages
Very resistant to many disinfectants, acid, alkali, drying, etc.
If not treated properly, TB can be fatal.
Contagious, spread through air by inhalation of airborne bacteria from infected
Tuberculosis (TB) is one of the most prevalent infections of human beings
and contributes considerably to illness and death around the world. It is spread
by inhaling tiny droplets of saliva from the coughs or sneezes of an infected
It is a slowly spreading, chronic, granulomatous bacterial infection,
characterized by gradual weight loss.
In1882 , Robert Koch discovered a staining
technique that allowed him to see the bacteria
that cause TB under a microscope.
Mycobacterium tuberculosis, the bacteria that
TB germs are most commonly found in the lungs, but sometimes they can move to other
parts of the body.
Common Sites of TB Disease
Central nervous system
Liver and Spleen
Bones and joints
Disseminated (miliary TB)
TB infection is caused by the same germs, but it’s less serious. People with TB
infection are not sick because they have fewer of the germs in their body, and the
germs are latent (sleeping). People with TB infection are not contagious.
TB disease occurs when the TB germs are active in a person’s body in large
numbers. People with TB disease usually feel sick, and have one or more symptoms
of TB disease. They may be infectious, which means they can pass the TB bacteria
on to others. If it’s not treated, TB disease can cause serious disability and even death.
TB Infection vs. TB Disease
Latent TB Infection Active TB Disease
TB germs are “asleep” in the body.
This phase can last for a very long time – even
TB germs are active and spreading.
They are damaging tissue in body.
Don’t look or feel sick. Chest x-ray is usually
Usually feel sick. Doctor will do special tests to
find where TB is harming in body.
TB infection cannot spread TB to other people. If the TB germs are in lungs, it can spread TB
to other people by coughing, sneezing, talking.
Usually treated by taking one medicine for 9
Treated by taking several TB medicines for at
least 6 months.
M. tuberculosis is carried in airborne particles, called droplet nuclei, of 1– 5 microns in
diameter. M. tuberculosis is transmitted through the air, not by surface contact.
Its spread from person to person in tiny microscopic droplets. Depending on the
environment, these tiny particles can remain suspended in the air for several hours.
M. tuberculosis may be expelled when an infectious person:
MODE OF TRANSMISSION
The symptoms my vary depending on what type of tuberculosis you contract.
Loss of appetite
Weight loss and fatigue
SIGNS AND SYMPTOMS
TB is an airborne disease caused by the bacterium Mycobacterium tuberculosis (M.
Mycobacterium tuberculosis complex refers to a group of Mycobacterium species
that can cause tuberculosis in humans.
Easier to contract with weak immune system.
1. Mycobacterium bovis
2. Mycobacterium africanum
3. Mycobacterium microti
4. Mycobacterium caprae
5. Mycobacterium pinnipedii
6. Mycobacterium canetti
7. Mycobacterium mungi
Drug-resistant strains of TB
emerged when an antibiotic fails
to kill all of the bacteria it targets.
Some TB bacteria have
developed resistance to the most
commonly used treatments, such
as isoniazid and rifampin.
DRUG –RESISTANT TB
1. HIV test
2. Medical history
3. Physical examination
4. Bacteriologic or histologic exam
(Chest radiograph if indicated)
Evaluation for TB
When someone comes into contact with tuberculosis or feels as if they become infected by
tuberculosis, they should call a doctor and order a skin test.
The doctor will inject a small amount of tuberculin under the skin.
If a person has been exposed to tuberculosis a swelling will develop around the spot where
the skin test is given.
The most commonly used diagnostic tool for tuberculosis is
A false +ve test may happen if you have been vaccinated recently with the Bacille
Calmette Guerin (BCG).
False –ve results may occur in certain population-including children, older people & with
This test use sophisticated technology to measure your immune system’s reaction to TB
Chest X-ray shows signs of TB, your doctor may take sample of your sputum- the mucus
that comes up when you cough
TEST AND DIAGNOSIS
Most TB is curable, but…
Four or more drugs required for the simplest regimen.
6-9 or more months of treatment required.
Person must be isolated until non-infectious.
Directly observed therapy to assure adherence/completion recommended.
Side effects and toxicity common
• May prolong treatment
• May prolong infectiousness
Other medical and psychosocial conditions complicate therapy
•TB may be more severe
•Drug-drug interactions common
CLASSIFICATION OF ANTI-TB
BASED ON CHEMICAL
1) Salicylic acid derivatives
Para amino salicylic acid
2) Pyridine derivatives
Isonicotinic acid hydrazide
3) Pyrazine derivatives
4) Ethylene Di-amino Butanol
FIRST LINE DRUGS
[Have high anti-tubercular efficacy as
well as low toxicity]
1. Rifampicin (R)
2. Isoniazid (I)
3. Pyrazinamide (P)
4. Ethambutol (E)
5. Streptomycin (S)
R I P E S
SECOND LINE DRUGS
[Either low anti-tubercular efficacy or high
toxicity or Both]
1. Fluroquinolones (F)
2. Amikacin (A)
3. Cyclosporin (C)
4. Ethionamide (E)
5. Para-aminosalicylic acid (Pas)
6. Capreomycin (C)
COCA - R 16
Refamycins are a group of macrocyclic antibiotics which are produced by Streptomyces
Eventually 7 rifamycins were developed they are Rifamycin A,B,C,D,E,S,SV.
Refampicin is a semi-synthetic rifamycin made from Rifamycin-B isolated from
STREPTOMYCES MEDITERRANEI in 1957.
Among the various rifamycins, rifamycin-B was the first Commercial product.
The first line antibiotic drug Rifampicin(RIF) interferes with RNA transcription in
mycobacterium tuberculosis. RIF binds to the β-subunits of the DNA-dependent- RNA-
Polymerase enzyme complex and inhibits transcription of messenger RNA (mRNA).
The m-RNA transcripts are essential requirements for protein synthesis.
So they are useful in treating tuberculosis, leprosy, Mycobacterium avium complex
(MAC) infection and Staphylococcus infections.
MECHANISIM OF ACTION
Hepatotoxic - hepatitis, liver failure in severe cases
Respiratory – breathlessness
Abdominal - nausea, vomiting, abdominal cramps.
Flu-like symptoms - with chills, fever, headache.
Certain bodily fluids, such as urine and tears, to become orange-red in color.
Refampicin is used as a first line drug in the treatment of
tuberculosis. As most of the tubercle bacilli develop resistance to
Refampicin. It is used in combination with other anti-tubercular
drugs in the MULTIPLE DRUG THERAPY to minimize the problem.
It is also used the treatment of leprosy.
Infection like endocarditis (inflammation of membrane lining
Oesteomyelitis(inflammation of bone)
It is used in the first-line therapy of brucellosis in combination
It is also an excellent drug for Pneumonia.
It is also used in combination with dapsone in Treating leprosy.
- It is tuberculocidal
- Structural similarity to Pyridoxine.
- First line medication in prevention and treatment of
- Isoniazid is available in tablet, syrup and injectable forms
(given I.M or I.V.)
-Bacteriostatic at low conc. & bactericidal at high conc.
- Especially against actively growing bacteria.
Inhibits the biosynthesis of mycolic acids, which are essential
constituents of the mycobacterial cell wall.
> 50 kg- 300mg/kg
(ISONICOTINIC ACID HYDRAZIDE (H)
1) Hepatitis - loss of appetite, nausea, vomiting, jaundice, and right upper
2) Peripheral neuropathy (deficiency of pyridoxine ).
4) Skin rashes
6) GI disturbances
8) optic neuritis and rarely convulsions
Isoniazid is manufactured from isonicotinic acid, which is produced from 4-
SYNTHESIS OF ISONIAZID
Chemically similar to INH.
It is weakly tuberculocidal.
More active in acidic medium.
It is a prodrug and converted into pyrazinoic acid in the body.
It inhibits mycolic acid synthesis, but by interacting with A different fatty acid
synthase encoding gene.
>50 kg- 1500mg
1) Hepatotoxicity- major adverse effect.
Inhibits arabinosyl transferases that are involved in mycobacterial cell wall
synthesis (It disrupts arabinogalactan synthesis by inhibiting the enzyme
>50 kg- 1000 mg
A) Optic neuritis: red -green color blindness
C) Skin rashes & joint pain
Reduction CH3CH2CH NH2
2-Nitro-1-butanol 2-amino butanol
ethylene dichloride -2HCl
It was the first effective drug developed for the treatment of
Streptomycin is the first aminoglycoside antibiotic which was
isolated from the actinomycetes bacteria STREPTOMYCES
GRISEUS and several related soil microorganisms.
Streptomycin was first discovered in 1943 by SELMAN ABRAHAM
WAKESMAN and received a Nobel prize in 1952. It was introduced primarily for
the treatment of tuberculosis.
Dose is reduced to 750mg in patients above 50 yr age 500 mg in above 65 yr
Streptomycin is made up of 3 basic structural units called…
1. Streptidine(a diguanidino compound)
2. Streptose (a aldose sugar)
Aminoglycosides binds to specific 30S – 50S subunit ribosomal proteins. Protein
synthesis is inhibited by them in at least three ways:
1.They Block the formation of initiation 70S ribosomal
2.They induce misreading of the code on the mRNA template
Causes incorporation of incorrect amino acids into peptide
resulting in a nonfunctional or abnormal protein synthesis.
MECHANISM OF ACTION
Auditory (Loss of hearing) or vestibular
damage(dizziness, vertigo) or both.
Neomycin, kanamycin, and amikacin
are the most ototoxic drugs,
Streptomycin and gentamicin are the
most vestibulo toxic.
Aminoglycosides are mainly excreted by
glomerular filtration and can be stored
up in kidney. It can cause acute renal
insufficiency and tubular necrosis.
Neomycin is the most nephrotoxic drug,
streptomycin is the least one.
C. Neuromuscular blockade
D. Skin reactions (Hypersensitivity
Skin rash, fever, eosinophilia and
anaphylactic shock. 30
Multiple-drug therapy to treat TB means taking several different
antitubercular drugs at the same time.
Drugs are combined to:
1) Delay the development of resistance
2) Reduce toxicity
3) Shorten the course of treatment
Most species of bacteria develop resistance to Refampicin.
Use of single drug Refampicin for tuberculosis will not be
That’s why it is used in combination with other anti-tubercular
drugs in multidrug therapy.
Drugs used most commonly to treat TB include…
MULTI DRUG THERAPY (MDT)
Two phases of drug therapy are generally used:
Initial phase: In this phase 3 drugs namely Refampicin, isoniazid, Pyrazinamide are
used. some times ethambutol drug is used .
All these drugs used for 2 months. (e.g: AKT4)
Continuation phase:-Two drugs i.e. Refampicin and isoniazid are to be used for a time
period of the next 4months. (e.g: R-Cinex-600)
Ventilate the room
Cover the mouth
Finish entire course of medication
World TB day is March 24. This annual event commemorates the date in 1882
when Dr. Robert Koch announced his discovery mycobacterium tuberculosis, the
bacteria that cause tuberculosis.
HELP PREVENT SPREAD OF TB
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