2. INTRODUCTION
MODE OF TRANSMISSION AND SYMTOMS
CAUSES
TEST AND DIAGNOSIS
CLASSIFICATION OF ANTI TB DRUGS
CONCLUSION
REFERENCE
CONTENTS
2
3. INTRODUCTION
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
TYPES
3
4. Mycobacterium tuberculosis
Highly aerobic
Gram positive
Non-motile rod
Infects lungs
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
person.
4
5. 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
person.
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
causes tuberculosis.
5
6. 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
Lungs
Pleura
Central nervous system
Liver and Spleen
Lymphatic system
Genitourinary systems
Bones and joints
Disseminated (miliary TB)
6
7. 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
many years.
TB germs are active and spreading.
They are damaging tissue in body.
Don’t look or feel sick. Chest x-ray is usually
normal.
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
months.
Treated by taking several TB medicines for at
least 6 months.
7
8. 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
Coughs
Sneezes
Speaks
Sings
laughs
8
9. The symptoms my vary depending on what type of tuberculosis you contract.
Fever
Chills
Night sweats
Loss of appetite
Weight loss and fatigue
SIGNS AND SYMPTOMS
9
10. CAUSES
TB is an airborne disease caused by the bacterium Mycobacterium tuberculosis (M.
tuberculosis).
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
10
11. 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
11
12. 1. HIV test
2. Medical history
3. Physical examination
4. Bacteriologic or histologic exam
(Chest radiograph if indicated)
Evaluation for TB
12
13. 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
Skin test
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
AIDS.
Blood test
This test use sophisticated technology to measure your immune system’s reaction to TB
bacteria.
Sputum test
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
13
14. 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
TREATMENT
14
15. CLASSIFICATION OF ANTI-TB
DRUGS
BASED ON CHEMICAL
MOIETY
1) Salicylic acid derivatives
Para amino salicylic acid
2) Pyridine derivatives
Isonicotinic acid hydrazide
Ethionamide
3) Pyrazine derivatives
Pyrazinamide
4) Ethylene Di-amino Butanol
derivatives
Ethambutol
5) Antibiotics
Streptomycin
Cycloserine
Rifampicin
Kanamycin 15
16. 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)
FACE PaC
NEWER DRUGS
1. Ciprofloxacin
2. Ofloxacin
3. Clarithromycin
4. Azithromycin
5. Rifabutin
COCA - R 16
17. Refamycins are a group of macrocyclic antibiotics which are produced by Streptomyces
mediterranei.
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.
REFAMPICIN
18. 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
18
19. 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.
ADVERSE EFFECTES
Dose- 10mg/kg
>50kg- 600mg
20. 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
the heart.)
Oesteomyelitis(inflammation of bone)
It is used in the first-line therapy of brucellosis in combination
with doxycline.
It is also an excellent drug for Pneumonia.
It is also used in combination with dapsone in Treating leprosy.
THERAPEUTIC USES
20
21. - It is tuberculocidal
- Structural similarity to Pyridoxine.
- First line medication in prevention and treatment of
tuberculosis.
- 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.
MOA
Inhibits the biosynthesis of mycolic acids, which are essential
constituents of the mycobacterial cell wall.
DOSE
5mg/kg
> 50 kg- 300mg/kg
ISONIAZID (INH)
(ISONICOTINIC ACID HYDRAZIDE (H)
21
22. 1) Hepatitis - loss of appetite, nausea, vomiting, jaundice, and right upper
quadrant pain.
2) Peripheral neuropathy (deficiency of pyridoxine ).
3) Fever
4) Skin rashes
5) Arthralgia
6) GI disturbances
7) Psychosis
8) optic neuritis and rarely convulsions
ADVERSE EFFECTS
22
23. Isoniazid is manufactured from isonicotinic acid, which is produced from 4-
methyl pyridine.
N
CH3
Oxidation
4-methyl pyridine
N
C OHO
N
C NHNH2O
Isoniazide
H2N NH2
Hydrazine
-H2O
SYNTHESIS OF ISONIAZID
23
24. 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.
MOA:
It inhibits mycolic acid synthesis, but by interacting with A different fatty acid
synthase encoding gene.
DOSE:
25mg/kg
>50 kg- 1500mg
ADVERSE EFFECTS:
1) Hepatotoxicity- major adverse effect.
2) Nausea
3) Vomiting
4) Fever
5) Hyperuricemia
PYRAZINAMIDE (PZA)
24
25. -Tuberculostatic
MOA:
Inhibits arabinosyl transferases that are involved in mycobacterial cell wall
synthesis (It disrupts arabinogalactan synthesis by inhibiting the enzyme
arabinosyl transferase).
DOSE:
15mg/kg
>50 kg- 1000 mg
ADVERSE EFFECTS:
A) Optic neuritis: red -green color blindness
B) Hyperuricaemia
C) Skin rashes & joint pain
ETHAMBUTOL
25
26. CH3CH2CH NO2
CH2OH
Reduction CH3CH2CH NH2
CH2OH
2-Nitro-1-butanol 2-amino butanol
CH3CH2CH NH2
CH2OH
(2 moles)
ClCH2CH2Cl
ethylene dichloride -2HCl
CH3CH2CH
H
N
CH2OH
H2
C
Ethambutol
H2
C CHCH2CH3
CH2OH
26
27. STREPTOMYCIN
Tuberculocidal
It was the first effective drug developed for the treatment of
tuberculosis.
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
age.
28. Streptomycin is made up of 3 basic structural units called…
1. Streptidine(a diguanidino compound)
2. Streptose (a aldose sugar)
3. N-methyl-L-glucosamine.
O
H
OH
H
H
CH2OH
HOH
NHCH3
O
OH
CHO
CH3
H OH
H
H NH.C.NH2
H
H
OHH
OH
HNH.C.NH2
H OH
O
NH
NH
N-methyl-L-glucosamine
Streptose
Streptidine
29. 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
mRNA complex
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.
3.Inhibit translocation
29
MECHANISM OF ACTION
30. A. Ototoxicity
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.
B. Nephrotoxicity
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
reactions)
Skin rash, fever, eosinophilia and
anaphylactic shock. 30
TOXICITY
31. 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
effective.
That’s why it is used in combination with other anti-tubercular
drugs in multidrug therapy.
Drugs used most commonly to treat TB include…
Refampicin
Isoniazid
Pyrazinamide
Ethambutol
MULTI DRUG THERAPY (MDT)
32. 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)
32
38. 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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