2. Content
Introduction
Mode of transmission
Sign and symptoms
Classification of Anti-Tuberculosis Drugs
Mechanism of action
Adverse effect
Multi drug resistance
Treatment
References
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3. Introduction
Tuberculosis (TB) is a bacterial infection spread through inhaling tiny
droplets from the coughs or sneezes of an infected person.
Tuberculosis (TB) is caused by a bacterium called Mycobacterium
tuberculosis. The bacteria usually attack the lungs, but TB bacteria can
attack any part of the body such as the kidney, spine, and brain.
A major health problem in developing countries.
In 2021 an estimated 10.6 million people fell ill with TB.
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4. Contd …
Mycobacterium tuberculosis
Highly aerobic
Gram positive ( special cell wall with Mycolic layer so weakly gram positive)
Acid fast staining ( Ziehl -Neelsen ) is use for staining this bacteria
Non-motile rod
Divides every 15-20 hours
Unable to digest by macrophages
Very resistant to many disinfectants, acid, alkali, drying
If not treated properly , TB can be fatal
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5. Contd …
Types :
PULMONARY Tuberculosis
AVIAN Tuberculosis (mycobacterium avium of birds)
BOVINE Tuberculosis (mycobacterium bovis of cattle)
MILIARY Tuberculosis/ Disseminated Tuberculosis (invade the blood stream and spread to
all body organs)
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6. Contd …
Latent TB
You have a TB infection, but the bacteria in your body are inactive and cause no symptoms.
Latent TB , also called inactive TB or TB infection, isn't contagious.
Active TB
Also called TB disease, this condition makes you sick and, in most cases, can spread to
others.
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7. Mode of Transmission
Tuberculosis is transmitted through the air, not by surface contact.
Tuberculosis (TB) is transmitted from an infected person to a susceptible person in
airborne particles, called droplet nuclei.
These are 1–5 microns in diameter. These infectious droplet nuclei are tiny water
droplets with the bacteria that are released when persons who have pulmonary
tuberculosis cough, sneeze, laugh, shout etc.
These tiny droplet nuclei remain suspended in the air for up to several hours.
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8. Sign and symptoms
• Coughing for three or more weeks.
• Coughing up blood or mucus.
• Chest pain, or pain with breathing or coughing.
• Unintentional weight loss.
• Fatigue.
• Fever.
• Night sweats.
• Chills
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9. Classification of Anti-Tuberculosis Drugs
The antitubercular drugs are classified as first line, second line drugs based on their
efficacy, side effects, toxicity, availability and cost.
The first-line antitubercular drugs are
Streptomycin
Rifampicin
Ethambutol
Isoniazid
Pyrazinamide
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10. Contd …
Tuberculosis can be cured by using first line drugs with the success rate of up to 95%. If the treatment fails
because of the bacterial resistance or intolerance to one or more drugs, second line drugs are used.
There are six classes of second line drugs used for the treatment of TB.
Amino glycosides: amikacin, kanamycin
Polypeptides: capreomycin, viomycin
Fluoroquinolones: ciprofloxacin, gatifloxacin , moxifloxacin
Thioamides: ethionamide, prothionamide
Isoxazolidinone : cycloserine
Salicylic acid: p-aminosalicylic acid
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11. Contd …
WHO categorization of second-line antituberculosis drugs recommended for the treatment of rifampicin
resistant and multidrug-resistant tuberculosis.
Group A: fluoroquinolones
• Levofloxacin
• Moxifloxacin
• Gatifloxacin
Group B: second-line injectable agents
• Amikacin
• Capreomycin
• Kanamycin
• Streptomycin
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12. Contd …
Group C: other core second-line agents
• Ethionamide/prothionamide
• Cycloserine/terizidone
• Linezolid
• Clofazimine
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14. Mechanism of Action
Rifamycin:
Rifampin binds to 𝛽 subunit of DNA-dependent RNA polymerase (rpoB) to form a stable drug-enzyme
complex. Drug binding suppresses chain formation in RNA synthesis.
Bacterial Resistance
The prevalence of rifampin-resistant isolates are 1 in every 107 to 108 bacilli.
Microbial resistance to rifampin is due to an alteration of the target of this drug, rpoB, with resistance in 86% of
cases due to mutations at codons 526 and 531 of the rpoB gene .
Rifamycin monoresistance occurs at higher rates when patients with AIDS and multi-cavitary TB are treated
with either rifapentine or rifabutin.
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15. Therapeutic uses
Rifampin for oral administration is available alone and as a fixed-dose combination
with isoniazid or with isoniazid and pyrazinamide (50 mg of isoniazid, 120 mg of
rifampin, and 300 mg pyrazinamide; RIFATER)
The dose of rifampin for treatment of tuberculosis in adults is 600 mg, given once daily,
either 1 hour before or 2 hours after a meal.
Children should receive 10-20 mg/kg given in the same way. Rifabutin is administered
at 5 mg/kg/day and rifapentine at 10 mg/kg once a week.
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16. Adverse effect
temporary discoloration (yellow, reddish-orange, or brown color) of your skin, teeth,
saliva, urine, stool, sweat, and tears)
itching.
flushing.
headache.
drowsiness.
dizziness.
lack of coordination.
difficulty concentrating.
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17. Contd …
PYRAZINAMIDE
(structural analogue of nicotinamide, activated by pyrazinamide (encoded by pncA) into
it's active form pyrazinoic acid)
genes involved in resistance:
pncA (encoding a pyrazinamide)
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18. Contd …
ISONIAZID
activated form inhibits mycolic acid biosynthesis
genes involved in resistance:
katG (encoding a catalase-peroxidase needed for activation)
inhA ( encoding a enoyl-acyl carrier protein)
kasA (encoding a beta-ketoacyl acyl carrier protein synthase)
possibly involved : ahpc, furA
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19. Metabolism and activation of isoniazid: The prodrug isoniazid is metabolized in humans by NAT2 isoforms to
its principal metabolite, N-acetyl isoniazid, which is excreted by the kidney. Isoniazid diffuses into mycoplasma
where it is “activated” by KatG (oxidase/peroxidase) to the nicotinoyl radical, which reacts spontaneously with
NAD+ or NADP+ to produce adducts that inhibit important enzymes in cell wall and nucleic acid synthesis.
DHFR, dihydrofolate reductase.
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20. Contd …
ETHAMBUTOL
Ethambutol hydrochloride (MYAMBUTOL) is a water-soluble and heat-stable compound.
inhibits arabinogalactan transfer into the cell wall
genes involved in resistance:
embB gene in the embCAB operon
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21. Contd …
STREPTOMYCIN
Aminocyclitol glycoside antibiotic, binds to 16S rRNA and inhibits translational
initiation
genes involved in resistance:
rrs (16S rRNA gene)
rpsL (encoding ribosomal protein S12)
FLUOROQUINOLONES
bind to DNA gyrase and inhibit supercoiling
Ciprofloxacin
Ofloxacin
genes involved in resistance: gyrA gene 21
22. Contd…
KANAMYCIN , AMIKACIN , VIOMYCIN :
aminoglycoside antibiotics that inhibit protein synthesis
genes involved in resistance: rrs (16S rRNA gene)
CYCLOSERINE
(D-cycloserine = analogue of D-alanine that inhibits cell wall synthesis)
genes involved in resistance : alrA, D-alanine racemase gene
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25. Multidrug-Resistant TB
Multidrug-resistant TB (MDR TB) is caused by TB bacteria that are resistant to at least isoniazid and
rifampin, the two most potent TB drugs. These drugs are used to treat all persons with TB disease.
Pre-Extensively Drug-resistant TB (pre-XDR TB)
Pre-Extensively Drug-resistant TB (pre-XDR TB) is a type of MDR TB caused by TB bacteria that
are resistant to isoniazid, rifampin, and a fluroquinolone OR by TB bacteria that are resistant to
isoniazid, rifampin, and a second-line injectable (amikacin, capreomycin, and kanamycin).
Extensively Drug-resistant TB (XDR TB)
Extensively drug-resistant TB (XDR TB) is a rare type of MDR TB caused by TB bacteria that are
resistant to isoniazid and rifampin, a fluroquinolone, and a second-line injectable (amikacin,
capreomycin, and kanamycin) OR by TB bacteria that are resistant to isoniazid, rifampin, a
fluroquinolone, and bedaquiline or linezolid.
Because XDR TB is resistant to the most potent TB drugs, patients are left with treatment options that
are much less effective.
XDR TB is of special concern for people with HIV infection or other conditions that can weaken the
immune system. These people are more likely to develop TB disease once they are infected, and also
have a higher risk of death once they develop TB.
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26. Treatment
Levofloxacin and moxifloxacin are the two most frequently recommended agents, and
the WHO has recommended the use of these drugs for the treatment of MDR-TB.
The optimal dose of levofloxacin is 750 mg once daily and that of moxifloxacin is 400
mg once daily.
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27. Directly Observed Therapy (DOT)
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.
DOT helps patients finish TB therapy as quickly as possible, without unnecessary gaps.
DOT helps prevent TB from spreading to others.
DOT decreases the risk of drug-resistance resulting from erratic or incomplete
treatment.
DOT decreases the chances of treatment failure and relapse.
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28. References
"Goodman & Gilman's: The Pharmacological Basis of Therapeutics
https://www.cdc.gov/
https://www.ncbi.nlm.nih.gov/books/NBK557666/
https://www.researchgate.net/publication/340102047_INTRODUCTION_OF_TUBER
CULOSIS_DISEASE_AND_CLASSIFICATION_OF_ANTI_TUBERCULOSIS_DRU
GS
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