This document discusses the anti tubercular drugs. It provides information about the classification[first line (isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin) and second line drugs(ethionamide,prothionamide, cycloserine, para amino salicylic acid and fluoroquinolones)], mechanism of action, pharmacokinetics, adverse effects, dose and brand names of antitubercular drugs. Tuberculosis incidence in india and world

1. TOPIC : ANTI TUBERCULAR DRUGS
SUBMITTED TO;
Ms. Neelam Painuly
Associate Professor
Sopr.Neelam@dbuu.ac.in
SoPR, DBUU, Dehradun
SUBMITTED BY;
Mr. B Vishnu Vardhan
Student, M.Pharm Pharmacology
vishnubattala008@gmail.com
SoPR, DBUU, Dehradun
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 1

2. ANTI TUBERCULAR DRUGS
Anti tubercular drugs are group of medicines used to treat the tuberculosis.
 INTRODUCTION :
 A significant health issue, mycobacterium tuberculosis, affects around one-
third of the world's population in all nations with limited resources. In basic
terms, A persistent granulomatous illness is TB.
 TB is now a condition that needs to be reported, according to the Indian
government.
 In India, all TB cases receive free treatment as part of a government program
that covers TB control and treatment.
 The Revised National Tuberculosis Control Programe (RNTCP), was
introduced in 1997, and in 2010 its treatment guidelines undergo further
revisions.
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 2

3.  DIAGNOSIS :
To diagnose TB infection, healthcare professionals do an exam that includes:
1. Listening to your breathe with stethoscope.
2. Checking for swollen lymph nodes.
3. Asking questions about your symptoms.
 TB TESTS:
1. Tuberculosis is suspected.
2. You were likely exposed to a person with active TB disease.
3. You have health risk for active TB disease.
4. Skin test
5. Blood test
6. X ray
7. Sputum test
8. Other lab tests
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 3

4.  CLASSIFICATION OF ANTI-TUBERCULOSIS DRUGS:
The anti-TB medications can be categorized based on their clinical
effectiveness into:
 First line: These medications are frequently used because of their great
anti-tubercular efficacy and low toxicity.
 Second line: These medications are reserved for use because they are
either more poisonous, less effective against tuberculosis, or both.
 FIRST LINE ANTI-TUBERCULAR DRUGS:
1. Isoniazid
2. Rifampicin
3. Pyrazinamide
4. Ethambutol
5. Streptomycin
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5.  SECOND LINE ANTI-TUBERCULAR DRUGS:
1. Ethionamide
2. Prothionamide
3. Cycloserine
4. Terizidone
5. Para-Aminosalicylic Acid
6. Rifabutin
7. Thiacetazone
 FLUOROQUINOLONES
1. Ofloxacin
2. Levofloxacin
3. Moxifloxacin
4. Ciprofloxacin
 INJECTIBLE DRUGS
1. Kanamycin
2. Amikacin
3. Capreomycin
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 5

6.  FIRST LINE OF DRUGS:
• ISONIAZID (ISONICOTONIC ACID HYDRAZIDE, H):
 PROPERTIES& MECHANISM OF ACTION:
1. Isoniazid is primarily tuberculocidal.
2. It is one of the cheap anti tubercular drugs.
3. Isoniazid works by inhibiting the production of mycolic acids(mycobacteria's cell walls
include certain fatty acid components called mycolic acids).
4. Highly selective for mycobacterium.
 RESISTANCE:
1. This prodrug is catalase-peroxidase (KatG) enzyme-activated.
2. Since there is no cross resistance with the other antitubercular medications, they are
always used in combination.
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 6

7.  PHARMACOKINETICS:
1. Absorption: absorbed completely via oral route.
2. Distribution: affects all bodily tissues, tubercular cavities, placenta and meninges.
3. Metabolism: highly metabolized in liver; N-acetylation is the most important pathway.
4. Excretion: acetylated product is excreted through urine.
 ADVERSE EFFECTS:
1. Most patients tolerate it well.
2. The primary dose-dependent adverse consequences include peripheral neuritis and
neurological disorders.
3. Hepatitis is a major adverse effect that is more frequent in elderly persons and drinkers.
It is rare in children.
4. Hepatotoxicity is caused by dose-related damage to liver cells, which can be reversed by
discontinuing use of the medicine.
5. Lethargy, rashes, fever, acne, and arthritis are some of the other adverse effects.
 BRAND NAMES: ISONEX (100mg, 300mg tabs), ISOKIN (100mg tab).
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 7

8. • RIFAMPIN (RIFAMPICIN, R):
 PROPERTIES & MECHANISM OF ACTION:
1. Streptomyces mediterranei produces a semi-synthetic derivative of rifamycin B, which is
effective against both gram-positive and gram-negative bacteria, including M.
tuberculosis.
2. Rifampin suppresses RNA synthesis by interacting using the mycobacterial DNA-
dependent RNA polymerase beta subunit.
 RESISTANCE:
1. 1 in 107 bacilli are resistant to rifampin.
2. Mutations are resulted in binding of rifampin to RNA polymerase.
 PHARMACOKINETICS:
1. Absorption: It is well absorbed orally; however, food reduces absorption, therefore take
with an empty stomach. It penetrates intracellularly.
2. Distribution: It is broadly dispersed throughout the body.
3. Metabolism: The liver converts it to an active deacylated metabolite.
4. Excretion: Mostly in bile, but also in urine.
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 8

9. • PYRAZINAMIDE:
 PROPERTIES AND MOA:
1. Chemically equal to isoniazid, and weakly tuberculocidal which is more active in the acidic
medium.
2. Its inclusion in the duration time of treatment to reduce the risk of relapse and extremely
successful for the first two months of the course of therapy.
3. The mechanism of pyrazinamide is unknown, although like isoniazid, it is transformed in the
mycobacterial cell wall into pryazonic acid by the enzyme pyrazinamidase, which accumulates in
the acidic media and inhibits mycolic acid formation.
 RESISTANCE:
1. If administered alone, resistance develops quickly owing to mutations in the pncA gene.
2. Impaired uptake of pyrazinamide.
 PHARMACOKINETICS:
1. Absorption: Well absorbed via oral route.
2. Distribution: Widely diffused and has high penetration in the cerebrospinal fluid; so it is highly
used in the treatment of meningeal TB.
3. Metabolism: Metabolism by liver.
4. Excretion: Eliminated by urine.
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 9

10.  ADVERSE EFFECTS:
1. Hepatotoxicity is a prevalent issue, particularly in Western countries.
2. Inhibits hyperuricemia caused by uric acid production in the kidney.
3. Contraindicated in patients suffering from the liver disease and safety of usage during
pregnancy period is uncertain.
4. Other side effects include:
Abdominal distress, Flushing, Fever.
 BRAND NAMES: PYZINA (0.5, 0.75, 1.0 g tabs), RIZAP (0.75, 1.0 g tabs);
 TB Incidence
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 10

11. • STREPTOMYCIN:
 PROPERTIES AND MECHANISM OF ACTION:
1. It is the first clinically used antitubercular drug in the year 1947.
2. Streptomycin is effective against tuberculosis, although less effective than isoniazid and rifampin.
3. Due to poor cell penetration, it only affects extracellular bacilli, thus other medications are necessary to
remove the illness.
4. And they are irreversible inhibitors of protein synthesis.
 RESISTANCE:
1. When administered alone, resistance builds quickly, and the majority of patients experience a recurrence.
 PHARMACOKINETICS:
1. Absorption: poorly absorbs from the GI tract, IM or IV route usually administered.
2. Distribution: It does not pass into the CSF, although it does enter tubercular cavities.
3. Metabolism: Not metabolised
4. Excretion: It is renally excreted with unchanged form.
 ADVERSE EFFECTS:
1. Contraindicated in pregnancy due to risk of foetal ototoxicity.
2. Vestibular and auditory nerve damage and renal damage.
3. Hypersensitivity reactions are very rare.
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 11

12.  SECOND LINE OF DRUGS:
• ETHONAMIDE:
 PROPERTIES AND MOA:
1. Chemically comparable to isoniazid, but it also has a sulphurous content and a
comparable mode of action.
2. Mycobacteria transform it into an active intermediate metabolite that prevents the
formation of mycolic acid.
3. The majority of resistance is caused by mutations in the genes encoding the ethonamide
activating enzyme.
 PHARMACOKINETICS: absorbed completely via oral route, distributed in all over the body
and penetrates into CSF, metabolised in liver and excreted through urine.
 SIDE EFFECTS: hepatitis, anorexia, nausea, vomiting, salivation, metallic taste, and pain in
the epigastrium.
 BRAND NAMES: ETHIDE, MYOBID, ETHIKOX 250mg tab.
It is also used as a reserve drug in leprosy disease.
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 12

13. • PROTHIONAMIDE:
1. A near counterpart of ethionamide in terms of pharmacokinetics, side effects, and
antimycobacterial properties and actions.
2. In terms of clinical efficacy, it is deemed equivalent to ethionamide for treating MDR-TB and
MAC infections.
 BRAND NAMES: PROTHICID, PETHIDE 250 mg tab.
• CYCLOSERINE:
1. The antibiotic derived from S. orchidaceus is a tuberculostatic agent that functions as an
analogue of D-alanine.
2. It prevents the formation of bacterial cell walls by deactivating the enzyme that links two D-
alanine residues and racemizes L-alanine.
 PHARMACOKINETICS: oral absorption is so good, it diffuses all over the body and roughly one-
third of a dosage is metabolised, with the remaining portion eliminated as unaltered urine.
 ADVERSE EFFECTS: mostly neurological; over 50% of patients have neuropsychiatric symptoms,
such as sadness, drowsiness, headaches, tremors, and speech slurring.
Individuals having a past history of convulsions or mental disorders should not use this medication.
 BRAND NAMES: CYCLORINE, COXERIN, MYSER 250 mg caps.
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 13

14.  PARA-AMINO SALICYLIC ACID:
1. It is a sulphonamide derivative and acts by inhibition of folate synthetase.
2. It has tuberculostatic effect.
3. Resistance to para-amino salicylic acid is poor to develop.
 PHARMACOKINETICS: absorbed completely via oral route and all across the body, with
the exception of the CSF, 50% of the drug is acetylated and excreted rapidly glomerular
filtration and tubular secretion.
 ADVERSE EFFECTS: recurrent anorexia, nausea, and epigastric discomfort make patients
less receptive to the treatment. Other side effects include fever, rashes, malaise,
hypokalemia, goitre, liver malfunction, and seldom, blood dyscrasias.
 BRAND NAMES: SODIUM-PAS 0.5g tab, 80/100 granules.
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 14

15. • FLUOROQUINOLONES:
1. Fluoroquinolones, such as ofloxacin, levofloxacin, ciprofloxacin, and moxifloxacin, are
newly developed powerful anti-TB medications that are bactericidal and a good
substitute for first-line medications.
2. This class of antibiotics inhibits DNA gyrases and further prevents DNA synthesis.
3. Primary indication is the treatment of resistant TB.
 PHARMACOKINETICS: well absorbed via oral route, widely distributed in body fluids and
tissues and eliminates from urine by tubular secretion or glomerular filtration and some
quantity through bile in the form of faeces.
 ADVERSE EFFECTS: nausea, vomiting, diarrhoea, CNS effects like confusion, insomnia,
dizziness, anxiety and seizures.
Skin rashes are common.
 DOSE:
1. OFLOXACIN 800 mg once daily.
2. LEVOFLOXACIN 750 mg once daily.
3. MOXIFLOXACIN 400 mg once daily.
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16.  References:
1. http://library.unisel.edu.my/equip-
unisel/custom/ebook_catalog/ebook/EssentialsofMedicalPharmacology.pdf
2. https://www.slideshare.net/LingarajAnawal/antitubercular-drugs-232425340
3. https://idoc.pub/documents/kd-tripathi-essentials-of-medical-pharmacologyunitedvrg-
2013pdf-vnd59gjmkrlx
4. http://repository-tnmgrmu.ac.in/19150/1/200100122_Ganapathy_Raja.pdf
5. http://www.mpapalghar.in/resources/KD_Tripathi_-
_Essentials_of_Medical_Pharmacology__6th_Edition_1477380487135.pdf
SoPR, DEV BHOOMI UTTARAKHAND UNIVERSITY DEHRADUN 16