Pathophysiology and Treatment of Tuberculosis with detailed classification of drugs used along with detailed drug profiles of important drugs

1. 10/10/2017 1
Presented by-
Mukul Sunil Tambe.
M. Pharm. Sem. I
Pharmacology
Roll No. 8

2. Introduction
Tuberculosis infection
Anti-tubercular drugs
DOTS
References
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CONTENTS:

3. Mycobacterium tuberculosis

Highly infectious disease
6th major cause of deaths in India
Affecting health professionals as well
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INTRODUCTION:

4. 
INTRODUCTION
(CNTD.):
SYMPTOMS DIAGNOSIS
Radiology (commonly
chest x-rays),
A tuberculin skin test,
Blood tests,
Microscopic examination
and microbiological culture
of bodily fluids.
Treatment is difficult and
requires long courses of
multiple antibiotics.
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5. 
1. First line drugs
These drugs have high antituberculosis efficacy and low toxicity and are
used routinely
 Isoniazide Ethambutol
 Rifampin Streptomycin
 Pyrazinamide
2. Second line
They are used occasionally because of bacterial resistance or high
toxicity
 Thaicetazone
 Paraaminosalicylic Acid Ciprofloxacin
 Ethionamide Clarythromycin
 Cycloserine Kanamycin
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Anti-tubercular Drugs

6. 
First-line anti-tuberculosis medication in prevention and
treatment of TB.
Never used alone because highly prone to produce
resistance.
Also has an antidepressant effect, and it was one of the
first antidepressants discovered.
It is cheapest drug.
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ISONIAZIDE:

7. 
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MECHANISM OF ACTION :
 Active in acidic and alkaline
medium
 Inhibition of synthesis of mycolic
acid which are unique fatty acid
component of mycobacterial cell
wall
 Breakdown of cell wall
 Leakage of cell contents
 Cell death

8. 
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INTERACTIONS AND
ADVERSE EFFECTS
Interactions
 Aluminum hydroxide inhibits
Isoniazid absorption
 Isoniazid inhibits phenytoin,
carbamazepine, diazepam and
warfarin metabolism
Adverse effects
 Peripheral neuritis
 Mental disturbances
 Rarely convulsions
 Hepatitis is major adverse effect
 Rashes, fever, acne arthralgia

9.  Obtained by streptomyces mediterranei
 Major addition to the cocktail-drug treatment of tuberculosis and
inactive meningitis, along with isoniazid, ethambutol,
pyrazinamide and streptomycin.
 It must be administered regularly daily for several months
without break; otherwise, the risk of drug-resistant tuberculosis is
greatly increased.
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RIFAMPIN

10. 
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MECHANISM OF
ACTION :
 Inhibits DNA-dependent RNA
polymerase in bacterial cells by
binding its beta-subunit
 Preventing transcription to RNA
 Preventing subsequent translation to
proteins
 Inhibition of cell growth

11. 
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INTERACTIONS AND ADVERSE
EFFECTS
 Interactions
 Enhances own and other
drugs metabolism like
warfarin, oral
contraceptives,
corticosteroids,
sulfonylureas, Digitoxin,
steroids, ketoconazole
 Adverse effects
 Hepatitis
 Jaundice
 Respiratory syndrome
 Shock and renal failure
 Flushing, rash
 Flu syndrome-fever, chills, headache,
malaise and bone pain
 Abdominal syndrome-nausea
vomiting abdominal cramps
 Urine and other secretion may
become orange red but it is harmless

12. 
 It is usually given in combination with other tuberculosis
medications, such as isoniazid, rifampicin and
pyrazinamide.
 It must be administered regularly daily for several months
without break; otherwise, the risk of drug-resistant
tuberculosis is greatly increased.
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ETHAMBUTOL:

13. 
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MECHANISM OF ACTION :
 Ethambutol
 Blockage of Arabinosyl
Transferases
 No Polymerization of
Arabinoglycan
 Interferences in cell wall
synthesis

14. 
INTERACTIONS AND
ADVERSE EFFECTS
Interactions
 Antacids
 over-the-counter
medicines,
 vitamins,
 herbal products
Adverse effects
 Optic neuritis (hence contraindicated in
children below six years of age)
 Red-green color blindness
 Peripheral neuropathy
 Arthralgia
 Hepatotoxicity
 Hyperuricaemia
 Milk skin reaction
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15. 
 Streptomycin is an antibiotic used to treat a number of
bacterial infections.
 This includes tuberculosis, Mycobacterium avium
complex, endocarditis, brucellosis, plague, tularemia and
rat bite fever.
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STREPTOMYCIN:

16. 
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MECHANISM OF ACTION :
1. Interference with initiation of complex formation of peptides.
2. Misreading of mRNA, which causes incorporation of incorrect
Amino acids into the peptide.
3. Breakdown of polysomes into non-functional monosomes.

17. 
INTERACTIONS AND
ADVERSE EFFECTS
Interactions
 Allergic Conditions.
Conditions in which it
should not be given:
1. Dehydration
2. Neuromuscular
Blockade
3. Ototoxicity
4. Renal Dysfunction
Adverse effects
 Feeling like the world
spinning,
 Vomiting,
 Numbness of the face,
 Fever and rash
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18. 
 It is not generally recommended for the treatment of latent
tuberculosis.
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PYRAZINAMIDE:

19. 
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MECHANISM OF ACTION :

20. 
INTERACTIONS AND
ADVERSE EFFECTS
Interactions
 Allergic Conditions.
Conditions in which it
should not be given:
1. Gout
2. Hepatotoxicity
3. Liver Disease
4. Renal Dysfunction
5. Diabetes Mellitus
6. Hemodialysis
Adverse effects
 Joint pains
 Nausea and vomiting,
 Anorexia,
 Skin rash, Urticaria,
 Pruritus, Dysuria,
 Interstitial nephritis,
 Malaise
 Rarely porphyria
 Fever.
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21. 
Drug Absorption Distribution Metabolism Excretion
Isoniazid Orally & i/m Distributes in
CSF, Serum
Acetylation in
Liver
Renal
Rifampin Orally (Food
retards abs)
60%-90%
Plasma binding
Plasma T1/2=1.5
to 5 Hrs. Liver
60%-65% Fecal
Ethambutol Orally Well distributed Liver 50% unchanged
in Urine
Streptomycin Poor orally
i/m
Conc. In Liver,
Kidney &
Skeletal Muscles
Liver Max.
Unchanged in
urine
Pyrazinamide Orally Cross BBB Plasma T1/2=9
to 10 Hrs. Liver
Renal
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PHARMACOKINETICS:

22. 
DRUG Mechanism of
Action
Adverse effects Drug Interactions
Cycloserine Inhibition of Alanine
racemerase & D-
alanine ligase
Headache,
Irritability,
Depression,
Psychosis,
Convulsions
With Tramadol,
increases risks of
Tremors
PASA Amino salicylic acid
is decarboxylated to
produce CO2 & 3
aminophenol
Hepatitis, Diarrhea,
Haemolysis
Slows the phenytoin
elimination
Ethionamide Inhibits mycolic acid
synthesis
Dizziness, Loss of
appetite, metallic
taste
Worsens liver
damage along with
Rifampin.
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SECOND LINE DRUGS:

23. 
 The two antibiotics most commonly used are rifampicin and
isoniazid.
 TB requires much longer periods of treatment (around 6 to 24
months) to entirely eliminate mycobacteria from the body
 This 6-12 months treatment is replaced by 6 months, possibly
due to better understanding of biology of TB
 The goals of therapy are:
 Kill dividing bacilli,
 Prevent emergence of resistance,
 Drug combinations are preferred to maximize the above
actions together , isoniazid and rifampin are efficacious drugs
and their combination is used.
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TREATMENT OF TB

24.  Directly Observed Treatment Short-course (DOTS) strategy is the
management package that ensures effective diagnosis and treatment of
infectious cases
 On March 24, 1997, the Director-General of the World Health Organization
declared, “the DOTS strategy for TB control represents the most important
public health breakthrough of the decade, in terms of lives which will be
saved”
 The DOTS strategy consists of increased commitment, effective diagnosis,
standard treatment given under direct observation, secure drug supply and
systematic monitoring and evaluation of all patients started on treatment
 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.
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DIRECTLY OBSERVED
TREATMENT SHORT-COURSE
(DOTS)

25. 
1. Essentials of medical pharmacology, 5th edition by
Tripathi, 2004, page no.698-708
2. Essentials of Pharmacotherapeutics by FSK Barar,
434-441
3. www.wikepedia.org/wiki/treatment_of_tuberculosi
s
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REFERENCES: