This slideshare is meant to provide knowledge about deadly disease TB and medications employed in treatment and cure of TB.

1. Anti Tuberculous Drugs And
Patient Counseling
Dr. Yamini D. Shah
Associate Professor
L.M.College Of Pharmacy, Ahmedabad
email id: ydslmcp@gmail.com

2. TUBERCULOSIS ?
• Chronic granulomatous disease caused
by Mycobacterium tuberculosis.
• Tuberculosis typically attacks the lungs,
but can also affect other parts of the
body.
• It is spread through the air when people
who have an active TB infection cough,
sneeze, or otherwise transmit respiratory
fluids through the air.

3. TUBERCULOSIS AND GLOBAL CHALLENGES
Tuberculosis (TB) persists as a global public health problem of serious magnitude
requiring urgent attention. Current global efforts to control TB have three distinct but
overlapping dimensions: humanitarian, public health, and economic.

4. MAGNITUDE OF THE PROBLEM
Source: WHO Geneva; WHO Report 2013: Global Tuberculosis Control; Surveillance, Planning and
Financing
Global annual incidence = 9.1 million
India annual incidence = 1.9 million
India is 17th among
22 High Burden
Countries (in terms
of TB incidence rate)

5. PROBLEM OF TB IN INDIA

8. ESTIMATED INCIDENCE OF TB IN
INDIA*
National 75
North Zone 95
East Zone 75**
West Zone 80
South Zone 75**
North
West East
South
** For programme monitoring
purpose estimated cases in East &
South zones have been kept at the
national level of 75 and this is
within the upper limit of CI or ARTI
in these zones

9. EVOLUTION OF TB CONTROL IN INDIA
 1950s-60s Important TB research at TRC and NTI
 1962 National TB Programme (NTP)
 1992 Programme Review
 only 30% of patients diagnosed;
 of these, only 30% treated successfully
 1993 RNTCP pilot began
 1998 RNTCP scale-up
 2001 450 million population covered
 2004 >80% of country covered
 2006 Entire country covered by RNTCP

10. SOCIALAND ECONOMIC BURDEN OF TB IN INDIA
Estimated burden per year
• Indirect costs to society $3 billion
• Direct costs to society $300 million
• Productive work days lost due to TB illness 100 million
• Productive work days lost due to TB deaths 1.3 billion
• School drop-outs due to parental TB 300,000
• Women rejected by families due to TB 100,000
TRC, Socio-economic impact of TB on patients and family in India, Int J Tub Lung Dis 1999 3: 869-877

11. PHYSIOLOGY & STRUCTURE
 Gram +ve , aerobic acid fast bacilli.
 Resistant to disinfectant ,detergent.
 Capable of intracellular growth.
 Human are the only natural reservoir.
TUBERCULOSIS DIAGNOSIS
 Clinical (presenting symptomsTB)
 Diagnostic Imaging(X-Rays)
 Bacteriology (smears, cultures)
 Pathology of biopsy specimens
 Epidemiological Factors

14. Medical History
• HIV status
• Symptoms of disease
• History of TB exposure, infection, or disease
• Past TB treatment and Demographic risk factors for TB
• Other medical conditions that increase risk for TB disease

15. EVALUATION TEST FOR TB
Emerging Rapid Methods
 Fast Plaque TB uses phage amplification technology.
 ELISA(QuantiFERON–TB)
 Enzyme-Linked immuno spot (ELISPOT). ELISPOT proved highly
useful to detect active tuberculosis in Adults and children.
Microscopic Observation Drug Susceptibility Assay. ( MODS )
 A new method gained importance in several reviews.
 Use a tissue culture plate based assay with use of Middle Brook
7HG. Needs a inverted light microscope.
 Even the drug resistance can be tested with Rifampicin, and
Isoniazid.

16. Non Specific Tests: Tuberculin Test ( Mantoux Test )
 Test to be interpreted in relation to clinical evaluation.
 Even the induration of 5 mm to be considered positive when tested on HIV
patients. Lacks specificity.
Specimen Collection Procedure
 Obtain 3 sputum specimens for smear examination and culture
 Spot, first morning, spot. Follow infection control precautions during specimen
collection
Sputum Smear Examination
 Always aim for three specimens at each exam
 Always store at a cool temperature and away from sunlight to preserve the
quality of specimens. 3 respiratory specimens will detect 90% of smear-positive
cases

17. AFB Smear-microscopy Acid Fast Smear Showing Tb Bacilli

18. Chest Radiograph
 Diagnosis of PTB solely on basis of
CXR not encouraged
 May have unusual appearance in HIV-
positive persons
 CXR is helpful in HIV+, smear -
negative patients
 Cannot confirm diagnosis of TB Arrow points to cavity in
patient's right upper lobe.

19. SEROLOGY IN TUBERCULOSIS.
• Several serological methods were evaluated.
• But never gained the acceptance of the majority of the clinicians.
• Serological tests are low sensitivity.
• Many physicians depend on serology in extra pulmonary tuberculosis.
HIV/AIDS - TUBERCULOSIS
• Consider the HIV status
• Identify the severity of Tuberculosis.
• Early use of chest radiography.
• Maximal number of sputum smear examinations.
• Sputum concentration methods to be encouraged even by smaller laboratories.
• Explore the use of Florescent Microscopy.
• All smear negative specimens should be cultured.

20. EXTRA PULMONARY TUBERCULOSIS
• Optimal specimen collection a priority,
• Molecular Methods are growing need.
• Clinicians start drug regimes on empirical basis.
• Several serological tests for antibody determinations are evaluated.
PULMONARY TB
• Productive, prolonged cough (duration of 2-3 weeks)
• Chest pain and Hemoptysis (bloody sputum)
• Signs may vary based on HIV status
ATYPICAL MYCOBACTERIUM
• Needs different drug regimes, unlike typical Mycobacterium isolates.
• Now a gowning concern in the era of AIDS.

21. FUTURE PERCEPTIONS
• It is highly essential to explore and discover rapid, simple, and
accurate tuberculosis diagnostic tools.
• A massive investment, greater scientific interest, political
commitment a top priority,
• Man power development, Human resource utilization a greater
concern.
• Microscopy and Florescent Microscopy utilization should be
immediate concern, and strengthening of treatment initiation
protocols.
• Effective methods in diagnosing smear negative patients a growing
priority.

22. ANTI-TUBERCULOSIS TREATMENT
• ISONIAZIDE (INH), [H]
• RIFAMPIN [R]
• PYRAZINAMIDE [Z]
• ETHAMBUTOL[E]
• STREPTOMYCIN [S]
• AMIKACIN
• AMINOSALICYCLIC ACID
• CAPREOMYCIN
• CIPROFLOXACIN
• CLOFAZIMINE
• CYCLOSERINE
• ETHIONAMIDE
• LEVOFLOXACIN
• RIFABUTIN
• RIFAPENTINE
FIRST LINE DRUGS SECOND LINE DRUGS

23. Standard Regimen And Dosing Frequency For
TB Patients

24. Recommended Doses Of First-line Anti-tuberculosis
Drugs For Adults

25. Mechanism of
action
The activated form of isoniazid - forms a covalent complex with an
inh-A (Acyl carrier protein -AcpM) and KasA, a ß-ketoacyl carrier
protein synthetase, which blocks mycolic acid synthesis and kills the
cell.
Absorption Rapid and complete; rate can be slowed with food. Peak Plasma Time:
1-2 hr
Distribution All body tissues and fluids including CSF; crosses placenta; enters
breast milk Protein Bound: 10-15%
Metabolism Hepatic ( fast, slow acetylators)
Elimination From 50 to 70 percent of a dose of isoniazid is excreted in the urine
within 24 hours
Half life Fast acetylators: 0.5 to 1.6 hours. Slow acetylators: 2 to 5 hours.
Adverse effects Peripheral neuritis
Hepatitis
Psychosis
Seizures
Anorexia
GIT discomfort
Fever
ISONIAZID

26. Mechanism of
action
Rifampin binds to the β subunit of bacterial DNA–dependent RNA
polymerase and thereby inhibits RNA synthesis. Resistance results
from any one of several possible point mutations in repoB, the gene for
the β subunit of RNA polymerase.
Absorption PO well absorbed; food may delay absorption
Peak plasma time: 2-4 hr
Distribution Highly lipophilic; crosses blood-brain barrier well, with or without
inflammation
Protein bound: 80%
Metabolism Metabolized by liver; undergoes enterohepatic recirculation
Elimination Feces (60-65%) and urine (~30%) as unchanged drug
Half life 3-4 hr (prolonged in hepatic impairment); in end-stage renal disease,
1.8-11 hr
Adverse effects Hepatotoxicity
GIT disturbances
Flu-like syndrome
CNS symptoms – drowsiness, ataxia, confusion, peripheral neuropathy
Hypersensitivity reactions
Staining of secretions
RIFAMPICIN

27. Mechanism of
action
Susceptible strains release pyrazinamidase, which converts PZA to
pyrazinoic acid (POA). POA decreases the pH below that which
retards the growth of M. tuberculosis and inhibiting the fatty acid
synthesis .
Absorption well absorbed
Distribution Protein binding: 50%.widely into body tissues and fluids including
liver, lung, and CSF. Relative diffusion from blood into CSF: adequate
with or without inflammation . CSF: blood level ratio: inflamed
meninges: 100%
Metabolism hepatic
Elimination urine (4% as unchanged drug)
Half life 9-10 hr
Adverse effects Malaise, Nausea, Vomiting , Anorexia, Arthralgia, Myalgia, Fever,
Rash, Itching, Acne, Photosensitivity, Gout, Dysuria, Porphyria,
Thrombocytopenia, Hepatotoxicity, Interstitial nephritis.
Pyrazinamide

28. Mechanism of
action
Ethambutol inhibits mycobacterial arabinosyl transferases. Arabinosyl
transferases are involved in the polymerization reaction of
arabinoglycan, an essential component of the mycobacterial cell wall.
Absorption Bioavailability: ~80%
Peak Plasma Time: 2-4 hr
Distribution Widely throughout body; concentrated in kidneys, lungs, saliva, and
red blood cells CSF: blood level ratio: 0% (normal meninges); 25%
(inflamed meninges) Protein binding: 20-30%
Metabolism Hepatic (20%) to inactive metabolite
Elimination ~50% urine; ~50% feces as unchanged drug.
Half life 2.5-3.6 hr; 7-15 hr (end-stage renal disease)
Adverse effects Acute gout or hyperuricemia, Abdominal pain, Anaphylaxis,
Confusion, disorientation, Fever, Headache, LFT abnormalities,
Malaise, Nausea
Optic neuritis; symptoms may include decreased acuity, color
blindness or visual defects (usually reversible with discontinuation)
Peripheral neuritis
Rash
Ethambutol

29. Mechanism of
action
Irreversibly inhibits bacterial protein synthesis. Protein synthesis is
inhibited in at least three ways:
1. Interference with the initiation complex of peptide formation.
2. Misreading of mRNA, which causes incorporation of incorrect
aminoacids into the peptide, resulting in a nonfunctional or
toxic protein.
3. Breakup of polysomes into nonfunctional monosomes.
Absorption well absorbed; not absorbed from gut
Distribution To extracellular fluid including serum, abscesses, ascitic, pericardial,
pleural, synovial, lymphatic, & peritoneal fluids; crosses placenta;
small amounts enter breast milk
Metabolism Protein Bound: 34%
Elimination urine (90% as unchanged drug); feces, saliva, sweat, & tears (<1%)
Half life newborns: 4-10 hr; adults: 2-4.7 hr, prolonged with renal impairment
Adverse effects Hypotension, Neurotoxicity, Drowsiness, Drug fever, Skin rash,
Nausea, Vomiting, Eosinophilia , Arthralgia, Tremor, Ototoxicity
(auditory, vestibular), Nephrotoxicity.
Streptomycin

30. Mechanism of
action
Aminosalicylic acid is a folate synthesis antagonist that is active
almost exclusively against mycobacterium tuberculosis.
It is structurally similar to p-amino benzoic acid(PABA) and the
sulfonamides.
Absorption T max is about 6 h
Distribution About 50% to 60% is protein bound.
Elimination 80% is excreted in the urine with at least 50% excreted in acetylated
form.
Half life The t 1/2 of free aminosalicylic acid is 26.4 min.
Adverse effects Nausea; vomiting; diarrhea; abdominal pain, Goiter with or without
myxedema., Hypersensitivity (eg, fever, skin eruptions, leukopenia,
thrombocytopenia, hemolytic anemia, jaundice, hepatitis,
encephalopathy, Loffler syndrome, vasculitis).
PARAAMINO SALICYLIC ACID

31. Mechanism of
action
Ethionamide, like pyrazinamide, is a nicotinic acid derivative related
to isoniazid. It is thought that ethionamide undergoes intracellular
modification and acts in a similar fashion to isoniazid.
Absorption Completely absorbed following oral administration. Bioavailability
approximately 100%.
Distribution Volume of distribution 93.5 L. Approximately 30% bound to proteins.
Metabolism Metabolism: Hepatic . Metabolized to the active metabolite sulfoxide,
and several inactive metabolites. The sulfoxide metabolite has been
demonstrated to have antimicrobial activity against Mycobacterium
tuberculosis.
Elimination Less than 1% of the oral dose is excreted as ethionamide in urine.
Half life 2 to 3 hours
Adverse effects Disorder of gastrointestinal tract (50%)
Postural hypotension
Dizziness
Drowsiness
Headache
Peripheral neuropathy
Psychosis
ETHIONAMIDE

32. Mechanism of
action
It inhibits the incorporation of D- alanine into peptidoglycan
pentapeptide by inhibiting alanine racemase, which converts L-alanine
to D- alanine, and D- alanyl-D –alanine ligase (finally inhibits
mycobacterial cell wall synthesis).
Cycloserine used exclusively to treat tuberculosis caused by
mycobacterium tuberculosis resistant to first line agents
Absorption Rapidly and almost completely absorbed (70 to 90%) from the
gastrointestinal tract following oral administration.
Distribution CSF concentration equal to that in plasma
Metabolism liver
Elimination urine
Half life with normal renal function is 10 hours, and is prolonged in patients with
impaired renal function.
Adverse effects Confusion
Dizziness
Headache
Seizure
Psychosis
CYCLOSERINE

33. Mechanism of
action
Bacteriostatic- inhibits cyclopropanaton of cell wall mycolic acids.
Half life 12 hrs
Adverse effects hepatitis, exfoliative dermatitis, SJS, bone marrow depression rarely
Common: Abdominal discomfort, loose motions, rashes, mild anemia,
anorexia.
THIOACETAZONE
Mechanism of
action
Bactericidal and believed to inhibit protein synthesis by binding to 30 S
ribosomal subunit.
Elimination urine
Adverse effects Agranulocytosis, Anorexia, Diarrhea, Dyspnea, Elevated BUN,
Enterocolitis, Headache, Incr salivation, Muscle cramps, Nausea,
Nephrotoxicity, Neurotoxicity, Ototoxicity, Pruritus.
KANAMYCIN

34. Mechanism of
action
Binds to 50S ribosomal subunit of susceptible microorganisms and
blocks dissociation of peptidyl t-RNA from ribosomes, causing RNA-
dependent protein synthesis to arrest; does not affect nucleic acid
synthesis
Absorption Rapidly absorbed
Bioavailability: 37%; variable effect with food
Peak plasma time: 2.3-4 hr
Distribution Extensively distributed into skin, lungs, sputum, tonsils, and cervix;
penetrates cerebrospinal fluid (CSF) poorly
Metabolism Metabolized in liver
Elimination Immediate release, ~70 hr; extended release, 59 hr
Half life Excretion: Feces (50% as unchanged drug), urine (5-12%)
Adverse effects Diarrhea ,Nausea ,Abdominal pain ,Loose stool ,Cramping ,Vaginitis
,Dyspepsia ,Flatulence ,Vomiting ,Malaise,Agitation, Allergic reaction,
Anemia, Anorexia, Candidiasis, Chest pain, Conjunctivitis, Constipation,
Dermatitis (fungal), Dizziness, Eczema
AZITHROMYCIN

35. Mechanism of
action
Semisynthetic macrolide antibiotic that reversibly binds to P site of 50S
ribosomal subunit of susceptible organisms and may inhibit RNA-
dependent protein synthesis by stimulating dissociation of peptidyl t-
RNA from ribosomes, thereby inhibiting bacterial growth
Absorption Highly stable in presence of gastric acid (unlike erythromycin); food
delays but does not affect extent of absorption
Distribution Distributed widely into most body tissues except central nervous system
(CNS)
Protein bound: 42-50%
Metabolism Partially metabolized by CYP3A4
Metabolites: 14-OH clarithromycin (active)
Elimination Approximates normal glomerular filtration rate (GFR)
Excretion: Urine (30-55%)
Half life Immediate release, 3-7 hr; active metabolite, 5-9 hr
Adverse effects Gastrointestinal effects, general, Abnormal taste, Diarrhea, Nausea,
Vomiting, Abdominal pain, Rash, Dyspepsia, Headache, Elevated
prothrombin time,Anaphylaxis, Anxiety, Clostridium difficile colitis,
Dizziness, Dyspnea, Elevated liver function tests
CLARITHROMYCIN

36. Mechanism of
action
Irreversibly binds to 30S subunit of bacterial ribosomes; blocks
recognition step in protein synthesis; causes growth inhibition. For
gram-negative bacterial coverage of infections resistant to gentamicin
and tobramycin
Absorption IM: May be delayed in bedridden patient
Distribution 0.25-0.4 L/kg, primarily into extracellular fluid (highly hydrophilic);
penetrates blood-brain barrier when meninges inflamed; crosses
placenta.
Elimination urine (94-98%)
Half life 2-3 hr
Adverse effects Neurotoxicity, Nephrotoxicity (if trough >10 mg/L), Ototoxicity,
Hypotension, Headache, Drug fever, Rash, Nausea, Vomiting,
Eosinophilia, Tremor, Arthralgia
AMIKACIN

37. Mechanism of
action
Inhibits DNA-dependent RNA polymerase
Absorption readily, 53%
Distribution body tissues including the lungs, liver, spleen, eyes, & kidneys
Vd: 9.32 L/kg
Protein Bound: 85%
Bioavailability: absolute: HIV: 20%
Metabolism hepatic CYP3A4 to active and inactive metabolites
Elimination Urine: 10% as unchanged drug, 53% as metabolites
Feces: 10% as unchanged drug, 30% as metabolites
Half life 45 hr (range: 16-69 hr)
Adverse effects Discoloration of urine, Neutropenia, Leukopenia, Rash ,
Thrombocytopenia, Abdominal pain, Diarrhea , Eructation , Headache,
Nausea/vomiting, Anorexia, Flatulence
RIFABUTIN

38. Mechanism of
action
They inhibit bacterial DNA synthesis by inhibiting bacterial
topoisomerase II (DNA Gyrase) and topoisomerase IV.
Inhibition of DNA Gyrase prevents the relaxation of supercoiled DNA
that is required for normal transcription and replication.
Inhibition of topoisomerase IV interferes with separation of replicated
chromosomal DNA into the daughter cells during cell division.
Absorption Rapidly absorbed orally- but food delays absorption,
Distribution High tissue penetration: lungs, sputum, muscle, prostate but low in CSF
Elimination Excreted primarily in urine, urinary and biliary concentrations are 10-50
times more than plasma
Half life 3-8hrs,
Adverse effects Nausea, vomiting,diarrhoea(most common). Headache, dizziness,
insomnia, skin rash, photosensitivity. Damage growing cartilage and
cause an arthropathy. Tendinitis, tendon rupture.
FLUOROQUINOLONES

39. Determining Drug Completion
1) Within 3 months for initial phase
2) Within 6 months for 4-month continuation phase
 Consider therapy interrupted if target doses not met within
specified time period
Management of Initial Phase Treatment Interruptions
• If lapse > 14 days, start from beginning
• If lapse < 14 days, continue treatment to complete total doses
warranted (if can be completed within 3 months)

40. • If received > 80% continuation-phase doses and:
1) sputum AFB smear negative on initial presentation, further
therapy not necessary
2) sputum AFB smear positive on initial presentation, continue
to complete full course
• If received < 80% continuation-phase doses and:
1) lapse < 3 months duration, continue to complete full course
(as long as all doses can be completed within 6 months)
2) lapse was 3 months or greater, then start initial phase 4-drug
regimen from the beginning

41. COMMON ADVERSE REACTIONS TO DRUG TREATMENT
Caused by Adverse Reaction Signs and Symptoms
Ethambutol Eye damage Blurred or changed vision, Changed color vision
Rifamycins
• Rifabutin
• Rifapentine
• Rifampin
Thrombocytopenia
GIT intolerance
Drug interactions
Easy bruising
Slow blood clotting
Upset stomach
Interferes with certain medications, such as birth
control pills, birth control implants, and methadone
treatment
Isoniazid,
Pyrazinamide,
or
Rifampin
Hepatitis Abdominal pain, Abnormal liver function test
Fatigue
Lack of appetite
Nausea, Vomiting
Yellowish skin or eyes, Dark urine
Isoniazid Peripheral neuropathy Tingling sensation in hands and feet
Pyrazinamide GIT intolerance
Arthralgia
Arthritis
Upset stomach, vomiting, lack of appetite
Joint aches
Gout (rare)
Streptomycin Ear damage
Kidney damage
Balance problems
Hearing loss, Ringing in the ears
Abnormal kidney function test results

42. DRUG INTERACTIONS
 Relatively few drug interactions substantially change concentrations of
antituberculosis drugs
 Antituberculosis drugs sometimes change concentrations of other drugs
 Rifamycins can decrease serum concentrations of many drugs, (e.g., most
of the HIV-1 protease inhibitors), to subtherapeutic levels
 Isoniazid increases concentrations of some drugs (e.g., phenytoin) to
toxic levels

43. RELAPSE
 A patient’s cultures become and remain negative while receiving
antituberculosis drugs, but at some point after completion of therapy:
 patient develops culture-positive TB disease again, or
 patient experiences clinical or radiographic deterioration consistent
with active TB disease
 Most relapses occur within the first 12 months after completion of
therapy
 Patients with cavitation on initial chest radiograph and a positive culture at
completion of 2 months of therapy are at increased risk of relapse with
standard 6-month regimens
 Patients with relapse are at increased risk for acquired drug resistance,
especially if the therapy was not directly observed

44. TREATMENT FAILURE
 Defined as positive cultures after 4 months of treatment in patients
for whom medication ingestion was ensured
 Single new drug should never be added to a failing regimen; it may
lead to acquired resistance to the added drug
 Add at least three new drugs (e.g., fluoroquinolone, ethionamide,
and an injectable drug: SM, amikacin, kanamycin, or capreomycin)
to the existing regimen being cognizant of the possibility of drug
resistance

45. DRUG RESISTANCE
 Established only by drug-susceptibility testing
 Treatment of TB caused by drug-resistant organisms should be done
in close consultation with an expert
 Patients not on DOT in the past or who had irregular treatment are at
risk of drug resistance
 Consider the following expanded regimen for drug resistance:
 INH, RIF, PZA, EMB plus three additional agents based on
probability of in vitro susceptibility (e.g., fluoroquinolone,
ethionamide, or an injectable drug: SM, amikacin, kanamycin, or
capreomycin)

46. SPECIAL TREATMENT SITUATIONS HIV/AIDS
 Treatment for HIV-positive patients same as for HIV-negative
patients, except
 Once-weekly INH-rifapentine in continuation phase is
contraindicated in HIV-positive patients
 Twice-weekly INH-RIF or INH-rifabutin should not be used
in patients with CD4+ T-lymphocyte counts less than 100/l
 Every effort should be made to use a rifamycin-based regimen for
the entire course of therapy

47. SPECIAL TREATMENT SITUATIONS (CHILDREN)*
 Thrice-weekly therapy not recommended
Recommended duration of treatment is 6 months (absence of factors
associated with increased risk of relapse)
Use DOT
 Treat young children (<5 years old) with three (rather than four) drugs in
initial phase (i.e., INH, RIF, and PZA)
 EMB not recommended unless increased likelihood of INH resistance or
diagnosis of adult-like TB**
* Defined as persons <15 years old
**Defined as upper-lobe infiltration and cavitation associated with sputum
production

48. TREATMENT SITUATIONS EXTRAPULMONARY TB
 Similar treatment regimen for pulmonary TB*
 6- to 9-month regimens that include INH and RIF are effective
 Corticosteroids used as adjunctive therapy for patients with TB
meningitis and pericarditis
 If PZA cannot be used in the initial phase, continuation phase must
be increased to 7 months
* Except for central nervous system (CNS) TB, including meningitis; length of
therapy is 9-12 months

49. TREATMENT SITUATIONS PREGNANCY - BREASTFEEDING
 Untreated TB represents greater hazard to a woman and her child than
treatment of disease
 Treatment of pregnant woman with suspected TB should be started if
probability of TB is moderate to high
 Initial phase treatment regimen should consist of INH, RIF, and EMB
 SM should not be substituted for EMB because of possible teratogenic
effects
 PZA not generally recommended for pregnant women in the United States

50. TREATMENT SITUATIONS RENAL INSUFFICIENCY-
END-STAGE RENAL DISEASE
 Renal insufficiency complicates management of TB because some
antituberculosis medications are cleared by the kidneys
 Dosage should not be decreased because peak serum concentrations may be
too low; smaller doses may decrease drug efficacy
 Dosing interval of antituberculosis drugs should be increased
 Most drugs can be given 3 times weekly after hemodialysis; for some drugs,
dose must be adjusted

51. SPECIAL TREATMENT SITUATIONS HEPATIC DISEASE
 Must consider regimens with fewer hepatotoxic agents for patients with
liver disease
 Recommended regimens:
1) Treatment without PZA Initial phase (2 months): INH, RIF, and
EMB Continuation phase (7 months): INH and RIF
2) Treatment without INH Initial phase (2 months): RIF, PZA, and
EMB Continuation phase (4 months): RIF, EMB, and PZA

52. REFERENCES
1. Continuing education credit will be awarded through: CDC’s Public Health
Training Network (PHTN) http://phppo.cdc.gov/phtnonline
2. MMWR at http://www.cdc.gov/mmwr
3. CDC’s Morbidity and Mortality Weekly Report:http://www.cdc.gov/mmwr
4. American Thoracic Society:
http://www.thoracic.org/adobe/statements/treattb.pdf
5. Recent Advances in Multi-Drug-Resistant Tuberculosis and RNTCP
Gagandeep Singh Grover and Jaspreet TakkarIndian J Community Med. 2008
October; 33(4): 219–223.
6. DOTS-Plus Guidelines-Central TB Division, Directorate General of Health
Services, Ministry of Health & Family Welfare, Nirman Bhavan, New Delhi
– 110011