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Page 1: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Anti-tubercular drugs

Prof. Anuradha Nischal

Page 2: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS

• Affects the lungs but can also affect other parts of the body.

Page 3: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

It is currently estimated that 1/2 of the world's population (3.5 billion) is infected with Mycobacterium tuberculosis.

Epidemiology

Page 4: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• Pulmonary tuberculosis

• Droplets

• Patients with the active disease (bacilli) expel them into the air by:– coughing– sneezing

Transmission

Page 5: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Signs & symptoms

• A bad cough that lasts 3 weeks or longer

• Coughing up blood or sputum (phlegm from deep inside the lungs)

• Fever• Weakness or fatigue• Weight loss• Anorexia• mailaise• Pain in the chest

Page 6: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Group 1

• First line oral ATDs

Group 2

• Injectible ATDs

Group 3

• Flouroquinolones

Group 4

• Second line oral ATDs

Group 5

• Drugs with unclear efficacy

Page 7: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Group 1/First line drugs include:                                       

ISONIAZID RIFAMPICIN PYRAZINAMIDE ETHAMBUTOL

most potent and best tolerated oral drugs HIGH EFFICACY AND LOW TOXICITY

Page 8: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Group 2/Injectable ATDs

Streptomycin Kanamycin

AmikacinCapreomycin

potent, bactericidal, but injectable drugs

Page 9: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Group 3/Flouroquinolones    

Ofloxacin Levofloxacin

Moxifloxacin Ciprofloxacin(resistance) so removed

 potent bactericidal well tolerated oral drugs. MDR  

Page 10: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Group 4/Second line oral drugs include:                                    ETHIONAMIDE PROTHIONAMIDE CYCLOSERINE TERIZODONE p-AMINOSALICYLIC ACID

    less effective, bacteriostatic, more toxic drugs for resistant tuberculosis

                                

Page 11: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Group 5/Drugs with unclear efficacy Thiacetazone

Clarithromycin Clofazimine Linezolid Amoxicillin/clavulanate Imipenem/cilastin

Drugs with uncertain efficacy, may be used for XDR

Page 12: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

ISONIAZID[H]

Cheapest ATD Mycobactericidal Bactericidal for rapidly growing bacilli

Quiscent ones are only inhibited Extra and intracellular bacilli Equally active in acidic & alkaline

medium.

Page 13: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

MOA

• Inhibits mycolic acids synthesis (unique component MBCW)

• High selectivity for mycobacteria

Page 14: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

MOA of INH:

ISONIAZID Kat G( catalase peroxidase in mycobacteria)Reactive metabolite

Inh A & Kas A

Inh DHFR Inh DNA syn

Inhibits the synthesis of Mycolic Acid

Page 15: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.
Page 16: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Mechanism of Resistance

• High level resistance is due to mutation in catalase peroxidase (Kat G) gene

Resistance may also develop due to mutation in Kas A & Inh A gene

• Efflux Of INH

• Loss of INH concentrating ability of bacteria

Page 17: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• Absorption: completely absorbed orally

• Distribution: penetrate all body tissue tubercular cavities, placenta & meninges

• Metabolism: in liver

• Excretion: in urine

• C/I known hypersensitivity acute hepatic disease

Page 18: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Peripheral NeuropathyAnd neurological manifestations

Paresthesias, numbness, mental disturbances most important dose dependent toxic effects.

• Pyridoxine deficiency• Interference with activation of pyridoxine and its

increased excretion in urine

Page 19: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• Q- Why Vitamin B6 is given with INH

Pyridoxine deficiency

Interference with activation of pyridoxine and its increased excretion in urine

Page 20: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• Pyridoxine given prophylactically(10mg/day) prevents neurotoxicity

• INH neurotoxicity is treated by pyridoxine 100mg/day

Page 21: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

WHOM

Must: Diabetics, Chr. Alcoholics, malnourished, pregnant, lactating & HIV infected patients

Page 22: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

HepatitisCommon in older adults & alcoholicsDose related damage to hepatic cellsreversible

Page 23: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

RIFAMPICIN[R]• Semi synthetic derivative of Rifamycin B from St.

meditarranei

• Bactericidal: Bactericidal efficacy ≈ INH• Extra & intracellular bacteria

Good sterilising property & resistance preventing action.

• All sub populations; best on spurters

Page 24: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

MOA

Rifampicin inhibits synthesis of R.N.A.

It binds to β subunit of mycobacterial DNA dependent RNA polymerase & blocks its polymerising function

Resistance develop due to mutation in rpo B gene( codes for RNA polymerase); X bind mammalian RNA polymerase (Basis for selectivity).

Page 25: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Other bacteria

Activity against other gram positive and gram negative bacteria

• Staph• N. meningitidis• H. influenzae• E.coli• Kleibseilla• Psuedomonas• Proteus• Legionella

Page 26: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• M. leprae is highly sensitive• MAC & other mycobacteria are moderately susceptible.

Page 27: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Pk• Absorption Well absorbed from g.i tract Food also interferes with abs; empty stomach

• Distribution widely distributed. Penetration intracellularly & enters • tubercular cavities

• Caseous masses • Placenta

• Metabolism Chiefly in liver to an active deacetylated metabolite. Which is excreted mainly in bile some in urine also. (30-70%). R and its metabolite undergoes enterohepatic circulation

T1/2 varies from 2-5 hrs

Page 28: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Adverse effects:HEPATITIS a major adverse effectUrine and secretions become orange-red in colour• Cutaneous syndrome• Flu syndrome• Abdominal syndrome

SERIOUS BUT RARE• Respiratory syndrome: breathlessness• Purpura, haemolysis, shock and renal failure

Page 29: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

INTERACTIONSRifampicin is a microsomal enzyme inducer

• It induces several CYP 450 iso enzymes• Thus enhances its own metabolism as well as of other drugs including:Warfarin, OCPs, Corticosteroids, Anti-fungal drugs, Digitoxin, Protease inhibitors, NRTIs, etc.

Increase dose; alternative method  

Page 30: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Why should Rifampicin not given with OCP?

Page 31: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Other uses

LeprosyProphylaxis of meningococcal & H. influenzae meningitis & carrier state

MRSABrucellosis.

Page 32: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

PYRAZINAMIDE

Weakly tuberculocidalMore active in acidic medium

More lethal to intracellular bacteria & bacteria at the site of inflammation Highly effective during 1st 2 months

By killing the residual intracellular bacteria it has good sterilizing activity

Page 33: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• Its inclusion has enabled duration of treatment to be shortened & reduced risk of relapse

One third reduction in the duration of anti-TB therapy & a two third reduction in TB relapse

• This led to reduction in duration of therapy to 6 mths, producing the short course ctx

Page 34: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

MOA

Pyrazinamide

Mycobacterial Pyrazinamidase

Pyrazinoic Acid (gets accumulated in

acidic medium)

Inhibits Mycolic Acid Synthesis

Page 35: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

+• Pyrazinoic acid also disrupts mycobacterial cell

membrane and its transport function

• Resistance develops rapidly if used alone & is due to mutation of gene pncA

Page 36: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• Absorption : Well absorbed orally

• Distribution : good penetration to all body

tissue & CSF• Metabolism: extensively in liver

• Excreted in urine

T1/2 6-10hrs

Dose: 25-30mg/kg/dayAdverse effects:

Page 37: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Hepatotoxicity (dose dependent); occurs at 40mg/kg/day; hepatic disease in 15%. Regimens employed currently 15-30 mg/kg/day are much safer.

Hyperuricemia; inhibits excretion of urates. In nearly all patients. May ppt acute episodes of gout.

Arthralgia, nausea, vomiting, dysuria, malaise and fever, loss of diabetes control

Page 38: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

ETHAMBUTOL[E]

Only Tuberculostatic drug among 1st line drugs.

Added to RHZ hastens the rate of sputum conversion and prevents the development of resistance.

Primarily added for this reason.

Page 39: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

MOA E Inhibits Mycobact. Arabinosyl

Transferase III

Arabinogalactan synthesis

Essential component of Myco. Cell

wall; disrupts the assembly of mycobacterial cell wall.

Page 40: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

PK

• Absorption: Well absorbed from g.i.t.• Distribution : Widely distributed• T1/2 ~ 4hrs

• Excretion: Glomerular filtration & tubular secretion

Dose to be reduced in Renal failure

Page 41: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Side effects:Loss of visual acuity (reversible)

loss of color vision

Field Defect due to optic neuritis Dose & duration dependent toxicity.

Pt should be instructed to stop the drug at first indication of visual impairment. Visual toxicity: reversible

Page 42: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• Contra-indication; In children <6yrs and Creatinine clearance <50ml/min

• Hyperuricaemia

Page 43: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

FQs

• Ofloxacin• Levofloxacin• Ciprofloxacin• Moxifloxacin

New potent oral mycobactericidal drugs

Page 44: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• Primary indication Drug resistant TBkey component of all regimens for MDR TB

• Alternative to first line

Substitution of Ethambutol with Mfx has been found to enhance rate of bacterial killing & cause faster sputum conversionPossibility of decreasing the duration of treatment to less than 6 months

Page 45: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• Mfx is the most active FQ against M. TB• Lvx is more active than Ofx & Cfx

Dose:• Ofloxacin: 800mg OD• Levofloxacin 750 mg OD• Moxifloxacin 400mg OD

Page 46: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Goal of AT CTx

• Kill dividing bacilli• Kill persisting bacilli• Prevent emergence of resistance.

Page 47: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Goal of AT CTx

Kill dividing bacilli• Reduce bacillary load• Achieve quick sputum negativity• Patient non-contagious• Transmission interupted• Quick symptomatic reliefKill persisting bacilli• Effect cure & prevent relapse

Page 48: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Goal of AT CTx

Prevent emergence of resistance.• So that bacteria remain susceptible to the drugs

Page 49: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Short Course Chemotherapy

Who has introduced 6-8 months multidrug “short course” regimens under DOTS programme. 

Page 50: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

•4 drugs

Page 51: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Multidrug therapy

HRZE

Page 52: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

4 drugs/Multidrug therapy

Page 53: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Why?????

• Use of single drug in tuberculosis results in the emergence of resistant organisms and relapse in almost 3/4th of patients. 

• Combination:• H & R most potent bactericidalCombination synergisticDuration of therapy shortened from >12 months to 9 months

Page 54: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• Z acts on intracellular bacteriaIt has very good sterilizing activityAddition of  Pyrizinamide further reduces duration from 9 to 6 months

• E is bacteriostatic mainly serves to prevent resistance and may hasten sputum conversion

• Single daily dose• AKT-4

Page 55: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• Cost• Convenience• Feasibility• Decreased resistance

Page 56: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

TREATMENT CATEGORIES

CATEGORY-I

New cases

Page 57: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Category I

• New case • Sputum positive for Mycobacterium TB 

Page 58: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Category II

• Smear positive TB patients• Exposed to ATT in the past• Did not complete the course• Or took irregular medication• Or relapsed after responding• Failed to respond; failures

Higher risk of harbouring DR bacilli

Page 59: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Two phases

Intensive phase

Continuation phase

Page 60: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Intensive phase

• 4-5 drugs• 2-3 months• Rapidly kill the bacilli

Bring about sputum conversionAfford symptomatic relief

Continuation phase

• 2-3 drugs• 4-5 months

Remaining (few) bacilli eliminatedSo that relapse does not occur

Page 61: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Category Intensive phase Continuous phase

Duration(months)

Comment

I 2 HRZE daily 4 HR daily 6 Optimal

2 HRZE daily 4 HR thrice weekly

6 Acceptable if DOT ensured

2 HRZE thrice weekly

4 HR thrice weekly

6 Acceptable if DOT ensured

II  2 HRZES daily+1 HRZE daily

5 HRE daily 8 For patient with low/medium risk of MDR-TB.

Emperical (Standardized) MDR regimen

Emperical(Standardized)MDR regimen

18-24Till DST

For patient with high risk of MDR-TB.Failures, 2nd default, contact of MDR

Tt of TB Guidelines, 4th edition (2010), WHO , Geneva.

Page 62: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Category two

• Thrice weekly option not available for retreatment categories

• Assess risk of MDR-TB (DST)

Page 63: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Recommended dosesDrug Daily dose

mg/kg maximum

3 times per week dose

mg/kg maximum

Isoniazid 5(4-6)                          300 mg 10(8-12)                     900 mg

Rifamin  10(8-12)                      600 mg 10(8-12)                     600mg

Pyrazinamide  25(20-30) 35(30-40)

Ethambutol  15(15-20) 30(25-35)

Streptomycin  15(12-18) 15(12-18)         1000mg

Tt of TB Guidelines, 4th edition (2010), WHO , Geneva.

Page 64: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Multiple Drug Resistance(MDR)

• Defined as Resistance to both Isoniazid and Rifampin (compulsorily) and number of other(1st line drugs)

• Rapid course    With worse outcomes

Page 65: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• 2.8% of all new cases• 12-17% of retreatment cases• Treatment is difficult  as second line drugs    are less efficacious, less convenient, more expensive and toxic for longer duration 

Page 66: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

General principles

MDR Regimen• At least 4 drugs• Include drugs from group I to group IVGp I drugs                 (except H;R)         2+ one injectable; Gp II                           1One FQ; Gp III                                         1One/two Gp IV drugs                             2

Page 67: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

General principles

Gp I drugs

2; (except H;R)

Page 68: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Standardized RNTCP regimen for MDR-TB

Intensive phase6 drugs; 6-9 months;

• Kanamycin• Ofloxacin• Ethionamide• Cycloserine• Pyrazinamide• Ethambutol

Continuous Phase4 drugs; 18 months

• Ofloxacin• Ethionamide• Cycloserine• Ethambutol

+ Pyridoxine 100 mg/day

RNTCP DOT plus guidelines;2010.

Page 69: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Extensively Drug Resistant(XDR)• This term is applied to bacilli that are resistant to at

least four most effective cidal drugs, i.e. Cases resistant to INH Rifampicin Flouroquinolone and one of  Kanamycin/Amikacin/Capreomycin

• Virtually untreatable• Mortality is very high, particularly among HIV positive patients.

Page 70: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

detected or diagnosed

• Standardized MDR regimen must be stopped immediately

• Expert panel may decide on instituting treatment with group v drugs

• Uncertain efficacy• Expensive

Page 71: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Chemoprophylaxis

• INH: 300mg daily X 6 monthsChildren : 10 mg /Kg 

• INH resistanceH(5 mg/kg)+R(10 mg/kg; max: 600 mg)X 3 months

• If INH cannot be used : R X 4 months

Page 72: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Whom

• Contacts of open cases• Children with Mx positive & TB pt in the family• Neonate of TB mother• Pt of leukemia

–Diabetes– Silicosis–HIV positive–C. steroid therapy; who show +ve Montoux

Page 73: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Pregnancy

• S contraindicated; ototoxicity

USA • Z not recommended

INDIA• Avoid Z• 2HRE+7HR

Page 74: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

• Treatment should not be withheld or delayed     because of pregnancy

• All pregnant women being treated with INH should receive pyridoxine 10-25 mg/day

Page 75: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

Lactation

• All ATDs compatible with breast feeding• Full course should be given to mother

Infant: • BCG vaccination• 6 month INH prophylaxis after ruling out active TB.

Page 76: Anti-tubercular drugs Prof. Anuradha Nischal. Deadly infectious disease caused by MYCOBACTERIUM TUBERCULOSIS Affects the lungs but can also affect other.

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