tuberculosis 01

8/13/2019 Tuberculosis 01

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TUBERCULOSIS

Infectious disease caused by Mycobacteriumtuberculosis

Rod 4mm in length


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TUBERCULOSIS

Robert Koch (1843 1910)

Declared the discovery of Mycobacterium

tuberculosis on 24thMarch, 1882


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TUBERCULOSIS

Typical Mycobacteria:

Mycobacterium tuberculosis

Mycobacterium bovis


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TUBERCULOSIS

Atypical Mycobacteria:

Mycobacterium avium

Mycobacterium intracellulare

Mycobacterium scrofulaceum

Together known as

Mycobacterium Avium Complex (MAC)


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TUBERCULOSIS

Atypical Mycobacteria:

Mycobacterium kanasaii

Mycobacterium xenopi

Mycobacterium malmonese


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TUBERCULOSIS

Characteristics of tubercle bacilli:

Acid Fast Bacilli(AFB)

Multiplies slowly Naturally reistant to common antibiotics

Cell wall contains mycolic acid

Can remain dormant for long period

Forms granuloma in infected tissue(Tiny lesion, about 1mm in diameter composed of

predominantly epithelioid cells and rimmed at theperiphery by lymphoid cells)


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TUBERCULOSIS

Characteristics of tubercle bacilli:

Acquire resistance to the effective drug if

given a chance

Persists in macrophages & within caseouslesion, which are the main source of relapse


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TUBERCULOSIS

Modes of transmission:

Inhalation

Intake of infected milk

Direct contact with certain articles used

by the patients


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TUBERCULOSIS

Sterilization of sputum:

Direct sunlight kills bacilli in 5minutes

HeatDistroyed in 20 minutes at60 C and in 5 minutes at 70C

Sodium Hypochlorite (1%) killsrapidly

Resists 5%phenol for several hours


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TUBERCULOSIS

Prevention:

BCG (Bacillus Calmette Guerin) -Vaccine consisting of live bacilli without

virulence. Originally developed frombovine straingrown many years inlaboratory

80% protection against TB for 15 Yrs

Protection for child esp. against miliarytuberculosis and tuberculous meningitis


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TUBERCULOSIS

Symptoms: IN PTB

Cough for more than 3 weeks

Coughing blood

Pain in the chest >3 weeks

Weight loss


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TUBERCULOSIS

Diagnosis:

Sputum Test

X-ray chest

Tuberculin (Mantoux) skin test InjectingPPD intradermally.

Not very reliable

Culture


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The Course of Tuberculosis

Primary complex

Progressive Primary tuberculosis

Spread to pleura

Acute cavitaion of focus

Haematogenous spread


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Infection & patient defences


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Complications of primary complex


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Physiologic population of

Mycobacterium Rapidly multiplying organisms or extracellular

organismsor active organisms

Intermittently multiplying organisms or

Intercaseous organismsor semidormant

organisms

Slowly multiplying organisms or intracellularorganisms

Dormant organisms


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Typesof tuberculosis

Pulmonary TB

PrimaryComplex

Or

GohnsComplex

Miliary TB

Progressive

Primary TB

Pleural effusion

PneumoniaBronchopneumonia

Extra-

pulmonary

TB


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First Line anti-TB drugs

Isoniazid (INH) H

Rifampicin R

Streptomycin S

Pyrazinamide Z

Ethambutol E Thiacetazone T


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Second line anti-TB drugs

Cycloserine

PAS

Ethionamide

Prothionamide

Sparfloxacin

Ofloxacin

Ciprofloxacin

Kanamycin

Amikacin

Capreomycin

Viomycin

Etc.


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Isoniazid (INH)

Administration : Oral

Absorption : Totally absorbed from GIT

T max : 1-2 hours

Half-life : 1-3 hours

Distribution : All body cells & fluid

Metabolism : In liver

Excretion : In urine

Mode of action : Inhibits the biosynthesis of Mycolic acidUsage in pregnancy : Safe


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Isoniazid (INH)

Dosage : 300 mg/day (Adults)

5 mg/kg/day (Children)

Side effects : Generalized skin rashes

Drug induced hepatitis

Peripheral neuropathy, producing

tingling and numbness of the hands

and feet. It can be treated by giving100-200 mg pyridoxine daily.

It can be prevented by giving

10 mg pyridoxine daily


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Rifampicin


Absorption : Well absorbed when taken in empty

stomach.Food delays & reduces absorption

C max : 600 mg 4 7-9 mcg/ml

T max : 2-3 hours

Half life : 2-3 hours


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Rifampicin

Distribution : Good penetration to all tissues,

due to lipid solubility


Excretion : In faeces and urine

Mode of action : Bactericidal.Inhibits an enzyme called

DNA dependent RNA polymerase

which help in RNA synthesis


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Rifampicin

Dosage : Adults: 50 kg: 600 mg/day

Children: 10 mg/kg/dayTo be given in empty stomach,

half an hour before breakfast

Usage in pregnancy : Safe

Side effects : Liver damage

Nausea, anorexia, diarrhoea etc.


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Rifampicin

Drug interaction : Rifampicin stimulates liver enzymes,

which may breakdown other drugs

more rapidly than normal.

So half-life of prednisolone, digoxin,

ketoconazole, anticoagulants and

oral contraceptives decreased.


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Pyrazinamide


Absorption : Well absorbed

C max : 35 mcg/ml

T max : 2 hours

Half life : 10 hours


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Pyrazinamide

Distribution : Good distribution in all body tissues &

fluids


Excretion : In urine

Mode of action : Inside the macrophages, in acidic pH

it gets converted in to pyrazinoic acid

which is bactericidal


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Pyrazinamide

Dosage : < 50 kg body weight : 1.5 gm

50 74 kg : 2 gm

>74 kg : 2.5 gm

Usage in pregnancy : Though safety in pregnancy is not yet

established, WHO & IUATLD recommends use of Z in a 6

month regimen including R,H & Z.

Side effects : Hepatotoxicity

Arthralgia

Gouty arthritis


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Ethambutol

Advantage : Prevent the emergence of drug resistance

when added to main bactericidal drugs


Absorption : About 80% of the oral dose is absorbed

C max : 15 25 mg/kg 4 2-5 mcg/ml

50 mg/kg 4 10 mcg/ml


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Ethambutol

T max : 2-4 hours

Half life : 5 hours

Distribution : Distributed in lungs, RBCs and penetrates

inflamed meninges

Excretion : In urine, mostly as unchanged drugs


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Ethambutol

Mode of action : Inhibits synthesis of ribonucleic

acid and also inhibits mycolic acid

incorporation into bacterial cellwall

Dosage : 15 mg/kg of body weight/day

For resistant cases 25 mg/kg ofbody weight once daily for 6o days

followed by 15 mg/kg once daily


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Ethambutol

Side effects : Retrobulbar neuritis leading to blindness

Can be reversed, if administration of thedrug discontinued in the early stages itself.


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Action of drugs on various physiologic population

Drug Extracellular Caseous Intracellular

H +++ ++ +

R+++ +++ ++

S

+++ - -

Z - - +++

E ++ - ++


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Chemotherapy

Conventional chemotherapy

Short Course Chemotherapy

Intermittent Therapy

DOTS


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-Objectives of Intensive Phase-

To arrest the progress of the disease

To prevent complications

To make patient noninfectious

To prevent development of MDR TB

To relieve the disabling symptoms


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-Objectives of Continuation Phase-

To eradicate pathogen

To prevent development of MDR TB

To prevent relapse


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Chemotherapy

Guidelines given by

WHO (World Health Organiztion

IUATLD (International Union AgainstTuberculosis & Lung Disease)


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ChemotherapyPrinciples

Must include minimum 2 bactericidal drugs

INH for complete regimen if bacillus is not

resistent to INH Rifampicin at least in intensive phase

Pyrazinamide should be used in intensive phase

S & E should not replace Z in intensive phase

A single drug should not be added to failing regimen

Relapse is suggestive of non-compliance orresistance


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Dosage chart of essential anti -TB drugs

Essential

Anti-TB DrugsRecommended dose (Mg/Kg)

Daily 3 days/week 2 days/week

Isoniazid 5 (4-6) 10 (8-12) 15 (13-17)

Rifampicin 10 (8-12) 10 (8-12) 10 (8-12)

Pyrazinamide 25 (20-30) 35 (30-40) 50 (40-60)

Streptomycin

15 (12-18) 15 (12-18) 15 (12-18)Ethambutol 15 (15-20) 30 (25-35) 45 (40-50)

Thiacetazone 2.5 Not applicable

WHOs TB treatment categories:


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TB

Treatment

Category TB patients

Alternative TB treatment regimens

Initial phase Continuation

phaseI

New smear-positive PTB;New smear-negative PTB with

extensive parenchymal

involvement;

New cases of severe forms ofextra-pulmonary TB

2EHRZ(SHRZ)

2EHRZ(SHRZ)

2EHRZ(SHRZ)

6HE

4HR

4H3R3

II Sputum smear-positive;

Relapse;

Treatment failure;

Treatment after interruption

2SHRZE/1HRZE

2SHRZE/1HRZE

5HRE

5H3R3E3

III New smear negative PTB

(other than category I);

new less severe forms of

extra-pulmonary TB

2HRZ

(If the patient is

HIV+ add E)

6HE

4HR

4H3R3

WHO s TB treatment categories:

Category IV Chronic case : Sputum positive after re-treatment

WHOs TB treatment categories:


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TB

Treatment

Category TB patients

Alternative TB treatment regimens

Initial phase Continuation

phase

I

New smear-positive PTB;New smear-negative PTB with

extensive parenchymal

involvement;

New cases of severe forms ofextra-pulmonary TB

2 months Tetra-cox

or

2 months Roko Kit

or

2 months Tricox +Streptomycin I nj .

6 months

Themibutol

plus

or4 months

TicinexII Sputum smear-positive;

Relapse;

Treatment failure;Treatment after interruption

3 months Tetra-cox

or Roko Kit along

with StreptomycinInj. first 2 months

5 months

Thre

III New smear negative PTB

(other than category I);

new less severe forms of

extra-pulmonary TB

2 months

Tricox

(If the patient is HIV+

give Tetracox/Roko Kit)

6 Themibutol

plus

or

4 Ticinex

WHO s TB treatment categories:


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Fixed Dose Combinations

Geneva Workshop 1995 lists advantages:

Prevention of acquired drug resistance

Elimination of monotherapy

Ensuring that R is being taken by the patient

Reduction in the number of the tablets

Better acceptability Simplifies dosage regimen

Improvement in compliance


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According to American Thoracic Society: Enhance patient compliance

Reduce the risk of inappropriate monotherapy

Prevent secondary drug resistance


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Our FDCs:

Tetracox

Thre

Tricox


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Our anti-TB brands

Tetracox

Each tablet contains:Rifampicin - 225 mg

Isoniazid - 150 mg

Pyrazinamide - 750 mg

Ethambutol HCl

400 mg

For the intensive phase of

I & II Category

Ensures all 4 cardinal drugsPrevents monotherapy

Ensures simplified prescription

Prevents relapse

Dosage: 2 tablets per day

half an hour before

breakfast.


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Our anti-TB brands

Tetracox - Competitors

Forecox - Macleodes

R-cinex-EZLupin

RHZ Plus- Overseas

AKT FD Lupin

(R-150, H-100, Z-500, E-400)


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Our anti-TB brands

Roko Kit

Each kit contains:One tablet of Rifampicin 450 mg

One tablet of ( Ethambutol 800 mg + INH 300mg)

Two tablets of pyrazinamide 750 mg each


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Our anti-TB brands

Roko Kit

For the intensive phase in 1st& 2ndCategoryAll four cardinal drugs are ensured

Dosage convenience

One kit a day


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Our anti-TB brands

Roko KitCompetitors

AKT-4 Lupin

R-450 Z-750E-800+H-300+ Z-750+ +

4-D- Novartis

R-450+ H-300 E-800 Z-750Z-750+ + +


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Our anti-TB brands

Tricox


Isoniazid - 150 mg

Pyrazinamide - 500 mg

For the intensive phase of

III Category

Ensures all 3 drugs neededPrevents monotherapy


Prevents relapse

Dosage: 2 tablets per day


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Our anti-TB brands

Tricox - Competitors

Caviter Forte - Merind (Wockhardt)

(H-150+Z-750+R-225)

3-FD - Novartis

(H-150+Z-750+R-225)

RHZ - Overseas

(H-150 + Z-500 + R-225)


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Our anti-TB brands

Thre


Isoniazid - 300 mg

Ethambutol - 800 mg

For the continuation phase of

Category II

Ensures all 3 drugs neededPrevents monotherapy


Prevents relapse

Convenient dosage

Dosage: 1 tablet per day


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Our anti-TB brands

Thre - Competitors

Monto-3 - Shreya

(H-300+E-800+R-450)

Rcinex-E - Lupin

(H-300+E-800+R-450)

AKT-3 - Lupin

(1 cap of R450 & 1 tab of E800+H300)


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Our anti-TB brands

Ticinex


Isoniazid - 300 mg

For the continuation phase of

Category I & III

Ensures the 2 drugs neededPrevents monotherapy


Prevents relapse

Convenient dosage

Dosage: 1 tablet per day


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Our anti-TB brands

Ticinex - Competitors

R-Cinex - Lupin

Montonex Forte - Shreya

Macox Plus - Macleods

Rimactazid - Novartis


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Our anti-TB brands

Ticinex Kid


Isoniazid - 50 mg

Competitors:

R-Cinex Kid Tablets - Lupin(R-100 + H-100)

Rimactazid DT Tablet - Novartis

(R-100 + H-50)

Montonex Forte Kid-DT Tablets

- Shreya

(R-100 + H-50)


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Our anti-TB brands

Themibutol

(Ethambutol)Strengths:

200 mg

400 mg

600 mg800 mg

1000 mg

Competitors:

Combutol Lupin

Ecox Macleods

MyambutolWyeth

MycobutolCadila Pharma

MycostatOverseas


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Our anti-TB brands

Themibutol Plus

(E-800 + H-300)

Themibutol Plus 1000

(E-1000 + H-300)

Competitors:

Combunex Lupin

CoxridWyeth

Myconex-800Cadila Pharma

Isokoxi-800 Shreya


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Our anti-TB brands

Ticin

(Rifampicin)Strengths:

150 mg

300 mg

450 mg

Competitors:

R-cin Lupin

Macox Macleods

Rimactane - Novartis

Montomycin Shreya

MonocinOverseas


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Our anti-TB brands

Ticimide

(Pyrazinamide)Strengths:

500 mg

750 mg

Competitors:

Pyzina Lupin

Macrozide Macleods

PZA CIBA - Novartis

Montozin Shreya

ActizidOverseas


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Multi Drug Resistant Tuberculosis(MDR-TB)

Tuberculosis produced bytubercle bacilli resistant to

one or more anti-TB

drugs.


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Principles of MDR-TB Treatment

Will require at least some second-line drugs

Must use what is likely to be the most effective drugs.

Must not aim to keep drugs in reserve. Prefer drugs which the patient has not taken previously.

If bacilli remain sensitive to a standard drug, it can be

added to the regimen. But do not rely on it.

Continued .


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Initial regimen should consist of at least 3 drugs,

preferably 4 or 5 to which the bacilli are likely to

be fully sensitive.

Adding Z during 3 months is desirable, even if

previously used, as resistance is usually unlikely

Continued ..


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Acuspar (Sparfloxacin)ideal drug to treat MDR-TB

Because:

1. Only quinolone showing activity against

17 out of 23 multidrug resistant strains of

M. tuberculosis

2. There is no cross-resistance with rifampicin and

isoniazid.

3. More potent than ciprofloxacinContinued


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When the patients sputum has converted to

negative, one or more drugs, preferably weaker

drugs, which are causing side effects, can bewithdrawn.

Other drugs should be continued for at least 18

months after sputum conversion to prevent

relapse.


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Ethiocid(Tablets of Ethionamide 250 mg.)

Mode of action:

Bactericidal.

Acts by inhibiting protein synthesis in the bacterial

cell and also inhibits mycolic acid synthesis.

Strains resistant to H, S & PAS remain sensitive to

ethionamide.


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Pharmacokinetics:

Half-life 2 hours

T max

3 hoursRapidly and widely distributed

Conc. in blood and various organs are approximately equal

Significant concentrations become available in CSF

Apprx. 50% of the patients do not tolerate single doselarger than 500 mg as it produces severe GI disturbances


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Second line drug to treat MDR-TB as part of aregimen

Contraindications:

Severe hypersensitivity to ethionamideSevere hepatic damage

Pregnancy


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May intensify the adverse effects of other anti-TBdrugs administered concurrently

Pyridoxin should be given if neuropathy haddeveloped on previous INH therapy

DosageAdults 0.5 to 1 gm daily in divided dosee with mealsChildren 12 to 15 mg/kg/day(max. 750mg/day) in

divided doses with meals


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Prothicid(Tablets of Prothionamide 250 mg.)

Very similar to ethionamide

Except, prothionamide is much better tolerated

Indications, dosage, side effects and precautionssame as that of ethionamide

tuberculosis 01

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