Introduction to Tuberculosis

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Dr. Rajendra K. Panda, M.D Faculty, Deptt. Of Pharmacology S.C.B. Medical College, Cuttack Pharmacotherapy of tuberculosis(I)

INTRODUCTION: : 

INTRODUCTION: Tuberculosis is a chr. Inf. disease - caused by M.tuberculosis/M.bovis - mainly affecting the lung causing PTB - also affect other parts causing EPTB Characterized by -Cough lasting > 3 wks and not respond. to usual antibiotic -Production of purulent, sometimes blood- stained sputum - Evening rise of temp. - Night sweats -Weight loss

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Highest estimated TB rates per capita were in Africa 25 - 49 50 - 99 100 - 299 < 10 10 - 24 No estimate per 100 000 pop 300 or more

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Most TB cases were in India and China 10 000 - 99 999 100 000 - 999 999 < 1 000 1 000 - 9 999 Number of cases 1 000 000 or more

Transmission of the disease : 

Transmission of the disease

Mycobacterium tuberculosis : 

Mycobacterium tuberculosis gram +ve bacilli Non motile, non sporing,& noncapsulated Strict aerobes Branching filamentous forms ≈ fungal mycelium =>MYCOBACTERIUM A.F.B => when stained by Carbol Fuschin by Z-N Stain they resist decolorisation by 25% H2S04 &Abs.alcohol Cell wall is lipid rich with mycolic acid which is essential & unique component

Mycobacterial Cell Wall : 

Mycobacterial Cell Wall Arabinoglycan Peptidoglycan Mycolates Lipoarabinomannan(LAM) Porin Lipid Bilayer Acyl lipid

Diff. Subpopulation of M. tb : 

Diff. Subpopulation of M. tb Rapid Growing Slow growing Spurters Dormant

RISK FACTORS : 

RISK FACTORS HIV infection Children exposed to high risk adults Close contacts of persons known or suspected to have active disease Silicosis Prolonged corticosteroid therapy Other immunosuppressive therapy Low body weight (10% or more below the ideal) Diabetes mellitus Residents and employees of high-risk congregate settings Patients with CRF

Difficult to treat: : 

Difficult to treat: 1. Most antibiotics are effective against rapidly growing organism in contrast to M.tb slow growing 2 Mycobacterium Cell can be dormant, thus completely resistant to many antibiotics or killed very slowly by few drugs 3 The lipid rich mycobacterium Cell wall is impermeable to many drugs. 4 A substantial proportion are intracellular &chemotherapeutic agents penetrate poorly 5 Mycobacterium =>develop resistance to any single drug 6 Caseation &fibrosis block the b.v. supplying necrotic area thus penetration of antitubercular drug difficult

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Diagnosis of Pulmonary TB

X- Ray Findings : 

X- Ray Findings

Aims of Treatment : 

Aims of Treatment Prevent death Cure the pt. Prevent relapse Prevent transmission Prevent development of Drug resistance

Classification of AntitubercularDrugs : 

Classification of AntitubercularDrugs First line Drug(Essential AntiTB) High Anti TB effect Acceptable degree of toxicity Used routinely - ISONIAZID(H) -RIFAMPICIN(R) -PYRAZINAMIDE(Z) - ETHAMBUTOL(E) - STREPTOMYCIN(S)

Contd. : 

Contd. SECOND LINE DRUG (RESERVE ANTI TB DRUG) -low anti tb effect - high toxicity -or both -used in special circumstances only - PAS -AMIKACIN NEWER DRUGS -CAPREOMYCIN -CIPROFLOXACILLIN -ETHIONAMIDE -OFLOXACILLIN -CLARITHROMYCIN -KANAMYCIN -AZITHROMYCIN -CYCLOSERINE -KANAMYCIN - RIFABUTIN

Rationale behind Combination Therapy : 

Rationale behind Combination Therapy To prevent emergence of resistant bacilli Drugs like H & R act synergistically & Z is more active during the inflammatory states Duration of treatment is reduced To act simultaneously with all subpopulation of Mycobacterium tuberculosis

Specific t/t for other categories : 

Specific t/t for other categories M.A.C Clari/Azith+E+/-Rifabutin M. kansassi H+R+E M.fort.complex Amikacin+Doxycycline M.marinum Rifampin +Ethambutol

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Thank You